title: Pandemic influenza preparedness and health systems challenges in Asia: results from rapid analyses in 6 Asian countries

text: BACKGROUND: Since 2003, Asia-Pacific, particularly Southeast Asia, has received substantial attention because of the anticipation that it could be the epicentre of the next pandemic. There has been active investment but earlier review of pandemic preparedness plans in the region reveals that the translation of these strategic plans into operational plans is still lacking in some countries particularly those with low resources. The objective of this study is to understand the pandemic preparedness programmes, the health systems context, and challenges and constraints specific to the six Asian countries namely Cambodia, Indonesia, Lao PDR, Taiwan, Thailand, and Viet Nam in the prepandemic phase before the start of H1N1/2009. METHODS: The study relied on the Systemic Rapid Assessment (SYSRA) toolkit, which evaluates priority disease programmes by taking into account the programmes, the general health system, and the wider socio-cultural and political context. The components under review were: external context; stewardship and organisational arrangements; financing, resource generation and allocation; healthcare provision; and information systems. Qualitative and quantitative data were collected in the second half of 2008 based on a review of published data and interviews with key informants, exploring past and current patterns of health programme and pandemic response. RESULTS: The study shows that health systems in the six countries varied in regard to the epidemiological context, health care financing, and health service provision patterns. For pandemic preparation, all six countries have developed national governance on pandemic preparedness as well as national pandemic influenza preparedness plans and Avian and Human Influenza (AHI) response plans. However, the governance arrangements and the nature of the plans differed. In the five developing countries, the focus was on surveillance and rapid containment of poultry related transmission while preparation for later pandemic stages was limited. The interfaces and linkages between health system contexts and pandemic preparedness programmes in these countries were explored. CONCLUSION: Health system context influences how the six countries have been preparing themselves for a pandemic. At the same time, investment in pandemic preparation in the six Asian countries has contributed to improvement in health system surveillance, laboratory capacity, monitoring and evaluation and public communications. A number of suggestions for improvement were presented to strengthen the pandemic preparation and mitigation as well as to overcome some of the underlying health system constraints.


title: Structure of dimeric full-length human ACE2 in complex with B0AT1

text: Angiotensin-converting enzyme 2 (ACE2) is the surface receptor for SARS coronavirus (SARS-CoV), directly interacting with the spike glycoprotein (S protein). ACE2 is also suggested to be the receptor for the new coronavirus (2019-nCoV), which is causing a serious epidemic in China manifested with severe respiratory syndrome. B0AT1 (SLC6A19) is a neutral amino acid transporter whose surface expression in intestinal cells requires ACE2. Here we present the 2.9 Å resolution cryo-EM structure of full-length human ACE2 in complex with B0AT1. The complex, assembled as a dimer of ACE2-B0AT1 heterodimers, exhibits open and closed conformations due to the shifts of the peptidase domains (PDs) of ACE2. A newly resolved Collectrin-like domain (CLD) on ACE2 mediates homo-dimerization. Structural modelling suggests that the ACE2-B0AT1 complex can bind two S proteins simultaneously, providing important clues to the molecular basis for coronavirus recognition and infection.


title: A qualitative enquiry into strategic and operational responses to Covid‐19 challenges in South Asia

text: The Covid‐19 epidemic is a public health emergency of international concern. It poses a massive risk for the human race across the planet, calling for the need to take measures at the local, regional, national, and global levels. South Asian countries stand more vulnerable to the pandemic due to their dense population, poor infrastructure, and low surveillance system. This paper aims to understand the challenges from the Covid‐19 pandemic for South Asia; and investigates the strategic and operational responses to this pandemic by policymakers and healthcare professionals, respectively, in South Asia. The study uses interviews and opinions of policymakers and doctors, from the South Asian region, involved in tackling the Covid‐19 crisis. The qualitative analysis is performed on these interviews and opinions by using NVivo 12 software. The findings indicate that policymakers and healthcare providers across South Asia have been showing efficient teamwork while dealing with this pandemic. The healthcare administrators being at the operational level, convey the challenges they face to the policymakers who then respond to them at a strategic level.


title: High-dose dietary zinc oxide mitigates infection with transmissible gastroenteritis virus in piglets

text: BACKGROUND: Zinc (Zn) supplementation has been shown to reduce the incidence of diarrhea and to protect animals from intestinal diseases, but the mechanisms of this protective effect against virus infection in vivo have not yet been elucidated. Transmissible gastroenteritis virus (TGEV) causes diarrhea in piglets with an age-dependent decrease of severity. RESULTS: We used 60 weaned piglets that were divided into three groups to evaluate the effect of different Zn levels added to a conventional diet (50 mg Zn/kg diet, Zn(low), control group). The other groups received the diet supplemented with ZnO at final concentrations of 150 mg Zn/kg diet (Zn(med)), or 2,500 mg/kg diet (Zn(high)). Oral challenge infection with TGEV was performed when the pigs had been fed for 1 week with the respective diet. Half of the piglets of each group were sacrificed at day 1 and 18 after challenge infection. Fecal consistency was improved and body weights increased in the Zn(high) group when compared to the other groups, but no direct effect of Zn concentrations in the diet on fecal TGEV shedding and mucosal immune responses was detectable. However, in the Zn(high) group, we found a prevention of villus atrophy and decreased caspase-3-mediated apoptosis of jejunal epithelium. Furthermore, pigs receiving high Zn diet showed a down-regulation of interferon (IFN)-α, oligoadenylate synthetase (OAS), Zn transporter SLC39A4 (ZIP4), but up-regulation of metallothionein-1 (MT1), as well as the Zn transporters SLC30A1 (ZnT1) and SLC30A5 (ZnT5). In addition, forskolin-induced chloride secretion and epithelial resistance were controlled at a physiological level in the Zn(high) but not the other groups. Finally, in the Zn(high) group, we documented an earlier and higher systemic TGEV-specific serum antibody response. CONCLUSIONS: These results suggest that high dietary Zn could provide enhanced protection in the intestinal tract and stimulate the systemic humoral immune response against TGEV infection.


title: Network opportunity

text: Our developing scientific understanding of complex networks is being usefully applied in a wide set of financial systems. What we've learned from the 2008 crisis could be the basis of better management of the economy — and a means to avert future disaster.


title: The Roles of CCR7 for the Homing of Memory CD8+ T Cells into Their Survival Niches

text: Memory CD8+ T cells in the immune system are responsible for the removal of external Ags for a long period of time to protect against re-infection. Naïve to memory CD8+ T cell differentiation and memory CD8+ T cell maintenance require many different factors including local environmental factors. Thus, it has been suggested that the migration of memory CD8+ T cells into specific microenvironments alters their longevity and functions. In this review, we have summarized the subsets of memory CD8+ T cells based on their migratory capacities and described the niche hypothesis for their survival. In addition, the basic roles of CCR7 in conjunction with the migration of memory CD8+ T cells and recent understandings of their survival niches have been introduced. Finally, the applications of altering CCR7 signaling have been discussed.


M-V Test validation and accreditation in the clinical virology laboratory


title: Detection of the Middle East Respiratory Syndrome Coronavirus Genome in an Air Sample Originating from a Camel Barn Owned by an Infected Patient

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus that has been circulating in the Arabian Peninsula since 2012 and causing severe respiratory infections in humans. While bats were suggested to be involved in human MERS-CoV infections, a direct link between bats and MERS-CoV is uncertain. On the other hand, serological and virological data suggest dromedary camels as the potential animal reservoirs of MERS-CoV. Recently, we isolated MERS-CoV from a camel and its infected owner and provided evidence for the direct transmission of MERS-CoV from the infected camel to the patient. Here, we extend this work and show that identical MERS-CoV RNA fragments were detected in an air sample collected from the same barn that sheltered the infected camel in our previous study. These data indicate that the virus was circulating in this farm concurrently with its detection in the camel and in the patient, which warrants further investigations for the possible airborne transmission of MERS-CoV.


Are genetic vaccines the right weapon against Covid-19?


title: Detection of Four Human Coronaviruses in Respiratory Infections in Children: A One-Year Study in Colorado

text: Lower respiratory tract infections are the leading cause of death in children worldwide. Studies on the epidemiology and clinical associations of the four human non-SARS human coronaviruses (HCoVs) using sensitive polymerase chain reaction (PCR) assays are needed to evaluate the clinical significance of HCoV infections worldwide. Pediatric respiratory specimens (1,683) submitted to a diagnostic virology laboratory over a 1-year period (December 2004–November 2005) that were negative for seven respiratory viruses by conventional methods were tested for RNA of four HCoVs using sensitive RT-PCR assays. Coronavirus RNAs were detected in 84 (5.0%) specimens: HCoV-NL63 in 37 specimens, HCoV-OC43 in 34, HCoV-229E in 11, and HCoV-HKU1 in 2. The majority of HCoV infections occurred during winter months, and over 62% were in previously healthy children. Twenty-six (41%) coronavirus positive patients had evidence of a lower respiratory tract infection (LRTI), 17 (26%) presented with vomiting and/or diarrhea, and 5 (8%) presented with meningoencephalitis or seizures. Respiratory specimens from one immunocompromised patient were persistently positive for HCoV-229E RNA for 3 months. HCoV-NL63-positive patients were nearly twice as likely to be hospitalized (P = 0.02) and to have a LRTI (P = 0.04) than HCoV-OC43-positive patients. HCoVs are associated with a small, but significant number (at least 2.4% of total samples submitted), of both upper and lower respiratory tract illnesses in children in Colorado. Our data raise the possibility that HCoV may play a role in gastrointestinal and CNS disease. Additional studies are needed to investigate the potential roles of HCoVs in these diseases.


title: Reduction of Natural Killer but Not Effector CD8 T Lymphoyctes in Three Consecutive Cases of Severe/Lethal H1N1/09 Influenza A Virus Infection

text: BACKGROUND: The cause of severe disease in some patients infected with pandemic influenza A virus is unclear. METHODOLOGY/PRINCIPAL FINDINGS: We present the cellular immunology profile in the blood, and detailed clinical (and post-mortem) findings of three patients with rapidly progressive infection, including a pregnant patient who died. The striking finding is of reduction in natural killer (NK) cells but preservation of activated effector CD8 T lymphocytes; with viraemia in the patient who had no NK cells. Comparison with control groups suggests that the reduction of NK cells is unique to these severely ill patients. CONCLUSION/SIGNIFICANCE: Our report shows markedly reduced NK cells in the three patients that we sampled and raises the hypothesis that NK may have a more significant role than T lymphocytes in controlling viral burden when the host is confronted with a new influenza A virus subtype.


title: Evaluating performance of metagenomic characterization algorithms using in silico datasets generated with FASTQSim

text: Background In silico bacterial, viral, and human truth datasets were generated to evaluate available metagenomics algorithms. Sequenced datasets include background organisms, creating ambiguity in the true source organism for each read. Bacterial and viral datasets were created with even and staggered coverage to evaluate organism identification, read mapping, and gene identification capabilities of available algorithms. These truth datasets are provided as a resource for the development and refinement of metagenomic algorithms. Algorithm performance on these truth datasets can inform decision makers on strengths and weaknesses of available algorithms and how the results may be best leveraged for bacterial and viral organism identification and characterization. Source organisms were selected to mirror communities described in the Human Microbiome Project as well as the emerging pathogens listed by the National Institute of Allergy and Infectious Diseases. The six in silico datasets were used to evaluate the performance of six leading metagenomics algorithms: MetaScope, Kraken, LMAT, MetaPhlAn, MetaCV, and MetaPhyler. Results Algorithms were evaluated on runtime, true positive organisms identified to the genus and species levels, false positive organisms identified to genus and species level, read mapping, relative abundance estimation, and gene calling. No algorithm out performed the others in all categories, and the algorithm or algorithms of choice strongly depends on analysis goals. MetaPhlAn excels for bacteria and LMAT for viruses. The algorithms were ranked by overall performance using a normalized weighted sum of the above metrics, and MetaScope emerged as the overall winner, followed by Kraken and LMAT. Conclusions Simulated FASTQ datasets with well-characterized truth data about microbial community composition reveal numerous insights about the relative strengths and weaknesses of the metagenomics algorithms evaluated. The simulated datasets are available to download from the Sequence Read Archive (SRP062063).


title: Is respiratory viral infection really an important trigger of asthma exacerbations in children?

text: We performed a prospective cohort study from September 2003 to December 2004 to delineate attributing the effect of different respiratory viral infections including newly discovered ones to asthma exacerbations in children in Hong Kong. One hundred and fourteen children aged 6–14 years with chronic stable asthma and on regular inhaled steroid were monitored for respiratory symptoms over a full calendar year from recruitment. They would attend the study clinic if peak expiratory flow rate decreased to below 80% of their baselines, if they met a predefined symptom score, or if parents subjectively felt them developing a cold. Virological diagnosis using virus culture, antigen detection, and polymerase chain reaction methods on nasal swab specimens would be attempted for all these visits irrespective of triggers. Physician diagnosed outcome of each episode was documented. Three hundred and five episodes of respiratory illnesses were captured in the cohort. Nasal specimens were available in 166 episodes, 92 of which were diagnosed as asthma exacerbations, and 74 non-asthma related episodes. Respiratory viruses were detected in 61 of 166 episodes (36.7%). There was no significant difference in virus detection rate between asthma exacerbations (32 out of 97 episodes, 34.8%) and non-asthma respiratory illnesses (29 out of 79 episodes, 39.2%). Although newly discovered respiratory viruses were identified in these episodes, rhinovirus was the commonest organism associated with both asthma exacerbations and non-asthma related episodes. Plausible explanations for much lower virus detection rate than previously reported include improved personal hygiene and precautionary measures taken during respiratory tract infections in the immediate post-severe acute respiratory syndrome period together with a significant contribution of other adverse factors like environmental air pollution. We conclude that not all viral infections in children with asthma lead to an asthma exacerbation and the attributing effect of different triggers of asthma exacerbations in children vary across different time periods and across different localities.


title: Coccidioidomycosis as a Common Cause of Community-acquired Pneumonia

text: The early manifestations of coccidioidomycosis (valley fever) are similar to those of other causes of community-acquired pneumonia (CAP). Without specific etiologic testing, the true frequency of valley fever may be underestimated by public health statistics. Therefore, we conducted a prospective observational study of adults with recent onset of a lower respiratory tract syndrome. Valley fever was serologically confirmed in 16 (29%) of 55 persons (95% confidence interval 16%–44%). Antimicrobial medications were used in 81% of persons with valley fever. Symptomatic differences at the time of enrollment had insufficient predictive value for valley fever to guide clinicians without specific laboratory tests. Thus, valley fever is a common cause of CAP after exposure in a disease-endemic region. If CAP develops in persons who travel or reside in Coccidioides-endemic regions, diagnostic evaluation should routinely include laboratory evaluation for this organism.


title: Reporting, Recording and Communication of COVID-19 Cases in Workplace: Data Protection as a Moving Target

text: In response to concerns related to privacy in the context of COVID-19, recently European and national Data Protection Authorities (DPA) issued guidelines and recommendations addressing variety of issues related to processing of personal data for preventive purposes. One of the recurring questions in these guidelines related to the rights and responsibilities of employers and employees in reporting, recording and communicating COVID-19 cases in workplace. National Data Protection Authorities in some cases adopted different approaches regarding duties in reporting and communicating the COVID-19 cases, however, they unanimously stressed importance of adopting privacy preserving approaches to avoid raising concerns about surveillance and stigmatization. We stress that in view of increasing use of new data collection and sharing tools such as “tracing and warning” apps, associated privacy related risks should be evaluated on an ongoing manner. In addition, the intricacies of different settings where such apps may be used should be taken into consideration when assessing the associated risks and benefits.


title: Limited Transmission of Turkey Coronavirus in Young Turkeys by Adult Alphitobius diaperinus (Coleoptera: Tenebrionidae)

text: We examined the role of lesser mealworm, Alphitobius diaperinus (Panzer), in the transmission of an enteric disease of turkeys caused by a coronavirus. Turkey coronavirus (TCV) from two sources was studied, one isolate (NC95) was embryo propagated, the second was TCV infected material from turkeys diagnosed with poult enteritis mortality syndrome (PEMS). Beetles were fed virus-infected feces mixed with chicken feed. Transmission of virus was effectively halted by surface sterilization of the beetles. Turkey poults administered beetle homogenates infected with TCV+ PEMS that had not been surface sterilized had reduced weight gains and 50% mortality. Mortality and weight gains were not effected in the NC95 group. Virus isolation procedures were performed to determine NC95 viability at varying time intervals. Beetles were dissected and the guts removed 1, 12, and 24 h after the initial viral feeding. Whole beetles were also examined for comparison. Whole beetles and beetle guts were homogenized and injected into turkey eggs for embryo propagation. Direct immunofluorescence was used to determine the presence of TCV. A. diaperinus were capable of mechanical transmission of TCV. However, only turkey embryos receiving whole beetle and beetle gut homogenates within 1 h of feeding on the virus were positive for TCV. Laboratory studies demonstrating PEMS transmission by A. diaperinus are continuing.


title: Two deletion variants of Middle East respiratory syndrome coronavirus found in a patient with characteristic symptoms

text: Significant sequence variation of Middle East respiratory syndrome coronavirus (MERS CoV) has never been detected since it was first reported in 2012. A MERS patient came from Korea to China in late May 2015. The patient was 44 years old and had symptoms including high fever, dry cough with a little phlegm, and shortness of breath, which are roughly consistent with those associated with MERS, and had had close contact with individuals with confirmed cases of MERS.After one month of therapy with antiviral, anti-infection, and immune-enhancing agents, the patient recovered in the hospital and was discharged. A nasopharyngeal swab sample was collected for direct sequencing, which revealed two deletion variants of MERS CoV. Deletions of 414 and 419 nt occurred between ORF5 and the E protein, resulting in a partial protein fusion or truncation of ORF5 and the E protein. Functional analysis by bioinformatics and comparison to previous studies implied that the two variants might be defective in their ability to package MERS CoV. However, the mechanism of how these deletions occurred and what effects they have need to be further investigated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-017-3361-x) contains supplementary material, which is available to authorized users.


title: Prevention of Travel-Related Infectious Diseases in Families of Internationally Adopted Children

text: Pretravel consultation before international adoption must encompass standard advice for those who travel, advice for those who are exposed to the newly adopted child, and information about caring for a new child during travel. Children who travel to meet siblings may need special accommodations before and during travel. Data on the health of internationally adopted children illustrate the risk of exposing family members and close contacts to some infectious diseases during or after international adoption. Parents, family members, and close contacts of the newly adopted child should be given advice to reduce their own and their child's risk. Targeted preadoption counseling, close attention to hygiene and safety advice, and prompt identification and treatment of infections lead to the safest and most trouble-free adoption travel experience.


title: IFITM3 and Susceptibility to Respiratory Viral Infections in the Community

text: Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM 1,2, and 3) are viral restriction factors that mediate cellular resistance to several viruses. We have genotyped a possible splice-site altering single-nucleotide polymorphism (rs12252) in the IFITM3 gene in 34 patients with H1N1 influenza and severe pneumonia, and >5000 individuals comprising patients with community-acquired mild lower respiratory tract infection and matched controls of Caucasian ancestry. We found evidence of an association between rs12252 rare allele homozygotes and susceptibility to mild influenza (in patients attending primary care) but could not confirm a previously reported association between this single-nucleotide polymorphism and susceptibility to severe H1N1 infection.


title: Maoto, a Traditional Japanese Herbal Medicine, Inhibits Uncoating of Influenza Virus

text: We previously reported in randomized controlled trials that maoto, a traditional herbal medicine, showed clinical and virological efficacy for seasonal influenza. In this study, a culturing system for influenza was used to test the effect of maoto. A549 cells in the culture were infected with influenza virus A (PR8) and followed after treatment with maoto; the virus titers in the culture supernatant, intracellular viral proteins, and viral RNA were determined. When infected cells were cultured with maoto for 24 hr, the virus titer and protein were significantly reduced compared with medium only. Other subtypes, A/H3N2, H1N1pdm, and B, were also inhibited by maoto. Proliferation of viral RNA in a 6 hr culture was inhibited by maoto in the early phase, especially in the first 30 min. Focusing on the entry step of the influenza virus, we found that endosomal pH, regulated by vacuolar-type H(+) ATPase (V-ATPase) located in the membrane, was increased when treated with maoto. We also found that uncoating of influenza viruses was also inhibited by maoto, resulting in the increase of the number of virus particles in endosomes. These results strongly suggest that the inhibition of endosomal acidification by maoto results in blocking influenza virus entry to cytoplasm, probably through the inhibition of V-ATPase. The present study provides evidence that supports the clinical use of maoto for the treatment of influenza.


title: Novel ionophores active against La Crosse virus identified through rapid antiviral screening

text: Bunyaviruses are significant human pathogens, causing diseases ranging from hemorrhagic fevers to encephalitis. Among these viruses, La Crosse virus (LACV), a member of the California serogroup, circulates in the eastern and midwestern United States. While LACV infection is often asymptomatic, dozens of cases of encephalitis are reported yearly. Unfortunately, no antivirals have been approved to treat LACV infection. Here, we developed a method to rapidly test potential antivirals against LACV infection. From this screen, we identified several potential antiviral molecules, including known antivirals. Additionally, we identified many novel antivirals that exhibited antiviral activity without affecting cellular viability. Valinomycin, a potassium ionophore, was among our top targets. We found that valinomycin exhibited potent anti-LACV activity in multiple cell types in a dose-dependent manner. Valinomycin did not affect particle stability or infectivity, suggesting that it may preclude virus replication by altering cellular potassium ions, a known determinant of LACV entry. We extended these results to other ionophores and found that the antiviral activity of valinomycin extended to other viral families including bunyaviruses (Rift Valley fever virus, Keystone virus), enteroviruses (Coxsackievirus, rhinovirus), flavirivuses (Zika), and coronaviruses (229E and MERS-CoV). In all viral infections, we observed significant reductions in virus titer in valinomycin-treated cells. In sum, we demonstrate the importance of potassium ions to virus infection, suggesting a potential therapeutic target to disrupt virus replication. No antivirals are approved for the treatment of bunyavirus infection. The ability to rapidly screen compounds and identify novel antivirals is one means to accelerate drug discovery for viruses with no approved treatments. We used this approach to screen hundreds of compounds against La Crosse virus, an emerging bunyavirus that causes significant disease, including encephalitis. We identified several known and previously unidentified antivirals. We focused on a potassium ionophore, valinomycin, due to its promising in vitro antiviral activity. We demonstrate that valinomycin, as well as a selection of other ionophores, exhibits activity against La Crosse virus as well as several other distantly related bunyaviruses. We finally observe that valinomycin has activity against a wide array of human viral pathogens, suggesting that disrupting potassium ion homeostasis with valinomycin may be a potent host pathway to target to quell virus infection.


title: Indoor air quality audit implementation in a hotel building in Portugal

text: Abstract Hotels are designed to provide high levels of comfort for guests; however, frequent complaints related to uncomfortable thermal environment and inadequate indoor air quality (IAQ) appear. On the other hand, there is little research concerning IAQ audits of hotels up to now. This study is aimed to establish and demonstrate the comprehensive IAQ audit approach for hotel buildings, based on Portugal national laws. A 4-star hotel building in Portugal is used as a case study to demonstrate the IAQ audit application and evaluate its comprehensiveness and usefulness to the hotel or facility managers. The systematic approach involves the measurement of physical parameters – temperature (dry bulb), relative humidity and the concentration of the suspended particulate matter (PM10) – the monitoring of the concentrations of selected chemical indicators – carbon dioxide (CO2), carbon monoxide (CO), formaldehyde (HCHO) and total volatile organic compounds (TVOCs) – and the measurements of biological indicators (bacteria, fungi, Legionella). In the present case, air exchange rates are measured by the concentration-decay method using metabolic CO2 as the tracer gas. The comprehensive IAQ audit revealed four main problems in the hotel building: (1) insufficient ventilation rate; (2) too high particle concentration in some rooms; (3) contamination by Legionella of the sanitary hot-water circuit; (4) poor filtration effectiveness in all air handling units (AHUs).


title: Socio-physical liveability through socio-spatiality in low-income resettlement archetypes - A case of slum rehabilitation housing in Mumbai, India

text: This study looks into the socio-physical liveability through socio-spatiality in low-income settlement archetypes. Paradoxically, recently mushrooming slum rehabilitation housing which have delivered secured tenure to its inhabitants, face threats of being deserted from lack of socio-physical liveability. Recurring of informality issues has advocated to investigate the reasons behind the ‘rebound’ phenomenon. This study explores the efficacy of socio-spatiality and its linkages with socio-physical liveability, taking Mumbai slum rehabs as case study. A comparative analysis of the current built-environment indicators and liveability status of major informal archetypes was performed, followed by analyses of the socio-physical problems associated with it. A critical evaluation of the rehabilitation housing of Mumbai highlights the problems caused by the current dense built-environment design. Reflecting on global instances, this article demonstrates the significance of socio-spatiality and suggests environmentally sustainable indicator-based built-environment recommendations, which if implemented in the forthcoming slum rehab housing planning, would enhance well-being and liveability among the low-income sector in future. While analysing the ‘rebound’ phenomenon, this study delivered a heuristics of socio-physical liveability, built-environment and their respective indicators. This method would aid the architects, planners and policymakers in reshaping the forth-coming built-environment while safeguarding the socio-physical liveability of the low-income sector.


title: The nucleolus and viral infection

text: The nucleolus is a subnuclear structure of eukaryocytes. It was thought that nucleolus only participates in the biogenesis and processing of rRNA. However, more and more evidence shows that it has many other functions, such as tRNA precursor processing, stress sensing and it is also involved in gene silencing, senescence and cell cycle regulation. Here, we summarize the recent understandings about the nucleolar functions, the regulation of nucleolar localization of proteins and the role that the nucleolus plays in virus infection, in which some related studies of Herpes simplex virus type 1 (HSV-1) US11, UL24 and bovine herpesvirus-1 infected cell protein 27 (BICP27) carried out in our lab will also be included.


title: An Australian Response to the COVID-19 Pandemic and its Implications on the Practice of Neurosurgery.

text: Abstract Objective This study was designed to assess the impact of public health policy in Australia in response to the Coronavirus disease 2019 (COVID-19) pandemic on the delivery of neurosurgical services. Being essential services, we postulated that there would not be a decrease in elective and emergency neurosurgical presentations and surgeries. Methods This is a prospective, observational, epidemiological study in strict adherence to the STROBE guidelines. It is a cross-sectional, multicentric study involving five tertiary neurosurgical centres to capture all public neurosurgical admissions in Queensland during the last three months (Feb-April, 2020) of significant public health policy changes to combat COVID-19. Results An analysis of the 1,298 admissions for the Queensland population of 5.07 million Australians demonstrated a decrease in the number of elective and emergency admissions. The decline in elective admissions, particularly degenerative spine, benign neoplasms and vascular pathologies, was a direct response of government strategy to curb activity to urgent surgical interventions only. Moreover, a trend towards decline in emergency admissions was also noted, partly explained by fewer trauma, but partly attributed to a decline in vascular pathologies including subarachnoid haemorrhage. Conclusions In comparison to Europe and North America, this study demonstrates the impact of proactive public health measures in Australia that successfully flattened the COVID-19 curve, whilst facilitating ongoing care of the acutely unwell neurosurgical patients.


title: Proteomic analysis of swine serum following highly virulent classical swine fever virus infection

text: BACKGROUND: Classical swine fever virus (CSFV) belongs to the genus Pestivirus within the family Flaviviridae. Virulent strains of classical swine fever virus (CSFV) cause severe disease in pigs characterized by immunosuppression, thrombocytopenia and disseminated intravascular coagulation, which causes significant economic losses to the pig industry worldwide. METHODS: To reveal proteomic changes in swine serum during the acute stage of lethal CSFV infection, 5 of 10 pigs were inoculated with the virulent CSFV Shimen strain, the remainder serving as uninfected controls. A serum sample was taken at 3 days post-infection from each swine, at a stage when there were no clinical symptoms other than increased rectal temperatures (≥40°C). The samples were treated to remove serum albumin and immunoglobulin (IgG), and then subjected to two-dimension differential gel electrophoresis. RESULTS: Quantitative intensity analysis revealed 17 protein spots showing at least 1.5-fold quantitative alteration in expression. Ten spots were successfully identified by MALDI-TOF MS or LTQ MS. Expression of 4 proteins was increased and 6 decreased in CSFV-infected pigs. Functions of these proteins included blood coagulation, anti-inflammatory activity and angiogenesis. CONCLUSION: These proteins with altered expression may have important implications in the pathogenesis of classical swine fever and provide a clue for identification of biomarkers for classical swine fever early diagnosis.


Surgery at the time of COVID‐19 pandemic: initial evidence of safe practice


title: Underweight, overweight, and obesity as independent risk factors for hospitalization in adults and children from influenza and other respiratory viruses

text: BACKGROUND: The relationship between obesity and risk of complications described during the 2009 influenza pandemic is poorly defined for seasonal influenza and other viral causes of influenza‐like illness (ILI). METHODS: An observational cohort of hospitalized and outpatient participants with ILI was conducted in six hospitals in Mexico. Nasopharyngeal swabs were tested for influenza and other common respiratory pathogens. RESULTS: A total of 4778 participants were enrolled in this study and had complete data. A total of 2053 (43.0%) had severe ILI. Seven hundred and seventy‐eight (16.3%) were positive for influenza, 2636 (55.2%) were positive for other viral respiratory pathogens, and 1364 (28.5%) had no respiratory virus isolated. Adults with influenza were more likely to be hospitalized if they were underweight (OR: 5.20), obese (OR: 3.18), or morbidly obese (OR: 18.40) compared to normal‐weight adults. Obese adults with H1N1 had a sixfold increase in odds of hospitalization over H3N2 and B (obese OR: 8.96 vs 1.35, morbidly obese OR: 35.13 vs 5.58, respectively) compared to normal‐weight adults. In adults with coronavirus, metapneumovirus, parainfluenza, and rhinovirus, participants that were underweight (OR: 4.07) and morbidly obese (OR: 2.78) were more likely to be hospitalized as compared to normal‐weight adults. All‐cause influenza‐like illness had a similar but less pronounced association between underweight or morbidly obesity and hospitalization. CONCLUSIONS: There is an increased risk of being hospitalized in adult participants that are underweight or morbidly obese, regardless of their viral pathogen status. Having influenza, however, significantly increases the odds of hospitalization in those who are underweight or morbidly obese.


The reality of dying in an intensive care unit with Covid-19 during the pandemic


Bending the arc of COVID-19 through a principled food systems approach


title: SARS-CoV-2 productively infects human gut enterocytes

text: The virus severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) can cause coronavirus disease 2019 (COVID-19), an influenza-like disease that is primarily thought to infect the lungs with transmission via the respiratory route. However, clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2) is highly expressed on differentiated enterocytes. In human small intestinal organoids (hSIOs), enterocytes were readily infected by SARS-CoV and SARS-CoV-2 as demonstrated by confocal- and electron-microscopy. Consequently, significant titers of infectious viral particles were detected. mRNA expression analysis revealed strong induction of a generic viral response program. Hence, intestinal epithelium supports SARS-CoV-2 replication, and hSIOs serve as an experimental model for coronavirus infection and biology


title: Should RT‐PCR be considered a gold standard in the diagnosis of Covid‐19?

text: To face the new Covid‐19 pandemic, the need for early and accurate diagnosis of the disease among suspected cases quickly became obvious for effective management, and for better control of the spread of the disease in the population. Since the beginning of this disease epidemic caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), reverse transcriptase polymerase chain reaction (RT‐PCR) has routinely been used to confirm diagnosis. However, several authors have pointed out the poor performance of this technique, particularly in terms of sensitivity.(1,2) This article is protected by copyright. All rights reserved.


title: Chapter 11 Acute Exacerbations in Patients With Idiopathic Pulmonary Fibrosis

text: Abstract In spite of many studies, the real nature, etiology, pathobiology, and therapy of acute exacerbation (AEx) of idiopathic pulmonary fibrosis (IPF) are not clear. It seemed that AEx-IPF may be an acute acceleration of the underlying fibroproliferative process triggered by various extrinsic or unknown insults in the patients with IPF, who have a predisposition to abnormal wound healing and exaggerated fibrosis. This chapter summarizes the previous studies on etiology/triggering factors, risk factors, prognosis, and therapeutic trials with the introduction of the new consensus definition and diagnostic criteria, which remove “idiopathic” from the 2007 consensus definition, to improve the feasibility of future researches.


title: First detection of SARS-CoV-2 by real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay in pleural fluid

text: Abstract COVID-19 is a pandemic infection due to a novel coronavirus (SARS-CoV-2) spreading, resulting in a wide range of clinical features, from asyntomatic carriers to acute respiratory distress syndrome. The gold standard for diagnosis is nucleic acid detection by real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR) in naso-pharyngeal swabs, but, due to limitations in its sensitivity, thoracic imaging plays a crucial, complementary role in diagnostic work-up and it allows also to reveal atypical findings and potential alternative target for sampling, such as pleural effusion. Although not common, pleural involvement has been described in a minority of patients. Here, we describe the first case of SARS-CoV-2 RT-PCR detection in pleural fluid obtained by means of ultrasound-guided thoracentesis and report its main characteristics. Pleural effusion is not a common finding in COVID-19 infection, but a prompt recognition of this potential localization may be useful to optimize diagnostic work-up as well as management of these patients.


title: Polyomaviruses-associated respiratory infections in HIV-infected and HIV-uninfected children

text: Abstract Background Two recently discovered polyomaviruses (PyV), WU and KI, have been identified in respiratory-tract specimens from children with acute respiratory infections, although there are limited data in HIV-infected children. Objectives To determine the prevalence and clinical manifestations of WUPyV and KIPyV-associated lower respiratory tract infections (LRTIs) hospitalization in HIV-infected and -uninfected children; and probe the role of pneumococcal co-infection. Study design Nasopharyngeal aspirates were collected from a cohort of 39,836 children randomized to receive 9-valent pneumococcal conjugate vaccine (PCV9) or placebo when hospitalized for LRTIs, and were screened by PCR for WUPyV, KIPyV and other respiratory viruses. Results In placebo-recipients the prevalence of WUPyV was 6.3% (18/285) in HIV-infected and 13.9% (66/476) in HIV-uninfected children (p =0.002). In WUPyV-positive LRTIs HIV-infected children had lower oxygen saturation at admission and a higher case fatality rate (11.1% vs. 0%; p =0.04). KIPyV was identified in 10.2% (29/285) of HIV-infected and in 7.4% (35/476) of HIV-uninfected placebo-recipients with LRTIs (p =0.13). HIV-infected compared to HIV-uninfected children with KIPyV-positive LRTIs had lower oxygen saturation, higher respiratory rate and longer duration of hospitalization. Co-infections with other respiratory-viruses were detected in 65.5% of WUPyV-positive LRTIs and in 75.0% of KIPyV-positive LRTIs. Among HIV-uninfected children, there was a lower incidence of hospitalization for clinical pneumonia episodes in which KIPyV (80%; 95% CI: 41, 93) and WUPyV (49%; 95% CI: 9, 71) were identified among PCV9-recipients compared to placebo-recipients. Conclusions Polyomaviruses were commonly identified in HIV-infected and -uninfected children hospitalized for LRTIs, frequently in association with other viruses and may contribute to the pathogenesis of pneumococcal pneumonia.


title: Public perceptions of non-pharmaceutical interventions for reducing transmission of respiratory infection: systematic review and synthesis of qualitative studies

text: BACKGROUND: Non-pharmaceutical public health interventions may provide simple, low-cost, effective ways of minimising the transmission and impact of acute respiratory infections in pandemic and non-pandemic contexts. Understanding what influences the uptake of non-pharmaceutical interventions such as hand and respiratory hygiene, mask wearing and social distancing could help to inform the development of effective public health advice messages. The aim of this synthesis was to explore public perceptions of non-pharmaceutical interventions that aim to reduce the transmission of acute respiratory infections. METHODS: Five online databases (MEDLINE, PsycINFO, CINAHL, EMBASE and Web of Science) were systematically searched. Reference lists of articles were also examined. We selected papers that used a qualitative research design to explore perceptions and beliefs about non-pharmaceutical interventions to reduce transmission of acute respiratory infections. We excluded papers that only explored how health professionals or children viewed non-pharmaceutical respiratory infection control. Three authors performed data extraction and assessment of study quality. Thematic analysis and components of meta-ethnography were adopted to synthesise findings. RESULTS: Seventeen articles from 16 studies in 9 countries were identified and reviewed. Seven key themes were identified: perceived benefits of non-pharmaceutical interventions, perceived disadvantages of non-pharmaceutical interventions, personal and cultural beliefs about infection transmission, diagnostic uncertainty in emerging respiratory infections, perceived vulnerability to infection, anxiety about emerging respiratory infections and communications about emerging respiratory infections. The synthesis showed that some aspects of non-pharmaceutical respiratory infection control (particularly hand and respiratory hygiene) were viewed as familiar and socially responsible actions to take. There was ambivalence about adopting isolation and personal distancing behaviours in some contexts due to their perceived adverse impact and potential to attract social stigma. Common perceived barriers included beliefs about infection transmission, personal vulnerability to respiratory infection and concerns about self-diagnosis in emerging respiratory infections. CONCLUSIONS: People actively evaluate non-pharmaceutical interventions in terms of their perceived necessity, efficacy, acceptability, and feasibility. To enhance uptake, it will be necessary to address key barriers, such as beliefs about infection transmission, rejection of personal risk of infection and concern about the potential costs and stigma associated with some interventions.


title: Sexual Health in the SARS-CoV-2 Era

text: Sexual contact carries some risk for exposure to infection with severe acute respiratory syndrome coronavirus 2 during the coronavirus disease 2019 pandemic. This commentary provides clinicians with guidance on how to address sexual health and activity with patients in this context.


title: Inflammatory Bowel Disease in the COVID-19 Pandemic – the Patients‘ Perspective

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is affecting lives worldwide. The influence of inflammatory bowel disease (IBD) medication and IBD itself on COVID-19 is controversial. Additionally, IBD focused guidance is scarce. OBJECTIVE: To determine COVID-19 prevalence/exposure, perception and information sources, medication compliance, patient behaviour and physician contact among patients with IBD compared with non-IBD controls. METHODS: A cross-sectional anonymous survey of patients with IBD (N=415) at one university IBD clinic and one gastroenterology practice, matched 4:1 with control participants (N=116), was performed. RESULTS: Patients with IBD had high fear of infection. The fear was more pronounced in patients taking immunosuppressants and it extended to hospitals, private practices and public places, such as supermarkets. IBD patients reported leaving their homes less frequently than their peers without IBD. A total of 90% of patients with IBD reported washing their hands more frequently. Patients taking immunosuppressants were concerned about interactions between medication and COVID-19, whereas patients taking 5-aminosalicylates were not. Nonetheless, 96.4% of patients adhered to continuing their medication. Patients sought guidance primarily from television and internet news sites. Video consultations were found to be a suitable solution for a subset of patients who are young, have a high level of fear and leave their home less frequently than their peers, whereas overall acceptance of video consultations was limited. CONCLUSION: Patients with IBD are significantly more affected by the COVID-19 pandemic than their non-IBD peers, but they continue to adhere to their medication regimens. IBD focused COVID-19 information should be actively conveyed.


title: Stem Cell Research Responds to COVID-19: Deepak Srivastava, Fiona Watt, and George Daley

text: COVID-19 shutdowns have impacted research institutions across the globe. Cell Stem Cell asked Deepak Srivastava, Fiona Watt, and George Daley to share their perspectives on leadership during this crisis and how their institutions are supporting the scientific community to address this global health crisis.


A twin challenge to handle: COVID‐19 with pregnancy


title: Structural Proteins in Severe Acute Respiratory Syndrome Coronavirus-2

text: Abstract What began with a sign of pneumonia-related respiratory disorders in China has now become a pandemic named by WHO as Covid-19 known to be caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The SARS-CoV-2 are newly emerged β coronaviruses belonging to the Coronaviridae family. SARS-CoV-2 has a positive viral RNA genome expressing open reading frames that code for structural and non-structural proteins. The spike, nucleocapsid, membrane, and envelope proteins are structural proteins. The S1 subunit of spike protein facilitates ACE2 mediated virus attachment and S2 subunit for membrane fusion. The presence of glutamine, asparagine, leucine, phenylalanine and serine amino in SARS-CoV-2 enhanced ACE2 binding. The N protein is composed of a serine-rich linker region sandwiched between N terminal (NTD) and C terminal (CTD). These terminals play a role in viral entry and its processing post entry. The NTD of SARS-CoV-2 N protein forms orthorhombic crystals and binds to the viral genome. The linker region contains phosphorylation sites that regulate its functioning. The CTD promotes nucleocapsid formation. Envelope proteins contain an NTD, hydrophobic domain and C terminal which form viroporins needed for viral assembly. Membrane proteins hydrophilic C terminal and amphipathic N terminal. Its long-form promotes spike incorporations and interaction with E facilitate virion production. As each protein is essential in viral functioning, this review describes the insights of SARS-CoV-2 structural proteins that would help in developing therapeutic strategies by targeting each protein to curb the rapidly growing pandemic.


title: Crystal structure of the C-terminal 2’,5’-phosphodiesterase domain of group A rotavirus protein VP3

text: In response to viral infections, the mammalian innate immune system induces the production of the second messenger 2’-5’ oligoadenylate (2–5A) to activate latent ribonuclease L (RNase L) that restricts viral replication and promotes apoptosis. A subset of rotaviruses and coronaviruses encode 2’,5’-phosphodiesterase enzymes that hydrolyze 2–5A, thereby inhibiting RNase L activation. We report the crystal structure of the 2’,5’-phosphodiesterase domain of group A rotavirus protein VP3 at 1.39 Å resolution. The structure exhibits a 2H phosphoesterase fold and reveals conserved active site residues, providing insights into the mechanism of 2–5A degradation in viral evasion of host innate immunity.


title: Las crisis de salud pública en una sociedad desarrollada. Aciertos y limitaciones en España. Informe SESPAS 2010

text: Resumen La percepción, la aceptabilidad y la gestión de los riesgos son construcciones sociales, por lo que en el manejo de las crisis de salud pública la distancia entre hechos y creencias y sentimientos pone a prueba la capacidad de respuesta de las instituciones oficiales sanitarias ante alarmas que pueden ser objetivas, potenciales o imaginarias. Del balance de la experiencia española ante crisis sanitarias destaca como punto fuerte la presencia de profesionales clínicos y de salud pública en una organización capaz de dar respuestas adecuadas, si bien la estructura política española, casi federal, tiene ventajas e inconvenientes. Como puntos débiles destacan la escasa relevancia concedida a la salud pública y una gestión sanitaria excesivamente dependiente de los aparatos partitocráticos. Tanto transferir a los profesionales sanitarios mayores espacios en las decisiones sobre la identificación y la gestión de las crisis (con transparencia) como limitar la inercia burocrática pueden ayudar a mejorar la gestión de las crisis sanitarias. Para algunos, las crisis pueden suponer oportunidades (no siempre legítimas) de negocio o protagonismo, por lo que la percepción de las crisis cada día será más ajena a los expertos y más determinada por colectivos interesados en propagarlas o aportar soluciones. Se necesita avanzar en el desarrollo participativo de estrategias de respuesta a las crisis emergentes, pero más aún en la implicación de todos los niveles sanitarios en su elaboración y conocimiento. Abstract The perception, acceptability and management of risks are social construction. Consequently, in managing public health crises, the gap between facts, beliefs and feelings tests the responsiveness of official institutions to health alarms that can be objective, potential, or imaginary. On balance, a strong point of the Spanish experience of health crises is the presence of clinicians and public health officers working in an organization capable of responding adequately, although the quasi-federal Spanish political structure has both advantages and disadvantages. Weaknesses include the low profile given to public health and a management structure that relies too heavily on partitocracy. The management of these crises could be improved by transferring greater scope to health professionals in decisions about crisis identification and management (with transparency) and limiting bureaucratic inertia. For some, health crises involve visibility or business opportunities (not always legitimate). Therefore, the perception of crisis will increasingly rest less in the hands of experts and more in those of groups interested in spreading these crises or in providing solutions. While progress is needed to develop participation in strategies to respond to emerging crises, even more essential is the involvement of all healthcare levels in their preparation and dissemination.


Increased fetuin A levels in Helicobacter pylori infection: a missing link between H. pylori and insulin resistance?


title: The impact of implementing respiratory point-of-care testing in a regional haemato-oncology unit

text: Respiratory point-of-care tests (POCT), detecting influenza A, influenza B and respiratory syncytial virus (RSV), were implemented in response to recent RSV outbreaks at a regional haemato-oncology unit in Glasgow. We provide a descriptive study of pre- and post- POCT implementation, which suggests POCT reduce the time taken to receive results and increase diagnostic rates in outpatients. It is likely that the reduction in turn-around-time afforded by POCT also lead to a faster time to antiviral treatment, prompt isolation and a reduction in the number of hospital acquired infections.


title: Low mortality rates related to respiratory virus infections after bone marrow transplantation

text: Respiratory viruses (RVs) frequently cause severe respiratory disease in bone marrrow transplant (BMT) recipients. To evaluate the frequency of RV, nasal washes were collected year-round from BMT recipients with symptoms of upper respiratory tract infection (URI). Direct immunofluorescence assay was performed for respiratory syncytial virus (RSV), influenza (Flu) A and B, adenovirus and parainfluenza (Paraflu) virus. Patients with RSV pneumonia or with upper RSV infection, but considered at high risk for developing RSV pneumonia received aerosolized ribavirin. Oseltamivir was given to patients with influenza. A total of 179 patients had 392 episodes of URI. In all, 68 (38%) tested positive: RSV was detected in 18 patients (26.4%), Flu B in 17 (25%), Flu A in 11 (16.2%) and Paraflu in 7 (10.3%). A total of 14 patients (20.6%) had multiple RV infections or coinfection. RSV pneumonia developed in 55.5% of the patients with RSV-URI. One of the 15 patients (6.6%) with RSV pneumonia died. Influenza pneumonia was diagnosed in three patients (7.3%). RSV and influenza infections peaked in fall–winter and winter–spring months, respectively. We observed decreased rates of influenza and parainfluenza pneumonia and low mortality because of RSV pneumonia. The role of antiviral interventions such as aerosolized ribavirin and new neuraminidase inhibitors remains to be defined in randomized trials.


title: Development and implementation of a molecular diagnostic platform for daily rapid detection of 15 respiratory viruses

text: Acute respiratory tract infections are caused by a large number of viruses. Diagnostic methods have until recently been available only for a limited number of these viruses. With the objective to achieve sensitive assays for all respiratory viruses, a rational workflow in the laboratory, and a short turn‐around time, a real‐time PCR diagnostic platform for daily rapid detection of 15 respiratory viruses was developed. The system was evaluated on 585 stored nasopharyngeal aspirates from hospitalized children. Previous analysis by immunofluorescence and virus isolation identified viruses in 37% of the samples while the new PCR diagnostic panel detected 57% virus positive samples. The new platform was introduced in the laboratory in October 2007 and has then fully replaced the standard immunofluorescence assay for rapid detection of viruses and virus isolation. J. Med. Virol. 81:167–175, 2009. © 2008 Wiley‐Liss, Inc.


title: Towards a genomics-informed, real-time, global pathogen surveillance system

text: The recent Ebola and Zika epidemics demonstrate the need for the continuous surveillance, rapid diagnosis and real-time tracking of emerging infectious diseases. Fast, affordable sequencing of pathogen genomes — now a staple of the public health microbiology laboratory in well-resourced settings — can affect each of these areas. Coupling genomic diagnostics and epidemiology to innovative digital disease detection platforms raises the possibility of an open, global, digital pathogen surveillance system. When informed by a One Health approach, in which human, animal and environmental health are considered together, such a genomics-based system has profound potential to improve public health in settings lacking robust laboratory capacity. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrg.2017.88) contains supplementary material, which is available to authorized users.


title: Battling COVID-19 Pandemic: Sphingosine-1-Phosphate Analogs as an Adjunctive Therapy?

text: With the sudden outbreak of COVID-19 patient worldwide and associated mortality, it is critical to come up with an effective treatment against SARS-CoV-2. Studies suggest that mortality due to COVID 19 is mainly attributed to the hyper inflammatory response leading to cytokine storm and ARDS in infected patients. Sphingosine-1-phosphate receptor 1 (S1PR1) analogs, AAL-R and RP-002, have earlier provided in-vivo protection from the pathophysiological response during H1N1 influenza infection and improved mortality. Recently, it was shown that the treatment with sphingosine-1-phosphate receptor 1 analog, CYM5442, resulted in the significant dampening of the immune response upon H1N1 challenge in mice and improved survival of H1N1 infected mice in combination with an antiviral drug, oseltamivir. Hence, here we suggest to investigate the possible utility of using S1P analogs to treat COVID-19.


title: SARS‐CoV‐2, skin lesions and the need of a multidisciplinary approach

text: COVID‐19 is a disease caused by severe acute respiratory syndrome coronavirus 2 of the genus Betacoronavirus (SARS‐CoV‐2). It was first described in Wuhan (China) on December 2019 and has spread to become a pandemic. Its clinical presentation is mainly characterized by cough, fever and dyspnea, although many other symptoms have been described within its presentation pattern. In some cases, it causes an acute respiratory distress that has lead to the death of thousands of people around the world. Furthermore, different types of skin lesions have been described during the infection period of illness.1 In this exceptional situation of global health emergency, physicians are undertaking research work in order to achieve notions on the etiopathogenesis of these skin lesions. The first report of cutaneous manifestations described different forms of skin lesions such as erythematous rash, urticaria and chicken‐pox‐like vesicles.2 Further studies have classified 5 different type of skin lesions, and associated them with patient demographics, timing in relation to symptoms of the disease, severity and prognosis.


Reinventing the wheel in ARDS: Awake proning in COVID-19


title: Porcine respiratory coronavirus spread in Catalunya, Spain, a previously infection-free area

text: Abstract A retrospective study of sera from seven commercial pig herds was conducted from May 1985 to July 1989, showing that antibodies against Porcine Respiratory Coronavirus (PRCV) were first detected in Spain in September 1986. During 1991 a stratified sampling of breeding herds was conducted to establish prevalence to PRCV or Transmissible Gastroenteritis Virus (TGEV) infections in Catalunya (northeast Spain). An antibody-capture ELISA was used for PRCV- and/or TGEV-antibodies, while a competitive inhibition ELISA tested for TGEV-specific antibodies. This study revealed 91.1% positive sera and 96.7% positive farms to PRCV and/or TGEV with a gradual increase in prevalence during 1991, which was more noticeable in small herds. Of the total 569 herds tested, 65.2% were positive only to PRCV, 8.6% were positive to TGEV and 22.8% had mixed infections. The first appearance of antibodies coincided with large importation of feeder pigs from Belgium and Holland. This prevalence is much higher than previously reported in other regions of Spain.


title: Low testosterone levels predict clinical adverse outcomes in SARS‐CoV‐2 pneumonia patients

text: BACKGROUND: The pandemic of new severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS‐CoV‐2) has stressed the importance of effective diagnostic and prognostic biomarkers of clinical worsening and mortality. Epidemiological data showing a differential impact of SARS‐CoV‐2 infection on women and men have suggested a potential role for testosterone (T) in determining gender disparity in the SARS‐CoV‐2 clinical outcomes. OBJECTIVES: To estimate the association between T level and SARS‐CoV‐2 clinical outcomes (defined as conditions requiring transfer to higher or lower intensity of care or death) in a cohort of patients admitted in the respiratory intensive care unit (RICU). MATERIALS AND METHODS: A consecutive series of 31 male patients affected by SARS‐CoV‐2 pneumonia and recovered in the respiratory intensive care unit (RICU) of the “Carlo Poma” Hospital in Mantua were analyzed. Several biochemical risk factors (ie, blood count and leukocyte formula, C‐reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, D‐dimer, fibrinogen, interleukin 6 (IL‐6)) as well as total testosterone (TT), calculated free T (cFT), sex hormone–binding globulin (SHBG), and luteinizing hormone (LH) were determined. RESULTS: Lower TT and cFT were found in the transferred to ICU/deceased in RICU group vs groups of patients transferred to IM or maintained in the RICU in stable condition. Both TT and cFT showed a negative significant correlation with biochemical risk factors (ie, the neutrophil count, LDH, and PCT) but a positive association with the lymphocyte count. Likewise, TT was also negatively associated with CRP and ferritin levels. A steep increase in both ICU transfer and mortality risk was observed in men with TT < 5 nmol/L or cFT < 100 pmol/L. DISCUSSION AND CONCLUSION: Our study demonstrates for the first time that lower baseline levels of TT and cFT levels predict poor prognosis and mortality in SARS‐CoV‐2‐infected men admitted to RICU.


title: Cytokine determinants of viral tropism

text: The specificity of a given virus for a ceil type, tissue or species — collectively known as viral tropism — is an important factor in determining the outcome of viral infection in any particular host. Owing to the increased prevalence of zoonotic infections and the threat of emerging and re-emerging pathogens, gaining a better understanding of the factors that determine viral tropism has become particularly important. In this Review, we summarize our current understanding of the central role of antiviral and pro-inflammatory cytokines, particularly the interferons and tumour necrosis factor, in dictating viral tropism and how these cytokine pathways can be exploited therapeutically for cancer treatment and to better counter future threats from emerging zoonotic pathogens.


title: The evolution of disease: anthropological perspectives on epidemiologic transitions

text: BACKGROUND: The model of epidemiologic transitions has served as a guiding framework for understanding relationships between patterns of human health and disease and economic development for the past several decades. However, epidemiologic transition theory is infrequently employed in epidemiology. OBJECTIVE: Moving beyond Omran's original formulation, we discuss critiques and modifications of the theory of epidemiologic transitions and highlight some of the ways in which incorporating epidemiologic transition theory can benefit theory and practice in epidemiology. DESIGN: We focus on two broad contemporary trends in human health that epidemiologic transition theory is useful for conceptualizing: the increased incidence of chronic inflammatory diseases (CIDs), such as allergic and autoimmune diseases, and the emergence and reemergence of infectious disease. RESULTS: Situating these trends within epidemiologic transition theory, we explain the rise in CIDs with the hygiene hypothesis and the rise in emerging and reemerging infections with the concept of a third epidemiologic transition. CONCLUSIONS: Contextualizing these trends within epidemiologic transition theory reveals implications for clinical practice, global health policies, and future research within epidemiology.


title: A survey of the health and safety conditions of apartment buildings in Hong Kong

text: Abstract A high-density built environment poses challenges to the idea of sustainable development in respect of health (e.g. SARS outbreak) and safety (e.g. fire and structural problems). To examine the seriousness of the high-density problem, this study aims to survey the health and safety performance of apartment buildings in a densely populated city, Hong Kong, using a simplified assessment scheme. An assessment scheme based on a hierarchy of building performance indicators concerning the quality of: (a) architectural design, (b) building services design, (c) the surrounding environment, (d) operations and maintenance, and (e) management approaches was developed. One hundred forty (140) apartment buildings were surveyed and assessed through site inspections, desk searches, and interviews. A performance analysis was conducted to examine and compare the overall health and safety performance of the buildings. We found that there were considerable variations in health and safety conditions across buildings, even though they are located within a single district. Most of the variations in building health and safety conditions were attributed to differences in building management systems rather than building design. Enhancing strategic management approaches (e.g. a better delineation of owners’ rights and duties) appears to be the most critical factor that underperformers should consider in order to improve their buildings.


title: Building International Genomics Collaboration for Global Health Security

text: Genome science and technologies are transforming life sciences globally in many ways and becoming a highly desirable area for international collaboration to strengthen global health. The Genome Science Program at the Los Alamos National Laboratory is leveraging a long history of expertise in genomics research to assist multiple partner nations in advancing their genomics and bioinformatics capabilities. The capability development objectives focus on providing a molecular genomics-based scientific approach for pathogen detection, characterization, and biosurveillance applications. The general approaches include introduction of basic principles in genomics technologies, training on laboratory methodologies and bioinformatic analysis of resulting data, procurement, and installation of next-generation sequencing instruments, establishing bioinformatics software capabilities, and exploring collaborative applications of the genomics capabilities in public health. Genome centers have been established with public health and research institutions in the Republic of Georgia, Kingdom of Jordan, Uganda, and Gabon; broader collaborations in genomics applications have also been developed with research institutions in many other countries.


title: Genetic characteristics and polymorphisms in the chicken interferon-induced transmembrane protein (IFITM3) gene

text: The interferon-induced transmembrane protein 3 (IFITM3) gene is classified as a small interferon-stimulated gene and is associated with a broad spectrum of antiviral functions against several fatal enveloped viruses, including influenza A viruses (IAVs). The rs12252 single nucleotide polymorphism (SNP) of the IFITM3 gene in humans was associated with susceptibility to H1N1 influenza in a 2009 pandemic. In addition, overexpression of the IFITM3 protein potently inhibits the highly pathogenic avian influenza H5N1 virus in ducks and chickens. Although chickens are a major host of influenza viruses and the IFITM3 gene participates in the host antiviral system, studies on chicken IFITM3 gene are very rare. To investigate the genetic characteristics of the chicken IFITM3 gene, we performed direct sequencing and alignment in 108 Dekalb White and 72 Ross breeds. We also investigated the genotype and haplotype frequencies and linkage disequilibrium of the IFITM3 gene polymorphisms and evaluated whether the non-synonymous SNPs are deleterious. We found significantly different genotype, allele and haplotypes frequencies between two chicken breeds, Dekalb White and Ross. Furthermore, we compared and analyzed the promoter structure of the chicken IFITM3 gene with that of several species. We found that birds have a long C-terminal domain and inverted topology of the IFITM3 protein compared to mammals. We also identified fourteen genetic polymorphisms in the chicken IFITM3 gene. L100 M and N125H were predicted as ‘probably damaging’ and L100 M can alter the length of its conserved intracellular loop (CIL). Furthermore, chickens, but not mammals, contain CpG islands (CGIs) in this promoter region.


title: Biologics increase the risk of SARS‐CoV‐2 infection and hospitalization, but not ICU admission and death: Real‐life data from a large cohort during red‐zone declaration

text: During COVID‐19 outbreak there are discordant opinions toward the impact on biologics in psoriatic (PsO) patients. Thus we performed a single‐center case‐control study in Lombardia, the Italian region with the higher number of COVID‐19 confirmed cases. We enrolled 1193 PsO patients treated with biologics and small molecules and we used the entire Lombardia population as controls. Notably, 17 PsO patients COVID‐19 confirmed were quarantined at home and five hospitalized, no PsO patients were admitted to intensive care unit (ICU) or died. With respect to the general population of Lombardy, patients on biologics were at higher risk to test positive for COVID‐19 (odds ratio [OR] 3.43 [95% confidence interval (CI) 2.25‐5.73], P < .0001), to be self‐quarantined at home (OR 9.05 [95% CI 5.61‐14.61], P < .0001) and hospitalized (OR 3.59 [95% CI 1.49‐8.63], P = .0044), however, not increased risk of ICU admission or death were found. PsO patients on biologics should be carefully monitored with telemedicine during COVID‐19 outbreak and early treated at home to limit hospital overwhelm.


title: Telemedicine for preoperative assessment during a COVID-19 pandemic: Recommendations for clinical care

text: Limiting the spread of the disease is key to controlling the COVID-19 pandemic. This includes identifying people who have been exposed to COVID-19, minimizing patient contact, and enforcing strict hygiene measures. To prevent healthcare systems from becoming overburdened, elective and non-urgent medical procedures and treatments have been postponed, and primary health care has broadened to include virtual appointments via telemedicine. Although telemedicine precludes the physical examination of a patient, it allows collection of a range of information prior to a patient's admission, and may therefore be used in preoperative assessment. This new tool can be used to evaluate the severity and progression of the main disease, other comorbidities, and the urgency of the surgical treatment as well as preferencing anesthetic procedures. It can also be used for effective screening and triaging of patients with suspected or established COVID-19, thereby protecting other patients, clinicians and communities alike.


title: Affordable Enteric Virus Detection Techniques Are Needed to Support Changing Paradigms in Water Quality Management

text: In light of water quality monitoring paradigms shifting to a more holistic approach, it is essential that environmental microbiologists embrace new methodological developments in clinical virology to create rapid, laboratory‐free methods for the identification of wastewater pollution. It is widely accepted that routine monitoring of fecal indicator bacteria (FIB) does not adequately reflect human health risks associated with fecal pollution, especially risks posed by viruses. Enteric viruses are typically more resistant to wastewater treatment and persist longer in the environment than FIB. Furthermore, enteric viruses often have extremely low infectious doses. Currently, the incorporation of sanitary surveys, short‐term monitoring of reference pathogens, exploratory quantitative microbial risk assessments, and predictive ecological models is being championed as the preferred approach to water management. In addition to improved virus concentration methods, simple, point‐of‐use tests for enteric viruses and/or improved viral indicators are needed to complement this emerging paradigm and ensure microbial safety worldwide.


I May Not Care About the Tenure Clock, but Enough Already!


Electronic cigarettes and vaping: toxicological awareness is increasing


title: Assessment of the Antiviral Properties of Recombinant Porcine SP-D against Various Influenza A Viruses In Vitro

text: The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D) belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral agent against influenza A viruses (IAVs) in vitro. To determine the range of antiviral activity, thirty IAVs of the subtypes H1N1, H3N2 and H5N1 that originated from birds, pigs and humans were selected and tested for their sensitivity to recombinant SP-D. Using these viruses it was shown by hemagglutination inhibition assay, that recombinant porcine SP-D was more potent than recombinant human SP-D and that especially higher order oligomeric forms of SP-D had the strongest antiviral activity. Porcine SP-D was active against a broad range of IAV strains and neutralized a variety of H1N1 and H3N2 IAVs, including 2009 pandemic H1N1 viruses. Using tissue sections of ferret and human trachea, we demonstrated that recombinant porcine SP-D prevented attachment of human seasonal H1N1 and H3N2 virus to receptors on epithelial cells of the upper respiratory tract. It was concluded that recombinant porcine SP-D holds promise as a novel antiviral agent against influenza and further development and evaluation in vivo seems warranted.


title: Role of bronchoscopy during non invasive ventilation in hypercapnic respiratory failure

text: Abstract Introduction Non invasive positive pressure ventilation (NIPPV) is the first line treatment for hypercapnic acute respiratory failure (ARF) secondary to COPD exacerbation in selected patients. Limited data exist supporting the use of fiberoptic bronchoscopy (FOB) during this clinical setting. The aim of this study is to assess the role of FOB during NIPPV in patients with decompensated COPD acute exacerbation. Methods This study is a randomized prospective case control pilot study carried out on 50 patients - admitted to critical care units at Alexandria University Hospital, Egypt - suffering from hypercapnic ARF secondary to COPD exacerbation with Kelly Matthay Score from 2 to 4. All patients received NIPPV. Patients were divided randomly into 2 equal groups: group I (cases) (25 patients) was subjected to additional intervention of early FOB during the first 6–12h from admission while group II (control) (25 patients) received the conventional treatment and NIPPV only. Outcome parameters measured were changes in ABG data, duration of NIPPV, rate of its success, ICU stay and mortality as well as the safety of FOB and possible complications. Results No significant difference was detected between the 2 groups regarding the baseline characteristics. No serious complications happened from FOB, and Oxygen desaturation happened in 4/25 patients (16%), Tachycardia in 2/25 patients (8%). In group I, 23 patients (92%) were successfully weaned from NIPPV versus 16 patients (64%) in group II (p =0.037). Total duration of NIPPV was 28.52h in group I versus 56.25h in group II (p =0.001). Length of ICU stay was 4.84days in group I versus 8.68days in group II (p =0.001). Only 1 patient died in group I versus 3 patients in group II (p =0.609). Conclusion The early application of FOB during NIPPV in patients with ARF due to COPD exacerbation was shown to be safe. Significant improvement in the outcome of patients who underwent FOB was noticed in terms of improved ABG data, shorter duration of NIPPV, higher percentage of success and shorter ICU stay while no significant difference was detected in mortality.


title: Chapter 42 Group IV Viruses Single-Stranded (+)Sense RNA

text: The Group IV viruses have a positive sense genome. Positive sense RNA can be translated directly into protein, without a DNA intermediate and without creating a complementary RNA strand. To replicate its genome, though, a complementary DNA strand is required. The positive RNA strand serves as a template for an RNA-dependent RNA polymerase, yielding a complementary RNA strand, to form a dimer with the template strand. The double-stranded RNA subsequently serves as the template for a new positive sense genome. The positive strand RNA genome is independently infectious, for most Group IV viruses. This means that in the absence of a capsid, envelope, or enclosed proteins, the RNA molecule, when inserted into a cell, is capable of using host cell machinery to construct additional viruses. There are six subclasses of the Group IV single-stranded positive-sense RNA viruses: Picornaviridae, Togaviridae, Coronaviridae, Hepeviridae, Caliciviridae, Flaviviridae, and Astroviridae. As expected, within each class, viruses share structural similarities; but there are no properties, other than the defining property of a (+)-sense single stranded RNA genome, that extends to all six classes of the Group IV viruses. For example, some classes have envelopes (i.e., Flaviviridae, Togaviridae, Coronaviridae), and others do not (i.e., Caliciviridae, Picornaviridae, Hepeviridae, and Astroviridae). Keywords West nile fever, Yellow fever, Dengue fever, Epidemic polyarthritis, Sindbis fever, Western equine encephalomyelitis, German measles, Hepatitis


title: Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19

text: ABSTRACT: An outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in Wuhan, China, at the end of 2019 has become a global pandemic. Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. We have reviewed previously published studies on SARS and recent studies on SARS-CoV-2 infection, named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), confirming that many other organs besides the lungs are vulnerable to the virus. ACE2 catalyzes angiotensin II conversion to angiotensin-(1–7), and the ACE2/angiotensin-(1–7)/MAS axis counteracts the negative effects of the renin-angiotensin system (RAS), which plays important roles in maintaining the physiological and pathophysiological balance of the body. In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1–7)/MAS after infection may also contribute to multiple organ injury in COVID-19. The SARS-CoV-2 spike glycoprotein, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1–7)/MAS may help attenuate organ injuries. GRAPHICAL ABSTRACT: SARS-CoV-2 enters lung cells via the ACE2 receptor. The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury. [Image: see text]


Telecardiología en tiempos de la pandemia de COVID-19


title: Impact de l’épidémie de Coronavirus-19 sur l’activité chirurgicale en ORL

text: Resume But: Le but de cette étude est d’évaluer l’impact de la pandémie Covid-19 sur l’activité chirurgicale de trois services d’ORL d’Ile-de-France, une région fortement touchée par l'épidémie. Matériel et Méthodes: Le nombre et la nature des interventions chirurgicales a été recueilli au sein de trois services d’ORL franciliens universitaires du 17/03/2020 au 17/04/2020 et du 18/03/2019 au 18/04/2019. Le centre 1 est un service adulte généraliste à orientation otologique. Le centre 2 est un service adulte généraliste à orientation cancérologique. Le 3ème centre est exclusivement pédiatrique. Une analyse comparative de la baisse de l’activité chirurgicale a été effectuée entre 2019 et 2020. Objectif: Analyser la baisse de l’activité chirurgicale Résultats: Les 3 centres ont opéré 540 patients en 2019, versus 89 en 2020, soit une baisse de 84%. Cette diminution est de 89% dans le centre 1, de 61% dans le centre 2, et 95% dans le centre pédiatrique. L’activité otologique a baissé de 97%, endonasale de 91%, cervicale de 54%, plastique de 82%, et trans-orale de 85%. Le nombre de chirurgies pour cancer cutané a diminué (24 contre 9), alors que le nombre total de cervicotomies pour cancer est resté stable (18 contre 22). Le nombre de trachéotomies programmées est passé de 8 à 22. Conclusion: Le nombre d’interventions chirurgicales en ORL a chuté de 84% pendant le premier mois de l’épidémie Covid-19. Cette baisse d’activité est principalement aux dépens de la chirurgie fonctionnelle. L’activité oncologique a pu être préservée. Les structures hospitalières devront absorber un surplus d’activité majeur lors de l’après-crise.


title: Molecular characterization and phylogenetic analysis of porcine epidemic diarrhea virus (PEDV) field isolates in Korea

text: Porcine epidemic diarrhea virus (PEDV) has caused enteric disease with devastating impact since the first identification of PEDV in 1992 in Korea. In this study, we investigated molecular epidemiology, showed genetic diversity, and analyzed phylogenetic relationships of Korean PEDV field isolates with other PEDV reference strains. Genetic analysis of the complete M and ORF3 genes showed that each PEDV group had several unique characteristics, and this indicated that specific groups of PEDVs may be differentiated from the other PEDVs by specific nucleotide differences. Especially, ORF3 gene analysis can be used for discrimination between vaccine and wild-type PEDVs. Sequence and phylogenetic analysis showed that recent, prevalent Korean PEDV field isolates have close relationships to Chinese field strains and differ genetically from European strains and vaccine strains used in Korea. These results raise questions as to whether a new type of PEDV vaccine may be necessary for preventing PEDV infection more effectively in Korea.


title: Histopathology and genetic susceptibility in COVID‐19 pneumonia

text: The clinical features of COVID‐19 range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension. Little is known about the mechanisms behind observed episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects. As in other diseases, the answer to some of these questions may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping, which enable mechanistic insights into the differences in pathogenesis and underlying immunological and tissue regenerative response patterns. We will aim to provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease.


Deubiquitinating Activity of the SARS-CoV Papain-Like Protease


title: Akute Bronchitis

text: Abstract Acute bronchitis is one of the most frequent diagnoses made by family doctors and occurs in circa 5% of adults per year, cumulating during winter and autumn. Diagnosis is made purely clinically. Predominant symptoms are cough, fever, headache and pain in the limbs as well as general malaise. It can be concluded that the underlying cause is usually a viral infection. Antibiotic therapy as a routine treatment is currently not recommended as it shortens the course of the disease only marginally. Treatment is purely symptomatical, with no evidence of the usefulness of mycolytic or antitussive agents. Patients who suffer from obstruction may benefit from beta-mimetics. If symptoms last longer than three weeks, other diseases should be taken into consideration. The main differential diagnosis is pneumonia. It should be taken into account that patients show an increased prevalence for developing chronic bronchitis or bronchial asthma.


title: Economic review

text: Abstract Severe acute respiratory syndrome (SARS) has taken its toll on Japanese companies operating in East Asia, according to a Japan External Trade Organization (JETRO) survey conducted in June.


title: Hazard control by segregation in food factories

text: Factories are segregated primarily for protecting the product from the environment, segregation of raw materials and finished product, segregation of wet and dry materials, provision of mechanical and electrical services and health and safety issues (e.g. boiler rooms, chemical stores, fire hazards, noise limitation). Ready-to-eat (RTE) products factories have begun to further segregate or ‘zone’ production areas for food safety or hygiene reasons. A series of higher hygiene zones have been created to protect the product from microbiological cross-contamination events after it has been heat treated or decontaminated. There has also been the recognition that non-microbiological hazards, particularly allergens, and label declaration issues such as ‘suitable for vegetarians’, ‘organic’, ‘does not contain GM materials’ or ‘Kosher/Halal’ have to be controlled by segregating them from other product ingredients.


Infectious Bronchitis Coronavirus Induces Cell-Cycle Perturbations


title: Chapter 20 The potential of exosomes as theragnostics in various clinical situations

text: Abstract Exosomes are membrane-bound cargo measuring 30–140nm comprised of a lipid bilayer containing various proteins, RNAs, DNAs, and bioactive lipids that can be transferred between cells. They have been shown to be produced and released by many different types of healthy and diseased cells. Exosomes are secreted by all types of cells in culture, and are also found in various body fluids including blood, saliva, urine, and breast milk. Exosomes are essential for healthy physiological as well as pathological processes. In addition to their normal function, exosomes are involved in the development and progression of various diseases, potentiating cellular stress and damage. Pathogens take advantage of exosome release from infected host cells by manipulating host-derived exosomes to evade the immune system responses. Exosomes are involved in other pathological conditions such as neurodegenerative diseases, liver diseases, heart failure, cancer, diabetes, kidney diseases, osteoporosis and atherosclerotic cardiovascular disease. Hence, we can exploit exosomes as biomarkers and vaccines and modify them rationally for therapeutic interventions including tissue engineering. Further studies on exosomes will explore their potential and provide new methodology for effective clinical diagnostics and therapeutic strategies: such uses can be called exosome theragnostics. This chapter reviews the potential theragnostic (diagnostic and therapeutic) application of exosomes in major organ systems in clinical fields.


title: Detection and Cellular Tropism of Porcine Astrovirus Type 3 on Breeding Farms

text: Astroviruses cause disease in a variety of species. Yet, little is known about the epidemiology of a majority of astroviruses including porcine astrovirus type 3 (PoAstV3), which is a putative cause of polioencephalomyelitis in swine. Accordingly, a cross-sectional study was conducted on sow farms with or without reported PoAstV3-associated neurologic disease in growing pigs weaned from those farms. Additionally, a conveniently selected subset of piglets from one farm was selected for gross and histologic evaluation. The distribution of PoAstV3 in the enteric system was evaluated through in situ hybridization. PoAstV3, as detected by RT-qPCR on fecal samples, was frequently detected across sows and piglets (66–90%) on all farms (65–85%). PoAstV3 was detected subsequently at a similar detection frequency (77% vs 85%) on one farm after three months. Viral shedding, as determined by the cycle quantification value, suggests that piglets shed higher quantities of virus than adult swine. No link between gastrointestinal disease and PoAstV3 was found. However, PoAstV3 was detected by in situ in myenteric plexus neurons of piglets elucidating a possible route of spread of the virus from the gastrointestinal tract to the central nervous system. These data suggest PoAstV3 has endemic potential, is shed in the feces at greater quantities by suckling piglets when compared to sows, and infection is widespread on farms in which it is detected.


title: Viral exanthem in COVID‐19, a clinical enigma with biological significance

text: Since December 2019, the COVID‐19 (1) has spread throughout the world at a staggering speed. As of March 30, 2020, the confirmed case number has reached 693,224 globally and the COVID‐19 has claimed 33,106 lives(2). Current researches emphasize on understanding of transmission patterns, severity, clinical features, and risk factors for infection, but the data remain limited.


title: The use of nucleic acid hybridization to detect human coronaviruses

text: We have applied an RNA: RNA hybridization test for the detection of human coronavirus 229E. This test is undergoing further development but already allows a diagnosis of HCV 229E infection within 48 hours.


title: An assessment of World Health Organization criteria for severe acute respiratory syndrome in patients with cancer

text: BACKGROUND: The differential diagnosis of severe acute respiratory syndrome (SARS) in patients with cancer can be challenging. Although diagnostic criteria for SARS have been issued by the World Health Organization (WHO), simple adoption of the established criteria may lead to overdiagnosis in patients with cancer or to an increase in the risk of spreading SARS within cancer hospitals. METHODS: The authors report their experience with the exclusion and quarantine of patients with cancer during the peak of the SARS epidemic in Beijing, China. The patients included 4 males and 7 females with a median age of 66 years (range, 39–73 years). RESULTS: All 11 patients met the WHO diagnostic criteria for probable SARS. Among those 11 patients with probable SARS, only 1 had confirmed SARS; for the other 10 patients, the possibility of SARS infection was ruled out. CONCLUSIONS: Special attention must be paid to patients with cancer who have symptoms similar to those seen in SARS. Although the WHO diagnostic criteria for SARS should be widely accepted, they are not definite or practical in certain populations. Cancer 2004;100:1374–8. © 2004 American Cancer Society.


title: To ease anxiety over coronavirus, leaders prescribe dose of common sense

text: Wash hands thoroughly.


title: The respiratory virome and exacerbations in patients with chronic obstructive pulmonary disease

text: INTRODUCTION: Exacerbations are major contributors to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), and respiratory bacterial and viral infections are an important trigger. However, using conventional diagnostic techniques, a causative agent is not always found. Metagenomic next-generation sequencing (mNGS) allows analysis of the complete virome, but has not yet been applied in COPD exacerbations. OBJECTIVES: To study the respiratory virome in nasopharyngeal samples during COPD exacerbations using mNGS. STUDY DESIGN: 88 nasopharyngeal swabs from 63 patients from the Bergen COPD Exacerbation Study (2006–2010) were analysed by mNGS and in-house qPCR for respiratory viruses. Both DNA and RNA were sequenced simultaneously using an Illumina library preparation protocol with in-house adaptations. RESULTS: By mNGS, 24/88 samples tested positive. Sensitivity and specificity, as compared with PCR, were 96% and 98% for diagnostic targets (23/24 and 1093/1120, respectively). Additional viral pathogens detected by mNGS were herpes simplex virus type 1 and coronavirus OC43. A positive correlation was found between Cq value and mNGS viral normalized species reads (log value) (p = 0.002). Patients with viral pathogens had lower percentages of bacteriophages (p<0.001). No correlation was found between viral reads and clinical markers. CONCLUSIONS: The mNGS protocol used was highly sensitive and specific for semi-quantitative detection of respiratory viruses. Excellent negative predictive value implicates the power of mNGS to exclude any pathogenic respiratory viral infectious cause in one test, with consequences for clinical decision making. Reduced abundance of bacteriophages in COPD patients with viral pathogens implicates skewing of the virome during infection, with potential consequences for the bacterial populations, during infection.


Toward Precision Delivery of Extracorporeal Membrane Oxygenation in Coronavirus Disease 2019 Cardiorespiratory Failure


title: Lessons learned from the COVID‐19 pandemic

text: The Coronavirus Disease 2019 (COVID-19) outbreak raises unique ethical dilemmas because it makes demands on society from all sectors of life, nationally and across the globe. Health professionals must deal with decisions about the allocation of scarce resources that can eventually cause moral distress and may affects one's mental health. Everybody must deal with restrictions on freedom of movement that have shut down whole economies in an attempt to flatten the epidemic curve.


title: Forecasting COVID-19 epidemic in India and high incidence states using SIR and logistic growth models

text: BACKGROUND: Ever since the Coronavirus disease (COVID-19) outbreak emerged in China, there has been several attempts to predict the epidemic across the world with varying degrees of accuracy and reliability. This paper aims to carry out a short-term projection of new cases; forecast the maximum number of active cases for India and select high-incidence states; and evaluate the impact of three weeks lock down period using different models. METHODS: We used Logistic growth curve model for short term prediction; SIR models to forecast the cumulative, maximum number of active cases and peak time; and Time Interrupted Regression model to evaluate the impact of lockdown and other interventions. RESULTS: The predicted cumulative number of cases for India was 58,912 (95% CI: 57,960, 59,853) by May 08, 2020 and the observed number of cases was 59,695. The model predicts a cumulative number of 1,02,974 (95% CI: 1,01,987, 1,03,904) cases by May 22, 2020 As per SIR model, the maximum number of active cases is projected to be 57,449 on May 18, 2020. The time interrupted regression model indicates a decrease of 149 daily new cases after the lock down period which is statistically not significant. CONCLUSION: The Logistic growth curve model predicts accurately the short-term scenario for India and high incidence states. The prediction through SIR model may be used for planning and prepare the health systems. The study also suggests that there is no evidence to conclude that there is a positive impact of lockdown in terms of reduction in new cases.