title: Antibacterial performance of a novel photocatalytic-coated cordierite foam for use in air cleaners

text: Abstract A novel titanium dioxide-coated cordierite foam (TiO2/cordierite foam) was developed for use in air cleaners. By a simple impregnation procedure, TiO2 nanoparticles were immobilized firmly onto the surface of a cordierite foam substrate through high-temperature (500°C) calcination. The strong bactericidal performance of the fabricated foam was evaluated by a newly developed test method for complex three-dimensional through-pore structures. This method could trace 5–6log units of decrease in bacterial cell numbers in an air environment, thus meeting the criteria of both the JIS and ISO standard test methods. With 0.25mWcm−2 of UV-A irradiation for 24h, the bactericidal rate of the TiO2/cordierite foam exceeded 99.9% for five types of airborne or droplet-based infectious pathogens: Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Legionella pneumophila (L. pneumophila), Klebsiella pneumoniae (K. pneumoniae), and methicillin-resistant Staphylococcus aureus (MRSA). The results of repeat testing, where the same sample was used three times, revealed that the bactericidal rate for E. coli was maintained at 99.9% in the second and third use, indicating that the TiO2/cordierite foam possesses a long-term bactericidal action. The TiO2/cordierite foam also exhibited a high photocatalytic degradation capability on gaseous acetaldehyde, which is associated with sick building syndrome, and volatile organic compounds to generate CO2 and H2O. The results demonstrated that TiO2-coated cordierite foam has great potential for use in air-cleaning filters with not only high bactericidal performance to remove pathogens in the air and in droplets, but also strong decontaminating and deodorizing functionality.


title: A Reverse Genetics System for Cypovirus Based on a Bacmid Expressing T7 RNA Polymerase

text: Dendrolimus punctatus cypovirus (DpCPV), belonging to the genus Cypovirus within the family Reoviridae, is considered the most destructive pest of pine forests worldwide. DpCPV has a genome consisting of 10 linear double-stranded RNA segments. To establish a reverse genetics system, we cloned cDNAs encoding the 10 genomic segments of DpCPV into three reverse genetics vectors in which each segment was transcribed under the control of a T7 RNA polymerase promoter and terminator tagged with a hepatitis delta virus ribozyme sequence. We also constructed a vp80-knockout Autographa californica multiple nucleopolyhedrovirus bacmid to express a T7 RNA polymerase codon-optimized for Sf9 cells. Following transfection of Sf9 cells with the three vectors and the bacmid, occlusion bodies (OBs) with the typical morphology of cypovirus polyhedra were observed by optical microscopy. The rescue system was verified by incorporation of a HindIII restriction enzyme site null mutant of the 9th genomic segment. Furthermore, when we co-transfected Sf9 cells with the reverse genetics vectors, the bacmid, and an additional vector bearing an egfp gene flanked with the 5′ and 3′ untranslated regions of the 10th genomic segment, aggregated green fluorescence co-localizing with the OBs was observed. The rescued OBs were able to infect Spodopetra exigua larvae, although their infectivity was significantly lower than that of wild-type DpCPV. This reverse genetics system for DpCPV could be used to explore viral replication and pathogenesis and to facilitate the development of novel bio-insecticides and expression systems for exogenous proteins.


title: A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease

text: The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.


title: Lung Cancer and the COVID-19 pandemic: Recommendations from the Brazilian Thoracic Oncology Group

text: New cases of the novel coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to rise worldwide following the declaration of a pandemic by the World Health Organization (WHO). The current pandemic has completely altered the workflow of health services worldwide. However, even during this critical period, patients with other diseases, like cancer, need to be properly treated. A few reports have shown that mortality due to SARS-CoV-2 is higher in elderly patients and those with other active comorbidities, including cancer. Patients with lung cancer are at risk of pulmonary complications from COVID-19, and as such, the risk/benefit ratio of local and systemic anticancer treatment has to be considered. For each patient, several factors, including age, comorbidities, and immunosuppression, as well as the number of hospital visits for treatment, can influence this risk. The number of cases is rising exponentially in Brazil, and it is important to consider the local characteristics when approaching the pandemic. In this regard, the Brazilian Thoracic Oncology Group has developed recommendations to guide decisions in lung cancer treatment during the SARS-CoV-2 pandemic. Due to the scarcity of relevant data, discussions based on disease stage, evaluation of surgical treatment, radiotherapy techniques, systemic therapy, follow-up, and supportive care were carried out, and specific suggestions issued. All recommendations seek to reduce contagion risk by decreasing the number of medical visits and hospitalization, and in the case of immunosuppression, by adapting treatment schemes when possible. This statement should be adjusted according to the reality of each service, and can be revised as new data become available.


title: Neurosurgery services in Dr. Sardjito General Hospital, Yogyakarta, Indonesia, during COVID-19 pandemic: an experience from a developing country

text: Abstract Background Most articles describing the effect of the COVID-19 pandemic on neurosurgical services have been from developed countries. We attempt to report our experience in carrying out neurosurgical services in Dr. Sardjito General Hospital, Yogyakarta, Indonesia, during the time of the pandemic. Methods To collect information on the effect of the pandemic in Indonesia and Yogyakarta, we gathered data from the Indonesian Ministry of Health online database for the national data and local government records for the local data (including records of Dr. Sardjito General Hospital Division of Neurosurgery). Results Compared to other countries, Indonesia has not been severely hit by the impact of COVID-19. To raise the understanding of the natural history of the pandemic, we grouped the period into four different phases: Phase 1 (there was confirmed cases in Indonesia but no cases found in Yogyakarta), Phase 2 (the first case in Yogyakarta detected), Phase 3 (the time when the cumulative cases surpass its peak), and Phase 4 (the pandemic ends). At the time of this writing, we were still in Phase 2 and in this phase, we experienced a decrease in the number of emergency surgical procedures, from an average of 4 to 2.4 procedures per week. Moreover, the number of elective operations dropped from an average of 12 to 9 procedures per week. Conclusions A pandemic, such as COVID-19, reduces both inpatient and outpatient neurosurgical activities. A comprehensive plan can improve both utilization and safety of the neurosurgical staff.


title: Mammary gland development is delayed in mice deficient for aminopeptidase N

text: Development of the mammary gland requires the coordinated action of proteolytic enzymes during two phases of remodelling. Firstly, new ducts and side-branches thereof need to be established during pregnancy to generate an extensive ductal tree allowing the secretion and transport of milk. A second wave of remodelling occurs during mammary involution after weaning. We have analysed the role of the cell surface protease aminopeptidase N (Anpep, APN, CD13) during these processes using Anpep deficient and Anpep over-expressing mice. We find that APN deficiency significantly delays mammary gland morphogenesis during gestation. The defect is characterised by a reduction in alveolar buds and duct branching at mid-pregnancy. Conversely over-expression of Anpep leads to accelerated ductal development. This indicates that Anpep plays a critical role in the proteolytic remodelling of mammary tissue during adult mammary development.


COVID-19 and the role of 3D printing in medicine


COVID-19 and Wound Care – A Canadian Perspective


title: Prevalence and genetic diversity analysis of human coronaviruses among cross-border children

text: BACKGROUND: More than a decade after the outbreak of human coronaviruses (HCoVs) SARS in Guangdong province and Hong Kong SAR of China in 2002, there is still no reoccurrence, but the evolution and recombination of the coronaviruses in this region are still unknown. Therefore, surveillance on the prevalence and the virus variation of HCoVs circulation in this region is conducted. METHODS: A total of 3298 nasopharyngeal swabs samples were collected from cross-border children (<6 years, crossing border between Southern China and Hong Kong SAR) showing symptoms of respiratory tract infection, such as fever (body temperature > 37.5 °C), from 2014 May to 2015 Dec. Viral nucleic acids were analyzed and sequenced to study the prevalence and genetic diversity of the four human coronaviruses. The statistical significance of the data was evaluated with Fisher chi-square test. RESULTS: 78 (2.37%; 95%CI 1.8-2.8%) out of 3298 nasopharyngeal swabs specimens were found to be positive for OC43 (36;1.09%), HKU1 (34; 1.03%), NL63 (6; 0.18%) and 229E (2;0.01%). None of SARS or MERS was detected. The HCoVs predominant circulating season was in transition of winter to spring, especially January and February and NL63 detected only in summer and fall. Complex population with an abundant genetic diversity of coronaviruses was circulating and they shared homology with the published strains (99-100%). Besides, phylogenetic evolutionary analysis indicated that OC43 coronaviruses were clustered into three clades (B,D,E), HKU1 clustered into two clades(A,B) and NL63 clustered into two clades(A,B). Moreover, several novel mutations including nucleotides substitution and the insertion of spike of the glycoprotein on the viral surface were discovered. CONCLUSIONS: The detection rate and epidemic trend of coronaviruses were stable and no obvious fluctuations were found. The detected coronaviruses shared a conserved gene sequences in S and RdRp. However, mutants of the epidemic strains were detected, suggesting continuous monitoring of the human coronaviruses is in need among cross-border children, who are more likely to get infected and transmit the viruses across the border easily, in addition to the general public.


title: Quantitative Analysis and Prognostic Implication of SARS Coronavirus RNA in the Plasma and Serum of Patients with Severe Acute Respiratory Syndrome

text: Background: The availability of an early diagnostic tool for severe acute respiratory syndrome (SARS) would have major public health implications. We investigated whether the SARS coronavirus (SARS-CoV) can be detected in serum and plasma samples during the early stages of SARS and studied the potential prognostic implications of such an approach. Methods: We developed two real-time quantitative reverse transcription-PCR (RT-PCR) assays, one for the polymerase and the other for the nucleocapsid region of the virus genome, for measuring the concentration of SARS-CoV RNA in serum/plasma samples from SARS patients. Plasma samples were obtained from 12 confirmed SARS patients on the day of hospital admission, as well as on days 7 and 14 after fever onset. Serum samples were also obtained from 23 confirmed SARS patients on the day of hospital admission, 11 of whom subsequently required intensive care. Viral RNA was extracted from the plasma/serum samples. The extracted RNA was subjected to analysis by the RT-PCR assays. Results: The RT-PCR system for the polymerase region detected SARS-CoV RNA in 50% of plasma and 78% of serum samples from SARS patients during the first week of illness. The detection rates for plasma dropped to 25% at day 14 after fever onset. The median serum SARS-CoV concentrations in patients who required and did not require intensive care unit admission during the course of hospitalization were 5800 and 140 copies/mL, respectively (Mann–Whitney test, P <0.005). These data were confirmed by the RT-PCR system for the nucleocapsid region, which showed an even higher detection rate of 87%. The correlation between the results obtained by the two RT-PCR systems was high (Pearson correlation analysis, r = 0.998; P <0.001). Conclusion: Plasma/serum SARS-CoV quantification represents a potentially useful early diagnostic and prognostic tool for SARS.


title: Just the Facts: Protected code blue – Cardiopulmonary resuscitation in the emergency department during the coronavirus disease 2019 pandemic

text: Emergency medical services (EMS) is called for a 65-year-old man with a 1-week history of cough, fever, and mild shortness of breath now reporting chest pain. Vitals on scene were HR 110, BP 135/90, SpO2 88% on room air. EMS arrives at the emergency department (ED). As the patient is moved to a negative pressure room, he becomes unresponsive with no palpable pulse. What next steps should be discussed in order to protect the team and achieve the best possible patient outcome?


Emergency abdominal surgery in COVID‐19 patients: a note of caution from Wuhan


title: 新型冠状病毒肺炎流行期肺部手术的初步建议

text: In December 2019, China diagnosed the first patient with 2019 novel coronavirus disease (COVID-19), and the following development of the epidemic had a huge impact on China and the whole world. For patients with lung occupying lesions, the whole process of diagnosis and treatment can not be carried out as usual due to the epidemic. For thoracic surgeons, the timing of surgical intervention should be very carefully considered. All thoracic surgeons in China should work together to develop the proper procedures for the diagnosis and treatment in this special situation, and continuously update the recommendations based on epidemic changes and further understanding of COVID-19. Here, we only offer some preliminary suggestions based on our own knowledge for further reference and discussion.


title: Do Viruses Exchange Genes across Superkingdoms of Life?

text: Viruses can be classified into archaeoviruses, bacterioviruses, and eukaryoviruses according to the taxonomy of the infected host. The host-constrained perception of viruses implies preference of genetic exchange between viruses and cellular organisms of their host superkingdoms and viral origins from host cells either via escape or reduction. However, viruses frequently establish non-lytic interactions with organisms and endogenize into the genomes of bacterial endosymbionts that reside in eukaryotic cells. Such interactions create opportunities for genetic exchange between viruses and organisms of non-host superkingdoms. Here, we take an atypical approach to revisit virus-cell interactions by first identifying protein fold structures in the proteomes of archaeoviruses, bacterioviruses, and eukaryoviruses and second by tracing their spread in the proteomes of superkingdoms Archaea, Bacteria, and Eukarya. The exercise quantified protein structural homologies between viruses and organisms of their host and non-host superkingdoms and revealed likely candidates for virus-to-cell and cell-to-virus gene transfers. Unexpected lifestyle-driven genetic affiliations between bacterioviruses and Eukarya and eukaryoviruses and Bacteria were also predicted in addition to a large cohort of protein folds that were universally shared by viral and cellular proteomes and virus-specific protein folds not detected in cellular proteomes. These protein folds provide unique insights into viral origins and evolution that are generally difficult to recover with traditional sequence alignment-dependent evolutionary analyses owing to the fast mutation rates of viral gene sequences.


title: Examining the inclusion of patients and their family members in infection prevention and control policies and guidelines across Bangladesh, Indonesia, and South Korea

text: BACKGROUND: Although familial involvement during inpatient care is not uncommon in western countries, the types of caring activities that family members in Asian countries provide are significantly different. These activities may place the family member at risk from a health care–associated infection. This study aimed to examine whether the role of patients’ families has been accounted for in the infection prevention and control (IPC) guidelines and policy, using examples from Bangladesh (low-income country), Indonesia (middle-income country), and South Korea (high-income country). METHODS: The World Health Organization website and Institutional Repository for Information Sharing, Centers for Disease Control and Prevention website, Australian Government Web Archive, Open Grey, Grey Matters, World Bank, and advanced Google search, as well as the Health Department/Ministry of Health websites for each target country and 4 western countries (Australia, Canada, England, and the United States) were searched. Other databases, such as Embase, Medline, CINAHL, Global Health, ProQuest databases, Google scholar, Web of Science, and Scopus were also searched. This was to review the reflection of the cultural influence in IPC policies/guidelines by reviewing those from the global organizations, which are often used as a blueprint for policy development, as well as those from western countries, which hold different cultures in care arrangement. Search was conducted with attention to the key areas: definition and role of carer in the acute health care facility, involvement of patients/family members in IPC activities, patient and family member hand hygiene, and IPC education. RESULTS: Ninety-two articles were identified based on the criteria for the study. Only 6 acknowledged that care is provided to hospitalized patients by their family members, and only 1 recommended that family members receive the same level of training as health care workers on IPC precautions. Other guides recommended the provision of information on IPC measures as means of patient involvement in the IPC program. Recognition of family caregivers or inclusion of them in the IPC strategies was not included in the target countries’ guidelines. CONCLUSIONS: Although health care workers are the primary actors when it comes to providing care in acute health care settings, it is important to expand the IPC guides by considering the role of other caregivers. Policies and guidelines should reflect the cultural influence over healthcare. This is especially true when cultural values strongly influence over healthcare arrangements and the healthcare accommodates these cultural influences in the practice. Further work needs to be undertaken on the level of training/education provided to family members in Bangladesh, Indonesia, and South Korea.


title: Hematopoietic Cell Transplantation Provides an Immune-tolerant Platform for Myoblast Transplantation in Dystrophic Dogs

text: Duchenne Muscular Dystrophy (DMD) is the most common and severe form of muscular dystrophy in humans. The goal of myogenic stem cell transplant therapy for DMD is to increase dystrophin expression in existing muscle fibers and to provide a source of stem cells for future muscle generation. Although syngeneic myogenic stem cell transplants have been successful in mice, allogeneic transplants of myogenic stem cells were ineffective in several human trials. To determine whether allogeneic muscle progenitor cells can be successfully transplanted in an immune-tolerant recipient, we induced immune tolerance in two DMD-affected (cxmd) dogs through hematopoietic cell transplantation (HCT). Injection of freshly isolated muscle-derived cells from the HCT donor into either fully or partially chimeric xmd recipients restored dystrophin expression up to 6.48% of wild-type levels, reduced the number of centrally located nuclei, and improved muscle structure. Dystrophin expression was maintained for at least 24 weeks. Taken together, these data indicate that immune tolerance to donor myoblasts provides an important platform from which to further improve myoblast transplantation, with the goal of restoring dystrophin expression to patients with DMD.


Standhaft in turbulenten Zeiten


title: Public Mental Health Crisis during COVID-19 Pandemic, China

text: The 2019 novel coronavirus disease emerged in China in late 2019–early 2020 and spread rapidly. China has been implementing emergency psychological crisis interventions to reduce the negative psychosocial impact on public mental health, but challenges exist. Public mental health interventions should be formally integrated into public health preparedness and emergency response plans.


title: Stability of Porcine Epidemic Diarrhea Virus on Fomite Materials at Different Temperatures

text: Indirect transmission of porcine epidemic diarrhea virus (PEDV) ensues when susceptible animals contact PEDV-contaminated fomite materials. Although the survival of PEDV under various pHs and temperatures has been studied, virus stability on different fomite surfaces under varying temperature conditions has not been explored. Hence, we evaluated the survival of PEDV on inanimate objects routinely used on swine farms such as styrofoam, rubber, plastic, coveralls, and other equipment. The titer of infectious PEDV at 4 °C decreased by only 1 to 2 log during the first 5 days, and the virus was recoverable for up to 15 days on Styrofoam, aluminum, Tyvek(®) coverall, cloth, and plastic. However, viral titers decreased precipitously when stored at room temperature; no virus was detectable after one day on all materials tested. A more sensitive immunoplaque assay was able to detect virus from Styrofoam, metal, and plastic at 20 days post application, representing a 3-log loss of input virus on fomite materials. Recovery of infectious PEDV from Tyvek(®) coverall and rubber was above detection limit at 20 days. Our findings indicate that the type of fomite material and temperatures impact PEDV stability, which is important in understanding the nuances of indirect transmission and epidemiology of PEDV.


title: Generation, characterization and therapeutic potential of anti-feline TNF-alpha MAbs for feline infectious peritonitis

text: Abstract Feline infectious peritonitis (FIP) is a lethal infectious disease affecting domestic and wild cats. Several reports suggested that TNF-alpha is related to the progression of FIP. Thus, the administration of a feline TNF-alpha-neutralizing antibody to cats with FIP may reduce the disease progression. In this study, we have prepared nine monoclonal antibodies (MAbs) that recognize feline TNF-alpha. All MAbs neutralized recombinant TNF-alpha. The 50% inhibitory concentrations (IC50) of the MAbs for the cytotoxicity of recombinant TNF-alpha were 5–684ng/ml. MAb 2–4 exhibited high neutralizing activity against natural TNF-alpha derived from FIPV-infected macrophages, and was confirmed to inhibit the following feline TNF-alpha-induced conditions in vitro: (i) an increase in the survival rate of neutrophils from cats with FIP, (ii) aminopeptidase N (APN) mRNA expression in macrophages, and (iii) apoptosis of a feline T-lymphocyte cell line.


title: Legume Lectins Inhibit Human Parainfluenza Virus Type 2 Infection by Interfering with the Entr

text: Three lectins with different sugar binding specificities were investigated for anti-viral activity against human parainfluenza virus type 2 (hPIV-2). The lectins, concanavalin A (Con A), lens culinaris agglutinin (LCA) and peanut agglutinin (PNA), inhibited cell fusion and hemadsorption induced by hPIV-2. Virus nucleoprotein (NP) gene synthesis was largely inhibited, but fusion (F) and hemagglutinin-neuraminidase (HN) gene syntheses were not. An indirect immunofluorescence study showed that Con A inhibited virus NP, F and HN protein syntheses, but LCA did not completely inhibit them, and that PNA inhibited only NP protein synthesis. Using a recombinant green fluorescence protein-expressing hPIV-2, without matrix protein (rghPIV-2ΔM), it was found that virus entry into the cells was not completely prevented. The lectins considerably reduced the number of viruses released compared with that of virus infected cells. The lectins bound to cell surface within 10 min, and many aggregates were observed at 30 min. Con A and LCA slightly disrupted actin microfilaments and microtubules, but PNA had almost no effect on them. These results indicated that the inhibitory effects of the lectins were caused mainly by the considerable prevention of virus adsorption to the cells by the lectin binding to their receptors.


title: Structural, functional, and immunological characterization of bovine herpesvirus-1 glycoprotein gl expressed by recombinant baculovirus

text: Abstract The major glycoprotein complex gl of bovine herpesvirus-1 was expressed at high levels (36 μg per 1 × 106 cells) in insect cells using a recombinant baculovirus. The recombinant gl had an apparent molecular weight of 116 kDa and was partially cleaved to yield 63-kDa (glb) and 52-kDa (glc) subunits. This processing step was significantly less efficient in insect cells than the analogous step in mammalian cells, even though the cleavage sites of authentic and recombinant gl were shown to be identical. The oligosaccharide linkages were mostly endoglycosidase-H-sensitive, in contrast to those of authentic gl, which has mostly endoglycosidase-H-resistant linkages and an apparent molecular weight of 130/74/55 kDa. Despite the reduced cleavage and altered glycosylation, the recombinant glycoprotein was transported and expressed on the surface of infected insect cells. These surface molecules were biologically active as demonstrated by their ability to induce cell-cell fusion. Fusion was inhibited bythree monoclonal antibodies specific for antigenic domains I and IV on gl. Domain I maps to the extracellular region of the carboxy terminal fragment glc and domain IV to the very amino terminus of the glb fragment, indicating that domains mapping in two distinct regions of gl function in cell fusion. Monoclonal antibodies specific for eight different epitopes recognized recombinant gl, indicating that the antigenic characteristics of the recombinant and authentic glycoproteins are similar. In addition, the recombinant gl was as immunogenic as the authentic gl, resulting in the induction of gl-specific antibodies in cattle.


title: Respiratory viruses identified in western Canadian beef cattle by metagenomic sequencing and their association with bovine respiratory disease

text: Bovine respiratory disease (BRD) causes considerable economic losses in North America. The pathogenesis involves interactions between bacteria, viruses, environment and management factors. Primary viral infection can increase the risk of secondary fatal bacterial infection. The objective of this study was to use metagenomic sequencing to characterize the respiratory viromes of paired nasal swabs and tracheal washes from western Canadian feedlot cattle, with or without BRD. A total of 116 cattle (116 nasal swabs and 116 tracheal washes) were analysed. The presence of influenza D virus (IDV), bovine rhinitis A virus (BRAV), bovine rhinitis B virus (BRBV), bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) was associated with BRD. Agreement between identification of viruses in nasal swabs and tracheal washes was generally weak, indicating that sampling location may affect detection of infection. This study reported several viruses for the first time in Canada and provides a basis for further studies investigating candidate viruses important to the prevention of BRD.


title: The more involved in lead-zinc mining risk the less frightened: A psychological typhoon eye perspective

text: Abstract In China, the current situation is that people under indirect threat from unprotected lead-zinc mining tends to oppose it, whereas people under direct threat are likely to ‘sail close to the wind’. To understand this puzzle-like phenomenon, we surveyed 220 residents in a lead-zinc mining area located in Fenghuang County of China. We found that: 1) The degree of risk perception of villagers living around the mining site correlated inversely with their degree of involvement in mining risk. We refer to this as the ‘‘involvement’’ version of the psychological typhoon eye effect. 2) Perceived benefit and perceived harm provided a satisfactory explanation for this ‘‘involvement’’ version of the psychological typhoon eye effect. 3) Risk perception was negatively related to support for the relevant policy which we viewed as constituting a sort of voting behavior. The results may have implications for better understanding how benefited individuals respond to environmental health risks.


title: Association of Cardiovascular Disease with Coronavirus Disease 2019 (COVID-19) Severity: A Meta-Analysis

text: Abstract Observational studies have reported an association between underlying cardiovascular diseases (CVD) and worse prognosis in COVID-19 patients, but this still remains unclear. We conducted a meta-analysis of recent studies that reported the association of CVD with worse prognosis and increased mortality in COVID-19 patients. Literature search through PubMed, the Cochrane Library, and Embase was completed by 2 reviewers from November 1, 2019 to April 20, 2020. Inclusion criteria were observational case-control or cohort studies on COVID-19 patients with a history of CVD included, which reported outcomes of COVID-19 infection severity, clearly outlined the definition of “severe disease” and with sample size >10. Data were abstracted independently by 2 authors. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe) and mortality (non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate pooled odds ratio (OR) with 95% confidence interval (95% CI) for each outcome. A total of 18 studies (n= 4,858 patients) were included. Sixteen studies were from China, while 2 were from the United States. Pre-existing CVD was associated with a significantly increased risk of a severe form of COVID-19 (OR= 3.14; 95% CI 2.32-4.24; I2=0%; Q= 8.68, p=0.73) and overall risk of COVID-19 all-cause mortality (OR= 11.08; 95% CI: 2.59-47.32; I2=55%; p=0.11). However, this study did not find a significant association between previous history of CVD and mortality in severe COVID-19 disease (OR=1.72; 95% CI: 0.97-3.06, I2=0%, p=0.46). Pre-existing CVD is associated with worse outcomes among patients with COVID-19. Clinicians and policymakers need to take account of these findings in implementing risk stratification models.


Molecular and diagnostic clinical virology in real time


title: Molecular drug-organiser: Synthesis, characterization and biological evaluation of penicillin V and/or nalidixic acid calixarene-based podands

text: Abstract Two well-known antibiotic heterocycles, the ‘quinolone’ nalidixic acid and the β-lactam penicillin V, active at different levels of the bacterial growth process, have been attached via an ether–ester junction to the p-tert-butylcalix[4]arene lower rim, in alternate position. The resulting hydrophobic molecular drug-organisers were fully characterized, and evaluated over two Gram negative and three Gram positive reference strains, using disk diffusion assays with disks impregnated with solution of title compound in pure DMSO. An interesting activity was observed over Staphylococcus aureus ATCC 25923 with the dissymmetrical podand incorporating one penicillin and one nalidixic ester moieties.


title: Microneedle Mediated Transdermal Delivery of Protein, Peptide and Antibody Based Therapeutics: Current Status and Future Considerations

text: The success of protein, peptide and antibody based therapies is evident - the biopharmaceuticals market is predicted to reach $388 billion by 2024 [1], and more than half of the current top 20 blockbuster drugs are biopharmaceuticals. However, the intrinsic properties of biopharmaceuticals has restricted the routes available for successful drug delivery. While providing 100% bioavailability, the intravenous route is often associated with pain and needle phobia from a patient perspective, which may translate as a reluctance to receive necessary treatment. Several non-invasive strategies have since emerged to overcome these limitations. One such strategy involves the use of microneedles (MNs), which are able to painlessly penetrate the stratum corneum barrier to dramatically increase transdermal drug delivery of numerous drugs. This review reports the wealth of studies that aim to enhance transdermal delivery of biopharmaceutics using MNs. The true potential of MNs as a drug delivery device for biopharmaceuticals will not only rely on acceptance from prescribers, patients and the regulatory authorities, but the ability to upscale MN manufacture in a cost-effective manner and the long term safety of MN application. Thus, the current barriers to clinical translation of MNs, and how these barriers may be overcome are also discussed.


title: The infection control audit: The standardized audit as a tool for change

text: BACKGROUND: Health care workers' compliance with infection control practices and principles is vital in preventing the spread of disease. One tool to assess infection control practice in clinical areas is the infection control audit; however, many institutions do not approach this in a systematic fashion. METHODS: Key features of the infection control audit were identified by the infection control team and developed into a standardized format for review of clinical areas. The audit incorporates a review of the physical layout, protocols and policies, knowledge of basic infection control principles, and workplace practice review. RESULTS: Over the last 13 years, the infection control unit has completed 17 audits involving 1525 employees. Four-hundred-one staff members have filled out questionnaires that assessed their understanding of standard precautions. A total of 257 recommendations have been made, and 95% of these have been implemented. The majority of recommendations address separation of clean and dirty supplies, hand hygiene compliance, hand hygiene signage, proper use of barriers, and environmental cleaning. CONCLUSION: The infection control audit is an opportunity to implement changes and to introduce remedial measures in collaboration with various departments and services. A standardized approach to the audit allows benchmarking of practices across the institution and enhances standards of care.


Is social media really impacting urogynecology?


title: Characterization of the African Swine Fever Virus Decapping Enzyme during Infection

text: African swine fever virus (ASFV) infection is characterized by a progressive decrease in cellular protein synthesis with a concomitant increase in viral protein synthesis, though the mechanism by which the virus achieves this is still unknown. Decrease of cellular mRNA is observed during ASFV infection, suggesting that inhibition of cellular proteins is due to an active mRNA degradation process. ASFV carries a gene (Ba71V D250R/Malawi g5R) that encodes a decapping protein (ASFV-DP) that has a Nudix hydrolase motif and decapping activity in vitro. Here, we show that ASFV-DP was expressed from early times and accumulated throughout the infection with a subcellular localization typical of the endoplasmic reticulum, colocalizing with the cap structure and interacting with the ribosomal protein L23a. ASFV-DP was capable of interaction with poly(A) RNA in cultured cells, primarily mediated by the N-terminal region of the protein. ASFV-DP also interacted with viral and cellular RNAs in the context of infection, and its overexpression in infected cells resulted in decreased levels of both types of transcripts. This study points to ASFV-DP as a viral decapping enzyme involved in both the degradation of cellular mRNA and the regulation of viral transcripts. IMPORTANCE Virulent ASFV strains cause a highly infectious and lethal disease in domestic pigs for which there is no vaccine. Since 2007, an outbreak in the Caucasus region has spread to Russia, jeopardizing the European pig population and making it essential to deepen knowledge about the virus. Here, we demonstrate that ASFV-DP is a novel RNA-binding protein implicated in the regulation of mRNA metabolism during infection, making it a good target for vaccine development.


title: Chinese hesitancy on avian flu

text: The time has come for China to start pulling its weight as a participant in the global response to bird flu — and to learn to collaborate more openly.


title: An enigmatic Maastrichtian small benthic Foraminifera of the Tarbur Formation (Iran, Zagros zone)

text: The Maastrichtian carbonates of the Tarbur Formation from the Zagros zone (SW Iran) are very rich in larger Foraminifera. Additionally, smaller benthic Foraminifera occur as well, one of them presented here as Covidaria pinnata n. gen., n. sp. It occurs abundantly at the Mandegan section within two levels corresponding to the lower photic zone. Based on the existence of a central pile along with an umbilical plate, and the lacks of true interiomarginal apertures, likely represented by a perforate surface, the suprageneric placing of Covidaria n. gen. remains controversial. The ultimate aperture is represented by a central elongate double-bifid slot that arguably lies on a finely perforated and heavy feathered apertural face. Based on the reduced dimensions and lack of dimorphism the new taxon could be considered an epifaunal or shallow-infaunal r-strategist.


title: Homeless Persons with Mental Illness and COVID Pandemic: Collective efforts from India

text: COVID-19 pandemic had made an unprecedented impact on worldwide public psychiatry and society. India has entered into a total lockdown by invoking the special provision of Epidemic Diseases Act of 1897 and Disaster Management Act, 2015. The complete lockdown policy has a direct and indirect impact on Homeless Persons with Mental Illness (HPMI) concerning shelter, basic needs and access to health care and spreads and acquire COVID infection. In this manuscript, we highlight the collective efforts undertaken by both the Government and Civil Society in providing care and prevention COVID to HPMI during the lockdown in India.


title: Human Coronavirus NL63 Open Reading Frame 3 encodes a virion-incorporated N-glycosylated membrane protein

text: BACKGROUND: Human pathogenic coronavirus NL63 (hCoV-NL63) is a group 1 (alpha) coronavirus commonly associated with respiratory tract infections. In addition to known non-structural and structural proteins all coronaviruses have one or more accessory proteins whose functions are mostly unknown. Our study focuses on hCoV-NL63 open reading frame 3 (ORF 3) which is a highly conserved accessory protein among coronaviruses. RESULTS: In-silico analysis of the 225 amino acid sequence of hCoV-NL63 ORF 3 predicted a triple membrane-spanning protein. Expression in infected CaCo-2 and LLC-MK2 cells was confirmed by immunofluorescence and Western blot analysis. The protein was detected within the endoplasmatic reticulum/Golgi intermediate compartment (ERGIC) where coronavirus assembly and budding takes place. Subcellular localization studies using recombinant ORF 3 protein transfected in Huh-7 cells revealed occurrence in ERGIC, Golgi- and lysosomal compartments. By fluorescence microscopy of differently tagged envelope (E), membrane (M) and nucleocapsid (N) proteins it was shown that ORF 3 protein colocalizes extensively with E and M within the ERGIC. Using N-terminally FLAG-tagged ORF 3 protein and an antiserum specific to the C-terminus we verified the proposed topology of an extracellular N-terminus and a cytosolic C-terminus. By in-vitro translation analysis and subsequent endoglycosidase H digestion we showed that ORF 3 protein is N-glycosylated at the N-terminus. Analysis of purified viral particles revealed that ORF 3 protein is incorporated into virions and is therefore an additional structural protein. CONCLUSIONS: This study is the first extensive expression analysis of a group 1 hCoV-ORF 3 protein. We give evidence that ORF 3 protein is a structural N-glycosylated and virion-incorporated protein.


title: Patterns of between-farm contacts via professionals in Sweden

text: BACKGROUND: Infectious diseases of livestock have negative consequences for animal production as well as animal health and welfare and can be transmitted between farms via direct (live animal movements) as well as indirect (via physical vectors such as, people, transport vehicles and fomites) contacts. The objective of the study was to examine the travel patterns of professionals visiting Swedish farms (veterinarians, milk tanker drivers, artificial inseminators, maintenance technicians and livestock hauliers). This was done by obtaining records of the farms visited by a sample of professionals in the above categories in one week in January, one week in April, one week in July and one week in October in the Swedish counties Västerbotten, Södermanland, Västergötland and Skåne. RESULTS: There were twelve participating organisations, and data was provided for one to three individuals/vehicles/veterinary practices per professional category and per geographic region (except for dairy service technicians and livestock hauliers who did not provide data from all regions). There was a trend towards larger areas covered and smaller number of farms visited per week in the north, but exceptions occurred and there were regional variations. Generally, the greatest areas were travelled by milk tankers and livestock hauliers, and the profession travelling over the smallest areas tended to be the veterinarians. Milk tankers visited most farms per week, one milk tanker could visit between 23 and 90 farms per week and travel over areas between 717 km(2) and 23,512 km(2) per week. CONCLUSIONS: Valuable insight into the travel patterns of Swedish professionals has emerged although the implications of the study largely concern highly infectious diseases. Movement of live animals pose the greatest risk for the spread of infectious animal diseases; however indirect contacts are important for many diseases. The results of this study indicate that in Sweden a highly contagious disease might spread over a large area in the time span of one incubation period, which ought to be kept in mind in case of an outbreak and in outbreak investigations. The difficulties in contacting some professionals visiting farms could be a problem in an outbreak situation.


title: Biosafety threats of the rapidly established labs for SARS-CoV-2 tests in China

text: To increase the capacity of identifying coronavirus disease 2019 (COVID-19) infection, many Biosafety Level 2 (BSL-2) labs have been established in a short period of time for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid tests all over the world. However, their biosafety has not been evaluated, which could have been the first gateway to SARS-CoV-2 transmission. During 9-11 March, 2020, the first comprehensive evaluation of the biosafety in all 89 labs qualified for conducting SARS-CoV-2 tests in Sichuan Province of China was conducted. The degree of compliance with 39 criteria in five categories was evaluated: biosafety requirements for lab activities (14 criteria), sample transfer, acceptance and management (6 criteria), waste management (9 criteria), personnel training and protection (4 criteria), and lab environmental disinfection, emergency plans and accident handling (6 criteria). Our results revealed that, although an overall median compliance rate of 94.6% for 39 criteria, only four of 89 labs met all of them. Criteria in personnel training and protection have been most satisfactorily met, followed by lab environmental disinfection, emergency plans and accident handling. The most severe risk was the lack of automatic doors at the main entrance or in core operation areas, especially among labs in CDC and hospitals. This risk, together with failure for keeping pressure in the core operation areas 25±5 Pa (mainly among labs in the third-party testing agencies), may cause accidental exposure to biological agents from lab activities. Other severe risk included failure for standard labeling of SARS-CoV-2 wastes and lacking regular monitoring of sterilization effects. Our findings would provide experiences and lessons for strengthening lab biosafety in other Chinese provinces, and also serve as an important reference for many other countries where such labs are being or will be quickly built for fighting the COVID-19.


title: Maximum Likelihood Estimation of the Negative Binomial Dispersion Parameter for Highly Overdispersed Data, with Applications to Infectious Diseases

text: BACKGROUND: The negative binomial distribution is used commonly throughout biology as a model for overdispersed count data, with attention focused on the negative binomial dispersion parameter, k. A substantial literature exists on the estimation of k, but most attention has focused on datasets that are not highly overdispersed (i.e., those with k≥1), and the accuracy of confidence intervals estimated for k is typically not explored. METHODOLOGY: This article presents a simulation study exploring the bias, precision, and confidence interval coverage of maximum-likelihood estimates of k from highly overdispersed distributions. In addition to exploring small-sample bias on negative binomial estimates, the study addresses estimation from datasets influenced by two types of event under-counting, and from disease transmission data subject to selection bias for successful outbreaks. CONCLUSIONS: Results show that maximum likelihood estimates of k can be biased upward by small sample size or under-reporting of zero-class events, but are not biased downward by any of the factors considered. Confidence intervals estimated from the asymptotic sampling variance tend to exhibit coverage below the nominal level, with overestimates of k comprising the great majority of coverage errors. Estimation from outbreak datasets does not increase the bias of k estimates, but can add significant upward bias to estimates of the mean. Because k varies inversely with the degree of overdispersion, these findings show that overestimation of the degree of overdispersion is very rare for these datasets.


title: The efficient Lamarckian spread of life in the cosmos

text: In this Chapter we discuss the various mechanisms that are available for the possible transfer of cosmic microbial living systems from one cosmic habitat to another. With the 100 or so habitable planets that are now known to exist in our galaxy alone transfers of cometary dust carrying life including fragments of icy planetoids/asteroids would be expected to occur on a routine basis. It is thus easy to view the galaxy as a single connected “biosphere” of which our planet Earth is a minor component. The Hoyle–Wickramasinghe Panspermia paradigm provides a cogent biological rationale for the actual widespread existence of Lamarckian modes of inheritance in terrestrial systems (which we review here). Thus the Panspermia paradigm provides the raison d'etre for Lamarckian Inheritance. Under a terrestrially confined neoDarwinian viewpoint such an association may have been thought spurious in the past. Our aim here is to outline the main evidence for rapid terrestrial-based Lamarckian-based evolutionary hypermutation processes dependent on reverse transcription-coupled mechanisms among others. Such rapid adaptation mechanisms would be consistent with the effective cosmic spread of living systems. For example, a viable, or cryo-preserved, living system traveling through space in a protective matrix will of necessity need to adapt rapidly and proliferate on landing in a new cosmic niche. Lamarckian mechanisms thus come to the fore and supersede the slow (blind and random) genetic processes expected under neoDarwinian Earth centred theories.


title: Association of the insulin resistance marker TyG index with the severity and mortality of COVID-19

text: BACKGROUND: The triglyceride and glucose index (TyG) has been proposed as a marker of insulin resistance. This study aims to evaluate the association of the TyG index with the severity and mortality of coronavirus disease 2019 (COVID-19). METHODS: The study included a cohort of 151 patients with COVID-19 admitted in a tertiary teaching hospital in Wuhan. Regression models were used to investigate the association between TyG with severity and mortality of COVID-19. RESULTS: In this cohort, 39 (25.8%) patients had diabetes, 62 (41.1%) patients were severe cases, while 33 (22.0%) patients died in hospital. The TyG index levels were significantly higher in the severe cases and death group (mild vs. severe 8.7 ± 0.6 vs. 9.2 ± 0.6, P < 0.001; survivor vs. deceased 8.8 ± 0.6 vs. 9.3 ± 0.7, P < 0.001), respectively. The TyG index was significantly associated with an increased risk of severe case and mortality, after controlling for potential confounders (OR for severe case, 2.9, 95% CI 1.2–6.3, P = 0.007; OR for mortality, 2.9, 95% CI 1.2–6.7, P = 0.016). The associations were not statistically significant for further adjustment of inflammatory factors. CONCLUSION: TyG index was closely associated with the severity and morbidity in COVID-19 patients, thus it may be a valuable marker for identifying poor outcome of COVID-19.


title: In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

text: BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first broke out in Wuhan (China) and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection. METHODS: The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells. Physiologically-based pharmacokinetic models (PBPK) were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen whilst considering the drug’s safety profile. RESULTS: Hydroxychloroquine (EC(50)=0.72 μM) was found to be more potent than chloroquine (EC(50)=5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance. CONCLUSIONS: Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.


title: Viral interference with antibody and complement

text: Abstract Viruses have evolved strategies to evade immunity mediated by antibody and complement. Herpesviruses and coronaviruses encode IgG Fc binding proteins that inhibit IgG activity, enabling the virus or infected cell to escape antibody attack. Herpesviruses, vaccinia virus and HIV-1 have the capacity to interfere with complement, either by incorporation of cellular complement regulatory proteins into the virion envelope or cell membrane, or by expression of viral molecules that mimic functions of complement regulatory proteins. The structure and biological activities of herpes simplex virus type 1 (HSV-1) glycoproteins gE, gI and gC are described. These glycoproteins protect HSV from immune attack; HSV-1 gE/gI form a complex that binds the Fc domain of IgG while gC is a C3b binding complement regulatory protein, providing a survival advantage to the virusin vitroandin vivoby inhibiting immune functions.


title: Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging

text: The specific packaging of the hepatitis C virus (HCV) genome is hypothesised to be driven by Core-RNA interactions. To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We postulated that interactions of these motifs, as well as sub-motifs which were present in HCV genomes at statistically significant levels, with the Core protein may drive virion assembly. We mutated 8 of these predicted motifs within the HCV infectious molecular clone JFH-1, thereby producing a range of mutant viruses predicted to possess altered RNA secondary structures. RNA replication and viral titre were unaltered in viruses possessing only one mutated structure. However, infectivity titres were decreased in viruses possessing a higher number of mutated regions. This work thus identified multiple novel RNA motifs which appear to contribute to genome packaging. We suggest that these structures act as cooperative packaging signals to drive specific RNA encapsidation during HCV assembly.


title: Glial cells suppress post-encephalitic CD8(+) T lymphocytes through PD-L1

text: Engagement of the programmed death (PD)-1 receptor on activated cells by its ligand (PD-L1) is a mechanism for suppression of activated T-lymphocytes. Microglia, the resident inflammatory cells of the brain, are important for pathogen detection and initiation of innate immunity, however, a novel role for these cells as immune regulators has also emerged. PD-L1 on microglia has been shown to negatively regulate T-cell activation in models of multiple sclerosis and acute viral encephalitis. In this study, we investigated the role of glial cell PD-L1 in controlling encephalitogenic CD8(+) T-lymphocytes, which infiltrate the brain to manage viral infection, but remain to produce chronic neuroinflammation. Using a model of chronic neuroinflammation following murine cytomegalovirus (MCMV)-induced encephalitis, we found that CD8(+) T-cells persisting within the brain expressed PD-1. Conversely, activated microglia expressed PD-L1. In vitro, primary murine microglia, which express low basal levels of PD-L1, upregulated the co-inhibitory ligand upon IFN-γ-treatment. Blockade of the PD-1: PD-L1 pathway in microglial: CD8(+) T-cell co-cultures increased T-cell IFN-γ and interleukin (IL)-2 production. We observed a similar phenomenon following blockade of this co-inhibitory pathway in astrocyte: CD8(+) T-cell co-cultures. Using ex vivo cultures of brain leukocytes, including microglia and CD8(+) T-cells, obtained from mice with MCMV-induced chronic neuroinflammation, we found that neutralization of either PD-1 or PD-L1 increased IFN-γ production from virus-specific CD8(+) T-cells stimulated with MCMV IE1(168-176) peptide. These data demonstrate that microglia and astrocytes control antiviral T-cell responses and suggest a therapeutic potential of PD1: PD-L1 modulation to manage the deleterious consequences of uncontrolled neuroinflammation.


title: Journal of Clinical Monitoring and Computing 2018–2019 end of year summary: respiration

text: This paper reviews 28 papers or commentaries published in Journal of Clinical Monitoring and Computing in 2018 and 2019, within the field of respiration. Papers were published covering endotracheal tube cuff pressure monitoring, ventilation and respiratory rate monitoring, lung mechanics monitoring, gas exchange monitoring, CO(2) monitoring, lung imaging, and technologies and strategies for ventilation management.


title: Role for Maternal Asthma in Severe Human Metapneumovirus Lung Disease Susceptibility in Children

text: BACKGROUND: Severity of human metapneumovirus (hMPV) lower respiratory illness (LRTI) is considered similar to that observed for respiratory syncytial virus (RSV). However, differences in severity between these pathogens have been noted, suggesting the degree of illness may vary in different populations. Moreover, a potential association between hMPV and asthma also suggests that hMPV may preferentially affect asthmatic subjects. METHODS: In a population-based surveillance study in children aged <2 years admitted for severe LRTI in Argentina, nasopharyngeal aspirates were tested by RT-PCR for hMPV, RSV, influenza A, and human rhinovirus. RESULTS: Of 3947 children, 383 (10%) were infected with hMPV. The hospitalization rate for hMPV LRTI was 2.26 per 1000 children (95% confidence interval [CI], 2.04–2.49). Thirty-nine (10.2%) patients infected with hMPV experienced life-threatening disease (LTD; 0.23 per 1000 children; 95% CI, .16–.31/1000), and 2 died (mortality rate 0.024 per 1000; 95% CI, .003–.086). In hMPV-infected children birth to an asthmatic mother was an increased risk for LTD (odds ratio, 4.72; 95% CI, 1.39–16.01). We observed a specific interaction between maternal asthma and hMPV infection affecting risk for LTD. CONCLUSIONS: Maternal asthma increases the risk for LTD in children <2 years old hospitalized for severe hMPV LRTI.


title: An intelligent device for diagnosing avian diseases: Newcastle, infectious bronchitis, avian influenza

text: Abstract In commercial poultry production there are a number of diseases which are of particular importance due to the heavy economic losses that can arise if a flock becomes infected. The development of an automated and rapid disease detection system would therefore be of considerable benefit to both production and animal welfare. This study represents an intelligence device for diagnosing avian diseases by using Data-mining methods and Dempster-Shafer evidence theory (D-S). 14-day-old chickens were divided into four groups. Each group was deliberately infected with a disease: Newcastle Disease (ND), Bronchitis Virus (BV), Avian Influenenza (AI), and the last group was considered as control samples. Fast Fourier Transform (FFT) and Discrete Wavelet Transform (DWT) were used to process the chicken’s sound signals in frequency and time-frequency domains, respectively. In order to achieve information, 25 statistical features from frequency domains, and 75 statistical features from time-frequency domains were extracted. During dimensionality reduction stage, the best features of the sound signals were selected, using improved distance evaluation (IDE) method. The chicken’s sound signals were analyzed in two consecutive days after virus infection. Support vector machine (SVM) was used as the classifier in this study. The first classification was done with SVM and based on sound features in frequency and time-frequency domains with accuracy of 41.35 and 83.33%, respectively. The accuracy of the method based on D-S infusion of sound data reached 91.15%. The developed model based on achievement result could diagnose Newcastle Disease, Bronchitis Virus and Avian Influenza from sound signals.


title: Unconventional Use of LC3 by Coronaviruses through the Alleged Subversion of the ERAD Tuning Pathway

text: Pathogens of bacterial and viral origin hijack pathways operating in eukaryotic cells in many ways in order to gain access into the host, to establish themselves and to eventually produce their progeny. The detailed molecular characterization of the subversion mechanisms devised by pathogens to infect host cells is crucial to generate targets for therapeutic intervention. Here we review recent data indicating that coronaviruses probably co-opt membranous carriers derived from the endoplasmic reticulum, which contain proteins that regulate disposal of misfolded polypeptides, for their replication. In addition, we also present models describing potential mechanisms that coronaviruses could employ for this hijacking.


title: Potential use of Turmeric in COVID‐19

text: Turmeric (Curcuma longa L.) is an integral part of Asian culture which has been used in traditional medicine systems like Ayurveda, Unani and Siddha owing to its wide array of medicinal properties since centuries. Curcumin, the predominant curcumoid in turmeric, influences multiple signaling pathways and been found to possess anti‐inflammatory, anti‐oxidant, antimicrobial, hypoglycemic, wound healing, chemopreventive, chemosensitising and radiosensitising properties.(1) To enhance the bioavailability of curcumin, newer technologies such as adjuvant, nanoparticles, liposomes, micelles and phospholipid complexes are evaluated in the process of drug development. It is documented to be most efficacious in high doses at around 6‐7 gm per day which is well tolerated orally.(1) It has been widely used as a common household remedy for cough, sore throat and respiratory ailments in Asia.


title: Microbiologic Characteristics, Serologic Responses, and Clinical Manifestations in Severe Acute Respiratory Syndrome, Taiwan

text: The genome of one Taiwanese severe acute respiratory syndrome-associated coronavirus (SARS-CoV) strain (TW1) was 29,729 nt in length. Viral RNA may persist for some time in patients who seroconvert, and some patients may lack an antibody response (immunoglobulin G) to SARS-CoV >21 days after illness onset. An upsurge of antibody response was associated with the aggravation of respiratory failure.


title: A RT-PCR Assay for the Detection of Coronaviruses from Four Genera

text: Abstract Background During the past two decades, three novel coronaviruses (CoVs) have emerged to cause international human epidemics with severe morbidity. CoVs have also emerged to cause severe epidemics in animals. A better understanding of the natural hosts and genetic diversity of CoVs are needed to help mitigate these threats. Objective To design and evaluate a molecular diagnostic tool for detection and identification of all currently recognized and potentially future emergent CoVs from the Orthocoronavirinae subfamily. Study design and Results We designed a semi-nested, reverse transcription RT-PCR assay based upon 38 published genome sequences of human and animal CoVs. We evaluated this assay with 14 human and animal CoVs and 11 other non-CoV respiratory viruses. Through sequencing the assay's target amplicon, the assay correctly identified each of the CoVs; no cross-reactivity with the 11 common respiratory viruses was observed. The limits of detection ranged from 4 to 4 × 102 copies/reaction, depending on the CoV species tested. To assess the assay's clinical performance, we tested a large panel of previously studied specimens: 192 human respiratory specimens from pneumonia patients, 5 clinical specimens from COVID-19 patients, 81 poultry oral secretion specimens, 109 pig slurry specimens, and 31 aerosol samples from a live bird market. The amplicons of all RT-PCR-positive samples were confirmed by Sanger sequencing. Our assay performed well with all tested specimens across all sample types. Conclusions This assay can be used for detection and identification of all previously recognized CoVs, including SARS-CoV-2, and potentially any emergent CoVs in the Orthocoronavirinae subfamily.


title: Thoracic computerized tomographic (CT) findings in 2009 influenza A (H1N1) virus infection in Isfahan, Iran

text: BACKGROUND: Pandemic 2009 H1N1 influenza A virus arrived at Isfahan in August 2009. The virus is still circulating in the world. The abnormal thoracic computerized tomographic (CT) scan findings vary widely among the studies of 2009 H1N1 influenza. We evaluated the thoracic CT findings in patients with 2009 H1N1 virus infection to describe findings compared to previously reported findings, and to suggest patterns that may be suggestive for 2009 influenza A (H1N1) in an appropriate clinical setting. METHODS: Retrospectively, the archive of all patients with a diagnosis of 2009 H1N1 influenza A were reviewed, in Al-Zahra Hospital in Isfahan, central Iran, between September 23(rd) 2009 to February 20(th) 2010. Out of 216 patients with confirmed 2009 influenza A (H1N1) virus, 26 cases with abnormal CT were enrolled in the study. Radiologic findings were characterized by the type and pattern of opacities and zonal distribution. RESULTS: Patchy infiltration (34.6%), lobar consolidation (30.8%), and interstitial infiltration (26.9%) with airbronchogram (38.5%) were the predominant findings in our patients. Bilateral distribution was seen in 80.8% of the patients. Only one patient (3.8%) showed ground-glass opacity, predominant radiographic finding in the previous reports and severe acute respiratory syndrome (SARS). CONCLUSIONS: The most common thoracic CT findings in pandemic H1N1 were patchy infiltration, lobar consolidation, and interstitial infiltration with airbronchogram and bilateral distribution. While these findings can be associated with other infections; they may be suggestive to 2009 influenza A (H1N1) in the appropriate clinical setting. Various radiographic patterns can be seen in thoracic CT scans of the influenza patients. Imaging findings are nonspecific.


title: Molecular and antigenic characteristics of Massachusetts genotype infectious bronchitis coronavirus in China

text: Abstract In this study, 418 IBVs were isolated in samples from 1717 chicken flocks. Twenty-nine of the isolates were classified as the Massachusetts genotype. These 29 isolates, as well as two previously isolated Massachusetts genotype IBV strains, were studied further. Of the 31 strains, 24 were H120-like and two were M41-like isolates as determined by complete genomic sequence analysis, indicating that most of the IBV isolates were likely the reisolated vaccine virus. The remaining five IBV isolates, ck/CH/LHB/111172, ck/CH/LSD/111219, ck/CH/LHB/130598, ck/CH/LDL/110931, and ck/CH/LHB/130573, were shown to have originated from natural recombination events between an H120-like vaccine strain and other types of viruses. The virus cross-neutralization test found that the antigenicity of ck/CH/LHB/111172, ck/CH/LSD/111219, and ck/CH/LHB/130598 was similar to that of H120. Vaccination with the H120 vaccine offered complete protection against challenge with these isolates. However, isolates ck/CH/LDL/110931 and ck/CH/LHB/130573 were serotypically different from their parental viruses and from other serotypes in this study. Furthermore, vaccination with the H120 vaccine did not provide protection against challenge with these two isolates. The results of this study demonstrated that recombination is the mechanism that is responsible for the emergence of new serotype strains, and it has the ability to alter virus serotypes. Therefore, IBV surveillance of chicken flocks vaccinated with IBV live vaccines, as well as the consideration of new strategies to effectively control IBV infection using inactivated or/and genetically engineered vaccines, is of great importance.


title: Using Drugs to Keep Learning Active During a Pandemic

text: The rapid switch to delivering material via web-conferencing modalities such as Zoom© has been an adjustment for both students and faculty, particularly for schools with a heavy active-learning-based curriculum At the Dell Medical School (DMS), we employ a flipped-classroom approach to deliver the first-year basic sciences [1, 2] In our flipped-classroom sessions at DMS, students view videos, listen to podcasts, or engage with tailored pre-reading prior to coming to the class where they work in small group activities (approx-imately 5 students per group) Maintaining small group active learning during the COVID-19 pandemic using distance learning is a challenge fraught with barriers [3] One promising strategy that I used to deliver active, flipped-classroom pharmacology sessions entails using the breakout room feature of Zoom© This simple act of splitting students up into smaller groups appears to come close to approximating small group interaction typically leveraged in the classroom For example, Zoom© breakout rooms were used in tandem with a flipped-classroom activity to cover the clinical pharmacology of drugs for diabetes, including clinically relevant adverse effects and pharmacokinetics In this session, students were provided a blank table with missing variables and information on the common and serious adverse effects, lipid changes, ability to cause weight gain or weight loss, and route of administration for representative agents from each of the major classes of drugs used to treat diabetes (Fig 1) Prior to the session, students were asked to watch a brief video on the pharmacology of the drugs for diabetes with a focus on the adverse effects and pharmacokinetics (mecha-nism of action, while revisited in the video, was covered in the first half of the year) The following day, a set of instructions and the table were provided "just-in-time" at the start of the 30-min-long session Briefly, students were randomly assigned to one of eight groups (corresponding to a single diabetes drug row on the table in Fig 1) The students were instructed to work together for 15 min to assemble the information to populate the table for their groups' drug and select a "spokesperson" who would present their findings to the overall class upon reconvening Students were encouraged to "recall" the information they learned from the pre-class video Thus, there are loose, but deliberately incorporated, elements of both peer-instruction and retrieval practice built into the exercise [4] As the students worked in their groups, I moved back and forth among the groups as an observer Following small group discussions in the breakout rooms, students were brought back to the main room where their spokesperson reported out their findings The correct answers were then sequentially revealed to the class following each groups' online presentation A total of 40 students (out of 50 students) in our M1 class of 2023 were in attendance for this session Therefore, despite organizing and deploying this emergency remote teaching session at a moment's notice at the beginning of the pandemic lockdown, it came close to replicating the flipped-classroom environment we typically use in-person with similar numbers of students and levels of engagement Pedagogically, one of the goals of this session is for students to "retrieve" information they learned the night before from the video for discussion with their group, thereby strengthening their memory retention of the information Additionally, inclusion of a column on "lipid changes" induced by the different agents, which can vary depending on the source or reference you consult, proved to be a key


Performing abdominal surgery during the COVID‐19 epidemic in Wuhan, China: a single‐centred, retrospective, observational study


title: Telehealth Transformation: COVID-19 and the rise of Virtual Care

text: The novel coronavirus disease-19 (COVID-19) pandemic has altered our economy, society and healthcare system. While this crisis has presented the US healthcare delivery system with unprecedented challenges, the pandemic has catalyzed rapid adoption of telehealth or the entire spectrum of activities used to deliver care at a distance. Using examples reported by US healthcare organizations including ours, we describe the role telehealth has played in transforming healthcare delivery during the three phases of the US COVID-19 pandemic: 1) Stay-at-Home Outpatient Care; 2) Initial COVID-19 Hospital Surge, and 3) Post-Pandemic Recovery. Within each of these three phases, we examine how people, process and technology work together to support a successful telehealth transformation. Whether healthcare enterprises are ready or not, the new reality is that virtual care has arrived.


title: Transcriptomic Profiling in Childhood H1N1/09 Influenza Reveals Reduced Expression of Protein Synthesis Genes

text: We compared the blood RNA transcriptome of children hospitalized with influenza A H1N1/09, respiratory syncytial virus (RSV) or bacterial infection, and healthy controls. Compared to controls, H1N1/09 patients showed increased expression of inflammatory pathway genes and reduced expression of adaptive immune pathway genes. This was validated on an independent cohort. The most significant function distinguishing H1N1/09 patients from controls was protein synthesis, with reduced gene expression. Reduced expression of protein synthesis genes also characterized the H1N1/09 expression profile compared to children with RSV and bacterial infection, suggesting that this is a key component of the pathophysiological response in children hospitalized with H1N1/09 infection.


title: Model Parameters and Outbreak Control for SARS

text: Control of the 2002–2003 severe acute respiratory syndrome (SARS) outbreak was based on rapid diagnosis coupled with effective patient isolation. We used uncertainty and sensitivity analysis of the basic reproductive number R(0) to assess the role that model parameters play in outbreak control. The transmission rate and isolation effectiveness have the largest fractional effect on R(0). We estimated the distribution of the reproductive number R(0) under perfect isolation conditions. The distribution lies in the interquartile range 0.19–1.08, with a median of 0.49. Even though the median of R(0) is <1, we found that 25% of our R(0) distribution lies at R(0) > 1, even with perfect isolation. This implies the need to simultaneously apply more than one method of control.


Applying to Radiation Oncology Amid a Pandemic


title: HATRIC: a study of Pelargonium sidoides root extract EPs®7630 (Kaloba®) for the treatment of acute cough due to lower respiratory tract infection in adults—study protocol for a double blind, placebo-controlled randomised feasibility trial

text: BACKGROUND: Acute lower respiratory tract infection is a common acute infection managed in primary care. The current dominant management strategy in the UK is antibiotics, despite widespread publicity regarding antimicrobial resistance and evidence that the small benefits of antibiotics do not outweigh the harms. There is a need to address the rising problem of antibiotic resistance by providing credible alternative strategies, which reduce symptom burden. There is sufficient evidence to recommend the use of Pelargonium sidoides root extract in order to warrant undertaking an independent clinical trial. We propose a feasibility study to demonstrate our ability to recruit and retain patients and conduct a placebo-controlled trial of Pelargonium sidoides extract EPs®7630 in lower respiratory tract infection where pneumonia is not suspected. Both the tablet and liquid formulations will be included. METHODS: The HATRIC trial is a double-blind randomised placebo-controlled feasibility study aiming to determine the potential to conduct a fully powered trial of Pelargonium sidoides root extract as an alternative to the inappropriate use of antibiotics for acute bronchitis in UK primary care. Primary care sites will be equally randomised to one of two formulation groups (tablet or liquid preparation). Additionally, within each site, patients will be evenly randomised to active or placebo treatment. Antibiotic consumption will be monitored during the trial, but the use of a delayed prescription strategy is encouraged. The target sample size for this study is 160 patients overall or 40 per arm, recruited from approximately 20 primary care sites. The analysis will be descriptive focusing on estimation with no formal comparison of groups taking place. DISCUSSION: If this trial demonstrates the feasibility of recruitment and delivery, we will seek funding for a fully powered placebo-controlled trial of Pelargonium sidoides root extract for the treatment of lower respiratory tract infections in primary care. TRIAL REGISTRATION: HATRIC was registered on the ISRCTN registry (ISRCTN17672884) on 16 August 2018.


Detect to Protect


Multi-Cultural Project Initiative: An inclusive representation of “Coronavirus Guidelines for America”


title: A case of acute disseminated encephalomyelitis following Mycoplasma pneumoniae infection

text: We report a case of acute disseminated encephalomyelitis (ADEM) secondary to Mycoplasma pneumoniae infection that failed to improve with methylprednisolone and intravenous immunoglobulin (IVIG); who responded with plasmapheresis. A 21- year- old female with an unremarkable medical history, initially presented to an outside hospital with fever and an influenza-like illness and was subsequently intubated for worsening sensorium. Brain magnetic resonance imaging was suggestive of ADEM or vasculitis for which she received five days of pulse steroids and IVIG. She showed no signs of improvement and was transferred to our hospital for plasmapheresis. Her work up revealed an elevated IgM antibody and positive sputum for Mycoplasma pneumonia by polymerase chain reaction, suggesting the pathogen as the culprit for her ADEM. Intravenous azithromycin and daily plasmapheresis were initiated for seven consecutive days. Following commencement of her treatment, the patient experienced good recovery and was subsequently extubated. She continued to improve with physical therapy and gained mobility, with the help of a walker. Patients commonly present with ADEM following viral infection or vaccination and less frequently post bacterial infection. The current treatment of ADEM due to Mycoplasma pneumoniae is based on limited case reports. Our patient poorly responded to pulse steroids and IVIG, while she markedly improved on azithromycin and plasmapheresis. In patients presenting with encephalopathic signs and neurological manifestations following pneumonia; Mycoplasma pneumoniae infection and subsequent immune-mediated demyelination should be considered.


title: A realistic two-strain model for MERS-CoV infection uncovers the high risk for epidemic propagation

text: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory illness with a case fatality rate (CFR) of 35,5%. The highest number of MERS-CoV cases are from Saudi-Arabia, the major worldwide hotspot for this disease. In the absence of neither effective treatment nor a ready-to-use vaccine and with yet an incomplete understanding of its epidemiological cycle, prevention and containment measures can be derived from mathematical models of disease epidemiology. We constructed 2-strain models to predict past outbreaks in the interval 2012–2016 and derive key epidemiological information for Macca, Madina and Riyadh. We approached variability in infection through three different disease incidence functions capturing social behavior in response to an epidemic (e.g. Bilinear, BL; Non-monotone, NM; and Saturated, SAT models). The best model combination successfully anticipated the total number of MERS-CoV clinical cases for the 2015–2016 season and accurately predicted both the number of cases at the peak of seasonal incidence and the overall shape of the epidemic cycle. The evolution in the basic reproduction number (R(0)) warns that MERS-CoV may easily take an epidemic form. The best model correctly captures this feature, indicating a high epidemic risk (1≤R(0)≤2,5) in Riyadh and Macca and confirming the alleged co-circulation of more than one strain. Accurate predictions of the future MERS-CoV peak week, as well as the number of cases at the peak are now possible. These results indicate public health agencies should be aware that measures for strict containment are urgently needed before new epidemics take off in the region.


title: Covid-19 Pandemic and Current Medical Interventions

text: Abstract First humanoid coronavirus was discovered in the middle of 1960s, the class of viruses are considered to be a huge threat. The first onset of human coronavirus, SARS (SARS-CoV) appeared in 2003 which spanned five continents having lethal effects on human population accompanied by The Middle East Respiratory Syndrome Coronavirus in 2012 with a death rate of 35%. The viruses remain a threat till date and are of serious concern since no vaccine or specified drug therapy has been approbated for treating human coronaviruses. The viruses became a pandemic worldwide with the emergence of Wuhan coronavirus (2019-nCoV). SARS-CoV2 viral manifestation poses a serious human life risk by causing acute lung injury and various respiratory outcomes and has become a global concern. High pathogenicity and transmission rate of the viral strain has become the spotlight of research community throughout the world. With the ongoing studies on viral structure and host interactions, the intricacy of the viral proteome structure and replication cycle proposes a need to explore our understanding of host factors playing role in viral multiplication cycle. This review provides insight into our prevalent perception of coronavirus-host interactions, structure of SARS-CoV2, receptor mediated entry of virus inside the human cells, ongoing clinical trials and drug therapies and treatments that are being used to combat COVID-19 targeting viral fusion, replication and its multiplication.


title: Organ Transplantation during COVID‐19 Pandemic: Making the Best Patient Care Decision

text: It is with great interest and sadness that we read the experience of Akalin et al. and Pereira et al. with unprecedented mortality (18‐28%) in transplant recipients in New York City, New York. High mortality reports in transplant patients have created anxiety among some community practitioners as evidence as to why transplants should not be performed at this time, contrary to the recommendations from multiple transplant organizations.


title: Activation of NF-κB by the Full-length Nucleocapsid Protein of the SARS Coronavirus

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) is the major causative agent for the worldwide outbreak of SARS in 2003. The mechanism by which SARS-CoV causes atypical pneumonia remains unclear. The nuclear factor kappa B (NF-κB) is a key transcription factor that activates numerous genes involved in cellular immune response and inflammation. Many studies have shown that NF-κB plays an important role in the pathogenesis of lung diseases. In this study, we investigated the possible regulatory interaction between the SARS-CoV nucleocapsid (N) protein and NF-κB by luciferase activity assay. Our results showed that the SARS-CoV N protein can significantly activate NF-κB only in Vero E6 cells, which are susceptible to SARS-CoV infection, but not in Vero or HeLa cells. This suggests that NF-κB activation is cell-specific. Furthermore, NF-κB activation in Vero E6 cells expressing the N protein is dose-dependent. Further experiments showed that there is more than one function domain in the N protein responsible for NF-κB activation. Our data indicated the possible role of the N protein in the pathogenesis of SARS.


title: A review of rabbit and rodent production medicine

text: This review article outlines the essentials of production medicine (factors affecting production colony output) in rabbits and rodents, emphasizing the importance of routine management methods and record-keeping as well as disease control. Common management regimes and production diseases of the important rodent species are covered.


title: Effects of Hand Hygiene Campaigns on Incidence of Laboratory-confirmed Influenza and Absenteeism in Schoolchildren, Cairo, Egypt

text: To evaluate the effectiveness of an intensive hand hygiene campaign on reducing absenteeism caused by influenza-like illness (ILI), diarrhea, conjunctivitis, and laboratory-confirmed influenza, we conducted a randomized control trial in 60 elementary schools in Cairo, Egypt. Children in the intervention schools were required to wash hands twice each day, and health messages were provided through entertainment activities. Data were collected on student absenteeism and reasons for illness. School nurses collected nasal swabs from students with ILI, which were tested by using a qualitative diagnostic test for influenza A and B. Compared with results for the control group, in the intervention group, overall absences caused by ILI, diarrhea, conjunctivitis, and laboratory-confirmed influenza were reduced by 40%, 30%, 67%, and 50%, respectively (p<0.0001 for each illness). An intensive hand hygiene campaign was effective in reducing absenteeism caused by these illnesses.


title: Murine viral hepatitis involves NK cell depletion associated with virus-induced apoptosis

text: Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent animal model for the study of immunological disorders related to acute and chronic hepatitis. In this study, we have verified if the fulminant hepatitis induced by MHV3 could be related to an impairment of innate immunity. Groups of three C57BL/6 mice were infected with the pathogenic L2-MHV3 or attenuated YAC-MHV3 viruses, and the natural killer (NK) cell populations from liver, spleen and bone marrow were analysed. The percentage of intrahepatic NK1·1(+)T cell receptor (TCR)(−) cells did not increase while NK1·1(+)TCR(inter) cells decreased in both L2-MHV3- and YAC-MHV3-infected mice. Concurrently, splenic and myeloid NK1·1(+) cells decreased in L2-MHV3-infected mice. However, the cytotoxic activity of NK cells increased in liver and decreased in bone marrow from pathogenic L2-MHV3-infected mice while no modification was detected in YAC-MHV3-infected mice. Flow cytometric analysis revealed that both normal and larger splenic or myeloid NK cells decreased more in pathogenic L2-MHV3-infected mice than in attenuated YAC-MHV3-infected mice. In vitro viral infections of interleukin (IL)-15-stimulated lymphoid cells from liver and bone marrow revealed that L2-MHV3 induced higher decreases in cell viability of NK1·1(+) cells than the YAC-MHV3 variant. The NK cell decreases were due to the viral permissivity leading to cytopathic effects characterized by cell rounding, syncytia formation and apoptosis. Larger NK(+) syncytia were observed in L2-MHV3-infected cells than in YAC-MHV3-infected cells. These results suggest that NK cell production is impaired by viral infection favouring fulminant hepatitis.


title: A Local Crash Course in Global Pandemics

text: Clinical experience from the epicenter of the U.S. coronavirus disease 2019 (COVID-19) outbreak.


title: Managing stress during the coronavirus disease 2019 pandemic and beyond: Reappraisal and mindset approaches

text: The novel coronavirus disease 2019 (COVID-19) pandemic is a truly global public health crisis with substantive human, social, and economic costs. The pandemic and the associated preventive 'lockdown' measures have also given rise to a parallel mental health crisis, with elevated levels of chronic stress observed in the general population. Stress levels are also likely to be higher among at-risk groups such as those who have become employed or are on furlough, those in essential services with higher risk of exposure, and those from underserved communities. Development of efficacious means to assist individuals in effectively managing their during the pandemic and beyond is an imperative. We outline how stress reappraisal interventions offer a potentially efficacious, cost effective strategy to manage pandemic-related stress and minimize deleterious health consequences. Specifically, we advocate two stress management strategies: stress reappraisal, which involves prompting individuals to appraise stress as challenging and to be approached rather than threatening and to be avoided, and stress mindsets, which involves highlighting the enhancing nature of stress. We outline how these strategies may be implemented during the pandemic as part of interventions aimed at promoting stress management and better mental health during the pandemic and as communities emerge from lockdown. This article is protected by copyright. All rights reserved.


title: Modeling [(18)F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge

text: BACKGROUND: The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. (18)F-Fluorodeoxyglucose ([(18)F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [(18)F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [(18)F]-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (K(i)) in responsive lymphoid tissue. METHODS: Multiple [(18)F]-FDG-PET and CT images were acquired on a PET/CT clinical scanner modified to operate in a biosafety level 4 environment prior to and up to 29 days after MERS-CoV aerosol exposure. Time activity curves of various lymphoid tissues were reconstructed to follow the [(18)F]-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate K(i) for lymphoid tissues by Patlak plot. RESULTS: Two-way repeated measures analysis of variance revealed alterations in K(i) that was associated with the time point (p < 0.001) after virus exposure and the location of lymphoid tissue (p = 0.0004). As revealed by a statistically significant interaction (p < 0.0001) between these two factors, the pattern of K(i) changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in K(i) was observed in mediastinal lymph nodes (LNs) that correlated to K(i) changes in axillary LNs. Changes in LNs K(i) were concurrent with elevations of monocytes in peripheral blood. CONCLUSIONS: [(18)F]-FDG-PET is able to detect subtle changes in host immune response to contain a subclinical virus infection. Full quantitative analysis is the preferred approach rather than semiquantitative analysis using standardized uptake value for detection of the immune response to the virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13550-015-0143-x) contains supplementary material, which is available to authorized users.


title: Coronavirus infection and immune system: an insight of COVID-19 in cancer patients

text: The novel coronavirus respiratory illness (COVID-19) is a public health emergency of global concern. Patients with cancer are at high risk of infections, due to an overall immunocompromised status. However, this connection is not straightforward for coronavirus (CoV) infection, in which the host immune response is the main driver of tissue damage. We performed a thorough review of data on CoV pathogenesis and morbidity rate in cancer patients, through the analysis of the previous CoV pandemics. Considering the interaction between CoV and the host immune system, cancer patients receiving immunotherapy might be more at risk for an aberrant immune response in case of infection, and might therefore deserve additional precautions. The limited available data do not allow us to provide practical indications for the management of cancer patients in this critical situation. Efforts should be made to prospectively collect data, to identify effective interventions to guide treatment decision.


COVID-19 und Schmerz – Call for Papers


title: Rapid Adaptation of Breast Radiotherapy Utilization during the COVID-19 Pandemic at a Large Academic Cancer Centre in Canada

text: BACKGROUND: Mitigation strategies to balance the risk of COVID-19 infection against oncologic risk in breast cancer patients undergoing radiotherapy have been deployed. To this end, shorter hypofractionated regimens have been recommended where appropriate, with prioritization of radiotherapy by oncologic risk and omission or deferral of radiotherapy for lower risk cases. Timely adoption of these measures reduces COVID-19 risk to both patients and health care workers, and preserves resources. Herein we present our early response and adaptation of breast radiotherapy utilization during the COVID-19 pandemic at a large academic cancer centre in Canada. METHODS: A state of emergency was announced in Ontario on March 17, 2020 due to the COVID-19 pandemic. Emergency guidelines were instituted. To examine our response, the number of weekly breast RT starts, type of breast RT, and patient age were compared from March 1 to April 30, 2020 to the same period in 2019. RESULTS: Following the declaration of emergency in Ontario, there was a decrease of 39% in radiotherapy starts in 2020 compared to 2019 (79 vs. 129, p<0.001). There was a relative increase in the proportion of patients receiving regional nodal irradiation (RNI) in 2020 compared to 2019 (46% vs. 29%, respectively), with the introduction of hypofractionated RNI in 2020 (27 of 54 cases, 50%). A smaller proportion of patients starting radiotherapy were aged > 50 years in 2020, 66% (78/118) vs. 83% (132/160) in 2019, p=0.0027. CONCLUSIONS: A significant reduction in breast radiotherapy starts was noted during the early response to the COVID-19 pandemic, with prioritization of radiotherapy to patients associated with higher oncologic risk requiring RNI. A quick response to a health care crisis is critical, and is of particular importance for higher volume cancer sites where the potential impact on resources is greater.


title: Fish reproductive biology - reflecting on five decades of fundamental and translational research

text: Driven by the broad diversity of species and physiologies and by reproduction-related bottlenecks in aquaculture, the field of fish reproductive biology has rapidly grown over the last five decades. This review provides my perspective on the field during this period, integrating fundamental and applied developments and milestones. Our basic understanding of the brain-pituitary-gonadal axis led to overcoming the failure of farmed fish to ovulate and spawn in captivity, allowing us to close the fish life cycle and establish a predictable, year-round production of eggs. Dissecting the molecular and hormonal mechanisms associated with sex determination and differentiation drove technologies for producing better performing mono-sex and reproductively-sterile fish. The growing contingent of passionate fish biologists, together with the availability of innovative platforms such as transgenesis and gene editing, as well as new models such as the zebrafish and medaka, have generated many discoveries, also leading to new insights of reproductive biology in higher vertebrates including humans. Consequently, fish have now been widely accepted as vertebrate reproductive models. Perhaps the best testament of the progress in our discipline is demonstrated at the International Symposia on Reproductive Physiology of Fish (ISRPF), at which our scientific family has convened every four years since the grandfather of the field, the late Ronald Billard, organized the inaugural 1977 meeting in Paimpont, France. As the one person who has been fortunate enough to attend all of these meetings since their inception, I have witnessed first-hand the astounding evolution of our field as we capitalized on the molecular and biotechnological revolutions in the life sciences, which enabled us to provide a higher resolution of fish reproductive and endocrine processes, answer more questions, and dive into deeper comprehension. Undoubtedly, the next (five) decades will be similarly exciting as we continue to integrate physiology with genomics, basic and translational research, and the small fish models with the aquacultured species.


COVID-19 pandemic, healthcare providers’ contamination and death: an international view