title: Rhinovirus identification by BglI digestion of picornavirus RT-PCR amplicons

text: Abstract Rhinoviruses are the main cause of the common cold and precipitate the majority of asthma exacerbations. RT-PCR followed by internal probe hybridisation or Southern blotting, or nested PCRs are currently the most sensitive methods for their identification. However, none of the published techniques can differentiate satisfactorily rhinoviruses from other picornaviruses. Examination of the restriction maps of sequenced rhinoviruses, revealed a highly conserved BglI restriction site (GCCnnnnnGGC), located exactly in the middle of the 380-bp amplicon generated with the OL26–OL27 primer pair, which has been used extensively in the past to identify picornaviruses. Such a site was either not present, or positioned differently in other picornaviruses of known sequence. It was, therefore, considered that digestion of rhinovirus amplicons with this enzyme would result in two equal length fragments, generating a single 190-bp band in gel electrophoresis. In contrast, either one undigested 380-bp band or a double-band pattern would appear in amplicons from other picornaviruses. To test this hypothesis, Bgl digestions of OL26–OL27 amplicons from cultured and wild-type rhinoviruses, whose identity was confirmed by acid lability, as well as from echo, polio and coxsackie viruses were carried out. All rhinovirus samples were digested successfully generating single bands. Among the other picornaviruses, only 6.6% presented a single band pattern, while the rest were as predicted from the model. With a sensitivity of 100% and a specificity over 90%, the method described, which is rapid and remarkably easy to perform, can be used to distinguish rhinoviruses from other picornaviruses to a considerable extent.


title: Asymptotic profile in selection–mutation equations: Gauss versus Cauchy distributions

text: In this paper, we study the asymptotic (large time) behaviour of a selection–mutation–competition model for a population structured with respect to a phenotypic trait when the rate of mutation is very small. We assume that the reproduction is asexual, and that the mutations can be described by a linear integral operator. We are interested in the interplay between the time variable t and the rate ε of mutations. We show that depending on [Formula: see text] , the limit [Formula: see text] with [Formula: see text] can lead to population number densities which are either Gaussian-like (when α is small) or Cauchy-like (when α is large).


title: Oral immunogenicity of the plant derived spike protein from swine-transmissible gastroenteritis coronavirus

text: Transgenic plants represent an inexpensive alternative to classical fermentation systems for production of recombinant subunit vaccines. Transgenic potato plants were created that express the N-terminal domain of the glycoprotein S (N-gS) from Transmissible gastroenteritis coronavirus (TGEV), containing the major antigenic sites of the protein. Extracts from potato tubers expressing N-gS were inoculated intraperitoneally to mice, and the vaccinated mice developed serum IgG specific for TGEV. Furthermore, when potato tubers expressing N-gS were fed directly to mice, they developed serum antibodies specific for gS protein, demonstrating the oral immunogenicity of the plant derived spike protein from TGEV.


title: AlGaN/GaN high electron mobility transistors for protein–peptide binding affinity study

text: Abstract Antibody-immobilized AlGaN/GaN high electron mobility transistors (HEMTs) were used to detect a short peptide consisting of 20 amino acids. One-binding-site model and two-binding-site model were used for the analysis of the electrical signals, revealing the number of binding sites on an antibody and the dissociation constants between the antibody and the short peptide. In the binding-site models, the surface coverage ratio of the short peptide on the sensor surface is relevant to the electrical signals resulted from the peptide–antibody binding on the HEMTs. Two binding sites on an antibody were observed and two dissociation constants, 4.404×10−11 M and 1.596×10−9 M, were extracted from the binding-site model through the analysis of the surface coverage ratio of the short peptide on the sensor surface. We have also shown that the conventional method to extract the dissociation constant from the linear regression of curve-fitting with Langmuir isotherm equation may lead to an incorrect information if the receptor has more than one binding site for the ligand. The limit of detection (LOD) of the sensor observed in the experimental result (∼10pM of the short peptide) is very close to the LOD (around 2.7–3.4pM) predicted from the value of the smallest dissociation constants. The sensitivity of the sensor is not only dependent on the transistors, but also highly relies on the affinity of the ligand-receptor pair. The results demonstrate that the AlGaN/GaN HEMTs cannot only be used for biosensors, but also for the biological affinity study.


title: Responding to the COVID‐19 Crisis: Transformative Governance in Switzerland

text: In the ongoing coronavirus disease 2019 (COVID‐19) crisis, uncertain and experimental forms of governance have emerged. Administrative routines and established management techniques have dissolved amid emergency actions and management by the state of exception. We refer to these emerging governance forms as transformative governance. Discussing examples from Switzerland, we illustrate how policy responses to COVID‐19 reflect transformative governance. These examples raise four issues that characterize transformative governance research and practice: (i) the evidence base of policy‐making; (ii) the role of the state in transformative governance; (iii) the potential of experimental governance; and (iv) the paradigms driving policy change. Our study demonstrates that these issues imply different opportunities and risks of transformative governance, which we discuss in detail.


title: Clinical Features of COVID‐19‐Infected Patients With Elevated Liver Biochemistries: A Multicenter, Retrospective Study

text: In December 2019, an outbreak of coronavirus disease 2019 (COVID‐19) emerged in Wuhan, China. Although it has been reported that some COVID‐19 patients showed elevated liver biochemistries, there are few studies regarding clinical features and prognosis of these patients. In this multicenter, retrospective study, we collected data on laboratory‐confirmed COVID‐19 patients from three hospitals in Wuhan, China, who died or were discharged between February 1, 2020, and February 20, 2020. The data on demographics, comorbidities, clinical symptoms, laboratory examinations on admission, complications, treatment, and outcome were collected. A total of 482 patients were enrolled in this study. Of those, 142 (29.5%) patients showed abnormal liver biochemistries on admission, and patients with elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) accounted for 67.6%, 69.0%, and 16.2%, respectively. Those with abnormal liver biochemistries showed higher percentages of severe cases and comorbidities and were more likely to have dyspnea, chest distress or pain, and increased hemoglobin (Hb) on admission. Higher rates of complications and mortality and worse recovery when discharged were observed in patients with abnormal AST or TBIL. The multivariable regression analysis showed that chest distress or pain (odds ratio [OR], 1.765; P = 0.018), dyspnea (OR, 2.495; P = 0.001), elevated C‐reactive protein [CRP] level (OR, 1.007; P = 0.008), elevated white blood count (WBC) (OR, 1.139; P = 0.013), and elevated Hb concentration (OR, 1.024; P = 0.001) were independent factors associated with elevated liver biochemistries in COVID‐19 patients. Conclusion: Elevated liver biochemistries were common in COVID‐19 patients. Patients with hypoxia or severe inflammation are more likely to experience increased liver biochemistries on admission. Those with abnormal AST or TBIL on admission are more likely to suffer from severe complications and death.


title: Genetic polymorphisms in mouse genes regulating age-sensitive and age-stable T cell subsets

text: To see whether genetic polymorphisms regulate inter-individual differences in T cell subset levels, we have conducted a genome scan in two populations of mice, bred as the progeny of a cross between CB6F1 females and C3D2F1 males. The data document quantitative trait loci (QTL) with statistically significant effects on CD4, CD8, and CD8 memory T cells, and on subsets of CD4 and CD8 T cells that express P-glycoprotein. Some of the loci detected were robust, in the sense that they produced effects of similar size both in mated female mice, and in a population that included male and female virgin animals. Some of the effects were stable, in that they were apparent at both 8 and 18 months of age, but others were age-specific, showing effects either at 8 or at 18 months but not at both ages. Genes that had an effect on the same T cell subset were in almost all cases additive rather than epistatic, and their combined effects could produce large overall effects, leading in the most dramatic case to a two-fold difference in CD8 memory cells. The analysis also documented two QTL, on chromosomes 4 and 13, that regulate an age-sensitive composite index of T cell subset pattern which has been shown previously to be a predictor of life expectancy in these mice. The analysis thus reveals both subset-specific genes and others which modulate the overall pattern of age-sensitive changes in T cell subset distributions.


title: Tracheostomy in a patient with severe acute respiratory syndrome

text: The coronavirus which causes severe acute respiratory syndrome (SARS) is a virulent and highly contagious organism. Of the 1755 SARS patients in Hong Kong, over 400 were healthcare workers. Meticulous attention to infection control and teamwork are essential to minimize cross-contamination and prevent staff from contracting the illness. These points are especially pertinent when anaesthetizing SARS patients for high-risk procedures such as tracheostomy. We describe the management of such a case.


title: Emerging strains of porcine epidemic diarrhoea virus (PEDv) in Mexico

text: As an emerging disease, the porcine epidemic diarrhoea virus has caused substantial economic losses to the pork industry in Mexico, leading to piglet mortality rates of up to 100%. For detection, sequencing and genetic characterization of the virus, 68 samples of one‐week‐old piglets from pork farms in 17 states of Mexico were analysed. In total, 53 samples were positive by real‐time RT‐PCR, confirming the presence of the virus in 15 states. Twenty‐eight samples from 10 states were amplified by endpoint RT‐PCR, and 20 sequences of the spike gene were obtained. A phylogenetic analysis based on the spike gene demonstrated that all Mexican strains are in Group II and are classified as non‐Indel‐S emerging variants. Three strains showed amino acid insertions: PEDv/MEX/GTO/LI‐DMZC15/2015 and PEDv/MEX/QRO/LI‐DMZC45/2016 showed one amino acid insertion ((424)Y(425) and (447)D(448), respectively), and PEDv/MEX/QRO/LI‐DMZC49/2019 showed one and two amino acid insertions ((422)C(423) and (537)SQ(538)), with the second insertion in the COE region. These results provide evidence of the prevalence of emerging, non‐Indel‐S strains of the virus are currently circulating in Mexico during 2016–2018, when three of which have amino acid insertions: PEDv/MEX/GTO/IN‐DMZC15/2015 and PEDv/MEX/QRO/IN‐DMZC45/2016 have one amino acid insertion each ((424)Y(425) and (447)D(448), respectively), and PEDv/MEX/QRO/IN‐DMZC49/2019 has one ((422)C(423)) and two amino acid insertions ((537)SQ(538)), the latter being in the COE region, which could generate new antigenic variants.


Considerations for the outpatient practice in pediatric surgery during the novel SARS-CoV-2Pandemic


title: Chapter Fifteen Nasal Vaccine Delivery

text: Abstract The mucosal surfaces represent the major site of entry of many pathogens, and major challenges in vaccine development include safety and stability in a suitable dosage form. Micro- and nanocarrier-based delivery systems as nasal vaccines induce humoral, cellular, and mucosal immunity. The nasal route of vaccination could also offer immunity at several distant mucosal sites (oral, rectal, vaginal, and pulmonary), which is considered a simplified and cost-effective mode of vaccination with enhanced patient compliance. Most of the nasal vaccine delivery systems in the form of microparticulates, nanoparticulates, and liposomes are currently under development and prove to offer immunity in animal models. The importance and potential of the nasal route of administration for vaccines is unexplored, and this chapter outlines the opportunities, challenges, and potential delivery solutions to facilitate the development of improved nasal vaccines for infectious diseases.


title: Bat influenza viruses: Making a double agent of MHC class II

text: Abstract Major histocompatibility complex class II has recently been identified as a cellular receptor for bat influenza viruses. Here, we discuss the possible implications of viral exploitation of this critical host defense molecule and highlight the need for more intense study of bat-influenza virus interactions.


title: Zinc and respiratory tract infections: Perspectives for COVID-19 (Review)

text: In view of the emerging COVID-19 pandemic caused by SARS-CoV-2 virus, the search for potential protective and therapeutic antiviral strategies is of particular and urgent interest. Zinc is known to modulate antiviral and antibacterial immunity and regulate inflammatory response. Despite the lack of clinical data, certain indications suggest that modulation of zinc status may be beneficial in COVID-19. In vitro experiments demonstrate that Zn(2+) possesses antiviral activity through inhibition of SARS-CoV RNA polymerase. This effect may underlie therapeutic efficiency of chloroquine known to act as zinc ionophore. Indirect evidence also indicates that Zn(2+) may decrease the activity of angiotensin-converting enzyme 2 (ACE2), known to be the receptor for SARS-CoV-2. Improved antiviral immunity by zinc may also occur through up-regulation of interferon α production and increasing its antiviral activity. Zinc possesses anti-inflammatory activity by inhibiting NF-κB signaling and modulation of regulatory T-cell functions that may limit the cytokine storm in COVID-19. Improved Zn status may also reduce the risk of bacterial co-infection by improving mucociliary clearance and barrier function of the respiratory epithelium, as well as direct antibacterial effects against S. pneumoniae. Zinc status is also tightly associated with risk factors for severe COVID-19 including ageing, immune deficiency, obesity, diabetes, and atherosclerosis, since these are known risk groups for zinc deficiency. Therefore, Zn may possess protective effect as preventive and adjuvant therapy of COVID-19 through reducing inflammation, improvement of mucociliary clearance, prevention of ventilator-induced lung injury, modulation of antiviral and antibacterial immunity. However, further clinical and experimental studies are required.


title: Severe Acute Lung Injury Related to COVID‐19 Infection: A Review and the Possible Role for Escin

text: Acute lung injury (ALI) represents the most severe form of the viral infection sustained by coronavirus disease 2019 (COVID‐19). Today, it is a pandemic infection, and even if several compounds are used as curative or supportive treatment, there is not a definitive treatment. In particular, antiviral treatment used for the treatment of several viral infections (eg, hepatitis C, HIV, Ebola, severe acute respiratory syndrome–coronavirus) are today used with a mild or moderate effect on the lung injury. In fact, ALI seems to be related to the inflammatory burst and release of proinflammatory mediators that induce intra‐alveolar fibrin accumulation that reduces the gas exchange. Therefore, an add‐on therapy with drugs able to reduce inflammation, edema, and cell activation has been proposed as well as a treatment with interferon, corticosteroids or monoclonal antibodies (eg, tocilizumab). In this article reviewing literature data related to the use of escin, an agent having potent anti‐inflammatory and anti‐viral effects in lung injury, we suggest that it could represent a therapeutic opportunity as add‐on therapy in ALI related to COVID‐19 infection.


title: An integrated microfluidic system for rapid diagnosis of dengue virus infection

text: This study reports an integrated microfluidic system which utilizes virus-bound magnetic bead complexes for rapid serological analysis of antibodies associated with an infection by the dengue virus. This new microfluidic system integrates one-way micropumps, a four-membrane-type micromixer, two-way micropumps and an on-chip microcoil array in order to simultaneously perform the rapid detection of immunoglobulin G (IgG) and immunoglobulin M (IgM). An IgM/IgG titer in serum is used to confirm the presence of dengue virus infection. By utilizing microfluidic technologies and virus-bound magnetic beads, IgG and IgM in the serum samples are captured. This is followed by purification and isolation of these beads utilizing a magnetic field generated from the on-chip array of microcoils. Any interfering substances in the biological fluids are washed away automatically by the flow generated by the integrated pneumatic pumps. The fluorescence-labelled secondary antibodies are bound to the surface of the IgG/IgM complex attached onto the magnetic beads. Finally, the entire magnetic complex sandwich is transported automatically into a sample detection chamber. The optical signals are then measured and analyzed by a real-time optical detection module. The entire process is performed automatically on a single chip within 30 min, which is only 1/8th of the time required for a traditional method. More importantly, the detection limit has been improved to 21 pg, which is about 38 times better when compared to traditional methods. This integrated system may provide a powerful platform for the rapid diagnosis of dengue virus infection and other types of infectious diseases.


title: Chronic Kidney Disease-Associated Immune Dysfunctions: Impact of Protein-Bound Uremic Retention Solutes on Immune Cells

text: Regardless of the primary disease responsible for kidney failure, patients suffering from chronic kidney disease (CKD) have in common multiple impairments of both the innate and adaptive immune systems, the pathophysiology of which has long remained enigmatic. CKD-associated immune dysfunction includes chronic low-grade activation of monocytes and neutrophils, which induces endothelial damage and increases cardiovascular risk. Although innate immune effectors are activated during CKD, their anti-bacterial capacity is impaired, leading to increased susceptibility to extracellular bacterial infections. Finally, CKD patients are also characterized by profound alterations of cellular and humoral adaptive immune responses, which account for an increased risk for malignancies and viral infections. This review summarizes the recent emerging data that link the pathophysiology of CKD-associated immune dysfunctions with the accumulation of microbiota-derived metabolites, including indoxyl sulfate and p-cresyl sulfate, the two best characterized protein-bound uremic retention solutes.


title: SWAB team instead of SWAT team ‐ students as front‐line force during the COVID‐19 Pandemic

text: A Special Weapons and Tactics (SWAT) team is trained to deal with troubling situations. The SARS‐CoV‐2 pandemic confronted health care systems with different challenges. In Europe, the first COVID‐19 patients presented in late February 2020. Our region was among the most severely affected in central Europe. Therefore, front‐line operations, such as emergency departments (ED), were highly stressed by immediate demand for diagnostic swab‐testing, and additional personnel were urgently needed within a short time. In the meantime, clinical activities of medical students (MS) were on hold, and teaching had to be restructured to online formats. However, we expected that MS would benefit tremendously from learning opportunities through active involvement in this pandemic.


title: Viral Metagenomics on Animals as a Tool for the Detection of Zoonoses Prior to Human Infection?

text: Many human viral infections have a zoonotic, i.e., wild or domestic animal, origin. Several zoonotic viruses are transmitted to humans directly via contact with an animal or indirectly via exposure to the urine or feces of infected animals or the bite of a bloodsucking arthropod. If a virus is able to adapt and replicate in its new human host, human-to-human transmissions may occur, possibly resulting in an epidemic, such as the A/H1N1 flu pandemic in 2009. Thus, predicting emerging zoonotic infections is an important challenge for public health officials in the coming decades. The recent development of viral metagenomics, i.e., the characterization of the complete viral diversity isolated from an organism or an environment using high-throughput sequencing technologies, is promising for the surveillance of such diseases and can be accomplished by analyzing the viromes of selected animals and arthropods that are closely in contact with humans. In this review, we summarize our current knowledge of viral diversity within such animals (in particular blood-feeding arthropods, wildlife and domestic animals) using metagenomics and present its possible future application for the surveillance of zoonotic and arboviral diseases.


title: Cellular entry of the porcine epidemic diarrhea virus

text: Abstract Porcine epidemic diarrhea virus (PEDV), a coronavirus discovered more than 40 years ago, regained notoriety recently by its devastating outbreaks in East Asia and the Americas, causing substantial economic losses to the swine husbandry. The virus replicates extensively and almost exclusively in the epithelial cells of the small intestine resulting in villus atrophy, malabsorption and severe diarrhea. Cellular entry of this enveloped virus is mediated by the large spike (S) glycoprotein, trimers of which mediate virus attachment to the target cell and subsequent membrane fusion. The S protein has a multidomain architecture and has been reported to bind to carbohydrate (sialic acid) and proteinaceous (aminopeptidase N) cell surface molecules. PEDV propagation in vitro requires the presence of trypsin(-like) proteases in the culture medium, which capacitates the fusion function of the S protein. Here we review the current data on PEDV entry into its host cell, including therein our new observations regarding the functional role of the sialic acid binding activity of the S protein in virus infection. Moreover, we summarize the recent progress on the proteolytic activation of PEDV S proteins, and discuss factors that may determine tissue tropism of PEDV in vivo.


title: Enterovirus infections of the central nervous system

text: Abstract Enteroviruses (EV) frequently infect the central nervous system (CNS) and induce neurological diseases. Although the CNS is composed of many different cell types, the spectrum of tropism for each EV is considerable. These viruses have the ability to completely shut down host translational machinery and are considered highly cytolytic, thereby causing cytopathic effects. Hence, CNS dysfunction following EV infection of neuronal or glial cells might be expected. Perhaps unexpectedly given their cytolytic nature, EVs may establish a persistent infection within the CNS, and the lasting effects on the host might be significant with unanticipated consequences. This review will describe the clinical aspects of EV-mediated disease, mechanisms of disease, determinants of tropism, immune activation within the CNS, and potential treatment regimes.


title: Evidence for a common mucosal immune system in the pig

text: Abstract The majority of lymphocytes activated at mucosal sites receive instructions to home back to the local mucosa, but a portion also seed distal mucosa sites. By seeding distal sites with antigen-specific effector or memory lymphocytes, the foundation is laid for the animal's mucosal immune system to respond with a secondary response should to this antigen be encountered at this site in the future. The common mucosal immune system has been studied quite extensively in rodent models but less so in large animal models such as the pig. Reasons for this paucity of reported induction of the common mucosal immune system in this species may be that distal mucosal sites were examined but no induction was observed and therefore it was not reported. However, we suspect that the majority of investigators simply did not sample distal mucosal sites and therefore there is little evidence of immune response induction in the literature. It is our hope that more pig immunologists and infectious disease experts who perform mucosal immunizations or inoculations on pigs will sample distal mucosal sites and report their findings, whether results are positive or negative. In this review, we highlight papers that show that immunization/inoculation using one route triggers mucosal immune system induction locally, systemically, and within at least one distal mucosal site. Only by understanding whether immunizations at one site triggers immunity throughout the common mucosal immune system can we rationally develop vaccines for the pig, and through these works we can gather evidence about the mucosal immune system that may be extrapolated to other livestock species or humans.


title: Effect of TiO(2)/V(2)O(5) substitution on the optical and radiation shielding properties of alkali borate glasses: A Monte Carlo investigation

text: In this paper, we used Geant4 Monte Carlo simulations to investigate the effect of TiO(2)/V(2)O(5) substitution on the radiation shielding properties of alkali borate glasses in the chemical form of 30Li(2)O+55B(2)O(3)+5ZnO + xTiO(2)+(10 − x)V(2)O(5), where x = 0, 2.5, 5, 7.5, and 10 mol%. Also, the optical properties were examined by evaluating several factors such as molar refraction (R(m)), metallization criterion (M), molar polarizability (α(m)), dielectric coefficients (static and optical), optical transmission (T), and reflection loss (R(L)). The radiation shielding properties of the tested glasses was estimated by determining the mass attenuation coefficient, and other related factors such as the tenth value layer (TVL), the mean free path (MFP), the electron total stopping powers (Ψ(e)) and the electron continuous slowing down approximation range (CSDA) (Φ(e)) for different energy values. The results of Geant4 Monte Carlo were compared with the theoretical values calculated by XCOM platform. The results revealed that the TiO(2)/V(2)O(5) substitution had a remarkable influence on the gamma shielding properties for the tested glasses. On the other hand, the optical properties slightly changed by the TiO(2)/V(2)O(5) substitution. The gamma shielding properties of the tested glasses were compared with many samples in terms of MFP. The present glasses showed superior features to apply for optical and radiation shielding applications.


title: Production and characterization of anti-peptide monoclonal antibodies with specificity for staphylococcal enterotoxins A and B

text: Abstract A synthetic peptide containing selected epitopes from staphylococcal enterotoxin A (SEA) and enterotoxin B (SEB) was used to produce monoclonal antibodies (Mabs) to respective enterotoxins in a single fusion procedure. The peptide inhibited the reaction of polyclonal anti-SEA or anti-SEB antisera with their homologous enterotoxin, thus showing that the chosen epitopes are part of the antibody-inducing enterotoxin sequences. Two Mabs, Mab-A and Mab-B, reacted with both the peptide and with either SEA or SEB. Used in a double antibody sandwich ELISA, the Mabs were able to quantitate the native SEA or SEB toxins at nanogram levels.


The Imperative to Vaccinate


title: Alisporivir Inhibition of Hepatocyte Cyclophilins Reduces HBV Replication and Hepatitis B Surface Antigen Production

text: Background & Aims Cyclophilins are host factors required for hepatitis C virus replication. Cyclophilin inhibitors such as alisporivir have shown strong anti–hepatitis C virus activity in vitro and in clinical studies. However, little is known about whether hepatocyte cyclophilins are involved in the hepatitis B virus (HBV) life cycle. We investigated the effects of 2 cyclophilin inhibitors (alisporivir and NIM811) on HBV replication and hepatitis B surface antigen (HBsAg) production in cell lines. Methods Liver-derived cell lines producing full-length HBV and HBsAg particles, owing to stable (HepG2215) or transient (HuH-7) transfection, or infected with HBV (HepaRG cells; Invitrogen [Carlsbad, CA]), were incubated with alisporivir or NIM811 alone, or alisporivir in combination with a direct antiviral (telbivudine). The roles of individual cyclophilins in drug response was evaluated by small interfering RNA knockdown of cyclophilin (CYP)A, CYPC, or CYPD in HepG2215 cells, or CYPA knockdown in HuH-7 cells. The kinetics of antiviral activity were assessed based on levels of HBV DNA and HBsAg and Southern blot analysis. Results In HepG2215, HuH-7, and HepaRG cells, alisporivir reduced intracellular and secreted HBV DNA, in a dose-dependent manner. Knockdown of CYPA, CYPC, or CYPD (reduced by 80%) significantly reduced levels of HBV DNA and secreted HBsAg. Knockdown of CYPA significantly reduced secretion of HBsAg, leading to accumulation of intracellular HBsAg; the addition of alisporivir greatly reduced levels of HBsAg in these cells. The combination of alisporivir and telbivudine had greater antiviral effects than those of telbivudine or alisporivir alone. Conclusions Alisporivir inhibition of cyclophilins in hepatocyte cell lines reduces replication of HBV DNA and HBsAg production and secretion. These effects are potentiated in combination with direct antiviral agents that target HBV-DNA polymerase.


title: Neospora caninum, A potential cause of reproductive failure in dairy cows from Northern Greece

text: Abstract Neospora caninum infection has been reported in a large number of intermediate hosts, such as ruminants, rabbits, mice, etc. but neosporosis has emerged as a serious disease in cattle and dogs worldwide. Abortions and other infertility issues have been reported in the infected cows, leading to great economic losses in farmers. The aim of our study was to assess N. caninum seroprevalence in dairy cattle from Northern Greece (region of Xanthi) by using the indirect fluorescent antibody technique. Blood samples were collected from 875 Holstein – Friesian dairy cows and tested for Neospora caninum antibodies. Among the cows that were studied, 184 (21.03%) were positive for N. caninum antibodies and concurrently their farms had a known previous history of infertility problems, such as abortions, increased number of artificial inseminations needed for conception, increased rate of returning to estrus and retention of fetal membranes.


The many mechanisms of action of Chloroquine: to use or not to use (in COVID‐19) that is the question


title: Human Bocavirus quantitative DNA detection in French children hospitalized for acute bronchiolitis

text: Abstract Background Human Bocavirus (HBoV) is a newly discovered parvovirus whose role as a causative agent of respiratory disease remains unclear. Study design We investigated the presence of HBoV by quantitative PCR in the nasopharyngeal samples of 192 French children consecutively hospitalized for acute bronchiolitis. Other common respiratory viruses were detected using immunofluorescence assays, cell culture detection, or RT-PCR assays. Results HBoV was detected in 24 (12.5%) of 192 study children. In 14/192 cases (7%) HBoV was the sole isolate and in 10/192 (5%) it was part of a mixed viral infection. HBoV was the third most common pathogen detected after respiratory syncytial virus (45/192; 23%) and rhinovirus (24/192; 12%). It occurred more often in infants aged 1–12 months (P =0.002). Median levels of HBoV DNA genome in respiratory samples were significantly higher in patients with single HBoV infection than in patients with mixed respiratory viral infection with HBoV (4×108 copies/ml vs. 2×103 copies/ml, P <0.001). Conclusions Our data suggest that HBoV at a high viral load could be an etiologic agent of respiratory tract disease, whereas the exact role of HBoV at a low viral load, as etiological cause or as pathophysiological co-factor of respiratory diseases, remains to be determined.


title: The Okinawa Infectious Diseases Initiative

text: At the Kyushu–Okinawa Group of Eight summit in 2000, Japan announced the Okinawa Infectious Diseases Initiative (IDI) and pledged to spend US$3 billion over a five year period to combat infectious and parasitic diseases in developing countries. The IDI has exceeded expectations, spending more than US$4 billion over four years. The IDI is a unique initiative with its own philosophical basis and specifically tailored interventions and measures that helped to initiate worldwide political and financial commitments in the fight against infectious diseases. Notably, it promoted partnerships among stakeholders and emphasized comprehensive and inter-sectoral approaches (i.e. coordination and collaboration between health and other sectors). It helped to create a new vision of what is possible in the global effort against communicable diseases and has been instrumental in shaping the changing environments of development assistance, poverty reduction and other trends to reduce the impact of infectious and parasitic diseases.


title: The Effect of Recycled Water Information Disclosure on Public Acceptance of Recycled Water—Evidence from residents of Xi'an, China

text: Recycled water, the secondary water source of a city, is vital to alleviate regional water resource shortage and promote environmental conservation. The attitude and acceptance toward recycled water of the public, its direct user, hold the key to the implementation of a recycled water project. Currently, the public’s low intention of using recycled water constitutes the biggest obstacle to its popularization. To identify the factors of public acceptance of recycled water and their influence path, this study analyzes the effect mechanism of information disclosure of recycled water on the public’s acceptance of it based on the consciousness-context-behavior theory and by adopting a structural equation model. The results are as follows: (1) The public’s consciousness of water saving, risk perception of recycled water, and consciousness of environmental responsibility can effectively promote public acceptance of recycled water; (2) The consciousness of water saving and that of environmental responsibility have a significant effect on public acceptance of recycled water, and so do the consciousness of water saving and the risk perception of recycled water; and (3) Recycled water information disclosure has the most significant regulatory effect on consciousness and public acceptance.


title: Successful resolution of dermatophyte mycetoma following terbinafine treatment in two cats

text: Microsporum canis sensitive to itraconazole and terbinafine was isolated from two cats presented with generalized dermatophytosis and dermatophyte mycetoma. Itraconazole therapy was withdrawn through lack of efficacy in one cat (a Persian) and unacceptable adverse effects in the other (a Maine Coon). Both cats achieved clinical and mycological cure after 12–14 weeks therapy with 26–31 mg kg(−1) terbinafine every 24 h per os (PO). Clinical signs in the Maine Coon resolved completely after 7 weeks treatment. Four weeks of therapy with additional weekly washes with a 2% chlorhexidine/2% miconazole shampoo following clipping produced a 98% reduction in the Persian cat's mycetoma, which was then surgically excised. Recurrent generalized dermatophytosis in the Persian cat has been managed with pulse therapy with 26 mg kg(−1) terbinafine every 24 h PO for 1 week in every month. No underlying conditions predisposing to dermatophytosis were found in either cat despite extensive investigation. Terbinafine administration was associated with mild to moderate lethargy in the Persian cat, but no other adverse effects or changes in blood parameters were seen. To the best of the authors’ knowledge this is the first report of a dermatophyte mycetoma in a Maine Coon and of successful resolution of this condition in cats following terbinafine therapy.


title: Precision epidemiology for infectious disease control

text: Advances in genomics and computing are transforming the capacity for the characterization of biological systems, and researchers are now poised for a precision-focused transformation in the way they prepare for, and respond to, infectious diseases. This includes the use of genome-based approaches to inform molecular diagnosis and individual-level treatment regimens. In addition, advances in the speed and granularity of pathogen genome generation have improved the capability to track and understand pathogen transmission, leading to potential improvements in the design and implementation of population-level public health interventions. In this Perspective, we outline several trends that are driving the development of precision epidemiology of infectious disease and their implications for scientists’ ability to respond to outbreaks.


title: Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB

text: Hepatitis C virus (HCV) and the malaria parasite Plasmodium use the membrane protein CD81 to invade human liver cells. Here we mapped 33 host protein interactions of CD81 in primary human liver and hepatoma cells using high-resolution quantitative proteomics. In the CD81 protein network, we identified five proteins which are HCV entry factors or facilitators including epidermal growth factor receptor (EGFR). Notably, we discovered calpain-5 (CAPN5) and the ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene B (CBLB) to form a complex with CD81 and support HCV entry. CAPN5 and CBLB were required for a post-binding and pre-replication step in the HCV life cycle. Knockout of CAPN5 and CBLB reduced susceptibility to all tested HCV genotypes, but not to other enveloped viruses such as vesicular stomatitis virus and human coronavirus. Furthermore, Plasmodium sporozoites relied on a distinct set of CD81 interaction partners for liver cell entry. Our findings reveal a comprehensive CD81 network in human liver cells and show that HCV and Plasmodium highjack selective CD81 interactions, including CAPN5 and CBLB for HCV, to invade cells.


Characteristics of health worker fatality in China during the outbreak of COVID-19 infection


title: Acute Stroke Care in a New York City Comprehensive Stroke Center during the COVID-19 Pandemic

text: BACKGROUND AND PURPOSE: The coronavirus disease-2019 (COVID-19) pandemic caused unprecedented demand and burden on emergency health care services in New York City. We aim to describe our experience providing acute stroke care at a comprehensive stroke center (CSC) and the impact of the pandemic on the quality of care for patients presenting with acute ischemic stroke (AIS). METHODS: We retrospectively analyzed data from a quality improvement registry of consecutive AIS patients at New York University Langone Health's CSC between 06/01/2019-05/15/2020. During the early stages of the pandemic, the acute stroke process was modified to incorporate COVID-19 screening, testing, and other precautionary measures. We compared stroke quality metrics including treatment times and discharge outcomes of AIS patients during the pandemic (03/012020-05/152020) compared with a historical pre-pandemic group (6/1/2019-2/29/2020). RESULTS: A total of 754 patients (pandemic-120; pre-pandemic-634) were admitted with a principal diagnosis of AIS; 198 (26.3%) received alteplase and/or mechanical thrombectomy. Despite longer median door to head CT times (16 vs 12 minutes; p=0.05) and a trend towards longer door to groin puncture times (79.5 vs. 71 minutes, p=0.06), the time to alteplase administration (36 vs 35 minutes; p=0.83), door to reperfusion times (103 vs 97 minutes, p=0.18) and defect-free care (95.2% vs 94.7%; p=0.84) were similar in the pandemic and pre-pandemic groups. Successful recanalization rates (TICI≥2b) were also similar (82.6% vs. 86.7%, p=0.48). After adjusting for stroke severity, age and a prior history of transient ischemic attack/stroke, pandemic patients had increased discharge mortality (adjusted OR 2.90 95% CI 1.77 – 7.17, p = 0.021) CONCLUSION: Despite unprecedented demands on emergency healthcare services, early multidisciplinary efforts to adapt the acute stroke treatment process resulted in keeping the stroke quality time metrics close to pre-pandemic levels. Future studies will be needed with a larger cohort comparing discharge and long-term outcomes between pre-pandemic and pandemic AIS patients.


title: Broad-spectrum antiviral activity of carbodine, the carbocyclic analogue of cytidine

text: Abstract Carbocyclic cytidine (C-Cyd) is a broad-spectrum antiviral agent active against DNA viruses [pox (vaccinia)], (+)RNA viruses [toga (Sindbis, Semliki forest), corona], (−)RNA viruses [orthomyxo (influenza), paramyxo (parainfluenza, measles), rhabdo (vesicular stomatitis)] and (±)RNA viruses (reo). The target enzyme of C-Cyd is supposed to be CTP synthetase that converts UTP to CTP. In keeping with this assumption are the observations that (i) C-Cyd effects a dose-dependent inhibition of RNA synthesis in both virus-infected and uninfected cells, and (ii) exogenous addition of either Urd or Cyd reverses both the antiviral and cytocidal activity of C-Cyd, whereas addition of dThd or dCyd fails to do so. The selectivity of C-Cyd against Sindbis, vesicular stomatitis and reo virus is markedly increased when C-Cyd is combined with Cyd (10 μg/mL). This combination may therefore be worth pursuing as a chemotherapeutic modality for the treatment of virus infections.


title: Exploring IRES Region Accessibility by Interference of Foot-and-Mouth Disease Virus Infectivity

text: Translation initiation of picornavirus RNA is driven by an internal ribosome entry site (IRES) element located upstream of the initiator codon. RNA structure organization as well as RNA-protein interaction plays a fundamental role in internal initiation. IRES activity has been mainly analyzed in the context of reporter genes, lacking regions of the viral genome potentially affecting translation efficiency. With the aim to understand the vulnerability of the IRES and translation start region to small molecules in the context of the viral genome, we designed a set of customized RNase-resistant 2′O-methyl antisense oligoribonucleotides (2′OMe AONs) based on RNA structure data. These AONs were then used to monitor their capacity to interfere viral RNA translation, and thus, to inhibit virus yield. Foot-and-mouth disease virus (FMDV) RNA translation can be initiated at two in-frame AUG codons. We show here that a 2′OMe AON complementary to AUG2 inhibited viral multiplication more efficiently than the one that targeted AUG1. Furthermore, the response of the viral RNA to AONs targeting the IRES region denoted important differences between tissue culture cells and cell-free systems, reinforcing the need to analyze viral RNA response in living cells. Importantly, we have identified four specific motifs within the IRES element that are targets for viral inhibitors both in tissue culture cells and in cell-free systems. The identified targets define accessible regions to small molecules, which disturb either the RNA structural organization or the RNA-protein interactions needed to initiate translation in FMDV RNA.


INFECTIONS, INFLAMMATORY MARKERS AND SCHIZOPHRENIA


title: Collaborative Intervention of Middle East Respiratory Syndrome: Rapid Response Team

text: On May 20th 2015, a 68 year old man was the first to be diagnosed with Middle East Respiratory Syndrome-Corona Virus (MERS-CoV) in Korea. He travelled to Bahrain, Saudi Arabia, and Qatar for 16 days. On May 4th 2015, the patient entered Korea, with febrile sense and respiratory symptoms that appeared on May 11th. The MERS-CoV Outbreak became worse and several patients had to be admitted throughout various hospitals starting at the beginning of June. This situation led to a nationwide chaos. The Rapid Response Team (RRT) was organized after the Korean government's calling for specialists that were composed of 15 Infectious disease Doctors and 2 Infection Control professionals on the 8th of June 2015. The main purpose of the RRT were: 1) consultation to the Government controlling MERS-CoV outbreak. 2) Visit hospitals that were exposed to MERS-CoV infected patients, and to provide advice regarding infection control strategy for rehabilitating of the exposed hospitals. Since June 8th, the RRT visited more than 10 hospitals and an effective consultation was carried out. Most of the hospitals were recovering from the MERS outbreak since early July. Cooperation between the government and private sector experts was very effective. The efforts of government and private sector experts overcame the initial chaos situation. It could prevent further deterioration of the MERS outbreak.


title: Relationship between post-SARS osteonecrosis and PAI-1 4G/5G gene polymorphisms

text: OBJECTIVE: To explore the correlation between post-severe acute respiratory symptom (SARS) patients with osteonecrosis, investigate the etiology of post-SARS osteonecrosis and select the sensitive molecular symbols for early diagnosis and distinguish the high-risk population. METHODS: The studied subjects were divided into two groups. Sixty-two post-SARS patients with osteonecrosis were one group, and 52 age- and sex-matched healthy people were as normal controlled group. Empty stomach blood samples from cubital veins were collected from both groups. Plasminogen activator inhibitor (PAI) by means of enzyme-linked immunosorbent assay and PAI-1 4G/5G polymorphism was detected by polymerase chain reaction and solid phase oligonucleotide assay. RESULTS: The blood agents of post-SARS patients changed obviously with 15.64 ± 13.85 U/ml while the control group 7.96 ± 4.27 U/ml; 4G/4G genotype for the PAI-1 polymorphism detected in post-SARS group was more than that of the control group, but had no statistical significance. The plasma PAI activity was related to homozygote 4G/4G genotype. This reveals that homozygote 4G/4G genotype may be a susceptible gene mark to Chinese osteonecrosis patients. CONCLUSION: Plasminogen activator inhibitor-1 is sensitive blood symbol for screening high-risk susceptible population; 4G/4G PAI-1 genotype may be an etiological factor in osteonecrosis.


title: Decreased expression of eukaryotic initiation factor 3f is an adverse prognostic factor for stage I–III gastric cancer

text: BACKGROUND: It has been demonstrated that eIF3f expression is significantly decreased in many human cancers, a fact which plays an important role in human cancer. However, the expression of eIF3f in gastric cancer (GC) is not well understood to date. Therefore, the aim of this study is to detect the expression of eIF3f in GC. METHODS: The expression of eIF3f was examined by immunohistochemistry in tissues with stage I to III GC and adjacent non-cancerous tissues (ANCT) of 195 gastrectomy specimens; clinicopathological results, including survival, were analyzed. RESULTS: The positive expression rate of eIF3f was significantly higher in ANCT tissues than in GC. eIF3f levels were correlated with more advanced tumor stages and likelihood of recurrence (all P <0.05). The Kaplan-Meier survival curves indicated that decreased expression of eIF3f could serve as a prognosis marker for poor outcome of GC patients (P = 0.04). CONCLUSIONS: eIF3f may play an important role in recurrence, thus representing a promising predictive marker for the prognosis of GC.


N-acetylcysteine as a potential treatment for novel coronavirus disease 2019


title: Ribosomal stress and Tp53-mediated neuronal apoptosis in response to capsid protein of the Zika virus

text: We report here that in rat and human neuroprogenitor cells as well as rat embryonic cortical neurons Zika virus (ZIKV) infection leads to ribosomal stress that is characterized by structural disruption of the nucleolus. The anti-nucleolar effects were most pronounced in postmitotic neurons. Moreover, in the latter system, nucleolar presence of ZIKV capsid protein (ZIKV-C) was associated with ribosomal stress and apoptosis. Deletion of 22 C-terminal residues of ZIKV-C prevented nucleolar localization, ribosomal stress and apoptosis. Consistent with a casual relationship between ZIKV-C-induced ribosomal stress and apoptosis, ZIKV-C-overexpressing neurons were protected by loss-of-function manipulations targeting the ribosomal stress effector Tp53 or knockdown of the ribosomal stress mediator RPL11. Finally, capsid protein of Dengue virus, but not West Nile virus, induced ribosomal stress and apoptosis. Thus, anti-nucleolar and pro-apoptotic effects of protein C are flavivirus-species specific. In the case of ZIKV, capsid protein-mediated ribosomal stress may contribute to neuronal death, neurodevelopmental disruption and microcephaly.


title: Engineering Coronaviruses to Evaluate Emergence and Pathogenic Potential

text: A recent study provides a platform for generating infectious coronavirus genomes using sequence data, examining their capabilities of replicating in human cells and causing diseases in animal models, and evaluating therapeutics and vaccines. Similar approaches could be used to assess the potential of human emergence and pathogenicity for other viruses.


title: MERS and the dromedary camel trade between Africa and the Middle East

text: Dromedary camels are the most likely source for the coronavirus that sporadically causes Middle East respiratory syndrome (MERS) in humans. Serological results from archived camel sera provide evidence for circulation of MERS coronavirus (MERS-CoV) among dromedary camels in the Greater Horn of Africa as far back as 1983 and in Saudi Arabia as far back as 1992. High seroprevalences of MERS-CoV antibodies and the high virus prevalence in Saudi Arabian dromedary camels indicate an endemicity of the virus in the Arabian Peninsula, which predates the 2012 human MERS index case. Saudi Arabian dromedary camels show significantly higher MERS-CoV carrier rates than dromedary camels imported from Africa. Two MERS-CoV lineages identified in Nigerian camels were found to be genetically distinct from those found in camels and humans in the Middle East. This supports the hypothesis that camel imports from Africa are not of significance for circulation of the virus in camel populations of the Arabian Peninsula.


title: In utero infection with porcine reproductive and respiratory syndrome virus modulates leukocyte subpopulations in peripheral blood and bronchoalveolar fluid of surviving piglets

text: Abstract It is well known that piglets congenitally infected with porcine reproductive and respiratory syndrome virus (PRRSV) can be viremic at birth, and that preweaning mortality due to secondary infections often increases during acute outbreaks of PRRS. Therefore, an immunosuppressive effect of in utero infection has been suggested. The aim of the present study was to characterise the changes of leukocyte populations in piglets surviving in utero infection with PRRSV. A total of 27 liveborn uninfected control piglets and 22 piglets infected transplacentally with a Danish strain of PRRSV were included. At 2 and 4 weeks of age, 21 of 22 (96%) and 7 of 14 (50%) examined infected piglets were still viremic, whereas PRRSV could not be detected in the six infected piglets examined at 6 weeks of age. Flow cytometry analysis was used to determine the phenotypic composition of leukocytes in peripheral blood and bronchoalveolar lavage fluid (BALF) of 2-, 4- and 6-week-old infected piglets and age-matched uninfected controls. The key observation in the present study is that high levels of CD8+ cells constitute a dominant feature in peripheral blood and BALF of piglets surviving in utero infection with PRRSV. In BALF, the average high level of CD8+ cells in 2-week-old infected piglets (33.4±12.6%) was followed by a decline to 7.3±3.0 and 11.1±3.0% at 4 and 6 weeks of age. BALF of control piglets contained 1.6±0.9, 2.3±1.8 and 1.9±0.5% CD8+ cells, only. In peripheral blood, however, the average number of CD8+ cells remained at high levels in the infected piglets throughout the post-natal experimental period (2.8±1.9, 2.9±1.8 and 3.2±1.7×106 CD8+ cells/ml at 2, 4 and 6 weeks, respectively). In the controls, the average levels of CD8+ cells were 0.9±0.2, 1.9±1.7 and 1.6±0.5×106/ml, respectively. Furthermore, the numbers of CD2+, CD4+CD8+ and SLA-classII+ cells, respectively, in peripheral blood, together with the levels of CD2+ and CD3+ cells in BALF were increased in the infected piglets infected in utero compared to the uninfected controls. The kinetic analyses carried out in the present study reflect that in utero infection with PRRSV modulates immune cell populations in peripheral blood and BALF of surviving piglets. The observed changes are characterised by high levels of CD8+ cells supporting an important role of these cells in PRRSV infection. The present results, however, do not support the existence of post-natal immunosuppression following in utero infection with PRRSV.


title: Structural basis for catalysis and substrate specificity of a 3C-like cysteine protease from a mosquito mesonivirus

text: Abstract Cavally virus (CavV) is a mosquito-borne plus-strand RNA virus in the family Mesoniviridae (order Nidovirales). We present X-ray structures for the CavV 3C-like protease (3CLpro), as a free enzyme and in complex with a peptide aldehyde inhibitor mimicking the P4-to-P1 residues of a natural substrate. The 3CLpro structure (refined to 1.94 Å) shows that the protein forms dimers. The monomers are comprised of N-terminal domains I and II, which adopt a chymotrypsin-like fold, and a C-terminal α-helical domain III. The catalytic Cys-His dyad is assisted by a complex network of interactions involving a water molecule that mediates polar contacts between the catalytic His and a conserved Asp located in the domain II-III junction and is suitably positioned to stabilize the developing positive charge of the catalytic His in the transition state during catalysis. The study also reveals the structural basis for the distinct P2 Asn-specific substrate-binding pocket of mesonivirus 3CLpros.


title: Quantitative phosphoproteome on the silkworm (Bombyx mori) cells infected with baculovirus

text: BACKGROUND: Bombyx mori has become an important model organism for many fundamental studies. Bombyx mori nucleopolyhedrovirus (BmNPV) is a significant pathogen to Bombyx mori, yet also an efficient vector for recombinant protein production. A previous study indicated that acetylation plays many vital roles in several cellular processes of Bombyx mori while global phosphorylation pattern upon BmNPV infection remains elusive. METHOD: Employing tandem mass tag (TMT) labeling and phosphorylation affinity enrichment followed by high-resolution LC-MS/MS analysis and intensive bioinformatics analysis, the quantitative phosphoproteome in Bombyx mori cells infected by BmNPV at 24 hpi with an MOI of 10 was extensively examined. RESULTS: Totally, 6480 phosphorylation sites in 2112 protein groups were identified, among which 4764 sites in 1717 proteins were quantified. Among the quantified proteins, 81 up-regulated and 25 down-regulated sites were identified with significant criteria (the quantitative ratio above 1.3 was considered as up-regulation and below 0.77 was considered as down-regulation) and with significant p-value (p < 0.05). Some proteins of BmNPV were also hyperphosphorylated during infection, such as P6.9, 39 K, LEF-6, Ac58-like protein, Ac82-like protein and BRO-D. CONCLUSION: The phosphorylated proteins were primary involved in several specific functions, out of which, we focused on the binding activity, protein synthesis, viral replication and apoptosis through kinase activity.


title: Three 3D graphical representations of DNA primary sequences based on the classifications of DNA bases and their applications

text: Abstract In this article, we introduce three 3D graphical representations of DNA primary sequences, which we call RY-curve, MK-curve and SW-curve, based on three classifications of the DNA bases. The advantages of our representations are that (i) these 3D curves are strictly non-degenerate and there is no loss of information when transferring a DNA sequence to its mathematical representation and (ii) the coordinates of every node on these 3D curves have clear biological implication. Two applications of these 3D curves are presented: (a) a simple formula is derived to calculate the content of the four bases (A, G, C and T) from the coordinates of nodes on the curves; and (b) a 12-component characteristic vector is constructed to compare similarity among DNA sequences from different species based on the geometrical centers of the 3D curves. As examples, we examine similarity among the coding sequences of the first exon of beta-globin gene from eleven species and validate similarity of cDNA sequences of beta-globin gene from eight species.


Enfermedad COVID-19: el hospital del futuro ya está aquí


title: Molecular and Cellular Mechanisms for PRRSV Pathogenesis and Host Response to Infection

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) has caused tremendous amounts of economic losses to the swine industry for more than three decades, but its control is still unsatisfactory. A significant amount of information is available for host cell-virus interactions during infection, and it is evident that PRRSV has evolved to equip various strategies to disrupt the host antiviral system and provide favorable conditions for survival. The current study reviews viral strategies for modulations of cellular processes including innate immunity, apoptosis, microRNAs, inflammatory cytokines, and other cellular pathways.


title: Kinedoc, CISMeF et COVID-19: la nécessité de référencer les brochures pédagogiques pour le patient

text: Résumé La crise inédite du Covid-19 a fait apparaitre le besoin de recenser et de diffuser des supports didactiques thérapeutiques à destination des patients (auto-rééducation) en complément des séances, notamment dans le cadre du télésoin. Kinedoc, la banque documentaire francophone, a collaboré avec le D2IM du CHU de Rouen pour créer ce nouveau type de documents en adaptant le moteur de recherche du CISMeF qui recense déjà des publications similaires dans d’autres domaines. Désormais, il sera possible de trouver et de télécharger dans Kinedoc des brochures thérapeutiques dont le Collège de la Masso-Kinésithérapie (CMK) aura préalablement validé la conformité. Chaque société savante, association ou kinésithérapeute/physiothérapeute peut proposer de partager ses « brochures pédagogiques pour le patient », en les envoyant par courriel à cette adresse : secretariat@college-mk.org. Abstract With this unprecedented Covid-19 crisis, appeared the need to draw up a list and to spread pedagogical and therapeutic media for patients (self-rehabilitation), in addition to sessions, particularly in "telehealth". Kinedoc, a French database, collaborated with the D2IM of Rouen’s university hospital to create this new type of documents, adjusting CISMeF’s search engine, which has already listed similar publications in other fields. From now on, it will be possible to find and download in Kinedoc therapeutic brochures certified by the "Collège de la Masso-Kinésithérapie" (CMK). Every academic society, association or physiotherapist can suggest sharing its "pedagogical brochures for patients" by sending them to this address: secretariat@college-mk.org.


title: Redesigning a PhD measurement course for a new era in nursing science

text: Abstract Measurement is at the core of the research process. At the PhD level, students need to develop an in-depth understanding of measures relevant to their area of work and refine their knowledge of measurement issues. Traditionally, measurement coursework in Nursing focused on the psychometric evaluation of instruments measuring cognition and behavior. However, in the age of Big Data, precision medicine, and translational science, PhD students need to develop knowledge and skills relevant to these fields and to collaborate with experts from the different disciplines. Therefore, Nursing faculty need to recognize the state-of-the-science of nursing research and tend to a variety of measurement issues across a spectrum of operationalized concepts. Herein we present an overview of learning outcomes, instructional content and methods of delivery for a contemporary PhD-level course on measurement for Nursing Science. We also present our experience in the design, implementation, and evaluation of a novel PhD measurement course.


title: The role of the hotel industry in the response to emerging epidemics: a case study of SARS in 2003 and H1N1 swine flu in 2009 in Hong Kong

text: BACKGROUND: The global travel and tourism industry has been rapidly expanding in the past decades. The traditional focus on border screening, and by airline and cruise industries may be inadequate due to the incubation period of an infectious disease. This case study highlights the potential role of the hotel industry in epidemic preparedness and response. METHODS: This case study focuses on the epidemic outbreaks of SARS in 2003 and H1N1 swine flu in 2009 in Hong Kong, and the subsequent guidelines published by the health authority in relation to the hotel industry in Hong Kong which provide the backbone for discussion. RESULTS: The Metropole Hotel hastened the international spread of the 2003 SARS outbreak by the index case infecting visitors from Singapore, Vietnam, Canada as well as local people via close contact with the index case and the environmental contamination. The one-week quarantine of more than 300 guests and staff at the Metropark Hotel during the 2009 H1N1 swine flu exposed gaps in the partnership with the hotel industry. The subsequent guidelines for the hotel industry from the Centre of Health Protection focused largely on the maintenance of hygiene within the hotel premises. CONCLUSION: Positive collaborations may bring about effective preparedness across the health and the tourism sectors for future epidemics. Regular hygiene surveillance at hotel facilities, and developing coordination mechanism for impending epidemics on the use of screening, swift reporting and isolation of infected persons may help mitigate the impact of future events. Preparedness and contingency plans for infectious disease control for the hotel industry requires continuous engagement and dialogue.


title: Tropism and replication of Middle East respiratory syndrome coronavirus from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study

text: Summary Background Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic infection causing severe viral pneumonia, with index cases having resided in or recently travelled to the Arabian peninsula, and is a global concern for public health. Limited human-to-human transmission, leading to some case clusters, has been reported. MERS-CoV has been reported in dromedary camels but phenotypic characterisation of such viruses is limited. We aimed to compare MERS-CoV isolates from dromedaries in Saudi Arabia and Egypt with a prototype human MERS-CoV to assess virus replication competence and cell tropism in ex-vivo cultures of human bronchus and lung. Methods We characterised MERS-CoV viruses from dromedaries in Saudi Arabia and Egypt and compared them with a human MERS-CoV reference strain. We assessed viral replication kinetics and competence in Vero-E6 cells (rhesus monkey), tissue tropism in cultures of ex-vivo human bronchial and lung tissues, and cytokine and chemokine induction, gene expression, and quantification of viral RNA in Calu-3 cells (human respiratory tract). We used mock-infected tissue as negative controls for ex-vivo experiments and influenza A H5N1 as a positive control for cytokine and chemokine induction experiments in Calu-3 cells. Findings We isolated three dromedary strains, two from Saudi Arabia (Dromedary/Al-Hasa-KFU-HKU13/2013 [AH13] and Dromedary/Al-Hasa-KFU-HKU19D/2013 [AH19D]), and one from Egypt (Dromedary/Egypt-NRCE-HKU270/2013 [NRCE-HKU270]). The human and dromedary MERS-CoV strains had similar viral replication competence in Vero-E6 cells and respiratory tropism in ex-vivo cultures of the human respiratory tract, and had similar ability to evade interferon responses in the human-respiratory-tract-derived cell line Calu-3. Interpretation The similarity of virus tropism and replication competence of human and dromedary MERS-CoV from the Arabian peninsula, and genetically diverse dromedary viruses from Egypt, in ex-vivo cultures of the human respiratory tract suggests that dromedary viruses from Saudi Arabia and Egypt are probably infectious to human beings. Exposure to zoonotic MERS-CoV is probably occurring in a wider geographical region beyond the Arabian peninsula. Funding King Faisal University, Egyptian National Research Centre, Hong Kong Food and Health Bureau, National Institute of Allergy and Infectious Diseases, and European Community Seventh Framework Program.


title: Challenges presented by MERS corona virus, and SARS corona virus to global health

text: Numerous viral infections have arisen and affected global healthcare facilities. Millions of people are at severe risk of acquiring several evolving viral infections through several factors. In the present article we have described about risk factors, chance of infection, and prevention methods of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV), human coronaviruses (CoVs) frequently cause a normal cold which is mild and self-restricting. Zoonotic transmission of CoVs such as the newly discovered MERS-CoV and SARS-CoV, may be associated with severe lower respiratory tract infection. The present review provides the recent clinical and pathological information on MERS and SARS. The task is to transform these discoveries about MERS and SARS pathogenesis and to develop intervention methods that will eventually allow the effective control of these recently arising severe viral infections. Global health sector has learnt many lessons through the recent outbreak of MERS and SARS, but the need for identifying new antiviral treatment was not learned. In the present article we have reviewed the literature on the several facets like transmission, precautions and effectiveness of treatments used in patients with MERS-CoV and SARS infections.


title: COVID-19 and diabetes mellitus: An unholy interaction of two pandemics

text: Abstract Background and aims Diabetes mellitus is associated with poor prognosis in patients with COVID-19. On the other hand, COVID-19 contributes to worsening of dysglycemia in people with diabetes mellitus over and above that contributed by stress hyperglycemia. Herein, we have reviewed the two-way interactions between COVID-19 and diabetes mellitus. Methods We have performed an extensive literature search for articles in PubMed, EMBASE and Google Scholar databases till April 25, 2020, with the following keywords: “COVID-19”, “SARS-CoV-2”, “diabetes”, “diabetes mellitus”, “SARS”, “infection” and “management of diabetes mellitus” with interposition of the Boolean operator “AND”. Results Compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists in people with DM contribute to poor prognosis in COVID-19. On the contrary, direct β-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir) can contribute to worsening of glucose control in people with diabetes mellitus. Conclusions The two-way interaction between COVID-19 and diabetes mellitus sets up a vicious cycle wherein COVID-19 leads to worsening of dysglycemia and diabetes mellitus, in turn, exacerbates the severity of COVID-19. Thus, it is imperative that people with DM take all necessary precautions and ensure good glycemic control amid the ongoing pandemic.


title: The Functional Protein Microarray as Molecular Decathlete: A Versatile Player in Clinical Proteomics

text: Functional protein microarrays were developed as a high-throughput tool to overcome the limitations of DNA microarrays and to provide a versatile platform for protein functional analyses. Recent years have witnessed tremendous growth in the use of protein microarrays, particularly functional protein microarrays, to address important questions in the field of clinical proteomics. In this review, we will summarize some of the most innovative and exciting recent applications of protein microarrays in clinical proteomics, including biomarker identification, pathogen-host interactions, and cancer biology.


title: MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes sporadic zoonotic disease and healthcare-associated outbreaks in human. MERS is often complicated by acute respiratory distress syndrome (ARDS) and multi-organ failure(1,2). The high incidence of renal failure in MERS is a unique clinical feature not often found in other human coronavirus infections(3,4). Whether MERS-CoV infects the kidney and how it triggers renal failure are not understood(5,6). Here, we demonstrated renal infection and apoptotic induction by MERS-CoV in human ex vivo organ culture and a nonhuman primate model. High-throughput analysis revealed that the cellular genes most significantly perturbed by MERS-CoV have previously been implicated in renal diseases. Furthermore, MERS-CoV induced apoptosis through upregulation of Smad7 and fibroblast growth factor 2 (FGF2) expression in both kidney and lung cells. Conversely, knockdown of Smad7 effectively inhibited MERS-CoV replication and protected cells from virus-induced cytopathic effects. We further demonstrated that hyperexpression of Smad7 or FGF2 induced a strong apoptotic response in kidney cells. Common marmosets infected by MERS-CoV developed ARDS and disseminated infection in kidneys and other organs. Smad7 and FGF2 expression were elevated in the lungs and kidneys of the infected animals. Our results provide insights into the pathogenesis of MERS-CoV and host targets for treatment. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nmicrobiol.2016.4) contains supplementary material, which is available to authorized users.


title: Viral transport and the cytoskeleton

text: Abstract In the past decade, studies into the way in which intracellular bacterial pathogens hijack and subvert their hosts have provided many important insights into regulation of the actin cytoskeleton and cell motility, in addition to increasing our understanding of the infection process. Viral pathogens, however, may ultimately unlock more cellular secrets as they are even more dependent on their hosts during their life cycle.


title: Decrease in acute coronary syndrome presentations during the COVID19 pandemic in upstate New York

text: Abstract Introduction The COVID 19 virus is a devastating pandemic that has impacted the US healthcare system significantly. More than one study reported a significant decrease in acute coronary syndrome admissions during that pandemic which is still due to unknown reasons. Methods This is a retrospective non-controlled multi-centered study of 180 patients (117 males and 63 females) with acute coronary syndrome (STEMI and NSTEMI) admitted during March/April of 2019 and March/April 2020 in Upstate New York. Results A total of 113 patients (61.9% males, 38.1% females) with a mean age of 72.3±14.2 presented during March/April 2019 with ACS (STEMI + NSTEMI) while only 67 (70.1% males, 29.9% females) COVID 19 negative patients with a mean age of 65.1±14.5 presented during the same period (March/April) in 2020. This is a drop by 40.7% (P <.05) of total ACS cases during the COVID 19 pandemic. In NSTEMI patients, 36.4% presented late (>24hours of symptoms) during the COVID 19 pandemic in comparison with 2019 (27.1%, P =.033). Conclusion The COVID 19 pandemic led to a substantial drop by 40.7% (P <.05) of total ACS admissions in our area. This decrease in hospital admissions and late presentations can be a worrisome sign for an increase in future complications of myocardial infarctions.


title: The Fertility Quality of Life (FertiQoL) tool: development and general psychometric properties

text: Objective To develop the first international instrument to measure fertility quality of life, FertiQoL, in men and women experiencing fertility problems, to evaluate the preliminary psychometric properties of this new tool and to translate FertiQoL into multiple languages. Design Survey. Setting Online and fertility clinics in USA, Australia/New Zealand, Canada, and United Kingdom. Participants A total of 1,414 people with fertility problems. Intervention(s) None. Main Outcome Measure(s) FertiQoL. Result(s) FertiQoL consists of 36 items that assess core (24 items) and treatment-related (10 items) quality of life as well as overall life and physical health (2 items). Cronbach reliability statistics for the Core and Treatment FertiQoL (and subscales) were satisfactory, in the range of 0.72 and 0.92. Sensitivity analyses showed that FertiQoL detected expected relations between quality of life and gender, parity, and support seeking. FertiQoL was translated into 20 languages by the same translation team, with each translation verified by local bilingual fertility experts. Conclusion(s) FertiQoL is a reliable measure of the impact of fertility problems and its treatment on quality of life. Future research should establish its use in cross-cultural research and clinical work.


title: A nationwide survey of Leishmania infantum infection in cats and associated risk factors in Italy

text: Though scantly investigated, Leishmania infantum infection and clinical cases of leishmaniasis in cats have been recently reported in several countries of the Mediterranean basin, with large variability in prevalence data. A major limitation in the comparability of the data available is attributed to the differences in diagnostic techniques employed and cat populations sampled. The aim of this study was to assess the prevalence of L. infantum infection in owned cats across Italy by serological and molecular tests and the identification of potential risk factors. Blood samples from 2,659 cats from northern (n = 1,543), central (n = 471) and southern (n = 645) Italy were tested for antibodies against L. infantum, by an immunofluorescence antibody test and for the parasites’ DNA, by real-time PCR. Samples were additionally screened for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) proviral DNAs. An overall cumulative L. infantum prevalence of 3.9% was recorded by serology (3.3%) and/or qPCR (0.8%), with a higher rate (10.5%) in southern Italy. The risk of L. infantum infection in cats was significantly associated to the geographical areas (South vs North and Centre; p<0.0001), age class (from 19 months to 6 years old vs ≤18 months old, p = 0.0003), neutering status (not neutered vs neutered, p = 0.0028) and FIV infection (p = 0.0051).Though the role of cats in the epidemiology of L. infantum is still debated, our findings indicate that cats are exposed to and/or infected by this protozoan, mainly in endemic regions of Italy. Hence, a standardization of procedures for a prompt diagnosis of L. infantum infection in cats and for screening cat population is crucial for a better understanding of the epidemiology of feline leishmaniasis, and of the potential role of cats in the transmission cycle of zoonotic visceral leishmaniasis.


title: Management of the slowly emerging zoonosis, Hendra virus, by private veterinarians in Queensland, Australia: a qualitative study

text: BACKGROUND: Veterinary infection control for the management of Hendra virus (HeV), an emerging zoonosis in Australia, remained suboptimal until 2010 despite 71.4% (5/7) of humans infected with HeV being veterinary personnel or assisting a veterinarian, three of whom died before 2009. The aim of this study was to identify the perceived barriers to veterinary infection control and HeV management in private veterinary practice in Queensland, where the majority of HeV outbreaks have occurred in Australia. RESULTS: Most participants agreed that a number of key factors had contributed to the slow uptake of adequate infection control measures for the management of HeV amongst private veterinarians: a work culture characterised by suboptimal infection control standards and misconceptions about zoonotic risks; a lack of leadership and support from government authorities; the difficulties of managing biosecurity and public health issues from a private workforce perspective; and the slow pattern of emergence of HeV. By 2010, some infection control and HeV management changes had been implemented. Participants interviewed agreed that further improvements remained necessary; but also cautioned that this was a complex process which would require time. CONCLUSION: Private veterinarians and government authorities prior to 2009 were unprepared to handle new slowly emerging zoonoses, which may explain their mismanagement of HeV. Slowly emerging zoonoses may be of low public health significance but of high significance for specialised groups such as veterinarians. Private veterinarians, who are expected to fulfil an active biosecurity and public health role in the frontline management of such emerging zoonoses, need government agencies to better recognise their contribution, to consult with the veterinary profession when devising guidelines for the management of zoonoses and to provide them with greater leadership and support. We propose that specific infection control guidelines for the management of slowly emerging zoonoses in private veterinary settings need to be developed.


title: Porcine epidemic diarrhea in China

text: Abstract Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by Porcine epidemic diarrhea virus (PEDV) that characterized by vomiting, diarrhea, and dehydration. PEDV was first identified in the 1980s in China, and since then, it has become one of the most common viral causes of diarrhea. In October 2010, a large-scale outbreak of PED caused by a PEDV variant occurred in China, resulting in tremendous economic losses. This review presents a comprehensive description of PEDV history, prevalence, molecular features, and prevention and control strategies in China.


title: Disposition of the car☐y-terminus tail of rabbit lactase-phlorizin hydrolase elucidated by phosphorylation with protein kinase A in vitro and in tissue culture

text: Abstract The intracellular disposition of the car☐y-terminus tail of rabbit lactase-phlorizin hydrolase (LPH) is demonstrated, using a specific phosphorylation of Ser1916 by protein kinase A (PKA). This phosphorylation is shown to occur not only in vitro (with pure LPH and pure catalytic subunit of PKA), but also in an organ culture of the small intestine. Cholera toxin, which is known to act in vivo on the membranes of the small intestine, with severe clinical consequences, and to elevate the intracellular cyclic AMP of enterocytes, is shown to enhance significantly the phosphorylation of LPH in intact cells grown as an organ culture. These findings establish the cytosolic orientation of the car☐yterminus tail of LPH in situ, and raise the possibility that the tail itself and its phosphorylation by PKA may have a physiological or physiopathological significance.


COVID‐19: a major cause of cachexia and sarcopenia?


title: The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer

text: The generation of reducing equivalent NADPH via glucose-6-phosphate dehydrogenase (G6PD) is critical for the maintenance of redox homeostasis and reductive biosynthesis in cells. NADPH also plays key roles in cellular processes mediated by redox signaling. Insufficient G6PD activity predisposes cells to growth retardation and demise. Severely lacking G6PD impairs embryonic development and delays organismal growth. Altered G6PD activity is associated with pathophysiology, such as autophagy, insulin resistance, infection, inflammation, as well as diabetes and hypertension. Aberrant activation of G6PD leads to enhanced cell proliferation and adaptation in many types of cancers. The present review aims to update the existing knowledge concerning G6PD and emphasizes how G6PD modulates redox signaling and affects cell survival and demise, particularly in diseases such as cancer. Exploiting G6PD as a potential drug target against cancer is also discussed.


The Nucleocapsid Protein of SARS–CoV-2: a Target for Vaccine Development


title: Preparation for the United States Medical Licensing Examinations in the Face of COVID-19

text: The COVID-19 pandemic has led to the canceling and rescheduling of the United States Medical Licensing Examination (USMLE) examinations due to the nationwide closure of the Prometric testing centers, which poses a significant challenge to medical students. The rescheduling of a high-stakes board examination leads to significant stress and potential burnout. Students may need guidance to decrease anxiety and reframe their study plan while maintaining their knowledge. Here, we combined board examination coaching tips with specific worked examples to describe how to prevent burnout, give recommendations for scheduling, and suggest practical approaches to USMLE and other high-stakes examinations.


title: Land Use Change and Human Health

text: Human activity is dramatically changing the global landscape. These changes in land use and cover are, in turn, altering the dynamics of infectious disease transmission in numerous ways. They are creating new habitat and breeding sites for disease vectors that, in many cases, favor disease transmission. They are leading to direct exposure to pathogens by changing water quality and runoff patterns. They are altering the nature of human–wildlife interactions and creating new exposure routes. Not surprisingly, these changes are occurring coincident with a rise in new or reemerging infectious diseases. These are not merely academic concerns. The diseases impacted by these changes represent a large percentage of the total global burden of disease.


Cardiopulmonary resuscitation in the COVID-19 era – Will the risk-benefit shift in resource-poor settings?


title: Gastrointestinal Diseases of Ferrets

text: Disease of the gastrointestinal (GI) tract is common in ferrets. This chapter reviews diseases of the upper and lower GI tract in ferrets, discusses how to differentiate between causes of diarrhea and vomiting, and provides information to help formulate an appropriate treatment plan. Clinicians should be familiar with the more common GI disorders in ferrets and be able to recognize clinical signs and differentiate among potential diagnoses.


title: GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses

text: GS-5734 is a monophosphate prodrug of an adenosine nucleoside analog that showed therapeutic efficacy in a non-human primate model of Ebola virus infection. It has been administered under compassionate use to two Ebola patients, both of whom survived, and is currently in Phase 2 clinical development for treatment of Ebola virus disease. Here we report the antiviral activities of GS-5734 and the parent nucleoside analog across multiple virus families, providing evidence to support new indications for this compound against human viruses of significant public health concern.


A novel strategy to generate virus vaccines with expanded genetic codes


title: Estimating the risk of Middle East respiratory syndrome (MERS) death during the course of the outbreak in the Republic of Korea, 2015

text: Summary Objectives A large cluster of the Middle East respiratory syndrome (MERS) linked to healthcare setting occurred from May to July 2015 in the Republic of Korea. The present study aimed to estimate the case fatality ratio (CFR) by appropriately taking into account the time delay from illness onset to death. We then compare our estimate against previously published values of the CFR for MERS, i.e., 20% and 40%. Methods Dates of illness onset and death of the MERS outbreak in the Republic of Korea were extracted from secondary data sources. Using the known distribution of time from illness onset to death and an integral equation model, we estimated the delay-adjusted risk of MERS death for the South Korean cluster. Results Our most up-to-date estimate of CFR for the MERS outbreak in South Korea was estimated at 20.0% (95% confidence intervals (CI): 14.6, 26.2). During the course of the outbreak, estimate of the CFR in real time appeared to have decreased and become significantly lower than 40%. Conclusions The risk of MERS death in Korea was consistent with published CFR. The estimate decreased with time perhaps due to time-dependent increase in case ascertainment. Crude ratio of cumulative deaths to cases underestimates the actual risk of MERS death because of time delay from illness onset to death.


Reply to: Bioactive Lipids and Coronavirus (COVID-19)-further Discussion


title: Immunohistological demonstration of feline infectious peritonitis virus antigen in paraffin-embedded tissues using feline ascites or murine monoclonal antibodies

text: Abstract Feline infectious peritonitis (FIP) virus antigen was demonstrated after methanol, ethanol or formalin fixation in paraffin-embedded tissues by means of monoclonal and polyclonal antibodies. The monoclonal antibody was induced by immunization with transmissible gastroenteritis virus. Polyclonal antibodies were obtained by purification on protein A-Sepharose of ascites fluid from a cat with FIP. Almost all cats diagnosed as suffering from FIP by postmortem and histological examination exhibited FIP virus (FIPV) antigen in macrophages in granulomas whereas FIPV antigen was only once demonstrable in another location.


title: The impact of physical activity on psychological health during Covid-19 pandemic in Italy

text: The worldwide spread of COVID-19 has upset the normality of Italian daily life, forcing population to social distancing and self-isolation. Since the containment precautions also concern sport-related activities, home workout remained the only possibility to play sports and stay active during the pandemic. The present study aimed to examine changes in the physical activity levels during self-quarantine in Italy, and the impact of exercise on psychological health. A total of 2974 Italian subjects has completed an online survey, but only 2524 subjects resulted eligible for this study. The questionnaire measured the total weekly physical activity energy expenditure before and during quarantine (i.e. the sum of walking, moderate-intensity physical activities, and vigorous-intensity physical activities) in Metabolic Equivalent Task minutes per week (MET–min/wk) using an adapted version of International Physical Activity Questionnaire and their psychological well-being using the Psychological General Well Being Index. Of the 2524 Italian subjects included in the study, 1426 were females (56.4%) and 1098 males (43.6%). Total physical activity significantly decreased between before and during COVID-19 pandemic (Mean: 2429 vs. 1577 MET–min/wk, ∗∗∗∗p < 0.0001), in all age groups and especially in men (Female, mean: 1994 vs. 1443 MET–min/wk, ∗∗∗∗p < 0.0001; Male, mean: 2998 vs. 1754 MET–min/wk, ∗∗∗∗p < 0.0001). Furthermore, a significant positive correlation was found between the variation of physical activity and mental well-being (r = 0.07541, ∗∗∗p = 0.0002), suggesting that the reduction of total physical activity had a profoundly negative impact on psychological health and well-being of population. Based on this scientific evidence, maintaining a regular exercise routine is a key strategy for physical and mental health during a forced rest period like the current coronavirus emergency.


title: Residents’ awareness of the role of informal green spaces in a post-industrial city, with a focus on regulating services and urban adaptation potential

text: Abstract Urban green spaces (UGS) and the ecosystem services they provide are essential for the health and wellbeing of city dwellers. UGS are increasingly seen as a potential solution for sustainable urban planning and development. Informal green spaces (IGS), even though they may make up a large share of UGS, are often overlooked in this regard. This study examines residents’ awareness of the ecosystem services provided by IGS and their need for redevelopment. The data were collected through structured interviews in the immediate vicinity of selected IGS in the Polish city of Łódź. Łódź is typical of post-industrial European cities struggling with environmental (heatwaves, cloudbursts), social (aging, depopulation) and spatial (a neglected and dense city center) issues. Our results show that residents saw IGS as places able to provide a range of services, mostly of the regulating type, and even minor design interventions can improve the attractiveness of IGS. Taking this into account, we conclude that IGS are important vegetated areas in the city, which can be complementary to formal greenery.


title: A “possible” involvement of TNF-alpha in apoptosis induction in peripheral blood lymphocytes of cats with feline infectious peritonitis

text: Abstract Feline infectious peritonitis (FIP) cats show a decrease in peripheral blood lymphocyte counts, and a particularly marked decrease in T cells including CD4+ and CD8+ cells. In this study, we showed that lymphopenia observed in FIP cats was due to apoptosis, and that the ascitic fluid, plasma, and culture supernatant of peritoneal exudate cells (adherent cells with macrophage morphology, or PEC) from FIP cats readily induced apoptosis in specific pathogen-free cat peripheral blood mononuclear cells, particularly CD8+ cells. In addition, TNF-alpha released from macrophages and TNF-receptor (TNFR) 1 and TNFR2 mRNA expression in lymphocytes were closely involved in this apoptosis induction. In particular, in CD8+ cells cultured in the presence of the PEC culture supernatant, the expression levels of TNFR1 and TNFR2 mRNA were increased, indicating that CD8+ cells are more susceptible to apoptosis induction by TNF-alpha than other lymphocyte subsets, particularly B cells (CD21+ cells). The results of this study suggest that TNF-alpha, produced by virus-infected macrophages, is responsible for induction of apoptosis in uninfected T cells, primarily CD8+ T cells.


title: BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID‐19 therapy

text: Bruton's tyrosine kinase (BTK) signaling is involved in innate immune responses and regulates the production of proinflammatory cytokines that can contribute to COVID‐19 immunopathology. Clinical trials with BTK inhibitors in COVID‐19 treatment have been proposed, and previous studies have attempted to investigate the therapeutic effects of ibrutinib and underlying mechanisms in treating viral pneumonia. These attempts, however, did not consider potential off target effect of BTK inhibitors on T cell differentiation, function, and survival, which may be beneficial in treatment for COVID‐19. Here, we summarize the current knowledge of BTK/IL‐2‐inducible T‐cell kinase (ITK) signaling in immunopathology and lymphopenia and discuss the potential of BTK/ITK dual inhibitors such as ibrutinib in modulating immunopathology and lymphopenia, for COVID‐19 therapy.


In memory of Michael J. O. Wakelam (1955–2020): a pioneer in lipid signalling and lipidomics


title: Update on molecular techniques for diagnostic testing of infectious disease

text: The era of diagnostic molecular biology has arrived for small animal clinicians, and it is a near certainty that assays such as the PCR and RT-PCR will become more widely available for a wider array of infectious agents. Already there is an extensive list of infectious diseases of dogs and cats that have been investigated with molecular tools. A partial list is included in box 1. An understanding of the advantages and disadvantages of the molecular techniques and some of the questions these techniques can answer for clinicians can serve practitioners well in their approach to the diagnosis of infectious diseases in dogs and cats. It is likely that additional applications of these tools to small animal medicine will become apparent as investigators use and refine them for their research purposes, or as new uses emerge from human medical applications. Clinicians also are likely to reap the benefits of this knowledge. Because samples often are acquired easily from clinical patients in most practice settings, access to these tools puts all clinicians in the group of discoverers of new, or variations of, infectious diseases and their clinical manifestations.


title: Developing WHO rapid advice guidelines in the setting of a public health emergency

text: Abstract Objectives We describe newly established guidance for guideline developers at the World Health Organization (WHO) on the process and procedures for developing a rapid advice guideline in the context of a public health emergency (e.g., the 2014 Ebola epidemic). Study Design and Setting We based our approach on established rapid review methods, which were incorporated into existing WHO guideline development processes. Guidance was further informed by in-depth discussions of issues related to rapid guideline development with WHO staff (n = 6), who oversee the Organization's response to emergencies. Results We discuss criteria for considering if a rapid advice guideline is appropriate and feasible and outline the roles of various contributors across the phases of development. Further, we describe the methods and steps involved in performing rapid reviews, which are more fluid and iterative than for a standard guideline process. In general, rapid advice guidelines involve a shorter timeline, narrower scope, and the use of abbreviated methods for the evidence review. Conclusion Important differences exist between developing a standard guideline and a rapid advice guideline. However, the core principles for WHO guidelines apply to rapid advice guidelines including minimizing bias, applying transparent processes and the use of explicit methods.


title: Hesperetin protects crayfish Procambarus clarkii against white spot syndrome virus infection

text: Abstract Hesperetin is a natural flavanone compound, which mainly exists in lemons and oranges, and has potential antiviral and anticancer activities. In this study, hesperetin was used in a crayfish pathogen challenge to discover its effects on the innate immune system of invertebrates. The crayfish Procambarus clarkii was used as an experimental model and challenged with white spot syndrome virus (WSSV). Pathogen challenge experiments showed that hesperetin treatment significantly reduced the mortality caused by WSSV infection, while the VP28 copies of WSSV were also reduced. Quantitative reverse transcriptase polymerase chain reaction revealed that hesperetin increased the expression of several innate immune-related genes, including NF-kappaB and C-type lectin. Further analysis showed that hesperetin treatment plays a positive effects on three immune parameters like total hemocyte count, phenoloxidase and superoxide dismutase activity. Nevertheless, whether or not infected with WSSV, hesperetin treatment would significantly increase the hemocyte apoptosis rates in crayfish. These results indicated that hesperetin could regulate the innate immunity of crayfish, and delaying and reducing the mortality after WSSV challenge. Therefore, the present study provided novel insights into the potential therapeutic or preventive functions associated with hesperetin to regulate crayfish immunity and protect crayfish against WSSV infection, provide certain theoretical basis for production practice.


title: Cas d’une patiente de grand âge en hospitalisation aiguë pour une atteinte sévère de COVID-19: Aspects moteurs

text: Résumé Le virus SRAS-CoV-2, à l’origine de la pandémie actuelle de COVID-19, engendre des troubles respiratoires aigus qui peuvent conduire à une hospitalisation, essentiellement chez les personnes âgées. Le cas présenté est celui d’une patiente de grand âge présentant une atteinte pulmonaire sévère. Les évaluations motrices quotidiennes sur une semaine comprenaient le test Timed up and go, le test Five sit-to-stand, le test de force de serrage maximal et le recueil des constantes cardio-respiratoires (fréquence cardiaque, respiratoire et saturation en oxygène). Une évaluation cognitive et de la qualité de vie ont aussi été réalisés. Entre l’évaluation initiale et finale, la durée de réalisation du Timed Up and Go a diminué de 4.9 s, la performance au Five sit-to-stand est restée relativement stable, dans un contexte de sevrage de l’oxygène, de maintien de la saturation et d’une augmentation de la fréquence respiratoire. Malgré un pronostic péjoratif, l’amélioration respiratoire de la patiente s’est accompagnée d’améliorations motrices fonctionnelles. Les relations de régulations motrices et cardio-respiratoires sont discutées. Abstract The SARS-CoV-2 virus at the origin of the current COVID-19 pandemic is causing acute respiratory disorders that may lead to hospitalization, mainly in the elderly. The case presented is that of an old age patient with severe lung disease. Daily motor assessments over 1 week included Timed up and go test, the Five sit-to-stand test, the grip test and the collection of cardiorespiratory constants (heart rate, respiratory rate and 02 saturation). A cognitive and quality of life assessments were performed. Between the initial and final evaluation, the time taken to complete the Timed Up and Go decreased by 4.9 sec, the performance at the five sit-to-stand remained relatively stable, in a context of oxygen withdrawal, maintenance of saturation and an increase in respiratory rate. Despite a poor prognosis, the patient's respiratory improvement was accompanied by functional motor improvements. The relationship between motor and cardiorespiratory regulation is discussed.