title: A potent germline-like human monoclonal antibody targets a pH-sensitive epitope on H7N9 influenza hemagglutinin

text: The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Å) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA. m826 fully protects mice against lethal challenge with H7N9 virus through mechanisms likely involving antibody-dependent cell-mediated cytotoxicity (ADCC). Interestingly, immunogenetic analysis indicates that m826 is a germline antibody and m826-like sequences can be identified in H7N9-infected patients, healthy adults and newborn babies. These m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a tool for exploring mechanisms of virus infection inhibition by antibodies.


Emporiatrics: The growing area of concern


title: Enhanced Intrapulmonary Delivery of Anticancer siRNA for Lung Cancer Therapy Using Cationic Ethylphosphocholine-based Nanolipoplexes

text: Here, we report a cationic nanolipoplex as a pulmonary cellular delivery system for small-interfering RNA (siRNA). Six nanoliposomes differing in cationic lipids were formulated and screened in vitro and in vivo for cellular delivery functions in lung cells/tissues. Although the six nanoliposomes showed similar siRNA delivery efficiency in vitro, they exhibited significant differences in pulmonary cellular delivery functions in vivo. Among the various nanoliposomes, cationic dioleoyl-sn-glycero-3-ethylphosphocholine and cholesterol (ECL)-based nanoliposomes showed the highest pulmonary cellular delivery in vivo and the lowest cytotoxicity in vitro. The delivery efficiency of fluorescent siRNA in ECL nanoliposomes was 26.2-fold higher than that of naked siRNA in vivo. Treatment with Mcl1 (myeloid cell leukemia sequence 1)-specific siRNA (siMcl1) using ECL nanolipoplexes reduced target expression in B16F10 cell lines, whereas control, luciferase-specific siGL2 in ECL nanolipoplexes did not. In metastatic lung cancer mouse models induced by B16F10 or Lewis lung carcinoma (LLC) cells, intratracheal administration of siMcl1 in ECL nanolipoplexes significantly silenced Mcl1 mRNA and protein levels in lung tissue. Reduced formation of melanoma tumor nodules was observed in the lung. These results demonstrate the utility of ECL nanoliposomes for pulmonary delivery of therapeutic siRNA for the treatment of lung cancers and potentially for other respiratory diseases.


title: Analysis of Coronavirus Temperature-Sensitive Mutants Reveals an Interplay between the Macrodomain and Papain-Like Protease Impacting Replication and Pathogenesis

text: Analysis of temperature-sensitive (ts) mutant viruses is a classic method allowing researchers to identify genetic loci involved in viral replication and pathogenesis. Here, we report genetic analysis of a ts strain of mouse hepatitis virus (MHV), tsNC11, focusing on the role of mutations in the macrodomain (MAC) and the papain-like protease 2 (PLP2) domain of nonstructural protein 3 (nsp3), a component of the viral replication complex. Using MHV reverse genetics, we generated a series of mutant viruses to define the contributions of macrodomain- and PLP2-specific mutations to the ts phenotype. Viral replication kinetics and efficiency-of-plating analysis performed at permissive and nonpermissive temperatures revealed that changes in the macrodomain alone were both necessary and sufficient for the ts phenotype. Interestingly, mutations in the PLP2 domain were not responsible for the temperature sensitivity but did reduce the frequency of reversion of macrodomain mutants. Coimmunoprecipitation studies are consistent with an interaction between the macrodomain and PLP2. Expression studies of the macrodomain-PLP2 portion of nsp3 indicate that the ts mutations enhance proteasome-mediated degradation of the protein. Furthermore, we found that during virus infection, the replicase proteins containing the MAC and PLP2 mutations were more rapidly degraded at the nonpermissive temperature than were the wild-type proteins. Importantly, we show that the macrodomain and PLP2 mutant viruses trigger production of type I interferon in vitro and are attenuated in mice, further highlighting the importance of the macrodomain-PLP2 interplay in viral pathogenesis. IMPORTANCE Coronaviruses (CoVs) are emerging human and veterinary pathogens with pandemic potential. Despite the established and predicted threat these viruses pose to human health, there are currently no approved countermeasures to control infections with these viruses in humans. Viral macrodomains, enzymes that remove posttranslational ADP-ribosylation of proteins, and viral multifunctional papain-like proteases, enzymes that cleave polyproteins and remove polyubiquitin chains via deubiquitinating activity, are two important virulence factors. Here, we reveal an unanticipated interplay between the macrodomain and the PLP2 domain that is important for replication and antagonizing the host innate immune response. Targeting the interaction of these enzymes may provide new therapeutic opportunities to treat CoV disease.


title: Estimating the early death toll of COVID-19 in the United States

text: BACKGROUND: Efforts to track the severity and public health impact of the novel coronavirus, COVID-19, in the US have been hampered by testing issues, reporting lags, and inconsistency between states. Evaluating unexplained increases in deaths attributed to broad outcomes, such as pneumonia and influenza (P&I) or all causes, can provide a more complete and consistent picture of the burden caused by COVID-19. METHODS: We evaluated increases in the occurrence of deaths due to P&I above a seasonal baseline (adjusted for influenza activity) or due to any cause across the United States in February and March 2020. These estimates are compared with reported deaths due to COVID-19 and with testing data. RESULTS: There were notable increases in the rate of death due to P&I in February and March 2020. In a number of states, these deaths pre-dated increases in COVID-19 testing rates and were not counted in official records as related to COVID-19. There was substantial variability between states in the discrepancy between reported rates of death due to COVID-19 and the estimated burden of excess deaths due to P&I. The increase in all-cause deaths in New York and New Jersey is 1.5–3 times higher than the official tally of COVID-19 confirmed deaths or the estimated excess death due to P&I. CONCLUSIONS: Excess P&I deaths provide a conservative estimate of COVID-19 burden and indicate that COVID-19-related deaths are missed in locations with inadequate testing or intense pandemic activity.


Senegal faces the coronavirus disease −19 challenge


title: Drug repurposing against COVID-19: focus on anticancer agents

text: BACKGROUND: The very limited time allowed to face the COVID-19 pandemic poses a pressing challenge to find proper therapeutic approaches. However, synthesis and full investigation from preclinical studies to phase III trials of new medications is a time-consuming procedure, and not viable in a global emergency, such as the one we are facing. MAIN BODY: Drug repurposing/repositioning, a strategy effectively employed in cancer treatment, can represent a valid alternative. Most drugs considered for repurposing/repositioning in the therapy of the COVID-19 outbreak are commercially available and their dosage and toxicity in humans is well known, due to years (or even decades) of clinical use. This can allow their fast-track evaluation in phase II–III clinical trials, or even within straightforward compassionate use. Several drugs being re-considered for COVID-19 therapy are or have been used in cancer therapy. Indeed, virus-infected cells are pushed to enhance the synthesis of nucleic acids, protein and lipid synthesis and boost their energy metabolism, in order to comply to the “viral program”. Indeed, the same features are seen in cancer cells, making it likely that drugs interfering with specific cancer cell pathways may be effective as well in defeating viral replication. SHORT CONCLUSION: To our knowledge, cancer drugs potentially suitable for facing SARS-CoV-2 infection have not been carefully reviewed. We present here a comprehensive analysis of available information on potential candidate cancer drugs that can be repurposed for the treatment of COIVD-19.


title: Dermatological findings in SARS‐CoV‐2 positive patients: An observational study from North India

text: A novel coronavirus (severe acute respiratory syndrome corononavirus‐2; SARS‐CoV‐2) has affected millions of people across the world. The coronavirus disease (COVID‐19) resulting from SARS‐CoV‐2 manifests in variable clinical severity, featuring both respiratory and extra‐respiratory symptoms. Dermatological manifestations of COVID‐19 are sparsely reported. To study the various dermatological findings in SARS‐CoV‐2 positive patients in Indian population. This article is protected by copyright. All rights reserved.


title: Respiratory Conditions in Coronavirus Disease 2019 (COVID-19): Important Considerations Regarding Novel Treatment Strategies to Reduce Mortality

text: Abstract A novel virus named 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) causes symptoms that are classified as coronavirus disease (COVID-19). Respiratory conditions are extensively described among more serious cases of COVID-19, and the onset of acute respiratory distress syndrome (ARDS) is one of the hallmark features of critical COVID-19 cases. ARDS can be directly life-threatening because it is associated with low blood oxygenation levels and can result in organ failure. There are no generally recognized effective treatments for COVID-19, but treatments are urgently needed. Anti-viral medications and vaccines are in the early developmental stages and may take many months or even years to fully develop. At present, management of COVID-19 with respiratory and ventilator support are standard therapeutic treatments, but unfortunately such treatments are associated with high mortality rates. Therefore, it is imperative to consider novel new therapeutic interventions to treat/ameliorate respiratory conditions associated with COVID-19. Alternate treatment strategies utilizing clinically available treatments such as hyperbaric oxygen therapy (HBOT), packed red blood cell (pRBC) transfusions, or erthropoiesis-stimulating agent (ESA) therapy were hypothesized to increase oxygenation of tissues by alternative means than standard respiratory and ventilator treatments. It was also revealed that alternative treatments currently being considered for COVID-19 such as chloroquine and hydroxychloroquine by increasing hemoglobin production and increasing hemoglobin availability for oxygen binding and acetazolamine (for the treatment of altitude sickness) by causing hyperventilation with associated increasing levels of oxygen and decreasing levels of carbon dioxide in the blood may significantly ameliorate COVID-19 respiratory symptoms. In conclusion, is recommend, given HBOT, pRBC, and ESA therapies are currently available and routinely utilized in the treatment of other conditions, that such therapies be tried among COVID-19 patients with serious respiratory conditions and that future controlled-clinical trials explore the potential usefulness of such treatments among COVID-19 patients with respiratory conditions.


title: MCPIP1 negatively regulate cellular antiviral innate immune responses through DUB and disruption of TRAF3-TBK1-IKKε complex

text: Abstract IFNβ innate immune plays an essential role in antiviral immune. Previous reports suggested that many important regulatory proteins in innate immune pathway may be modified by ubiquitin and that many de-ubiquitination (DUB) proteins may affect immunity. Monocyte chemotactic protein-inducing protein 1 (MCPIP1), one of the CCCH Zn finger-containing proteins, was reported to have DUB function, but its effect on IFNβ innate immune was not fully understood. In this study, we uncovered a novel mechanism that may explain how MCPIP1 efficiently inhibits IFNβ innate immune. It was found that MCPIP1 negatively regulates the IFNβ expression activated by RIG-I, STING, TBK1, IRF3. Furthermore, MCPIP1 inhibits the nuclear translocation of IRF3 upon stimulation with virus, which plays a key role in type I IFN expression. Additionally, MCPIP1 interacts with important modulators of IFNβ expression pathway including IPS1, TRAF3, TBK1 and IKKε. Meanwhile, the interaction between the components in TRAF3-TBK1-IKKε complex was disrupted by MCPIP1. These results collectively suggest MCPIP1 as an innate immune regulator encoded by the host and point to a new mechanism through which MCPIP1 negatively regulates IRF3 activation and type I IFNβ expression.


title: Stem Cells and Cell Therapy Approaches in Lung Biology and Diseases

text: Cell-based therapies with embryonic or adult stem cells, including induced pluripotent stem cells, have emerged as potential novel approaches for several devastating and otherwise incurable lung diseases including emphysema, pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome. Although initial studies suggested engraftment of exogenously administered stem cells in lung, this is now generally felt to be a rare occurrence of uncertain physiologic significance. However, more recent studies have demonstrated paracrine effects of administered cells, including stimulation of angiogenesis and modulation of local inflammatory and immune responses in mouse lung disease models. Based on these studies and on safety and initial efficacy data from trials of adult stem cells in other diseases, groundbreaking clinical trials of cell-based therapy have been initiated for pulmonary hypertension and for chronic obstructive pulmonary disease. In parallel, the identity and role of endogenous lung progenitor cells in development and in repair from injury and potential contribution as lung cancer stem cells continue to be elucidated. Most recently, novel bioengineering approaches have been applied to develop functional lung tissue ex vivo. Advances in each of these areas will be described in this review with particular reference to animal models.


title: A survey of SNOMED CT implementations

text: Abstract The Systematised Nomenclature of Medicine Clinical Terms (SNOMED CT) has been designated as the recommended clinical reference terminology for use in clinical information systems around the world and is reported to be used in over 50 countries. However, there are still few implementation details. This study examined the implementation of SNOMED CT in terms of design, use and maintenance issues involved in 13 healthcare organisations across eight countries through a series of interviews with 14 individuals. While a great deal of effort has been spent on developing and refining SNOMED CT, there is still much work ahead to bring SNOMED CT into routine clinical use.


title: Sequence of the genome RNA of rubella virus: Evidence for genetic rearrangement during togavirus evolution

text: Abstract The nucleotide sequence of the rubella virus (RUB) genomic RNA was determined. The RUB genomic RNA is 9757 nucleotides in length [excluding the poly(A) tail] and has a G/C content of 69.5%, the highest of any RNA virus sequenced to date. The RUB genomic RNA contains two long open reading frames (ORFs), a 5′-proximal ORF of 6656 nucleotides and a 3′-proximal ORF of 3189 nucleotides which encodes the structural proteins. Thus, the genomic organization of RUB is similar to that of alphaviruses, the other genus of the Togavirus family, and the 5′-proximal ORF of RUB therefore putatively codes for the nonstructural proteins. Sequences homologous to three regions of nucleotide sequence highly conserved among alphaviruses (a stem-and-loop structure at the 5′ end of the genome, a 51-nucleotide conserved sequence near the 5′ end of the genome, and a 20-nucleotide conserved sequence at the subgenomic RNA start site) were found in the RUB genomic RNA. Amino acid sequence comparisons between the nonstructural ORF of RUB and alphaviruses revealed only one short (122 amino acids) region of significant homology, indicating that these viruses are only distantly related. This region of homology is located at the NH2 terminus of nsP3 in the alphavirus genome. The RUB nonstructural protein ORF contains two global amino acid motifs conserved in a large number of positive-polarity RNA viruses, a motif indicative of helicase activity and a motif indicative of replicase activity. The order of the helicase motif and the nsP3 homology region in the RUB genome is reversed with respect to the alphavirus genome indicating that a genetic rearrangement has occurred during the evolution of these viruses.


title: Disease Management of Dairy Calves and Heifers

text: This article focuses on the most important diseases of dairy calves and heifers and presents clinical approaches that can improve detection, diagnosis, and treatment of herd-based problems. A systematic herd investigation strategy is pivotal to define the problems, understand important risk factors, develop a plan, and make recommendations for disease management accurately. A review of records, colostrum and feeding routines, housing and bedding management, routine procedures, vaccination, and treatment protocols begins the investigation and determines which diagnostic procedures and testing strategies are most useful. Disease management is most effective when the problem source is well defined and the exposure can be limited, calf immunity can be enhanced, or a combination of both. Screening examinations performed regularly or done at strategic time points improves detection of disease, can be used to monitor treatment outcomes, and can avoid disease outbreaks.


Mental health of medical professionals during the covid‐19 pandemic in Togo


title: Effect of different routes of immunization with bovine rotavirus on lactogenic antibody response in mice

text: Summary The effect of different routes of immunization with either live or killed bovine rotavirus (BRV) on the production of lactogenic antibody response in mice was evaluated. The routes of immunization were intramuscular (IM), oral (O) or intradermal in the mammary region (IMam). Following immunization, serum antibody responses were monitored by an enzyme linked immunosorbent assay (ELISA). Following whelping, the mice were allowed to stay with their mother until sacrificed on alternate days post-parturition from day 1–11. Milk from their stomach was collected for antibody titration by ELISA and virus neutralization test. Regardless of the routes of immunization, a rapid increase in serum anti-rotavirus antibody titers was observed for the first 5 wk after immunization followed by a gradual decline. After parturition, the mean antibody titer of lacteal secretions, as determined by ELISA, increased gradually for 7 days with the greatest increase on day 9, followed by a decrease in anti-rotavirus antibody. These titers also correlated with antibody titers in milk as measured by virus neutralization test. The best lactogenic antibody response was observed when IMam × IM × 2 route of immunization was used with live BRV as the antigen. Interestingly, immunization via the oral route with killed BRV also resulted in good antibody responses. In contrast, in the group where killed BRV was used, animals receiving 3× orally had the highest antibody titer. The distribution of different antibody subtypes in milk samples revealed IgG to be the predominant antibody followed by IgM and IgA. Irrespective of the route of administration, there was an increase in IgA on day 9 as compared to day 1 in most of the groups. The significant role played by mucosal immunity in passive protection and the possible ways to modulate subtype specific lactogenic immune response are discussed. Animals models; Lactogenic immunity; Rotaviruses


title: Using web search queries to monitor influenza-like illness: an exploratory retrospective analysis, Netherlands, 2017/18 influenza season

text: BACKGROUND: Despite the early development of Google Flu Trends in 2009, standards for digital epidemiology methods have not been established and research from European countries is scarce. AIM: In this article, we study the use of web search queries to monitor influenza-like illness (ILI) rates in the Netherlands in real time. METHODS: In this retrospective analysis, we simulated the weekly use of a prediction model for estimating the then-current ILI incidence across the 2017/18 influenza season solely based on Google search query data. We used weekly ILI data as reported to The European Surveillance System (TESSY) each week, and we removed the then-last 4 weeks from our dataset. We then fitted a prediction model based on the then-most-recent search query data from Google Trends to fill the 4-week gap (‘Nowcasting’). Lasso regression, in combination with cross-validation, was applied to select predictors and to fit the 52 models, one for each week of the season. RESULTS: The models provided accurate predictions with a mean and maximum absolute error of 1.40 (95% confidence interval: 1.09–1.75) and 6.36 per 10,000 population. The onset, peak and end of the epidemic were predicted with an error of 1, 3 and 2 weeks, respectively. The number of search terms retained as predictors ranged from three to five, with one keyword, ‘griep’ (‘flu’), having the most weight in all models. DISCUSSION: This study demonstrates the feasibility of accurate, real-time ILI incidence predictions in the Netherlands using Google search query data.


title: Development of non-traumatic osteonecrosis of the femoral head requires toll-like receptor 7 and 9 stimulations and is boosted by repression on nuclear factor kappa B in rats

text: Non-traumatic osteonecrosis of the femoral head (ONFH) often occurs after corticosteroid therapy in patients with inflammatory diseases. Recent studies suggest that toll-like receptor (TLR) signaling may contribute to the pathogenesis of inflammatory diseases, and that the reason for corticosteroid therapy for inflammatory diseases is related to the anti-inflammatory activities of corticosteroids through the reduction of NF-κB. We hypothesized that the administration of TLR ligands in combination with corticosteroid causes ONFH and that transcription factors may contribute to the pathogenesis of ONFH. The aim of the study was to evaluate (1) the incidence of ONFH in rats after the administration of TLR7 or TLR9 ligands together with methylprednisolone (MPSL) and (2) whether transcription factors contribute to the development of ONFH. Male Wistar rats (n=148) were divided into five groups as follows: Group 1: Saline+MPSL, Group 2: Imiquimod+Saline, Group 3: Imiquimod+MPSL, Group 4: CpG-C+MPSL, Group 5: Imiquimod+BAY11-7082+MPSL. As a result, ONFH was observed in 0 of 12 rats in Group 1, in 1 of 10 in Group 2, in 6 of 12 in Group 3, in 4 of 12 in Group 4, in 0 of 9 in Group 5. MPSL treatment did not significantly affect IRF7 activity, whereas NF-κB activity was significantly repressed in Group 2 and Group 3. Furthermore, the repression in interferon regulatory factor 7 (IRF7) activity by BAY11-7082 interfered with the development of ONFH simultaneously with the MPSL treatment-induced repression in NF-κB activity. In conclusion, in the present study, corticosteroid treatment after the administration of TLR7 or TLR9 ligands caused ONFH. Repression in NF-κB activity by corticosteroid treatment boosted the development of ONFH.


title: Importance of cholesterol for infection of cells by transmissible gastroenteritis virus

text: Abstract In this study, we addressed the question whether cholesterol is important for transmissible gastroenteritis virus (TGEV), a porcine coronavirus, in the initiation of an infection. We found that cholesterol depletion from the cellular membrane by methyl-β-cyclodextrin (MβCD) significantly impaired the efficiency of TGEV infection. Infectivity was also reduced after depleting cholesterol from the viral envelope. This finding is surprising because coronaviruses bud from a pre-Golgi compartment which is expected to be low in cholesterol compared to the plasma membrane. Addition of exogenous cholesterol resulted in a restoration of the infectivity confirming our conclusion that efficient TGEV infection requires cholesterol in both the viral and the cellular membranes. Our data raise the possibility that the viral and cellular proteins involved in the entry process may be associated with cholesterol-rich membrane microdomains.


title: Dermatologic surgery training during the COVID‐19 era

text: COVID-19, a novel coronavirus, has spread throughout the world. Because of exponential growth, social distancing is a critical strategy to decrease transmission Thus, educational medical communities from many countries have transitioned to online didactics1 . Recommendations to cancel all non-urgent visits have been proposed2 . Our dermatology department has canceled all elective outpatient visits and surgeries. Consequently, trainees' surgical skills have been severely affected. To continue our educational program, we have implemented measures to help our trainees continue learning and maintaining surgical skills.


title: Current status on the development of pseudoviruses for enveloped viruses

text: Emerging and reemerging infectious diseases have a strong negative impact on public health. However, because many of these pathogens must be handled in biosafety level, 3 or 4 containment laboratories, research and development of antivirals or vaccines against these diseases are often impeded. Alternative approaches to address this issue have been vigorously pursued, particularly the use of pseudoviruses in place of wild‐type viruses. As pseudoviruses have been deprived of certain gene sequences of the virulent virus, they can be handled in biosafety level 2 laboratories. Importantly, the envelopes of these viral particles may have similar conformational structures to those of the wild‐type viruses, making it feasible to conduct mechanistic investigation on viral entry and to evaluate potential neutralizing antibodies. However, a variety of challenging issues remain, including the production of a sufficient pseudovirus yield and the inability to produce an appropriate pseudotype of certain viruses. This review discusses current progress in the development of pseudoviruses and dissects the factors that contribute to low viral yields.


Transforming food and agriculture systems with agroecology


Management strategies and role of telemedicine in a Surgery Unit during COVID-19 outbreak


title: Molecular decoys: antidotes, therapeutics and immunomodulators

text: Receptor–ligand interactions are fundamental to the regulation of cell physiology, enabling the communication between cells and their environment via signal transduction. Receptors are also exploited by toxins and infectious agents to mediate pathogenesis. Over the past 20 years, however, this bi-partite paradigm for cellular regulation, that is, receptors and their ligands, has been revised to include an unforeseen participant namely, soluble receptors or molecular decoys. Decoys function as nature's modifiers of potent responses such as inflammation, stimulation of cell proliferation and triggering apoptosis. Decoys not only provide the means to fine tune the regulation of these phenomena; they also serve as potential leads for the development of recombinant anti-toxins, anti-viral agents and novel therapeutics for combating cancer and inflammatory disease.


title: Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13

text: Abstract Severe acute respiratory syndrome (SARS) is an infectious disease with a strong potential for transmission upon close personal contact and is caused by the SARS-coronavirus (CoV). However, there are no natural or synthetic compounds currently available that can inhibit SARS-CoV. We examined the inhibitory effects of 64 purified natural compounds against the activity of SARS helicase, nsP13, and the hepatitis C virus (HCV) helicase, NS3h, by conducting fluorescence resonance energy transfer (FRET)-based double-strand (ds) DNA unwinding assay or by using a colorimetry-based ATP hydrolysis assay. While none of the compounds, examined in our study inhibited the DNA unwinding activity or ATPase activity of human HCV helicase protein, we found that myricetin and scutellarein potently inhibit the SARS-CoV helicase protein in vitro by affecting the ATPase activity, but not the unwinding activity, nsP13. In addition, we observed that myricetin and scutellarein did not exhibit cytotoxicity against normal breast epithelial MCF10A cells. Our study demonstrates for the first time that selected naturally-occurring flavonoids, including myricetin and scultellarein might serve as SARS-CoV chemical inhibitors.


title: Establishing a surveillance network for severe lower respiratory tract infections in Korean infants and young children

text: To reduce morbidity and mortality through integrated case management, a pilot study to detect respiratory viruses in patients with acute lower respiratory infections (ALRIs) was designed as part of a nationwide surveillance for this disease in Korea. The study population consisted of hospitalized patients under the age of 5 years with bronchiolitis, pneumonia, croup, or acute respiratory distress syndrome. A prospective 6-month study was performed. Two hundred and ninety-seven nasopharyngeal secretions were collected and multiplex reverse transcriptase polymerase chain reactions (RT-PCR)/polymerase chain reactions (PCR) were performed to detect respiratory viruses. If there were any positive RT-PCR/PCR results, viral cultures were proceeded for confirmation. Respiratory viruses were identified in 49.6% of 296 patients. The detection rates were as follows: respiratory syncytial virus (RSV) was the most commonly detected in 52.7% (87/165), human metapneumovirus (hMPV) in 15.8%, human corona virus (hCoV) in 5.5%, adenovirus in 9.7%, human bocavirus (hBoV) in 5.5%, parainfluenza virus (PIV) in 3.6%, rhinovirus (RV) in 4.2%, and the influenza virus in 3% of the patients with ALRIs. The consistent rate of positive results between RT-PCR and viral culture was 92% (105/114). Using our methods to detect viral causes seemed to be acceptable for the national surveillance of severe acute respiratory infections in infants and children.


title: Ebola Emergency Preparedness: Simulation Training for Frontline Health Care Professionals

text: INTRODUCTION: At Brigham and Women's Hospital, we identified the need for a comprehensive training program designed to prepare frontline staff to safely manage a patient with Ebola viral disease (EVD). The primary goal of this program was to ensure the safety of staff, patients, and the general public by training staff in the correct use of personal protective equipment (PPE) before, during, and after care of patients with EVD. METHODS: We delivered a 4-hour experiential training program to frontline health care professionals who would be expected to care for a patient with EVD. The program occurred in a simulation center with multiple flexible spaces and consisted of demonstration, multiple skills practice sessions, and a patient simulation case. We analyzed completed pre- and posttraining questionnaires. The questionnaire assessed their subjective level of confidence in three key areas: donning and doffing PPE, performing clinical skills while wearing PPE, and management of a contamination breach. RESULTS: This program was effectively deployed in the STRATUS Center for Medical Simulation over a 4-month period, with 220 health care professionals participating in the training and 195 participants completing the pre-/posttraining questionnaires. Our intervention significantly increased the confidence of participants on each primary objective (p = .001 for all three stations). DISCUSSION: This interprofessional simulation-based program has been shown to be a well-received method of training clinicians to manage patients collaboratively during an EVD outbreak. Our intent is that the skills taught in this training program would also be transferable to management of other infectious diseases in the clinical setting.


title: Better Tests, Better Care: Improved Diagnostics for Infectious Diseases

text: In this IDSA policy paper, we review the current diagnostic landscape, including unmet needs and emerging technologies, and assess the challenges to the development and clinical integration of improved tests. To fulfill the promise of emerging diagnostics, IDSA presents recommendations that address a host of identified barriers. Achieving these goals will require the engagement and coordination of a number of stakeholders, including Congress, funding and regulatory bodies, public health agencies, the diagnostics industry, healthcare systems, professional societies, and individual clinicians.


title: Non‐human viruses developed as therapeutic agent for use in humans

text: Viruses usually infect a restricted set of host species, and only in rare cases does productive infection occur outside the natural host range. Infection of a new host species can manifest as a distinct disease. In this respect, the use of non‐human viruses in clinical therapy may be a cause for concern. It could provide the opportunity for the viruses to adapt to the new host and be transferred to the recipient's relatives or medical caretakers, or even to the normal host species. Such environmental impact is evidently undesirable. To forecast future clinical use of non‐human viruses, a literature study was performed to identify the viruses that are being considered for application as therapeutic agents for use in humans. Twenty‐seven non‐human virus species were identified that are in (pre)clinical development, mainly as oncolytic agents. For risk management, it is essential that the potential environmental consequences are assessed before initiating clinical use, even if the virus is not formally classified as a genetically modified organism. To aid such assessment, each of these viruses was classified in one of five relative environmental risk categories, ranging from “Negligible” to “Very High”. Canary pox virus and the Autographa californica baculovirus were assigned a “Negligible” classification, and Seneca Valley virus, murine leukemia virus, and Maraba virus to the “High” category. A complicating factor in the classification is the scarcity of publicly available information on key aspects of virus biology in some species. In such cases the relative environmental risk score was increased as a precaution. Copyright © 2011 John Wiley & Sons, Ltd.


One oral and maxillofacial surgeon’s attitude toward the COVID-19 pandemic


title: EL CUIDADO HUMANIZADO EN LA MUERTE POR COVID-19: A PROPÓSITO DE UN CASO

text: RESUMEN La población mundial está sufriendo una pandemia por infección del virus SARS-Cov-2, que provoca la enfermedad COVID-19. En España, la tasa de crecimiento de la epidemia es del 6,79% desde la activación del estado de alarma y un porcentaje de defunciones del 9,07% del total de infectados. Las recomendaciones del Ministerio de Sanidad para profesionales de la salud en contacto con personas infectadas, o sospecha de ello, incluyen la colocación de dispositivos de protección individual (mascarilla FPP2, guantes, bata impermeable, gorro, y gafas protectoras o pantalla). Una vez colocado todo el material, es necesario reflexionar acerca de la humanización de los cuidados enfermeros a las personas en situación agónica infectadas por COVID-19, a propósito de un caso. La pretensión es la puesta en valor del pensamiento enfermero para salvar esa distancia, y mantener unos cuidados lo más humanos y cercanos posibles, al final de la vida. ABSTRACT The world population is experiencing a pandemic due to infection with the SARS-Cov-2 virus, which causes the COVID-19 disease. In Spain, the growth rate of the epidemic is 6.79% since the alarm activation with 9,1% of deaths of the total infected. Recommendations of the National Government to prevent health professional contagion include the placement of personal protection devices (FPP2 mask, gloves, waterproof gown, hat, and protective glasses or screen). Once all the material is in place, it is necessary to argue about the humanization of nursing caring in people suffering dying situation, who are infected with COVID-19, regarding a clinical case. The aim is to enhance nursing thinking to bridge that distance, and maintain care as human and close as possible, at the end of life.


title: HealthMap: Global Infectious Disease Monitoring through Automated Classification and Visualization of Internet Media Reports

text: OBJECTIVE: Unstructured electronic information sources, such as news reports, are proving to be valuable inputs for public health surveillance. However, staying abreast of current disease outbreaks requires scouring a continually growing number of disparate news sources and alert services, resulting in information overload. Our objective is to address this challenge through the HealthMap.org Web application, an automated system for querying, filtering, integrating and visualizing unstructured reports on disease outbreaks. DESIGN: This report describes the design principles, software architecture and implementation of HealthMap and discusses key challenges and future plans. MEASUREMENTS: We describe the process by which HealthMap collects and integrates outbreak data from a variety of sources, including news media (e.g., Google News), expert-curated accounts (e.g., ProMED Mail), and validated official alerts. Through the use of text processing algorithms, the system classifies alerts by location and disease and then overlays them on an interactive geographic map. We measure the accuracy of the classification algorithms based on the level of human curation necessary to correct misclassifications, and examine geographic coverage. RESULTS: As part of the evaluation of the system, we analyzed 778 reports with HealthMap, representing 87 disease categories and 89 countries. The automated classifier performed with 84% accuracy, demonstrating significant usefulness in managing the large volume of information processed by the system. Accuracy for ProMED alerts is 91% compared to Google News reports at 81%, as ProMED messages follow a more regular structure. CONCLUSION: HealthMap is a useful free and open resource employing text-processing algorithms to identify important disease outbreak information through a user-friendly interface.


title: Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors

text: A small library of 36 functionalized benzophenone thiosemicarbazone analogs has been prepared by chemical synthesis and evaluated for their ability to inhibit the cysteine proteases cathepsin L and cathepsin B. Inhibitors of cathepsins L and B have the potential to limit or arrest cancer metastasis. The six most active inhibitors of cathepsin L (IC(50) < 85 nM) in this series incorporate a meta-bromo substituent in one aryl ring along with a variety of functional groups in the second aryl ring. These six analogs are selective for their inhibition of cathepsin L versus cathepsin B (IC(50) > 10,000 nM). The most active analog in the series, 3-bromophenyl-2′-fluorophenyl thiosemicarbazone 1, also efficiently inhibits cell invasion of the DU-145 human prostate cancer cell line.


COVID-19 (SARS-CoV-2 Infection) and Children: Pediatric Neurologist’s Perspective


title: The Novel Coronavirus Disease (COVID‐19) Complicated by Pulmonary Embolism and Acute Respiratory Distress Syndrome

text: Acute respiratory distress syndrome and coagulopathy played an important role in morbidity and mortality of severe COVID‐19 patients. A higher frequency of PE than expected in COVID‐19 patients was recently reported. The presenting symptoms for PE were untypical including dyspnea, which is one of the major symptoms in severe COVID‐19, especially in those patients with ARDS. We reported two COVID‐19 cases with coexisting complications of PE and ARDS, aiming to consolidate the emerging knowledge of this global health emergency and raise the awareness that the hypoxemia or severe dyspnea in COVID‐19 may be related to PE and not necessarily always due to the parenchymal disease. This article is protected by copyright. All rights reserved.


title: GeoSES: A socioeconomic index for health and social research in Brazil

text: The individual’s socioeconomic conditions are the most relevant to predict the quality of someone’s health. However, such information is not usually found in medical records, making studies in the area difficult. Therefore, it is common to use composite indices that characterize a region socioeconomically, such as the Human Development Index (HDI). The main advantage of the HDI is its understanding and adoption on a global scale. However, its applicability is limited for health studies since its longevity dimension presents mathematical redundancy in regression models. Here we introduce the GeoSES, a composite index that summarizes the main dimensions of the Brazilian socioeconomic context for research purposes. We created the index from the 2010 Brazilian Census, whose variables selection was guided by theoretical references for health studies. The proposed index incorporates seven socioeconomic dimensions: education, mobility, poverty, wealth, income, segregation, and deprivation of resources and services. We developed the GeoSES using Principal Component Analysis and evaluated its construct, content, and applicability. GeoSES is defined at three scales: national (GeoSES-BR), Federative Unit (GeoSES-FU), and intra-municipal (GeoSES-IM). GeoSES-BR dimensions showed a good association with HDI-M (correlation above 0.85). The model with the poverty dimension best explained the relative risk of avoidable cause mortality in Brazil. In the intra-municipal scale, the model with GeoSES-IM was the one that best explained the relative risk of mortality from circulatory system diseases. By applying spatial regressions, we demonstrated that GeoSES shows significant explanatory potential in the studied scales, being a compelling complement for future researches in public health.


title: Early Vascular Surgery Response to the COVID-19 Pandemic: Results of a Nationwide Survey

text: OBJECTIVES: The COVID-19 pandemic has had major implications for the United States healthcare system. This survey study sought to identify practice changes, understand current personal protection equipment (PPE) use, and determine how caring for patients with COVID-19 differs for vascular surgeons practicing in states with high COVID-19 case numbers versus low case numbers. METHODS: A fourteen-question online survey regarding the effect of the COVID-19 pandemic on vascular surgeons’ current practice was sent to 365 vascular surgeons across the country via REDCap from 4/14/2020 to 4/21/2020 with responses closed on 4/23/2020. The survey response was analyzed with descriptive statistics. Further analyses were performed to evaluate whether responses from states with the highest number of COVID-19 cases (New York, New Jersey, Massachusetts, Pennsylvania and California) differed from those with lower case numbers (all other states). RESULTS: A total of 121 vascular surgeon responded (30.6%) to the survey. All high-volume states were represented. The majority of vascular surgeons are reusing PPE The majority of respondents worked in an academic setting (81.5%) and were performing only urgent and emergent cases (80.5%) during preparation for the surge. This did not differ between high case and low COVID case states (p=0.285). High case states were less likely to perform a lower extremity intervention for critical limb ischemia (60.8% vs. 77.5%, p=0.046), but otherwise case types did not differ. Most attendings work with residents (90.8%) and limited their exposure to procedures on suspected/confirmed COVID-19 cases (56.0%). Thirty-eight percent of attendings have been redeployed within the hospital to a vascular access service, and/or other service outside of vascular surgery. This was more frequent in high case volume states compared to low case volume states (p=0.039). The majority of vascular surgeons are reusing PPE (71.4%) and N95 masks (86.4%), and 21% of vascular surgeons feel that they do not have adequate PPE to perform clinical their duties. CONCLUSION: The initial response to the COVID-19 pandemic has resulted in reduced elective cases with primarily only urgent and emergent cases being performed. A minority of vascular surgeons have been redeployed outside of their specialty, however, this is more common among states with high case numbers. Adequate PPE remains an issue for almost a quarter of vascular surgeons who responded to this survey.


title: ESTATINAS EN COVID-19: ¿EXISTE ALGÚN FUNDAMENTO?

text: RESUMEN El coronavirus tipo 2 del síndrome respiratorio agudo grave (SARS-CoV-2) es el agente causal de la enfermedad por coronavirus 2019 (COVID-19). El síndrome de distress respiratorio agudo constituye la principal causa de muerte por COVID-19 y ocurre por una respuesta inflamatoria exagerada que provoca la liberación de citosinas pro-inflamatorias como interleucinas y factor de necrosis tumoral alfa (TNF-α). Las estatinas son fármacos hipolipemiantes con efectos pleiotrópicos. Han demostrado beneficio en el manejo de enfermedades inflamatorias y autoinmunes como el lupus eritematoso sistémico, la artritis reumatoide y la esclerosis múltiple. Además, debido a sus propiedades inmunomoduladoras se han utilizado en el tratamiento de diversas enfermedades infecciosas como neumonía adquirida en la comunidad e influenza. En esta revisión analizamos los fundamentos fisiopatológicos que apoyan el uso de estatinas como tratamiento coadyuvante en pacientes con COVID-19. ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19). Acute respiratory distress syndrome is the main cause of death from COVID-19 and occurs due to an exaggerated inflammatory response that causes the release of pro-inflammatory cytokines such as interleukins and tumor necrosis factor-alpha (TNF-α). Statins are lipid lowering drugs with pleiotropic effects. They have shown benefit in the management of inflammatory and autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Furthermore, due to their immunomodulatory properties, they have been used in the treatment of various infectious diseases such as community-acquired pneumonia and influenza. In this review we analyze the pathophysiological foundations that support the use of statins as an adjunctive treatment in patients with COVID-19.


title: Water and Pathogenic Viruses Inactivation—Food Engineering Perspectives

text: Water is an essential component of food structures and biological materials. The importance of water as a parameter affecting virion stability and inactivation has been recognized across disciplinary areas. The large number of virus species, differences in spreading, likelihood of foodborne infections, unknown infective doses, and difficulties of infective virus quantification are often limiting experimental approaches to establish accurate data required for detailed understanding of virions’ stability and inactivation kinetics in various foods. Furthermore, non-foodborne viruses, as shown by the SARS-CoV-2 (Covid-19) pandemic, may spread within the food chain. Traditional food engineering benefits from kinetic data on effects of relative humidity (RH) and temperature on virion inactivation. The stability of enteric viruses, human norovirus (HuNoV), and hepatitis A (HAV) virions in food materials and their resistance against inactivation in traditional food processing and preservation is well recognized. It appears that temperature-dependence of virus inactivation is less affected by virus strains than differences in temperature and RH sensitivity of individual virus species. Pathogenic viruses are stable at low temperatures typical of food storage conditions. A significant change in activation energy above typical protein denaturation temperatures suggests a rapid inactivation of virions. Furthermore, virus inactivation mechanisms seem to vary according to temperature. Although little is known on the effects of water on virions’ resistance during food processing and storage, dehydration, low RH conditions, and freezing stabilize virions. Enveloped virions tend to have a high stability at low RH, but low temperature and high RH may also stabilize such virions on metal and other surfaces for several days. Food engineering has contributed to significant developments in stabilization of nutrients, flavors, and sensitive components in food materials which provides a knowledge base for development of technologies to inactivate virions in foods and environment. Novel food processing, particularly high pressure processing (HPP) and cold plasma technologies, seem to provide efficient means for virion inactivation and food quality retention prior to packaging or food preservation by traditional technologies.


Nachrichtenteil für Grundwasser-Heft 2/2020


title: Hindsight Is 2019—the Year in Clinical Microbiology

text: Much changed in clinical microbiology in 2019, and, like the organisms, we, as clinical microbiologists, are responsible to detect, characterize, and teach others about our discipline. Also, it is important for us to adapt to changes in the field. In this review, I highlight some of the papers, practices, and regulatory issues that defined 2019 for our field, from my perspective.


title: A scoring system for predicting results of influenza rapid test in children: A possible model facing overwhelming pandemic infection

text: Background The pandemic novel influenza H1N1 (swine) influenza A virus (H1N1v) infection has caused large-scale community infection in Taiwan. Anxiety developed in the general public and physicians faced a huge challenge in many aspects. We conducted this prospective study to develop a scoring system based on the clinical manifestations for predicting the results of influenza rapid testing, as a surrogate of influenza rapid testing, to lower the anxiety and decrease the burden for the test. Methods From September 1, 2009 to October 5, 2009, pediatric patients who received influenza rapid tests were enrolled, and questionnaires were recorded and analyzed in the first 2 weeks. A further scoring system was conducted to predict the results of influenza rapid tests and validated in the next 3 weeks. Results Eight hundred and forty-five children were enrolled in our study. In the first phase, data from 506 patients showed that those with age ≥ 5 years, fever ≥ 38°C, contact history of influenza A infection, myalgia, lethargy, sore throat, cough, and headache had a higher risk of positive results (odds ratio: 1.1–2.53). A scoring system was designed, with ≥5 points indicating acceptable sensitivity (69.5%) and specificity (63.6%). Three hundred and thirty-nine patients in the second phase were enrolled to validate the scoring system and the positive and negative predictive values were 52.0% and 73.8%. Conclusion The emergence of H1N1v infection is not only an important medical issue, but also a socioeconomic problem. Based on easily available clinical information, we develop a scoring system as a preliminary screening tool for the general public and first-line health care providers to evaluate the possibility of influenza virus infection. Although this study was limited by the sensitivity of rapid tests, this type of model may be a surrogate weapon when faced with overwhelming pandemic infection in the future, especially in areas with scarce medical resources.


title: Superinfection exclusion of vaccinia virus in virus-infected cell cultures

text: Abstract Vaccinia virus-infected BSC 40 cells do not permit the replication of superinfecting vaccinia virus. The extent of superinfecting virus propagation depends on the time of superinfection; there is 90% exclusion by 4 hr after the initial infection, and more than 99% by 6 hr. When superinfection is attempted at 6 hr after infection, the superinfecting virus is incapable of carrying out DNA replication or early gene transcription, demonstrating that an early event in the virus life cycle is inhibited. The rate of adsorption of the superinfecting virus is unaltered which shows that exclusion is affected at a point between adsorption and early gene transcription. In order to exclude superinfection, the primary infecting virus does not require replication of its DNA or expression of its late genes but it must express one or more early genes.


title: G6PD variant distribution in sub-Saharan Africa and potential risks of using chloroquine/hydroxychloroquine based treatments for COVID-19

text: Chloroquine/hydroxychloroquine have been proposed as potential treatments for COVID-19. These drugs have warning labels for use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Analysis of whole-genome sequence data of 458 individuals from sub-Saharan Africa showed significant G6PD variation across the continent. We identified nine variants, of which four are potentially deleterious to G6PD function, and one (rs1050828) that is known to cause G6PD deficiency. We supplemented data for the rs1050828 variant with genotype array data from over 11,000 Africans. Although this variant is common in Africans overall, large allele frequency differences exist between sub-populations. African sub-populations in the same country can show significant differences in allele frequency (e.g. 16.0% in Tsonga vs 0.8% in Xhosa, both in South Africa, p = 2.4 × 10(3)). The high prevalence of variants in the G6PD gene found in this analysis suggests that it may be a significant interaction factor in clinical trials of chloroquine and hydrochloroquine for treatment of COVID-19 in Africans.


title: Challenges and opportunities for enhancing biotechnology and technology transfer in developing countries

text: Abstract Biotechnological innovation is gaining increased recognition as an important tool for improving global health. The challenge, however, lies in defining the role of technology transfer to develop therapies for diseases prevalent in developing countries. During the past decade, a large disparity emerged between the developed and developing world in accessing affordable medicines because of the pharmaceutical industry's focus on health areas bearing greatest profits. Discussed herein are several mechanisms that provide partial solutions to this challenge. The Office of Technology Transfer of the US National Institutes of Health has increased its technology licensing pertaining to neglected diseases to partners in developing regions. Establishing partnerships through the transfer of technologies and assisting indigenous institutions build R and D capacity may positively impact policies on protection of intellectual property rights and increase multinational company investments in lesser-developed countries. This will most probably result in the development of more accessible therapies for those in need.


title: Purification, primary structure, and biological activity of the high-mannose N-glycan-specific lectin from cultivated Eucheuma denticulatum

text: Three isolectins from cultivated Eucheuma denticulatum were isolated. They were commonly monomeric proteins of about 28 kDa with a range of averaged molecular weights from 27,834 to 27,868 Da among the isolectins and shared almost the same 20 N-terminal amino acid sequences. Complementary DNA (cDNA) cloning based on the rapid amplification cDNA ends (RACE) methods elucidated the full-length sequence of EDA-2 which encodes 269 amino acids, including initiating methionine, with four tandemly repeated domains of about 67 amino acids. The primary structure of EDA-2 is highly similar to those of the high-mannose N-glycan specific lectins including Oscillatoria agardhii (OAA) and Burkholderia oklahomensis EO147 (BOA) from cyanobacteria, Myxococcus xanthus (MBHA) and Pseudomonas fluorescens Pf0-1 (PFL) from bacteria, and ESA-2 from a macro red alga. The hemagglutination activities were commonly inhibited by the glycoproteins bearing high-mannose N-glycans, but not by monosaccharides examined, including mannose. In a direct binding experiment with pyridylaminated oligosaccharides, an isolectin EDA-2 exclusively bound to high-mannose type N-glycans, but not to other glycans that include complex types and a core pentasaccharide of N-glycans, indicating that it recognized the branched oligomannoside moiety. Its binding activity was subtly different among the oligomannoside structures examined, showing that the lectin has preference affinity for high-mannose type N-glycans with an exposed (α1-3) mannose residue in the D2 arm. Interestingly, EDAs, the mixture of three isolectins inhibited the growth of shrimp pathogenic bacterium, Vibrio alginolyticus, although it did not affect the growth of V. parahaemolyticus and V. harveyi. Growth inhibition of V. alginolyticus with EDAs was not observed in the presence of yeast mannan bearing high-mannose N-glycans, suggesting that EDAs caused the activity through binding to the target receptor(s) on the surface of V. alginolyticus. These results indicate that cultivated carrageenophyte E. denticulatum is a good source of a lectin(s) that may be useful as a carbohydrate probe and an antibacterial reagent.


title: COVID-19: Lessons From the Disaster That Can Improve Health Professions Education

text: COVID-19 has disrupted every aspect of the U.S. health care and health professions education systems, creating anxiety, suffering, and chaos and exposing many of the flaws in the nation’s public health, medical education, and political systems. The pandemic has starkly revealed the need for a better public health infrastructure and a health system with incentives for population health and prevention of disease as well as outstanding personalized curative health. It has also provided opportunities for innovations in health care and has inspired courageous actions of residents, who have responded to the needs of their patients despite risk to themselves. In this Invited Commentary, the author shares lessons he learned from 3 earlier disasters and discusses needed changes in medical education, health care, and health policy that the COVID-19 pandemic has revealed. He encourages health professions educators to use the experiences of this pandemic to reexamine the current curricular emphasis on the bioscientific model of health and to broaden the educational approach to incorporate the behavioral, social, and environmental factors that influence health. Surveillance for disease, investment in disease and injury prevention, and disaster planning should be basic elements of health professions education. Incorporating innovations such as telemedicine, used under duress during the pandemic, could alter educational and clinical approaches to create something better for students, residents, and patients. He explains that journals such as Academic Medicine can provide rapid, curated, expert advice that can be an important counterweight to the misinformation that circulates during disasters. Such journals can also inform their readers about new training in skills needed to mitigate the ongoing effects of the disaster and prepare the workforce for future disasters.


title: Bacterial target-specific photocatalyst for the enhancement of antibacterial property to targets

text: Abstract A bacterial target-specific titanium oxide (TiO2) photocatalyst was developed for the enhancement of selective inactivation of targeted bacteria. An antibacterial composition comprising TiO2 particles immobilized with a bacterial-specific antibody having affinity to bacteria of interest was prepared via a carbodiimide hydrochloride/N-hydroxysulfosuccinimide (EDC/NHS) coupling reaction between polyacrylic acid (PAA) coated TiO2 and an antibody. As a model case, an antibody to Escherichia coli was conjugated with the PAA-coated TiO2 (TiO2-AbE). We evaluated the enhancement of the antibacterial effect of TiO2-AbE against target E. coli, compared with its effect on other bacteria that lack affinity for the antibody used. The TiO2-AbE inactivated approximately 90% of the E. coli at 15min, whereas the raw TiO2 inactivated approximately 20% of the E. coli after the same period of time under UV irradiation. The TiO2-AbE did not show an enhanced antibacterial effect against non-target bacteria. We infer that close contact between TiO2 particles and E. coli, as a result of the specificity of the antibody, can enhance the direct transfer of reactive oxygen species (ROS) generated by TiO2 particles to the cellular surface under UV irradiation and result in rapid and efficient inactivation of the targeted bacteria. The strategy presented here will facilitate the combination of other receptors and TiO2 particles for the preparation of highly selective and photocatalytic composites to prevent or remediate contamination by unwanted bacteria in a wide variety of natural and man-made systems.


The positive of stool test for SARS-CoV-2: a report of 9 cases in Changsha, outside Wuhan, China


title: Development of Reverse Transcription Loop-Mediated Isothermal Amplification Assays Targeting SARS-CoV-2

text: Epidemics of coronavirus disease 2019 (COVID-19) now have >100,000 confirmed cases worldwide. Diagnosis of COVID-19 is currently performed by quantitative RT-PCR methods, but the capacity of quantitative RT-PCR methods is limited by their requirement of high-level facilities and instruments. Herein, reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays to detect genomic RNA of SARS-CoV-2, the causative virus of COVID-19, were developed and evaluated. RT-LAMP assays in this study can detect as low as 100 copies of SARS-CoV-2 RNA. Cross-reactivity of RT-LAMP assays to other human coronaviruses was not observed. A colorimetric detection method was adapted for this RT-LAMP assay so that the tests potentially performed in higher throughput.


title: Coronavirus Disease 2019 (COVID-19) in Children - What We Know So Far and What We Do Not

text: Pediatric coronavirus disease-19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis. Mortality in children appears rare. Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission. It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)- Angiotensin converting enzyme 2 (ACE2). Laboratory findings and chest imaging may not be specific in children with COVID-19. Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions. This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment. The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic.


title: Uniformed Service Nurses' Experiences with the Severe Acute Respiratory Syndrome Outbreak and Response in Taiwan

text: Severe Acute Respiratory Syndrome (SARS) had an enormous effect on Taiwan's public health and the nation's economy. To prevent the spread of the epidemic, the government implemented strategies and measures for the control of the epidemic. The Ministry of National Defense also fully supported epidemic prevention by mobilizing all necessary human and material resources. Under the plan executed by the Ministry of National Defense, the SongShan Armed Forces Hospital became Taiwan's first hospital dedicated exclusively for the treatment of patients with SARS. Uniformed Service Nurses' devoted to caring for patients with SARS during the outbreak made significant contributions to the prevention and control of SARS.


title: Detection of respiratory viruses using a multiplex real-time PCR assay in Germany, 2009/10

text: The aim of this study was to determine the prevalence of respiratory viruses and to prospectively evaluate the performance of the fast-track diagnostics (FTD) respiratory pathogens multiplex PCR assay shortly after the 2009/10 influenza pandemic. Highly sensitive monoplex real-time PCR assays served as references. Discrepant results were further analyzed by the xTAG RVP Fast assay. A total of 369 respiratory samples from children and adults were collected prospectively in Germany from December 2009 until June 2010. The sensitivity and specificity of the FTD assay after resolution of discrepant results was 92.2 % and 99.5 %, respectively. Lowest specificity of the FTD assay was observed for human bocavirus. Multiple detections were recorded in 33/369 (8.9 %) of the samples by monoplex PCR and in 43/369 (11.7 %) using the FTD assay. The most prevalent viruses were respiratory syncytial virus and human metapneumovirus. Only pandemic influenza virus A/H1N1 (2009), and not seasonal influenza virus, was detected. Viruses other than influenza virus accounted for the majority of acute respiratory infections. The FTD assay can be easily implemented in general diagnostic laboratories and facilitate the optimization of patient-management schemes.


title: Sequencing of the human IG light chain loci from a hydatidiform mole BAC library reveals locus-specific signatures of genetic diversity

text: Germline variation at immunoglobulin gene (IG) loci is critical for pathogen-mediated immunity, but establishing complete reference sequences in these regions is problematic because of segmental duplications and somatically rearranged source DNA. We sequenced BAC clones from the essentially haploid hydatidiform mole, CHM1, across the light chain IG loci, kappa (IGK) and lambda (IGL), creating single haplotype representations of these regions. The IGL haplotype is 1.25Mb of contiguous sequence with four novel V gene and one novel C gene alleles and an 11.9kbp insertion. The IGK haplotype consists of two 644kbp proximal and 466kbp distal contigs separated by a gap also present in the reference genome sequence. Our effort added an additional 49kbp of unique sequence extending into this gap. The IGK haplotype contains six novel V gene and one novel J gene alleles and a 16.7kbp region with increased sequence identity between the two IGK contigs, exhibiting signatures of interlocus gene conversion. Our data facilitated the first comparison of nucleotide diversity between the light and IG heavy (IGH) chain haplotypes within a single genome, revealing a three to six fold enrichment in the IGH locus, supporting the theory that the heavy chain may be more important in determining antigenic specificity.


title: Evaluation of the Utility of Radiography in Acute Bronchiolitis

text: Objectives To determine the proportion of radiographs inconsistent with bronchiolitis in children with typical presentation of bronchiolitis and to compare rates of intended antibiotic therapy before radiography versus those given antibiotics after radiography. Study design We conducted a prospective cohort study in a pediatric emergency department of 265 infants aged 2 to 23 months with radiographs showing either airway disease only (simple bronchiolitis), airway and airspace disease (complex bronchiolitis), and inconsistent diagnoses (eg, lobar consolidation). Results The rate of inconsistent radiographs was 2 of 265 cases (0.75%; 95% CI 0-1.8). A total of 246 children (92.8%) had simple radiographs, and 17 radiographs (6.9%) were complex. To identify 1 inconsistent and 1 complex radiograph requires imaging 133 and 15 children, respectively. Of 148 infants with oxygen saturation >92% and a respiratory disease assessment score <10 of 17 points, 143 (96.6%) had a simple radiograph, compared with 102 of 117 infants (87.2%) with higher scores or lower saturation (odds ratio, 3.9; 95% CI, 1.3-14.3). Seven infants (2.6%) were identified for antibiotics pre-radiography; 39 infants (14.7%) received antibiotics post-radiography (95% CI, 8-16). Conclusions Infants with typical bronchiolitis do not need imaging because it is almost always consistent with bronchiolitis. Risk of airspace disease appears particularly low in children with saturation higher than 92% and mild to moderate distress.


title: Comparative study of a blocking enzyme-linked immunosorbent assay and the immunoperoxidase monolayer assay for the detection of antibodies to the porcine reproductive and respiratory syndrome virus in pigs

text: Abstract A blocking enzyme-linked immunosorbent assay (ELISA) for detecting antibodies to the porcine reproductive and respiratory syndrome virus (PRRSV) in pig sera was developed and compared with the immunoperoxidase monolayer assay (IPMA), the most widely used serological diagnostic test in Europe. The blocking ELISA was specific and more sensitive than the IPMA when applied to field sera and to sera which were collected early after an experimental infection with PRRSV. Problems with high background activity as observed in IPMA or indirect ELISA were not encountered.


title: Antimicrobial strategies: An option to treat allergy?

text: Abstract Respiratory infections by bacteria and viruses often trigger symptoms of asthma in both adults and children. This observation and subsequent mechanistic studies have demonstrated important interactions among allergens, microbes and the atopic host. The mechanisms responsible for microbe-induced asthma exacerbations are only incompletely understood. A focal point of current research is the inflammatory response of the host following an encounter with a pathogenic microbe, including variations in chemokine and cytokine production and resulting in changes in bronchial hyper-responsiveness and lung function. Direct bronchial infection, exposure of nerves with resulting neurogenic inflammation and a deviated host immune response are among the mechanisms underlying these functional disorders. Lately, suboptimal innate immune responses, expressed as defective interferon production, have gained attention as they might be amenable to intervention. This review describes the suggested mechanisms involved in the complex interactions between ‘asthmagenic’ microbes, the immune system and atopy, based on in-vitro and in-vivo experimental models and epidemiological evidence. In addition, it provides a synopsis of potential therapeutic strategies either directly against the microorganisms or in respect to the associated inflammation.


title: Research and control of parasitic diseases in Japan: current position and future perspectives

text: Between 1950 and 1980, Japan eliminated several major parasitic diseases. In 1998, the Japanese Hashimoto Initiative was the first global programme to target parasitic diseases. Thereafter, Japan expanded its international cooperation to cover infectious diseases through integrated development programmes to improve health, to alleviate poverty and to help to achieve the Millennium Development Goals of the United Nations. Parasite control remains a major component of all subsequent operations. Opportunities to build upon past successes in order to improve the situation in the developing world – in addition to tackling emerging national threats – are promising. Substantial challenges remain and Japan has introduced major national reforms to try to overcome them.


title: Feline non-suppurative meningoencephalomyelitis. A clinical and pathological study

text: Abstract A spontaneous neurological disease in cats characterized by behavioural and motor disturbances was investigated by clinical, morphological and immunological methods. Neuropathological examination showed a marked inflammatory reaction in the cerebral leptomeninges and the grey matter of the brain. In the white matter, the reaction was moderate. The changes consisted of perivascular cuffing by mononuclear cells and neuronal damage. The brain stem (thalamus, mesencephalon, caudal colliculus) was most severely affected. The spinal cord and its leptomeninges were involved to a lesser degree. The histopathological picture as well as the laboratory findings suggests a viral cause of the disease. The morphology of the disease and serological as well as immunohistochemical results indicate that this disorder is different from previously known feline viral encephalitides.


title: Avoidance of oxidative‐stress perturbation in yeast bioprocesses by proteomic and genomic biostrategies?

text: Aims: Bioprocess oxidative stress caused by many reactive oxygen species (ROS) can lead to largely irreversible perturbation of yeast bioprocesses. These include the production of proteins derived from recombinant DNA yeast technology (aerobically grown Saccharomyces cerevisiae). These proteins include rennin, amyloglucosidases (glucamylases), interferons, interleukins, insulin, monoclonal antibodies, tissue plasminogen activators (t‐PA), sexually transmitted disease antigens, and measles, mumps and rubella antigens, growth hormones, somatotropin, blood clotting factors VIII and XIII. In addition, there may be a demand for severe acute respiratory syndrome–coronavirus antigens, hepatitis A, B and C viral‐selected antigens, HIV retroviral antigens, influenza antigens, trypanosomal antigens, and foot and mouth disease antigens. Prevention of oxidative stress has been achieved by application of antioxidant redox metalloenzymes such as superoxide dismutases (containing Cu/Zn cytosolic, Mn mitochondrial and Fe bacterial) glutathione peroxidases (and other Se‐containing proteins and enzymes such as the thioredoxins), catalases (Fe‐containing), cytochrome c peroxidases (Fe‐containing), ceruloplasmins (Cu‐containing), metallothionines (these cysteine thiol‐rich proteins bind ions of cadmium and mercury) and tyrosinases(Cu‐containing). Methods and Results: ROS are generated inadvertently by single metal valency couples such as FeII/FeIII and by FeIII/FeV present in 2700 (including 57 human) isoforms in cytochromes P450 mixed‐function oxidases (EC 1·14·14·1; O(2) : mono‐oxygenase NADPH/NADH requiring). In addition, mixed‐metal couples such as valency unmatched forms in CuI/FeII and FeIII/MnIV can recycle electrons. Moreover, proteins/protein chaperone couples can recycle electrons, often where futile‐recycling systems have been instigated. Furthermore, oxidized membrane phospholipids (R) can form ROOH (lipid hydroperoxides) and ROH (lipid alkoxides) that can generate ROS through Fenton chemistry (iron‐catalysed) chain reactions. Utilization of chain‐breaking antioxidants such as vitamin E (α‐tocopherol) in the lipid phase and vitamin C (ascorbate) in the aqueous phase can terminate these ROS‐producing reactions. Conclusions: The main significance of the study is that proteomic strategies of relief from bioprocess perturbation by ROS of yeast fermentations (used to manufacture proteins required in the food and therapeutic bioindustries) may become possible through addition of selected proteins (including metalloenzymes). The main impact of the study is that the utilization of genetically modified (GM) yeast produced by recombinant DNA technology genomic strategies could circumvent the bioprocessing problems that otherwise result from the bioprocess perturbations: this is as a result of oxidative stress caused by ROS, which is avoidable by deployment of appropriate antioxidants such as vitamins E, C and D (and antioxidant proteins and enzymes often of microbial origin via recombinant DNA technology).


title: Pneumonic vs Nonpneumonic Acute Exacerbations of COPD

text: Study objective To describe and compare the background, clinical manifestations, disease course, and infectious etiologies of pneumonic acute exacerbations (PNAE) vs nonpneumonic acute exacerbations (NPAE) of COPD. Design A prospective, observational study. Setting A tertiary university medical center in southern Israel. Patients Twenty-three hospitalizations for PNAE and 217 hospitalizations for NPAE were included in the study. Paired sera were obtained for each of the hospitalizations and were tested serologically for 12 pathogens. Only a significant change in antibody titers or levels was considered diagnostic. Results No significant differences were found between the two groups for any of the parameters related to COPD or comorbidity. The clinical type of the exacerbation was not significantly different between the groups. Compared to NPAE, patients with PNAE had lower Po 2 values at hospital admission (p = 0.004) but higher rates of abrupt onset (p = 0.005), ICU admissions (p = 0.006), invasive mechanical ventilation (p = 0.01), mortality (p = 0.007), and longer hospital stay (p = 0.001). In 22 PNAE hospitalizations (96%) and in 153 NPAE hospitalizations (71%), at least one infectious etiology was identified (p = 0.001). Mixed infection was found in 13 patients with PNAE (59%) and in 59 patients with NPAE (39%; not significant [NS]). Viral etiology was identified in 18 patients with PNAE (78%) compared with 99 patients with NPAE (46%; p = 0.003). Pneumococcal etiology was found in 10 patients with PNAE (43%) and in 38 patients with NPAE (18%; p = 0.006). An atypical etiology was identified in 8 patients with PNAE (35%) and 64 patients with NPAE (30%; NS). Conclusions Community-acquired pneumonia is common among patients hospitalized for an acute exacerbation of COPD and is generally manifested by more severe clinical and laboratory parameters. In PNAE, compared to NPAE, viral and pneumococcal etiologies are more common, but the rate of atypical pathogens is similar. The therapeutic significance of these findings should be investigated further.


title: Sequence of mouse hepatitis virus A59 mRNA 2: Indications for RNA recombination between coronaviruses and influenza C virus

text: Abstract The nucleotide sequence of the unique region of coronavirus MHV-A59 mRNA 2 has been determined. Two open reading frames (ORF) are predicted: ORF1 potentially encodes a protein of 261 amino acids; its amino acid sequence contains elements which indicate nucleotide binding properties. ORF2 predicts a 413 amino acids protein; it lacks a translation initiation codon and is therefore probably a pseudogene. The amino acid sequence of ORF2 shares 30% homology with the HA1 hemagglutinin sequence of influenza C virus. A short stretch of nucleotides immediately upstream of ORF2 shares 83% homology with the MHC class I nucleotide sequences. We discuss the possibilitythat both similarities are the result of recombinations and present a model for the acquisition and the subsequent inactivation of ORF2; the model applies also to MHV-A59-related coronaviruses in which we expect ORF2 to be still functional.


title: Synthesis and antiviral activity of novel glycyrrhizic acid conjugates with D-amino acid esters

text: Glycyrrhizic acid (GA) conjugates with methyl and ethyl esters of D-amino acids (D-Trp, D-Phe, D-Tyr, D-Val, D-Leu) have been synthesized by the activated esters method using mixtures of N-hydroxybenzotriazole or N-hydroxysuccinimide with N,N′-dicyclohexylcarbodiimide. GA conjugate with D-Trp ethyl ester exhibited antiviral activity against influenza viruses A/H3N2, A/H1N1/pdm09, A/H5N1, B (SI > 10–29), and HRSV (SI > 25). GA conjugate with D-Trp methyl ester inhibited influenza virus A/H1N1/pdm09 (SI > 30).


title: Clinical features of the first cases and a cluster of Coronavirus Disease 2019 (COVID-19) in Bolivia imported from Italy and Spain

text: Abstract Introduction In March 2020, Coronavirus Disease 2019 (COVID-19) arrived in Bolivia. Here, we report the main clinical findings, and epidemiological features of the first series of cases, and a cluster, confirmed in Bolivia. Methods For this observational, retrospective and cross-sectional study, information was obtained from the Hospitals and the Ministry of Health for the cases that were laboratory-diagnosed and related, during March 2020. rRT-PCR was used for the detection of the RNA of SARS-CoV-2 following the protocol Charité, Berlin, Germany, from nasopharyngeal swabs. Results Among 152 suspected cases investigated, 12 (7.9%) were confirmed with SARS-CoV-2 infected by rRT-PCR. The median age was 39 years (IQR 25–43), six of them male. Two cases proceed from Italy and three from Spain. Nine patients presented fever, and cough, five sore throat, and myalgia, among other symptoms. Only a 60 y-old woman with hypertension was hospitalized. None of the patients required ICU nor fatalities occurred in this group. Conclusions This is the first report of surveillance of COVID-19 in Bolivia, with patients managed mainly with home isolation. Preparedness for a significant epidemic, as is going on in other countries, and the deployment of response plans for it, in the country is now taking place to mitigate the impact of the COVID-19 pandemic in the population.


Severe gastroenteritis with secondary fever in a 10-month-old boy


title: The membrane-spanning segment of invariant chain (Iγ) contains a potentially cleavable signal sequence

text: Abstract The human invariant chain (Iγ) of class II histocompatibility antigens spans the membrane of the endoplasmic reticulum once. It exposes a small amino-terminal domain on the cytoplasmic side and a carboxyterminal, glycosylated domain on the exoplasmic side of the membrane. When the exoplasmic domain of Iγ is replaced by the cytoplasmic protein chloramphenicol acetyltransferase (CAT), CAT becomes the exoplasmic, glycosylated domain of the resulting membrane protein IγCAT∗. Deletion of the hydrophilic cytoplasmic domain from IγCAT gives rise to a secreted protein from which an amino-terminal segment is cleaved, most likely by signal peptidase. We conclude that the membrane-spanning region of Iγ contains a signal sequence in its amino-terminal half and that hydrophilic residues at the amino-terminal end of a signal sequence can determine cleavage by signal peptidase.


SARS-COV-2 infection in cancer patients undergoing checkpoint blockade: clinical course and outcome


title: Information needs and seeking behaviour among health professionals working at public hospital and health centres in Bahir Dar, Ethiopia

text: BACKGROUND: Universal access to information for health professionals is a need to achieve “health for all strategy.” A large proportion of the population including health professionals have limited access to health information in resource limited countries. The aim of this study is to assess information needs among Ethiopian health professionals. METHODS: A cross sectional quantitative study design complemented with qualitative method was conducted among 350 health care workers in Feburary26-June5/2012. Pretested self-administered questionnaire and observation checklist were used to collect data on different variables. Data entry and data analysis were done using Epi-Info version 3.5.1 and by SPSS version19, respectively. Descriptive statistics and multivariate regression analyses were applied to describe study objectives and identify the determinants of information seeking behaviours respectively. Odds ratio with 95% CI was used to assess the association between a factor and an outcome variable. RESULTS: The majority of the respondents acknowledged the need of health information to their routine activities. About 54.0% of respondents lacked access to health information. Only 42.8% of respondents have access to internet sources. Important barriers to access information were geographical, organizational, personal, economic, educational status and time. About 58.0% of the respondents accessed information by referring their hard copies and asking senior staff. Age, sex, income, computer literacy and access, patient size, work experience and working site were significantly associated with information needs and seeking behaviour. CONCLUSIONS: The health information seeking behaviour of health professional was significant. The heaklth facilities had neither informationcenter such as library, nor internet facilities. Conducting training on managing health information, accessing computer and improving infrastructures are important interventions to facilitate evidence based descions.


title: Human monoclonal antibodies as candidate therapeutics against emerging viruses and HIV-1

text: More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) — for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.


title: Activation of human monocytes after infection by human coronavirus 229E

text: Abstract Human coronaviruses (HCoV) are recognized respiratory pathogens that may be involved in other pathologies such as central nervous system (CNS) diseases. To investigate whether leukocytes could participate in respiratory pathologies and serve as vector for viral spread towards other tissues, the susceptibility of human leukocytic cell lines and peripheral blood mononuclear cells (PBMC) to HCoV-229E and HCoV-OC43 infection was investigated. Human primary monocytes/macrophages were susceptible to HCoV-229E infection, but strongly restricted HCoV-OC43 replication. Moreover, productive HCoV-229E infection of primary monocytes and of the THP-1 monocytic cell line led to their activation, as indicated by the production of pro-inflammatory mediators, including TNF-α, CCL5, CXCL10 and CXCL11 and MMP-9. Moreover, an in vitro chemotaxis assay showed that motility towards chemokines of THP-1 cells and primary monocytes was increased following an acute or persistent HCoV-229E infection. Taken together, these results suggest that infected monocytes could serve as a reservoir for HCoV-229E, become activated, participate in the exacerbation of pulmonary pathologies, as well as serve as potential vectors for viral dissemination to host tissues, where it could be associated with other pathologies.


title: Considerations for Heart Failure Care During the Coronavirus Disease 2019 (COVID-19) Pandemic

text: Abstract The coronavirus disease 2019 (COVID-19) pandemic has affected the care of patients with HF who contract COVID-19 as well as those without COVID-19 who have been impacted by the restructuring of health care delivery. Patients with HF and other cardiovascular comorbidities are at risk for severe disease and complications of infection. Similarly, COVID-19 has been demonstrated to cause myocarditis and may be implicated in new-onset cardiomyopathy. During this pandemic, special considerations are needed for patients with advanced HF, including those supported by durable left ventricular assist devices (LVADs) and heart transplant recipients. The purpose of this review is to summarize emerging data regarding the development of HF secondary to COVID-19, COVID-19 infection in patients with advanced HF, and the implications of the pandemic on care for non-infected patients with HF.


American Association for Bronchology and Interventional Pulmonology (AABIP) Statement on the Use of Bronchoscopy and Respiratory Specimen Collection in Patients With Suspected or Confirmed COVID-19 Infection


title: Practical workflow recommendations for emergency endotracheal intubation in csritically ill patients with COVID-19 based on the experience of Wuhan Union Hospital

text: • The condition of some patients with COVID-19 progress rapidly and require aggressive treatments and intensive care, and most of them required endotracheal intubation for mechanical ventilation. • Emergency endotracheal intubation in critically ill patients with COVID-19 has posed a huge challenge to the expertise and self-protection of anesthesiologists. • Anesthesiologists from the frontline of Wuhan, China, of fighting against the epidemic brought first-hand experience about emergency endotracheal intubation in critically ill patients with COVID-19 to colleagues.


Chilblain‐like lesions during the COVID‐19 pandemic: should we really worry?


title: Relapsing and remitting viral diseases of the nervous system

text: Abstract Virus infections can recur intermittently as is painfully appreciated by sufferers of recurrent lesions caused by the herpesvirus. The mechanisms of viral exacerbation and remission have become of interest in the neurosciences with circumstantial evidence that some role is played by viruses in multiple sclerosis. Epidemiological data indicate that multiple sclerosis results from exposure to a virus in childhood followed by a long latency period. The clinical course is typically remitting and relapsing, and the brain and spinal cord contain multifocal demyelinative lesions of different ages. Studies of slow viral infections have now provided many explanations for long incubation periods and studies of both acute and persistent viral infections have shown varied mechanisms of demyelination. Several recent studies of latent and persistent viral infections have provided thought-provoking data on episodic disease.


title: An optimized method for enumerating CNS derived memory B cells during viral-induced inflammation

text: Abstract Background CNS inflammation resulting from infection, injury, or neurodegeneration leads to accumulation of diverse B cell subsets. Although antibody secreting cells (ASC) within the inflamed CNS have been extensively examined, memory B cell (Bmem) characterization has been limited as they do not secrete antibody without stimulation. Moreover, unlike human Bmem, reliable surface markers for murine Bmem remain elusive. New method Using a viral encephalomyelitis model we developed a modified limiting dilution in vitro stimulation assay to convert CNS-derived virus specific Bmem into ASC. Comparison with existing methods Stimulation methods established for lymphoid tissue cells using prolonged stimulation with viral lysate resulted in substantial ASC loss and minimal Bmem to ASC conversion of CNS-derived cells. By varying stimulation duration, TLR activators, and culture supplements, we achieved optimal conversion by culturing cells with TLR7/8 agonist R848 in the presence of feeder cells for 2days. Results Flow cytometry markers CD38 and CD73 characterizing murine Bmem from lymphoid tissue showed more diverse expression patterns on corresponding CNS-derived B cell subsets. Using the optimized TLR7/8 stimulation protocol, we compared virus-specific IgG Bmem versus pre-existing ASC within the brain and spinal cord. Increasing Bmem frequencies during chronic infection mirrored kinetics of ASC. However, despite initially similar Bmem and ASC accumulation, Bmem prevailed in the brain, but were lower than ASC in the spinal cord during persistence. Conclusion Simultaneous enumeration of antigen-specific Bmem and ASC using the Bmem assay optimized for CNS-derived cells enables characterization of temporal changes during microbial or auto-antigen induced neuroinflammation.


title: Complete Genome Sequences of SARS-CoV-2 Strains Detected in Malaysia

text: We sequenced four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Malaysia during the second wave of infection and found unique mutations which suggest local evolution. Circulating Malaysian strains represent introductions from different countries, particularly during the first wave of infection. Genome sequencing is important for understanding local epidemiology.


title: Airway disease phenotypes in animal models of cystic fibrosis

text: In humans, cystic fibrosis (CF) lung disease is characterised by chronic infection, inflammation, airway remodelling, and mucus obstruction. A lack of pulmonary manifestations in CF mouse models has hindered investigations of airway disease pathogenesis, as well as the development and testing of potential therapeutics. However, recently generated CF animal models including rat, ferret and pig models demonstrate a range of well characterised lung disease phenotypes with varying degrees of severity. This review discusses the airway phenotypes of currently available CF animal models and presents potential applications of each model in airway-related CF research.


title: Hospital infectious disease emergency preparedness: A survey of infection control professionals

text: BACKGROUND: Hospital preparedness for infectious disease emergencies is imperative for local, regional, and national response planning. METHODS: A secondary data analysis was conducted of a survey administered to Infection Control Professionals (ICPs) in May, 2005. RESULTS: Most hospitals have ICP representation on their disaster committee, around-the-clock infection control support, a plan to prioritize health care workers to receive vaccine or antivirals, and non-health care facility surge beds. Almost 20% lack a surge capacity plan. Some lack negative pressure rooms for current patient loads or any surge capacity. Less than half have a plan for rapid set-up of negative pressure, and Midwest hospitals are less likely than other areas to have such plans. Smaller hospitals have less negative pressure surge capacity than do larger hospitals. About half have enough health care workers to respond to a surge that involves ≤50 patients; few can handle ≥100 patients. Many do not have sufficient ventilators or can handle ≤10 additional ventilated patients. Most do not have enough National Institute for Occupational Safety and Health–approved respirators, and less than half have sufficient surgical masks to handle a significant surge. CONCLUSIONS: United States hospitals lack negative pressure, health care worker, and medical equipment/supplies surge capacity. Hospitals must continue to address gaps in infectious disease emergency planning.


‘Test, re-test, re-test’: using inaccurate tests to greatly increase the accuracy of COVID-19 testing


title: Full Genomic Characterization of a Saffold Virus Isolated in Peru

text: While studying respiratory infections of unknown etiology we detected Saffold virus in an oropharyngeal swab collected from a two-year-old female suffering from diarrhea and respiratory illness. The full viral genome recovered by deep sequencing showed 98% identity to a previously described Saffold strain isolated in Japan. Phylogenetic analysis confirmed the Peruvian Saffold strain belongs to genotype 3 and is most closely related to strains that have circulated in Asia. This is the first documented case report of Saffold virus in Peru and the only complete genomic characterization of a Saffold-3 isolate from the Americas.


title: Evaluation of antiviral - passive - active immunization (“sandwich”) therapeutic strategy for functional cure of chronic hepatitis B in mice

text: BACKGROUND: Chronic Hepatitis B (CHB) remains a major problem for global public health. Viral persistence and immune defects are the two major reasons for CHB, and it was hypothesized that based on a transient clearance of serum viral DNA and HBsAg “window stage”, active immunization against hepatitis B virus (HBV) might initiate effective host immune responses versus HBV to achieve functional cure of CHB. METHODS: Two experimental mouse models that mice hydrodynamic injected HBV DNA or infected with recombinant AAV/HBV were used. The “sandwich” therapeutic effect by using a potent human anti-HBsAg neutralizing monoclonal antibody (G12) in combination with antiviral drug tenofovir disoproxil fumarate (TDF), followed by active immunization with HBsAg-HBsAb (mYIC) was evaluated. FINDINGS: A single G12 injection rapidly cleared serum HBsAg in HDI-HBV carrier mice, with a synergistic effect in decreasing viral DNA load when TDF was given orally. When both serum viral DNA and HBsAg load became low or undetectable, mYIC was administered. A more effective clearance of viral DNA and HBsAg was observed and serum HBsAb was developed only in these “sandwich”-treated mice. Efficient intrahepatic anti-HBV immune responses were also observed in these mice, including the formation of aggregates of myeloid cells with CD8(+)T cells and increased TNF-α, granzyme B production. INTERPRETATION: The “sandwich” combination therapy not only efficiently decreased HBsAg and HBV DNA levels but also induced effective cellular and humoral immunity, which may result in functional cure of CHB.


title: Ethical Implementation of Immunity Passports During the COVID-19 Pandemic

text: A number of countries are planning the use of “immunity passports” as a way to ease restrictive measures and allow infected and recovered people to return to work during the COVID-19 pandemic. This paper brings together key scientific uncertainties regarding the use of serological tests to assure immune status and a public health ethics perspective to inform key considerations in the ethical implementation of immunity passport policies. Ill-conceived policies have the potential to cause severe unintended harms that could result in greater inequity, the stigmatization of certain sectors of society, and heightened risks and unequal treatment of individuals due to erroneous test results. Immunity passports could, however, be used to achieve collective benefits and benefits for specific populations besides facilitating economic recovery. We conclude that sector-based policies that prioritize access to testing based on societal need are likely to be fairer and logistically more feasible, while minimizing stigma and reducing incentives for fraud. Clear guidelines need to be set out for which sectors of society should be prioritized for testing, and rigorous mechanisms should be in place to validate test results and identify cases of reinfection.