title: An unusual cause of fever of unknown origin with enlarged lymph nodes—relapsing polychondritis: A case report

text: INTRODUCTION: Fever of unknown origin (FUO) is a common initial presentation leading to a diagnostic challenge. PATIENT CONCERNS: A 3-month history of moderate-to-high fever was reported in an otherwise healthy 54-year-old man. Enhanced computed tomography (CT) scans of his chest showed a remarkable progressive enlargement of bilateral cervical, supraclavicular, hilar, and mediastinal lymph nodes within 2 weeks. Bronchofibroscopy manifested obvious luminal stenosis with swelling, thick pale mucosa, and disappearing of structures of trachea cricoid cartilage, followed by a 18F-fluorodeoxyglucose positron-emission tomography–computed tomography (18F-FDG PET/CT) with intense symmetric FDG uptake in larynx, tracheobronchial tree, and hilar, mediastinal, and axillary lymph nodes being demonstrated. DIAGNOSIS: A diagnosis of relapsing polychondritis (RP) was finally reached. INTERVENTIONS: The patient received methylprednisolone 40 mg daily with a gradual tapering in a 4-month follow-up. OUTCOMES: The patient experienced no relapse of fever and lymph nodes enlargement in the 4-month follow-up. LESSONS: Even though long-term fever with multiple lymphadenectasis usually lead to a diagnosis of lymphoma, the bronchoscopic features and evidence from 18F-FDG PET/CT in this case were much more approximate to RP, indicating an importance of a sensible differential diagnosis of RP in patients who present with nonspecific features such as FUO and lymph nodes enlargement. Keeping a high index of clinical suspicion in these patients can help recognize uncommon of RP and promote diagnosis and treatment. Our case highlights the significance of 18F-FDG PET/CT in helping reaching the diagnosis of RP in this condition. This report provides new data regarding the diagnostic difficulties of this rare type of autoimmune disease, and further investigations are needed as cases accumulate.


Working Together to Meet the Needs of Patients with Inflammatory Bowel Diseases


title: Non-COVID-19 emergencies: where have all the patients gone?

text: • Early in the pandemic, numbers of patients undergoing non-COVID-19 emergent CTs dropped sharply but diagnostic yield did not increase, suggesting potentially undiagnosed emergencies in patients not seen in healthcare institutions.


title: One-health approach as counter-measure against “autoimmune” responses in biosecurity

text: Abstract This Swine flu pandemic of 2009 and the potential Avian flu threat of 2011–2012 have revived a most challenging debate on protection against infectious diseases. The response to the Swine flu pandemic has been ambivalent, both on the societal (political) and the scientific level. While some scientists warned against potential massive loss of human lives and urged for immediate and large-scale vaccination, others accused them of unnecessary scaremongering, arguing that the pandemic would not be that severe. The lab-created virulent Avian flu virus – which has been created in order to ‘fight’ a potential Avian flu pandemic – sparked a fierce debate on the dual-use risks of such a pre-emptive strategy. This article involves an analysis of the medical-political response to these recent viral threats using Peter Sloterdijk's immunological framework as diagnostic tool. In his trilogy Spheres Sloterdijk uses immunological concepts to analyse and assess the contemporary biopolitical situation. It shows how drawing a parallel between the functioning of the biological immune system and “immune responses” on socio-political level enables to assess and reconceptualise biosecurity. It demonstrates that ideas such as “nature is the biggest terrorist” – as advanced by many virologists – sometimes result in exaggerated “immunisation responses”. This strong defensive attitude sometimes brings about collateral damage. In other words, fierce biosecurity measures sometimes risk developing into “autoimmune” responses that actually destruct the body politic they are meant to protect. By drawing on recent insights in the functioning of the biological immune system it is shown how a One-Health approach that incorporates a broader and nuanced “immunological” repertoire could act as counter-measure against “autoimmune” responses in biosecurity.


title: Fibroblast growth factor 2 (FGF2) and FGF receptor expression in an experimental demyelinating disease with extensive remyelination

text: Fibroblast growth factor 2 (FGF2) is an excellent candidate to regulate remyelination based on its proposed actions in oligodendrocyte lineage cell development in conjunction with its involvement in CNS regeneration. To assess the potential for FGF2 to play a role in remyelination, we examined the expression pattern of FGF2 and FGF receptors (FGFRs) in an experimental demyelinating disease with extensive remyelination. Adult mice were intracranially injected with murine hepatitis virus strain A‐59 (MHV‐A59) to induce focally demyelinated spinal cord lesions that spontaneously remyelinate, with corresponding recovery of motor function. Using kinetic RT‐PCR analysis of spinal cord RNA, we found significantly increased levels of FGF2 mRNA transcripts, which peaked during the initial stage of remyelination. Analysis of tissue sections demonstrated that increased levels of FGF2 mRNA and protein were localized within demyelinated regions of white matter, including high FGF2 expression associated with astrocytes. The expression of corresponding FGF receptors was significantly increased in lesion areas during the initial stage of remyelination. In normal and lesioned white matter, oligodendrocyte lineage cells, including progenitors and mature cells, were found to express multiple FGFR types (FGFR1, FGFR2, and/or FGFR3). In addition, in lesion areas, astrocytes expressed FGFR1, FGFR2, and FGFR3. These findings indicate that, during remyelination, FGF2 may play a role in directly regulating oligodendrocyte lineage cell responses and may also act through paracrine or autocrine effects on astrocytes, which are known to synthesize other growth factors and immunoregulatory molecules that influence oligodendrocyte lineage cells. J. Neurosci. Res. 62:241–256, 2000. Published 2000 Wiley‐Liss, Inc.


title: Is targeting Akt a viable option to treat advanced-stage COVID-19 patients?

text: One of the primary reasons for high mortality in the advanced stage coronavirus disease-2019 (COVID-19) patients is the uncontrolled inflammation in the lungs leading to acute respiratory distress syndrome (ARDS). Controlling the pathological inflammation in the ARDS lungs without compromising the immune system's fight against the virus is indeed a daunting task. In this situation, an appropriate therapeutic target would be the one that will not only reverse the damaging inflammation and promote resolution but also helps to check the root cause of the virus infection. Akt is a potential therapeutic target for the advanced stage COVID-19 patients; its inhibition will potentially suppress the pathological inflammation, cytokine storm, fibroproliferation, and platelet activation associated with COVID-19, and at the same time prevent scarring and promote resolution in injured lungs. As pharmacological inhibition of Akt has also been reported to inhibit ACE2 expression, a receptor for the virus entry into the lung cells, targeting Akt for COVID-19 looks a viable option.


title: The Value That Infectious Diseases Physicians Bring to the Healthcare System

text: While a career in infectious diseases (ID) has always been challenging and exciting, recognition of the value that ID physicians provide to the healthcare system as a whole, over and above the value they provide to individual patients, has been poor in this system. In response to this disparity, the Infectious Diseases Society of America Clinical Affairs Committee has long endeavored to quantify the value of ID physicians to the system, which is challenging in part because of the many avenues through which they influence healthcare. We discuss data showing that ID physicians improve clinical outcomes, positively impact transitions of care, and direct system-level improvements through infection prevention and antimicrobial stewardship. We identify areas where value-based care provides additional future opportunities for ID physicians. A Clinical Affairs Committee–sponsored study of ID physicians’ positive impact on patient outcomes shows that few medical specialties are better positioned to positively impact the Triple Aim approach—better health, better care, and lower per capita cost—that is the principle tenet of healthcare system reform.


title: RSV‐induced bronchiolitis but not upper respiratory tract infection is accompanied by an increased nasal IL‐18 response

text: The aim of this study was to investigate potential differences in the local nasal immune response between bronchiolitis and upper respiratory tract infection induced by respiratory syncytial virus (RSV). Nasal brush samples were obtained from 14 infants with RSV bronchiolitis and from 8 infants with RSV upper respiratory tract infection. The samples were taken during infection (acute phase) and 2–4 weeks later (convalescent phase). Cytospin preparations were stained immunohistochemically for T cells, macrophages, and eosinophils. Staining also took place for intercellular adhesion molecule‐1 (ICAM‐1), T‐helper 1 (Th1)‐like (interleukin‐12 [IL‐12], interferon‐γ [IFN‐γ]), Th2‐like (IL‐4, IL‐10), and proinflammatory cytokines (IL‐6, IL‐8, IL‐18). During both RSV‐induced bronchiolitis and upper respiratory tract infection, cellular inflammation was observed. This was characterised by an increase in the numbers of nasal macrophages, which tended to be higher in bronchiolitis than in upper respiratory tract infection. Numbers of T lymphocytes and ICAM‐1 positive cells increased during both bronchiolitis and upper respiratory tract infection. There were no differences between numbers in the groups. Interestingly, a distinct nasal proinflammatory cytokine response was observed in RSV‐induced bronchiolitis. This is characterised by an increase in the number of IL‐18 positive cells. This increase is specific for bronchiolitis, as a similar increase could not be detected in RSV‐induced upper respiratory tract infection. Numbers of IL‐6 and IL‐12 positive cells were higher in both bronchiolitis and upper respiratory tract infection, and there were no differences between the groups. By contrast, the number of IL‐8, IFN‐γ, IL‐4, and IL‐10‐positive cells remained constant. In conclusion, clear differences were found in nasal immune responses of children with RSV‐induced upper respiratory tract infection or bronchiolitis. The induction of a strong IL‐18 response was typical for bronchiolitis, as this could not be observed in RSV‐induced upper respiratory tract infection, and could explain the eosinophilia that is observed frequently during bronchiolitis. J. Med. Virol. 71:290–297, 2003. © 2003 Wiley‐Liss, Inc.


title: Interdisciplinarity

text: Abstract Interdisciplinarity employs multiple academic fields of knowledge in order to create a comprehensive understanding of a globally relevant phenomenon, a region, or its people, and to find solutions to concrete problems. Interdisciplinarity evolved in the 20th century in response to the institutionalization and segmentation of academic research and major transitions in society. Many geography departments have interdisciplinary profiles, but the daily practice of interdisciplinarity depends on the networks of individual academics. The results of interdisciplinary collaboration include research books, textbooks, and journal articles, the market of which continues to diversify. Authors of interdisciplinary textbooks and teachers of interdisciplinary classes must pay special attention to teaching philosophy and communication skills in order to satisfy the needs of a heterogeneous body of students interested in interdisciplinary learning. Interdisciplinarity means different things in different contexts, and practices and challenges vary. Some see interdisciplinarity as an exciting opportunity, while others feel threatened by the downsides of crossing disciplinary boundaries.


title: Modeling and analysis of epidemic spreading on community network with node's birth and death

text: Abstract In this paper, a modified susceptible infected susceptible (SIS) epidemic model is proposed on community structure networks considering birth and death of node. For the existence of node's death would change the topology of global network, the characteristic of network with death rate is discussed. Then we study the epidemiology behavior based on the mean-field theory and derive the relationships between epidemic threshold and other parameters, such as modularity coefficient, birth rate and death rates (caused by disease or other reasons). In addition, the stability of endemic equilibrium is analyzed. Theoretical analysis and simulations show that the epidemic threshold increases with the increase of two kinds of death rates, while it decreases with the increase of the modularity coefficient and network size.


title: Cancer management challenge in a developing country in COVID-19 pandemic: reflection of a group of Moroccan oncologists

text: Management of cancer patients during the COVID-19 pandemic is a worldwide challenge – in particular in developing countries where the risk of saturation of health facilities and intensive care beds must be minimized. The first case of COVID-19 was declared in Morocco on 2 March 2020, after which a panel of Moroccan experts, consisting of medical oncologists from universities and regional and private oncology centers, was promptly assembled to conduct a group reflection on cancer patient's management. The main objective is to protect the immunocompromised population from the risk of COVID-19, while maintaining an adequate management of cancer, which can quickly compromise their prognosis. Recommendations are provided according to each clinical situation: patients undergoing treatment, new cases, hospitalized patients, palliative care and surveillance.


title: Exploring COVID-19 stress and its factors in Bangladesh: A perception-based study

text: BACKGROUND: The COVID-19 pandemic has aggregated mental health sufferings throughout the entire world. Suicide completions are the extreme consequences of COVID-19 related psychological burdens, which was reported in many countries including Bangladesh. However, there are lack of study assessing COVID-19 related human stress and its’ associations with other relevant factors affecting quality of life in the country, and which were explored in the present study. METHODS: An online based survey was carried out among 340 Bangladeshi adult populations (65.90% male; mean age 26.23 ± 6.39) by utilizing the socio-demographics, possible human stress due to COVID-19 pandemic and its consequences. Dataset were analysed through a set of statistical tools e.g., T-test, one-way ANOVA, Pearson's Correlation Matrix (PCM), Principal Component Analysis (PCA), and Cluster Analysis (CA). RESULTS: About 85.60% of the participants are in COVID-19-related stress, which results in sleep shortness, short temper, and chaos in family. Fear of COVID-19 infection (i.e., self and/or family member(s), and/or relatives), hampering scheduled study plan and future career, and financial difficulties are identified as the main causes of human stress. Results of PCM explain the relationship among the factors of human stress, and found economic hardship and food crisis are linked together causes stress of mass people, while hamper of formal education and future plan create stress of career seeker. T-test, and one-way ANOVA illustrate demographic characteristics (i.e., occupation, age, gender, and marital status) have significant effects on elevated mental stress. Moreover, PCA and CA results revealed significant interface among the respondents’ perception and factors of human stress, which matched with the existing scenario of the country. CONCLUSIONS: Considering the present findings, it is essential to introduce time-oriented policy, and implement care monitoring plans in the country, which may help in managing the pandemic as well as nurturing the public mental health to combat COVID-19 related psychological challenges.


title: Developments in Transduction, Connectivity and AI/Machine Learning for Point-of-Care Testing

text: We review some emerging trends in transduction, connectivity and data analytics for Point-of-Care Testing (POCT) of infectious and non-communicable diseases. The patient need for POCT is described along with developments in portable diagnostics, specifically in respect of Lab-on-chip and microfluidic systems. We describe some novel electrochemical and photonic systems and the use of mobile phones in terms of hardware components and device connectivity for POCT. Developments in data analytics that are applicable for POCT are described with an overview of data structures and recent AI/Machine learning trends. The most important methodologies of machine learning, including deep learning methods, are summarised. The potential value of trends within POCT systems for clinical diagnostics within Lower Middle Income Countries (LMICs) and the Least Developed Countries (LDCs) are highlighted.


title: Survival functions for defining a clinical management Lost To Follow-Up (LTFU) cut-off in Antiretroviral Therapy (ART) program in Zomba, Malawi

text: BACKGROUND: While, lost to follow-up (LTFU) from antiretroviral therapy (ART) can be considered a catch-all category for patients who miss scheduled visits or medication pick-ups, operational definitions and methods for defining LTFU vary making comparisons across programs challenging. Using weekly cut-offs, we sought to determine the probability that an individual would return to clinic given that they had not yet returned in order to identify the LTFU cut-off that could be used to inform clinical management and tracing procedures. METHODS: Individuals who initiated ART with Dignitas International supported sites (n = 22) in Zomba, Malawi between January 1 2007-June 30 2010 and were ≥ 1 week late for a follow-up visit were included. Lateness was categorized using weekly cut-offs from ≥1 to ≥26 weeks late. At each weekly cut-off, the proportion of patients who returned for a subsequent follow-up visit were identified. Cumulative Distribution Functions (CDFs) were plotted to determine the probability of returning as a function of lateness. Hazard functions were plotted to demonstrate the proportion of patients who returned each weekly interval relative to those who had yet to return. RESULTS: In total, n = 4484 patients with n = 7316 follow-up visits were included. The number of included follow-up visits per patient ranged from 1–10 (median: 1). Both the CDF and hazard function demonstrated that after being ≥9 weeks late, the proportion of new patients who returned relative to those who had yet to return decreased substantially. CONCLUSIONS: We identified a LTFU definition useful for clinical management. The simple functions plotted here did not require advanced statistical expertise and were created using Microsoft Excel, making it a particularly practical method for HIV programs in resource-constrained settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12911-016-0290-7) contains supplementary material, which is available to authorized users.


title: Molecular Aspects of Co-morbidities in COVID-19 Infection

text: Coronaviruses are a group of enveloped viruses with single-stranded non-segmented positive-sense RNA genomes In December 2019, SARS-CoV-2 appeared in China for the first time and quickly spread throughout the world Although certain medications suggested for other afflictions tend to be potentially effective for curing the infection, there is no approved vaccination or drug available for this virus yet Comprehension of the disease molecular pathogenesis could provide useful tools for COVID-19 patients in surveillance, prognosis, treatment, vaccine development and therapeutic targeting The present research aims to summarize the association in COVID-19 patients between molecular dimensions of comorbidities with clinical and preclinical information Developing an ACE2 inhibitor could be a possible therapeutic target Plasmin is another possible candidate both in diagnosis and treatment areas All predicted biomarkers must be validated either through randomized clinical trials or experimental assays before clinical application in patients


title: Global health security: the wider lessons from the west African Ebola virus disease epidemic

text: The Ebola virus disease outbreak in West Africa was unprecedented in both its scale and impact. Out of this human calamity has come renewed attention to global health security—its definition, meaning, and the practical implications for programmes and policy. For example, how does a government begin to strengthen its core public health capacities, as demanded by the International Health Regulations? What counts as a global health security concern? In the context of the governance of global health, including WHO reform, it will be important to distil lessons learned from the Ebola outbreak. The Lancet invited a group of respected global health practitioners to reflect on these lessons, to explore the idea of global health security, and to offer suggestions for next steps. Their contributions describe some of the major threats to individual and collective human health, as well as the values and recommendations that should be considered to counteract such threats in the future. Many different perspectives are proposed. Their common goal is a more sustainable and resilient society for human health and wellbeing.


title: STAT1 and pathogens, not a friendly relationship

text: Abstract STAT1 belongs to the STAT family of transcription factors, which comprises seven factors: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B and STAT6. STAT1 is a 91 kDa protein originally identified as the mediator of the cellular response to interferon (IFN) α, and thereafter found to be a major component of the cellular response to IFNγ. STAT1 is, in fact, involved in the response to several cytokines and to growth factors. It is activated by cytokine receptors via kinases of the JAK family. STAT1 becomes phosphorylated and forms a dimer which enters the nucleus and triggers the transcription of its targets. Although not lethal at birth, selective gene deletion of STAT1 in mice leads to rapid death from severe infections, demonstrating its major role in the response to pathogens. Similarly, in humans who do not express STAT1, there is a lack of resistance to pathogens leading to premature death. This indicates a key, non-redundant function of STAT1 in the defence against pathogens. Thus, to successfully infect organisms, bacterial, viral or parasitic pathogens must overcome the activity of STAT1, and almost all the steps of this pathway can be blocked or inhibited by proteins produced in infected cells. Interestingly, some pathogens, like the oncogenic Epstein–Barr virus, have evolved a strategy which uses STAT1 activation.


title: The Molecular Aspect of Antitumor Effects of Protease Inhibitor Nafamostat Mesylate and Its Role in Potential Clinical Applications

text: Nafamostat mesylate (NM), a synthetic serine protease inhibitor first placed on the market by Japan Tobacco in 1986, has been approved to treat inflammatory-related diseases, such as pancreatitis. Recently, an increasing number of studies have highlighted the promising effects of NM in inhibiting cancer progression. Alone or in combination treatments, studies have shown that NM attenuates various malignant tumors, including pancreatic, colorectal, gastric, gallbladder, and hepatocellular cancers. In this review, based on several activating pathways, including the canonical Nuclear factor-κB (NF-κB) signaling pathway, tumor necrosis factor receptor-1 (TNFR1) signaling pathway, and tumorigenesis-related tryptase secreted by mast cells, we summarize the anticancer properties of NM in existing studies both in vitro and in vivo. In addition, the efficacy and side effects of NM in cancer patients are summarized in detail. To further clarify NM's antitumor activities, clinical trials devoted to validating the clinical applications and underlying mechanisms are needed in the future.


title: Fusion core structure of the severe acute respiratory syndrome coronavirus (SARS‐CoV): In search of potent SARS‐CoV entry inhibitors

text: Severe acute respiratory coronavirus (SARS‐CoV) spike (S) glycoprotein fusion core consists of a six‐helix bundle with the three C‐terminal heptad repeat (HR2) helices packed against a central coiled‐coil of the other three N‐terminal heptad repeat (HR1) helices. Each of the three peripheral HR2 helices shows prominent contacts with the hydrophobic surface of the central HR1 coiled‐coil. The concerted protein–protein interactions among the HR helices are responsible for the fusion event that leads to the release of the SARS‐CoV nucleocapsid into the target host‐cell. In this investigation, we applied recombinant protein and synthetic peptide‐based biophysical assays to characterize the biological activities of the HR helices. In a parallel experiment, we employed a HIV‐luc/SARS pseudotyped virus entry inhibition assay to screen for potent inhibitory activities on HR peptides derived from the SARS‐CoV S protein HR regions and a series of other small‐molecule drugs. Three HR peptides and five small‐molecule drugs were identified as potential inhibitors. ADS‐J1, which has been used to interfere with the fusogenesis of HIV‐1 onto CD4(+) cells, demonstrated the highest HIV‐luc/SARS pseudotyped virus‐entry inhibition activity among the other small‐molecule drugs. Molecular modeling analysis suggested that ADS‐J1 may bind to the deep pocket of the hydrophobic groove on the surface of the central coiled‐coil of SARS‐CoV S HR protein and prevent the entrance of the SARS‐CoV into the host cells. J. Cell. Biochem. 104: 2335–2347, 2008. © 2008 Wiley‐Liss, Inc.


title: Treatment with novel RSV Ig RI-002 controls viral replication and reduces pulmonary damage in immunocompromised Sigmodon hispidus

text: Respiratory syncytial virus (RSV) is a significant cause of bronchiolitis and pneumonia in several high health risk populations, including infants, elderly and immunocompromised individuals. Mortality in hematopoietic stem cell transplant recipients with lower respiratory tract RSV infection can exceed 80%. It has been shown that RSV replication in immunosuppressed individuals is significantly prolonged, but the contribution of pulmonary damage, if any, to the pathogenesis of RSV disease in this susceptible population is not known. In this work, we tested RI-002, a novel standardized Ig formulation containing a high level of RSV-neutralizing Ab, for its ability to control RSV infection in immunocompromised cotton rats Sigmodon hispidus. Animals immunosuppressed by repeat cyclophosphamide injections were infected with RSV and treated with RI-002. Prolonged RSV replication, characteristic of immunosuppressed cotton rats, was inhibited by RI-002 administration. Ab treatment reduced detection of systemic dissemination of viral RNA. Importantly, pulmonary interstitial inflammation and epithelial hyperplasia that were significantly elevated in immunosuppressed animals were reduced by RI-002 administration. These results indicate the potential of RI-002 to improve outcome of RSV infection in immunocompromised subjects not only by controlling viral replication, but also by reducing damage to lung parenchyma and epithelial airway lining, but further studies are needed.


title: Ventilator-associated pneumonia involving Aspergillus flavus in a patient with coronavirus disease 2019 (COVID-19) from Argentina

text: Coronavirus disease 2019 (COVID‐19), caused by the novel coronavirus SARS-CoV-2, emerged in Wuhan, China, in December 2019 and rapidly spread around the world. Invasive aspergillosis has been reported as a complication of severe influenza pneumonia among intensive care patients. Similarities between COVID-19 and influenza pneumonia, together with limited published case series, suggest that aspergillosis may be an important complication of COVID-19. This report describes a case of ventilator-associated pneumonia caused by Aspergillus flavus in a patient with COVID-19 from Buenos Aires, Argentina.


title: Development and Validation of a Clinical Risk Score for Intensive Care Resource Utilization After Colon Cancer Surgery: a Practical Guide to the Selection of Patients During COVID-19

text: BACKGROUND: The purpose of this study was to develop and validate a prediction model and clinical risk score for Intensive Care Resource Utilization after colon cancer surgery. METHODS: Adult (≥ 18 years old) patients from the 2012 to 2018 ACS-NSQIP colectomy-targeted database who underwent elective colon cancer surgery were identified. A prediction model for 30-day postoperative Intensive Care Resource Utilization was developed and transformed into a clinical risk score based on the regression coefficients. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow goodness-of-fit test. The model was validated in a separate test set of similar patients. RESULTS: In total, 54,893 patients underwent an elective colon cancer resection, of which 1224 (2.2%) required postoperative Intensive Care Resource Utilization. The final prediction model retained six variables: age (≥ 70; OR 1.90, 95% CI 1.68–2.14), sex (male; OR 1.73, 95% CI 1.54–1.95), American Society of Anesthesiologists score (III/IV; OR 2.52, 95% CI 2.15–2.95), cardiorespiratory disease (yes; OR 2.22, 95% CI 1.94–2.53), functional status (dependent; OR 2.81, 95% CI 2.22–3.56), and operative approach (open surgery; OR 1.70, 95% CI 1.51–1.93). The model demonstrated good discrimination (AUC = 0.73). A clinical risk score was developed, and the risk of requiring postoperative Intensive Care Resource Utilization ranged from 0.03 (0 points) to 19.0% (8 points). The model performed well on test set validation (AUC = 0.73). CONCLUSION: A prediction model and clinical risk score for postoperative Intensive Care Resource Utilization after colon cancer surgery was developed and validated.


title: Inpatient Electronic Consultations (E-consults) in Allergy/Immunology

text: Abstract Background Electronic consultations (e-consults) are asynchronous clinician to clinician exchanges within the electronic health record (EHR). Objective We sought to demonstrate the utility of e-consults in allergy/immunology (A/I) inpatient consultations. Methods Inpatients ≥ 18 years of age for whom an A/I consultation was requested were eligible for an e-consult. An e-consult was completed if considered appropriate by the A/I physician with recommendations made in the EHR. In-person consultation was performed for inpatients if deemed necessary. Likert scale satisfaction data was collected from requesting providers after the e-consultation. Cost was calculated using time-based billing codes plus the cost of penicillin allergy evaluation, if appropriate. Results Of the 109 inpatient consults, 78 (71.6%) were completed through an e-consult, and 31 (28.4%) were completed by an in-person consult. The most common indication for inpatient consult was evaluation of penicillin allergy in 73 (67%) patients. The most common reason to complete an in-person consult was the need to complete penicillin skin testing in 17 of the 31 (55%) patients. E-consults were completed in less time than in-person consults (15 minutes [IQR: 10 to 15], versus 60 minutes [IQR: 45 to 60], p < 0.001 and had a shorter turnaround time (1 hour [IQR: 0.5 to 2], versus 7 hours [IQR: 3 to 19], p < 0.001. Management recommendations were followed at a similar rate regardless of type of consult (88% of e-consults versus 96% of in-person consults, p=0.162). 97% of requesting providers reported an “excellent” or “good” impression of e-consults. E-consults were less costly than in-person consults. Conclusions E-consults have utility in providing inpatient allergy/immunology consultation, and may have advantages over in-person evaluation, while adequately maintaining provider satisfaction.


title: Diagnostic Techniques: Serological and Molecular Approaches

text: Virus laboratory diagnostics has an increasingly important role in modern patient care. Virological methods are needed to investigate the etiology of acute viral infection or the reactivation of a latent infection, as well as to follow virus load in antiviral treatments. Serological assays are also used for screening of blood products for the risk of certain chronic infections, evaluation of the immune status, and need for prophylatic treatments in connection with organ transplantations. For diagnostic purposes the following approaches can be used: demonstration of presence of infectious virus or its structural components directly from a patient's specimens or investigation of specific antibody response in serum specimes. Virus isolation is used to demonstrate infectious virus in a patient's specimens, whereas nucleic acid amplification techniques, like polymerase chain reaction (PCR), are widely used to detect virus nucleic acids. Virus antigens are investigated by antigen detection assays. Serological diagnosis is based on either the demonstration of the presence of virus-specific IgM antibodies or a significant increase in the levels of specific IgG antibodies. Immunoassays are the most commonly used serological assays. Point-of-care tests (POC tests), both for antigens and antibodies, are also becoming more and more common in diagnostic use. In order to reach the best diagnostic efficiency for each patient it is important to select the most suitable method using the right sample collected at the right time.


title: Diarreas agudas

text: Las diarreas agudas, 1,5 mil millones de casos al año en el mundo, representan la primera causa de mortalidad en el niño. En su mayoría podrían prevenirse con una prescripción adecuada, rehidratando intensamente durante las primeras horas a la vez que se vigila estrechamente la evolución del peso del niño y de la clínica, y comparando la cantidad de solución bebida con el peso y la abundancia de las heces, los vómitos y la orina.


Performing dermoscopy in the COVID‐19 pandemic


title: BSACI guidelines for the management of allergic and non‐allergic rhinitis

text: This guidance for the management of patients with allergic and non‐allergic rhinitis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and paediatricians practicing in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a web‐based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are clinical classification of rhinitis, aetiology, diagnosis, investigations and management including subcutaneous and sublingual immunotherapy. There are also special sections for children, co‐morbid associations and pregnancy. Finally, we have made recommendations for potential areas of future research.


title: Mechanistic and topological explanations in medicine: the case of medical genetics and network medicine

text: Medical explanations have often been thought on the model of biological ones and are frequently defined as mechanistic explanations of a biological dysfunction. In this paper, I argue that topological explanations, which have been described in ecology or in cognitive sciences, can also be found in medicine and I discuss the relationships between mechanistic and topological explanations in medicine, through the example of network medicine and medical genetics. Network medicine is a recent discipline that relies on the analysis of various disease networks (including disease-gene networks) in order to find organizing principles in disease explanation. My aim is to show how topological explanations in network medicine can help solving the conceptual issues that pure mechanistic explanations of the genetics of disease are currently facing, namely the crisis of the concept of genetic disease, the progressive geneticization of diseases and the dissolution of the distinction between monogenic and polygenic diseases. However, I will also argue that topological explanations should not be considered as independent and radically different from mechanistic explanations for at least two reasons. First, in network medicine, topological explanations depend on and use mechanistic information. Second, they leave out some missing gaps in disease explanation that require, in turn, the development of new mechanistic explanations. Finally, I will insist on the specific contribution of topological explanations in medicine: they push us to develop an explanation of disease in general, instead of focusing on single explanations of individual diseases. This last point may have major consequences for biomedical research.


title: Macroeconomic Effect of Infectious Disease Outbreaks

text: Abstract This article highlights the important macroeconomic effects of communicable disease outbreaks, focusing especially on evidence from computablegeneral equilibrium analyses. It illustrates how, in particular, labor supply and behavior change effects have been estimated using retrospective analysis and macroeconomic models.


title: Spread and Impact of COVID-19 in China: A Systematic Review and Synthesis of Predictions From Transmission-Dynamic Models

text: Background: Coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019 and quickly spread throughout China and the rest of the world. Many mathematical models have been developed to understand and predict the infectiousness of COVID-19. We aim to summarize these models to inform efforts to manage the current outbreak. Methods: We searched PubMed, Web of science, EMBASE, bioRxiv, medRxiv, arXiv, Preprints, and National Knowledge Infrastructure (Chinese database) for relevant studies published between 1 December 2019 and 21 February 2020. References were screened for additional publications. Crucial indicators were extracted and analysed. We also built a mathematical model for the evolution of the epidemic in Wuhan that synthesised extracted indicators. Results: Fifty-two articles involving 75 mathematical or statistical models were included in our systematic review. The overall median basic reproduction number (R(0)) was 3.77 [interquartile range (IQR) 2.78–5.13], which dropped to a controlled reproduction number (R(c)) of 1.88 (IQR 1.41–2.24) after city lockdown. The median incubation and infectious periods were 5.90 (IQR 4.78–6.25) and 9.94 (IQR 3.93–13.50) days, respectively. The median case-fatality rate (CFR) was 2.9% (IQR 2.3–5.4%). Our mathematical model showed that, in Wuhan, the peak time of infection is likely to be March 2020 with a median size of 98,333 infected cases (range 55,225–188,284). The earliest elimination of ongoing transmission is likely to be achieved around 7 May 2020. Conclusions: Our analysis found a sustained R(c) and prolonged incubation/ infectious periods, suggesting COVID-19 is highly infectious. Although interventions in China have been effective in controlling secondary transmission, sustained global efforts are needed to contain an emerging pandemic. Alternative interventions can be explored using modelling studies to better inform policymaking as the outbreak continues.


title: Synthetic long oligonucleotides to generate artificial templates for use as positive controls in molecular assays: drug resistance mutations in influenza virus as an example

text: BACKGROUND: Positive controls are an integral component of any sensitive molecular diagnostic tool, but this can be affected, if several mutations are being screened in a scenario of a pandemic or newly emerging disease where it can be difficult to acquire all the necessary positive controls from the host. This work describes the development of a synthetic oligo-cassette for positive controls for accurate and highly sensitive diagnosis of several mutations relevant to influenza virus drug resistance. RESULTS: Using influenza antiviral drug resistance mutations as an example by employing the utility of synthetic paired long oligonucleotides containing complementary sequences at their 3' ends and utilizing the formation of oligonucleotide dimers and DNA polymerization, we generated ~170bp dsDNA containing several known specific neuraminidase inhibitor (NAI) resistance mutations. These templates were further cloned and successfully applied as positive controls in downstream assays. CONCLUSION: This approach significantly improved the development of diagnosis of resistance mutations in terms of time, accuracy, efficiency and sensitivity, which are paramount to monitoring the emergence and spread of antiviral drug resistant influenza strains. Thus, this may have a significantly broader application in molecular diagnostics along with its application in rapid molecular testing of all relevant mutations in an event of pandemic.


title: Host range, host specificity and hypothesized host shift events among viruses of lower vertebrates

text: The successful replication of a viral agent in a host is a complex process that often leads to a species specificity of the virus and can make interspecies transmission difficult. Despite this difficulty, natural host switch seems to have been frequent among viruses of lower vertebrates, especially fish viruses, since there are several viruses known to be able to infect a wide range of species. In the present review we will focus on well documented reports of broad host range, variations in host specificity, and host shift events hypothesized for viruses within the genera Ranavirus, Novirhabdovirus, Betanodavirus, Isavirus, and some herpesvirus.


title: Blood donation and the global COVID‐19 pandemic: areas for social science research

text: In the context of the global COVID‐19 pandemic, blood collection agencies (BCAs) around the world are operating under unprecedented conditions. As social scientists in donor research in Canada, Australia, and the Netherlands, we provide some early observations on donor and public responses to the pandemic and identify areas for donor research moving forward. Given the significant variation among countries and BCAs, we cannot claim to present an exhaustive list that will apply to all countries and BCAs; however, we consider the following topic areas to be important based on our observations and knowledge of donation scholarship.


title: Risk Factors for Mortality and Respiratory Support in Elderly Patients Hospitalized with COVID-19 in Korea

text: BACKGROUND: The mortality risk of coronavirus disease 2019 (COVID-19) is higher in patients with older age, and many elderly patients are reported to require advanced respiratory support. METHODS: We reviewed medical records of 98 patients aged ≥ 65 years who were hospitalized with COVID-19 during a regional outbreak in Daegu/Gyeongsangbuk-do province of Korea. The outcome measures were in-hospital mortality and the treatment with mechanical ventilation (MV) or high-flow nasal cannula (HFNC). RESULTS: The median age of the patients was 72 years; 55.1% were female. Most (74.5%) had at least one underlying condition. Overall case fatality rate (CFR) was 20.4%, and median time to death after admission was 8 days. The CFR was 6.1% among patients aged 65–69 years, 22.7% among those aged 70–79 years, and 38.1% among those aged ≥ 80 years. The CFR among patients who required MV was 43.8%, and the proportion of patients received MV/HFNC was 28.6%. Nosocomial acquisition, diabetes, chronic lung diseases, and chronic neurologic diseases were significant risk factors for both death and MV/HFNC. Hypotension, hypoxia, and altered mental status on admission were also associated with poor outcome. CRP > 8.0 mg/dL was strongly associated with MV/HFNC (odds ratio, 26.31; 95% confidence interval, 7.78–88.92; P < 0.001), and showed better diagnostic characteristics compared to commonly used clinical scores. CONCLUSION: Patients aged ≥ 80 years had a high risk of requiring MV/HFNC, and mortality among those severe patients was very high. Severe initial presentation and laboratory abnormalities, especially high CRP, were identified as risk factors for mortality and severe hospital course.


title: Rates of asymptomatic respiratory virus infection across age groups

text: Respiratory viral infections are a leading cause of disease worldwide. A variety of respiratory viruses produce infections in humans with effects ranging from asymptomatic to life-treathening. Standard surveillance systems typically only target severe infections (ED outpatients, hospitalisations, deaths) and fail to track asymptomatic or mild infections. Here we performed a large-scale community study across multiple age groups to assess the pathogenicity of 18 respiratory viruses. We enrolled 214 individuals at multiple New York City locations and tested weekly for respiratory viral pathogens, irrespective of symptom status, from fall 2016 to spring 2018. We combined these test results with participant-provided daily records of cold and flu symptoms and used this information to characterise symptom severity by virus and age category. Asymptomatic infection rates exceeded 70% for most viruses, excepting influenza and human metapneumovirus, which produced significantly more severe outcomes. Symptoms were negatively associated with infection frequency, with children displaying the lowest score among age groups. Upper respiratory manifestations were most common for all viruses, whereas systemic effects were less typical. These findings indicate a high burden of asymptomatic respiratory virus infection exists in the general population.


title: The COVID-19 pandemic: biological evolution, treatment options and consequences

text: The spread of novel coronavirus SARS-CoV-2, the cause of the pandemic COVID-19 has emerged as a global matter of concern in the last couple of months. It has rapidly spread around the globe, which initially began in the city of Wuhan, People’s Republic of China and is hypothesized to originate from the group of Rhinolophus bats. Till date, there has been no clinically proven vaccine against the SARS-CoV-2 and thus the doctors are employing the other well-known techniques, which have previously successfully tackled similar other human coronaviruses. To prevent the further spread of COVID-19, doctors are advising isolation of the infected patients, and also regular washing of hands and the use of face mask for the common people. In the wake of the COVID-19 outbreak, the countries are going for nationwide lockdown as the only preventive measure to avert community transmission of this disease, which is having economic, social and psychological effect on the general mass. Therefore, this comprehensive review article encapsulates the biological evolution of human coronaviruses, probable treatment and control strategies to combat COVID-19 and, its impact on human life.


title: Update on the management of acute pharyngitis in children

text: Streptococcal pharyngitis is a very common pathology in paediatric age all over the world. Nevertheless there isn't a joint agreement on the management of this condition. Some authors recommend to perform a microbiological investigation in suspected bacterial cases in order to treat the confirmed cases with antibiotics so to prevent suppurative complications and acute rheumatic fever. Differently, other authors consider pharyngitis, even streptococcal one, a benign, self-limiting disease. Consequently they wouldn't routinely perform microbiological tests and, pointing to a judicious use of antibiotics, they would reserve antimicrobial treatment to well-selected cases. It has been calculated that the number of patients needed to treat to prevent one complication after upper respiratory tract infections (including sore throat), was over 4000. Even the use of the Centor score, in order to evaluate the risk of streptococcal infection, is under debate and the interpretation of the test results may vary considerably. Penicillin is considered all over the world as first line treatment, but oral amoxicillin is also accepted and, due to its better palatability, can be a suitable option. Macrolides should be reserved to the rare cases of proved allergy to β-lactams. Cephalosporins can be used in patients allergic to penicillin (with the exception of type I hypersensibility) and have been also proposed to treat the relapses.


title: CD8-deficient SJL mice display enhanced susceptibility to Theiler’s virus infection and increased demyelinating pathology

text: Theiler’s murine encephalomyelitis virus (TMEV) infection of the central nervous system (CNS) induces a chronic, progressive demyelinating disease in susceptible mouse strains characterized by inflammatory mononuclear infiltrates and spastic hind limb paralysis. Our lab has previously demonstrated a critical role for TMEV- and myelin-specific CD4(+) T cells in initiating and perpetuating this pathology. It has however, also been shown that the MHC class I loci are associated with susceptibility/resistance to TMEV infection and persistence. For this reason, we investigated the contribution of CD8(+) T cells to the TMEV-induced demyelinating pathology in the highly susceptible SJL/J mouse strain. Here we show that β2M-deficient SJL mice have similar disease incidence rates to wild-type controls, however β2M-deficient mice demonstrated earlier onset of clinical disease, elevated in vitro responses to TMEV and myelin proteolipid (PLP) epitopes, and significantly higher levels of CNS demyelination and macrophage infiltration at 50 days post-infection. β2M-deficient mice also displayed a significant elevation in persisting viral titers, as well as an increase in macrophage-derived pro-inflammatory cytokine mRNA expression in the spinal cord at this same time point. Taken together, these results indicate that CD8(+) T cells are not required for clinical or histologic disease initiation or progression in TMEV-infected SJL mice. Rather, these data stress the critical role of CD4(+) T cells in this capacity and further emphasize the potential for CD8(+) T cells to contribute to protection from TMEV-induced demyelination.


Global health and moral values


title: PCR assay for the detection and the identification of atypical canine coronavirus in dogs

text: Abstract Comparative sequence analysis of the PCR products of the M gene and fragments of the pol1a and pol1b genes of canine coronavirus (CCoV) have demonstrated that two separate clusters of CCoV are present in dogs. This note describes a PCR assay to identify atypical CCoV strains with nucleotide substitutions in the M gene. A total of 177 faecal samples from dogs CCoV positive previously with the PCR assay were analysed. Sixty-two of the 177 samples were amplified with the PCR described in the present study and were thus considered atypical CCoVs. The specificity of the PCR typing assay was confirmed by sequence analysis of the PCR products.


title: Comparative efficacy of hand hygiene agents in the reduction of bacteria and viruses

text: BACKGROUND: Health care-associated infections most commonly result from person-to-person transmission via the hands of health care workers. METHODS: We studied the efficacy of hand hygiene agents (n = 14) following 10-second applications to reduce the level of challenge organisms (Serratia marcescens and MS2 bacteriophage) from the hands of healthy volunteers using the ASTM-E-1174-94 test method. RESULTS: The highest log(10) reductions of S marcescens were achieved with agents containing chlorhexidine gluconate (CHG), triclosan, benzethonium chloride, and the controls, tap water alone and nonantimicrobial soap and water (episode 1 of hand hygiene, 1.60-2.01; episode 10, 1.60-3.63). Handwipes but not alcohol-based handrubs were significantly inferior from these agents after a single episode of hand hygiene, but both groups were significantly inferior after 10 episodes. After a single episode of hand hygiene, alcohol/silver iodide, CHG, triclosan, and benzethonium chloride were similar to the controls in reduction of MS2, but, in general, handwipes and alcohol-based handrubs showed significantly lower efficacy. After 10 episodes, only benzethonium chloride (1.33) performed as well as the controls (1.59-1.89) in the reduction of MS2. CONCLUSIONS: Antimicrobial handwashing agents were the most efficacious in bacterial removal, whereas waterless agents showed variable efficacy. Alcohol-based handrubs compared with other products demonstrated better efficacy after a single episode of hand hygiene than after 10 episodes. Effective hand hygiene for high levels of viral contamination with a nonenveloped virus was best achieved by physical removal with a nonantimicrobial soap or tap water alone.


title: The bulky and the sweet: How neutralizing antibodies and glycan receptors compete for virus binding

text: Numerous viruses rely on glycan receptor binding as the initial step in host cell infection. Engagement of specific glycan receptors such as sialylated carbohydrates, glycosaminoglycans, or histo‐blood group antigens can determine host range, tissue tropism, and pathogenicity. Glycan receptor‐binding sites are typically located in exposed regions on viral surfaces—sites that are also generally prone to binding of neutralizing antibodies that directly interfere with virus‐glycan receptor interactions. In this review, we examine the locations and architecture of the glycan‐ and antibody‐binding sites in four different viruses with stalk‐like attachment proteins (reovirus, influenza virus, norovirus, and coronavirus) and investigate the mechanisms by which antibodies block glycan recognition. Those viruses exemplify that direct molecular mimicking of glycan receptors by antibodies is rare and further demonstrate that antibodies often partly overlap or bind sufficiently close to the receptor‐binding region to hinder access to this site, achieving neutralization partially because of the epitope location and partly due to their sheer size.


title: Novel Bat Alphacoronaviruses in Southern China Support Chinese Horseshoe Bats as an Important Reservoir for Potential Novel Coronaviruses

text: While bats are increasingly recognized as a source of coronavirus epidemics, the diversity and emergence potential of bat coronaviruses remains to be fully understood. Among 1779 bat samples collected in China, diverse coronaviruses were detected in 32 samples from five different bat species by RT-PCR. Two novel alphacoronaviruses, Rhinolophus sinicus bat coronavirus HKU32 (Rs-BatCoV HKU32) and Tylonycteris robustula bat coronavirus HKU33 (Tr-BatCoV HKU33), were discovered from Chinese horseshoe bats in Hong Kong and greater bamboo bats in Guizhou Province, respectively. Genome analyses showed that Rs-BatCoV HKU32 is closely related to BatCoV HKU10 and related viruses from diverse bat families, whereas Tr-BatCoV HKU33 is closely related to BtNv-AlphaCoV and similar viruses exclusively from bats of Vespertilionidae family. The close relatedness of Rs-BatCoV HKU32 to BatCoV HKU10 which was also detected in Pomona roundleaf bats from the same country park suggests that these viruses may have the tendency of infecting genetically distant bat populations of close geographical proximity with subsequent genetic divergence. Moreover, the presence of SARSr-CoV ORF7a-like protein in Rs-BatCoV HKU32 suggests a common evolutionary origin of this accessory protein with SARS-CoV, also from Chinese horseshoe bats, an apparent reservoir for coronavirus epidemics. The emergence potential of Rs-BatCoV HKU32 should be explored.


title: Psychopathological problems related to the COVID‐19 pandemic and possible prevention with music therapy

text: COVID-19 is having a profound effect on societies worldwide and the impact that it is having on children cannot be underestimated. Although Brodin (1) stated that the disease tends to be mild in children, psychopathological considerations allow us to assume that the pandemic will have a high risk of long-term paediatric psychiatric sequelae and interdisciplinary preventative measures are needed.


title: Physico-chemical properties of calf-diarrhea coronavirus

text: Abstract Replication of calf diarrhea coronavirus was not inhibited by 5-iodo-2′-deoxyuridine, indicating that the virus is an RNA virus. Sensitivity to ether and chloroform indicated that the virus is enveloped, and this was confirmed by electron microscopic observation of the virion. The virus was readily inactivated by trypsin and sodium deoxycholate. The virus was labile at 50°C in diluted medium, but readily stabilized in the presence of MgCl2. It was stable at pH 5 and 7, while a slight loss of infectivity was observed at pH 3. The virus was readily filtered through membrane filters of 200 and 100-nm pore sizes, but not through 50-nm filters. The buoyant density of the virion in CsCl was estimated to be 1.25 g/ml.


title: Airway protease/antiprotease imbalance in atopic asthmatics contributes to increased Influenza A virus cleavage and replication

text: Asthmatics are more susceptible to influenza infections, yet mechanisms mediating this enhanced susceptibility are unknown. Influenza virus hemagglutinin (HA) protein binds to sialic acid residues on the host cells. HA requires cleavage to allow fusion of the viral HA with host cell membrane, which is mediated by host trypsin-like serine protease. We show data here demonstrating that the protease:antiprotease ratio is increased in the nasal mucosa of asthmatics and that these changes were associated with increased proteolytic activation of influenza. These data suggest that disruption of the protease balance in asthmatics enhances activation and infection of influenza virus.


title: Antiviral effect of lithium chloride on infection of cells by canine parvovirus

text: Canine parvovirus type 2 causes significant viral disease in dogs, with high morbidity, high infectivity, and high mortality. Lithium chloride is a potential antiviral drug for viruses. We determined the antiviral effect of Lithium Chloride on canine parvovirus type 2 in feline kidney cells. The viral DNA and proteins of canine parvovirus were suppressed in a dose-dependent manner by lithium chloride. Further investigation verified that viral entry into cells was inhibited in a dose-dependent manner by lithium chloride. These results indicated that lithium chloride could be a potential antiviral drug for curing dogs with canine parvovirus infection. The specific steps of canine parvovirus entry into cells that are affected by lithium chloride and its antiviral effect in vivo should be explored in future studies.


title: Competing during a pandemic? Retailers’ ups and downs during the COVID-19 outbreak

text: The COVID-19 pandemic (that started in early 2020) is causing several disruptions in the short- and mid-term, to which businesses have to adapt. Some retailers have reacted to the emergency immediately, displaying a plethora of different intervention types. The authors aim to synthesize the challenges that retailers are facing during the COVID-19 emergency. We do this from the perspective of both consumers and managers, with the goal of providing guidelines on and examples of how retailers can handle this unprecedented situation.


title: Numerical study on the dispersion of airborne contaminants from an isolation room in the case of door opening

text: Abstract A negative pressure isolation room is built to accommodate and cure patients with highly infectious diseases. An absolutely airtight space effectively prevents infectious diseases from leaking out of the isolation room. Opening the door leads to a breakdown in isolation conditions and causes the dispersion of infectious air out of the isolation room. Extensively employed to manage smoke in cases of fires at subway and highway tunnels, a concept of controlling airflow is applied to the study. This study proposes a design of ventilation system to control air flow rate for containing airborne contaminant and preventing its spread to the adjacent rooms when the door to the isolation room is opened and closed. This paper employs computational fluid dynamics (CFD) as a more effective approach to examine the concentration maps of airborne contaminants and the airflow patterns of room air and discuss the influence of temperature differences between two rooms on airborne dispersion. Results show that an air velocity above 0.2 m/s via a doorway effectively prevents the spread of airborne contaminants out of the isolation room in the state of door opening.


title: Acute Physiology and Chronic Health Evaluation II Score as a Predictor of Hospital Mortality in Patients of Coronavirus Disease 2019

text: OBJECTIVES: Coronavirus disease 2019 has emerged as a major global health threat with a great number of deaths in China. We aimed to assess the association between Acute Physiology and Chronic Health Evaluation II score and hospital mortality in patients with coronavirus disease 2019, and to compare the predictive ability of Acute Physiology and Chronic Health Evaluation II score, with Sequential Organ Failure Assessment score and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65) score. DESIGN: Retrospective observational cohort. SETTING: Tongji Hospital in Wuhan, China. SUBJECTS: Confirmed patients with coronavirus disease 2019 hospitalized in the ICU of Tongji hospital from January 10, 2020, to February 10, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 178 potentially eligible patients with symptoms of coronavirus disease 2019, 23 patients (12.92%) were diagnosed as suspected cases, and one patient (0.56%) suffered from cardiac arrest immediately after admission. Ultimately, 154 patients were enrolled in the analysis and 52 patients (33.77%) died. Mean Acute Physiology and Chronic Health Evaluation II score (23.23 ± 6.05) was much higher in deaths compared with the mean Acute Physiology and Chronic Health Evaluation II score of 10.87 ± 4.40 in survivors (p < 0.001). Acute Physiology and Chronic Health Evaluation II score was independently associated with hospital mortality (adjusted hazard ratio, 1.07; 95% CI, 1.01–1.13). In predicting hospital mortality, Acute Physiology and Chronic Health Evaluation II score demonstrated better discriminative ability (area under the curve, 0.966; 95% CI, 0.942–0.990) than Sequential Organ Failure Assessment score (area under the curve, 0.867; 95% CI, 0.808–0.926) and CURB65 score (area under the curve, 0.844; 95% CI, 0.784–0.905). Based on the cut-off value of 17, Acute Physiology and Chronic Health Evaluation II score could predict the death of patients with coronavirus disease 2019 with a sensitivity of 96.15% and a specificity of 86.27%. Kaplan-Meier analysis showed that the survivor probability of patients with coronavirus disease 2019 with Acute Physiology and Chronic Health Evaluation II score less than 17 was notably higher than that of patients with Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 (p < 0.001). CONCLUSIONS: Acute Physiology and Chronic Health Evaluation II score was an effective clinical tool to predict hospital mortality in patients with coronavirus disease 2019 compared with Sequential Organ Failure Assessment score and CURB65 score. Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 serves as an early warning indicator of death and may provide guidance to make further clinical decisions.


title: High antibiotic prescription rates in hospitalized children with human metapneumovirus infection in comparison to RSV infection emphasize the value of point-of-care diagnostics

text: BACKGROUND: Respiratory infections are the main causes for hospitalization in children and a common reason for the initiation of antibiotic treatment. Rapid antigen detection tests and point-of-care mPCR-based assays provide a fast detection of viral pathogens. Nonetheless, the prescription rate of antibiotics for respiratory infections is exceedingly high. In particular, human metapneumovirus (hMPV) infections frequently cause antibiotic treatment. METHODS: Children hospitalized in our clinic with an acute respiratory infection between January 2008 and January 2013 were included in the present study. Data of 3799 children were analyzed retrospectively for clinical symptoms, laboratory findings, and antibiotic and inhalation treatment. We performed an in-house m-RT-PCR-ELISA method for pathogen detection. RESULTS: Pathogen detection was possible in 2464 patients. In 6.3%, hMPV and, in 24.0%, RSV were detected. Patients positively tested for hMPV received inhalation therapy in 62.9%; patients positive for RSV in 73.8%. Patients positive for hMPV were treated with antibiotics in 62.3%. Patients with RSV infection received antibiotic treatment in 44.4%; all others in 43.5%. Notably, a positive result in RSV-RADT was associated with reduced number of antibiotic treatment. CONCLUSION: hMPV infections inherit a two times higher probability of antibiotic treatment. There was no significant difference in laboratory findings or body temperature between hMPV infection and infections caused by other pathogens. Clinical symptoms seem not to differ from those in RSV illness. Nonetheless, RSV infections triggered significantly lower antibiotic prescription rates. A considerate application of a POC-mPCR for patients with RSV-like symptoms and age of 1 year and older with a negative RSV-RADT might lead to higher detection rates of hMPV and a reduction in prescription of antibiotics.


title: Headache as the Presenting Symptom in 2 Patients with COVID‐19 and a History of Migraine: 2 Case Reports

text: The Coronavirus disease 2019 (COVID‐19) pandemic has now affected more than five million people globally. Typical symptoms include fever, cough, and shortness of breath. Patients with underlying medical comorbidities such as cardiovascular disease and diabetes are more likely to become severely ill. To date there is limited information on how COVID‐19 affects patients with a history migraine. Here, we present the cases of 2 women with a history of migraine whose first symptom of COVID‐19 was a severe persistent headache.


title: Modernising epidemic science: enabling patient-centred research during epidemics

text: BACKGROUND: Emerging and epidemic infectious disease outbreaks are a significant public health problem and global health security threat. As an outbreak begins, epidemiological investigations and traditional public health responses are generally mounted very quickly. However, patient-centred research is usually not prioritised when planning and enacting the response. Instead, the clinical research response occurs subsequent to and separate from the public health response, and is inadequate for evidence-based decision-making at the bedside or in the offices of public health policymakers. DISCUSSION: The deficiencies of the clinical research response to severe acute respiratory syndrome, pandemic influenza, Middle East respiratory syndrome coronavirus and Ebola virus demonstrate that current research models do not adequately inform and improve the quality of clinical care or public health response. Three suggestions for improvements are made. First, integrate the data and sample collection needs for clinical and public health decision-making within a unified framework, combined with a risk-based, rather than a discipline-based, approach to ethical review and consent. Second, develop clinical study methods and tools that are specifically designed to meet the epidemiological and contextual challenges of emerging and epidemic infectious diseases. Third, invest in investigator-led clinical research networks that are primed and incentivised to respond to outbreak infections, and which can call on the support and resources of a central centre of excellence. CONCLUSIONS: It is crucial that the field of epidemic science matures to place patients at the heart of the response. This can only be achieved when patient-centred research is integrated in the outbreak response from day one and practical steps are taken to reduce the barriers to the generation of reliable and useful evidence.


title: Therapie viraler Atemwegsinfekte: Wirkprinzipien, Strategien und Ausblicke

text: Pulmonary viral infections are associated with substantial morbidity and socioeconomic costs. Rhinovirus, influenza A and B, adenovirus, parainfluenza, respiratory syncytial virus (RSV), and coronavirus are etiologies most often associated with infections of the upper and lower respiratory tract. Therapy of viral infections in nonimmunocompromised hosts has only developed slowly during recent years, despite the enormous socioeconomic impact. This is in part due to the complex virus/host interactions and numerous and varying mechanisms of infection. Neuraminidase inhibitors have produced notable progress in the therapeutic approaches to influenza-associated pulmonary infections and are at least able to shorten the duration of symptoms in selected patients. However, neuraminidase inhibitors can only be applied in specific infections and the spectrum of agents with antiviral activity is broad. This article summarizes major principles of antiviral efficacy and reviews recent clinical trials.


title: Measurement of lipocalin-2 and syndecan-4 levels to differentiate bacterial from viral infection in children with community-acquired pneumonia

text: BACKGROUND: In this study, we evaluated the lipocalin-2 (LIP2) and syndecan-4 (SYN4) levels in children who were hospitalized for radiologically confirmed CAP in order to differentiate bacterial from viral infection. The results regarding the LIP2 and SYN4 diagnostic outcomes were compared with the white blood cell (WBC) count and C reactive protein (CRP) levels. METHODS: A total of 110 children <14 years old who were hospitalized for radiologically confirmed CAP were enrolled. Serum samples were obtained upon admission and on day 5 to measure the levels of LIP2, SYN4, and CRP as well as the WBC. Polymerase chain reaction of the respiratory secretions and tests on blood samples were performed to detect respiratory viruses, Streptococcus pneumoniae, and Mycoplasma pneumoniae. RESULTS: CAP was considered to be due to a probable bacterial infection in 74 children (67.3 %) and due to a probable viral infection in 16 children (14.5 %). Overall, 84 children (76.4 %) were diagnosed with severe CAP. The mean values of the WBC count and the LIP2 and SYN4 levels did not differ among the probable bacterial, probable viral, and undetermined cases. However, the CRP serum concentrations were significantly higher in children with probable bacterial CAP than in those with probable viral disease (32.2 ± 55.5 mg/L vs 9.4 ± 17.0 mg/L, p < 0.05). The WBC count was the best predictor of severe CAP, but the differences among the studied variables were marginal. The WBC count was significantly lower on day 5 in children with probable bacterial CAP (p < 0.01) and in those with an undetermined etiology (p < 0.01). The CRP and LIP2 levels were significantly lower 5 days after enrollment in all of the studied groups, independent of the supposed etiology of CAP (p < 0.01 for all comparisons). No statistically significant variation was observed for SYN4. CONCLUSIONS: Measuring the LIP2 and SYN4 levels does not appear to solve the problem of the poor reliability of routine laboratory tests in defining the etiology and severity of pediatric CAP. Currently, the CRP levels and WBC, when combined with evaluation of clinical data, can be used to limit the overuse of antibiotics as much as possible and to provide the best treatment to the patient.


title: Spinned Poisson distribution with health management application

text: Consider a data collection setup during a spread of an infectious disease. Examples include severe acute respiratory syndrome (SARS) or influenza A virus H3N2. The health management in such scenarios quickly removes the infected cases before the data collection is completed. The estimate of the incidence rate or the chance for anyone to be immune requires using a correct probability distribution. The usual Poisson distribution is inappropriate because of the impact of removing infected cases on the incidence rate as well as observing a new case. An appropriate new probability distribution is derived and is named as spinned Poisson distribution. The statistical properties of the spinned Poisson distribution are developed and illustrated using infectious smallpox incidence in Abakaliki, Nigeria.


title: Targeting the World’s Slums as Fat Tails in the Distribution of COVID-19 Cases

text: A recent article by Corburn et al. lays out the policies that would help slum communities in the global south deal with COVID-19. That article notes the vulnerabilities of people in these informal settlements and argues that any assistance program must recognize these realities so that the policies do not further jeopardize the survival of large segments of the population of these communities. This note extends the arguments in that paper, focusing on some of the logistic issues involved in providing assistance to informal settlements. It argues that such assistance is essential not only for the help it would provide to people in these settlements but also because the residents of these communities should be key targets of assistance. Because of the location and occupation of most of the residents of these communities, targeting them simultaneously addresses health and economy-wide concerns generated by COVID-19. Their characteristics make them much more likely to be afflicted by the virus and spread it to others. The main conclusions of this note with respect to policy are that the scale of such assistance is likely to be larger than has so far been proposed, that in countries with limited testing ability slums provide one of the most effective places to target assistance, that the role of community groups in providing the assistance is difficult to exaggerate, and that philanthropy has a role to play in supporting innovation.


title: Will Children Reveal their Secret? The Coronavirus Dilemma

text: A recent ERJ editorial cited ACE2 upregulation as a key reason for the better outcomes of COVID-19 seen in paediatric patients. However, there is significant conflicting literature on the topic, and many questions about ACE2 physiology still unanswered


title: Chapter 21 In Silico Models From Simple Networks to Complex Diseases

text: Abstract In this chapter, we consider in silico modeling of diseases starting from some simple to some complex (and mathematical) concepts. Examples and applications of in silico modeling for some important categories of diseases (such as for cancers, infectious diseases, and neuronal diseases) are also given.


title: Vomiting, Diarrhea, Constipation, and Gastroenteritis

text: Diseases that cause vomiting, diarrhea, constipation, and gastroenteritis are major problems for populations worldwide. Patients, particularly infants, elderly, and immunocompromised individuals, may present at any point in a wide spectrum of disease states, underscoring the need for the clinician to treat these ailments aggressively. Several promising new treatment modalities, from oral rehydration solutions to antiemetic therapies, have been introduced over the past decade. Future directions include the use of probiotic agents and better tolerated rehydration solutions. Gastrointestinal disease will continue to be a focus worldwide in the search for better ways to cure illnesses associated with vomiting and diarrhea.


title: The Crosstalk of Endoplasmic Reticulum (ER) Stress Pathways with NF-κB: Complex Mechanisms Relevant for Cancer, Inflammation and Infection

text: Stressful conditions occuring during cancer, inflammation or infection activate adaptive responses that are controlled by the unfolded protein response (UPR) and the nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) signaling pathway. These systems can be triggered by chemical compounds but also by cytokines, toll-like receptor ligands, nucleic acids, lipids, bacteria and viruses. Despite representing unique signaling cascades, new data indicate that the UPR and NF-κB pathways converge within the nucleus through ten major transcription factors (TFs), namely activating transcription factor (ATF)4, ATF3, CCAAT/enhancer-binding protein (CEBP) homologous protein (CHOP), X-box-binding protein (XBP)1, ATF6α and the five NF-κB subunits. The combinatorial occupancy of numerous genomic regions (enhancers and promoters) coordinates the transcriptional activation or repression of hundreds of genes that collectively determine the balance between metabolic and inflammatory phenotypes and the extent of apoptosis and autophagy or repair of cell damage and survival. Here, we also discuss results from genetic experiments and chemical activators of endoplasmic reticulum (ER) stress that suggest a link to the cytosolic inhibitor of NF-κB (IκB)α degradation pathway. These data show that the UPR affects this major control point of NF-κB activation through several mechanisms. Taken together, available evidence indicates that the UPR and NF-κB interact at multiple levels. This crosstalk provides ample opportunities to fine-tune cellular stress responses and could also be exploited therapeutically in the future.


title: Managing a Specialty Service During the COVID-19 Crisis: Lessons From a New York City Health System

text: The COVID-19 pandemic has stretched health care resources to a point of crisis throughout the world. To answer the call for care, health care workers in a diverse range of specialties are being retasked to care for patients with COVID-19. Consequently, specialty services have had to adapt to decreased staff available for coverage coupled with a need to remain available for specialty-specific emergencies, which now require a dynamic definition. In this Invited Commentary, the authors describe their experiences and share lessons learned regarding triage of patients, staff safety, workforce management, and the psychological impact as they have adapted to a new reality in the Department of Neurosurgery at Montefiore Medical Center, a COVID-19 hot spot in New York City.


title: The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission

text: Speech droplets generated by asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasingly considered to be a likely mode of disease transmission. Highly sensitive laser light scattering observations have revealed that loud speech can emit thousands of oral fluid droplets per second. In a closed, stagnant air environment, they disappear from the window of view with time constants in the range of 8 to 14 min, which corresponds to droplet nuclei of ca. 4 μm diameter, or 12- to 21-μm droplets prior to dehydration. These observations confirm that there is a substantial probability that normal speaking causes airborne virus transmission in confined environments.


title: Characterisation of two enteroviruses isolated from Australian brushtail possums (Trichosurus vulpecula) in New Zealand

text: Two enteroviruses, designated W1 and W6, were isolated from intestinal contents of Australian brushtail possums (Trichosurus vulpecula) in New Zealand. The genomic sequences of W1 and W6 were 7390 and 7391 nucleotides (nt), respectively. Genetically, possum isolates W1 and W6 were related to bovine enterovirus serotype 2 (BEV-2) strains, especially to the strain PS87/Belfast, based on the capsid protein sequence. However, W1 and W6 formed a clade that was distinct from PS87Belfast based on nucleotide sequences of the 3′ and 5′-non-translated region and in the amino acid sequences of 2A, 3C and 3D. Possum isolates W1 and W6 grew more readily in possum kidney cells than in Madin-Darby bovine kidney (MDBK) cells, suggesting that co-evolution of W1 and W6 with possums has made them more adapted to possum cells.


title: Respiratory viruses detected in Mexican children younger than 5 years old with community-acquired pneumonia: a national multicenter study

text: Abstract Background Acute respiratory infections are the leading cause of mortality in children worldwide, especially in developing countries. Pneumonia accounts for 16% of all deaths of children under 5 years of age and was the cause of death of 935000 children in 2015. Despite its frequency and severity, information regarding its etiology is limited. The aim of this study was to identify respiratory viruses associated with community-acquired pneumonia (CAP) in children younger than 5 years old. Methods One thousand four hundred and four children younger than 5 years of age with a clinical and/or radiological diagnosis of CAP in 11 hospitals in Mexico were included. Nasal washes were collected, placed in viral medium, and frozen at −70°C until processing. The first 832 samples were processed using the multiplex Bio‐Plex/Luminex system and the remaining 572 samples using the Anyplex multiplex RT-PCR. Clinical data regarding diagnosis, clinical signs and symptoms, radiographic pattern, and risk factors were obtained and recorded. Results Of the samples tested, 81.6% were positive for viruses. Respiratory syncytial virus (types A and B) was found in 23.7%, human enterovirus/rhinovirus in 16.6%, metapneumovirus in 5.7%, parainfluenza virus (types 1–4) in 5.5%, influenza virus (types A and B) in 3.6%, adenovirus in 2.2%, coronavirus (NL63, OC43, 229E, and HKU1) in 2.2%, and bocavirus in 0.4%. Co-infection with two or more viruses was present in 22.1%; 18.4% of the samples were negative. Using biomass for cooking, daycare attendance, absence of breastfeeding, and co-infections were found to be statistically significant risk factors for the presence of severe pneumonia. Conclusions Respiratory syncytial virus (types A and B), human enterovirus/rhinovirus, and metapneumovirus were the respiratory viruses identified most frequently in children younger than 5 years old with CAP. Co-infection was present in an important proportion of the children.


Scientific Report of the Scientific Panel on Biological Hazards on “Food as a possible source of infection with highly pathogenic avian influenza viruses for humans and other mammals”


title: Severe acute respiratory syndrome coronavirus accessory proteins 6 and 9b interact in vivo

text: Abstract The 3′proximal one-third of the severe acute respiratory syndrome coronavirus (SARS-CoV) genome encodes the structural proteins and eight accessory proteins, including 3a, 3b, 6, 7a, 7b, 8a, 8b and 9b, varying in length from 39 to 274aa which do not share significant homology with viral proteins of known coronaviruses. The SARS-CoV protein 6 is 63 amino acids in length and has been previously involved in virus pathogenicity and replication. To further analyze this functions, the interaction of SARS-CoV protein 6 with other viral and/or cellular factors has been analyzed during SARS-CoV infective cycle. Protein 6 immunoprecipitation from extracts of SARS-CoV infected cells and mass spectrometry analysis revealed an interaction of viral proteins 6 and 9b in biologically relevant conditions. This interaction has been reinforced by co-localization of both proteins in the cytoplasm of SARS-CoV infected cells.


title: The race for treatments

text: It will take time to develop a coronavirus vaccine, but some existing drugs may help save lives before then, says Michael Le Page


International Society for Influenza and other Respiratory Viruses and the new journal


title: Dicistroviruses

text: The Dicistroviridae are a family of small icosahedral viruses with single-stranded RNA, positive-sense genomes that infect invertebrates. The genomes are organized with their nonstructural proteins encoded at the 5′ end with the structural proteins at the 3′ end. Characteristically, the two open reading frames are separated by an untranslated region that is capable of acting as an internal ribosome entry site (IRES). In addition to the structural proteins being expressed from this IRES, translation usually initiates from a noncanonical amino acid, generally alanine. The dicistroviruses share a number of characteristics, for example, virion structure, genomic organization, and the absence of subgenomic RNAs with other picorna-like viruses of plants, animals, and protists that suggest a shared evolutionary origin and a higher-order taxonomic grouping for such viruses. Most dicistroviruses, with the exception of cricket paralysis virus (CrPV), have restricted host ranges and only infect species from a single insect order. In contrast, CrPV is able to infect over 20 species of insects and several insect cell lines. Most dicistroviruses have vertical and horizontal components in their transmission and generally produce few noticeable disease symptoms. Infection with dicistroviruses does, however, usually result in a shortened life span and reduced fecundity of the host.


title: Synthesis, antimicrobial, anticancer, antiviral evaluation and QSAR studies of 4-(1-aryl-2-oxo-1,2-dihydro-indol-3-ylideneamino)-N-substituted benzene sulfonamides

text: Abstract A series of 4-(1-aryl-2-oxo-1,2-dihydro-indol-3-ylideneamino)-N-substituted benzenesulfonamide derivatives (1–32) was synthesized and evaluated for its in vitro antimicrobial, antiviral and cytotoxic activities. Antimicrobial results indicated that compounds (11) and (18) were found to be the most effective ones. In general, the synthesized compounds were bacteriostatic and fungistatic in their action. The cytotoxic screening results indicated that the compounds were less active than the standard drug 5-fluorouracil (5-FU). None of the compounds inhibited viral replication at subtoxic concentrations. In general, the presence of a pyrimidine ring with electron releasing groups and an ortho- and para-substituted benzoyl moiety favored antimicrobial activities. The results of QSAR studies demonstrated the importance of topological parameters, valence zero order molecular connectivity index (0 χ v ) and valence first order molecular connectivity index (1 χ v ) in describing the antimicrobial activity of synthesized compounds.


title: ASSISTED REPRODUCTION AND THROMBOEMBOLIC RISK IN COVID-19 PANDEMIC

text: Covid-19 pandemic has increased significantly to mortality in many countries with the number of infected cases increasing exponentially worldwide. One of the main determining factors of the poor prognosis in these patients is the development of coagulopathy. Moreover, it is well known that ART procedures confer a risk of thromboembolic complications. In this commentary we analize specific coexisting aspects between the thrombotic risk described during virus infection and that one reported in the context of assisted reproduction treatments. Based on known pathophysiological aspects of both virus infection and those identified during ovarian stimulation (OS), we found common elements that deserve to be taken into account. In the present context, any risk of hyperstimulation should be avoided. GnRh agonist triggering should be mandatory in high responders patients and/or with COVID infection. In both cases, the cycle should be segmented. We propose prophylactic with low molecular weigth heparin (LMWH) not only in those cases in which the oocyte recovery has been performed, but also in those in which the cancellation has been decided. In addition, the endometrial preparation to the frozen-thawed embryo transfers (FETs) should be using the transdermal route in order to minimize the higher thrombotic risk of the oral route.


Animal Arterivirus Infections


title: The systemic sclerosis patient in the COVID-19 era: the challenging crossroad between immunosuppression, differential diagnosis and long-term psychological distress

text: COVID-19 is a world health emergency which may inevitably affect the management of a complex autoimmune disease such as systemic sclerosis (SSc). Several SSc patients are frail and, in this pandemic, need a careful protection. The COVID-19 infection might complicate the clinical scenario of interstitial lung disease (ILD) in SSc because it determines a severe pneumonia characterized by radiological features similar to SSc-ILD. The striking CT similarities between the 2 diseases make it difficult to distinguish a worsening of SSc-ILD from COVID-19-ILD superinfection. Moreover, other aspects, like isolation during lock down, may cause a significant psychological stress which will pile up on the already difficult contact with the patients for a routine check-up. Moreover, the drug shortage is a real problem in these times. For these reasons, the rheumatologist in daily clinical practice should carefully differentiate the possible COVID-19 infection in order to optimize the patient management. Therefore, the challenge in everyday life will be to achieve in due time the differential diagnosis as well as the long-term psychological impact.


title: Development of polymerase chain reaction-based diagnostic tests for detection of Malsoor virus & adenovirus isolated from Rousettus species of bats in Maharashtra, India

text: BACKGROUND & OBJECTIVES: Bats are recognized as important reservoirs for emerging infectious disease and some unknown viral diseases. Two novel viruses, Malsoor virus (family Bunyaviridae, genus, Phlebovirus) and a novel adenovirus (AdV) (family, Adenoviridae genus, Mastadenovirus), were identified from Rousettus bats in the Maharashtra State of India. This study was done to develop and optimize real time reverse transcription - polymerase chain reaction (RT-PCR) assays for Malsoor virus and real time and nested PCR for adenovirus from Rousettus bats. METHODS: For rapid and accurate screening of Malsoor virus and adenovirus a nested polymerase chain reaction and TaqMan-based real-time PCR were developed. Highly conserved region of nucleoprotein gene of phleboviruses and polymerase gene sequence from the Indian bat AdV isolate polyprotein gene were selected respectively for diagnostic assay development of Malsoor virus and AdV. Sensitivity and specificity of assays were calculated and optimized assays were used to screen bat samples. RESULTS: Molecular diagnostic assays were developed for screening of Malsoor virus and AdV and those were found to be specific. Based on the experiments performed with different parameters, nested PCR was found to be more sensitive than real-time PCR; however, for rapid screening, real-time PCR can be used and further nested PCR can be used for final confirmation or in those laboratories where real-time facility/expertise is not existing. INTERPRETATION & CONCLUSIONS: This study reports the development and optimization of nested RT-PCR and a TaqMan-based real-time PCR for Malsoor virus and AdV. The diagnostic assays can be used for rapid detection of these novel viruses to understand their prevalence among bat population.


title: Identification of nucleolus localization signal of betanodavirus GGNNV protein α

text: Abstract Betanodavirus greasy grouper (Epinephelus tauvina) nervous necrosis viruses (GGNNV) protein α, a virus capsid protein, was detected in both nucleolus and cytoplasm of infected cells of Asian sea bass (SB) and transfected cells of SB and Cos-7 with pcDNA3.1/RNA2. To study its subcellular localization, ORF of protein α with 338 aa was fused with enhanced green fluorescent protein (EGFP) gene and was detected in transfected cells in the absence of other viral proteins. In both SB and Cos-7 cells, protein α was found to localize EGFP to the nucleolus and cytoplasm. Deletion mutants of protein α indicated that N-terminal 43 amino acid residues were required to import EGFP-α protein into the nucleolus. Further deletions within the 43 amino acid backbone, EGFP/33aa(1–33) and EGFP/30aa(14–43), localized to the nucleolus, suggesting that the 20 amino acids from 14 to 33 of protein α were the domain of nucleolus localization. To further determine the nucleolus targeting sequence, deletion mutations within the 20 amino acids of protein α were constructed. It was found that the deletion of 23RRR25, 29RRR31, or 23RRRANNRRR31 prevented the accumulation of EGFP fusion proteins into the nucleolus, demonstrating that 23RRRANNRRR31 contain the signal required for nucleolar localization. A similar distribution pattern of localization of protein α and its deletion mutants in SB and Cos-7 cells suggested that N-terminal residues of protein α 23RRRANNRRR31 constitute a nucleolus localization signal that functions in both fish and mammalian cells.


title: Knowledge, Attitudes and Practices Towards COVID-19: An Epidemiological Survey in North-Central Nigeria

text: The COVID-19 pandemic has become a major public health challenge globally with countries of the world adopting unprecedented infection prevention and control (IPC) measures to urgently curtail the spread of the COVID-19 virus. The knowledge, attitudes and practices (KAP) of the people toward COVID-19 is critical to understanding the epidemiological dynamics of the disease and the effectiveness, compliance and success of IPC measures adopted in a country. This study sought to determine the levels of KAP toward COVID-19 among residents of north-central Nigeria. A cross-sectional online survey with a semi-structured questionnaire using a Snowball sampling technique was conducted during the national lockdown. Data collected were analyzed using descriptive statistics, analysis of variance (ANOVA), Pearson’s correlation and regression tests. From a total of 589 responses received, 80.6, 59.6, 90.4 and 56.2% were from respondents between ages 18–39 years, males, had a college (Bachelor) degree or above and reside in urban areas respectively. Respondents had good knowledge (99.5%) of COVID-19, gained mainly through the internet/social media (55.7%) and Television (27.5%). The majority of the respondents (79.5%) had positive attitudes toward the adherence of government IPC measures with 92.7, 96.4 and 82.3% practicing social distancing/self-isolation, improved personal hygiene and using face mask respectively. However, 52.1% of the respondents perceived that the government is not doing enough to curtail COVID-19 in Nigeria. Pearson’s correlation showed significant relationship between knowledge of COVID-19 and attitude towards preventive measures (r = 0.177, p = 0.004, r = 0.137, p = 0.001). Although 61.8% of the respondents have no confidence in the present intervention by Chinese doctors, only 29.0% would accept COVID-19 vaccines when available. This study recorded good knowledge and attitudes among participants, however, community-based health campaigns are necessary to hold optimistic attitudes and practice appropriate intervention measures devoid of misconceptions.


title: Targeting drug delivery in the vascular system: Focus on endothelium()

text: The bloodstream is the main transporting pathway for drug delivery systems (DDS) from the site of administration to the intended site of action. In many cases, components of the vascular system represent therapeutic targets. Endothelial cells, which line the luminal surface of the vasculature, play a tripartite role of the key target, barrier, or victim of nanomedicines in the bloodstream. Circulating DDS may accumulate in the vascular areas of interest and in off-target areas via mechanisms bypassing specific molecular recognition, but using ligands of specific vascular determinant molecules enables a degree of precision, efficacy, and specificity of delivery unattainable by non-affinity DDS. Three decades of research efforts have focused on specific vascular targeting, which have yielded a multitude of DDS, many of which are currently undergoing a translational phase of development for biomedical applications, including interventions in the cardiovascular, pulmonary, and central nervous systems, regulation of endothelial functions, host defense, and permeation of vascular barriers. We discuss the design of endothelial-targeted nanocarriers, factors underlying their interactions with cells and tissues, and describe examples of their investigational use in models of acute vascular inflammation with an eye on translational challenges.


title: Synthesis and antimicrobial activity of amino acid and peptide derivatives of mycophenolic acid

text: The series of 16 novel amino acid and peptide mycophenolic acid (MPA) derivatives was obtained as potential antibacterial agents. Coupling of MPA with respective amines was optimized with condensing reagents such as EDCI/DMAP and T3P/TEA. Amino acid analogs were received both as methyl esters and also with the free carboxylic group. The biological activity of the products was tested on five references bacterial strains: Klebsiella pneumoniae ATCC 700603 (ESBL), Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus MRSA ATCC 43300, Staphylococcus aureus MSSA ATCC 25923. Peptide derivatives proved to be the most versatile ones, their MIC values relative to most strains was lower than MPA alone. It has been noted that the activity of amino acid derivatives depends on the configuration at the chiral center in the amino acid unit and methyl esters indicated better antimicrobial activity than analogs with free carboxylic group.


title: Role of Nonstructural Proteins in the Pathogenesis of SARS‐CoV‐2

text: We read with great interest the study authored by Angeletti et al. regarding the role of nonstructural proteins nsp2 and nsp3 in the pathogenesis of COVID‐19(1). COVID‐19 emerged in December 2019 in Wuhan City, Hubei Province, China and is caused by a novel viral variant belonging to the viral variant belonging to the Severe acute respiratory syndrome‐related coronavirus (SARS‐rCoV) species of subgenus Sarbecovirus, genus Betacoronavirus, family Coronaviridae and named SARS‐CoV‐2(2). This article is protected by copyright. All rights reserved.