title: The Location of the Protonated and Unprotonated Forms of Arbidol in the Membrane: A Molecular Dynamics Study

text: ABSTRACT: Arbidol is a potent broad-spectrum antiviral molecule for the treatment and prophylaxis of many viral infections. Viruses that can be inhibited by arbidol include enveloped and non-enveloped viruses, RNA and DNA viruses, as well as pH-independent and pH-dependent ones. These differences in viral types highlight the broad spectrum of Arb antiviral activity and, therefore, it must affect a common viral critical step. Arbidol incorporates rapidly into biological membranes, and some of its antiviral effects might be related to its capacity to interact with and locate into the membrane. However, no information is available of the molecular basis of its antiviral mechanism/s. We have aimed to locate the protonated (Arp) and unprotonated (Arb) forms of arbidol in a model membrane system. Both Arb and Arp locate in between the hydrocarbon acyl chains of the phospholipids but its specific location and molecular interactions differ from each other. Whereas both Arb and Arp average location in the membrane palisade is a similar one, Arb tends to be perpendicular to the membrane surface, whereas Arp tends to be parallel to it. Furthermore, Arp, in contrast to Arb, seems to interact stronger with POPG than with POPC, implying the existence of a specific interaction between Arp, the protonated from, with negatively charged phospholipids. This data would suggest that the active molecule of arbidol in the membrane is the protonated one, i.e., the positively charged molecule. The broad antiviral activity of arbidol would be defined by the perturbation it exerts on membrane structure and therefore membrane functioning. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00232-016-9876-3) contains supplementary material, which is available to authorized users.


title: Climate change impact on migration, travel, travel destinations and the tourism industry

text: Background: Climate change is not only increasing ambient temperature but also accelerating the frequency, duration and intensity of extreme weather and climate events, such as heavy precipitation and droughts, and causing sea level rise, which can lead to population displacement. Climate change-related reductions in land productivity and habitability and in food and water security can also interact with demographic, economic and social factors to increase migration. In addition to migration, climate change has also implications for travel and the risk of disease. This article discusses the impact of climate change on migration and travel with implications for public health practice. Methods: Literature review. Results: Migrants may be at increased risk of communicable and non-communicable diseases, due to factors in their country of origin and their country of destination or conditions that they experience during migration. Although migration has not been a significant driver of communicable disease outbreaks to date, public health authorities need to ensure that effective screening and vaccination programmes for priority communicable diseases are in place. Population growth coupled with socio-economic development is increasing travel and tourism, and advances in technology have increased global connectivity and reduced the time required to cover long distances. At the same time, as a result of climate change, many temperate regions, including high-income countries, are now suitable for vector-borne disease transmission. This is providing opportunities for importation of vectors and pathogens from endemic areas that can lead to cases or outbreaks of communicable diseases with which health professionals may be unfamiliar. Conclusion: Health systems need to be prepared for the potential population health consequences of migration, travel and tourism and the impact of climate change on these. Integrated surveillance, early detection of cases and other public health interventions are critical to protect population health and prevent and control communicabledisease outbreaks.


Co-infection cases of human common respiratory viruses in Beijing, 2010–2012


title: Combining Free Text and Structured Electronic Medical Record Entries to Detect Acute Respiratory Infections

text: BACKGROUND: The electronic medical record (EMR) contains a rich source of information that could be harnessed for epidemic surveillance. We asked if structured EMR data could be coupled with computerized processing of free-text clinical entries to enhance detection of acute respiratory infections (ARI). METHODOLOGY: A manual review of EMR records related to 15,377 outpatient visits uncovered 280 reference cases of ARI. We used logistic regression with backward elimination to determine which among candidate structured EMR parameters (diagnostic codes, vital signs and orders for tests, imaging and medications) contributed to the detection of those reference cases. We also developed a computerized free-text search to identify clinical notes documenting at least two non-negated ARI symptoms. We then used heuristics to build case-detection algorithms that best combined the retained structured EMR parameters with the results of the text analysis. PRINCIPAL FINDINGS: An adjusted grouping of diagnostic codes identified reference ARI patients with a sensitivity of 79%, a specificity of 96% and a positive predictive value (PPV) of 32%. Of the 21 additional structured clinical parameters considered, two contributed significantly to ARI detection: new prescriptions for cough remedies and elevations in body temperature to at least 38°C. Together with the diagnostic codes, these parameters increased detection sensitivity to 87%, but specificity and PPV declined to 95% and 25%, respectively. Adding text analysis increased sensitivity to 99%, but PPV dropped further to 14%. Algorithms that required satisfying both a query of structured EMR parameters as well as text analysis disclosed PPVs of 52–68% and retained sensitivities of 69–73%. CONCLUSION: Structured EMR parameters and free-text analyses can be combined into algorithms that can detect ARI cases with new levels of sensitivity or precision. These results highlight potential paths by which repurposed EMR information could facilitate the discovery of epidemics before they cause mass casualties.


title: Laparoscopic Major Hepatectomy—Technique and Outcomes

text: BACKGROUND: With technological innovations especially newer parenchymal transection devices, improved understanding of hepatic anatomy facilitated by better imaging, and reconstructions along with experiences gained from advanced minimal invasive procedures, laparoscopic liver surgery is gaining momentum with more than 5300 reported cases worldwide. Most of the published literature comprises nonanatomical and segmental resections with only few case series having major hepatic resections performed by minimally invasive approach. Aim of this article is to share our technique and experience of total laparoscopic major hepatectomy. METHODS: It is a retrospective analysis of prospectively maintained database of 56 patients, who underwent laparoscopic major hepatectomy for various indications during 2001 to 2013. RESULTS: Of 56 patients operated, 37 had malignant disease and 19 had benign lesions with mean size of 6.0 ± 2.8 cm. Thirty-four patients underwent right hepatectomy and 22 left with mean age of 54.8 ± 15.3 years. Mean operating time was 227.4 ± 51.8 min with mean blood loss 265.5 ± 143.4 ml and transfusion needed in 10.7 %. Pringle’s maneuver was used in 19.6 % with mean occlusion time of 34.0 ± 11.4 min. Liver-specific complications were observed in 12.5 % and overall complications in 19.6 %. Mean resection margin length in malignant lesions was 2.1 ± 0.9 cm, with <1 cm margin noted in 5.4 %. Median hospital stay was 8 days (6–29) with readmission rate of 8.9 %, re-intervention rate of 5.3 % and 90 days mortality of 1.7 %. CONCLUSION: Laparoscopic major liver resection is a formidable task. It requires considerable expertise in both, advanced laparoscopy, and liver surgery. It can be feasible, safe, and oncologically adequate in well-selected cases in experience hands.


title: Effect of deoxycholate, amphotericin B and fongizone on transmissible gastroenteritis coronavirus

text: Summary At a concentration of 2 μg/ml, neither amphotericin B nor deoxycholate had an inactivating effect upon transmissible gastroenteritis Coronavirus in-fectivity. However, amphothericin B stimulated plaque formatin in agarose and facilitated the entry of viral RNA into swine testis cells. The combination of amphotericin B + deoxycholate inactivated virus infectivity and induced a decrease in plaque diameter. Finally, in the presence of these agents, the production of infectious virus and interferon was unchanged.


title: CHEST Reviews: Addressing reduced laboratory-based pulmonary function testing during a pandemic

text: Abstract To reduce the spread of SARS-CoV-2, many pulmonary function testing (PFT) laboratories have been closed or have significantly reduced their testing capacity. As these mitigation strategies may be necessary for the next 6-18 months to prevent recurrent peaks in disease prevalence, fewer objective measurements of lung function will alter the diagnosis and care of patients with chronic respiratory diseases. PFTs, which include spirometry, lung volumes, and diffusion capacity measurement, are essential to the diagnosis and management of patients with asthma, COPD, and other chronic lung conditions. Both traditional and innovative alternatives to conventional testing must now be explored. These may include peak expiratory flow devices, electronic portable spirometers, portable exhaled nitric oxide measurement, airwave oscillometry devices, as well as novel digital health tools such as smartphone microphone spirometers, and mobile health technologies along integration of machine learning approaches. The adoption of some novel approaches may not merely replace but could improve existing management strategies and alter common diagnostic paradigms. With these options come important technical, privacy, ethical, financial, and medicolegal barriers that must be addressed. However, the COVID-19 pandemic also presents a unique opportunity to augment conventional testing by including innovative and emerging approaches to measuring lung function remotely in patients with respiratory disease. The benefits of such an approach have the potential to enhance respiratory care and empower patient self-management well beyond the current global pandemic.


Haunted with and hunting for viruses


title: Pneumonia caused by Mycobacterium tuberculosis

text: Tuberculosis (TB) is one of the top ten leading causes of death worldwide. The causative agent of TB is Mycobacterium tuberculosis. Acute tuberculous pneumonia (TP) is an acute form of pulmonary TB. However, acute TP and non-tuberculous community-acquired pneumonia can be easily confused, resulting in deterioration of TP due to delayed treatment. Therefore, rapid and accurate diagnosis of acute TP is crucial in order to stop the transmission of TB. Moreover, development of new diagnostic tools (technologies and approaches), and flexible application of different therapy schemes will help to reduce the incidence of TP and promote the goal of ending the TB epidemic.


title: L’exposition d’un nourrisson à un chien n’augmente pas le risque de sensibilisation ; elle semble même diminuer les risques de sensibilisation à d’autres pneumallergènes et le risque d’asthme à 4 ans ! C.

text: Unknown


title: Differential neurodegenerative phenotypes are associated with heterogeneous voiding dysfunction in a coronavirus-induced model of multiple sclerosis

text: Patients with multiple sclerosis (MS) develop a variety of lower urinary tract symptoms (LUTS). We previously characterized a murine model of neurogenic bladder dysfunction induced by a neurotropic strain of a coronavirus. In the present study, we further study the role of long-lasting neurodegeneration on the development of neurogenic bladder dysfunction in mice with corona-virus induced encephalitis (CIE). Long-term follow up study revealed three phenotypes of neurodegenerative symptom development: recovery (REC group), chronic progression (C-PRO group) and chronic disease with relapsing-remitting episodes (C-RELAP group). The levels of IL-1β in REC group, IL-10 in C-RELAP group, and IL-1β, IL-6, IL-10 and TNF-α in C-PRO group were diminished in the brain. The levels of TNF-α in REC group and INF-γ, IL-2, TGF-β and TNF-α in the C-PRO group were also diminished in the urinary bladder. Mice in C-RELAP group showed a delayed recovery of voiding function. In vitro contractility studies determined a decreased basal detrusor tone and reduced amplitude of nerve-mediated contractions in C-RELAP group, whereas C-PRO group had elevated muscle-mediated contractions. In conclusion, mice with CIE developed three phenotypes of neurologic impairment mimicking different types of MS progression in humans and showed differential mechanisms driving neurogenic bladder dysfunction.


title: Community-Based Assessment of Knowledge, Attitude, Practices and Risk Factors Regarding COVID-19 Among Pakistanis Residents During a Recent Outbreak: A Cross-Sectional Survey

text: Exceptional precautionary measures have been adopted to stop the transmission and control of COVID-19 through the world and Pakistan is facing lockdown in this scenario. Public loyalty to precautionary measures is affected by their knowledge, attitude, risk factors and practices (KAP) towards COVID-19. The present study was conducted among the Pakistani residents to observe the knowledge, attitude, practices and risk factors towards COVID-19 outbreak in Pakistan. A questionnaire was designed, and a cross-sectional survey was conducted among participants of the study area. Participants were asked the questions regarding knowledge, attitude, practices and risk factors towards COVID-19. Data were analyzed by SPSS and t/F test and correlation was applied among the knowledge, attitude, risk factors and practices. A total of 1060 questionnaires were received. 1004 were included while 56 were excluded. The highest representation was from Punjab province (65.6%), female (63%) and age group of 21–30 years (62.1%). Most participants were single (85%), Muslim (99.4%), Urdu speaking (45.6%) and were graduates (51.5%). Most of the participants were students (52.9%) and were from economically middle-class families (40.8%). The knowledge was positively correlated with attitude and practices whereas negatively correlated with risk factors (P < 0.05). The attitude was negatively correlated with risk factor and positively correlated with practices. The risk factors and practices were positively correlated with each other. Health education program to improve the COVID-19 knowledge, attitude, practices and risk factors should be initiated to combat current health challenge.


Practice Corner COVID-19: What We Have Learned So Far


Autoimmune Reactions Against Myelin Basic Protein Induced by Corona and Measles Viruses


title: Delivery of SA35 and SA40 peptides in mice enhances humoral and cellular immune responses and confers protection against Cryptosporidium parvum infection

text: BACKGROUND: Cryptosporidium parvum is a major cause of diarrhea in children and ruminants at the earliest stages of life. Maternal antibodies represent the main shield of neonate mammals for most of the infections. Two recombinant antigens (SA35 and SA40), portions of two C. parvum proteins, were tested for their ability to induce immune responses in adult mice and for protection on neonate BALB/c mice born from females immunised by mucosal delivery of both peptides. METHODS: Adult BALB/c mice were intraperitoneally immunised with SA35 and SA40, separately or mixed, and their immune response was characterised. Furthermore, BALB/c pregnant mice were immunised by mucosal delivery with an SA35/40 mix, before and during pregnancy. Soon after birth, their offspring were infected with two doses (1 × 10(5) and 5 × 10(3)) of C. parvum oocysts and the parasitic burden was determined at 5 and 9 days post-infection. RESULTS: Intraperitoneal immunisation with SA35 and SA40 induced specific IgG and IgG1 in serum, specific IgA in the intestinal mucosa, increase of CD3+/CD4+ and CD30+ cells in splenocytes, which produced IFN-γ. Neonates born from immunised mice and infected with 1 × 10(5) oocysts showed a significant reduction of oocysts and intestinal forms (23 and 42%, respectively). A reduction of all parasitic forms (96%; P < 0.05) was observed when neonates were infected with 5 × 10(3) oocysts. CONCLUSIONS: SA35 and SA40 peptides induce specific humoral and cell-mediated immune responses to C. parvum in adult mice. Moreover, mucosal administration of the SA35/40 mix in pregnant mice reduces C. parvum burden in their litters.


title: Expression of the SARS-CoV-2 Entry Proteins, ACE2 and TMPRSS2, in Cells of the Olfactory Epithelium: Identification of Cell Types and Trends with Age

text: [Image: see text] The COVID-19 pandemic revealed that there is a loss of smell in many patients, including in infected but otherwise asymptomatic individuals. The underlying mechanisms for the olfactory symptoms are unclear. Using a mouse model, we determined whether cells in the olfactory epithelium express the obligatory receptors for entry of the SARS-CoV-2 virus by using RNAseq, RT-PCR, in situ hybridization, Western blot, and immunocytochemistry. We show that the cell surface protein ACE2 and the protease TMPRSS2 are expressed in sustentacular cells of the olfactory epithelium but not, or much less, in most olfactory receptor neurons. These data suggest that sustentacular cells are involved in SARS-CoV-2 virus entry and impairment of the sense of smell in COVID-19 patients. We also show that expression of the entry proteins increases in animals of old age. This may explain, if true also in humans, why individuals of older age are more susceptible to the SARS-CoV-2 infection.


title: Epidemiologic and Clinical Characteristics of 26 Cases of COVID-19 Arising from Patient-to-Patient Transmission in Liaocheng, China [Corrigendum]

text: [This corrects the article DOI: 10.2147/CLEP.S249903.].


title: Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation

text: Viral infections are important causes of morbidity and mortality after allogeneic stem cell hematopoietic transplantation (allo-HSCT). Although most viral infections present with asymptomatic or subclinical manifestations, viruses may result in fatal complications in severe immunocompromised recipients. Reactivation of latent viruses, such as herpesviruses, is frequent during the immunosuppression that occurs with allo-HSCT. Viruses acquired from community, such as the respiratory and gastrointestinal viruses, are also important pathogens of post-transplant viral diseases. Currently, molecular diagnostic methods have replaced or supplemented traditional methods, such as viral culture and antigen detection, in diagnosis of viral infections. The utilization of polymerase chain reaction facilitates the early diagnosis. In view of lacking efficacious agents for treatment of viral diseases, prevention of viral infections is extremely valuable. Application of prophylactic strategies including preemptive therapy reduces viral infections and diseases. Adoptive cellular therapy for restoring virus-specific immunity is a promising method in the treatment of viral diseases.


Applying Triage Principles of Mass Casualty Events to the SARS-Cov-2 Pandemic: From the Perspective of the Acute Care Surgeons at Long Island Jewish Medical Center in the COVID Epicenter of the United States


title: Testing the effectiveness of physical activity advice delivered via text messaging vs. human phone advisors in a Latino population: The On The Move randomized controlled trial design and methods

text: Abstract Physical inactivity is a key risk factor for a range of chronic diseases and conditions, yet, approximately 50% of U.S. adults fall below recommended levels of regular aerobic physical activity (PA). This is particularly true for ethnic minority populations such as Latino adults for whom few culturally adapted programs have been developed and tested. Text messaging (SMS) represents a convenient and accessible communication channel for delivering targeted PA information and support, but has not been rigorously evaluated against standard telehealth advising programs. The objective of the On The Move randomized controlled trial is to test the effectiveness of a linguistically and culturally targeted SMS PA intervention (SMS PA Advisor) versus two comparison conditions: a) a standard, staff-delivered phone PA intervention (Telephone PA Advisor) and b) an attention-control arm consisting of a culturally targeted SMS intervention to promote a healthy diet (SMS Nutrition Advisor). The study sample (N = 350) consists of generally healthy, insufficiently active Latino adults ages 35 years and older living in five northern California counties. Study assessments occur at baseline, 6, and 12 months, with a subset of participants completing 18-month assessments. The primary outcome is 12-month change in walking, and secondary outcomes include other forms of PA, assessed via validated self-report measures and supported by accelerometry, and physical function and well-being variables. Potential mediators and moderators of intervention success will be explored to better determine which subgroups do best with which type of intervention. Here we present the study design and methods, including recruitment strategies and yields. Trial Registration: clinicaltrial.gov Identifier = NCT02385591


title: T cell ageing: Effects of age on development, survival & function

text: Age associated decline of the immune system continues to be a major health concern. All components of innate and adaptive immunity are adversely affected to lesser or greater extent by ageing resulting in an overall decline of immunocompetence. As a result in the aged population, there is increased susceptibility to infection, poor responses to vaccination, and increased incidence of autoreactivity. There is an increasing focus on the role of T cells during ageing because of their impact on the overall immune responses. A steady decline in the production of fresh naïve T cells, more restricted T cell receptor (TCR) repertoire and weak activation of T cells are some of the effects of ageing. In this review we summarize our present understanding of the effects of ageing on naïve CD4 T cells and potential approaches for therapeutic interventions to restore protective immunity in the aged population.


docid: tyeyanyo

title: Characterization of a nucleic acid probe for the diagnosis of human coronavirus 229E infections

text: A cDNA copy of the HCV229E nucleocapsid protein gene was isolated and characterized. Sequence analysis predicts a nucleocapsid polypeptide of 389 amino acids with a molecular weight (mol. wt.) of 43,450. Single strand RNA probes derived from the cDNA copy hybridize specifically to HCV229E RNA and approximately 50 pg of intracellular viral RNA can be readily detected. The application of nucleic acid hybridization as a routine procedure for the diagnosis of HCV229E infection is discussed.


title: The Novel Coronavirus – A Snapshot of Current Knowledge

text: Another animal to human transmission of a coronavirus occurred in December 2019 on a live animal market in the Chinese city of Wuhan causing an epidemic in China, reaching now different continents. This minireview summarizes the research literature on the virological, clinical and epidemiological aspects of this epidemic published until end of February 2020.


title: Techniques actuelles de diagnostic des infections virales respiratoires en réanimation

text: Résumé Plusieurs centaines de virus respiratoires différents peuvent être détectés chez les patients atteints d'une infection virale respiratoire et hospitalisés dans un service de réanimation: virus influenza, virus respiratoire syncytial, virus para-influenza, adénovirus, coronavirus, rhinovirus, entérovirus, métapneumovirus humain, bocavirus… La recherche de ces virus doit être effectuée sur un prélèvement nasal ou trachéobronchique, riche en cellules épithéliales. Chez les patients immunodéprimés, il faut ajouter un lavage bronchoalvéolaire pour rechercher le cytomégalovirus et les adénovirus. La mise en évidence d'antigènes viraux par immunofluorescence (IF) ou technique immunoenzymatique dans les cellules infectées est en théorie la méthode la plus simple et rapide à utiliser. Comme pour toutes les techniques de diagnostic, la qualité du prélèvement est un déterminant majeur de son efficacité. Cette méthode est malheureusement peu sensible dans les infections respiratoires chez l'adulte. La recherche virale en culture, compliquée et de réponse tardive, peut être utile dans ce cas en raison de son efficacité. Les méthodes PCR sont plus efficaces: elles peuvent identifier les virus non détectés par les techniques conventionnelles et elles augmentent l'isolement des virus classiques. Elles permettent aussi d'identifier les sous-types viraux, d'étudier par séquençage la variabilité génétique des souches et de quantifier la charge virale respiratoire. Les techniques multiplex recherchant plusieurs virus directement dans les prélèvements sont les plus adaptées au diagnostic en raison du nombre de virus à rechercher. Des méthodes PCR en temps réel, fournissant un résultat rapide, ont été récemment développées. La richesse en cellules et le transport du prélèvement sont moins critiques pour les recherches virales en PCR que pour les techniques conventionnelles d'IF et de culture. De plus, les acides nucléiques persistent plus longtemps que les virus infectieux, permettant ainsi un diagnostic plus tardif. Néanmoins, dans un laboratoire de virologie clinique où la rapidité, le coût modéré et la simplicité des techniques sont des exigences prioritaires, le meilleur choix est d'utiliser séquentiellement l'IF et les PCR multiplex. Le développement des outils de PCR multiplex en temps réel est la priorité majeure du futur. Abstract Hundred viruses can be isolated in patients suffering from respiratory virus infections and hospitalised in intensive care unit (ICU): influenza virus, respiratory syncytial virus, para-influenza virus, adenovirus, coronavirus, rhinovirus, enterovirus, human metapneumovirus, bocavirus… Nasal or tracheobronchial specimens, which contain many epithelial cells will be used to isolate these common viruses. In immunocompromised patients a bronchoalveolar lavage has to be added to these specimens in order to detect cytomegalovirus and some adenovirus. The immunofluorescence or immunoenzymatic assays, which detect viral antigens in the infected cells are the easiest and fastest diagnostic methods, theoretically. As with other techniques, specimen quality is a major determinant of their performance. Unfortunately, the sensitivity of the antigen detection assays is low in respiratory infections in adults. Then the virus recovery by cell culture, which is usually more sensitive than the antigen detection assays, can be helpful. Many studies have reported more respiratory virus detections using nucleic acid testing such as PCR. They detect viruses, which are missed by conventional methods and increase the detection of common respiratory virus. Multiplex PCR assays have been developed, and these can simultaneously detect several viruses directly in clinical specimens. Nucleic acid testing can subtype viruses using subtype-specific primers, and analyse strain variation through genetic. It can be used also to quantify the viral load in clinical specimens. More recently real-time RT-PCR assays have been developed to get more rapidly the results of the nucleic acids assays. Specimen quality, timing and transportation conditions may be less critical for nucleic acid testing than for culture or antigen detection, as viable virus and intact infected cells need not to be preserved. Moreover, viral nucleic acids are detectable for several days longer into the clinical course than is cultivable virus, potentially allowing a diagnosis to be made in late-presenting patients. However, in a clinical virology laboratory, where the speed, low cost, and high sensitivity of the methods are required, the sequential use of antigen detection tests and multiplex PCR could be the best choice, particularly in the clinical setting of respiratory virus infections in adults hospitalised in ICU. In the future, the development of real-time multiplex PCR is likely to be top-priority.


title: Terminal complement inhibition dampens the inflammation during COVID‐19

text: Emerging evidence suggests that activation of the complement system is critical in the pathogenesis of the novel coronavirus, SARS‐CoV‐2, the causative agent of COVID‐19 related lung injury. Inhibition of the terminal complement pathway by targeting complement protein 5 (C5) may be an effective therapeutic intervention in CoV‐mediated disease.(1) Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired hematopoietic stem cell (HSC) disease characterized by intravascular haemolysis, increased thromboembolic risk and bone marrow failure.(2)


title: How should we treat pregnant women infected with SARS‐CoV‐2?

text: The health crisis caused by the novel SARS-cov-2 (formally called 2019-nCoV) related pandemic requires urgent action, including a necessary therapeutic response. Pregnant women are just as exposed as the general population and should not be excluded, because of their status, from discussions on effective and well tolerated candidate treatments.


title: Basic Approach to Veterinary Care of Ferrets

text: The approach to preventive medicine and basic veterinary care in ferrets is very similar to that used in dogs and cats. Special equipment needs are minimal, and pet ferrets can be easily incorporated into a general small animal practice. This chapter describes the unique aspects of handling, restraint, and clinical and treatment techniques used in ferrets.


Response to Letter to the Editor titled ‘Risk Modeling for Unplanned Intensive Care Unit (ICU) Admission’


title: Self-assembly of Severe Acute Respiratory Syndrome Coronavirus Membrane Protein

text: Coronavirus membrane (M) protein can form virus-like particles (VLPs) when coexpressed with nucleocapsid (N) or envelope (E) proteins, suggesting a pivotal role for M in virion assembly. Here we demonstrate the self-assembly and release of severe acute respiratory syndrome coronavirus (SARS-CoV) M protein in medium in the form of membrane-enveloped vesicles with densities lower than those of VLPs formed by M plus N. Although efficient N-N interactions require the presence of RNA, we found that M-M interactions were RNA-independent. SARS-CoV M was observed in both the Golgi area and plasma membranes of a variety of cells. Blocking M glycosylation does not appear to significantly affect M plasma membrane labeling intensity, M-containing vesicle release, or VLP formation. Results from a genetic analysis indicate involvement of the third transmembrane domain of M in plasma membrane-targeting signal. Fusion proteins containing M amino-terminal 50 residues encompassing the first transmembrane domain were found to be sufficient for membrane binding, multimerization, and Golgi retention. Surprisingly, we found that fusion proteins lacking all three transmembrane domains were still capable of membrane binding, Golgi retention, and interacting with M. The data suggest that multiple SARS-CoV M regions are involved in M self-assembly and subcellular localization.


title: Respiratory viral infection in lower airways of asymptomatic children

text: Aim: The aim of this study was to determine if asthmatic children have viruses more commonly detected in lower airways during asymptomatic periods than normal children. Methods: Fifty‐five asymptomatic children attending elective surgical procedures (14 with stable asthma, 41 normal controls) underwent non‐bronchoscopic bronchoalveolar lavage. Differential cell count and PCR for 13 common viruses were performed. Results: Nineteen (35%) children were positive for at least one virus, with adenovirus being most common. No differences in the proportion of viruses detected were seen between asthmatic and normal ‘control’ children. Viruses other than adenovirus were associated with higher neutrophil counts, suggesting that they caused an inflammatory response in both asthmatics and controls (median BAL neutrophil count, 6.9% for virus detected vs. 1.5% for virus not detected, p = 0.03). Conclusions: Over one‐third of asymptomatic children have a detectable virus (most commonly adenovirus) in the lower airway; however, this was not more common in asthmatics. Viruses other than adenovirus were associated with elevated neutrophils suggesting that viral infection can be present during relatively asymptomatic periods in asthmatic children.


title: Crystallographic, thermodynamic, and molecular modeling studies of the mode of binding of oligosaccharides to the potent antiviral protein griffithsin

text: The mode of binding of oligosaccharides to griffithsin, an antiviral lectin from the red alga Griffithsia sp., was investigated by a combination of X‐ray crystallography, isothermal titration calorimetry, and molecular modeling. The structures of complexes of griffithsin with 1→6α‐mannobiose and with maltose were solved and refined at the resolution of 2.0 and 1.5 Å, respectively. The thermodynamic parameters of binding of 1→6α‐mannobiose, maltose, and mannose to griffithsin were determined. Binding profiles of 1→6α‐mannobiose and mannose were similar with K (d) values of 83.3 μM and 102 μM, respectively. The binding of maltose to griffithsin was significantly weaker, with a fourfold lower affinity (K (d) = 394 μM). In all cases the binding at 30°C was entropically rather than enthalpically driven. On the basis of the experimental crystal structures, as well as on previously determined structures of complexes with monosaccharides, it was possible to create a model of a tridentate complex of griffithsin with Man(9)GlcNAc(2), a high mannose oligosaccharide commonly found on the surface of viral glycoproteins. All shorter oligomannoses could be modeled only as bidentate or monodentate complexes with griffithsin. The ability to mediate tight multivalent and multisite interactions with high‐mannose oligosaccharides helps to explain the potent antiviral activity of griffithsin. Proteins 2007. © 2007 Wiley‐Liss, Inc.


The effect of substance P on asthmatic rat airway smooth muscle cell proliferation, migration, and cytoplasmic calcium concentration in vitro


title: Commentary: Challenges for PhD students during COVID‐19 pandemic: Turning crisis into an opportunity

text: COVID‐19 results in the suspension of life all over the world. Universities suspended their academic activities except for online courses for undergrad and grad students. However, PhD students in both biochemistry and molecular biology fields must hold their experiments at the laboratories. Even under these extreme circumstances, the academic journey of a master's or PhD student should not be stopped; on contrary, they need to use these times to improve their knowledge related to their fields. Therefore, they can turn this COVID‐19 crisis into an opportunity for themselves.


title: Wuchang Fangcang Shelter Hospital: Practices, Experiences, and Lessons Learned in Controlling COVID-19

text: In early January 2020, the outbreak of the new corona virus pneumonia (Corona Virus Disease 2019, COVID-19) occurred. Wuhan, the capital city of Hubei province, became the epicenter of the disease in China. The rapid growth of patients had exceeded the maximum affordability of local medical resources. A large comprehensive gymnasium was converted into Wuchang Fangcang Shelter Hospital in order to provide adequate medical beds and appropriate care for the confirmed patients with mild to moderate symptoms. For these hospitalized patients with COVID-19, medication became the mainstay of therapy. From 5th February to 10th March, a team of pharmacists successfully completed drug supplies and pharmaceutical services for 1124 patients and approximately 800 medical staff, and, while doing so, received zero complaint, and experienced zero disputes and zero pharmacist infection. This paper summarizes the development and construction of the pharmacy, human resource allocation of pharmacists, pharmacy administration, and pharmaceutical services. It aims to review a 34-day period of pharmaceutical practice and serve as a reference for other health professionals working on COVID-19 prevention and treatment in other regions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42399-020-00382-1) contains supplementary material, which is available to authorized users.


title: The association between blood eosinophil percent and bacterial infection in acute exacerbation of chronic obstructive pulmonary disease

text: Introduction: The use of antibiotics is based on the clinician’s experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD. Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events. Methods: We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017. Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission. Results: A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events). In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (P=0.010 and P=0.001, respectively). In logistic regression analysis, the rates of only bacterial pathogen identification [odds ratios =1.744; 95% confidence interval, 1.107–2.749; P=0.017] and bacterial-viral pathogen co-identification [odds ratios=2.075; 95% confidence interval, 1.081–3.984; P=0.028] were higher in the group with eosinophil count less than 2%. Conclusion: In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events. Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment.


title: Airborne rhinovirus detection and effect of ultraviolet irradiation on detection by a semi-nested RT-PCR assay

text: BACKGROUND: Rhinovirus, the most common cause of upper respiratory tract infections, has been implicated in asthma exacerbations and possibly asthma deaths. Although the method of transmission of rhinoviruses is disputed, several studies have demonstrated that aerosol transmission is a likely method of transmission among adults. As a first step in studies of possible airborne rhinovirus transmission, we developed methods to detect aerosolized rhinovirus by extending existing technology for detecting infectious agents in nasal specimens. METHODS: We aerosolized rhinovirus in a small aerosol chamber. Experiments were conducted with decreasing concentrations of rhinovirus. To determine the effect of UV irradiation on detection of rhinoviral aerosols, we also conducted experiments in which we exposed aerosols to a UV dose of 684 mJ/m(2). Aerosols were collected on Teflon filters and rhinovirus recovered in Qiagen AVL buffer using the Qiagen QIAamp Viral RNA Kit (Qiagen Corp., Valencia, California) followed by semi-nested RT-PCR and detection by gel electrophoresis. RESULTS: We obtained positive results from filter samples that had collected at least 1.3 TCID(50 )of aerosolized rhinovirus. Ultraviolet irradiation of airborne virus at doses much greater than those used in upper-room UV germicidal irradiation applications did not inhibit subsequent detection with the RT-PCR assay. CONCLUSION: The air sampling and extraction methodology developed in this study should be applicable to the detection of rhinovirus and other airborne viruses in the indoor air of offices and schools. This method, however, cannot distinguish UV inactivated virus from infectious viral particles.


title: COVID-19: Unique public health issues facing Black, Asian and minority ethnic communities

text: Abstract The 2019 coronavirus disease is a serious public health emergency, with serious adverse implications for populations, healthcare systems, and economies globally. Recently, concerns have been raised about possible association between ethnicity, incidence and outcomes of COVID-19 arisen from early government data. In this review, we will explore the possible association using both recent COVID-19 studies and studies of previous pandemics. We call for data on ethnicity to be routinely collected by governments, as part of international collaboration, alongside other patient demographics and further research to robustly determine magnitude of association. Moreover, governments must learn from previous pandemics and recommended strategies to mitigate risks on minority ethnicities due to socioeconomic disadvantages.


title: Oncology Nursing During a Pandemic: Critical Reflections in the Context of COVID-19

text: Abstract Objectives To provide a critical reflection of COVID-19 in the context of oncology nursing and provide recommendations for caring for people affected by cancer during this pandemic. Data sources Electronic databases including CINAHL, MEDLINE, PsychINFO, Scopus, professional websites, and grey literature were searched using Google scholar. Conclusion Nurses are key stakeholders in developing and implementing policies regarding standards of care during COVID-19 pandemic. This pandemic poses several challenges for oncology services. Oncology nurses are providing a pivotal role in the care and management of the novel COVID-19 in the year landmarked as the International Year of the Nurse. Implications for practice It is too early to tell what shape this pandemic will take and its impact on oncology care. However, several important clinical considerations have been discussed to inform oncology nursing care and practice.


title: The Role of Macrophage Polarization in Infectious and Inflammatory Diseases

text: Macrophages, found in circulating blood as well as integrated into several tissues and organs throughout the body, represent an important first line of defense against disease and a necessary component of healthy tissue homeostasis. Additionally, macrophages that arise from the differentiation of monocytes recruited from the blood to inflamed tissues play a central role in regulating local inflammation. Studies of macrophage activation in the last decade or so have revealed that these cells adopt a staggering range of phenotypes that are finely tuned responses to a variety of different stimuli, and that the resulting subsets of activated macrophages play critical roles in both progression and resolution of disease. This review summarizes the current understanding of the contributions of differentially polarized macrophages to various infectious and inflammatory diseases and the ongoing effort to develop novel therapies that target this key aspect of macrophage biology.


What can academia learn from XMRV studies?


title: Caregiver Burden in Multiple Sclerosis: Recent Trends and Future Directions

text: PURPOSE OF REVIEW: In spite of recent advances in treatment, many people with multiple sclerosis (MS) require ongoing care and support. Informal caregivers can experience burden as a result of their role, with possible implications for quality of life (QOL). We review recent research examining MS caregiver experience to (1) understand current risk factors for caregiver burden and (2) identify possible strategies for increasing carer well-being. RECENT FINDINGS: MS caregiver experience is highly variable and can be predicted by a variety of care recipient, caregiver and contextual factors. Burden is not the only characteristic associated with care, with positive consequences also reported. Emerging research suggests a number of ways in which carers can be better supported. SUMMARY: Identifying and meeting the needs of MS caregivers offers the best way of delivering tailored support. Future research should focus on the development of psychosocial supports, while acknowledging the needs of those caring for different MS patient populations.


Letter to Editor Response to Covid-19 Endocrinology & Diabetology


Total parenteral nutritional therapy of a foal with diarrhoea from which parvovirus‐like particles were identified


title: Clinical evidence for repurposing chloroquine and hydroxychloroquine as antiviral agents: a systematic review

text: BACKGROUND: Repurposing hydroxychloroquine (HCQ) and chloroquine (CQ) as antiviral agents is a re-emerging topic with new viral epidemics. OBJECTIVES: To summarize evidence from human clinical studies for using HCQ or CQ as antiviral agents for any viral infection. DATA SOURCES: PubMed, EMBASE, Scopus, Web of Science for published studies without time or language restrictions. Cochrane Clinical Trial Registry and Chinese Clinical Trials Registry for trials registered after 2015. MedRxiv for pre-prints within the last 12 months. STUDY ELIGIBILITY CRITERIA: Interventional and prospective observational studies (with or without a control group) PARTICIPANTS: Adults and children with a confirmed viral infection. INTERVENTION: Use of chloroquine or hydroxychloroquine as antiviral agents in one or more groups of the study. METHODS: Two authors independently screened abstracts and all authors agreed on eligible studies. A meta-analysis was planned if similar studies were available in terms of participants, intervention, comparator and outcomes. RESULTS: Nineteen studies were eligible (HIV: 8, HCV: 2, Dengue: 2, Chikungunya: 1, COVID-19: 6) including two pre-prints. Nine and ten studies assessed CQ and HCQ respectively. Benefits of either drug for viral load suppression in HIV is inconsistent. CQ is ineffective in curing dengue (high certainty evidence) and may have little or no benefit in curing chikungunya (low-certainty evidence). The evidence for COVID-19 infection is rapidly evolving but at this stage we are unsure if CQ or HCQ has any benefit in clearing viraemia (very low certainty evidence). CONCLUSIONS: Using HCQ or CQ for HIV/HCV infections is clinically irrelevant now as other effective antivirals are available for viral load suppression (HIV) and cure (HCV). There is no benefit of CQ in dengue and the same conclusion is likely for chikungunya infection. More evidence is needed to confirm if HCQ or CQ is beneficial in COVID-19 infection.


title: The COVID-19 response must integrate people living with HIV needs in Sub-Saharan Africa: the case of Mali

text: The first COVID-19 cases in Mali were reported almost 1 month after the first case in the African continent. However, the outbreak continues to spread faster there than in other countries which, along with Mali, successfully tackled the 2014 Ebola outbreak in Africa. Given this context, specific actions targeting people living with HIV (PLWH) are needed to reinforce prevention. Community-based involvement is crucial to ensure continuity of care and treatment for PLWH. Furthermore, the health of frontline healthcare workers must take priority in any actions taken. The long-established trustful relationship between NGOs and PLWH in Mali is indispensable to disseminate key messages about COVID-19.


title: The Origin, Dynamic Morphology, and PI4P-Independent Formation of Encephalomyocarditis Virus Replication Organelles

text: Picornaviruses induce dramatic rearrangements of endomembranes in the cells that they infect to produce dedicated platforms for viral replication. These structures, termed replication organelles (ROs), have been well characterized for the Enterovirus genus of the Picornaviridae. However, it is unknown whether the diverse RO morphologies associated with enterovirus infection are conserved among other picornaviruses. Here, we use serial electron tomography at different stages of infection to assess the three-dimensional architecture of ROs induced by encephalomyocarditis virus (EMCV), a member of the Cardiovirus genus of the family of picornaviruses that is distantly related. Ultrastructural analyses revealed connections between early single-membrane EMCV ROs and the endoplasmic reticulum (ER), establishing the ER as a likely donor organelle for their formation. These early single-membrane ROs appear to transform into double-membrane vesicles (DMVs) as infection progresses. Both single- and double-membrane structures were found to support viral RNA synthesis, and progeny viruses accumulated in close proximity, suggesting a spatial association between RNA synthesis and virus assembly. Further, we explored the role of phosphatidylinositol 4-phosphate (PI4P), a critical host factor for both enterovirus and cardiovirus replication that has been recently found to expedite enterovirus RO formation rather than being strictly required. By exploiting an EMCV escape mutant, we found that low-PI4P conditions could also be overcome for the formation of cardiovirus ROs. Collectively, our data show that despite differences in the membrane source, there are striking similarities in the biogenesis, morphology, and transformation of cardiovirus and enterovirus ROs, which may well extend to other picornaviruses.


Covid-19: Japan ends state of emergency but warns of "new normal".


title: BCG as a game-changer to prevent the infection and severity of COVID-19 pandemic

text: Abstract The impact of COVID-19 is changing country wise and depends on universal immunization policies. COVID-19 badly affects countries that did not have universal immunization policies or having them only for the selective population of countries (highly prominent population) like Italy, USA, UK, Netherland, etc. Universal immunization of BCG can provide great protection against the COVID-19 infection because the BCG vaccine gives broad protection against respiratory infections. BCG vaccine induces expressions of the gene that are involved in the antiviral innate immune response against viral infections with long-term maintenance of BCG vaccine-induced cellular immunity. COVID-19 cases are reported very much less in the countries with universal BCG vaccination policies such as India, Afghanistan, Nepal, Bhutan, Bangladesh, Israel, Japan, etc. as compared to without BCG implemented countries such as the USA, Italy, Spain, Canada, UK, etc. BCG vaccine provides protection for 50 to 60 years of immunization, so the elderly population needs to be revaccinated with BCG. Several countries started clinical trials of the BCG vaccine for health care workers and elderly people. BCG can be uses as a prophylactic treatment until the availability of the COVID-19 vaccine.


title: A putative diacidic motif in the SARS-CoV ORF6 protein influences its subcellular localization and suppression of expression of co-transfected expression constructs

text: BACKGROUND: The ORF6 protein is one of the eight accessory proteins of the severe acute respiratory syndrome coronavirus (SARS-CoV). Numerous properties of ORF6 have been documented and this study focuses on two of these, namely, its ability to suppress the expression of co-transfected expression constructs and its subcellular localization to vesicular structures. RESULTS: Using a transient transfection system, ORF6's ability to suppress the expression of co-transfected expression constructs was measured in a quantitative manner. While ORF6 does not have a global effect on protein synthesis, quantitative real-time PCR revealed that it down-regulated the mRNA level of the co-transfected myc-nsp8 gene. Furthermore, alanine substitution of a diacidic cluster motif (aa53-56) in the ORF6 gene caused a reduction in the suppression of expression of co-transfected myc-nsp8 gene. Our previous study revealed that ORF6 localized to vesicular structures in SARS-CoV infected Vero E6 cells. Here, ORF6 was observed to be localized to similar vesicular structures in Vero E6 cells which have been transiently transfected with a mammalian expression plasmid encoding for untagged ORF6. ORF6 showed partial colocalization with cellular proteins CD63 and Lamp1, suggesting that the vesicular structures may be a subpopulation of endosomal/lysosomal vesicles. The alanine substitution of the diacidic cluster motif also altered the subcellular localization of the ORF6 protein, indicating a potential relationship between the subcellular localization of the ORF6 protein and its ability to suppress the expression of co-transfected expression constructs. CONCLUSIONS: By combining quantitative real-time PCR and transient transfection system, a simple and safe method is established to measure ORF6's ability to suppress the expression of co-transfected myc-nsp8. In addition, immunofluorescence analysis revealed that the subcellular localization of ORF6 when expressed on its own is similar to that observed in SARS-CoV infected cells. Through the use of these two assays, a putative diacidic motif in the ORF6 protein was found to influence its subcellular localization and ability to suppress the expression of co-transfected expression constructs.


title: Detection of influenza D virus in bovine respiratory disease samples, UK

text: Influenza D is a newly described virus of cattle, pigs and small ruminants first detected in North America during 2011. Cattle have been shown to be the main viral reservoir and mounting evidence indicates that infection with influenza D may contribute to the development of bovine respiratory disease. The virus has been detected across the United States, Europe and Asia. To date, influenza D has not been reported in the UK. During the winter and spring of 2017/2018, we performed molecular testing of cattle submitted for post‐mortem examination where respiratory disease signs were present. We detected influenza D virus in 8.7% of cases, often as the sole viral agent and always in conjunction with bacterial co‐infection with one or more agents. Viral RNA was present in both the upper and lower respiratory tract and pathological changes in lung tissues were observed alongside signs of concurrent bacterial infections. Sequencing of one UK isolate revealed that it is similar to viruses from the Republic of Ireland and Italy.


title: COVID‐19: Lessons to be learnt from a once‐in‐a‐century global pandemic

text: The year 2020 will mark a once‐in‐a‐century global event: the outbreak and pandemic of COVID‐19. On the 31 December 2019 the World Health Organization (WHO) reported a cluster of pneumonia‐like cases of a novel coronavirus zoonosis in Wuhan City, Hubei Province, China. The outbreak was due to a new or novel coronavirus, which would later be called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2).


title: Studying Evolutionary Adaptation of MERS-CoV

text: Forced viral adaptation is a powerful technique employed to study the ways viruses may overcome various selective pressures that reduce viral replication. Here, we describe methods for in vitro serial passaging of Middle East respiratory syndrome coronavirus (MERS-CoV) to select for mutations which increase replication on semi-permissive cell lines as described in Letko et al., Cell Rep 24, 1730–1737, 2018.


title: Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers

text: Abstract Background and aims COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). Methods We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. Results From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. Conclusion Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider.


title: Natural and nature-inspired stilbenoids as antiviral agents

text: Viruses continue to be a major threat to human health. In the last century, pandemics occurred and resulted in significant mortality and morbidity. Natural products have been largely screened as source of inspiration for new antiviral agents. Within the huge class of plant secondary metabolites, resveratrol-derived stilbenoids present a wide structural diversity and mediate a great number of biological responses relevant for human health. However, whilst the antiviral activity of resveratrol has been extensively studied, little is known about the efficacy of its monomeric and oligomeric derivatives. The purpose of this review is to provide an overview of the achievements in this field, with particular emphasis on the source, chemical structures and the mechanism of action of resveratrol-derived stilbenoids against the most challenging viruses. The collected results highlight the therapeutic versatility of stilbene-containing compounds and provide a prospective insight into their potential development as antiviral agents.


title: Antiviral Protection by IFITM3 In Vivo

text: PURPOSE OF REVIEW: Interferon-induced transmembrane protein 3 (IFITM3) is a cellular restriction factor that blocks fusion between virus and host membranes. Here, we provide an introduction to IFITM3 and the biochemical regulation underlying its antiviral activity. Further, we analyze and summarize the published literature examining phenotypes of IFITM3 knockout mice upon infections with viral pathogens and discuss the controversial association between single nucleotide polymorphisms (SNPs) in the human IFITM3 gene and severe virus infections. RECENT FINDINGS: Recent publications show that IFITM3 knockout mice experience more severe pathologies than wild-type mice in diverse virus infections, including infections with influenza A virus, West Nile virus, Chikungunya virus, Venezuelan equine encephalitis virus, respiratory syncytial virus, and cytomegalovirus. Likewise, numerous studies of humans of Chinese ancestry have associated the IFITM3 SNP rs12252-C with severe influenza virus infections, though examinations of other populations, such as Europeans, in which this SNP is rare, have largely failed to identify an association with severe infections. A second SNP, rs34481144-A, found in the human IFITM3 promoter has also recently been reported to be a risk allele for severe influenza virus infections. SUMMARY: There is significant evidence for a protective role of IFITM3 against virus infections in both mice and humans, though additional work is required to identify the range of pathogens restricted by IFITM3 and the mechanisms by which human SNPs affect IFITM3 levels or functionality.


title: Emerging Infections

text: Infectious diseases, whether caused by bacteria, viruses, or parasites, are complex, dynamic, and constantly evolving. Some emerge or reemerge in human populations as they cross the species barrier from animals to humans, and once they have infected humans they may be asymptomatic or cause disease. If they cause disease, they may maintain their virulence or decrease in virulence with further passage through human populations. While some of these infectious agents transmit easily from human to human causing epidemics or pandemics, others may not be transmissible, but continue to sporadically infect humans as zoonotic infections. Still others, like HIV infection, may eventually become endemic infectious diseases in humans.


title: Nuclear Reprogramming of Somatic Nucleus Hybridized With Embryonic Stem Cells by Electrofusion

text: Cell fusion is a powerful tool for understanding the molecular mechanisms of epigenetic reprogramming. In hybrid cells of somatic cells and pluripotential stem cells, including embryonic stem (ES) and embryonic germ cells, somatic nuclei acquire pluripotential competence. ES and embryonic germ cells retain intrinsic trans activity to induce epigenetic reprogramming. For generating hybrid cells, we have used the technique of electrofusion. Electrofusion is a highly effective, reproducible, and biomedically safe in vitro system. For successful cell fusion, two sequential steps of electric pulse stimulation are required for the alignment (pearl chain formation) of two different types of cells between electrodes in response to alternating current stimulation and for the fusion of cytoplasmic membranes by direct current stimulation. Optimal conditions for electrofusion with a pulse generator are introduced for ES and somatic cell fusion. Topics in the field of stem cell research include the successful production of cloned animals via the epigenetic reprogramming of somatic cells and contribution of spontaneous cell fusion to generating intrinsic plasticity of tissue stem cells. Cell fusion technology may make important contributions to the fields of epigenetic reprogramming and regenerative medicine.


title: Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range

text: BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.


docid: fovqhiaa

title: Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a public health emergency. The widely used reverse transcription PCR (RT-PCR) method has limitations for clinical diagnosis and treatment. METHODS: A total of 323 samples from 76 COVID-19 confirmed patients were analyzed by droplet digital PCR (ddPCR) and RT-PCR based two target genes (ORF1ab and N). Nasal swabs, throat swabs, sputum, blood, and urine were collected. Clinical and imaging data were obtained for clinical staging. RESULTS: In 95 samples tested positive by both methods, the cycle threshold (Ct) of RT-PCR was highly correlated with the copy numbed of ddPCR (ORF1ab gene, R(2) = 0.83; N gene, R(2) = 0.87). 4 (4/161) negative and 41 (41/67) single-gene positive samples tested by RT-PCR were positive according to ddPCR with viral load ranging from 11.1 to 123.2 copies/test. Then the viral load of respiratory samples was compared and the average viral load in sputum (17429 ± 6920 copies/test) was found to be significantly higher than in throat swabs (2552 ± 1965 copies/test, p < 0.001) and nasal swabs (651 ± 501 copies/test, p < 0.001). Furthermore, the viral load in the early and progressive stages were significantly higher than that in the recovery stage (46800 ± 17272 vs 1252 ± 1027, p < 0.001) analyzed by sputum samples. CONCLUSIONS: Quantitative monitoring of viral load in lower respiratory tract samples helps to evaluate disease progression, especially in cases of low viral load.


title: Viren, virusähnliche und auf Viren hinweisende Strukturen beim Karzinom des Nasopharynx

text: Five cases of nasopharyngeal carcinoma with typically elevated EB- virus-antigen-titer were studied by light- and electron microscopic methods. Within the cytoplasm corona viruses in different forms, regular capsid-like particles with a diameter of 60 nm, tubuloreticular aggregates, and pathologic alterations of the membranes of the endoplasmatic reticulum could be found. The nuclei of the tumor cells often showed particles within the nucleoplasm with an average diameter of 100 nm containing a central core; the appearance of the particles is similar to that of herpes viruses as shown in the literature concerning EB-viruses. Atypic mitoses are common as well as free nucleoplasma-like condensates within the ground cytoplasm. Multiple doubling of the membranes of the endoplasmatic reticulum are characteristic for the tumor cell cytoplasm. Myelin figures are often situated within the enlarged tubules of the E. R., within mitochondria and within the nuclei. The results are discussed concerning the possible viral etiology of nasopharyngeal carcinoma. We do not believe that the particles found within the nucleoplasm have a relation to nuclear pores. The arguments are discussed.


title: Design and optimization of peptide nanoparticles

text: BACKGROUND: Various supra-molecular structures form by self-assembly of proteins in a symmetric fashion. Examples of such structures are viruses, some bacterial micro-compartments and eukaryotic vaults. Peptide/protein-based nanoparticles are emerging in synthetic biology for a variety of biomedical applications, mainly as drug targeting and delivery systems or as vaccines. Our self-assembling peptide nanoparticles (SAPNs) are formed by a single peptide chain that consists of two helical coiled-coil segments connected by a short linker region. One helix is forming a pentameric coiled coil while the other is forming a trimeric coiled coil. RESULTS: Here, we were studying in vitro and in silico the effect of the chain length and of point mutations near the linker region between the pentamer and the trimer on the self-assembly of the SAPNs. 60 identical peptide chains co-assemble to form a spherical nanoparticle displaying icosahedral symmetry. We have stepwise reduced the size of the protein chain to a minimal chain length of 36 amino acids. We first used biochemical and biophysical methods on the longer constructs followed by molecular dynamics simulations to study eleven different smaller peptide constructs. We have identified one peptide that shows the most promising mini-nanoparticle model in silico. CONCLUSIONS: An approach of in silico modeling combined with in vitro testing and verification yielded promising peptide designs: at a minimal chain length of only 36 amino acids they were able to self-assemble into proper nanoparticles. This is important since the production cost increases more than linearly with chain length. Also the size of the nanoparticles is significantly smaller than 20 nm, thus reducing the immunogenicity of the particles, which in turn may allow to use the SAPNs as drug delivery systems without the risk of an anaphylactic shock. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12951-015-0119-z) contains supplementary material, which is available to authorized users.


“Acute” monoclonal gammopathy in severe COVID-19


title: Fast Mass-Production of Medical Safety Shields under COVID-19 Quarantine: Optimizing the Use of University Fabrication Facilities and Volunteer Labor

text: COVID-19 pandemic provoked a number of restrictive measures, such as the closure or severe restriction of border transit for international trading traffic, quarantines and self-isolation. This caused a series of interrelated consequences that not only prevent or slow down the spread of disease, but also impact the medical systems’ capability to treat the patients and help their recovery. In particular, steeply growing demand for medical safety goods cannot be satisfied by regular suppliers due to the shortage of raw materials originating from other countries or remotely located national sources, under conditions of quarantined manpower. The current context inevitably brings back memories (and records!) of the situation 80 years ago, when WWII necessitated major effort directed at the rapid build-up of low-cost mass production to satisfy all aspects of war-time need. In the present short report we document a successful case of fast mass-production of light transparent medical safety face shields (thousands per day) realized in Skolkovo Institute of Science and Technology (Skoltech) at Fablab and Machine Shop Shared Facility (Skoltech FabLab). The demand for safety face shields by tens of hospitals in Moscow and other cities rapidly ramped up due to the need to protect medical staff during patient collection and transportation to hospitals, and within both the infected (“red”) and uninfected (“green”) zones. Materials selection for sterilizable transparent materials was conducted based on the analysis of merit indices, namely, minimal weight at given stiffness and minimal cost at given stiffness. Due to the need for permanent wear, design was motivated by low weight and comfortable head fixation, along with high production efficiency. The selection of minimal tooling in University fabrication workshops and the use of distributed volunteer labor are discussed.


Will the COVID‐19 Pandemic Really Change the Governance of Global Value Chains?


title: Corticosteroid Guidance for Pregnancy during COVID-19 Pandemic

text: The novel coronavirus disease 2019 (COVID-19) pandemic is causing a necessary, rapid adjustment within the field of obstetrics. Corticosteroid use is a mainstay of therapy for those women delivering prematurely. Unfortunately, corticosteroid use has been associated with worse outcomes in COVID-19 positive patients. Given this information, it is necessary that obstetricians adjust practice to carefully weigh the fetal benefits with maternal risks. Therefore, our institution has examined the risks and benefits and altered our corticosteroid recommendations. Key Points: Corticosteroid use is an important part of prematurity treatment because it provides benefit to the fetus. Corticosteroid use may be related with increased morbidity and mortality in novel coronavirus disease 2019 (COVID-19). Therefore, during the COVID-19 pandemic, an alteration in current corticosteroid practices is necessary to uniquely weigh the maternal risks and fetal benefits.


How Can I Take Care Of You? The Dermatologist Meets Patients’ Needs During The Covid19 Pandemic


title: Respiratory Virus Detection and Clinical Diagnosis in Children Attending Day Care

text: BACKGROUND: Respiratory viruses often have been studied in children with respiratory tract infection (RTI), but less knowledge exists about viruses in asymptomatic children. We have studied the occurrence of a broad panel of respiratory viruses in apparently healthy children attending day care, taking into account the influence of possible confounding factors, such as age, clinical signs of respiratory tract infection (RTI), location (day-care section) and season. METHODS: We have studied 161 children in two day-care centers, each with separate sections for younger and older children, during four autumn and winter visits over a two-year period. A total of 355 clinical examinations were performed, and 343 nasopharyngeal samples (NPS) were analyzed by semi-quantitative, real-time, polymerase chain reaction (PCR) tests for 19 respiratory pathogens. RESULT: Forty-three percent of all NPS were PCR-positive for ≥ 1 of 13 virus species, with high species variation during visits. Rhinovirus 26% (88/343 NPS), enterovirus 12% (40/343) and parechovirus 9% (30/343) were detected in every visit, and the rates varied in relation to age, day-care section and season. Ten other viruses were detected in ≤ 3% of the NPS. Generally, viruses occurred together in the NPS. In 24% (79/331) of the clinical examinations with available NPS, the children had clear signs of RTI, while in 41% (135/331) they had mild signs, and in 35% (117/331) the children had no signs of RTI. Moreover, viruses were found in 70% (55/79) of children with clear signs of RTI, in 41% (55/135) with mild signs and in 30% (35/117) without any signs of RTI (p < 0.001). CONCLUSIONS: Positive PCR tests for respiratory viruses, particularly picornaviruses, were frequently detected in apparently healthy children attending day care. Virus detection rates were related to age, presence of clinical signs of RTI, location in day care and season.


docid: zcqsffxy

title: Novel coronavirus-like particles targeting cells lining the respiratory tract

text: Virus like particles (VLPs) produced by the expression of viral structural proteins can serve as versatile nanovectors or potential vaccine candidates. In this study we describe for the first time the generation of HCoV-NL63 VLPs using baculovirus system. Major structural proteins of HCoV-NL63 have been expressed in tagged or native form, and their assembly to form VLPs was evaluated. Additionally, a novel procedure for chromatography purification of HCoV-NL63 VLPs was developed. Interestingly, we show that these nanoparticles may deliver cargo and selectively transduce cells expressing the ACE2 protein such as ciliated cells of the respiratory tract. Production of a specific delivery vector is a major challenge for research concerning targeting molecules. The obtained results show that HCoV-NL63 VLPs may be efficiently produced, purified, modified and serve as a delivery platform. This study constitutes an important basis for further development of a promising viral vector displaying narrow tissue tropism.


title: Techno-economic analysis of a transient plant-based platform for monoclonal antibody production

text: Plant-based biomanufacturing of therapeutic proteins is a relatively new platform with a small number of commercial-scale facilities, but offers advantages of linear scalability, reduced upstream complexity, reduced time to market, and potentially lower capital and operating costs. In this study we present a detailed process simulation model for a large-scale new “greenfield” biomanufacturing facility that uses transient agroinfiltration of Nicotiana benthamiana plants grown hydroponically indoors under light-emitting diode lighting for the production of a monoclonal antibody. The model was used to evaluate the total capital investment, annual operating cost, and cost of goods sold as a function of mAb expression level in the plant (g mAb/kg fresh weight of the plant) and production capacity (kg mAb/year). For the Base Case design scenario (300 kg mAb/year, 1 g mAb/kg fresh weight, and 65% recovery in downstream processing), the model predicts a total capital investment of $122 million dollars and cost of goods sold of $121/g including depreciation. Compared with traditional biomanufacturing platforms that use mammalian cells grown in bioreactors, the model predicts significant reductions in capital investment and >50% reduction in cost of goods compared with published values at similar production scales. The simulation model can be modified or adapted by others to assess the profitability of alternative designs, implement different process assumptions, and help guide process development and optimization.


title: Antiviral therapeutic approaches for human rhinovirus infections

text: Human rhinoviruses are the primary etiological agent of the common cold. This infection can be mild and self-limiting in immunocompetent hosts, but can be associated with bronchiolitis in infants, pneumonia in the immunosuppressed and exacerbations of pre-existing pulmonary conditions such as asthma or chronic obstructive pulmonary disease. Many of these conditions can place significant economic costs upon healthcare infrastructure. There is currently no licensed vaccine for rhinovirus, as the large variety of rhinovirus serotypes has posed significant challenges for research. In this review, we discuss current knowledge around antiviral drugs and small molecule inhibitors of rhinovirus infection, as well as antiviral host defense peptides as exciting prospects to approach the development of novel therapeutics which target human rhinovirus.


docid: uhhtvdif

title: Chemo-enzymatic synthesis of site-specific isotopically labeled nucleotides for use in NMR resonance assignment, dynamics and structural characterizations

text: Stable isotope labeling is central to NMR studies of nucleic acids. Development of methods that incorporate labels at specific atomic positions within each nucleotide promises to expand the size range of RNAs that can be studied by NMR. Using recombinantly expressed enzymes and chemically synthesized ribose and nucleobase, we have developed an inexpensive, rapid chemo-enzymatic method to label ATP and GTP site specifically and in high yields of up to 90%. We incorporated these nucleotides into RNAs with sizes ranging from 27 to 59 nucleotides using in vitro transcription: A-Site (27 nt), the iron responsive elements (29 nt), a fluoride riboswitch from Bacillus anthracis (48 nt), and a frame-shifting element from a human corona virus (59 nt). Finally, we showcase the improvement in spectral quality arising from reduced crowding and narrowed linewidths, and accurate analysis of NMR relaxation dispersion (CPMG) and TROSY-based CEST experiments to measure μs-ms time scale motions, and an improved NOESY strategy for resonance assignment. Applications of this selective labeling technology promises to reduce difficulties associated with chemical shift overlap and rapid signal decay that have made it challenging to study the structure and dynamics of large RNAs beyond the 50 nt median size found in the PDB.


docid: vskiyqop

title: How bad will it get?

text: While the coronavirus death rate may be lower than some estimates, case numbers may be far higher, reports Debora MacKenzie


title: The macroPARP genes parp‐9 and parp‐14 are developmentally and differentially regulated in mouse tissues

text: The macroPARPs Parp‐9 and Parp‐14 are macro domain containing poly(ADP‐ribose) polymerases involved in transcriptional regulation in response to immunoregulatory cytokines. Their genes reside in the same locus (16B3), and the Parp‐9 gene lies head‐to‐head and shares its promoter with the gene encoding its partner, Bbap. Here, we provide a detailed analysis of Parp‐9, Parp‐14, and Bbap expression during mouse development and adulthood. Parp‐9 is developmentally regulated, and prominently expressed in the thymus and specific regions of the brain and gut. In adults, highest expression is maintained in the thymus and intestine. Parp‐14 is more weakly expressed, mainly in the thymus during development and in adulthood. In addition, we show that Bbap is essentially coexpressed with Parp‐9 during development and in adult mouse. However, the different levels of their transcripts detected in the developing brain and gut suggest that Bbap and Parp‐9 display both common and independent tissue‐specific regulations. Developmental Dynamics 237:209–215, 2008. © 2007 Wiley‐Liss, Inc.


title: Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study

text: OBJECTIVE: Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. STUDY DESIGN: Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0–18 years, being treated at a children’s oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher’s exact test and Mann-Whitney U test were used for group comparisons. RESULTS: At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9–74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. CONCLUSION: The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts.


Zoonotic Diseases in India


title: FAVORABLE ANAKINRA RESPONSES IN SEVERE COVID-19 PATIENTS WITH SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

text: SUMMARY Dysregulation of inflammation is hypothesized to play a crucial role in the severe complications of COVID-19, with IL-1/IL-6 pathway being central. Here, we report on the treatment of eight severe COVID-19 pneumonia patients-- seven hospitalized in intensive care units (ICUs) in Greece and one non-ICU patient in the Netherlands-- with the interleukin-1 receptor antagonist Anakinra. All patients scored positive for the hemophagocytosis score (HScore) and were diagnosed with secondary hemophagocytic lymphohistocytosis (sHLH) characterized by pancytopenia, hyper-coagulation, acute kidney injury and hepatobiliary dysfunction. At the end-of-treatment, ICU patients had less need for vasopressors, significantly improved respiratory function and lower HScore. Although three patients died, the mortality was lower than historical series of patients with sHLH in sepsis. These data suggest that administration of Anakinra may be beneficial for treating severe COVID-19 patients with sHLH as determined by the HScore and support the need for larger clinical studies to validate this concept.


title: Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics

text: The objective of this Personal View is to compare transmissibility, hospitalisation, and mortality rates for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with those of other epidemic coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and pandemic influenza viruses. The basic reproductive rate (R(0)) for SARS-CoV-2 is estimated to be 2·5 (range 1·8–3·6) compared with 2·0–3·0 for SARS-CoV and the 1918 influenza pandemic, 0·9 for MERS-CoV, and 1·5 for the 2009 influenza pandemic. SARS-CoV-2 causes mild or asymptomatic disease in most cases; however, severe to critical illness occurs in a small proportion of infected individuals, with the highest rate seen in people older than 70 years. The measured case fatality rate varies between countries, probably because of differences in testing strategies. Population-based mortality estimates vary widely across Europe, ranging from zero to high. Numbers from the first affected region in Italy, Lombardy, show an all age mortality rate of 154 per 100 000 population. Differences are most likely due to varying demographic structures, among other factors. However, this new virus has a focal dissemination; therefore, some areas have a higher disease burden and are affected more than others for reasons that are still not understood. Nevertheless, early introduction of strict physical distancing and hygiene measures have proven effective in sharply reducing R(0) and associated mortality and could in part explain the geographical differences.


title: Chapter 38 Animal Models of Human Viral Diseases

text: Abstract As the threat of exposure to emerging and reemerging viruses within a naive population increases, it is vital that the basic mechanisms of pathogenesis and immune response be thoroughly investigated. By using animal models in this endeavor, the response to viruses can be studied in a more natural context to identify novel drug targets, and assess the efficacy and safety of new products. This is especially true in the advent of the Food and Drug Administration's animal rule. Although no one animal model is able to recapitulate all the aspects of human disease, understanding the current limitations allows for a more targeted experimental design. Important facets to be considered before an animal study are the route of challenge, species of animals, biomarkers of disease, and a humane endpoint. This chapter covers the current animal models for medically important human viruses, and demonstrates where the gaps in knowledge exist.


Earthquakes, economic crisis and, now, Covid-19: the cry of yell of Central Italy.


title: COVID-19 detection using deep learning models to exploit Social Mimic Optimization and structured chest X-ray images using fuzzy color and stacking approaches

text: Abstract Coronavirus causes a wide variety of respiratory infections and it is an RNA-type virus that can infect both humans and animal species. It often causes pneumonia in humans. Artificial intelligence models have been helpful for successful analyses in the biomedical field. In this study, Coronavirus was detected using a deep learning model, which is a sub-branch of artificial intelligence. Our dataset consists of three classes namely: coronavirus, pneumonia, and normal X-ray imagery. In this study, the data classes were restructured using the Fuzzy Color technique as a preprocessing step and the images that were structured with the original images were stacked. In the next step, the stacked dataset was trained with deep learning models (MobileNetV2, SqueezeNet) and the feature sets obtained by the models were processed using the Social Mimic optimization method. Thereafter, efficient features were combined and classified using Support Vector Machines (SVM). The overall classification rate obtained with the proposed approach was 99.27%. With the proposed approach in this study, it is evident that the model can efficiently contribute to the detection of COVID-19 disease.


title: An overview of functional nanoparticles as novel emerging antiviral therapeutic agents

text: Abstract Research on highly effective antiviral drugs is essential for preventing the spread of infections and reducing losses. Recently, many functional nanoparticles have been shown to possess remarkable antiviral ability, such as quantum dots, gold and silver nanoparticles, nanoclusters, carbon dots, graphene oxide, silicon materials, polymers and dendrimers. Despite their difference in antiviral mechanism and inhibition efficacy, these functional nanoparticles-based structures have unique features as potential antiviral candidates. In this topical review, we highlight the antiviral efficacy and mechanism of these nanoparticles. Specifically, we introduce various methods for analyzing the viricidal activity of functional nanoparticles and the latest advances in antiviral functional nanoparticles. Furthermore, we systematically describe the advantages and disadvantages of these functional nanoparticles in viricidal applications. Finally, we discuss the challenges and prospects of antiviral nanostructures. This topic review covers 132 papers and will enrich our knowledge about the antiviral efficacy and mechanism of various functional nanoparticles.


title: Chapter 4 Structure, Organization, and Development of the Mucosal Immune System of the Respiratory Tract

text: Abstract The respiratory tract is served by a variety of lymphoid tissues, including the tonsils, adenoids, nasal-associated lymphoid tissue (NALT), and bronchus-associated lymphoid tissue (BALT), as well as the lymph nodes that drain the upper and lower respiratory tract. Each of these tissues uses unique mechanisms to acquire antigens and respond to pathogens in the local environment and supports immune responses that are tailored to protect those locations. This chapter will review the important features of NALT and BALT and define how these tissues contribute to immunity in the upper and lower respiratory tract, respectively.


title: Human Parvovirus 4: A harmless bystander or a pathogen of severe acute respiratory illness

text: Abstract Introduction Severe Acute Respiratory Infection (SARI) is an important cause of morbidity and mortality worldwide, caused by a large number of viral and bacterial agents. PARV4 is a recently identified virus detected in human blood and variety of tissues, but its disease association with SARI could not be established. Objective In the present case control study, we aim to investigate the association of PARV4 with SARI. Methods The Nasal and Throat swab (NS/TS) samples of 241 cases and 146 healthy controls were tested for most common respiratory viruses and PARV4 by real-time PCR. Results PARV4 was detected in 64(26.55%) SARI cases and only one healthy control (0.68%). PARV4 was the most common viral agent detected in SARI cases. A strong association of PARV4 is seen with severe respiratory illness. Conclusion Detection of PARV4 in a significantly higher number of SARI cases, in comparison with controls, suggests association of PARV4 with SARI. PARV4 genotype 2 is the only circulating strain detected in our study.


title: Ischemic stroke associated with novel coronavirus 2019: a report of three cases

text: Introduction: There is limited evidence about the neurological manifestations of COVID-19 in infected patients. In this report, we describe three patients with ischemic stroke associated with COVID-19 infection. Methods: We report 3 cases of adult patients with ischemic stroke and novel coronavirus 2019 infection. Case 1 is an 88-year-old female with acute left hemiplegia and right peripheral facial paresis that she had a fever along with stroke symptoms. Case 2 is an 85-year-old female with left hemiplegia and drowsiness who had a weakness, asthenia, and dry cough 3 days before appearing stroke signs. Case 3 is a 55-year-old male with acute Brocaʼs aphasia and right hemiplegia who experience fever and respiratory problems 3 days after admission. Results: The clinical symptoms of infected patients with COVID-19 have been associated with severe symptoms of ischemic stroke. Two patients were admitted to the ICU. RT-PCR of the oropharyngeal sample was positive in three cases. All patients had the involvement of large cerebral arteries. Conclusion: The mechanism by which COVID-19 causes ischemic stroke is unknown but it is likely by production inflammatory cytokines or direct infection of cerebral arteries. Therefore, regarding the current situation of the COVID-19 pandemic, it is indispensable that the possible diagnosis of COVID-19 vasculopathy is considered in all ischemic strokes of unclear etiology.


title: Dermatologists and SARS‐CoV‐2: The impact of the pandemic on daily practice

text: Since the first case of “pneumonia of unknown aetiology” was diagnosed at the Wuhan Jinyintan Hospital in China on 30 December 2019, what was recognised thereafter as “severe acute respiratory syndrome coronavirus 2” (SARS‐CoV‐2) has spread over the four continents, causing the respiratory manifestations of Coronavirus disease‐19 (COVID‐ 19) and satisfying the epidemiological criteria for a label of “pandemic.” The ongoing SARS‐CoV‐2 pandemic is having a huge impact on dermatological practice including the marked reduction of face‐to‐face consultations in favour of teledermatology, the uncertainties concerning the outcome of COVID‐19 infection in patients with common inflammatory disorders such as psoriasis or atopic dermatitis receiving immunosuppressive/immunomodulating systemic therapies; the direct involvement of dermatologists in COVID‐19 care for patients assistance and new research needs to be addressed. It is not known yet, if skin lesions and derangement of the skin barrier could make it easier for SARS‐CoV‐2 to transmit via indirect contact; it remains to be defined if specific mucosal or skin lesions are associated with SARS‐CoV‐2 infection, although some unpublished observations indicate the occurrence of a transient varicelliform exanthema during the early phase of the infection. SARS‐CoV‐2 is a new pathogen for humans that is highly contagious, can spread quickly, and is capable of causing enormous health, economic and societal impacts in any setting. The consequences may continue long after the pandemic resolves, and new management modalities for dermatology may originate from the COVID‐19 disaster. Learning from experience may help to cope with future major societal changes.


title: Recognition of Natural Products as Potential Inhibitors of COVID-19 Main Protease (Mpro): In-Silico Evidences

text: ABSTRACT: SARS-CoV-2 (2019-nCoV) emerged in the back of December 2019 and proliferated rapidly across the globe. Scientists are attempting to investigate antivirals specific to COVID-19 treatment. The 2019-nCoV and SARS-CoV utilize the same receptor of the host which is COVID-19 of the main protease (Mpro).COVID-19 caused by SARS-CoV-2 is burdensome to overcome by presently acquired antiviral candidates. So the objective and purpose of this work was to investigate the plants with reported potential antiviral activity. With the aid of in silico techniques such as molecular docking and druggability studies, we have proposed several natural active compounds including glycyrrhizin, bicylogermecrene, tryptanthrine, β-sitosterol, indirubin, indican, indigo, hesperetin, crysophanic acid, rhein, berberine and β-caryophyllene which can be encountered as potential herbal candidate exhibiting anti-viral activity against SARS-CoV-2. Promising docking outcomes have been executed which evidenced the worthy of these selected herbal remedies for future drug development to combat coronavirus disease. GRAPHIC ABSTRACT: [Image: see text]


title: Viral detection profile in children with severe acute respiratory infection

text: Abstract Objectives The role of viral co-detection in children with severe acute respiratory infection is not clear. We described the viral detection profile and its association with clinical characteristics in children admitted to the Pediatric Intensive Care Unit (PICU) during the 2009 influenza A(H1N1) pandemic. Method Longitudinal observational retrospective study, with patients aged 0–18 years, admitted to 11 PICUs in Rio de Janeiro, with suspected H1N1 infection, from June to November, 2009. The results of respiratory samples which were sent to the Laboratory of Fiocruz/RJ and clinical data extracted from specific forms were analyzed. Results Of 71 samples, 38% tested positive for H1N1 virus. Of the 63 samples tested for other viruses, 58 were positive: influenza H1N1 (43.1% of positive samples), rhinovirus/enterovirus (41.4%), respiratory syncytial vírus (12.1%), human metapneumovirus (12.1%), adenovirus (6.9%), and bocavirus (3.5%). Viral codetection occured in 22.4% of the cases. H1N1-positive patients were of a higher median age, had higher frequency of fever, cough and tachypnea, and decreased leukometry when compared to H1N1-negative patients. There was no difference in relation to severity outcomes (number of organic dysfunctions, use of mechanical ventilation or amines, hospital/PICU length of stay or death). Comparing the groups with mono-detection and co-dection of any virus, no difference was found regarding the association with any clinical variable. Conclusions Other viruses can be implicated in SARI in children. The role of viral codetection has not yet been completely elucidated.


Perceived stress and anxiety during COVID-19 among psychiatry trainees


title: SARS‐COV‐2 infection presenting as ST‐elevationmyocardial infarction

text: We describe a patient presenting with chest discomfort, anterolateral ST elevation, and developing acute cardiogenic shock secondary to SARS‐COV‐2infection—patient zero presenting to our institution's cardiac catheterization laboratory. The emergent presentation with limited clinical information led to exposure of personnel. The diagnosis was complicated by two negative tests for SARS‐COV‐2, and high‐clinical suspicion from the patient's occupational history led to additional testing in order to confirm the diagnosis.