title: Epidemiological, clinical, and virological characteristics of 465 hospitalized cases of coronavirus disease 2019 (COVID‐19) from Zhejiang province in China

text: BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the associated coronavirus disease (COVID‐19) have spread throughout China. Previous studies predominantly focused on its place of origin, Wuhan, causing over estimation of the disease severity due to selection bias. We analyzed 465 confirmed cases in Zhejiang province to determine the epidemiological, clinical, and virological characteristics of COVID‐19. METHODS: Epidemiological, demographic, clinical, laboratory, and management data from qRT‐PCR confirmed COVID‐19 patients from January 17, 2020, to January 31, 2020, were collected, followed by multivariate logistic regression analysis for independent predictors of severe/critical‐type COVID‐19 and bioinformatic analysis for features of SARS‐CoV‐2 from Zhejiang province. RESULTS: Among 465 COVID‐19 patients, median age was 45 years, while hypertension, diabetes, and chronic liver disease were the most common comorbidities. History of exposure to the epidemic area was present in 170 (36.56%) and 185 (39.78%) patients were clustered in 77 families. Severe/critical‐type of COVID‐19 developed in 49 (10.54%) patients. Fever and cough were the most common symptoms, while diarrhea/vomiting was reported in 58 (12.47%) patients. Multivariate analysis revealed eight risk factors for severe/critical COVID‐19. Glucocorticoids and antibiotics were administered to 60 (12.90%) and 218(46.88%) patients, respectively. Bioinformatics showed four single amino acid mutations and one amino acid position loss in SARS‐CoV‐2 from Zhejiang province, with more similarity to humans than to viruses. CONCLUSIONS: SARS‐CoV‐2 showed virological mutations and more human transmission in Zhejiang province, indicating considerable epidemiological and clinical changes. Caution in glucocorticoid and antibiotics use is advisable.


title: Critical Care Transesophageal Echocardiography in Patients During The COVID-19 Pandemic

text: The COVID-19 pandemic has placed an extraordinary strain on healthcare systems across North America. Defining the optimal approach for managing a critically ill COVID-19 patient is rapidly changing. Goal-directed transesophageal echocardiography (TEE) is frequently used by physicians caring for intubated critically-ill patients as a reliable imaging modality that is well-suited to answer questions at bedside. A multi-disciplinary group of experts in point-of-care echocardiography and TEE representing intensive care, critical care cardiology and emergency medicine from the United States and Canada, convened to review the available evidence, share experiences, and produce a consensus statement aimed to provide clinicians with a framework to maximize the safety of patients and healthcare providers when considering TEE in critically ill patients during the COVID-19 pandemic. While transthoracic echocardiography (TTE) can provide the information needed in most patients, there are specific scenarios in which TEE represents the modality of choice. Among other critical care applications, TEE can allow hemodynamic assessment of patients during prone ventilation, perform serial evaluations of the lungs during recruitment maneuvers, guide cardiac arrest resuscitation, and facilitate veno-venous extra corporeal membrane oxygenation (VV-ECMO) cannulation. To aid other clinicians in performing TEE during the COVID-19 pandemic, we describe a set of principles and practical aspects for performing examinations with a focus on the logistics, personnel, equipment required before, during, and after an examination. In the right clinical scenario, TEE is a tool that can provide the information needed to deliver the best and safest possible care for the critically ill patient.


COVID‐19: The heart of the issue


title: Rethinking interleukin-6 blockade for treatment of COVID-19

text: Interleukin-6 (IL-6) is a pleiotropic cytokine with effects in immune regulation, inflammation, and infection. The use of drugs that inhibit IL-6 biological activity has been proposed as a treatment for patients with Coronavirus Disease 2019 (COVID-19). The rationale for this approach includes commitment to the concept that inflammation is a cause of lung damage in COVID-19 and belief that IL-6 is a pro-inflammatory molecule. Observational data thought to support IL-6 inhibition include elevated circulating IL-6 levels in COVID-19 patients and association between elevated IL-6 and poor clinical outcomes. However, IL-6 has significant anti-inflammatory properties, which calls into question the rationale for employing IL-6 blockade to suppress inflammation-induced tissue injury. Also, studies suggesting a beneficial role for IL-6 in the host response to infection challenge the strategy of using IL-6 blockade to treat COVID-19. In studies of recombinant IL-6 injected into human volunteers, IL-6 levels exceeding those measured in COVID-19 patients have been observed with no pulmonary adverse events or other organ damage. These observations question the role of IL-6 as a contributing factor in COVID-19. Clinical experience with IL-6 receptor antagonists such as tocilizumab demonstrates increase in severe and opportunistic infections, raising concern about using tocilizumab and similar agents to treat COVID-19. Trials of drugs to inhibit IL-6 activity in COVID-19 are ongoing and will shed light on the role of IL-6 in COVID-19 pathogenesis. However, until more information is available, providers should exercise caution in prescribing these therapies given the potential for patient harm.


title: VACCINATIONS | Viral

text: Vaccines are preparations of weakened or killed viruses or viral subunits that trigger specific protective immunity. Vaccination is the single most effective tool for preventing communicable disease, highlighted by the achievements of the smallpox and poliomyelitis eradication programs and the rise in infections for which no effective vaccine is available: human immunodeficiency virus, malaria, worms, and tuberculosis. World Health Organization initiatives target acute respiratory diseases in infancy and early childhood with novel immunization approaches. Effective vaccines are needed urgently for viral respiratory diseases, but progress has been disappointingly slow. Vaccine candidates often show reduced efficacy in infancy, in partially immune adults, the immunocompromised, and the elderly. However, several promising vaccines are in clinical trial, and it is likely that vaccines against respiratory syncytial virus and parainfluenza will be licensed within the next 5–10 years. Mucosally delivered influenza vaccine is now available, and novel adjuvants offer the prospect of better immunogenicity. Ideally, multivalent mucosal vaccines will be developed that provide protection against a spectrum of respiratory infections in specific target age groups.


title: Drug repurposing for breast cancer therapy: Old weapon for new battle

text: Abstract Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process of drug repurposing. Repositioning approach not only fastens the process of drug development but also offers more effective, cheaper, safer drugs with lesser/known side effects. During the last decade, drugs such as alkylating agents, anthracyclins, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors has been repositioned for breast cancer treatment. The repositioned drugs have been successfully used for the treatment of most aggressive triple negative breast cancer. The literature review suggest that serendipity plays a major role in the drug development. This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed.


Ebola virus disease: the ‘Black Swan’ in West Africa


title: Intravenous sufentanil-midazolam versus sevoflurane anaesthesia in medetomidine pre-medicated Himalayan rabbits undergoing ovariohysterectomy

text: Abstract Objective To compare physiological effects of sufentanil-midazolam with sevoflurane for surgical anaesthesia in medetomidine premedicated rabbits. Study design Prospective, randomized controlled experimental study. Animals Eighteen female Himalayan rabbits, weight 2.1 ± 0.1 kg. Methods Premedication with 0.1 mg kg−1 medetomidine and 5 mg kg−1 carprofen subcutaneously, was followed by intravenous anaesthetic induction with sufentanil (2.3 μg mL−1) and midazolam (0.45 mg mL−1). After endotracheal intubation, anaesthesia was maintained with sufentanil-midazolam (n = 9) or sevoflurane (n = 9). Ovariohysterectomy was performed. Intermittent positive pressure ventilation was performed as required. Physiological variables were studied perioperatively. Group means of physiologic data were generated for different anaesthetic periods. Data were compared for changes from sedation, and between groups by anova. Post-operatively, 0.05 mg kg−1 buprenorphine was administered once and 5 mg kg−1 carprofen once daily for 2–3 days. Rabbits were examined and weighed daily until one week after surgery. Results Smooth induction of anaesthesia was achieved within 5 minutes. Sufentanil and midazolam doses were 0.5 μg kg−1 and 0.1 mg kg−1, during induction and 3.9 μg kg−1 hour−1 and 0.8 mg kg−1 hour−1 during surgery, respectively. End-tidal sevoflurane concentration was 2.1% during surgery. Assisted ventilation was required in nine rabbits receiving sufentanil-midazolam and four receiving sevoflurane. There were no differences between groups in physiologic data other than arterial carbon dioxide. In rabbits receiving sevoflurane, mean arterial pressure decreased pre-surgical intervention, heart rate increased 25% during and after surgery and body weight decreased 4% post-operatively. Post-operative problems sometimes resulted from catheterization of the ear artery. Conclusion Sevoflurane and sufentanil-midazolam provided surgical anaesthesia of similar quality. Arterial blood pressure was sustained during sufentanil-midazolam anaesthesia and rabbits receiving sevoflurane lost body weight following ovariohysterectomy. Mechanical ventilation was required with both anaesthetic regimens. Clinical relevance Anaesthesia with sufentanil-midazolam in medetomidine premedicated healthy rabbits is useful in the clinical and the research setting, as an alternative to sevoflurane.


title: Anti-inflammatory and Antimicrobial Effects of Heat-clearing Chinese Herbs: A Current Review

text: ABSTRACT Inflammation is a normal immune response; but if the body’s regulation of inflammation is dysfunctional, then it will have an adverse effect on the body. Although use of modern drugs for inflammation has a relieving effect, it is still unsatisfactory. Moreover, the emergence of drug-resistant strains and even new kinds of microorganisms is causing significant morbidity and mortality. Recently, more attention has been focused on herbal medicine to treat various diseases because of the ability of the herbs to affect multiple target signaling pathways and their multiple mechanisms of action. Thus, a large number of studies have reported on the anti-inflammatory and antimicrobial effects of the traditional Chinese herbs. Literature survey was performed by conducting systematic electronic search in PubMed, Science Direct, Google Scholar, and in books. This review has listed 11 heat-clearing Chinese herbs (HCCHs) including Scutellaria baicalensis (黃芩 Huáng Qín), Coptis chinensis (黃連 Huáng Lián), Flos Lonicerae (金銀花 Jīn Yín Hūa), Forsythia suspensa (連翹 Lián Qiào), Isatidis Folium (大青葉 Dà Qīn Yè), Radix Isatidis (板藍根 Bǎn Lán Gēn), Viola yedoensis (紫花地丁 Zǐ Huā Dì Dīn), Pulsatilla Radix (白頭翁 Bái Tóu Wēn), Andrographis paniculata (穿心蓮 Chuān Xīn Lián), Houttuynia cordata (魚腥草 Yú Xīng Cǎo), and Patrinia Herba (敗醬草 Bài Jiàn Cǎo), which have anti-inflammatory and antimicrobial effects, and has described their effects through different mechanisms of action and multiple targets. Their ability to affect multiple target signaling pathways and their potential mechanisms of action contributing to their anti-inflammatory and antimicrobial activity may be related to their action of removing heat and counteracting toxicity. Further studies are needed on the collection of HCCHs to know the detailed mechanism of action of herbs in this group for the assessment of effective drug.


title: Buffalo: Asia ☆

text: Abstract Domestic buffaloes (Bubalus bubalis) of swamp type (for draught) and river type (for milk) dominate the tropical Asia with slightly more than 169.4 million. They breed throughout the year and produce two calves every 3 years and are fed mainly on straw, crop residues, and mineral supplements. Assisted reproductive technologies such as artificial insemination and embryo transfer have also been introduced and implemented in buffalo production with less success due to difficulty in detecting estrus. Providing good feed and feeding remain a challenge in buffalo husbandry due to limited feed resources. With improved management and proper breeding, the milk production from buffaloes has increased from 1500 to 5000l per lactation. The river type buffalo currently produces about 73.2 million tonnes of milk annually.


title: Respiratory syncytial virus subtype ON1/NA1/BA9 predominates in hospitalized children with lower respiratory tract infections

text: Respiratory syncytial virus (RSV) infection is the leading cause of acute respiratory tract disease in children less than 5 years old. The aim of this study was to further elucidate the molecular properties and clinical characteristics of RSV infection. The study sample included 238 patients <5 years old who were hospitalized with clinical symptoms of upper or lower respiratory tract infection (URTI or LRTI) in the Pediatric Department at the First People's Hospital of Chenzhou, South China in 2014. We subjected nasopharyngeal aspirate (NPA) or nasal swab (NS) samples from the patients to indirect fluorescence assay screens. RSV G genes were amplified by reverse transcription‐PCR (RT‐PCR) and sequenced. Of the 238 patients screened, 64 (26.8%) were confirmed to have RSV infections. Of those 64 confirmed RSV infection cases, 39 (60.9%) had subtype BA9, 13 (20.3%) had the recently identified subtype ON1, 11 (17.2%) had subtype NA1, and 1 (1.6%) had subtype GB2. The predominant presentation was LRTI with coughing, sputum production, fever, and wheezing. RSV subtype NA1 and BA9 infections were found mostly in infants, whereas the age distribution of subtype ON1 infections was more uniform across the age bands. Phylogenetic analysis indicated that, compared with the prototype strain A2, all ON1 and most NA1 isolates had lost one potential N‐glycosylation site at amino acid 251 and 249 due to T251K and N249Y substitution, respectively. These findings suggest that NA1, BA9, and ON1 are the dominant RSV subtypes causing respiratory tract infections in young children presenting to the hospital in South China. J. Med. Virol. 89:213–221, 2017. © 2016 Wiley Periodicals, Inc.


title: Innate immunogenetics: a tool for exploring new frontiers of host defence

text: Summary The discovery of innate immune genes, such as those encoding Toll-like receptors (TLRs), nucleotide-binding oligomerisation domain-like receptors (NLRs), and related signal-transducing molecules, has led to a substantial improvement of our understanding of innate immunity. Recent immunogenetic studies have associated polymorphisms of the genes encoding TLRs, NLRs, and key signal-transducing molecules, such as interleukin-1 receptor-associated kinase 4 (IRAK4), with increased susceptibility to, or outcome of, infectious diseases. With the availability of high-throughput genotyping techniques, it is becoming increasingly evident that analyses of genetic polymorphisms of innate immune genes will further improve our knowledge of the host antimicrobial defence response and help in identifying individuals who are at increased risk of life-threatening infections. This is likely to open new perspectives for the development of diagnostic, predictive, and preventive management strategies to combat infectious diseases.


title: A systematic review on silver nanoparticles-induced cytotoxicity: Physicochemical properties and perspectives

text: With the development of nanotechnology, silver nanoparticles (Ag-NPs) have become one of the most in-demand nanoparticles owing to their exponential number of uses in various sectors. The increased use of Ag-NPs-enhanced products may result in an increased level of toxicity affecting both the environment and living organisms. Several studies have used different model cell lines to exhibit the cytotoxicity of Ag-NPs, and their underlying molecular mechanisms. This review aimed to elucidate different properties of Ag-NPs that are responsible for the induction of cellular toxicity along with the critical mechanism of action and subsequent defense mechanisms observed in vitro. Our results show that the properties of Ag-NPs largely vary based on the diversified synthesis processes. The physiochemical properties of Ag-NPs (e.g., size, shape, concentration, agglomeration, or aggregation interaction with a biological system) can cause impairment of mitochondrial function prior to their penetration and accumulation in the mitochondrial membrane. Thus, Ag-NPs exhibit properties that play a central role in their use as biocides along with their applicability in environmental cleaning. We herein report a current review of the synthesis, applicability, and toxicity of Ag-NPs in relation to their detailed characteristics.


title: The N-95 mask: invaluable ally in the battle against the COVID-19 pandemic

text: The present COVID-19 pandemic, caused by the airborne SARS-CoV-2 virus, has highlighted the vital importance of appropriate personal protective equipment for all exposed health care workers The single most important part of this armor is the N-95 mask With the awareness that the virus is spread by both droplets and through the aerosolized route, the N-95 provides protection that a surgical mask cannot match This timely review looks at the special advantages that an N-95 offers over a surgical mask with specific reference to the COVID-19 epidemic It also emphasizes the crucial importance of ensuring quality masks with a proper fit Finally, with acute scarcities of N-95 masks being reported from hospitals globally, it reviews recent literature which attempts to prolong the life of these masks with extended use, reuse and decontamination of used masks


title: Functional Properties of the Predicted Helicase of Porcine Reproductive and Respiratory Syndrome Virus

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is a member of the positive-strand RNA virus family Arteriviridae. Although considerable research has focused on this important pathogen, little is known about the function of most PRRSV proteins. To examine characteristics of putative nonstructural proteins (nsp) encoded in ORF1b, which have been identified by nucleotide similarity to domains of equine arteritis virus, defined genomic regions were cloned and expressed in the pRSET expression system. One region, nsp10, encoded a protein with a putative helicase domain and was further examined for functional helicase-like activities. PRRSV nsp10 was found to possess a thermolabile and pH-sensitive NTPase activity that was modulated by polynucleotides and to unwind dsRNA in a 5′ to 3′ polarity. These results provide the first evidence of the functional properties of PRRSV helicase and further support the finding that nidovirus helicases possess properties that distinguish them from other viral helicases.


title: Mechanisms of Antiviral Activity of Iminosugars Against Dengue Virus

text: The antiviral mechanism of action of iminosugars against many enveloped viruses, including dengue virus (DENV), HIV, influenza and hepatitis C virus, is believed to be mediated by inducing misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum-resident α-glucosidase enzymes. This leads to reduced secretion and/or infectivity of virions and hence lower viral titres, both in vitro and in vivo. Free oligosaccharide analysis from iminosugar-treated cells shows that antiviral activity correlates with production of mono- and tri-glucosylated sugars, indicative of inhibition of ER α-glucosidases. We demonstrate that glucose-mimicking iminosugars inhibit isolated glycoprotein and glycolipid processing enzymes and that this inhibition also occurs in primary cells treated with these drugs. Galactose-mimicking iminosugars that have been tested do not inhibit glycoprotein processing but do inhibit glycolipid processing, and are not antiviral against DENV. By comparison, the antiviral activity of glucose-mimetic iminosugars that inhibit endoplasmic reticulum-resident α-glucosidases, but not glycolipid processing, demonstrates that inhibition of α-glucosidases is responsible for iminosugar antiviral activity against DENV. This monograph will review the investigations of many researchers into the mechanisms of action of iminosugars and the contribution of our current understanding of these mechanisms for optimising clinical delivery of iminosugars. The effects of iminosugars on enzymes other than glucosidases, the induction of ER stress and viral receptors will be also put into context. Data suggest that inhibition of α-glucosidases results in inhibited release of virus and is the primary antiviral mechanism of action of iminosugars against DENV.


title: Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirus

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS. Analysis of SARS-CoV spike glycoprotein (S) using recombinant plasmid and virus infections demonstrated that the S-precursor (proS) exists as a ∼190 kDa endoplasmic reticulum form and a ∼210 kDa Golgi-modified form. ProS is subsequently processed into two C-terminal proteins of ∼110 and ∼80 kDa. The membrane-bound proprotein convertases (PCs) furin, PC7 or PC5B enhanced the production of the ∼80 kDa protein. In agreement, proS processing, cytopathic effects, and viral titers were enhanced in recombinant Vero E6 cells overexpressing furin, PC7 or PC5B. The convertase inhibitor dec-RVKR-cmk significantly reduced proS cleavage and viral titers of SARS-CoV infected cells. In addition, inhibition of processing by dec-RVKR-cmk completely abrogated the virus-induced cellular cytopathicity. A fluorogenically quenched synthetic peptide encompassing Arg(761) of the spike glycoprotein was efficiently cleaved by furin and the cleavage was inhibited by EDTA and dec-RVKR-cmk. Taken together, our data indicate that furin or PC-mediated processing plays a critical role in SARS-CoV spread and cytopathicity, and inhibitors of the PCs represent potential therapeutic anti-SARS-CoV agents.


title: IgA-Ab response to spike glycoprotein of SARS-CoV-2 in patients with COVID-19: A longitudinal study

text: Abstract Validation studies of serological antibody tests must be properly designed for clinical, epidemiological and Public Health objectives such as confirmation of suspected COVID-19 cases, certification of seroconversion after infection, and epidemiological surveillance. We evaluated the kinetics of IgM, IgA and IgG SARS-CoV-2 antibodies in COVID-19 patients with confirmed (rRT-PCR) infection. We found that the IgA response appears and grows early, peaks at week 3, and it is stronger and more persistent than the IgM response. Further longitudinal investigations of virus-specific antibodies functions and of their protective efficacy over time are needed.


title: Immune responses and pathogenesis in persistently PCR‐positive patients with SARS‐CoV‐2 infection

text: Coronavirus disease (COVID‐19) caused by SARS‐CoV‐2 emerged in China in December 2019 and then rapidly spread worldwide. Why COVID‐19 patients with the same clinical condition have different outcomes remains unclear. This study aimed to examine the differences in the phenotype and functions of major populations of immune cells between COVID‐19 patients with same severity but different outcomes. Four common type adult inpatients with laboratory confirmed COVID‐19 from Beijing YouAn Hospital, Capital Medical University were included in this study. The patients were divided into two groups based on whether or not COVID‐19 PCR‐negative conversion occurred within three weeks. Peripheral blood samples were collected to compare the differences in the phenotype and functions of major populations of immune cells between the two groups of patients. The result shows that the proportions of CD3(+)CD8(+)CD38(+)HLA‐DR(+)CD27(‐) effector T killer cells generally declined, whereas that of CD3(+)CD4(+)CD8(+) double‐positive T cells (DPTs) increased in the persistently PCR‐positive patients. In summary, considering the imbalance between effector T killer cells/ CD3+CD4+CD8+ DPTs was a possible key factor for PCR‐negative conversion in COVID‐19 patients. This article is protected by copyright. All rights reserved.


title: Detecting Viral Outbreaks in Future Using Enhanced Environmental Surveillance

text: • Severe Acute Respiratory Syndrome Coronavirus 2 can be detected in the sewage system. • Sewage surveillance can estimate disease burden and recurrent epidemic dynamics. • Enhanced surveillance on sewage system can identify early warning calls.


title: Previous Hepatitis A Virus Infection Is Related to Slower Psychomotor Speed in Elderly Adults

text: BACKGROUND: Patients with chronic viral hepatitis are at a higher risk for cognitive dysfunction. Little is known about the association between hepatitis A virus (HAV) infection and cognitive function. METHODS: From the National Health and Nutrition Examination Survey, 1999–2002, we selected study participants (≥60 years, n = 1,529) without hepatitis B, C, or D virus infection; without previous hepatitis A vaccination; and without abnormal liver function. HAV-seropositive participants represented people with previous HAV infection. Psychomotor speed and executive functioning domain of cognitive function were measured by the Digit Symbol Substitution Test (DSST). RESULTS: HAV-seropositive participants had lower DSST scores than HAV-seronegative participants (weighted mean, 44.4 vs 53.9, p < .001). We designated HAV-seronegative participants as the reference group. Univariate analysis demonstrated that the weighted β coefficient of DSST score was −9.55 (95% confidence interval [CI] −9.57 to −9.54, p < .001) for the HAV-seropositive participants. In a multivariable model, the weighted adjusted β coefficient of DSST score was −2.48 (95% CI −2.49 to −2.46, p < .001) for the HAV-seropositive participants. CONCLUSION: HAV seropositivity is associated with slower psychomotor speed among the U.S. community-dwelling elders.


‘Led by the science’, evidence gaps, and the risks of aerosol transmission of SARS-COV-2


title: Design and validation of consensus-degenerate hybrid oligonucleotide primers for broad and sensitive detection of corona- and toroviruses

text: Abstract The ssRNA+ family Coronaviridae includes two subfamilies prototyped by coronaviruses and toroviruses that cause respiratory and enteric infections. To facilitate the identification of new distantly related members of the family Coronaviridae, we have developed a molecular assay with broad specificity. The consensus-degenerated hybrid oligonucleotide primer (CODEHOP) strategy was modified to design primers targeting the most conserved motifs in the RNA-dependent RNA polymerase locus. They were evaluated initially on RNA templates from virus-infected cells using a two-step RT-PCR protocol that was further advanced to a one-step assay. The sensitivity of the assay ranged from 102 to 106 and from 105 to 109 RNA copy numbers for individual corona-/torovirus templates when tested, respectively, with and without an excess of RNA from human cells. This primer set compared to that designed according to the original CODEHOP rules showed 10–103 folds greater sensitivity for 5 of the 6 evaluated corona-/torovirus templates. It detected 57% (32 of 56) of the respiratory specimens positive for 4 human coronaviruses, as well as stool specimens positive for a bovine torovirus. The high sensitivity and broad virus range of this assay makes it suitable for screening biological specimens in search for new viruses of the family Coronaviridae.


title: ANTIBODY FUSIONS REDUCE ONSET OF EXPERIMENTAL CRYPTOSPORIDIUM PARVUM INFECTION IN CALVES

text: Cryptosporidium parvum is one of the main causes of diarrhea in neonatal calves resulting in significant morbidity and economic losses for producers worldwide. We have previously demonstrated efficacy of a new class of antimicrobial antibody fusions in a neonatal mouse model for C. parvum infection. Here, we extend efficacy testing of these products to experimental infection in calves, the principal target species. Neonatal calves were challenged with C. parvum oocysts and concomitantly treated with antibody-biocide fusion 4H9-G1-LL37 over the course of four days. This resulted in reduced severity of the disease when compared to control animals. Overall clinical health parameters showed significant improvement in treated animals. Oocyst shedding was reduced in treated when compared to control animals. Control of oocyst shedding is a prerequisite for breaking the cycle of re-infection on dairy farms. Antibody-biocide fusion products thus have the potential to reduce the impact of the infection in both individual animals and in the herd.


title: Chilblains‐like lesions and COVID‐19

text: The publication entitled “Chilblains‐like lesions in children following suspected Covid‐19 infection” is very interesting [1]. Colonna et al. reported four children with suspected COVID‐19 cases with “[h]istology from one case showed signs of vasculitis with evident fibrin thrombus [1].” While various skin findings have been reported with COVID‐19 infection, the chilblains lesions have been reported from Italy and Spain, and sporadically from China, the starting point of disease pandemic [2‐5].


title: Standardized Testing Demonstrates Altered Odor Detection Sensitivity and Hedonics in Asymptomatic College Students as SARS-CoV-2 Emerged Locally

text: BACKGROUND: Anosmia is a recognized symptom of COVID-19, but the relationship of SARS-CoV-2 exposure with olfactory dysfunction remains enigmatic. This report adds unique data from healthy students tested as the virus emerged locally. METHODS: Standard psychometric measures assessed odor detection, identification and hedonics in healthy university students. Data from asymptomatic students (N=22), tested as SARS-CoV-2 unknowingly emerged locally, were compared to students tested just prior to local virus transmission (N=25), and our normative sample (N=272) tested over the previous 4 years. RESULTS: The exposed cohort demonstrated significantly reduced odor detection sensitivity compared to the students in the prior group (P=.01; d=0.77; CI 0.17, 1.36), with a distribution skewed towards less detection sensitivity (P=.03). Categorically, the exposed group was significantly more likely to have hyposmia (OR=7.7; CI, 3.1, 19.4), particularly the subset assessed in the final week before campus closure (OR=13.6; CI, 3.4, 35.7). The exposed group also rated odors as less unpleasant (P<.001, CLES=0.77, CI, 0.51, 1.56) which also showed a skewed distribution (P=.005). The groups had similar odor identification performance. CONCLUSION: Psychometric measures of odor detection sensitivity and hedonics may detect early SARS-CoV-2 exposure in asymptomatic and pre-symptomatic persons with normal odor identification. Viral detection by nasal associated lymphoid tissue is known to trigger systemic immune effects, but its activation may also reduce smell sensitivity and shift perception of the environment towards unpleasant, increasing the social isolation that may mitigate viral infection or transmission. Regular testing of odor detection and hedonics may have value for identifying regional viral exposure.


title: Evolutionary implications of Avian Infectious Bronchitis Virus (AIBV) analysis

text: For developing efficient vaccines, it is essential to identify which amino acid changes are most important to the survival of the virus. We investigate the amino acid substitution features in the Avian Infectious Bronchitis Virus (AIBV) antigenic domain of a vaccine serotype (DE072) and a virulent viral strain (GA98) to better understand adaptive evolution of AIBV. In addition, the SARS Coronavirus (SARS-CoV) was also analyzed in the same way. It is interesting to find that extreme comparability exists between AIBV and SARS in amino acid substitution pattern. It suggests that amino acid changes that result in overall shift of residue charge and polarity should be paid special attention to during the development of vaccines.


title: Azole-Resistant COVID-19-Associated Pulmonary Aspergillosis in an Immunocompetent Host: A Case Report

text: COVID-19-associated pulmonary aspergillosis (CAPA) is a recently described disease entity affecting patients with severe pulmonary abnormalities treated in intensive care units. Delays in diagnosis contribute to a delayed start of antifungal therapy. In addition, the emergence of resistance to triazole antifungal agents puts emphasis on early surveillance for azole-resistant Aspergillus species. We present a patient with putative CAPA due to Aspergillus fumigatus with identification of a triazole-resistant isolate during therapy. We underline the challenges faced in the management of these cases, the importance of early diagnosis and need for surveillance given the emergence of triazole resistance.


title: Reflections: a Daughter’s Experience of Parental Cancer and the Beginnings of Un Abrazo Para La Familia™

text: The author describes her impetus and journey in developing Un Abrazo Para La Familia™ [Embracing the Family] (Abrazo), 3 hours of cancer information presented in an educational and modular format and designed for low-income informal caregivers who are co-survivors of cancer. A rehabilitation-informed preventive intervention, Abrazo reflects the importance of family, culture, and socioeconomic background in its approach.


title: Sequencing the whole genome of infected human cells obtained from diseased patients – a proposed strategy for understanding and overcoming AIDS or other deadest virus-infected diseases

text: As the worry and pandemic about deadest virus such as AIDS and bird flu are intensified, eradical treatments for these virus-infected diseases are in high demand. However we currently know little about the virus involvement in human cells, which results poor therapeutic outcome. We propose that these viruses may penetrate into human genome in diseased cells that may finally result resistance to present applicable therapeutic options. Here proposes a strategy – sequence the whole genome (chromosomal as well as other genetic systems) of infected human cells obtained from diseased patients. This might help us to know greatly more about the consequences of virus infection and achieve biotherapy of specifically targeted in future.


title: Respiratory Tract Infections in Children in Primary Healthcare in Poland

text: Respiratory tract infections are the most common diseases in children. The aim of the study was to assess their frequency and antibiotic treatment in Poland. We retrospectively analyzed 91 randomly-selected children aged 0–17 years receiving care from birth in a large primary healthcare establishment in the city of Wroclaw in Poland. Respiratory tract infections were responsible for 25–40 % of all primary healthcare visits. The median of visits due to upper respiratory tract infections was 1.8 per year in all children and 2.0 per year in children 0–3 years old. Antibiotics were overused; the majority (57.4 %) of the respiratory infections were treated with antibiotics: acute tonsillitis in 90.7 %, bronchitis in 67.5 %, otitis media in 65.9 %, pneumonia in 60.9 %, non-specific upper respiratory tract infections in 25.8 %, laryngitis in 22.2 %, and sinusitis in 12.5 %. The higher the number of antibiotic therapies, the higher the total number of visits including visits due to respiratory tract infections. In conclusion, implementation of careful and responsible management of a rational use of antibiotics is urgently needed since a reduction in their use may lead to a decrease in the number of visits due to upper respiratory tract infections and a total number of primary care visits.


title: The early experiences of a single tertiary Italian emergency department treating COVID‐19 in children

text: Italy has been badly affected by COVID‐19, despite strict quarantine measures. Up to 1 June 2020, 2.1% of the positive cases in Italy were aged 0‐18 years, with no paediatric deaths (1). This paper focuses on the clinical features, laboratory and imaging data and outcomes of 24 patients admitted to the Emergency Department (ED) at IRCCS Gaslini Children’s Hospital, Genoa, Italy, from 24 February to 16 April 2020.


title: Phytoestrogenic molecule desmethylicaritin suppressed adipogenesis via Wnt/β-catenin signaling pathway

text: Abstract Epimedium flavonoids inhibit extravascular lipid deposition during prevention of steroid-associated osteonecrosis. Desmethylicaritin is a bioactive metabolite of Epimedium flavonoids in serum. As it is well known that estrogen inhibits aidpogenesis, so we hypothesized that desmethylicaritin as a phytoestrogen might have the potential to inhibit lipid deposition. This study was designed to investigate the effect of desmethylicaritin on adipogenesis and its underlying mechanism in vitro. Adipogenesis was assessed by Oil Red O staining in 3T3-L1 preadipocytes. Bromodeoxyuridine was used to test the clonal expansion. Further, the mRNA level and protein expression of adipgenic and related factors were detected by qRT-PCR and western blot, respectively. The nuclear location of β-catenin was identified using immunofluoresence assay. Our results showed that desmethylicaritin suppressed the adipogenesis in 3T3-L1 cells in a dose-dependent manner. In addition, desmethylicaritin inhibited clonal expansion during adipogenesis. Desmethylicaritin did not affect CCAAT/enhancer binding protein δ and β mRNA expression, but decreased the mRNA expression of CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, adipocyte lipid-binding protein and lipoprotein lipase. Desmethylicaritin up-regulated the mRNA expression of Wnt10b that was however down-regulated after adipogenic induction. Desmethylicaritin increased the protein expression of β-catenin both in the cytoplasm and nuclei and immunofluorescence results confirmed that desmethylicaritin increased nuclear translocation of β-catenin. Above findings implied that desmethylicaritin was able to inhibit adipogenesis and Wnt/β-catenin signaling pathway was regulated by desmethylicaritin in the process of suppression of adipogenesis. Above findings supported desmethylicaritin as a novel phytochemical agent for potential prevention of disorders involving lipid metabolism.


title: Detection of multiple viral sequences in the respiratory tract samples of suspected Middle East respiratory syndrome coronavirus patients in Jakarta, Indonesia 2015–2016

text: Abstract Objectives The identification and analysis of viral etiological agents from suspected Middle East respiratory syndrome coronavirus (MERS-CoV) cases admitted to Prof. Dr. Sulianti Saroso Infectious Disease Hospital (IDH) using molecular assays. Methods Biological samples were collected from 13 hospitalized patients suspected of MERS-CoV infection in Prof. Dr. Sulianti Saroso IDH from July 2015 to December 2016. The majority of patients presented with pneumonia, with symptoms including fever (≥37.5 °C), labored breathing, and cough, and with a history of travel to the Middle East. Viral RNA was isolated and converted to cDNA, which was used as a template for the detection of 12 viral panels using conventional PCR and sequencing. Results Viral etiological agents detected in the patients were enterovirus D68, dengue virus type 3, rhinovirus C, human coronavirus 229E, herpes simplex virus type 1, influenza virus H1N1, influenza virus H3N2, human metapneumovirus, and rhinovirus A60. Conclusions The sequences of nine viral agents under different taxa were detected in suspected MERS-CoV patients, including influenza virus, paramyxovirus, coronavirus, enterovirus, human metapneumovirus, and herpesvirus.


title: The duration of viral shedding of discharged patients with severe COVID-19

text: The 2019 coronavirus disease (COVID-19) has drawn global intensive attention(1-3). Most of studies paid attention to epidemiological, clinical, and radiological features of inpatients with COVID-19(1-3). However, little studies have focused on clinical characteristics of discharged patients with severe COVID-19, especially the duration of viral shedding.


title: Characteristics of the complement system gene expression deficiency in patients with symptomatic pulmonary embolism

text: Abstract Introduction Pulmonary embolism (PE) is a disease with a high mortality and morbidity rate, and the pathogenesis of PE remains still unclear. We aimed to investigate the gene expression differences of the complement system in peripheral blood mononuclear cells (PBMCs) from patients with symptomatic PE and controls. Methods Twenty cases of PE patients and twenty sex and age matched controls were recruited into the study. Human cDNA microarray analysis was used to detect the gene expression difference of the complement system between the two groups. Results 1). Expression of twenty-one genes encoding complement components was detected. In PE patients, expression of the genes encoding C1qα, C1qβ, C4b, C5 and Factor P was significantly greater (P<0.05) than controls, while C6, C7, C9, mannose-binding lectin (MBL) and mannan-binding lectin serine peptidase 1 (MASP1) mRNAs were lower (P<0.05) than controls. 2). Expression of seven genes encoding complement receptors was examined. In PE patients, CR1, integrin αM, integrin αX and C5aR mRNAs were significantly up-regulated (P<0.01) compared with controls. 3). Seven genes encoding complement regulators were examined. The mRNA expression of CD59 and CD55 was significantly up-regulated (P<0.05), whereas Factor I mRNA was significantly down-regulated (P<0.05) in PE patients than controls. Conclusions In PE patients, the mRNA expressions of complement components, receptors and regulators were unbalanced, suggesting dysfunction and/or deficiency of the complement system, which leads to decreased function of MAC-induced cell lysis in PE patients finally.


title: Glycyrrhizin as antiviral agent against Hepatitis C Virus

text: BACKGROUND: Hepatitis C virus is a major cause of chronic liver diseases which can lead to permanent liver damage, hepatocellular carcinoma and death. The presently available treatment with interferon plus ribavirin, has limited benefits due to adverse side effects such as anemia, depression, fatigue, and "flu-like" symptoms. Herbal plants have been used for centuries against different diseases including viral diseases and have become a major source of new compounds to treat bacterial and viral diseases. MATERIAL: The present study was design to study the antiviral effect of Glycyrrhizin (GL) against HCV. For this purpose, HCV infected liver cells were treated with GL at non toxic doses and HCV titer was measured by Quantitative real time RT-PCR. RESULTS AND DISCUSSION: Our results demonstrated that GL inhibit HCV titer in a dose dependent manner and resulted in 50% reduction of HCV at a concentration of 14 ± 2 μg. Comparative studies were made with interferon alpha to investigate synergistic effects, if any, between antiviral compound and interferon alpha 2a. Our data showed that GL exhibited synergistic effect when combined with interferon. Moreover, these results were verified by transiently transfecting the liver cells with HCV 3a core plasmid. The results proved that GL dose dependently inhibit the expression of HCV 3a core gene both at mRNA and protein levels while the GAPDH remained constant. CONCLUSION: Our results suggest that GL inhibit HCV full length viral particles and HCV core gene expression or function in a dose dependent manner and had synergistic effect with interferon. In future, GL along with interferon will be better option to treat HCV infection.


At the Epicentre: Hong Kong and the SARS Outbreak


title: Characteristics and Clinical Course and Outcome of COVID‐19 in Hispanic/Latino Patients in a Community Setting: A Retrospective Cohort Study

text: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus which causes coronavirus disease 2019 (COVID‐19), has caused significant morbidity and mortality worldwide. The Centers for Disease Control and Prevention (CDC) suggest several possible symptoms associated with coronavirus disease 2019 (COVID‐19), including cough, shortness of breath or difficulty breathing, fever, chills, muscle pain, sore throat, new loss of taste or smell, and less commonly nausea/vomiting/diarrhea.(1) This article is protected by copyright. All rights reserved.


Prevention and control of tuberculosis during air travel


title: DECLARACIÓN DE CONSENSO EN MEDICINA CRÍTICA PARA LA ATENCIÓN MULTIDISCIPLINARIA DEL PACIENTE CON SOSPECHA O CONFIRMACIÓN DIAGNÓSTICA DE COVID-19

text: Resumen El comportamiento de la infección por SARS-CoV-2 obligó a la Organización Mundial de la Salud a emitir una convocatoria global de activación de mecanismos de emergencia para atender la crisis de salud pública latente. Las Unidades de Cuidados Intensivos son uno de los principales recursos de los sistemas sanitarios dada la tasa de neumonías complicadas que presentan los pacientes infectados. En respuesta a los distintos lineamientos y diferentes niveles de evidencia de la información disponible, la Asociación Colombiana de Medicina crítica y Cuidados Intensivos (AMCI), convocó un equipo multidisciplinario de expertos en medicina crítica para establecer una declaratoria de consenso de buena práctica clínica para la atención de pacientes con COVID-19. Su objetivo es facilitar y estandarizar la toma de decisiones en los aspectos más relevantes desde la organización administrativa de las áreas de atención hasta el abordaje clínico del paciente, teniendo en cuenta la seguridad del personal sanitario, la infraestructura y recursos con los que cuenta el país para responder a la emergencia. Este documento está sujeto a la evolución del conocimiento y a los resultados de investigaciones en curso. Abstract The behaviour of the SARS-CoV-2 infection has forced World Health Organisation to call for the global activation of emergency and contingency mechanisms to respond to the world-wide public health crisis. Intensive Care Units are one of the main health care resources in this situation due to the number of expected cases of severe pneumonia from infected patients. Different guidelines and different levels of evidence from the available information have motivated Asociación Colombiana de Medicina crítica y Cuidados Intensivos (AMCI) to assemble a multidisciplinary team of experts in critical care medicine to prepare a consensus statement of good clinical practice for the care of patients with COVID-19. Its aim is to simplify and standardise decision-making in the most relevant aspects: from the administrative organisation of the care facilities, to the clinical approach of patients, taking into account the safety of health care professionals, and the infrastructure and resources available in Colombia to respond to the emergency. This document will be adapted to any new knowledge and results of on-going research.


title: Will Teledermatology be the silver lining during and after COVID‐19?

text: The novel coronavirus disease (COVID‐19) has limited traditional consultation and minimized healthcare access. Teledermatology has come to the rescue in this situation by extending consultation for non‐essential conditions to the comfort of patient's homes. This limits the risk of exposure of both doctors and patients to SARS‐Cov‐2. And while there is a reported increase in teleconsultations during the ongoing pandemic, there are some demerits that avert the shift to virtualized healthcare. The authors conducted an online survey to further understand the hesitancy, limitations, merits and the demographic of dermatologists who were conducive to teledermatology and this data was analysed and presented in this article. While teledermatology might never replace physical consultation, it definitely serves an adjunctive role in the post‐COVID‐era, provided adequate regulatory measures are in place. This article is protected by copyright. All rights reserved.


title: ACR Appropriateness Criteria® on Acute Respiratory Illness

text: In a patient with acute respiratory illness (cough, sputum production, chest pain, and/or dyspnea), the need for chest imaging depends on the severity of illness, age of the patient, clinical history, physical and laboratory findings, and other risk factors. Chest radiographs seem warranted when one or more of the following are present: age ≥ 40; dementia; a positive physical examination; hemoptysis; associated abnormalities (leukocytosis, hypoxemia); or other risk factors, including coronary artery disease, congestive heart failure, or drug-induced acute respiratory failure. Chest CT may be warranted in complicated cases of severe pneumonia and in febrile neutropenic patients with normal or nonspecific chest radiographic findings. Literature on the indications and usefulness of radiologic studies for acute respiratory illness in different clinical settings is reviewed.


title: Evolutionary Trajectory for the Emergence of Novel Coronavirus SARS-CoV-2

text: Over the last two decades, the world experienced three outbreaks of coronaviruses with elevated morbidity rates. Currently, the global community is facing emerging virus SARS-CoV-2 belonging to Betacoronavirus, which appears to be more transmissible but less deadly than SARS-CoV. The current study aimed to track the evolutionary ancestors and different evolutionary strategies that were genetically adapted by SARS-CoV-2. Our whole-genome analysis revealed that SARS-CoV-2 was the descendant of Bat SARS/SARS-like CoVs and bats served as a natural reservoir. SARS-CoV-2 used mutations and recombination as crucial strategies in different genomic regions including the envelop, membrane, nucleocapsid, and spike glycoproteins to become a novel infectious agent. We confirmed that mutations in different genomic regions of SARS-CoV-2 have specific influence on virus reproductive adaptability, allowing for genotype adjustment and adaptations in rapidly changing environments. Moreover, for the first time we identified nine putative recombination patterns in SARS-CoV-2, which encompass spike glycoprotein, RdRp, helicase and ORF3a. Six recombination regions were spotted in the S gene and are undoubtedly important for evolutionary survival, meanwhile this permitted the virus to modify superficial antigenicity to find a way from immune reconnaissance in animals and adapt to a human host. With these combined natural selected strategies, SARS-CoV-2 emerged as a novel virus in human society.


title: A strange new world

text: The new coronavirus may be upending our lives, but we aren't helpless against it


title: Transplant-Associated and Blood Transfusion-Associated Tropical and Parasitic Infections

text: Blood transfusion and transplantation may represent efficient mechanisms of spreading infectious agents to naive populations. In the developed countries, as a consequence of globalization, several factors such as international commerce, tourism, and immigration have acted as important features for the emergence or reemergence of infectious diseases previously referred to as tropical. This article reviews the relevant bacterial, protozoan and viral infections that are more frequently associated with blood transfusion and/or solid organ or marrow transplantation and may affect susceptible populations worldwide.


title: Elective surgery in the time of COVID-19

text: Abstract The COVID-19 pandemic has placed a significant strain on the United States health care system, and frontline healthcare workers are rapidly altering their professional responsibilities to help meet hospital needs. In an effort to decrease disease transmission and conserve personal protective equipment (PPE), surgeons have witnessed one of the most dramatic changes in their practices with rapidly decreasing numbers of elective surgeries.


title: The Senior Ferret (Mustela Putorius Furo)

text: Ferrets are an increasingly popular pet in the United States. They are active, gregarious pets that delight their owners with playful antics. One of the issues that ferret owners and veterinarians have had to deal with is their shortened life span. Although literature cites the life span of the ferret as 8 to 10 years, most veterinarians see ferrets as “old” at as early as 3 years of age. Most information on senior ferrets has focused on neoplastic diseases. This article discusses husbandry and nutritional issues of the aging ferret, more commonly seen geriatric diseases, and diagnostic and treatment options.


title: The role of phage display in therapeutic antibody discovery

text: Phage display involves the expression of selected proteins on the surface of filamentous phage through fusion with phage coat protein, with the genetic sequence packaged within, linking phenotype to genotype selection. When combined with antibody libraries, phage display allows for rapid in vitro selection of antigen-specific antibodies and recovery of their corresponding coding sequence. Large non-immune and synthetic human libraries have been constructed as well as smaller immune libraries based on capturing a single individual’s immune repertoire. This completely in vitro process allows for isolation of antibodies against poorly immunogenic targets as well as those that cannot be obtained by animal immunization, thus further expanding the utility of the approach. Phage antibody display represents the first developed methodology for high throughput screening for human therapeutic antibody candidates. Recently, other methods have been developed for generation of fully human therapeutic antibodies, such as single B-cell screening, next-generation genome sequencing and transgenic mice with human germline B-cell genes. While each of these have their particular advantages, phage display has remained a key methodology for human antibody discovery due its in vitro process. Here, we review the continuing role of this technique alongside other developing technologies for therapeutic antibody discovery.


title: Anthropological Perspectives on the Health Transition

text: Abstract The health transition is used to refer to the transitions in morbidity and mortality from infectious to noncommunicable disease, as a consequence of medical interventions and improvements in material conditions of living. Anthropologists and other social scientists have illustrated, however, that epidemiological trends are influenced by cultural, social, and behavioral determinants of health. These factors, with variations in the physical environment, have led to the continued prevalence of infectious disease concurrent with a rise in chronic and degenerative conditions. In this article, I discuss how anthropology has contributed to our understanding of health transitions, using specific diseases, conditions, and contexts to highlight the variable causes, understandings, and responses to such changes.


title: Epidemiological study of bovine norovirus infection by RT-PCR and a VLP-based antibody ELISA

text: Abstract Noroviruses, belonging to the family Caliciviridae, have been identified in human beings and in several animal species including cattle. The distribution of bovine norovirus infections was investigated by both RT-PCR to detect norovirus genomes and a virus-like particles-based ELISA to detect genotype 2 bovine norovirus antibodies. During a 1-year systematic study, a virus prevalence of 7.5% (CI 95%: [3.7; 13.4%]) (10 out of 133 samples) was found in stool samples from diarrhoeic calves screened by RT-PCR. Nucleotide sequencing performed on the polymerase region classified all the norovirus amplicons in the bovine norovirus genotype 2. Rather surprisingly, some rotavirus sequences were also detected. On the basis of the polymerase region, genotype 1 bovine norovirus was not identified. Other enteropathogens were found in all samples. By ELISA, a genotype 2 seroprevalence of 93.2% (CI 95%: [90.4; 95.3%]) was found from calves and adult cattle. Antibody levels against genotype 2 bovine noroviruses rose in the first 6 months of life and were maintained in adults. Together the results of virus prevalence and seroprevalence studies suggest that bovine norovirus infection occurs early in life and that re-infection with serologically related bovine noroviruses strains could occur in adult cattle as reported for rotaviruses. The antibody rise against genotype 2 bovine noroviruses in the adult cattle also suggests a short lived and/or strain specific immunity as already shown in human noroviruses. Genotype 2 bovine noroviruses are endemic in the region investigated.


title: Pathogenicity of glycoprotein C negative mutants of herpes simplex virus type 1 for the mouse central nervous system

text: Abstract A previous study from our laboratory showed that a mutant of herpes simplex virus type 1 (HSV-1), strain KOS-321, carrying a deletion in the structural gene for glycoprotein C (gC) had reduced pathogenicity for the mouse central nervous system when compared to the wild-type virus (Kümel et al., 1985). In this study, eight additional gC negative (gC−) mutants derived from KOS-321 were shown to vary widely in their ability to induce lethal encephalitis in female DBA/2 mice following intracerebral inoculation. This variation in virulence showed no correlation with thymidine kinase activity. One less virulent gC− strain, gC−39, was further studied to determine whether the neurovirulent phenotype could be restored by rescue of the gC gene using standard marker rescue cotransfection procedures. The resulting progeny contained 2% gC+ recombinant virions and was tested for its ability to cause encephalitis. Although this progeny had increased virulence, it was not attributable to the acquisition of the gC gene since passive immunization of mice with a pool of anti-gC monoclonal antibodies had no effect on the development of encephalitis and only gC−viruses were isolated from diseased brain tissues. In agreement with these findings, individual plaque-purified gC positive (gC+) virus recombinants were shown not to have been restored to the wild-type virus level of neurovirulence. It is concluded that gC is not a virulence determinant in this mouse model of HSV-induced encephalitis and that cotransfection procedures can induce additional mutations that affect viral pathogenesis.


title: Data analytics for novel coronavirus disease

text: This paper describes different aspects of novel coronavirus disease (COVID-19), presents visualization of the spread of the infection, and discusses the potential applications of data analytics on this viral infection. Firstly, a literature survey is done on COVID-19 highlighting a number of factors including its origin, its similarity with previous coronaviruses, its transmission capacity, its symptoms, etc. Secondly, data analytics is applied on a dataset of Johns Hopkins University to find out the spread of the viral infection. It is shown here that although the disease started in China in December 2019, the highest number of confirmed cases up to June 04, 2020 is in the USA. Thirdly, the worldwide increase in the number of confirmed cases over time is modelled here using a polynomial regression algorithm with degree 2. Fourthly, classification algorithms are applied on a dataset of 5644 samples provided by Hospital Israelita Albert Einstein of Brazil in order to diagnose COVID-19. It is shown here that multilayer perceptron (MLP), XGBoost and logistic regression can classify COVID-19 patients at an accuracy above 91%. Finally, a discussion is presented on the potential applications of data analytics in several important factors of COVID-19.


title: Role of a sentinel surveillance system in the context of global surveillance of infectious diseases

text: Summary In some nation states, sustained integrated global epidemiological surveillance has been weakened as a result of political unrest, disinterest, and a poorly developed infrastructure due to rapidly increasing global inequality. The emergence of severe acute respiratory syndrome has shown vividly the importance of sensitive worldwide surveillance. The Agency for Cooperation in International Health, a Japanese non-governmental organisation, has developed on a voluntary basis a sentinel surveillance system for selected target infectious diseases, covering South America, Africa, and Asia. The system has uncovered unreported infectious diseases of international importance including cholera, plague, and influenza; current trends of acute flaccid paralysis surveillance in polio eradication; and prevalence of HIV, syphilis, hepatitis B, and hepatitis C in individual areas covered by the sentinels. Despite a limited geographical coverage, the system seems to supplement disease information being obtained by global surveillance. Further development of this sentinel surveillance system would be desirable to contribute to current global surveillance efforts, for which, needless to say, national surveillance and alert system takes principal responsibility.


title: IFITM Proteins Incorporated into HIV-1 Virions Impair Viral Fusion and Spread

text: The interferon-induced transmembrane (IFITM) proteins protect cells from diverse virus infections by inhibiting virus-cell fusion. IFITM proteins also inhibit HIV-1 replication through mechanisms only partially understood. We show that when expressed in uninfected lymphocytes, IFITM proteins exert protective effects during cell-free virus infection, but this restriction can be overcome upon HIV-1 cell-to-cell spread. However, when present in virus-producing lymphocytes, IFITM proteins colocalize with viral Env and Gag proteins and incorporate into nascent HIV-1 virions to limit entry into new target cells. IFITM in viral membranes is associated with impaired virion fusion, offering additional and more potent defense against virus spread. Thus, IFITM proteins act additively in both productively infected cells and uninfected target cells to inhibit HIV-1 spread, potentially conferring these proteins with greater breadth and potency against enveloped viruses.


title: Contribution of the porcine aminopeptidase N (CD13) receptor density to porcine epidemic diarrhea virus infection

text: Abstract Porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), which belong to group 1 coronaviruses, are important viral pathogens in pigs causing lethal diarrhea. As with the other members in the group 1, theses viruses are also known to use the host aminopeptidase N (APN) as the major receptor for cell entry. Remarkably, it was found that they utilize distinct cultured cell lines for in vitro virus propagation, since PEDV could not be replicated in swine testis (ST) cells expressing native porcine APN (pAPN), which are highly susceptible to TGEV. To explain the mechanism causing this discrimination, we postulated that there may be a correlation between the pAPN expression level and PEDV infection. As a first step toward understanding the role of cellular receptor density in PEDV replication, therefore, sub-lines of ST cells stably overexpressing recombinant pAPN were generated. We initially confirmed that the control ST cells do express relatively low levels of endogenous pAPN. In contrast, in the engineered stable cell lines, a high level of recombinant pAPN expression was demonstrated. The introduction of a pAPN gene into nonpermissive ST cells was further found to be fully sufficient to support productive infection, revealing that constitutive overexpression of pAPN can directly rescue PEDV multiplication. We further assessed whether the pAPN enzymatic function is relevant to PEDV infection. The enzymatic active motif-null mutant pAPN still retained the ability to exert its receptor activity and consequently, to cause infectious virus production. Moreover, the only APN inhibitor blocking the protease activity site had no obvious negative effect on viral infection, indicating that the enzymatic role of APN is dispensable for the process of virus replication. Taken together, our results suggest that pAPN receptor density appears to be an important factor in contributing to efficient PEDV infection.


title: Air transport globalization, liberalization and sustainability: post-2001 policy dynamics in the United States and Europe

text: Abstract Against a context of international crisis in the air transport industry, this paper examines the implications of the ways in which strategies developed by key air transport stakeholders, as well as the contemporary dynamics of the globalized, liberalized market place, impact directly on sustainability issues. More specifically, the paper has two objectives. First, it discusses the policy ramifications of the interrelationships between the concepts of globalization, liberalization, and sustainability within the air transport industry. Second, the paper explores the import of these interrelationships as they interconnect with stakeholder strategies in the differing geopolitical contexts of the US and EU. Particular attention is given to airline network and frequency strategies. The paper concludes that while the financial sustainability of the airline industry is the overwhelming concern today, if this is essentially the short-term crisis that the airline industry claims it to be, the longer-term predictions of air transport growth will again bring environmental sustainability issues to the fore.


title: Nanoparticle detection of respiratory infection

text: Respiratory viruses are a constant concern for all demographics. Examples include established viruses such as respiratory syncytial virus (RSV), the leading cause of respiratory infection in infants and young children, and emerging viruses such as severe acute respiratory syndrome (SARS), which reached near pandemic levels in 2003, or H1N1 (swine) influenza. Despite this prevalence, traditional methods of virus detection are typically labor intensive and require several days to successfully confirm infection. Recently, however, nanoparticle‐based detection strategies have been employed in an effort to develop detection assays that are both sensitive and expedient. Each of these platforms capitalizes on the unique properties of nanoparticles for the detection of respiratory viruses. In this article, several nanoparticle‐based scaffolds are discussed.Gold nanoparticles (AuNPs) have been functionalized with virus specific antibodies or oligonucleotides. In each of these constructs, AuNPs act as both an easily conjugated scaffolding system for biological molecules and a powerful fluorescence quencher. AuNPs have also been immobilized and used as electrochemical transducers. They efficiently serve as a conducting interface of electrocatalyic activity making them a powerful tool in this application. Quantum dots (QDs) posses unique fluorescence properties that have also been explored for their application to virus detection when combined with direct antibody conjugation or streptavidin‐biotin binding systems. QDs have an advantage over many traditional fluorophores because their fluorescence properties can be finely tuned and they are resistant to photobleaching. The development of these nanoparticle‐based detection strategies holds the potential to be a powerful method to quickly and easily confirm respiratory virus infection. WIREs Nanomed Nanobiotechnol 2010 2 277–290 1.. Diagnostic Tools > In Vitro Nanoparticle-Based Sensing; 2.. Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease.


Uso de suero salino hipertónico en el tratamiento de la bronquiolitis


title: Battling COVID‐19: critical care and peri‐operative healthcare resource management strategies in a tertiary academic medical centre in Singapore

text: In December 2019, a cluster of atypical pneumonia cases were reported in Wuhan, China, and a novel coronavirus elucidated as the aetiologic agent. Although most initial cases occurred in China, the disease, termed coronavirus disease 2019, has become a pandemic and continues to spread rapidly with human‐to‐human transmission in many countries. This is the third novel coronavirus outbreak in the last two decades and presents an ensuing healthcare resource burden that threatens to overwhelm available healthcare resources. A study of the initial Chinese response has shown that there is a significant positive association between coronavirus disease 2019 mortality and healthcare resource burden. Based on the Chinese experience, some 19% of coronavirus disease 2019 cases develop severe or critical disease. This results in a need for adequate preparation and mobilisation of critical care resources to anticipate and adapt to a surge in coronavirus disease 2019 case‐load in order to mitigate morbidity and mortality. In this article, we discuss some of the peri‐operative and critical care resource planning considerations and management strategies employed in a tertiary academic medical centre in Singapore in response to the coronavirus disease 2019 outbreak.


title: Urbanisation and health in China

text: China has seen the largest human migration in history, and the country's rapid urbanisation has important consequences for public health. A provincial analysis of its urbanisation trends shows shifting and accelerating rural-to-urban migration across the country and accompanying rapid increases in city size and population. The growing disease burden in urban areas attributable to nutrition and lifestyle choices is a major public health challenge, as are troubling disparities in health-care access, vaccination coverage, and accidents and injuries in China's rural-to-urban migrant population. Urban environmental quality, including air and water pollution, contributes to disease both in urban and in rural areas, and traffic-related accidents pose a major public health threat as the country becomes increasingly motorised. To address the health challenges and maximise the benefits that accompany this rapid urbanisation, innovative health policies focused on the needs of migrants and research that could close knowledge gaps on urban population exposures are needed.


title: Und plötzlich geht immer mehr per Video: EBM-Honorar

text: Obwohl die Videosprechstunde zu einem Standard-Werkzeug des Vertragsarztes werden soll, waren die Bedingungen zunächst eher mager. Mittlerweile wurden die Honorare aber aufgebessert — zuletzt noch einmal im Zuge der COVID-19-Pandemie. Was mittlerweile geht, zeigen wir hier.


title: Investigation of a nosocomial outbreak of COVID-19 in a pediatric ward in South Korea: Successful control by early detection and extensive contact tracing with testing

text: We describe an outbreak investigation related to a paucisymptomatic 9-year-old girl with COVID-19 admitted at a pediatric ward in a tertiary hospital (South Korea). The pediatric wards were placed under cohort isolation and an extensive contact-tracing was carried out. Of 1,206 close and casual contacts, a female asymptomatic guardian, who was the mother (secondary case) of an infant that shared the room with the index patient, was found positive. Thirteen days after the diagnosis, her asymptomatic 2-year-old daughter (tertiary case) who contacted her at home was found positive. Early detection of an asymptomatic case based on epidemiologic link followed by extensive contact-tracing and testing for SARS-CoV-2 appears to be important in effectively containing a nosocomial outbreak of COVID-19.


title: Influenza Among Afebrile and Vaccinated Healthcare Workers

text: Background. To prevent transmission of influenza from healthcare workers (HCWs) to patients, many hospitals exclude febrile HCWs from working, but allow afebrile HCWs with respiratory symptoms to have contact with patients. During the 2013–2014 influenza season at our hospital, an influenza-positive HCW with respiratory symptoms but no fever was linked to a case of possible healthcare-associated influenza in a patient. Therefore, we implemented a temporary policy of mandatory influenza testing for HCWs with respiratory symptoms. Methods. From 3 January through 28 February 2014, we tested HCWs with respiratory symptoms for influenza and other respiratory pathogens by polymerase chain reaction of flocked nasopharyngeal swabs. HCWs also reported symptoms and influenza vaccination status, and underwent temperature measurement. We calculated the proportion of influenza-positive HCWs with fever and prior influenza vaccination. Results. Of 449 HCWs, 243 (54%) had a positive test for any respiratory pathogen; 34 (7.6%) HCWs tested positive for influenza. An additional 7 HCWs were diagnosed with influenza by outside physicians. Twenty-one (51.2%) employees with influenza had fever. Among influenza-infected HCWs, 20 had previously received influenza vaccination, 18 had declined the vaccine, and 3 had unknown vaccination status. There was no significant difference in febrile disease among influenza-infected employees who had received the influenza vaccine and those who had not received the vaccine (45% vs 61%; P = .32). Conclusions. Nearly half of HCWs with influenza were afebrile prior to their diagnosis. HCWs with respiratory symptoms but no fever may pose a risk of influenza transmission to patients and coworkers.


title: Guideline-Based Chinese Herbal Medicine Treatment Plus Standard Care for Severe Coronavirus Disease 2019 (G-CHAMPS): Evidence From China

text: Background: In January, national guidelines were developed and recommended for use throughout China to fight coronavirus disease 2019 (COVID-19). Chinese herbal medicine (CHM) was also included as part of the treatment plans at various stages of COVID-19. Methods: We conducted a pilot randomized, controlled trial in patients with severe COVID-19 in Wuhan, China. Eligible adult patients were randomly assigned in a 2:1 ratio to receive either CHM plus standard care or standard care alone for 7 days. The primary outcome was the change in the disease severity category of COVID-19 after treatment. Results: Between Jan 31, 2020, and Feb 19, 2020, 42 out of 100 screened patients were included in the trial: 28 in the CHM plus standard care group and 14 in the standard care alone group. Among 42 participants who were randomized (mean [SD] age 60.43 years [12.69 years]), 21 (21/42, 50%) were aged ≥65 years, 35 (35/42, 83%) were women, and 42 (42/42, 100%) had data available for the primary outcome. For the primary outcome, one patient from each group died during treatment; the odds of a shift toward death was lower in the CHM plus group than in the standard care alone group (common OR 0.59, 95% CI 0.148–2.352, P = 0.454). Three (two from the CHM plus group and one from the standard care alone group) patients progressed from severe to critical illness. After treatment, mild, moderate, and severe COVID-19 disease accounted for 17.86% (5/28) vs. 14.29% (2/28), 71.43% (20/28) vs. 64.29% (9/28), and 0% (0) vs. 7.14% (1/28) of the patients treated with CHM plus standard care vs. standard care alone. Conclusions: For the first time, the G-CHAMPS trial provided valuable information for the national guideline-based CHM treatment of hospitalized patients with severe COVID-19. The effects of CHM in COVID-19 may be clinically important and warrant further consideration and studies. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx. Uniqueidentifier: ChiCTR2000029418.


title: Risk and Management of Patients with Mastocytosis and MCAS in the SARS-CoV-2 (COVID-19) Pandemic: Expert Opinions *

text: Abstract The COVID-19 (SARS-CoV-2) pandemic has massively distorted our health care systems and caused catastrophic consequences in our affected communities. The number of victims continues to increase and patients at risk can only be protected to a degree, since the virulent state may be asymptomatic. Risk factors concerning COVID-19-induced morbidity and mortality include advanced age, an impaired immune system, cardiovascular or pulmonary diseases, obesity, diabetes mellitus, and cancer treated with chemotherapy. Here within, we discuss the risk and impact of COVID-19 in patients with mastocytosis and mast cell activation syndromes. As no published data are yet available, expert opinions are, by necessity, based on case experience and reports from patients. Whereas the overall risk to acquire the SARS-CoV-2 virus may not be elevated in mast cell disease, certain conditions may increase the risk of infected patients to develop severe COVID-19. These factors include certain co-morbidities, mast cell activation-related events affecting the cardiovascular or bronchopulmonary system and chemotherapy or immunosuppressive drugs. Therefore, such treatments should be carefully evaluated on a case-by-case basis during a COVID-19 infection. By contrast, other therapies, such as anti-mediator-type drugs, venom immunotherapy, or vitamin D, should be continued. Overall, patients with mast cell disorders should follow the general and local guidelines in the COVID-19 pandemic and advice from their medical provider.


RNA editing and the mitochondrial cryptogenes of kinetoplastid protozoa


title: Bats and Viruses: Emergence of Novel Lyssaviruses and Association of Bats with Viral Zoonoses in the EU

text: Bats in the EU have been associated with several zoonotic viral pathogens of significance to both human and animal health. Virus discovery continues to expand the existing understating of virus classification, and the increased interest in bats globally as reservoirs or carriers of zoonotic agents has fuelled the continued detection and characterisation of new lyssaviruses and other viral zoonoses. Although the transmission of lyssaviruses from bat species to humans or terrestrial species appears rare, interest in these viruses remains, through their ability to cause the invariably fatal encephalitis—rabies. The association of bats with other viral zoonoses is also of great interest. Much of the EU is free of terrestrial rabies, but several bat species harbor lyssaviruses that remain a risk to human and animal health. Whilst the rabies virus is the main cause of rabies globally, novel related viruses continue to be discovered, predominantly in bat populations, that are of interest purely through their classification within the lyssavirus genus alongside the rabies virus. Although the rabies virus is principally transmitted from the bite of infected dogs, these related lyssaviruses are primarily transmitted to humans and terrestrial carnivores by bats. Even though reports of zoonotic viruses from bats within the EU are rare, to protect human and animal health, it is important characterise novel bat viruses for several reasons, namely: (i) to investigate the mechanisms for the maintenance, potential routes of transmission, and resulting clinical signs, if any, in their natural hosts; (ii) to investigate the ability of existing vaccines, where available, to protect against these viruses; (iii) to evaluate the potential for spill over and onward transmission of viral pathogens in novel terrestrial hosts. This review is an update on the current situation regarding zoonotic virus discovery within bats in the EU, and provides details of potential future mechanisms to control the threat from these deadly pathogens.


title: Health Sector Initiatives for Disaster Risk Management in Ethiopia: A Narrative Review

text: Background: Natural and man-made disasters are prevailing in Ethiopia mainly due to drought, floods, landslides, earthquake, volcanic eruptions, and disease epidemics. Few studies so far have critically reviewed about medical responses to disasters and little information exists pertaining to the initiatives being undertaken by health sector from the perspective of basic disaster management cycle. This article aimed to review emergency health responses to disasters and other related interventions which have been undertaken in the health sector. Methods: Relevant documents were identified by searches in the websites of different sectors in Ethiopian and international non-governmental organizations and United Nations agencies. Using selected keywords, articles were also searched in the data bases of Medline, CINAHL, Scopus, and Google Scholar. In addition, pertinent articles from non-indexed journals were referred to. Results: Disaster management system in Ethiopia focused on response, recovery, and rehabilitation from 1974 to 1988; while the period between 1988 and 1993 marked the transition phase towards a more comprehensive approach. Theoretically, from 1993 onwards, the disaster management system has fully integrated the mitigation, prevention, and preparedness phases into already existing response and recovery approach, particularly for drought. This policy has changed the emergency response practices and the health sector has taken some initiatives in the area of emergency health care. Hence, drought early warning system, therapeutic feeding program in hospitals, health centers and posts in drought prone areas to manage promptly acute malnutrition cases have all been put in place. In addition, public health disease emergencies have been responded to at all levels of health care system. Conclusions: Emergency health responses to drought and its ramifications such as acute malnutrition and epidemics have become more comprehensive in the context of basic disaster management phases; and impacts of drought and epidemics seem to be declining. However, the remaining challenge is to address disasters arising from other hazards such as flooding in terms of mitigation, prevention, preparedness and integrating them in the health care system. Key Words: Disaster, Emergency Health, Health System, Ethiopia


title: Working experiences of nurses during the Middle East respiratory syndrome outbreak

text: AIMS: To explore working experiences of nurses during Middle East respiratory syndrome outbreak. BACKGROUND: Since the first case of Middle East respiratory syndrome was reported on May 20, 2015 in South Korea, 186 people, including health care workers, were infected, and 36 died. DESIGN: A qualitative descriptive study. METHODS: Seven focus groups and 3 individual in‐depth interviews were conducted from August to December 2015. Content analysis was used. RESULTS: The following 4 major themes emerged: “experiencing burnout owing to the heavy workload,” “relying on personal protective equipment for safety,” “being busy with catching up with the new guidelines related to Middle East respiratory syndrome,” and “caring for suspected or infected patients with caution.” Participants experienced burnout because of the high volume of work and expressed safety concerns about being infected. Unclear and frequently changing guidelines were 1 of the common causes of confusion. Participants expressed that they need to be supported while caring for suspected or infected patients. CONCLUSION: This study showed that creating a supportive and safe work environment is essential by ensuring adequate nurse staffing, supplying best‐quality personal protective equipment, and improving communication to provide the quality of care during infection outbreak.


Pulmonary embolism in a young pregnant woman with Covid-19


title: Vulnerability of Aboriginal health systems in Canada to climate change

text: Abstract Climate change has been identified as potentially the biggest health threat of the 21st century. Canada in general has a well developed public health system and low burden of health which will moderate vulnerability. However, there is significant heterogeneity in health outcomes, and health inequality is particularly pronounced among Aboriginal Canadians. Intervention is needed to prevent, prepare for, and manage climate change effects on Aboriginal health but is constrained by a limited understanding of vulnerability and its determinants. Despite limited research on climate change and Aboriginal health, however, there is a well established literature on Aboriginal health outcomes, determinants, and trends in Canada; characteristics that will determine vulnerability to climate change. In this paper we systematically review this literature, using a vulnerability framework to identify the broad level factors constraining adaptive capacity and increasing sensitivity to climate change. Determinants identified include: poverty, technological capacity constraints, socio-political values and inequality, institutional capacity challenges, and information deficit. The magnitude and nature of these determinants will be distributed unevenly within and between Aboriginal populations necessitating place-based and regional level studies to examine how these broad factors will affect vulnerability at lower levels. The study also supports the need for collaboration across all sectors and levels of government, open and meaningful dialogue between policy makers, scientists, health professionals, and Aboriginal communities, and capacity building at a local level, to plan for climate change. Ultimately, however, efforts to reduce the vulnerability of Aboriginal Canadians to climate change and intervene to prevent, reduce, and manage climate-sensitive health outcomes, will fail unless the broader determinants of socio-economic and health inequality are addressed.


Two parts of the equation: “Flattening the curve” and “Raising the line”


title: Critical neutralizing fragment of Zika virus EDIII elicits cross-neutralization and protection against divergent Zika viruses

text: Zika virus (ZIKV) infection remains a serious health threat due to its close association with congenital Zika syndrome (CZS), which includes microcephaly and other severe birth defects. As no vaccines are available for human use, continuous effort is needed to develop effective and safe vaccines to prevent ZIKV infection. In this study, we constructed three recombinant proteins comprising, respectively, residues 296–406 (E296-406), 298–409 (E298-409), and 301–404 (E301-404) of ZIKV envelope (E) protein domain III (EDIII) fused with a C-terminal Fc of human IgG. Our results demonstrated that E298-409 induced the highest titer of neutralizing antibodies against infection with nine ZIKV strains isolated from different hosts, countries, and time periods, and it maintained long-term anti-ZIKV immunogenicity to induce neutralizing antibodies. Pups born to mice immunized with E298-409 were fully protected against lethal challenge with two epidemic human ZIKV strains, 2015/Honduras (R103451) and 2015/Colombia (FLR). Passive transfer of anti-E298-409 mouse sera protected pups born to naive mice, as well as type I interferon receptor-deficient adult A129 mice, from lethal challenge with human ZIKV strains R103451 and FLR, and this protection was positively correlated with neutralizing antibodies. These data suggest that the critical neutralizing fragment (i.e., a fragment that can induce highly potent neutralizing antibodies against divergent ZIKV strains) of ZIKV EDIII is a good candidate for development as an effective and safe ZIKV subunit vaccine to protect pregnant mothers and their fetuses against ZIKV infection. The E298-409-specific antibodies can be used for passive immunization to prevent ZIKV infection in newborns or immunocompromised adults.


title: Human viral pathogens are pervasive in wastewater treatment center aerosols

text: Abstract Wastewater treatment center (WTC) workers may be vulnerable to diseases caused by viruses, such as the common cold, influenza and gastro-intestinal infections. Although there is a substantial body of literature characterizing the microbial community found in wastewater, only a few studies have characterized the viral component of WTC aerosols, despite the fact that most diseases affecting WTC workers are of viral origin and that some of these viruses are transmitted through the air. In this study, we evaluated in four WTCs the presence of 11 viral pathogens of particular concern in this milieu and used a metagenomic approach to characterize the total viral community in the air of one of those WTCs. The presence of viruses in aerosols in different locations of individual WTCs was evaluated and the results obtained with four commonly used air samplers were compared. We detected four of the eleven viruses tested, including human adenovirus (hAdV), rotavirus, hepatitis A virus (HAV) and Herpes Simplex virus type 1 (HSV1). The results of the metagenomic assay uncovered very few viral RNA sequences in WTC aerosols, however sequences from human DNA viruses were in much greater relative abundance.


title: Evaluation of the EpiCore outbreak verification system

text: OBJECTIVE: To describe a crowdsourced disease surveillance project (EpiCore) and evaluate its usefulness in obtaining information regarding potential disease outbreaks. METHODS: Volunteer human, animal and environmental health professionals from around the world were recruited to EpiCore and trained to provide early verification of health threat alerts in their geographical region via a secure, easy-to-use, online platform. Experts in the area of emerging infectious diseases sent requests for information on unverified health threats to these volunteers, who used local knowledge and expertise to respond to requests. Experts reviewed and summarized the responses and rapidly disseminated important information to the global health community through the existing event-based disease surveillance network, ProMED. FINDINGS: From March 2016 to September 2017, 2068 EpiCore volunteers from 142 countries were trained in methods of informal disease surveillance and use of the EpiCore online platform. These volunteers provided 790 individual responses to 759 requests for information addressing unverified health threats in 112 countries; 361 (45%) responses were considered to be useful. Most responses were received within hours of the requests. The responses led to 194 ProMED posts, of which 99 (51%) supported verification of an outbreak, were published on ProMED and sent to over 87 000 subscribers. CONCLUSION: There is widespread willingness among health professionals around the world to voluntarily assist efforts to verify and provide supporting information on unconfirmed health threats in their region. By linking this member network of health experts through a secure online reporting platform, EpiCore enables faster global outbreak detection and reporting.


title: An uncharacterized FMAG_01619 protein from Fusobacterium mortiferum ATCC 9817 demonstrates that some bacterial macrodomains can also act as poly-ADP-ribosylhydrolases

text: Macrodomains constitute a conserved fold widely distributed that is not only able to bind ADP-ribose in its free and protein-linked forms but also can catalyse the hydrolysis of the latter. They are involved in the regulation of important cellular processes, such as signalling, differentiation, proliferation and apoptosis, and in host-virus response, and for this, they are considered as promising therapeutic targets to slow tumour progression and viral pathogenesis. Although extensive work has been carried out with them, including their classification into six distinct phylogenetically clades, little is known on bacterial macrodomains, especially if these latter are able to remove poly(ADP-ribose) polymer (PAR) from PARylated proteins, activity that only has been confirmed in human TARG1 (C6orf130) protein. To extend this limited knowledge, we demonstrate, after a comprehensive bioinformatic and phylogenetic analysis, that Fusobacterium mortiferum ATCC 9817 TARG1 (FmTARG1) is the first bacterial macrodomain shown to have high catalytic efficiency towards O-acyl-ADP-ribose, even more than hTARG1, and towards mono- and poly(ADPribosyl)ated proteins. Surprisingly, FmTARG1 gene is also inserted into a unique operonic context, only shared by the distantly related Fusobacterium perfoetens ATCC 29250 macrodomain, which include an immunity protein 51 domain, typical of bacterial polymorphic toxin systems.


title: Measuring hope during the COVID-19 outbreak in the Philippines: development and validation of the state locus-of-Hope scale short form in Filipino

text: Various adaptations of the Dispositional Hope Scale have been validated and used for specific research and applied purposes. The Locus-of-Hope Scale was developed as a cultural adaptation that measures internal and external aspects of agency related to goal-pursuit that are typical in collectivist cultures. The scale has been used to account for variations in well-being-related factors in collectivist societies but still assumes that hope-related thoughts are dispositional. A State Locus-of-Hope Scale was developed to assess hope-related thinking concerning ongoing events and experience during the COVID-19 outbreak in the Philippines in March 2020. The 16-item scale in Filipino was adapted from a short version of Locus-of-Hope Scale. Using data from 3128 respondents, confirmatory factor analysis indicated a good fit between the four-factor model (compared to one-factor and two-factor models), supporting the scale’s structural validity. There was also good evidence for the subscales’ convergent and discriminant validity. Preliminary evidence for construct criterion validity was demonstrated by examining associations with well-being and anxiety. The results indicate the viability of the State Locus-of-Hope scale for assessing temporal hope-related thoughts that can inform efforts to understand how individuals engage in goal-related processes and maintain well-being in specific personal and social situations.


title: Genomic characterization of seven distinct bat coronaviruses in Kenya

text: Abstract To better understand the genetic diversity and genomic features of 41 coronaviruses (CoVs) identified from Kenya bats in 2006, seven CoVs as representatives of seven different phylogenetic groups identified from partial polymerase gene sequences, were subjected to extensive genomic sequencing. As a result, 15–16kb nucleotide sequences encoding complete RNA dependent RNA polymerase, spike, envelope, membrane, and nucleocapsid proteins plus other open reading frames (ORFs) were generated. Sequences analysis confirmed that the CoVs from Kenya bats are divergent members of Alphacoronavirus and Betacoronavirus genera. Furthermore, the CoVs BtKY22, BtKY41, and BtKY43 in Alphacoronavirus genus and BtKY24 in Betacoronavirus genus are likely representatives of 4 novel CoV species. BtKY27 and BtKY33 are members of the established bat CoV species in Alphacoronavirus genus and BtKY06 is a member of the established bat CoV species in Betacoronavirus genus. The genome organization of these seven CoVs is similar to other known CoVs from the same groups except for differences in the number of putative ORFs following the N gene. The present results confirm a significant diversity of CoVs circulating in Kenya bats. These Kenya bat CoVs are phylogenetically distant from any previously described human and animal CoVs. However, because of the examples of host switching among CoVs after relatively minor sequence changes in S1 domain of spike protein, a further surveillance in animal reservoirs and understanding the interface between host susceptibility is critical for predicting and preventing the potential threat of bat CoVs to public health.


title: Pre-existing immunity against vaccine vectors – friend or foe?

text: Over the last century, the successful attenuation of multiple bacterial and viral pathogens has led to an effective, robust and safe form of vaccination. Recently, these vaccines have been evaluated as delivery vectors for heterologous antigens, as a means of simultaneous vaccination against two pathogens. The general consensus from published studies is that these vaccine vectors have the potential to be both safe and efficacious. However, some of the commonly employed vectors, for example Salmonella and adenovirus, often have pre-existing immune responses in the host and this has the potential to modify the subsequent immune response to a vectored antigen. This review examines the literature on this topic, and concludes that for bacterial vectors there can in fact, in some cases, be an enhancement in immunogenicity, typically humoral, while for viral vectors pre-existing immunity is a hindrance for subsequent induction of cell-mediated responses.


title: Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry

text: Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC(50)) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections.