title: The framing of a sustainable development goals assessment in decarbonizing the construction industry – Avoiding “Greenwashing”

text: Abstract The aim of this paper is to contribute to the establishment of a robust framework for the assessment of Sustainable Development Goals (SDGs) in businesses, using the construction industry as an example and with the primary focus on combating climate change (SDG 13). We provide a critical analysis of a selection of relatively widely used SDG impact assessment tools, combined with a case study from the construction industry to explore how a meaningful SDG assessment can be framed with linkages between SDG 13 and other related SDGs. Our analysis points towards the importance of framing SDG assessments in a way that discourages “Greenwashing”. Any SDG assessment that relates to climate targets in line with the Paris Agreement should identify the processes and activities that can be expected to be particularly challenging in terms of their abatement. In our road construction work case, we identify four such hard-to-abate activities: 1) introducing biomass for renewable transportation fuels for use in construction equipment and heavy transport; 2) electrification of transport and industrial processes; 3) substitution as part of transitioning from fossil fuel use; and 4) applying carbon capture and storage technologies in the production of basic materials, such as cement and steel. The approach applied will avoid that businesses only focus on SDGs in situations where they are already performing well or can apply low-cost measures or that they only relate to the part of the supply chain that pertains to their own business (Scope 1 emissions). For an SDG assessment to provide basis for informed decisions regarding real change towards more sustainable and equitable corporate practices it should: (i) identify and include concrete measures to align with the terms of the Paris Agreement; (ii) include relevant value chains; and (iii) consider both the short-term and long-term effects of strategic choices.


title: In Silico Drug Discovery: Solving the “Target‐rich and Lead‐poor” Imbalance Using the Genome‐to‐drug‐lead Paradigm

text: Advances in genomics, proteomics, and structural genomics have identified a large number of protein targets. Virtual screening has gained popularity in identifying drug leads by computationally screening large numbers of chemicals against experimentally determined protein targets. In that context, there continues to be a “target‐rich and lead‐poor” imbalance, reflecting an insufficiency of chemists pursuing drug discovery in academia, the challenge of engaging more chemists in this area of research, and a paucity of available protein target structures. This imbalance in manpower and structural information can be ameliorated, in part, by adapting a “genome‐to‐drug‐lead” approach, in which chemicals can be virtually screened against computer‐predicted protein targets, within the context of the US National Science Foundation's petascale computing initiative. This approach offers a solution to reduce manpower requirements for more chemists to experimentally search for drug leads, which represent one of the greatest limitations to drug discovery and better exploits the extensive availability of drug targets at the gene level, ultimately improving the success of moving discoveries from the laboratory to the patient. Clinical Pharmacology &d Therapeutics (2007) 81, 30–34. doi:10.1038/sj.clpt.6100030


title: Influenza in Travelers: Epidemiology, Risk, Prevention, and Control Issues

text: Influenza is the most frequent travel related infection preventable by universally available vaccines, but preventive measures were neglected until recently. Since the spread of pandemic (H1N1) 2009, various public health measures have been promoted first to contain, then to mitigate, the pandemic. Some of these measures contradicted recommendations issued by the World Health Organization and were of questionable efficacy. However, travelers may benefit from targeted recommendations on influenza risk reduction (eg, by social distancing or immunization). These recommendations are particularly indicated for those with an increased personal risk profile and for those likely to be exposed to influenza patients.


title: Travel and migration associated infectious diseases morbidity in Europe, 2008

text: BACKGROUND: Europeans represent the majority of international travellers and clinicians encountering returned patients have an essential role in recognizing, and communicating travel-associated public health risks. METHODS: To investigate the morbidity of travel associated infectious diseases in European travellers, we analysed diagnoses with demographic, clinical and travel-related predictors of disease, in 6957 ill returned travellers who presented in 2008 to EuroTravNet centres with a presumed travel associated condition. RESULTS: Gastro-intestinal (GI) diseases accounted for 33% of illnesses, followed by febrile systemic illnesses (20%), dermatological conditions (12%) and respiratory illnesses (8%). There were 3 deaths recorded; a sepsis caused by Escherichia coli pyelonephritis, a dengue shock syndrome and a Plasmodium falciparum malaria. GI conditions included bacterial acute diarrhea (6.9%), as well as giardiasis and amebasis (2.3%). Among febrile systemic illnesses with identified pathogens, malaria (5.4%) accounted for most cases followed by dengue (1.9%) and others including chikungunya, rickettsial diseases, leptospirosis, brucellosis, Epstein Barr virus infections, tick-borne encephalitis (TBE) and viral hepatitis. Dermatological conditions were dominated by bacterial infections, arthropod bites, cutaneous larva migrans and animal bites requiring rabies post-exposure prophylaxis and also leishmaniasis, myasis, tungiasis and one case of leprosy. Respiratory illness included 112 cases of tuberculosis including cases of multi-drug resistant or extensively drug resistant tuberculosis, 104 cases of influenza like illness, and 5 cases of Legionnaires disease. Sexually transmitted infections (STI) accounted for 0.6% of total diagnoses and included HIV infection and syphilis. A total of 165 cases of potentially vaccine preventable diseases were reported. Purpose of travel and destination specific risk factors was identified for several diagnoses such as Chagas disease in immigrant travellers from South America and P. falciparum malaria in immigrants from sub-Saharan Africa. Travel within Europe was also associated with health risks with distinctive profiles for Eastern and Western Europe. CONCLUSIONS: In 2008, a broad spectrum of travel associated diseases were diagnosed at EuroTravNet core sites. Diagnoses varied according to regions visited by ill travellers. The spectrum of travel associated morbidity also shows that there is a need to dispel the misconception that travel, close to home, in Europe, is without significant health risk.


title: COVID‐19 and arterial hypertension: Hypothesis or evidence?

text: Investigations reported that hypertension, diabetes, and cardiovascular diseases were the most prevalent comorbidities among the patients with coronavirus disease 2019 (COVID‐19). Hypertension appeared consistently as the most prevalent risk factors in COVID‐19 patients. Some investigations speculated about the association between renin‐angiotensin‐aldosterone system (RAAS) and susceptibility to COVID‐19, as well as the relationship between RAAS inhibitors and increased mortality in these patients. This raised concern about the potential association between hypertension (and its treatment) and propensity for COVID‐19. There are only a few follow‐up studies that investigated the impact of comorbidities on outcome in these patients with conflicting findings. Hypertension has been proven to be more prevalent in patients with an adverse outcome (admission in intensive care unit, use of mechanical ventilation, or death). So far, there is no study that demonstrated independent predictive value of hypertension on mortality in COVID‐19 patients. There are many speculations about this coronavirus and its relation with different risk factors and underlying diseases. The aim of this review was to summarize the current knowledge about the relationship between hypertension and COVID‐19 and the role of hypertension on outcome in these patients.


title: Evaluation of a PCR-electrospray ionization mass spectrometry platform for detection and identification of fungal pathogens directly from prospectively collected bronchoalveolar lavage specimens

text: Abstract The incidence of invasive fungal infections is on the rise worldwide due to the growth of the immunocompromised population. We report here the use of a diagnostic assay that utilizes a universal extraction method, broad spectrum PCR amplification and analysis via electrospray ionization mass spectrometry (PCR/ESI-MS) to detect and identify more than 200 pathogenic fungi directly from bronchoalveolar lavage (BAL) specimens in less than 8 hours. In this study, we describe both analytical and clinical performance of the assay, when run with prospectively collected clinical BAL specimens. In 146 patients with probable and possible fungal infections defined by EORTC/MSG (European Organization for Research and Treatment of Cancer/Mycoses Study Group) criteria, the PCR/ESI-MS assay demonstrated a sensitivity of 90.9% (95% CI: 76.4–96.9%) and a specificity of 82.3% (95% CI: 74.2–88.2%). This data demonstrates the utility of a non-culture based broad fungal targets molecular diagnostic tool for rapid and accurate diagnosis of invasive fungal infections in patients at risk of developing fungal diseases.


Psychosocial impact of COVID‐19 for general workers


title: ELM: enhanced lowest common ancestor based method for detecting a pathogenic virus from a large sequence dataset

text: BACKGROUND: Emerging viral diseases, most of which are caused by the transmission of viruses from animals to humans, pose a threat to public health. Discovering pathogenic viruses through surveillance is the key to preparedness for this potential threat. Next generation sequencing (NGS) helps us to identify viruses without the design of a specific PCR primer. The major task in NGS data analysis is taxonomic identification for vast numbers of sequences. However, taxonomic identification via a BLAST search against all the known sequences is a computational bottleneck. DESCRIPTION: Here we propose an enhanced lowest-common-ancestor based method (ELM) to effectively identify viruses from massive sequence data. To reduce the computational cost, ELM uses a customized database composed only of viral sequences for the BLAST search. At the same time, ELM adopts a novel criterion to suppress the rise in false positive assignments caused by the small database. As a result, identification by ELM is more than 1,000 times faster than the conventional methods without loss of accuracy. CONCLUSIONS: We anticipate that ELM will contribute to direct diagnosis of viral infections. The web server and the customized viral database are freely available at http://bioinformatics.czc.hokudai.ac.jp/ELM/. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-254) contains supplementary material, which is available to authorized users.


title: Effects of Housing and Colostrum Feeding on Serum Immunoglobulins, Growth, and Fecal Scores of Jersey Calves 1

text: Abstract Ninety-six Jersey calves were used to evaluate the effects of housing and method of colostrum feeding on serum Ig concentrations, incidence and severity of scours, intake, and BW changes from birth to 35 d of age. Calves were separated from the dam and fed 2L of colostrum in nipple-bottles or allowed to nurse the dam for 3 d. Calves were housed in individual hutches or wooden pens in a barn. Intake of colostrum by calves allowed to nurse the dam was not controlled. Serum IgG and IgM concentrations at 24h of age were greater for calves that nursed the dam. Scours were less severe when calves were housed in hutches, but number of days scouring was unaffected by treatment. Calves fed colostrum in nipple-bottles and housed in the barn consumed more starter than did other calves from 3 to 5 wk of age. The BW were greater for calves allowed to nurse the dam and housed in hutches. Feed efficiency over the 35-d study was improved when calves nursed the dam. Optimal transfer of passive immunity and housing in hutches appeared to maximize health and growth in this study.


title: Reverse Genetics System for the Avian Coronavirus Infectious Bronchitis Virus

text: We have developed a reverse genetics system for the avian coronavirus infectious bronchitis virus (IBV) in which a full-length cDNA corresponding to the IBV genome is inserted into the vaccinia virus genome under the control of a T7 promoter sequence. Vaccinia virus as a vector for the full-length IBV cDNA has the advantage that modifications can be introduced into the IBV cDNA using homologous recombination, a method frequently used to insert and delete sequences from the vaccinia virus genome. Here, we describe the use of transient dominant selection as a method for introducing modifications into the IBV cDNA that has been successfully used for the substitution of specific nucleotides, deletion of genomic regions, and exchange of complete genes. Infectious recombinant IBVs are generated in situ following the transfection of vaccinia virus DNA, containing the modified IBV cDNA, into cells infected with a recombinant fowlpox virus expressing T7 DNA-dependant RNA polymerase.


title: Molecular and immunohistochemical detection of assemblage E, Giardia duodenalis in scouring North Dakota calves

text: Abstract Despite many reports on the shedding of Giardia parasites by scouring calves, the role of Giardia as a cause of calf diarrhea is still controversial. To elucidate the role of Giardia duodenalis in calf scours, diagnostic samples from 189 scouring calves were tested by different assays during a 1-year-study period. Giardia antigens were detected in 22/189 scouring calves by a fecal-based enzyme-linked immunosorbent assay and 10 of these were positive for assemblage E, G. duodenalis by polymerase chain reaction. Giardia trophozoites were demonstrated by immunohistochemistry in intestinal sections from five calves in which the parasites were spatially distributed in areas of microscopically detectable enteritis. Our data suggest that under certain circumstances, Giardia may cause intestinal lesions leading to calf scours. Gnotobiotic calf-based infectivity studies are needed if the pathogenicity of Giardia in calves is to be definitively determined.


title: Molecular structure and electron distribution of 4-nitropyridine N-oxide: Experimental and theoretical study of substituent effects

text: The molecular structure of 4-nitropyridine N-oxide, 4-NO(2)-PyO, has been determined by gas-phase electron diffraction monitored by mass spectrometry (GED/MS) and by quantum chemical calculations (DFT and MP2). Comparison of these results with those for non-substituted pyridine N-oxide and 4-methylpyridine N-oxide CH(3)-PyO, demonstrate strong substitution effects on structural parameters and electron density distribution. The presence of the electron-withdrawing –NO(2) group in para-position of 4-NO(2)-PyO results in an increase of the ipso-angle and a decrease of the semipolar bond length r(N→O) in comparison to the non-substituted PyO. The presence of the electron-donating –CH(3) group in 4-CH(3)-PyO leads to opposite structural changes. Electron density distribution in pyridine-N-oxide and its two substituted compounds are discussed in terms of natural bond orbitals (NBO) and quantum theory atoms in molecule (QTAIM).


title: Ethyl 4-(5-bromo-1H-indol-3-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

text: The title compound, C(23)H(25)BrN(2)O(3), crystallizes with two independent molecules in the asymmetric unit (Z′ = 2) which differ in the twist of the 5-bromo-1H-indole ring with respect to the plane of the 4-methyl-1,4,5,6,7,8-hexahydroquinoline ring [dihedral angles of 78.55 (9) and 89.70 (8)° in molecules A and B, respectively]. The indole ring is planar in both molecules [maximum deviations = 0.021 (3) and −0.020 (3) Å for the N atom] while the cyclohexene ring has adopts a sofa conformation. In the crystal, molecules are linked by pairs of N—H⋯O hydrogen bonds, forming dimers with R (1) (2)(6) ring motifs. These dimers are connected by N—H⋯O hydrogen bonds, generating chains along [110]. A C—H⋯O contact occurs between the independent molecules.


title: Surgical resection for liver cancer during the COVID-19 outbreak

text: During the 2019 novel coronavirus disease (COVID-19) outbreak, therapeutic strategies must be adapted for liver cancer patients balancing the benefit of surgical resection against the risk of contamination incurred by the patient. The impact of COVID-19 in liver cancer patients who undergo surgery is still unclear due to the scarcity of available data. Decisions to postpone scheduled surgery for high risk patients must be made.


Global research preparedness for outbreak-related critical illness


title: Synthetic Biology: Applications Come of Age

text: Synthetic biology is bringing together engineers and biologists to design and build novel biomolecular components, networks and pathways, and to use these constructs to rewire and reprogram organisms. These re-engineered organisms will change our lives in the coming years, leading to cheaper drugs, “green” means to fuel our cars, and targeted therapies to attack “superbugs” and diseases such as cancer. The de novo engineering of genetic circuits, biological modules, and synthetic pathways is beginning to address these critical problems and is being used in related practical applications.


title: Genome characterization of a novel porcine bocavirus

text: Using a high-throughput DNA sequencing method, one DNA sequence (contig01006), suspected to belong to a novel porcine bocavirus (PBoV), was found with a high rate of detection (19.6 %) in fecal samples from healthy piglets. Moreover, a novel PBoV (tentatively named PBoV3C) with a nearly complete genome sequence (5235 bp) was identified. PBoV3C exhibits typical genome characteristics of bocaviruses and shows the highest genomic sequence identity (78 % to 81 %) to PBoV3A/B (PBoV3/4-UK) and PBoV3D/E (PBoV3/4-HK), respectively. Phylogenetic and recombination analysis indicated high diversity, prevalence and complexity among the PBoVs. The phospholipase A2 (PLA2) site of VP1 and the secondary structure of VP2 of PBoV3C were also analyzed. Additionally, we propose a uniform method of PBoV nomenclature based on the VP1 gene.


title: Nature exposure and positive body image: (Re-)examining the mediating roles of connectedness to nature and trait mindfulness

text: Previous studies have reported a significant association between nature exposure and positive body image, but understandings of the mechanisms that help to explain this link remain nascent. Here, we considered the extent to which trait mindfulness and connectedness to nature, respectively, mediate the aforementioned relationship both in parallel and serially. An online sample of 398 participants (199 women, 196 men, 3 other; age M = 28.1 years) from the United Kingdom completed measures of self-reported nature exposure, mindful awareness and acceptance, connectedness to nature, and body appreciation. Results indicated that inter-correlations between scores on all measures were significant and positive. Following the elimination of non-significant pathways, path analysis resulted in an adequately-fitting model in which the direct relationship between nature exposure and body appreciation was significant. In addition, connectedness to nature – but not trait mindfulness – significantly mediated the direct relationship. Finally, we also found evidence of a serial mediation, where the association between nature exposure and body appreciation was mediated by mindful awareness followed by connectedness to nature. The implications of these results for scholarly and practitioner understanding of the impact of nature exposure on positive body image are discussed in conclusion.


Oil prices, climate change—health challenges in Saudi Arabia


Promoting and supporting children’s health and healthcare during COVID-19 – International Paediatric Association Position Statement


title: Respiratory Viruses and Asthma

text: Asthma remains the most prevalent chronic respiratory disorder, affecting people of all ages. The relationship between respiratory virus infection and asthma has long been recognized, though remains incompletely understood. In this article, we will address key issues around this relationship. These will include the crucial role virus infection plays in early life, as a potential risk factor for the development of asthma and lung disease. We will assess the impact that virus infection has on those with established asthma as a trigger for acute disease and how this may influence asthma throughout life. Finally, we will explore the complex interaction that occurs between the airway and the immune responses that make those with asthma so susceptible to the effects of virus infection.


title: Evaluation of the genetic variability found in Brazilian commercial vaccines for infectious bronchitis virus

text: Infectious bronchitis virus (IBV) is currently one of the most important pathogens in the poultry industry. The H120 and Ma5 are the only viral strains approved by the Brazilian government as the constituent of vaccines. Despite the systematic vaccination in Brazil, IBV has not yet been controlled and diseases associated with this virus have been reported in vaccinated chickens. Here, we investigated the genetic variability of H120 and Ma5 strains present in the IBV vaccines from different Brazilian manufacturers. We performed DNA sequencing analyses of the S1 spike glycoprotein gene to investigate its genetic variability and the presence of viral subpopulations among vaccines, between batches, and also in each vaccine after a single passage was performed in chicken embryonated eggs. Our results revealed up to 13 amino acid substitutions among vaccines and some of them were localized in regions of the S1 glycoprotein that play a role in virus–host interaction. Secondary nucleotide peaks identified in the chromatogram for the S1 gene sequence revealed that all original vaccines (H120 and Ma5) were composed by different subpopulations of IBV. Moreover, new viral subpopulations were also found in vaccines after a single passage in chicken embryonated eggs. These findings indicate that H120 and Ma5 viral strains used in vaccines market in Brazil can still mutate very rapidly during replication, leading to amino acid substitutions in proteins involved in the stimulation of the immune response, such as the S1 glycoprotein. Therefore, our data suggest that the genetic variability of these viral strains should be taken into consideration to ensure an effective immune response against IBV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-017-1515-2) contains supplementary material, which is available to authorized users.


docid: dwjijmwz

title: Nucleolar localization of influenza A NS1: striking differences between mammalian and avian cells

text: In mammalian cells, nucleolar localization of influenza A NS1 requires the presence of a C-terminal nucleolar localization signal. This nucleolar localization signal is present only in certain strains of influenza A viruses. Therefore, only certain NS1 accumulate in the nucleolus of mammalian cells. In contrast, we show that all NS1 tested in this study accumulated in the nucleolus of avian cells even in the absence of the above described C-terminal nucleolar localization signal. Thus, nucleolar localization of NS1 in avian cells appears to rely on a different nucleolar localization signal that is more conserved among influenza virus strains.


title: Clonal haematopoiesis and COVID‐19: A possible deadly liaison

text: We provide evidence for a linear correlation between the frequency of clonal haematopoiesis and COVID‐19 mortality rate. We discuss the mechanistic explanations for this association mediated by a pathological inflammatory response. Our hypothesis can be tested in COVID‐19‐infected patients and eventually lead to new approaches to risk stratification and therapy.


title: Coronary plague instability in severe acute respiratory syndrome

text: Abstract In his second week of severe acute respiratory syndrome (SARS) illness, a patient developed an unusually complicated course of acute coronary syndrome. One day after initial stabilization of a non-ST-elevated anterior myocardial infarction (MI), he sustained an ST-elevated anterior MI. Eight hours after emergency coronary intervention to the culprit lesion, he developed another ST-elevated MI in the inferior territory. Acute inflammation and cytokine storm in the immunopathological phase of SARS may play a role in coronary plague instability. Physicians should be alert to this potentially fatal complication and adopt appropriate vigilant and aggressive management strategies.


Regulation of Coronavirus Transcription: Viral and Cellular Proteins Interacting with Transcription-Regulating Sequences


title: Effects of air pollution on the respiratory health of children: a study in the capital city of India

text: Urban air pollutants cause a wide range of acute and chronic effects on the respiratory system of children that can be devastating. In this study, the respiratory health of children was assessed in the capital city of India where the level of air pollution is much above the National Ambient Air Quality Standards. The study was carried out in Delhi, and the findings were compared with those of rural West Bengal and Uttaranchal. The prevalence of respiratory symptoms was determined through a structured respiratory symptomlogy questionnaire and personal interviews. Air quality data were collected from Central and State Pollution Control Boards and also obtained by direct measurements using a portable aerosol monitor. Based on the data collected on the cohort of children participating in this study, 32.1% of children in Delhi suffered from respiratory problems in contrast to 18.2% of rural children (control). The respiratory symptoms were more prevalent in girls than in boys. A strong, statistically significant positive association was observed between PM(10) level in Delhi’s air and the prevalence of lower respiratory tract symptoms.


title: β adrenergic receptor modulated signaling in glioma models: promoting β adrenergic receptor-β arrestin scaffold-mediated activation of extracellular-regulated kinase 1/2 may prove to be a panacea in the treatment of intracranial and spinal malignancy and extra-neuraxial carcinoma

text: Neoplastically transformed astrocytes express functionally active cell surface β adrenergic receptors (βARs). Treatment of glioma models in vitro and in vivo with β adrenergic agonists variably amplifies or attenuates cellular proliferation. In the majority of in vivo models, β adrenergic agonists generally reduce cellular proliferation. However, treatment with β adrenergic agonists consistently reduces tumor cell invasive potential, angiogenesis, and metastasis. β adrenergic agonists induced decreases of invasive potential are chiefly mediated through reductions in the expression of matrix metalloproteinases types 2 and 9. Treatment with β adrenergic agonists also clearly reduce tumoral neoangiogenesis, which may represent a putatively useful mechanism to adjuvantly amplify the effects of bevacizumab. Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor receptor. We may accordingly designate βagonists to represent an enhancer of bevacizumab. The antiangiogenic effects of β adrenergic agonists may thus effectively render an otherwise borderline effective therapy to generate significant enhancement in clinical outcomes. β adrenergic agonists upregulate expression of the major histocompatibility class II DR alpha gene, effectively potentiating the immunogenicity of tumor cells to tumor surveillance mechanisms. Authors have also demonstrated crossmodal modulation of signaling events downstream from the β adrenergic cell surface receptor and microtubular polymerization and depolymerization. Complex effects and desensitization mechanisms of the β adrenergic signaling may putatively represent promising therapeutic targets. Constant stimulation of the β adrenergic receptor induces its phosphorylation by β adrenergic receptor kinase (βARK), rendering it a suitable substrate for alternate binding by β arrestins 1 or 2. The binding of a β arrestin to βARK phosphorylated βAR promotes receptor mediated internalization and downregulation of cell surface receptor and contemporaneously generates a cell surface scaffold at the βAR. The scaffold mediated activation of extracellular regulated kinase 1/2, compared with protein kinase A mediated activation, preferentially favors cytosolic retention of ERK1/2 and blunting of nuclear translocation and ensuant pro-transcriptional activity. Thus, βAR desensitization and consequent scaffold assembly effectively retains the cytosolic homeostatic functions of ERK1/2 while inhibiting its pro-proliferative effects. We suggest these mechanisms specifically will prove quite promising in developing primary and adjuvant therapies mitigating glioma growth, angiogenesis, invasive potential, and angiogenesis. We suggest generating compounds and targeted mutations of the β adrenergic receptor favoring β arrestin binding and scaffold facilitated activation of ERK1/2 may hold potential promise and therapeutic benefit in adjuvantly treating most or all cancers. We hope our discussion will generate fruitful research endeavors seeking to exploit these mechanisms.


Interleukin-6 as prognosticator in patients with COVID-19: IL-6 and Covid-19


title: Atypical presentation of COVID-19: Acute renal failure

text: Coronavirus disease (COVID-19) emerged in Wuhan, China, in December 2019 and rapidly became a global pandemic, with the number of confirmed infections worldwide reaching 1 million by the start of April 2020 and 3 million less than a month later. COVID-19 can be encountered with different clinical presentations. We present the case of a patient with COVID-19 in the etiology presenting with acute renal failure.


title: Possible Spread of adenovirus type 3 from poultry to humans: indirect evidence from an outbreak in China

text: Abstract Objective To explore the epidemiology and etiology for an outbreak of acute respiratory tract infection that occurred in one county of Jiangsu Province, China 2004. Methods Only cases meeting the case definition were included in the study. We reviewed the medical records of the cases who were admitted to the local hospitals, interviewed cases by a standard questionnaire, and then described the epidemiologic features and analyzed risk factors by means of a case-control study. We collected pharyngeal swab specimens and sent them to different laboratories for isolation and culture. The laboratory used different detection methods such as DIF, PCR, electron microscope examination and microneutralization assay, to identify and then type the positive specimens. Results A total of 871 cases were reported during the period from April 18 to July 4, 2004. The distribution of onset times presented two peaks, one in late May and another in middle June. The epidemic occurred mainly in the elementary and junior high schools in ten townships of one county, and the mean age of the cases was 12 years (range 7 months to 18 years). The course of the disease was acute, and was characterized by fever accompanied with sore throat and tonsillitis. The WBC count of cases was normal or elevated. The mean duration of illness was 5 days (range 2 to 12 days). No fatalities from illness were reported. A case-control study indicated that the possible risk factors were close contact with a case and/or poultry before onset and sharing of towels among members of the family. The typical CPE was observed through inoculating pharyngeal swab specimens into the HEP-2 cell cultures in different laboratories. An infection of adenovirus type 3 was verified by detecting positive specimens in different methods. Conclusion This investigation demonstrated that the acute respiratory infection in cases was caused by adenovirus type 3. Cases occurred in over 70 schools in ten townships in 2004, and the route of transmission was possibly close contact with cases or droplet transmission.


title: Kinetic Modeling of Local Epidemic Spread and Its Simulation

text: The local epidemic spread in physical space is modeled using the kinetic equation. In particular, the infection occurs via the binary interaction between the uninfected and infected individuals. Then, the local epidemic spread can be modeled on the basis of the stochastic Boltzmann type equation. In this paper, the normalized virus titer inside the infected human body is defined as the function of the elapsed time, which is measured from the infection time. Consequently, the probability of the infection at the binary human interaction increases, as the normalized virus titer inside the human body increases, whereas the normalized virus titer inside the infected human body decreases, after the normalized virus titer reaches to its maximum value, namely, unity, in the characteristic time. Numerical results indicate that the propagation speed of the boundary between the infected and uninfected domains depends on such a characteristic time, strongly, when the Knudsen number and temperature are fixed. Such a dependency of the propagation speed of the boundary between the infected and uninfected domains on the characteristic time can be described by the Fisher–Kolmogorov–Petrovsky–Piscounov equation which is introduced from the stochastic Boltzmann type equation. Finally, we consider three types of the human behavior as plausible actions to the local epidemic spread.


title: COVID‐19 and HIV co‐infection an emerging consensus

text: Toombs et al provide an important contribution to the emerging literature which seeks to establish if those People Living with Human Immunodeficiency Virus (PLWH) are disproportionately affected by the COVID-19 pandemic (1). Evidence from their case series have been consistent with the hypothesis that PLWH do not experience disproportionately greater hospital admission, morbidity, or mortality. This article is protected by copyright. All rights reserved.


docid: taehdjyk

title: RNA Respiratory Viruses in Solid Organ Transplantation


title: In Ovo Delivered Toll-Like Receptor 7 Ligand, Resiquimod Enhances Host Responses against Infectious Bronchitis Corona Virus (IBV) Infection

text: Toll-like receptor (TLR) 7 ligand, resiquimod, has been studied as an adjuvant and antiviral agent against several pathogens in chicken. Yet, the effectiveness of resiquimod against infectious bronchitis virus (IBV) infection has not been evaluated. In this study, we investigated the effectiveness of resiquimod delivered pre-hatch (in ovo) against IBV infection post-hatch identifying key mechanisms involved in resiquimod driven immune activation. First, we found an upregulation of interleukin (IL)-1β and interferon (IFN)-γ mRNA levels and considerable expansions of macrophage and cluster of differentiation (CD) 8α+ T cell populations in lungs of chicken as early as day one post-hatch, following pre-hatch delivery of resiquimod. Second, we observed that resiquimod was able to act as an adjuvant when resiquimod was delivered pre-hatch along with an inactivated IBV vaccine. Finally, when the resiquimod pretreated one-day-old chickens were infected with IBV, reduction in viral shedding via oral and fecal routes was observed at 3 days post- infection. Overall, this study shows that the pre-hatch delivered resiquimod increases cell-mediated immune responses in lungs with an advantage of reduction in IBV shedding.


title: Responsive immunization and intervention for infectious diseases in social networks

text: By using the microscopic Markov-chain approximation approach, we investigate the epidemic spreading and the responsive immunization in social networks. It is assumed that individual vaccination behavior depends on the local information of an epidemic. Our results suggest that the responsive immunization has negligible impact on the epidemic threshold and the critical value of initial epidemic outbreak, but it can effectively inhibit the outbreak of epidemic. We also analyze the influence of the intervention on the disease dynamics, where the vaccination is available only to those individuals whose number of neighbors is greater than a certain value. Simulation analysis implies that the intervention strategy can effectively reduce the vaccine use under the epidemic control.


docid: udvrdglk

title: In-silico studies in Chinese herbal medicines’ research: Evaluation of in-silico methodologies and phytochemical data sources, and a review of research to date

text: Abstract The available databases that catalogue information on traditional Chinese medicines are reviewed in terms of their content and utility for in-silico research on Chinese herbal medicines, as too are the various protein database resources, and the software available for use in such studies. The software available for bioinformatics and ‘omics studies of Chinese herbal medicines are summarised, and a critical evaluation given of the various in-silico methods applied in screening Chinese herbal medicines, including classification trees, neural networks, support vector machines, docking and inverse docking algorithms. Recommendations are made regarding any future in-silico studies of Chinese herbal medicines.


title: COVID‐19: Structural Predictions of Viral Success

text: Since the beginning of the 21(st) century, three coronaviruses have crossed the species barrier and caused serious human disease: severe acute respiratory syndrome coronavirus (SARS‐CoV) in November 2002 [1, 2], Middle‐East respiratory syndrome coronavirus (MERS‐CoV) in 2012 [3, 4], and SARS‐CoV‐2 in 2019 [5, 6]. SARS‐CoV‐2 [7], initially called 2019‐nCoV, is the etiological agent of COVID‐19, a highly contagious infectious illness that was first reported in December 2019 in Wuhan, China and subsequently spread globally [8]. As of May 24, 2020, COVID‐19 has caused >5,370,000 infections and >343,000 deaths worldwide [9].


title: Targeting viral entry as a strategy for broad-spectrum antivirals

text: The process of entry into a host cell is a key step in the life cycle of most viruses. In recent years, there has been a significant increase in our understanding of the routes and mechanisms of entry for a number of these viruses. This has led to the development of novel broad-spectrum antiviral approaches that target host cell proteins and pathways, in addition to strategies focused on individual viruses or virus families. Here we consider a number of these approaches and their broad-spectrum potential.


title: GENOMICS AND BIOINFORMATICS

text: This chapter discusses the basic principles of molecular biology regarding genome science and describes the major types of data involved in genome projects, including technologies for collecting them. Genome science is heavily driven by new technological advances that allow for rapid and inexpensive collection of various types of data. The emergence of genomic science has not simply provided a rich set of tools and data for studying molecular biology. It has been the catalyst for an astounding burst of interdisciplinary research, and it has challenged long-established hierarchies found in most institutions of higher learning. The next generation of biologists needs to be as comfortable at a computer workstation as they are at the lab bench. Recognizing this fact, many universities have already reorganized their departments and their curricula to accommodate the demands of genomic science.The chapter discusses practical applications and uses of genomic data. For example, in the foreseeable future, are gene therapies that can repair genetic defects.


title: Feline Infectious Peritonitis: An Immune-Mediated Coronaviral Vasculitis

text: Mainly through studies inducing experimental infection of susceptible cats, significant advances have recently been made in our understanding of the pathogenesis of FIP. Much of this knowledge should not presently be directly extrapolated to field cases of FIP, because the route of infection and challenge dose and strain of virus may be significantly different. Advances in the prevention and treatment of FIP will depend greatly on clarification of the exact nature of the several coronaviruses affecting cats and the role of cell-mediated immunity in resistance to FIPV.


Medical Radiation Sciences Clinical Students Discuss the ‘Soft Skills’ Utilized as Screeners During the COVID-19 Pandemic


title: Reproductive Diseases of the Backyard Hen

text: Abstract Reproductive diseases commonly occur in backyard hens, and the underlying cause is usually different from that of commercial-production hens. Because backyard hens typically live longer, are usually provided an adequate diet, and have relatively more space than commercial hens, the most common causes of their reproductive disease include neoplasia, egg-related peritonitis, persistent right oviduct, and old age. Conversely, other reproductive diseases including vent trauma and depletion of calcium are rarely diagnosed.


The ‘president’s drug’


title: Human Health Link to Invasive Species☆

text: Abstract Invasive species are currently a far-reaching, interdisciplinary topic given their broad impacts on biodiversity, economics, and human health, with representatives from all taxonomic levels (e.g., viruses, bacteria, algae, plants, invertebrates, large mammals). Researchers from different fields are working to build a framework for understanding how to best evaluate, quantify, and predict different kinds of impacts by non-indigenous species (NIS). In this context, there has been some controversy regarding the appropriate way to define invasive species and the invasion process, given the widespread use of these terms in both scientific and nonscientific frameworks. Although scientists have not unambiguously identified tax-independent characteristics that define all invasive species, the invasion process itself has been observed to progress through the same sequence of stages regardless of taxonomic identity (i.e., initial establishment, expansion, and saturation). Several non-exclusive hypotheses have been proposed to explain the successful establishment and spread of non-indigenous species in new environments. In the scenario of global change, species introductions and invasions are a major topic due to ecological impacts (e.g., changes in biodiversity), economic and social impacts (e.g., costs incurred for control or eradication or pests) and human health impacts (e.g., epidemics or increased exposure to hazards). Current research highlights the introduction and spread of non-indigenous species as both a consequence and cause of global change with repercussions on ecosystems, economies, and human societies.


title: GIS-based spatial modeling of COVID-19 incidence rate in the continental United States

text: Abstract During the first 90 days of the COVID-19 outbreak in the United States, over 675,000 confirmed cases of the disease have been announced, posing unprecedented socioeconomic burden to the country. Due to inadequate research on geographic modeling of COVID-19, we investigated county-level variations of disease incidence across the continental United States. We compiled a geodatabase of 35 environmental, socioeconomic, topographic, and demographic variables that could explain the spatial variability of disease incidence. Further, we employed spatial lag and spatial error models to investigate spatial dependence and geographically weighted regression (GWR) and multiscale GWR (MGWR) models to locally examine spatial non-stationarity. The results suggested that even though incorporating spatial autocorrelation could significantly improve the performance of the global ordinary least square model; these models still represent a significantly poor performance compared to the local models. Moreover, MGWR could explain the highest variations (adj. R2: 68.1%) with the lowest AICc compared to the others. Mapping the effects of significant explanatory variables (i.e., income inequality, median household income, the proportion of black females, and the proportion of nurse practitioners) on spatial variability of COVID-19 incidence rates using MGWR could provide useful insights to policymakers for targeted interventions.


title: In vitro anti-viral activity of the total alkaloids from Tripterygium hypoglaucum against herpes simplex virus type 1

text: Herpes simplex virus type 1 (HSV-1) is a commonly occurring human pathogen worldwide. There is an urgent need to discover and develop new alternative agents for the management of HSV-1 infection. Tripterygium hypoglaucum (level) Hutch (Celastraceae) is a traditional Chinese medicine plant with many pharmacological activities such as anti-inflammation, anti-tumor and antifertility. The usual medicinal part is the roots which contain about a 1% yield of alkaloids. A crude total alkaloids extract was prepared from the roots of T. hypoglaucum amd its antiviral activity against HSV-1 in Vero cells was evaluated by cytopathic effect (CPE) assay, plaque reduction assay and by RT-PCR analysis. The alkaloids extract presented low cytotoxicity (CC(50) = 46.6 μg/mL) and potent CPE inhibition activity, the 50% inhibitory concentration (IC(50)) was 6.5 μg/mL, noticeably lower than that of Acyclovir (15.4 μg /mL). Plaque formation was significantly reduced by the alkaloids extract at concentrations of 6.25 μg/mL to 12.5 μg/mL, the plaque reduction ratio reached 55% to 75 which was 35% higher than that of Acyclovir at the same concentration. RT-PCR analysis showed that, the transcription of two important delayed early genes UL30 and UL39, and a late gene US6 of HSV-1 genome all were suppressed by the alkaloids extract, the expression inhibiting efficacy compared to the control was 74.6% (UL30), 70.9% (UL39) and 62.6% (US6) respectively at the working concentration of 12.5μg/mL. The above results suggest a potent anti-HSV-1 activity of the alkaloids extract in vitro.


title: Critical Review and Uncertainty Analysis of Factors Influencing Influenza Transmission

text: Influenza remains a significant threat to public health, yet there is significant uncertainty about the routes of influenza transmission from an infectious source through the environment to a receptor, and their relative risks. Herein, data pertaining to factors that influence the environmental mediation of influenza transmission are critically reviewed, including: frequency, magnitude and size distribution and virus expiration, inactivation rates, environmental and self‐contact rates, and viral transfer efficiencies during contacts. Where appropriate, two‐stage Monte Carlo uncertainty analysis is used to characterize variability and uncertainty in the reported data. Significant uncertainties are present in most factors, due to: limitations in instrumentation or study realism; lack of documentation of data variability; or lack of study. These analyses, and future experimental work, will improve parameterization of influenza transmission and risk models, facilitating more robust characterization of the magnitude and uncertainty in infection risk.


title: Rising Tide: Responding to the Mental Health Impact of the COVID‐19 Pandemic

text: Now freely downloadable on the Anxiety and Depression Association of America website (https://adaa.org/sites/default/files/PhasedApproachtoCovid‐19.ver1.1%20(002).pdf) is a framework for COVID‐19 mental health response (see Table 1). This framework of phased interventions and resources is intended to assist health systems and programs impacted by the pandemic to plan for how to address current mental health issues arising as well as to prepare and plan for the continued needs of their communities, patients, and staff. This article is protected by copyright. All rights reserved.


title: Coronavirus disease 2019: favorable outcome in an immunosuppressed patient with multiple sclerosis

text: The rapid and global spread of severe acute respiratory syndrome coronavirus 2, a viral pathogen responsible for the development of the “coronavirus disease of 2019” (COVID-19), has developed into an unprecedented health crisis with considerable case fatality rate. Patients with comorbidities are considered to be at higher risk for severe disease with acute respiratory failure, intensive care unit admission, and/or death. Particular vigilance has been warranted regarding the continuation of immunosuppressive treatments since viral clearing may be hampered in such cases. In contrast, it has also been hypothesized that overactive immune responses may trigger a cytokine storm associated with clinical deterioration, which has generated an interest in certain immunosuppressant drugs as potential treatment for COVID-19. We would like to present the first case report of a patient who was formally diagnosed with COVID-19 while being under disease-modifying treatment with rituximab, an anti-CD20 B cell depleting agent, for multiple sclerosis. The clinical picture was mild for which we have tried to provide an immunopathological framework.


title: SARS

text: Abstract Severe acute respiratory syndrome (SARS) emerged in southern China in late 2002. It first spread within Guangdong Province and then to other parts of China. Via air travelers, it quickly reached various countries around the globe, causing several major hospital outbreaks. Within weeks, the causative agent, a previously unknown coronavirus (SARS-CoV), was identified, thanks to an unprecedented international effort led by the World Health Organization (WHO). Its origin was quickly traced to wild animals traded locally for culinary purposes. Masked palm civet and some other species seem to have acted as intermediate hosts. Since then, SARS-like coronaviruses were found in different bat species in China and elsewhere, and bats are now regarded as the wildlife reservoir for SARS-CoV. Fortunately, the SARS outbreak could be contained within months. Until July 2003, it had caused 8096 cases, with 774 deaths. Once adequate measures such as isolating patients and quarantining their contacts were strictly adhered to, further transmission between human beings could be interrupted. SARS is an example of how rapidly an infectious agent can spread in the modern world. At the same time, it should serve as a showcase of how international cooperation and modern science can help to combat the spread of infectious diseases.


From wet markets to Wal‐Marts: tracing alimentary xenophobia in the time of COVID‐19


title: BX-795 inhibits HSV-1 and HSV-2 replication by blocking the JNK/p38 pathways without interfering with PDK1 activity in host cells

text: BX-795 is an inhibitor of 3-phosphoinositide-dependent kinase 1 (PDK1), but also a potent inhibitor of the IKK-related kinase, TANKbinding kinase 1 (TBK1) and IKKɛ. In this study we attempted to elucidate the molecular mechanism(s) underlying the inhibition of BX-795 on Herpes simplex virus (HSV) replication. HEC-1-A or Vero cells were treated with BX-795 and infected with HSV-1 or HSV-2 for different periods. BX-795 (3.125-25 μmol/L) dose-dependently suppressed HSV-2 replication, and displayed a low cytotoxicity to the host cells. BX-795 treatment dose-dependently suppressed the expression of two HSV immediate-early (IE) genes (ICP0 and ICP27) and the late gene (gD) at 12 h postinfection. HSV-2 infection resulted in the activation of PI3K and Akt in the host cells, and BX-795 treatment inhibited HSV-2-induced Akt phosphorylation and activation. However, the blockage of PI3K/Akt/mTOR with LY294002 and rapamycin did not affect HSV-2 replication. HSV-2 infection increased the phosphorylation of JNK and p38, and reduced ERK phosphorylation at 8 h postinfection in the host cells; BX-795 treatment inhibited HSV-2-induced activation of JNK and p38 MAP kinase as well as the phosphorylation of c-Jun and ATF-2, the downstream targets of JNK and p38 MAP kinase. Furthermore, SB203580 (a p38 inhibitor) or SP600125 (a JNK inhibitor) dose-dependently inhibited the viral replication in the host cells, whereas PD98059 (an ERK inhibitor) was not effective. Moreover, BX-795 blocked PMA-stimulated c-Jun activation as well as HSV-2-mediated c-Jun nuclear translocation. BX-795 dose-dependently inhibited HSV-2, PMA, TNF-α-stimulated AP-1 activation, but not HSV-induced NF-κB activation. Overexpression of p38/JNK attenuated the inhibitory effect of BX-795 on HSV replication. BX-795 completely blocked HSV-2-induced MKK4 phosphorylation, suggesting that BX-795 acting upstream of JNK and p38 MAP kinase. In conclusion, this study identifies the anti-HSV activity of BX-795 and its targeting of the JNK/p38 MAP kinase pathways in host cells.


title: Unfolded protein response in hepatitis C virus infection

text: Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus of clinical importance. The virus establishes a chronic infection and can progress from chronic hepatitis, steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The mechanisms of viral persistence and pathogenesis are poorly understood. Recently the unfolded protein response (UPR), a cellular homeostatic response to endoplasmic reticulum (ER) stress, has emerged to be a major contributing factor in many human diseases. It is also evident that viruses interact with the host UPR in many different ways and the outcome could be pro-viral, anti-viral or pathogenic, depending on the particular type of infection. Here we present evidence for the elicitation of chronic ER stress in HCV infection. We analyze the UPR signaling pathways involved in HCV infection, the various levels of UPR regulation by different viral proteins and finally, we propose several mechanisms by which the virus provokes the UPR.


title: Health-Related Quality of Life in Common Variable Immunodeficiency Italian Patients Switched to Remote Assistance During the COVID-19 Pandemic

text: Background A rapidly expanding pandemic of the new coronavirus has become the focus of global scientific attention. Data are lacking on the impact of the pandemic caused by the severe acute respiratory syndrome coronavirus 2 on health-related quality of life among patients affected by primary antibody deficiencies (PADs). Objective To identify factors impacting the health-related-quality of life (HRQOL) among Italian patients affected by PADs switched to remote assistance at the time of the coronavirus disease 2019 pandemic. Methods The quality of life was surveyed in 158 patients with PADs by the Common Variable Immune Deficiency Quality of Life questionnaire, a disease-specific tool, and by the 12-item General Health Questionnaire, a generic tool to assess the risk of anxiety/depression. Since the beginning of the coronavirus disease 2019 epidemic, we shifted all patients with PADs to home therapy, and activated remote visits. Questionnaires were sent by email 4 weeks later. Common Variable Immune Deficiency Quality of Life questionnaire and 12-item General Health Questionnaire data scores were compared with the same set of data from a survey done in 2017. Results Of 210 patients, 158 (75%) agreed to participate. The quality of life was worse in the group of patients who were at risk of anxiety/depression at the study time. HRQOL was similar in patients forced to shift from hospital-based to home-based immunoglobulin treatment and in patients who continued their usual home-based replacement. The risk of anxiety/depression is associated with pandemia caused by the severe acute respiratory syndrome coronavirus 2 and with patients' fragility, and not with related clinical conditions associated with common variable immune deficiencies. Anxiety about running out of medications is a major new issue. Conclusions The coronavirus disease 2019 epidemic impacted HRQOL and the risk of anxiety/depression of patients with PADs. The remote assistance program was a useful possibility to limit personal contacts without influencing the HRQOL.


Severe Acute Respiratory Syndrome (SARS): An interim information paper for dental health care workers


title: Covid-19 and immunomodulation in IBD

text: The current coronavirus pandemic is an ongoing global health crisis due to covid-19, caused by severe acute respiratory syndrome coronavirus 2. Although covid-19 leads to little or mild flu-like symptoms in the majority of affected patients, the disease may cause severe, frequently lethal complications such as progressive pneumonia, acute respiratory distress syndrome and organ failure driven by hyperinflammation and a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In the context of IBD, several key questions arise. For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to covid-19 and the cytokine release syndrome associated with lung injury and fatal outcomes. Another highly relevant question is how to deal with immunosuppression and immunomodulation during the current pandemic in patients with IBD and whether immunosuppression affects the progress of covid-19. Here, the current understanding of the pathophysiology of covid-19 is reviewed with special reference to immune cell activation. Moreover, the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed.


title: Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection

text: Compared with other mammals, bats harbor more zoonotic viruses per species and do not demonstrate signs of disease on infection with these viruses. To counteract infections with viruses, bats have evolved enhanced mechanisms to limit virus replication and immunopathology. However, molecular and cellular drivers of antiviral responses in bats largely remain an enigma. In this study, we demonstrate that a serine residue in IRF3 is positively selected for in multiple bat species. IRF3 is a central regulator of innate antiviral responses in mammals. Replacing the serine residue in bat IRF3 with the human leucine residue decreased antiviral protection in bat cells, whereas the addition of this serine residue in human IRF3 significantly enhanced antiviral protection in human cells. Our study provides genetic and functional evidence for enhanced IRF3-mediated antiviral responses in bats and adds support to speculations that bats have positively selected for multiple adaptations in their antiviral immune responses.


title: Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses

text: BACKGROUND: Many respiratory viruses disproportionately impact the elderly. Likewise, advanced age correlated with more adverse disease outcomes following severe acute respiratory syndrome coronavirus (SARS-CoV) infection in humans. We used an aged African green monkey SARS-CoV infection model to better understand age-related mechanisms of increased susceptibility to viral respiratory infections. Nonhuman primates are critical translational models for such research given their similarities to humans in immune-ageing as well as lung structure. RESULTS: Significant age- and infection-dependent differences were observed in both systemic and mucosal immune compartments. Peripheral lymphocytes, specifically CD8 T and B cells were significantly lower in aged monkeys pre- and post- SARS-CoV infection, while neutrophil and monocyte numbers were not impacted by age or infection status. Serum proinflammatory cytokines were similar in both age groups, whereas significantly lower levels of IL-1beta, IL-18, IL-6, IL-12 and IL-15 were detected in the lungs of SARS-CoV-infected aged monkeys at either 5 or 10 days post infection. Total lung leukocyte numbers and relative frequency of CD8 T cells, B cells, macrophages and dendritic cells were greatly reduced in the aged host during SARS-CoV infection, despite high levels of chemoattractants for many of these cells in the aged lung. Dendritic cells and monocytes/macrophages showed age-dependent differences in activation and chemokine receptor profiles, while the CD8 T cell and B cell responses were significantly reduced in the aged host. In examination of viral titers, significantly higher levels of SARS-CoV were detected in the nasal swabs early, at day 1 post infection, in aged as compared to juvenile monkeys, but virus levels were only slightly higher in aged animals by day 3. Although there was a trend of higher titers in respiratory tissues at day 5 post infection, this did not reach statistical significance and virus was cleared from all animals by day 10, regardless of age. CONCLUSIONS: This study provides unique insight into how several parameters of the systemic and mucosal immune response to SARS-CoV infection are significantly modulated by age. These immune differences may contribute to deficient immune function and the observed trend of higher SARS-CoV replication in aged nonhuman primates.


title: Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP)

text: Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide. Although nucleos(t)ide analogs inhibiting viral reverse transcriptase are clinically available as anti-HBV agents, emergence of drug-resistant viruses highlights the need for new anti-HBV agents interfering with other targets. Here we report that cyclosporin A (CsA) can inhibit HBV entry into cultured hepatocytes. The anti-HBV effect of CsA was independent of binding to cyclophilin and calcineurin. Rather, blockade of HBV infection correlated with the ability to inhibit the transporter activity of sodium taurocholate cotransporting polypeptide (NTCP). We also found that HBV infection-susceptible cells, differentiated HepaRG cells and primary human hepatocytes expressed NTCP, while nonsusceptible cell lines did not. A series of compounds targeting NTCP could inhibit HBV infection. CsA inhibited the binding between NTCP and large envelope protein in vitro. Evaluation of CsA analogs identified a compound with higher anti-HBV potency, having a median inhibitory concentration <0.2 μM. Conclusion: This study provides a proof of concept for the novel strategy to identify anti-HBV agents by targeting the candidate HBV receptor, NTCP, using CsA as a structural platform. (Hepatology 2014;59:1726–1737)


title: Pathogenic murine coronaviruses I. Characterization of biological behavior in vitro and virus-specific intracellular RNA of strongly neurotropic JHMV and weakly neurotropic A59V viruses

text: Abstract JHM virus (JHMV) and A59 virus (A59V) are neurotropic members of the hepatoencephalitis group of murine coronaviridae. JHMV has a markedly greater neurotropism for weanling BALB/c mice than does A59V. Both viruses display one-hit kinetics when grown in vitro in 17CL-16 cells, a clone of BALB/c3T3 cells. Virus-specific intranuclear, cytoplasmic, and surface antigens have been observed for both viruses by immunofluorescence. The intranuclear antigen appears first at about 2 hr after infection (hpi) followed by the development of the cytoplasmic and surface antigens at 3 hpi at 38.5°. Most, if not all cells that develop the intranuclear antigen, produce cytoplasmic antigen and presumably progeny virus. Progeny virus production is independent of cell fusion and formation of syncytia. Virus-specific ribonucleoprotein is synthesized in the presence of 1 μg/ml actinomycin D, a concentration sufficient to inhibit the synthesis of cellular ribonucleoprotein species that have sedimentation properties similar to the virus-specific species. The virus-specific ribonucleoprotein species that is resistant to 10 mM EDTA, presumptive virion ribonucleoprotein, has a sedimentation value in sucrose of about 230 S for JHMV and 200 S for A59V. The species of virus-specific ribonucleoprotein that are sensitive to 10 mM EDTA presumptive messenger ribonucleoprotein, are about 40–100 S in sucrose for both viruses. The purified presumptive virion RNA is about 50 S in sucrose for both viruses. The major species of presumptive mRNA of both viruses is about 18 S with secondary species of about 28 S in sucrose. Denaturation of the virus-specific RNA with heat and dimethylsulfoxide does not appreciably alter the sedimentation profiles of either the presumptive virion RNA or mRNA species.


title: Chloroquine for SARS-CoV-2: Implications of Its Unique Pharmacokinetic and Safety Properties

text: Since in vitro studies and a preliminary clinical report suggested the efficacy of chloroquine for COVID-19-associated pneumonia, there is increasing interest in this old antimalarial drug. In this article, we discuss the pharmacokinetics and safety of chloroquine that should be considered in light of use in SARS-CoV-2 infections. Chloroquine is well absorbed and distributes extensively resulting in a large volume of distribution with an apparent and terminal half-life of 1.6 days and 2 weeks, respectively. Chloroquine is metabolized by cytochrome P450 and renal clearance is responsible for one third of total clearance. The lack of reliable information on target concentrations or doses for COVID-19 implies that for both adults and children, doses that proved effective and safe in malaria should be considered, such as ‘loading doses’ in adults (30 mg/kg over 48 h) and children (70 mg/kg over 5 days), which reported good tolerability. Here, plasma concentrations were < 2.5 μmol/L, which is associated with (minor) toxicity. While the influence of renal dysfunction, critical illness, or obesity seems small, in critically ill patients, reduced absorption may be anticipated. Clinical experience has shown that chloroquine has a narrow safety margin, as three times the adult therapeutic dosage for malaria can be lethal when given as a single dose. Although infrequent, poisoning in children is extremely dangerous where one to two tablets can potentially be fatal. In conclusion, the pharmacokinetic and safety properties of chloroquine suggest that chloroquine can be used safely for an acute virus infection, under corrected QT monitoring, but also that the safety margin is small, particularly in children. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40262-020-00891-1) contains supplementary material, which is available to authorized users.


title: From SARS to MERS, Thrusting Coronaviruses into the Spotlight

text: Coronaviruses (CoVs) have formerly been regarded as relatively harmless respiratory pathogens to humans. However, two outbreaks of severe respiratory tract infection, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), as a result of zoonotic CoVs crossing the species barrier, caused high pathogenicity and mortality rates in human populations. This brought CoVs global attention and highlighted the importance of controlling infectious pathogens at international borders. In this review, we focus on our current understanding of the epidemiology, pathogenesis, prevention, and treatment of SARS-CoV and MERS-CoV, as well as provides details on the pivotal structure and function of the spike proteins (S proteins) on the surface of each of these viruses. For building up more suitable animal models, we compare the current animal models recapitulating pathogenesis and summarize the potential role of host receptors contributing to diverse host affinity in various species. We outline the research still needed to fully elucidate the pathogenic mechanism of these viruses, to construct reproducible animal models, and ultimately develop countermeasures to conquer not only SARS-CoV and MERS-CoV, but also these emerging coronaviral diseases.


Feline infectious peritonitis intra vitam diagnosis: Approach and methods


title: Combined transcriptome and metabolite profiling reveals that IiPLR1 plays an important role in lariciresinol accumulation in Isatis indigotica

text: A lignan, lariciresinol, is an important efficacious compound for the antiviral effect of Isatis indigotica, a widely used herb for the treatment of colds, fever, and influenza. Although some rate-limiting steps of the lariciresinol biosynthetic pathway are well known, the specific roles of gene family members in I. indigotica in regulating lariciresinol production are poorly understood. In the present study, a correlation analysis between the RNA sequencing (RNA-Seq) expression profile and lignan content by using I. indigotica hairy roots treated with methyl jamonate (0.5 μM) at different time points as a source implicated that I. indigotica pinoresinol/lariciresinol reductase 1 (IiPLR1), but not IiPLR2 or IiPLR3, contributed greatly to lariciresinol accumulation. Gene silencing by RNA interference (RNAi) demonstrated that IiPLR1 indeed influenced lariciresinol biosynthesis, whereas suppression of IiPLR2 or IiPLR3 did not change lariciresinol abundance significantly. IiPLR1 was thus further characterized; IiPLR1 was constitutively expressed in roots, stems, leaves, and flowers of I. indigotica, with the highest expression in roots, and it responds to different stress treatments to various degrees. Recombinant IiPLR1 reduces both (±)-pinoresinol and (±)-lariciresinol efficiently, with comparative K(cat)/K(m) values. Furthermore, overexpression of IiPLR1 significantly enhanced lariciresinol accumulation in I. indigotica hairy roots, and the best line (ovx-2) produced 353.9 μg g(–1) lariciresinol, which was ~6.3-fold more than the wild type. This study sheds light on how to increase desired metabolites effectively by more accurate or appropriate genetic engineering strategies, and also provides an effective approach for the large-scale commercial production of pharmaceutically valuable lariciresinol by using hairy root culture systems as bioreactors.


docid: lmfalzni

title: Unique Fibrinogen-binding motifs in the Nucleocapsid Phosphoprotein of SARS CoV-2: Potential Implications in Host-Pathogen Interactions

text: Novel Coronavirus (SARS CoV-2), the etiological agent for the highly contagious Corona virus disease-2019 (COVID-19) pandemic has threatened global health and economy infecting around 5.8 million people and causing over 359,200 deaths (as of 28(th) May, 2020, https://www.worldometers.info/coronavirus/). The clinical manifestations of infected patients generally range from asymptomatic or mild to severe illness, or even death. The ability of the virus to evade the host immune response have been major reasons for high morbidity and mortality. One of the important clinical observations under conditions of critical illness show increased risk of developing disseminated intravascular coagulation. Molecular mechanisms of how SARS CoV-2 induces such conditions still remain unclear. This report describes the presence of two unique motifs in the SARS CoV-2 nucleocapsid phosphoprotein (N-protein) that can potentially interact with fibrinogen and possibly prothrombin. This is based on an established function of secretory proteins in Staphylococcus aureus (S. aureus)- coagulase, Efb (Extracellular fibrinogen binding) and vWBP (von Willebrand factor Binding Protein), which are known to regulate the blood clotting cascade and the functions of host immune response. It is hypothesized that having protein interaction motifs that are homologous to these S. aureus proteins, the N-protein of this virus can mimic their functions, which may in turn play a crucial role in formation of blood clots in the host and help the virus evade host immune response. However, this hypothesis needs to be tested in vitro. Considering the overwhelming increase in the incidence of SARS CoV-2 infection globally, this information may be useful for further investigation and could help in deducing new therapeutic strategies to combat advanced stages of this disease.


title: Implementing the comprehensive unit-based safety program model to improve the management of mechanically ventilated patients in Saudi Arabia

text: BACKGROUND: Ventilator-associated events are common in mechanically ventilated patients. They are associated with more days on mechanical ventilation, longer intensive care unit (ICU) stay, and increased risk of mortality. Theoretically, interventions that prevent ventilator-associated events should also reduce associated morbidity. We evaluated the Comprehensive Unit-based Safety Program approach to improve the care of mechanically ventilated patients. METHODS: All mechanically ventilated patients admitted to the ICU between October 1, 2015, and October 31, 2016, were prospectively monitored for the development of ventilator-associated events according to the National Healthcare Safety Network criteria. A process care bundle (endotracheal intubation with subglottic suctioning, head-of-bed elevation ≥30°, target sedation scores, daily spontaneous awakening trials, spontaneous breathing trials), daily delirium assessment, and an early mobility protocol were instituted. The bundle compliance, ventilator-associated events rates, ICU length of stay, and mortality rate were noted. The database allowed viewing of current rates, trends, and averages of all participating sites. RESULTS: In the study period, 2,321 patients were admitted to the ICU, and 1,231 required mechanical ventilation (10,342 ventilator days). There were 115 ventilator-associated events: 82 ventilator-associated conditions, 15 infection-related ventilator-associated conditions, and 18 possible cases of ventilator-associated pneumonia. The ICU mortality rate was 13.3%, compared with 28.7% for those mechanically ventilated patients with ventilator-associated events (P = .0001). There was increased compliance for spontaneous awakening trials (51.5%-76.9%, P = .0008) and spontaneous breathing trials (54.2%-72.2%, P = .02) and a decrease in infection-related ventilator-associated conditions (4.2-3.5 per 1,000 days), possible cases of ventilator-associated pneumonia (2.1-1.7 per 1,000 days), ICU mortality (45.3%-19.1%, P = .045), and ventilator-associated events associated mortality rates (33.3%-8.3%, P < .37). Physical therapy participation and mobility were 60.8% and 26.4%, respectively. CONCLUSION: The implementation of a multipronged program like the Comprehensive Unit-based Safety Program could improve the care processes and outcomes of mechanically ventilated patients.


docid: xjoucnpf

title: A fatal case of COVID‐19 infection presenting with an erythema multiforme‐like eruption and fever


title: Ongoing transcatheter aortic valve implantation (TAVI) practice amidst a global COVID-19 crisis: nurse-led analgesia for transfemoral TAVI

text: The current coronavirus disease 2019 (COVID-19) crisis has led to a relative unavailability of anaesthesiological support for non-acute cardiac care. Currently, transfemoral transcatheter aortic valve implantation (TF-TAVI) is predominantly performed as an elective catheterisation laboratory (cath lab) procedure. Hence, the performance of TAVI could come to a halt amidst the COVID-19 crisis. Our study population comprised 90 patients treated with TF-TAVI, with local analgesia performed by our dedicated cath lab nurses. The patients had a mean age of 80 ± 5 years and 59% were male, with a predicted surgical risk of 2.2 ± 0.9/3.1 ± 2.4% (Society of Thoracic Surgeons Predicted Risk of Mortality [STS-PROM] score/EuroSCORE II), depicting a contemporary, lower-risk population. The composite endpoint of device success (Valve Academic Research Consortium [VARC]-2) was reached in all patients. No patients showed more than mild paravalvular leakage (3/90, 3.3%). Overall, intravenous medication was sparsely used during the procedure, with 48 of the 90 (53%) patients receiving no unplanned intravenous medication. There was neither procedural nor in-hospital mortality. The performance of TF-TAVI using local analgesia only, managed by a dedicated nurse instead of an anaesthesiologist, was shown to be feasible and safe in a selected group of patients. This strategy may (temporarily) eliminate the need for an anaesthesiologist to be present in the cath lab and enables ongoing TAVI treatment amidst the global COVID-19 crisis.


title: Residency and Fellowship Program Accreditation: Effects of the Novel Coronavirus (COVID-19) Pandemic

text: The United States is now in the grip of pandemic. Surgical services have been severely disrupted and will be for at least several months. The pandemic poses unprecedented challenges to surgical residency and fellowship programs. In turn, there are unprecedented challenges to the process of accrediting those programs. This article delineates some of those challenges and the responses to them which are known, to date.


title: Comparison of epidemiological and clinical characteristics of COVID-19 patients with and without Wuhan exposure

text: BACKGROUND: A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure. METHODS: We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan. RESULTS: Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups. CONCLUSIONS: From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.


docid: gvzvvrfx

title: Hypoalbuminemia predicts the outcome of COVID‐19 independent of age and co‐morbidity

text: The coronavirus disease 2019 (COVID‐19) has evolved into a pandemic rapidly. Most of the literature show that the elevated liver enzymes in COVID‐19 are of little clinical significance. Lower albumin level is seen in severe COVID‐19 and is not parallel to the changes in alanine aminotransferase and aspartate aminotransferase levels. We aimed to explore the impact of hypoalbuminemia in COVID‐19. This retrospective cohort study included adult patients with confirmed COVID‐19. The relationship between hypoalbuminemia and death was studied using binary logistic analysis. A total of 299 adult patients were included, 160 (53.5%) were males and the average age was 53.4 ± 16.7 years. The median time from the onset of illness to admission was 3 days (interquartile ranges, 2‐5). Approximately one‐third of the patients had comorbidities. Hypoalbuminemia (<35 g/L) was found in 106 (35.5%) patients. The difference in albumin was considerable between survivors and non‐survivors (37.6 ± 6.2 vs 30.5 ± 4.0, P < .001). Serum albumin level was inversely correlated to white blood cell (r = –.149, P = .01) and neutrophil to lymphocyte ratio (r = −.298, P < .001). Multivariate analysis showed the presence of comorbidities (OR, 6.816; 95% CI, 1.361‐34.133), lymphopenia (OR, 13.130; 95% CI, 1.632‐105.658) and hypoalbuminemia (OR, 6.394; 95% CI, 1.315‐31.092) were independent predictive factors for mortality. In conclusion, hypoalbuminemia is associated with the outcome of COVID‐19. The potential therapeutic value of albumin infusion in COVID‐19 should be further explored at the earliest.


title: FIV cross-species transmission: an evolutionary prospective

text: Feline and primate immunodeficiency viruses (FIVs, SIVs, and HIV) are transmitted via direct contact (e.g. fighting, sexual contact, and mother-offspring transmission). This dynamic likely poses a behavioral barrier to cross-species transmission in the wild. Recently, several host intracellular anti-viral proteins that contribute to species-specificity of primate lentiviruses have been identified revealing adaptive mechanisms that further limit spread of lentiviruses between species. Consistent with these inter-species transmission barriers, phylogenetic evidence supports the prediction that FIV transmission is an exceedingly rare event between free-ranging cat species, though it has occurred occasionally in captive settings. Recently we documented that puma and bobcats in Southern California share an FIV strain, providing an opportunity to evaluate evolution of both viral strains and host intracellular restriction proteins. These studies are facilitated by the availability of the 2X cat genome sequence annotation. In addition, concurrent viral and host genetic analyses have been used to track patterns of migration of the host species and barriers to transmission of the virus within the African lion. These studies illustrate the utility of FIV as a model to discover the variables necessary for establishment and control of lentiviral infections in new species.


title: Spread of Infectious Disease Modeling and Analysis of Different Factors on Spread of Infectious Disease Based on Cellular Automata

text: Infectious diseases are an important cause of human death. The study of the pathogenesis, spread regularity, and development trend of infectious diseases not only provides a theoretical basis for future research on infectious diseases, but also has practical guiding significance for the prevention and control of their spread. In this paper, a controlled differential equation and an objective function of infectious diseases were established by mathematical modeling. Based on cellular automata theory and a compartmental model, the SLIRDS (Susceptible-Latent-Infected-Recovered-Dead-Susceptible) model was constructed, a model which can better reflect the actual infectious process of infectious diseases. Considering the spread of disease in different populations, the model combines population density, sex ratio, and age structure to set the evolution rules of the model. Finally, on the basis of the SLIRDS model, the complex spread process of pandemic influenza A (H1N1) was simulated. The simulation results are similar to the macroscopic characteristics of pandemic influenza A (H1N1) in real life, thus the accuracy and rationality of the SLIRDS model are confirmed.


title: Targeting the NF-κB pathway in asthma and chronic obstructive pulmonary disease

text: Abstract Asthma and chronic obstructive pulmonary disease are inflammatory lung disorders responsible for significant morbidity and mortality worldwide. While the importance of allergic responses in asthma is well known, respiratory viral and bacterial infections and pollutants especially cigarette smoke are important factors in the pathogenesis of both diseases. Corticosteroid treatment remains the first preference of treatment in either disease, however these therapies are not always completely effective, and are associated with side effects and steroid resistance. Due to such limitations, development of new treatments represents a major goal for both the pharmaceutical industry and academic researchers. There are now excellent reasons to promote NF-κB signalling intermediates and Rel family proteins as potential therapeutic targets for both asthma and chronic obstructive pulmonary disease. This notion is supported by the fact that much of the underlying inflammation of both diseases independent of stimuli, is mediated at least in part, by NF-κB mediated signalling events in several cell types. Also, a range of inhibitors of NF-κB signalling intermediates are now available, including DNA oligonucleotides and DNA-peptide molecules that act as NF-κB decoy sequences, small molecule inhibitors such as IKK-β inhibitors, and proteasome inhibitors affecting NF-κB signalling, that have either shown promise in animal models or have begun clinical trials in other disorders. This review will focus on the role of NF-κB in both diseases, will discuss its suitability as a target, and will highlight recent key studies that support the potential of NF-κB as a therapeutic target in these two important inflammatory lung diseases.


docid: xhsquecy

title: What should we ask the patients with epilepsy on telemedicine during COVID-19 crisis? A checklist for the clinicians

text: • Telemedicine is recommended as an option for outpatients due to the COVID-19. • Epileptologists are required to immediately change their practice to telemedicine. • We have developed an eight-point telemedicine checklist for epilepsy care.


title: ORF8a of SARS-CoV forms an ion channel: Experiments and molecular dynamics simulations

text: Abstract ORF8a protein is 39 residues long and contains a single transmembrane domain. The protein is synthesized using solid phase peptide synthesis and reconstituted into artificial lipid bilayers that forms cation-selective ion channels with a main conductance level of 8.9±0.8pS at elevated temperature (38.5°C). Computational modeling studies including multi nanosecond molecular dynamics simulations in a hydrated POPC lipid bilayer are done with a 22 amino acid transmembrane helix to predict a putative homooligomeric helical bundle model. A structural model of a pentameric bundle is proposed with cysteines, serines and threonines facing the pore.


title: Timing and Tips for Total Hip Arthroplasty in a Critically Ill COVID-19 Patient with a Femoral Neck Fracture: A Case Report

text: Expedited time to surgery following hip fracture is associated with decreased morbidity and mortality in appropriately optimized patients. However, the optimal timing of surgery in patients with novel coronavirus disease 2019 (COVID-19) infection remains unknown. This case report describes a patient with COVID-19 pneumonia complicated by multi-organ system failure requiring intubation who sustained a femoral neck fracture that required total hip arthroplasty (THA). This patient had a significant, deliberate delay in time to surgical intervention due to his critical state. When deciding the optimal timing for THA in COVID-19 patients we recommend utilizing inflammatory markers, such as procalcitonin and IL-6, as indicators of disease resolution and caution operative intervention when patients are nearing the 7-10(th) day of COVID-19 symptoms. Furthermore, implant cementation and spinal anesthesia in critically ill COVID-positive patients should be approached cautiously in the setting of pulmonary disease and multi-organ system failure. Close follow-up with medical doctors is recommended to minimize long-term sequelae and delay to baseline mobility.


title: Hendra in the news: Public policy meets public morality in times of zoonotic uncertainty

text: Abstract Public discourses have influence on policymaking for emerging health issues. Media representations of unfolding events, scientific uncertainty, and real and perceived risks shape public acceptance of health policy and therefore policy outcomes. To characterize and track views in popular circulation on the causes, consequences and appropriate policy responses to the emergence of Hendra virus as a zoonotic risk, this study examines coverage of this issue in Australian mass media for the period 2007–2011. Results demonstrate the predominant explanation for the emergence of Hendra became the encroachment of flying fox populations on human settlement. Depictions of scientific uncertainty as to whom and what was at risk from Hendra virus promoted the view that flying foxes were a direct risk to human health. Descriptions of the best strategy to address Hendra have become polarized between recognized health authorities advocating individualized behaviour changes to limit risk exposure; versus populist calls for flying fox control and eradication. Less than a quarter of news reports describe the ecological determinants of emerging infectious disease or upstream policy solutions. Because flying foxes rather than horses were increasingly represented as the proximal source of human infection, existing policies of flying fox protection became equated with government inaction; the plight of those affected by flying foxes representative of a moral failure. These findings illustrate the potential for health communications for emerging infectious disease risks to become entangled in other political agendas, with implications for the public's likelihood of supporting public policy and risk management strategies that require behavioural change or seek to address the ecological drivers of incidence.


title: Clinical Trials and Novel Pathogens: Lessons Learned from SARS

text: During the recent global outbreak of severe acute respiratory syndrome (SARS), thousands of patients received treatments of uncertain efficacy and known toxicity such as ribavirin and corticosteroids. Despite this, no controlled clinical trials assessing the efficacy of these agents were conducted. If a second global SARS outbreak occurred, clinicians would not have controlled data on which to base therapeutic decisions. We discuss the unique methodologic and logistical challenges faced by researchers who attempt to conduct controlled trials of therapeutic agents during an outbreak of a novel or unknown infectious pathogen. We draw upon our own experience in attempting to conduct a randomized controlled trial (trial) of ribavirin therapy for SARS and discuss the lessons learned. Strategies to facilitate future clinical trials during outbreaks of unknown or novel pathogens are also presented.


Enhancing Thoracic Surgical Trainee Competence in the COVID-19 Era: Challenges and Opportunities for Mentorship


title: COVID-19 and rhinology: A look at the future

text: The novel Coronavirus (COVID-19) has created a deadly pandemic that is now significantly impacting the United States. Otolaryngologists are considered high risk for contracting disease, as the virus resides in the nasal cavity, nasopharynx, and oropharynx. While valuable work has been publicized regarding several topics in Rhinology, we discuss other aspects of our specialty in further detail. There are several issues regarding Rhinologic practice that need to be clarified both for the current epidemic as well as for future expected “waves.” In addition, as the pandemic dies down, guidelines are needed to optimize safe practices as we start seeing more patients again. These include protocols pertinent to safety, in-office Rhinologic procedures, the substitution of imaging for endoscopy, and understanding the appropriate role of telemedicine. We discuss these aspects of Rhinology as well as practical concerns relating to telemedicine and billing, as these issues take on increasing importance for Rhinologists both in the present and the future.


title: Identifcation of differentially expressed long non-coding RNAs in CD4+ T cells response to latent tuberculosis infection

text: Summary Objective To identify differentially expressed long non-coding RNAs (lncRNAs) in CD4+ T cells triggered upon latent tuberculosis (TB) infection. Methods Expression profiles of lncRNAs and mRNAs in CD4+ T cells from individuals with latent TB infection (LTBI), active TB and healthy controls were analyzed by microarray assay and four lncRNAs were selected for validation using real time-quantitative polymerase chain reaction (RT-qPCR). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway based approaches were used to investigate biological functions and signaling pathways affected by the differentially expressed mRNAs. Results LncRNAs and mRNAs in CD4+ T cells were involved in LTBI and active TB disease. Compared with healthy controls, 449 lncRNAs and 461 mRNAs were deregulated in LTBI group, 1,113 lncRNAs and 1,490 mRNAs were deregulated in active TB group, as well as 163 lncRNAs and 187 mRNAs were differentially expressed in both LTBI and active TB group. It was worth noting that 41 lncRNAs and 60 mRNAs were deregulated between three groups. Most deregulated lncRNAs were from intergenic regions (∼50%), natural antisense to protein-coding loci (∼20%), or intronic antisense to protein-coding loci (∼10%). Significantly enriched signaling pathways based on deregulated mRNAs were mainly involved in mitogen-activated protein kinase (MAPK) signaling pathway, cytokine–cytokine receptor interaction, Toll-like receptor signaling pathway, etc. Conclusions The study was the first report of differentially expressed lncRNAs in CD4+ T cells response to TB infection and indicated that some lncRNAs may be involved in regulating host immune response to TB infection. Future studies are needed to further elucidate potential roles of these deregulated lncRNAs in LTBI and its reactivation.


title: SARS‐COV‐2 and infectivity: Possible increase in infectivity associated to integrin motif expression

text: SARS-COV2 represents the causal agent of a potentially fatal disease (COVID-19) that is actually of great global public health concern. SARS-COV2 has diffused throughout the world surprisingly fast demonstrating a far greater infectivity than previously known human coronaviruses and it is also responsible for an unusual high variety of symptoms in affected patients. This article is protected by copyright. All rights reserved.


Letter to the Editor concerning A study on infectivity of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) carriers by Gao et al


title: Pulmonary embolism in hospitalised patients with COVID-19

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is characterised by dyspnoea and abnormal coagulation parameters, including raised D-dimer. Data suggests a high incidence of pulmonary embolism (PE) in ventilated patients with COVID-19. OBJECTIVES: To determine the incidence of PE in hospitalised patients with COVID-19 and the diagnostic yield of Computer Tomography Pulmonary Angiography (CTPA) for PE. We also examined the utility of D-dimer and conventional pre-test probability for diagnosis of PE in COVID-19. PATIENTS/METHODS: Retrospective review of single-centre data of all CTPA studies in patients with suspected or confirmed COVID-19 identified from Electronic Patient Records (EPR). RESULTS: There were 1477 patients admitted with COVID-19 and 214 CTPA scans performed, of which n = 180 (84%) were requested outside of critical care. The diagnostic yield for PE was 37%. The overall proportion of PE in patients with COVID-19 was 5.4%. The proportions with Wells score of ≥4 (‘PE likely’) was 33/134 (25%) without PE vs 20/80 (25%) with PE (P = 0.951). The median National Early Warning-2 (NEWS2) score (illness severity) was 5 (interquartile range [IQR] 3–9) in PE group vs 4 (IQR 2–7) in those without PE (P = 0.133). D-dimer was higher in PE (median 8000 ng/mL; IQR 4665–8000 ng/mL) than non-PE (2060 ng/mL, IQR 1210–4410 ng/mL, P < 0.001). In the ‘low probability’ group, D-dimer was higher (P < 0.001) in those with PE but had a limited role in excluding PE. CONCLUSIONS: Even outside of the critical care environment, PE in hospitalised patients with COVID-19 is common. Of note, approaching half of PE events were diagnosed on hospital admission. More data are needed to identify an optimal diagnostic pathway in patients with COVID-19. Randomised controlled trials of intensified thromboprophylaxis are urgently needed.


title: What do we know about remdesivir drug interactions?

text: The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS‐Co‐V‐2) has resulted in a critical need to rapidly develop new pharmacologic interventions and disseminate information. This has led to confusing and conflicting information on drug efficacy. Remdesivir has emerged as a promising treatment for SARS‐Co‐V‐2 infection yet published clinical pharmacology and drug interaction studies are limited. Additional studies of the disposition of remdesivir, its active metabolite (GS‐441524), and its triphosphate metabolite (GS‐443902) are needed.


docid: ajqbljai

title: Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington

text: BACKGROUND: Long-term care facilities are high-risk settings for severe outcomes from outbreaks of Covid-19, owing to both the advanced age and frequent chronic underlying health conditions of the residents and the movement of health care personnel among facilities in a region. METHODS: After identification on February 28, 2020, of a confirmed case of Covid-19 in a skilled nursing facility in King County, Washington, Public Health–Seattle and King County, aided by the Centers for Disease Control and Prevention, launched a case investigation, contact tracing, quarantine of exposed persons, isolation of confirmed and suspected cases, and on-site enhancement of infection prevention and control. RESULTS: As of March 18, a total of 167 confirmed cases of Covid-19 affecting 101 residents, 50 health care personnel, and 16 visitors were found to be epidemiologically linked to the facility. Most cases among residents included respiratory illness consistent with Covid-19; however, in 7 residents no symptoms were documented. Hospitalization rates for facility residents, visitors, and staff were 54.5%, 50.0%, and 6.0%, respectively. The case fatality rate for residents was 33.7% (34 of 101). As of March 18, a total of 30 long-term care facilities with at least one confirmed case of Covid-19 had been identified in King County. CONCLUSIONS: In the context of rapidly escalating Covid-19 outbreaks, proactive steps by long-term care facilities to identify and exclude potentially infected staff and visitors, actively monitor for potentially infected patients, and implement appropriate infection prevention and control measures are needed to prevent the introduction of Covid-19.


COVID-19 et cancers. Synthèse des recommandations des sociétés savantes françaises et évolutions de celles-ci