title: Acute Exacerbation of Idiopathic Pulmonary Fibrosis

text: Abstract Acute exacerbation is a major cause of morbidity and mortality in patients with idiopathic pulmonary fibrosis. Although the real nature of it is still not clear and there is no proven effective therapy, progress has been made since the consensus definition and diagnostic criteria were proposed. The trial results of several new innovative therapies in idiopathic pulmonary fibrosis have suggested a potential for benefit in acute exacerbation of idiopathic pulmonary fibrosis, leading to double blind randomized clinical trials in this area. This article reviews the present knowledge on acute exacerbation of idiopathic pulmonary fibrosis, focusing on the triggering factors and treatment.


title: Potential Beneficial Actions of Fucoidan in Brain and Liver Injury, Disease, and Intoxication—Potential Implication of Sirtuins

text: Increased interest in natural antioxidants has brought to light the fucoidans (sulfated polysaccharides present in brown marine algae) as highly valued nutrients as well as effective and safe therapeutics against several diseases. Based on their satisfactory in vitro antioxidant potency, researchers have identified this molecule as an efficient remedy for neuropathological as well as metabolic disorders. Some of this therapeutic activity is accomplished by upregulation of cytoprotective molecular pathways capable of restoring the enzymatic antioxidant activity and normal mitochondrial functions. Sirtuin-3 has been discovered as a key player for achieving the neuroprotective role of fucoidan by managing these pathways, whose ultimate goal is retrieving the entirety of the antioxidant response and preventing apoptosis of neurons, thereby averting neurodegeneration and brain injuries. Another pathway whereby fucoidan exerts neuroprotective capabilities is by interactions with P-selectin on endothelial cells, thereby preventing macrophages from entering the brain proper. Furthermore, beneficial influences of fucoidan have been established in hepatocytes after xenobiotic induced liver injury by decreasing transaminase leakage and autophagy as well as obtaining optimal levels of intracellular fiber, which ultimately prevents fibrosis. The hepatoprotective role of this marine polysaccharide also includes a sirtuin, namely sirtuin-1 overexpression, which alleviates obesity and insulin resistance through suppression of hyperglycemia, reducing inflammation and stimulation of enzymatic antioxidant response. While fucoidan is very effective in animal models for brain injury and neuronal degeneration, in general, it is accepted that fucoidan shows somewhat limited potency in liver. Thus far, it has been used in large doses for treatment of acute liver injuries. Thus, it appears that further optimization of fucoidan derivatives may establish enhanced versatility for treatments of various disorders, in addition to brain injury and disease.


title: EAACI position statement on asthma exacerbations and severe asthma

text: Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult‐to‐treat asthma and severe treatment‐resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment‐resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult‐to‐control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult‐to‐control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.


title: Polmoniti nosocomiali acquisite sotto ventilazione meccanica

text: Le polmoniti sono la prima causa di infezione nosocomiale in rianimazione. Le polmoniti nosocomiali acquisite sotto ventilazione meccanica (PNAVM) compaiono dopo almeno 48 ore di ventilazione meccanica invasiva. Il loro meccanismo è multifattoriale, ma predomina la nozione di inalazione che compare dopo una colonizzazione orofaringea, gastrica o tracheale. Il tempo di comparsa permette di classificare queste PNAVM come precoci o tardive a seconda che compaiano prima o dopo il 5° giorno di ventilazione meccanica. La diagnosi può essere aiutata dalla clinica, essenzialmente grazie al punteggio CPIS (Clinical Pulmonary Infection Score), e dal lavaggio broncoalveolare (BAL), che sembra l’esame più utile per la diagnosi microbiologica. La diagnosi differenziale con una pneumopatia non batterica o anche non infettiva (neoplastica, infiammatoria, fibrotica) o la ricerca di un altro focolaio infettivo devono sempre essere discusse in funzione dell’orientamento clinico iniziale o del fallimento della terapia antibiotica. Il ricorso preferenziale alla ventilazione non invasiva, quando possibile, sembra utile per prevenire l’insorgenza di una pneumopatia nosocomiale. La posizione semiseduta del paziente a 30–45° è la sola misura profilattica veramente validata di prevenzione delle PNAVM. Il trattamento curativo delle polmoniti batteriche si basa in genere su una doppia terapia antibiotica. Quest’ultima può essere orientata dai dati di prelievi non invasivi, come le aspirazioni tracheali, realizzate in modo periodico e sistematico. La durata del trattamento è discussa, ma gli ultimi dati sono in favore di una terapia antibiotica relativamente breve, di 8 giorni.


docid: jjjxoszj

title: Global infectious diseases—The new norm for the United States?


title: Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review

text: Essential oils are complex mixtures isolated from aromatic plants which may possess antioxidant and anti-inflammatory activities of interest in thye food and cosmetic industries as well as in the human health field. In this work, a review was done on the most recent publications concerning their antioxidant and anti-inflammatory activities. At the same time a survey of the methods generally used for the evaluation of antioxidant activity and some of the mechanisms involved in the anti-inflammatory activities of essential oils are also reported.


title: Managing haematology and oncology patients during the COVID‐19 pandemic: interim consensus guidance

text: INTRODUCTION: A pandemic coronavirus, SARS‐CoV‐2, causes COVID‐19, a potentially life‐threatening respiratory disease. Patients with cancer may have compromised immunity due to their malignancy and/or treatment, and may be at elevated risk of severe COVID‐19. Community transmission of COVID‐19 could overwhelm health care services, compromising delivery of cancer care. This interim consensus guidance provides advice for clinicians managing patients with cancer during the pandemic. MAIN RECOMMENDATIONS: During the COVID‐19 pandemic: In patients with cancer with fever and/or respiratory symptoms, consider causes in addition to COVID‐19, including other infections and therapy‐related pneumonitis. For suspected or confirmed COVID‐19, discuss temporary cessation of cancer therapy with a relevant specialist. Provide information on COVID‐19 for patients and carers. Adopt measures within cancer centres to reduce risk of nosocomial SARS‐CoV‐2 acquisition; support population‐wide social distancing; reduce demand on acute services; ensure adequate staffing; and provide culturally safe care. Measures should be equitable, transparent and proportionate to the COVID‐19 threat. Consider the risks and benefits of modifying cancer therapies due to COVID‐19. Communicate treatment modifications, and review once health service capacity allows. Consider potential impacts of COVID‐19 on the blood supply and availability of stem cell donors. Discuss and document goals of care, and involve palliative care services in contingency planning. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This interim consensus guidance provides a framework for clinicians managing patients with cancer during the COVID‐19 pandemic. In view of the rapidly changing situation, clinicians must also monitor national, state, local and institutional policies, which will take precedence. ENDORSED BY: Australasian Leukaemia and Lymphoma Group; Australasian Lung Cancer Trials Group; Australian and New Zealand Children's Haematology/Oncology Group; Australia and New Zealand Society of Palliative Medicine; Australasian Society for Infectious Diseases; Bone Marrow Transplantation Society of Australia and New Zealand; Cancer Council Australia; Cancer Nurses Society of Australia; Cancer Society of New Zealand; Clinical Oncology Society of Australia; Haematology Society of Australia and New Zealand; National Centre for Infections in Cancer; New Zealand Cancer Control Agency; New Zealand Society for Oncology; and Palliative Care Australia.


docid: gbmjuhgv

title: The cellular protein nucleolin preferentially binds long-looped G-quadruplex nucleic acids()

text: BACKGROUND: G-quadruplexes (G4s) are four-stranded nucleic acid structures that form in G-rich sequences. Nucleolin (NCL) is a cellular protein reported for its functions upon G4 recognition, such as induction of neurodegenerative diseases, tumor and virus mechanisms activation. We here aimed at defining NCL/G4 binding determinants. METHODS: Electrophoresis mobility shift assay was used to detect NCL/G4 binding; circular dichroism to assess G4 folding, topology and stability; dimethylsulfate footprinting to detect G bases involved in G4 folding. RESULTS: The purified full-length human NCL was initially tested on telomeric G4 target sequences to allow for modulation of loop, conformation, length, G-tract number, stability. G4s in promoter regions with more complex sequences were next employed. We found that NCL binding to G4s heavily relies on G4 loop length, independently of the conformation and oligonucleotide/loop sequence. Low stability G4s are preferred. When alternative G4 conformations are possible, those with longer loops are preferred upon binding to NCL, even if G-tracts need to be spared from G4 folding. CONCLUSIONS: Our data provide insight into how G4s and the associated proteins may control the ON/OFF molecular switch to several pathological processes, including neurodegeneration, tumor and virus activation. Understanding these regulatory determinants is the first step towards the development of targeted therapies. GENERAL SIGNIFICANCE: The indication that NCL binding preferentially stimulates and induces folding of G4s containing long loops suggests NCL ability to modify the overall structure and steric hindrance of the involved nucleic acid regions. This protein-induced modification of the G4 structure may represent a cellular mechanosensor mechanism to molecular signaling and disease pathogenesis. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.


title: Reduction of porcine reproductive and respiratory syndrome virus (PRRSV) infection in swine alveolar macrophages by porcine circovirus 2 (PCV2)-induced interferon-alpha

text: Abstract Two common viral pathogens of swine, namely, porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV), were investigated in regard to their effects on monolayer cultures of swine alveolar macrophages (AMs). The purpose was to identify selected cellular changes and responses potentially associated with the clinical reactions of pigs infected with either or both of these viruses. Measurements included the (1) absolute and relative numbers of infected, viable, and apoptotic cells; (2) distribution of viral antigens; (3) levels of interferon-alpha (IFN-α) and tumor necrosis factor-alpha (TNF-α) produced and their association with the extent of virus-induced cytopathology. Four groups of AMs were studied, including mock-infected, PCV2 alone-infected (PCV2-A), PRRSV alone-infected (PRRSV-A), and PCV2 and PRRSV dually infected (PCV2/PRRSV) groups. The AMs of PCV2-A group had high antigen-containing rate without cell death. There was a marked increase in cell death and apoptosis in PRRSV-A group. However, a lower PRRSV-induced infectious rate, cell death, and apoptosis were seen in PCV2/PRRSV group. High levels of IFN-α production were detected in PCV2-infected groups, but not in mock-infected and PRRSV-A groups. The PRRSV-induced cytopathic effect (CPE) on MARC-145 cells or swine AMs was markedly reduced by pre-incubation of the cells with UV-treated or non-UV-treated supernatants of PCV2-infected AMs. In addition, the reduction in CPE was abolished when the supernatants of PCV2-infected AMs were pre-treated with a mouse anti-recombinant porcine IFN-α antibody. The results suggest that swine AMs were an important reservoir of PCV2; PCV2 infection reduced PRRSV infection and PRRSV-associated CPE in PCV2/PRRSV AMs; the reduction of PRRSV infection in AMs was mediated by IFN-α generated by PCV2 infection. The reduced PRRSV-associated CPE in AMs and increased pro-inflammatory cytokine production may lead to a more severe pneumonic lesion in those dually infected pigs.


title: Construction of recombinant Lactobacillus casei efficiently surface displayed and secreted porcine parvovirus VP2 protein and comparison of the immune responses induced by oral immunization

text: Lactobacillus casei ATCC 393 was selected as a bacterial carrier for the development of mucosal vaccine against porcine parvovirus (PPV) infection. The PPV major structural polypeptide VP2 was used as the model parvovirus antigen. Two inducible expression systems, namely pPG611.1 of the cell-surface expression system and pPG612.1 of the secretion expression system based on the xylose operon promoter were used to express the VP2 protein. The immunogenicity of recombinant strains producing VP2 protein in two cellular locations, cell-surface exposed and secreted, was compared to each other by immunizing mice through the intragastric administration. The two types of constructs were able to induce strong specific immune responses against VP2 via intragastric administration and maximum titres of IgA and IgG were attained on days 46 post oral immunization, while the highest antibody levels were obtained with the strain producing the VP2 protein in extracellular milieu. The induced antibodies demonstrated neutralizing effects on PPV infection.


title: Map location of lactate dehydrogenase-elevating virus (LDV) capsid protein (Vpl) gene

text: Abstract Lactate dehydrogenase-elevating virus (LDV) is currently classified within the Togaviridae family. In an effort to obtain further information on the characteristics of this virus, we have begun to sequence the viral RNA genome and to map the virion structural protein genes. A sequence of 1064 nucleotides, which represents the 3′ terminal end of the genome, was obtained from LDV cDNA clones. A 3′ noncoding region of 80 nucleotides followed by two complete open reading frames (ORFs) were found within this sequence. The two ORFs were in different reading frames and overlapped each other by 11 nucleotides. One ORF encoded a protein of 170 amino acids and the other ORF, located adjacent to the 3′ noncoding region of the viral genome, encoded a 114 amino acid protein. Thirty-three N-terminal residues were sequenced directly from purified LDV capsid protein, Vpi, and this amino acid sequence mapped to the ORF adjacent to the 3′ noncoding region. The presence of overlapping ORFs and the 3′ terminal map position of Vpi indicate that LDV differs significantly from the prototype alpha togaviruses.


title: Photosensitizing potential of tailored magnetite hybrid nanoparticles functionalized with levan and zinc (II) phthalocyanine

text: Abstract Phototherapies, including photodynamic therapy (PDT), have been widely used in the treatment of various diseases, especially for cancer. However, there is still a lack of effective, safe photosensitizers that would be well tolerated by patients. The combination of several methods (like phototherapy and hyperthermia) constitutes a modern therapeutic approach, which demands new materials based on components that are non-toxic without irradiation. Therefore, this study presents the synthesis and properties of novel, advanced nanomaterials in which the advantage features of the magnetic nanoparticles and photoactive compounds were combined. The primary purpose of this work was the synthesis of magnetic nanoparticles coated with biocompatible and antitumor polysaccharide - levan, previously unknown from scientific literature, and the deposition of potent photosensitizer – zinc(II) phthalocyanine on their surface. In order to better characterize the nature of the coating covering the magnetic core, the atomic force microscope analysis, a contact angle measurement, and the mechanical properties of pure levan and its blend with zinc(II) phthalocyanine films were investigated. This magnetic nanomaterial revealed the ability to generate singlet oxygen upon exposure to light. Finally, preliminary toxicity of obtained nanoparticles was tested using the Microtox® test – with and without irradiation.


title: From Orange Juice By-Product in the Food Industry to a Functional Ingredient: Application in the Circular Economy

text: In the orange juice industry, more than 50% of raw material becomes by-products that are rich in active compounds and have high nutritional content. Improved use of these by-products could represent a key strategy for a circular economy. The objective of this study was to produce a flour from orange juice by-product, characterize it, and then apply this flour to produce cookies. Orange by-product flour (OBPF) was characterized in terms of its chemical composition, dietary fiber, phenolic compounds, antioxidant potential, and hygroscopic properties. Subsequently, the effect of substituting wheat flour by OBPF in cookies was evaluated. OBPF presented a very high content of dietary fiber (73.61% dry matter (DM)), minerals (ash = 2.72% DM), and total phenolic compounds (534 ± 30 mg gallic acid equivalent (GAE)/100 g of DM). In general, the properties of cookies were not significantly influenced by using OBPF as a substitution for wheat flour. Sensorial analyses showed that cookies produced with 10% OBPF presented the higher scores. Therefore, OBPF showed interesting characteristics, suggesting its possible use in the development of fiber enriched foods such as cookies; and its production represents a key strategy for the orange juice processing industries towards the application of a circular economy in the food system.


title: Smell and taste disorders during COVID‐19 outbreak: A cross‐sectional study on 355 patients

text: BACKGROUND: As reported by increasing literature, a significant number of patients with SARS‐CoV‐2 infection developed smell/taste disorders. Aim of this study is to determine the prevalence and severity of these symptoms among laboratory‐confirmed SARS‐CoV‐2 patients. Secondary objective is to determine their onset/recovery time. METHODS: This cross‐sectional study was conducted from March 10 to 30, 2020 at Novara University Hospital during the COVID‐19 Italian outbreak. The 355 enrolled patients answered a questionnaire at 14th (or more) days after proven infection. RESULTS: The overall population prevalence of both smell/taste or one of the two disorders was 70%. They were first symptoms in 31 (8,7%) patients. Most patients reported a complete loss that in half of the cases (49.5%) was fully recovered after 14 days, with a median recovery time of 10 days. CONCLUSION: This study confirms a high prevalence of smell/taste disorders in COVID‐19 infection with self‐recovery for half cases after about 2 weeks.


Opportunities for Nursing Science to Advance Patient Care in the Time of COVID‐19: A Palliative Care Perspective


title: Manipulation of Intestinal Antiviral Innate Immunity and Immune Evasion Strategies of Porcine Epidemic Diarrhea Virus

text: Porcine epidemic diarrhea virus (PEDV) infection causes watery diarrhea, dehydration, and high mortality in neonatal pigs, due to its clinical pathogenesis of the intestinal mucosal barrier dysfunction. The host's innate immune system is the first line of defence upon virus invasion of the small intestinal epithelial cells. In turn, the virus has evolved to modulate the host's innate immunity during infection, resulting in pathogen virulence, survival, and the establishment of successful infection. In this review, we gather current knowledge concerning the interplay between PEDV and components of host innate immunity, focusing on the role of cytokines and interferons in intestinal antiviral innate immunity, and the mechanisms underlying the immune evasion strategies of PEDV invasion. Finally, we provide some perspectives on the potential prevention and treatment for PEDV infection.


Second isirv antiviral group conference: overview


Heart failure management during COVID‐19 outbreak in Italy. Telemedicine experience from a heart failure university tertiary referral centre


title: Brief report: International perspectives on the pediatric COVID‐19 experience

text: The 2019 novel coronavirus (SARS‐CoV‐2) is endangering human health worldwide; scarcity of published pediatric cases and current literature and the absence of evidence‐based guidelines necessitate international sharing of experience and personal communication. On 31 March 2020 the International Committee of the American Thoracic Society Pediatrics Assembly recorded an online podcast, during which pediatric pulmonologists worldwide shared their experience on the novel coronavirus disease (COVID‐19) in children. The aim was to share personal experience in organizing pediatric care in different health care settings globally, protecting health care workers, and isolation practices. This manuscript summarizes the common themes of the podcast which centered around three main topics: more benign clinical disease and progression in pediatric cases compared to adults, a strong need for strategies to protect health care workers, and social or economic disparities as a barrier to successful pandemic control.


title: Molecular epidemiology of rubella viruses involved in congenital rubella infections in São Paulo, Brazil, between 1996 and 2009

text: Rubella virus (RV) infection during the early stages of pregnancy can lead to serious birth defects, known as congenital rubella syndrome (CRS). This retrospective study was conducted between 1996 and 2009 with surveillance specimens collected from patients suspected of congenital rubella infection (CRI) and CRS. The clinical samples (nine amminiotic fluid, eight urine, eight blood, one conception product, and one placenta) were sent for viral isolation and genotyping. Twenty‐seven sequences were analysed and four genotypes (1a, 1B, 1G, and 2B) were identified in São Paulo that were involved in congenital infection. To our knowledge, this study is the first report that describes genetic diversity of the circulating rubella strains involved in CRI. J Med. Virol. 85:2034–2041, 2013. © 2013 Wiley Periodicals, Inc.


docid: tgowzrqo

title: Detection of the nucleocapsid protein of severe acute respiratory syndrome coronavirus in serum: Comparison with results of other viral markers

text: Abstract A capture enzyme-enhanced chemiluminescence immunoassay (ECLIA) based on three specific monoclonal antibodies to detect the nucleocapsid (N) protein of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in the serial serum samples from SARS patients was developed. The anti-SARS-CoV IgG and the viral RNA were also detected in the sera by ELISA and RT-PCR, respectively. During the first 10 days after onset, anti-SARS-CoV IgG, SARS-CoV RNA and the N protein were detected in 21.4, 42.9, and 90% of the patients’ sera, respectively. The detection rate of the N protein during days 11–15 of the disease was still significantly higher than those of anti-SARS-CoV IgG and SARS-CoV RNA. The data demonstrated that detection of the N protein with the capture ECLIA appears to be more useful than detection of other viral makers for rapid diagnosis of SARS in patients.


title: No Effect of a Homeopathic Preparation on Neonatal Calf Diarrhoea in a Randomised Double-Blind, Placebo-Controlled Clinical Trial

text: A double-blind, placebo-controlled clinical trial of a homeopathic treatment of neonatal calf diarrhoea was performed using 44 calves in 12 dairy herds. Calves with spontaneously derived diarrhoea were treated with either the homeopathic remedy Podophyllum (D30) (n = 24) or a placebo (n = 20). No clinically or statistically significant difference between the 2 groups was demonstrated. Calves treated with Podophyllum had an average of 3.1 days of diarrhoea compared with 2.9 days for the placebo group. Depression, inappetence and fever were presented equally in the 2 groups. These results support the widely held opinion that scientific proof for the efficacy of veterinary homeopathy is lacking. In the European Union this implies a considerable risk for animal welfare, since in some countries priority is given to homeopathic treatments in organic farming.


Infection control in countries with limited resources


title: The N-terminal heptad repeat region of reovirus cell attachment protein σ1 is responsible for σ1 oligomer stability and possesses intrinsic oligomerization function

text: Abstract The oligomerization domain of the reovirus cell attachment protein (σ1) was probed using the type 3 reovirus of synthesized in vitro. Trypsin cleaved the α1 protein (49K molecular weight) approximately in the middle and yielded a 26K N-terminal fragment and a 23K C-terminal fragment. Under conditions which allowed for the identification of intact σ1 in the oligomeric form (∼200K) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the N-terminal 26K fragment was found to exist as stable trimers (80K) and, to a less extent, as dimers (54K), whereas the C-terminal fragment remained in the monomeric form. A polypeptide (161 amino acids) containing the N-terminal heptad repeat region synthesized in vitro was capable of forming stable dimers and trimers. Using various criteria, we demonstrated that the stability of the intact σ1 oligomer is conferred mainly by the N-terminal heptad repeat region. Our results are summarized in a model in which individual heptad repeats are held together in a three-stranded α-helical coiled-coil structure via both hydrophobic and electrostatic interactions.


title: The development of vaccines against SARS corona virus in mice and SCID-PBL/hu mice

text: We have investigated to develop novel vaccines against SARS CoV using cDNA constructs encoding the structural antigen; spike protein (S), membrane protein (M), envelope protein (E), or nucleocapsid (N) protein, derived from SARS CoV. Mice vaccinated with SARS-N or -M DNA using pcDNA 3.1(+) plasmid vector showed T cell immune responses (CTL induction and proliferation) against N or M protein, respectively. CTL responses were also detected to SARS DNA-transfected type II alveolar epithelial cells (T7 cell clone), which are thought to be initial target cells for SARS virus infection in human. To determine whether these DNA vaccines could induce T cell immune responses in humans as well as in mice, SCID-PBL/hu mice was immunized with these DNA vaccines. As expected, virus-specific CTL responses and T cell proliferation were induced from human T cells. SARS-N and SARS-M DNA vaccines and SCID-PBL/hu mouse model will be important in the development of protective vaccines.


Monitor sewage to track spread of the coronavirus


title: A 72-Year-Old Woman With Respiratory Failure and Bilateral Ground-Glass Opacities

text: A 72-year-old woman with diabetes mellitus was admitted to our hospital because of dyspnea on exertion. Sputum cytologic evaluation revealed intranuclear inclusion bodies in the cells; we therefore considered viral pneumonia and performed a bronchoscopy. The bronchial washing fluid was positive for immunoperoxidase staining of herpes simplex virus type 1 (HSV1) and HSV1 polymerase chain reaction. The patient was diagnosed as having pneumonia due to HSV1 and was successfully treated with acyclovir.


title: Potential roles of social distancing in mitigating the spread of coronavirus disease 2019 (COVID-19) in South Korea

text: On January 20, 2020, the first COVID-19 case was confirmed in South Korea. After a rapid outbreak, the number of incident cases has been consistently decreasing since early March; this decrease has been widely attributed to its intensive testing. We report here on the likely role of social distancing in reducing transmission in South Korea. Our analysis suggests that transmission may still be persisting in some regions.


title: Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth

text: Porcine epidemic diarrhea virus (PEDV) replicates in the cytoplasm of infected cells, but its nucleocapsid (N) protein localizes specifically to the nucleolus. The mechanism of nuclear translocation, and whether N protein associates with particular nucleolar components, is unknown. In this study, we confirm that a nucleolar phosphoprotein nucleophosmin (NPM1) interacts and co-localizes with the N protein in the nucleolus. In vitro binding studies indicated that aa 148–294 of N and aa 118–188 of NPM1 were required for binding. Interestingly, N protein importation into the nucleolus is independent of the ability of NPM1 to shuttle between the nucleus and the cytoplasm. Furthermore, overexpression of NPM1 promoted PEDV growth, while knockdown of NPM1 suppressed PEDV growth. In addition, binding of N protein to NPM1 protects it from proteolytic degradation by caspase-3, leading to increased cell survival. Taken together, our studies demonstrate a specific interaction of the N protein with the host cell protein NPM1 in the nucleolus. The results suggest potential linkages among viral strategies for the regulation of cell survival activities, possibly through an interaction of N protein with NPM1 which prevents its proteolytic cleavage and enhances cell survival, thus ultimately promoting the replication of PEDV.


title: Evaluation of multiple ancillary therapies used in combination with an antimicrobial in newly received high-risk calves treated for bovine respiratory disease

text: Ancillary therapy (ANC) is commonly provided in conjunction with an antimicrobial when treating calves for suspected bovine respiratory disease (BRD) in an attempt to improve the response to a suspected BRD challenge. The first experiment evaluated the effects of 3 ANC in combination with an antimicrobial in high-risk calves treated for BRD during a 56-d receiving period. Newly received crossbred steers (n = 516; initial BW = 217 ± 20 kg) were monitored by trained personnel for clinical signs of BRD. Calves that met antimicrobial treatment criteria (n = 320) were then randomly assigned to experimental ANC treatment (80 steers/experimental ANC treatment): intravenous flunixin meglumine injection (NSAID), intranasal viral vaccination (VACC), intramuscular vitamin C injection (VITC), or no ANC (NOAC). Animal served as the experimental unit for all variables except DMI and G:F (pen served as the experimental unit for DMI and G:F). Within calves treated 3 times for BRD, those receiving NOAC had lower (P < 0.01) clinical severity scores (severity scores ranged from 0 to 4 on the basis of observed clinical signs and severity) and heavier (P = 0.01) BW than those receiving NSAID, VACC, or VITC at the time of third treatment. Between the second and third BRD treatments, calves receiving NOAC had decreased (P < 0.01) daily BW loss (−0.13 kg ADG) compared with those receiving NSAID, VACC, or VITC (−1.30, −1.90, and −1.41 kg ADG, respectively). There were no differences in rectal temperature, combined mortalities and removals, or overall performance among the experimental ANC treatments. Overall, morbidity and mortality attributed to BRD across treatments were 66.5% and 13.2%, respectively. After the receiving period, a subset of calves (n = 126) were allocated to finishing pens to evaluate the effects ANC administration on finishing performance, carcass characteristics, and lung scores at harvest. Ultrasound estimates, BW, and visual appraisal were used to target a common physiological end point for each pen of calves. There were no differences among the experimental ANC observed during the finishing period (P ≥ 0.11). In summary, the use of NSAID, VACC, and VITC do not appear to positively impact clinical health and could potentially be detrimental to performance during the receiving period in high-risk calves receiving antimicrobial treatment for suspected BRD.


Quantifying examination distance in ophthalmic assessments


title: A Contemporary Review of Neurological Sequelae of COVID-19

text: Coronavirus 2019 (COVID-19) is currently the center of what has become a public health crisis. While the virus is well-known for its trademark effects on respiratory function, neurological damage has been reported to affect a considerable proportion of severe cases. To characterize the neuro-invasive potential of this disease, a contemporary review of COVID-19 and its neurological sequelae was conducted using the limited, but growing, literature that is available. These neurological squeal are based on the manifestations that the virus has on normal central and peripheral nervous system function. The authors present the virology of the SARS-CoV-2 agent by analyzing its classification as an enveloped, positive-stranded RNA virus. A comprehensive timeline is then presented, indicating the progression of the disease as a public health threat. Furthermore, underlying chronic neurological conditions potentially lead to more adverse cases of COVID-19. SARS-CoV-2 may reach ACE2 receptors on neuronal tissue through mode of the general circulation. The CNS may also be susceptible to an immune response where a “cytokine storm” can manifest into neural injury. Histological evidence is provided, while symptoms such as headache and vertigo are highlighted as CNS manifestations of COVID-19. Treatment of these symptoms is addressed with paracetamol being recommended as a possible, but not conclusive, treatment to some CNS symptoms. The authors then discuss the peripheral nervous system sequelae and COVID's impact on causing chemosensory dysfunction starting with viral attack on olfactory sensory neurons and cells types within the lining of the nose. Histological evidence is also provided while symptoms such as anosmia and ageusia are characterized as PNS manifestations. Possible treatment options for these symptoms are then addressed as a major limitation, as anecdotal, and not conclusive evidence can be made. Finally, preventive measures of the neurological sequelae are addressed using a multidirectional approach. Postmortem examinations of the brains of COVID-19 patients are suggested as being a possible key to formulating new understandings of its neuropathology. Lastly, the authors suggest a more comprehensive neurological follow-up of recovered patients, in order to better characterize the neurological sequelae of this illness.


title: Nurses' willingness to take care of people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) — does a teaching intervention make a difference?

text: The aim of this study is to describe the impact of an education intervention programme on nurses' willingness to care for HIV-positive people in Lithuania. METHODS: The study utilizes a randomized controlled trial design (RCT). The total sample comprises 185 nurses working in medical, surgical and gynaecological units, and primary health care centres from the same hospital areas in three Lithuanian hospitals. The data were analyzed using SPSS 12.0 and descriptive statistics. FINDINGS: Our educational intervention did not have an impact on the nurses' willingness to take care of people living with HIV (PLHIV), as their level of willingness was high already before the education intervention. CONCLUSIONS: Further research on this issue is needed to try to understand the forces acting on our nursing staff in order to ensure appropriate care for PLHIV.


title: Home and Community-Based Physical Therapist Management of Adults With Post–Intensive Care Syndrome

text: More than 4 million adults survive a stay in the intensive care unit each year, with many experiencing new or worsening physical disability, mental health problems, and/or cognitive impairments, known as the post-intensive care syndrome (PICS). Given the prevalence and magnitude of physical impairments after critical illness, many survivors, including those recovering from COVID-19, could benefit from physical therapist services after hospital discharge. However, due to the relatively recent recognition and characterization of PICS, there may be limited awareness and understanding of PICS among physical therapists practicing in home healthcare and community-based settings. This lack of awareness may lead to inappropriate and/or inadequate rehabilitation service provision. While this perspective article provides information relevant to all physical therapists, it is aimed toward those providing rehabilitation services outside of the acute and post-acute inpatient settings. This article reports the prevalence and clinical presentation of PICS and provides recommendations for physical examination and outcomes measures, plan of care, and intervention strategies. The importance of providing patient and family education, coordinating community resources including referring to other healthcare team members, and community-based rehabilitation service options is emphasized. Finally, this perspective article discusses current challenges for optimizing outcomes for people with PICS and suggests future directions for research and practice.


title: Combining genetic and biochemical approaches to identify functional molecular contact points

text: Protein-protein interactions are required for many viral and cellular functions and are potential targets for novel therapies. Here we detail a series of genetic and biochemical techniques used in combination to find an essential molecular contact point on the duck hepatitis B virus polymerase. These techniques include differential immunoprecipitation, mutagenesis and peptide competition. The strength of these techniques is their ability to identify contact points on intact proteins or protein complexes employing functional assays. This approach can be used to aid identification of putative binding sites on proteins and protein complexes which are resistant to characterization by other methods.


title: Enhanced expression of TGFβ protein in lymphoid organs and lung, but not in serum, of pigs infected with a European field isolate of porcine reproductive and respiratory syndrome virus

text: Abstract Transforming growth factor β (TGFβ) is an immunomodulatory cytokine which is able to modulate the host immune response eliciting an inefficient response against pathogens. In this sense, the role of this cytokine in porcine reproductive and respiratory syndrome (PRRS) has been poorly studied and the reported results are contradictory. Thus, in the present study, the expression of TGFβ was analysed both at tissue (lymphoid organs and lung) and serum level to study its correlation with the expression of PRRS virus (PRRSV). To carry out this study, 32 pigs were inoculated with the European PRRSV field isolate 2982 and sequentially killed from 0dpi to the end of the study (24dpi). Blood and tissue samples were collected to determine the expression of PRRSV and TGFβ. PRRSV was detected in inoculated animals from 3dpi until the end of the study, however TGFβ was not detected in sera from inoculated animals. Contrary, an increase of TGFβ antigen was observed both in the lymphoid organs and in the lung of PRRSV-inoculated pigs when compared with control group. Since TGFβ play a role as an immunomodulatory cytokine of the immune response and also in the differentiation of regulatory T cells (Tregs), the upregulation of the TGFβ at tissue level may play a role in the impairment of the host immune response observed during PRRS, being observed a significant correlation between PRRSV and TGFβ expression at lung level.


title: Coronavirose systémique chez le furet (Mustela putorius) : intérêt de l’analyse histologique et immunohistochimique. À propos de trois cas

text: Résumé Contexte Une nouvelle coronavirose a été décrite chez le furet, notamment en Espagne et aux États-Unis, induite par un Coronavirus du groupe 1, proche du Coronavirus responsable de l’entérite catarrhale enzootique et à l’origine de lésions histologiques similaires à celle de la péritonite infectieuse féline (PIF) dans l’espèce féline. Objectif Démontrer l’origine virale de lésions pyogranulomateuses sévères au sein de tissus lymphoïdes ou viscéraux de trois furets. Méthodes Analyse histologique et immunohistochimique de lésions reçues au laboratoire suite à des autopsies ou des laparotomies exploratrices pratiquées par des vétérinaires. Résultats L’analyse histologique révèle une inflammation pyogranulomateuse multicentrique, touchant préférentiellement les nœuds lymphatiques abdominaux et différents organes abdominaux. L’analyse immunohistochimique permet la mise en évidence d’antigènes viraux de Coronavirus en position intramacrophagique au sein de lésions pyogranulomateuses ganglionnaires. Conclusion Ces trois cas d’inflammation pyogranulomateuse multicentrique sont dus à une coronavirose qui présente de nombreux points de ressemblance avec la PIF. Summary Background A disease resembling feline infectious peritonitis (FIP) has been recognized recently in ferrets, mostly in United States and in Spain. This disease is due to a Group 1 Coronavirus, closely related to the ferret enteric Coronavirus. Objective To demonstrate the viral origin of severe pyogranulomatous lymphoid and visceral lesions in three ferrets. Methods Histopathology and immunohistochemistry of lesions received in our laboratory. Results Severe pyogranulomatous inflammation was observed in the abdominal lymph nodes and in various organs. Positive labelling of Coronavirus antigen was demonstrated in macrophages in the pyogranulomatous lesions by immunohistochemistry. Conclusion The three cases of severe pyogranulomatous disseminated inflammation were due to a Coronavirus, causing a systemic coronavirosis in ferret with a high similarity to FIP.


Letter to the Editor: 'Medical Student Concerns Relating to Neurosurgery Education During COVID-19'


title: Demographic and environmental drivers of metagenomic viral diversity in vampire bats

text: Viruses infect all forms of life and play critical roles as agents of disease, drivers of biochemical cycles and sources of genetic diversity for their hosts. Our understanding of viral diversity derives primarily from comparisons among host species, precluding insight into how intraspecific variation in host ecology affects viral communities or how predictable viral communities are across populations. Here we test spatial, demographic and environmental hypotheses explaining viral richness and community composition across populations of common vampire bats, which occur in diverse habitats of North, Central and South America. We demonstrate marked variation in viral communities that was not consistently predicted by a null model of declining community similarity with increasing spatial or genetic distances separating populations. We also find no evidence that larger bat colonies host greater viral diversity. Instead, viral diversity follows an elevational gradient, is enriched by juvenile‐biased age structure, and declines with local anthropogenic food resources as measured by livestock density. Our results establish the value of linking the modern influx of metagenomic sequence data with comparative ecology, reveal that snapshot views of viral diversity are unlikely to be representative at the species level, and affirm existing ecological theories that link host ecology not only to single pathogen dynamics but also to viral communities.


title: Increased cytokine/chemokines in serum from asthmatic and non-asthmatic patients with viral respiratory infection

text: BACKGROUND: Respiratory viral infections can induce different cytokine/chemokine profiles in lung tissues and have a significant influence on patients with asthma. There is little information about the systemic cytokine status in viral respiratory-infected asthmatic patients compared with non-asthmatic patients. OBJECTIVES: The aim of this study was to determine changes in circulating cytokines (IL-1β, TNF-α, IL-4, IL-5) and chemokines (MCP1: monocyte chemoattractant protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in patients with an asthmatic versus a non-asthmatic background with respiratory syncytial virus, parainfluenza virus or adenovirus respiratory infection. In addition, human monocyte cultures were incubated with respiratory viruses to determine the cytokine/chemokine profiles. PATIENTS/METHODS: Patients with asthmatic (n = 34) and non-asthmatic (n = 18) history and respiratory infections with respiratory syncytial virus, parainfluenza, and adenovirus were studied. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in blood and culture supernatants was determined by ELISA. Monocytes were isolated by Hystopaque gradient and cocultured with each of the above-mentioned viruses. RESULTS: Similar increased cytokine concentrations were observed in asthmatic and non-asthmatic patients. However, higher concentrations of chemokines were observed in asthmatic patients. Virus-infected monocyte cultures showed similar cytokine/chemokine profiles to those observed in the patients. CONCLUSIONS: Circulating cytokine profiles induced by acute viral lung infection were not related to asthmatic status, except for chemokines that were already increased in the asthmatic status. Monocytes could play an important role in the increased circulating concentration of cytokines found during respiratory viral infections.


title: Impact of intercurrent respiratory infections on lung health in infants born <29 weeks with bronchopulmonary dysplasia

text: OBJECTIVE: Assess the impact of intercurrent respiratory infections in infants <29 weeks gestational age (GA). STUDY DESIGN: A retrospective cohort study of 111 infants born <29 weeks GA, controlling for bronchopulmonary dysplasia (BPD) severity and assessing pulmonary health over the first year of life through oxygen, diuretic and inhaled steroid use. RESULT: Regression analysis showed viral infections increased oxygen use (odds ratio (OR) of 15.5 (confidence interval (CI)=3.4, 71.3)). The trend test showed increasing numbers of viral infections were associated with increased oxygen (OR (95% CI)=6.4 (2.3 to 17.4), P=0.0003), diuretic (OR (95% CI)=2.4 (1.1to 5.2), P=0.02) and inhaled steroid use (OR (95% CI)=2.2 (1.003 to 5.2), P=0.049), whereas bacterial infections were not. CONCLUSION: Viral infections caused more long-term pulmonary morbidity/mortality than bacterial infections on premature lung health, even when controlling for BPD.


title: Virus-binding activity of the truncated C subunit of porcine aminopeptidase N expressed in Escherichia coli

text: Seven overlapping truncated forms of the C subunit of porcine aminopeptidase N (pAPN-C) were expressed in Escherichia coli. By western blotting and ELISA test, all recombinant proteins were recognized by the antibody against native porcine aminopeptidase N. Recombinant proteins, rpAPN-C2 (aa 623–722) and rpAPN-C3 (aa 673–772), had the highest binding activity with swine transmissible gastroenteritis virus among the truncated pAPN-C recombinant proteins. The overlapping region (aa 673–722) between rpAPN-C2 and rpAPN-C3 is indicated to play a key role in viral binding. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10529-011-0795-1) contains supplementary material, which is available to authorized users.


title: Treatment guidance for lung cancer patients during the COVID-19 pandemic

text: Abstract The global COVID-19 pandemic continues to escalate at a rapid pace inundating medical facilities and creating significant challenges globally. The risk of SARS-CoV-2 infection in cancer patients appears to be higher especially as they are more likely to present with an immunocompromised condition, either from the cancer itself or from the treatments they receive. A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment. Many aspects of the SARS-CoV-2 infection remain poorly characterized currently and even less is known about the course of infection in the context of a patient with cancer. As SARS-CoV-2 is highly contagious, the risk of infection directly affects the cancer patient being treated, other cancer patients in close proximity, and health care providers. Infection at any level for patients or providers can cause significant disruption to even the most effective treatment plans. Lung cancer patients, especially those with reduced lung function and cardiopulmonary co-morbidities are more likely to have increased risk and mortality from COVID-19 as one of its common manifestation is as an acute respiratory illness. The purpose of this manuscript is to present a practical multidisciplinary and international overview to assist in treatment for lung cancer patients during this pandemic, with the caveat that evidence is lacking in many areas. It is expected that firmer recommendations can be developed as more evidence becomes available.


title: Infections and coinfections by respiratory human bocavirus during eight seasons in hospitalized children

text: The human bocavirus (hBoV) has been identified in respiratory infections in children in a large number of studies. Despite this, the pathogenic role of the HBoV is under discussion. The main objectives of the study were: to determine the incidence of HBoV in hospitalized children; to describe the main clinical features of the positive children; and to compare the data with those from other viral infections in the same population. A prospective study was performed between 2005 and 2013 including children up to 14‐year old with respiratory infection admitted to the Severo Ochoa Hospital (Spain). Nasopharyngeal aspirates were taken from 3,275 patients and were tested for HBoV and other 15 respiratory viruses by RT‐nested PCR. HBoV was detected in 319 patients (9.9%); 80 cases as a single pathogen, and 239 cases (75%) as coinfections with other viruses. The HBoV was the fourth most common virus detected, behind respiratory syncytial virus (39.8%), rhinovirus (30.6%), and adenovirus (15%). The most common clinical diagnosis, in cases that HBoV was detected as a single pathogen was asthma exacerbation followed by pneumonia. A seasonal distribution was shown, with higher positivity rates in December and January. Children affected by HBoV were older than children infected by other viruses. Differences in terms of clinical diagnosis were found, bronchiolitis diagnosis was lower compared with the other viruses, and HBoV was associated with diagnosis of pneumonia, with increased use of antibiotics (41.8%), and radiographic infiltrates (47%). These findings could suggest a pathogenic role of HBoV in respiratory infections in children under 14 years of age. J. Med. Virol. 88:2052–2058, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.


title: Poor outcome and prolonged persistence of SARS‐CoV‐2 RNA in COVID‐19 patients with haematological malignancies; King's College Hospital experience

text: Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), emerged at the end of 2019 and caused an infection named COVID‐19 (Guan, Ni et al. 2020). Patients with compromised immune systems are at increased risk of complications but this risk is not precisely defined (Liang, Guan et al. 2020). Although age, gender, comorbidities and ethnicity are risk factors for adverse outcomes (Huang, Wang et al. 2020), various pre‐existing conditions, including haematological cancers, have also been reported to correlate with poor outcomes (Aries, Davies et al. 2020, He, Chen et al. 2020, Malard, Genthon et al. 2020, Martin‐Moro, Marquet et al. 2020, medRxiv 2020)


title: The changes of prevalence and etiology of pediatric pneumonia from National Emergency Department Information System in Korea, between 2007 and 2014

text: PURPOSE: Understanding changes in pathogen and pneumonia prevalence among pediatric pneumonia patients is important for the prevention of infectious diseases. METHODS: We retrospectively analyzed data of children younger than 18 years diagnosed with pneumonia at 117 Emergency Departments in Korea between 2007 and 2014. RESULTS: Over the study period, 329,380 pediatric cases of pneumonia were identified. The most frequent age group was 1–3 years old (48.6%) and the next was less than 12 months of age (17.4%). Based on International Classification of Diseases, 10th revision diagnostic codes, confirmed cases of viral pneumonia comprised 8.4% of all cases, pneumonia due to Mycoplasma pneumoniae comprised 3.8% and confirmed cases of bacterial pneumonia 1.3%. The prevalence of confirmed bacterial pneumonia decreased from 3.07% in 2007 and 4.01% in 2008 to 0.65% in 2014. The yearly rate of pneumococcal pneumonia also decreased from 0.47% in 2007 to 0.08% in 2014. A periodic prevalence of M. pneumoniae pneumonia (MP) was identified. CONCLUSION: The increased number of patients with pneumonia, bacterial pneumonia, pleural effusion, and empyema in 2011 and 2013–2014 resulted from an MP epidemic. We provide evidence that the frequency of confirmed cases of bacterial pneumonia and pneumococcal pneumonia has declined from 2007 to 2014, which can simultaneously reflect the effectiveness of the pneumococcal conjugate vaccine.


title: Comparison of Oral Prednisolone/Paracetamol and Oral Indomethacin/Paracetamol Combination Therapy in the Treatment of Acute Goutlike Arthritis: A Double-Blind, Randomized, Controlled Trial

text: STUDY OBJECTIVE: We compare the analgesic efficacy and adverse effects of oral prednisolone/acetaminophen and oral indomethacin/acetaminophen combination therapy in the treatment of acute goutlike arthritis in patients presenting to an emergency department (ED). METHODS: This is a double-blind, randomized, controlled study in a university hospital emergency department (ED) in the New Territories of Hong Kong. Patients older than 17 years and presenting between February 1, 2003, and June 30, 2004, with a clinical diagnosis of goutlike arthritis were randomized to receive either oral prednisolone/acetaminophen or oral indomethacin/acetaminophen combination therapy. Primary outcome measures were pain scores, time to resolution of symptoms and signs, and adverse effects. Secondary outcome measures were the need for additional acetaminophen and relapse rate. RESULTS: There were 90 patients randomized: 46 patients to the indomethacin group and 44 patients to the prednisolone group. Baseline characteristics, including pain scores, were similar in the 2 groups. Both treatment groups had a similar decrease in pain score in the ED. The mean rate of decrease in pain score with activity for indomethacin was −1.7±1.6 (SD) mm per day and for prednisolone was −2.9±2.0 (SD) mm per day (mean difference 1.2 mm/day; 95% confidence interval 0.4 to 2.0 mm/day; P=.0026). Although these differences were statistically significant, at no time was the difference in mean pain score greater than 13 mm. Therefore, it is unclear whether these differences are clinically significant. The mean total dose of acetaminophen consumed by the prednisolone group was significantly more than in the indomethacin group (mean 10.3 g, range 1 to 21 g versus mean 6.4 g, range 1 to 21 g). Twenty-nine patients in the indomethacin group and 12 patients in the prednisolone group experienced adverse effects (P<.05). The commonest adverse effects in the indomethacin group were nausea, indigestion, epigastric pain, dizziness, and gastrointestinal bleeding (N=5; 11%). None of the patients in the prednisolone group developed gastrointestinal bleeding. The relapse rate for both groups was similar. CONCLUSION: In the treatment of acute goutlike arthritis, oral prednisolone/acetaminophen combination is as effective as oral indomethacin/acetaminophen combination in relieving pain but is associated with fewer adverse effects.


Simple ideas to mitigate the impacts of the COVID-19 epidemic on refugees with chronic diseases


title: Study on the dynamic change law and correlation between CT imaging manifestations and cellular immunity of 2019 novel coronavirus disease

text: PURPOSE: To explore the dynamic changes and correlation between CT imaging manifestations and cellular immunity of COVID-19. MATERIALS AND METHODS: This retrospective review analyzed 23 patients with COVID-19, including 13 males and 10 females aged 27–70 years, with an average age of 48 years. Patients were divided into two groups: group A with 11 critical-severe patients, and group B with 12 common-mild patients. Clinical, laboratory, and radiological data were collected and analyzed. RESULTS: LYM, LYM (%), CD3+, CD4+, and CD8+ decreased, while NEU (%), CRP, and CT scores increased in all patients, WBC in group A increased. In group A, on day 10–12 after disease onset, CT scores and CRP reached the highest point, and day 13–15 LYM, LYM (%) reached the lowest but NEU (%) and WBC reached the highest, CD3+, CD4+ and CD8+ were at the lowest on day 10–15. In group B, on day 7–9, CT scores, NEU (%) and CRP reached the peak, but LYM, LYM (%), CD3+, CD4+ and CD8+ reached the lowest. In all patients, CT scores had a significantly negative correlation with CD3+, CD4+, CD8+, LYM (%), and LYM (p = 0.001, r = − 0.797; p = 0.008, r = − 0.698; p = 0.002, r = − 0.775; p < 0.001, r = − 0.785; p = 0.021, r = − 0.571, respectively), and a significantly positive correlation with WBC and NEU (%) (p < 0.001, r = 0.785; p = 0.003, r = 0.691, respectively). CONCLUSION: Dynamic changes of CT manifestations and cellular immunity of patients with COVID-19 were regular and correlation was high between these two parameters.


Expression and Structural Analysis of Infectious Bronchitis Virus Nucleoprotein


title: Von Kamelen und Krebsforschung: Ungelöste Fragen

text: Die moderne Medizin hat innerhalb der letzten Jahrzehnte große Fortschritte gemacht und viele Wirkstoffe an unerwarteten Orten entdeckt. Eine Forschungsrichtung beschäftigt sich nun mit der Nutzung von Kamelen, die in ihrem natürlichen Habitat schon lange als Lieferant von verschiedensten Heilmitteln gelten.


title: Pediatric Round Pneumonia

text: “Round pneumonia” or “spherical pneumonia” is a well-characterized clinical entity that seems to be less addressed by pediatricians in Taiwan. We herein report the case of a 7-year-old boy who presented with prolonged fever, cough, and chest X-rays showing a well-demarcated round mass measuring 5.9 × 5.6 × 4.3 cm in the left lower lung field, findings which were typical for round pneumonia. The urinary pneumococcal antigen test was positive, and serum anti-Mycoplasma pneumoniae antibody titer measurement using a microparticle agglutination method was 1:160 (+). After oral administration of antibiotics including azithromycin and amoxicillin/clavulanate, which was subsequently replaced by ceftibuten due to moderate diarrhea, the fever subsided 2 days later and the round patch had completely resolved on the 18th day after the diagnosis. Recent evidence suggests treating classical round pneumonia with antibiotics first and waiving unwarranted advanced imaging studies, while alternative etiologies such as abscesses, tuberculosis, nonbacterial infections, congenital malformations, or neoplasms should still be considered in patients with atypical features or poor treatment response.


title: Contact Heterogeneity, Rather Than Transmission Efficiency, Limits the Emergence and Spread of Canine Influenza Virus

text: Host-range shifts in influenza virus are a major risk factor for pandemics. A key question in the study of emerging zoonoses is how the evolution of transmission efficiency interacts with heterogeneity in contact patterns in the new host species, as this interplay influences disease dynamics and prospects for control. Here we use a synergistic mixture of models and data to tease apart the evolutionary and demographic processes controlling a host-range shift in equine H3N8-derived canine influenza virus (CIV). CIV has experienced 15 years of continuous transfer among dogs in the United States, but maintains a patchy distribution, characterized by sporadic short-lived outbreaks coupled with endemic hotspots in large animal shelters. We show that CIV has a high reproductive potential in these facilities (mean R(0) = 3.9) and that these hotspots act as refugia from the sparsely connected majority of the dog population. Intriguingly, CIV has evolved a transmission efficiency that closely matches the minimum required to persist in these refugia, leaving it poised on the extinction/invasion threshold of the host contact network. Corresponding phylogenetic analyses show strong geographic clustering in three US regions, and that the effective reproductive number of the virus (R(e)) in the general dog population is close to 1.0. Our results highlight the critical role of host contact structure in CIV dynamics, and show how host contact networks could shape the evolution of pathogen transmission efficiency. Importantly, efficient control measures could eradicate the virus, in turn minimizing the risk of future sustained transmission among companion dogs that could represent a potential new axis to the human-animal interface for influenza.


title: Re-imagining the future of diagnosis of Neglected Tropical Diseases

text: Neglected Tropical Diseases (NTDs) affect an estimated 1 billion people in 149 countries. The World Health Organization (WHO) prioritised 17 NTDs for control and elimination by 2020 and defined a Road Map to help countries reach these goals. Improved diagnostics for NTDs are essential for guiding treatment strategies at different thresholds of control, interruption of transmission, elimination and post-elimination surveillance. While substantial progress has been made in the last decade with chemotherapy, the same cannot be said of diagnostics, largely due to the perceived lack of a commercially viable market for NTD diagnostics. New sample in-answer out nucleic acid amplification technologies that can be performed at the point-of-care offer improved performance over current technologies and the potential to test for multiple pathogens using a single specimen. Finding commonalities for different NTDs in terms of geographic overlap, sentinel populations and treatment strategy will allow NTD programs to leverage these innovations to build cost-effective multiplex surveillance platforms. Connectivity solutions linking data from diagnostic laboratories and POC test readers/devices provide opportunities for automated surveillance systems to make health systems more efficient, improving patient outcomes and assessing impact of interventions in real time. New models of public–private product development partnerships are critical in leveraging diagnostic innovation in other priority area for better diagnosis, control and elimination of NTDs.


A SARS-CoV–Specific Protein Enhances Virulence of an Attenuated Strain of Mouse Hepatitis Virus


title: PSYCOVID-19, dispositif de soutien psychologique dans les champs de la santé mentale, du somatique et du médico-social

text: Résumé Au mois de décembre 2019, l’Organisation Mondiale de la Santé (OMS) recense les premiers cas d’une maladie infectieuse apparue en Chine en novembre de la même année. Générée par le nouveau coronavirus SARS-CoV2, elle est nommée COVID-19 pour COronaVirus Infectious Disease 2019. Rapidement, la diffusion de cette maladie inconnue a un retentissement planétaire : la contagiosité du virus est extrêmement importante et les suites sont potentiellement mortelles. En France, la population réagit initialement avec incrédulité, jusqu’à ce que la maladie atteigne l’Europe et que les premiers cas apparaissent sur le territoire français fin janvier 2020. Quelques semaines plus tard, le 16 mars 2020, le Président Macron déclare le pays « en guerre » contre le Covid-19. Le lendemain, la population est placée en confinement. L’activité du pays est à l’arrêt. Les écoles, les entreprises, les commerces, sont fermés. Les Français sont sidérés. Ils doivent soudainement affronter la peur : celle qu’eux ou leurs proches puissent tomber malades, celle de l’enfermement et de la restriction de libertés, celle de la précarité économique. Et surtout celle de l’inconnu. Afin de prévenir les conséquences désastreuses du séisme, des cellules d’écoute et de soutien psychologiques sont créées dans l’urgence, à l’échelon national. Elles sont destinées à soutenir le corps soignant, les malades et plus largement la population générale. Celle dédiée au département de la Gironde s’organise en quelques heures, sur le week-end du 21 mars 2020. La plateforme d’écoute COVIDPSY33 est ainsi mise en place à Bordeaux, par le Centre Hospitalier Charles Perrens, avec le soutien de l’Agence Régionale de Santé Nouvelle-Aquitaine (ARS). La cellule PSYCOVID-19 est créée de manière concomitante. Cette cellule de soutien d’aval travaille en collaboration avec la plateforme COVIDPSY33 et propose une aide psychologique à la population générale et aux soignants du secteur Bordeaux Rive Droite, Bordeaux Gare, Rives de Garonne, Rives d’Arcins et Sud Gironde. Elle couvre ainsi un territoire équivalent à environ la moitié du plus vaste département de France métropolitaine, la Gironde. Dans cet entretien, Samantha Al Joboory et Florence Monello, psychiatre et psychologue coordinatrices de PSYCOD-19, présentent ce dispositif de soutien psychologique. Abstract In December 2019 the World Health Organization (WHO) recorded the first cases of an infectious disease that appeared in China in November of the same year. Generated by the new coronavirus SARS-CoV2, it is quickly named COVID-19 for COronaVirus Infectious Disease 2019. The spread of this unknown disease will soon have worldwide consequences: the contagiousness of the virus is extremely high and potentially lethal. In France, the population initially reacted with disbelief until the disease reached Europe and the first cases appeared on French territory, at the end of January. A few weeks later, on 16 March 2020, President Macron declared the country "at war" against COVID-19. The next day the population was placed in lockdown. At the present time, the country's activity is at a standstill. Schools, businesses and shops are closed. The French citizens are astounded. They suddenly have to face fear: fear of falling ill or that a close relative may fall ill, fear of being locked up and experiencing restrictions of liberties, fear of economic precariousness. And, above all, fear of uncertainty. In order to prevent the mental consequences of this crisis, psychological support units have been created with urgency at national scale. These units are intended to support the healthcare professionals as well as the patients and more broadly, the general population.The unit responsible for the department of Gironde has been set up quickly, over the weekend of March 21, 2020. The COVIDPSY33 listening unit has thus been created in Bordeaux by the Charles Perrens Hospital with support from the AgenceRégionale de Santé Nouvelle-Aquitaine (ARS). Simultaneously, the PSYCOVID-19 unit was created. This additional unit works in collaboration with the COVIDPSY33 platform and offers psychological assistance to the general population and caregivers in the sectors of Bordeaux Rive Droite, Bordeaux Gare, Rives de Garonne, Rives d’Arcins and Sud Gironde. It thus covers an area equivalent to approximately half of Gironde, the largest department in metropolitan France. In the present interview, Samantha Al Joboory and Florence Monello, psychiatrist and psychologist coordinating PSYCOD-19, present this psychological support unit.


title: Topical rh‐aFGF: An effective therapeutic agent for facemask wearing‐induced pressure sores

text: Protecting healthcare workers is crucial during coronavirus disease 2019 (COVID‐19) pandemic and facemask wearing is considered an effective measure to prevent severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, long‐time use of a facemask can cause pressure sores on the ears and nose bridge and increase the risk of infection. The topical recombinant human acidic fibroblast growth factor (rh‐aFGF) was used to cure pressure sores for healthcare workers at Zhongfaxincheng campus of Tongji Hospital. The results from a small sample size survey conducted in Zhongfaxincheng campuses of Tongji Hospital showed that treatment with topical rh‐aFGF could significantly inhibit the progression of pressure sores and accelerate the wound healing with no apparent ill‐effects. Therefore, we propose that topical rh‐aFGF is an effective therapeutic agent for facemask wearing‐induced pressure sores and worth of popularizing and applying. This article is protected by copyright. All rights reserved.


title: Immune regulation and cytotoxic T cell activation of IL-10 agonists – Preclinical and clinical experience

text: Abstract The expansion and activation of tumor antigen reactive CD8+ T cells are primary goals of immunotherapies for cancer. IL-10 is an anti-inflammatory cytokine with an essential role in the development and proliferation of regulatory T cells, restricting myeloid and chronic inflammatory T cell responses. However, IL-10 is also essential for the expansion of antigen activated, tumor specific CD8+ T cells, leading to spontaneous tumor development in IL-10 deficient patients and mice. IL-10 induces IFNγ and cytotoxic mediators in antigen activated T cells. In clinical trials, monotherapy with recombinant, pegylated IL-10 (Pegilodecakin) induced objective responses in cancer patients. Patients receiving pegilodecakin had a systemic increase of IFNγ and granzymes, proliferation and expansion of immune checkpoint positive CD8+ T cells. Combination of pegilodecakin with anti-PD-1 appeared to improve on the efficacy of the single agents.


title: COVID-19 Silver Linings

text: A heightened state of alert due to the COVID-19 outbreak was declared by the Singapore Ministry of Health on February 7th, 2020. Within the hospital, team reorganizations, workflow revisions and physical segregation caused anxiety among healthcare workers (HCWs). Fear of the unknown, emotional and physical fatigue started to take their toll on HCWs. We share our learning journey over the first 8 weeks of COVID-19: the importance of acknowledging fears and questions, and transforming them to collective knowledge; the role of empathic, hands-on leadership which brings camaraderie and calms scepticism; the importance of validating efforts and acknowledging hardship; and most importantly, the security that comes from camaraderie, breaking down hierarchical barriers and motivating each other to keep on going.


title: Digital microbiology

text: BACKGROUND: Digitalisation and artificial intelligence have an important impact on the way microbiology laboratories will work in the near future. Opportunities and challenges lay ahead to digitalise the microbiological workflows. Making an efficient use of big data, machine learning, and artificial intelligence in clinical microbiology requires a profound understanding of data handling aspects. OBJECTIVE: This review article summarizes the most important concepts of digital microbiology. The article provides microbiologists, clinicians and data scientists a viewpoint and practical examples along the diagnostic process. SOURCES: We used peer-reviewed literature identified by a Pubmed search for digitalisation, machine learning, artificial intelligence and microbiology. CONTENT: We describe the opportunities and challenges of digitalisation in microbiological diagnostic process with various examples. We also provide in this context key aspects of data structure and interoperability, as well as legal aspects. Finally, we outline the way for applications in a modern microbiology laboratory. IMPLICATIONS: We predict that digitalization and the usage of machine learning will have a profound impact on the daily routine of the laboratory staff. Along the analytical process, the most important steps should be identified, where digital technologies can be applied and provide a benefit. The education of all staff involved should be adapted to prepare for the advances in digital microbiology.


title: Return to Normalcy? Principles on Resuming Surgical Services in the COVID-19 Era

text: The rapidly changing health care climate related to coronavirus disease 2019 (COVID-19) has resulted in numerous changes to health care systems and in practices that protect both the public and the workers who serve in hospitals around the country. As a result, these past few months have seen a drastic reduction in outpatient visits and surgical volumes. With phased reopening and appropriate guidance, health care systems are attempting to return to normal. Our institution has had the unique opportunity to already return operations back to full capacity. The experiences and lessons learned are described, and we provide guiding principles to allow for a safe and effective return to patient care.


The year of the nurses and the midwife: Nursing professionalism shining in the frontline of anti-epidemic and to be strengthened in the future


title: TaqMan real time RT-PCR assays for detecting ferret innate and adaptive immune responses

text: Abstract The ferret is an excellent model for many human infectious diseases including influenza, SARS-CoV, henipavirus and pneumococcal infections. The ferret is also used to study cystic fibrosis and various cancers, as well as reproductive biology and physiology. However, the range of reagents available to measure the ferret immune response is very limited. To address this deficiency, high-throughput real time RT-PCR TaqMan assays were developed to measure the expression of fifteen immune mediators associated with the innate and adaptive immune responses (IFNα, IFNβ, IFNγ, IL1α, IL1β, IL2, IL4, IL6, IL8, IL10, IL12p40, IL17, Granzyme A, MCP1, TNFα), as well as four endogenous housekeeping genes (ATF4, HPRT, GAPDH, L32). These assays have been optimized to maximize reaction efficiency, reduce the amount of sample required (down to 1ng RNA per real time RT-PCR reaction) and to select the most appropriate housekeeping genes. Using these assays, the expression of each of the tested genes could be detected in ferret lymph node cells stimulated with mitogens or infected with influenza virus in vitro. These new tools will allow a more comprehensive analysis of the ferret immune responses following infection or in other disease states.


title: Crystallization and preliminary crystallographic analysis of the heptad‐repeat complex of SARS coronavirus spike protein

text: The aetiological agent of an emergent outbreak of atypical pneumonia, severe acute respiratory syndrome (SARS), is a positive‐stranded RNA virus (SARS‐CoV) belonging to the Coronaviridae family with a genome that differs substantially from those of other known coronaviruses. Highly conserved heptad‐repeat (HR1 and HR2) regions in class I viral fusion proteins, including spike protein from SARS coronavirus, interact with each other to form a six‐helix bundle, which is called a fusion core. The crystal structure of the fusion core is expected to greatly facilitate drug design. Crystals of the fusion core of SARS‐CoV spike protein have been grown at 291 K using PEG 4000 as precipitant. The diffraction pattern of the crystal extends to 2.8 Å resolution at 100 K in‐house. The crystals have unit‐cell parameters a = 121.2, b = 66.3, c = 70.0 Å, α = γ = 90, β = 107.4° and belong to space group C2. Assuming the presence of six molecules per asymmetric unit, the solvent content is estimated to be about 28%.


title: Psychopharmacology of COVID-19

text: BACKGROUND: With the rapid, global spread of SARS-CoV-2, hospitals have become inundated with patients suffering from COVID-19. Consultation-liaison psychiatrists are actively involved in managing these patients and should familiarize themselves with how the virus and its proposed treatments can affect psychotropic management. The only FDA approved drug to treat COVID-19 is remdesivir, and other off-label medications used include chloroquine and hydroxychloroquine, tocilizumab, lopinavir/ritonavir, favipiravir, convalescent plasma therapy, azithromycin, vitamin C, corticosteroids, interferon and colchicine. PURPOSE: To provide an overview of the major safety considerations relevant to clinicians who prescribe psychotropics to patients with COVID-19, both related to the illness and its proposed treatments. METHODS: In this targeted review we performed structured literature searches in PubMed to identify articles describing the impacts of COVID-19 on different organ systems, the neuropsychiatric adverse effects of treatments, and any potential drug interactions with psychotropics. The articles most relevant to this manuscript were included. RESULTS: COVID-19 impacts multiple organ systems, including gastrointestinal, renal, cardiovascular, pulmonary, immunological, and hematological systems. This may lead to pharmacokinetic changes that impact psychotropic medications and increase sensitivity to psychotropic-related adverse effects. Additionally, several proposed treatments for COVID-19 have neuropsychiatric effects and potential interactions with commonly used psychotropics. CONCLUSION: Clinicians should be aware of the need to adjust existing psychotropics or avoid using certain medications in some COVID-19 patients. They should also be familiar with neuropsychiatric effects of medications being used to treat this disease. Further research is needed to identify strategies to manage psychiatric issues in this population.


docid: fcfanxtk

title: Preprints in medical research: Progress and principles

text: In this month’s editorial, the PLOS Medicine Editors discuss the role of preprints in human health research and propose a 3-part framework for ensuring benefit.


docid: tzboutbq

title: Comparing Human Metapneumovirus and Respiratory Syncytial Virus: Viral Co-Detections, Genotypes and Risk Factors for Severe Disease

text: BACKGROUND: It is unclarified as to whether viral co-detection and human metapneumovirus (HMPV) genotypes relate to clinical manifestations in children with HMPV and lower respiratory tract infection (LRTI), and if the clinical course and risk factors for severe LRTI differ between HMPV and respiratory syncytial virus (RSV). METHODS: We prospectively enrolled hospitalized children aged <16 years with LRTI from 2006 to 2015. Children were clinically examined, and nasopharyngeal aspirates were analyzed using semi-quantitative, real-time polymerase chain reaction tests for HMPV, RSV and 17 other pathogens. HMPV-positive samples were genotyped. RESULTS: A total of 171 children had HMPV infection. HMPV-infected children with single virus (n = 106) and co-detections (n = 65) had similar clinical manifestations. No clinical differences were found between HMPV genotypes A (n = 67) and B (n = 80). The HMPV-infected children were older (median 17.2 months) than RSV-infected children (median 7.3 months, n = 859). Among single virus-infected children, no differences in age-adjusted LRTI diagnoses were found between HMPV and RSV. Age was an important factor for disease severity among single virus-infected children, where children <6 months old with HMPV had a milder disease than those with RSV, while in children 12–23 months old, the pattern was the opposite. In multivariable logistic regression analysis for each virus type, age ≥12 months (HMPV), and age <6 months (RSV), prematurity, ≥1 chronic disease and high viral loads of RSV, but not high HMPV viral loads, were risk factors for severe disease. CONCLUSIONS: Among hospitalized children with LRTI, HMPV manifests independently of viral co-detections and HMPV genotypes. Disease severity in HMPV- and RSV-infected children varies in relation to age. A history of prematurity and chronic disease increases the risk of severe LRTI among HMPV- and RSV-infected children.


title: Comparative sequence analysis of a polymorphic region of the spike glycoprotein S1 subunit of enteric bovine coronavirus isolates

text: Complementary oligonucleotide primers which flank a 1146-nucleotide gene fragment (S1B: nt 1185 to 2333) encompassing a polymorphic region (nt 1368 to 1776) of the S1 subunit of bovine coronavirus spike glycoprotein were used for enzymatic amplification by PCR. We chose four clinical isolates, recovered from cases of epidemic diarrhea in neonatal calves in Québec dairy herds between 1987–1990, to specifically amplify and analyze their sequences in the selected genomic area. Nucleotide sequence analysis of the four clinical isolates indicated that their S1B gene fragments were highly conserved. We also compared the S1B gene sequences of the Québec BCV isolates to the published corresponding sequences from BCV-L9 [37], BCV-MEB [1], and BCV-F15 [3] reference strains. A high degree of similarity was demonstrated for all viruses, no deletions or insertions were observed, and the only variations that were identified consisted of nucleotide substitutions. The differing nucleotides and amino acids (aa) were not distributed randomly over the entire sequence but rather were clustered in the polymorphic region. Of these, four sporadic aa changes were located in antigenic domain II (aa residues 517 to 720) of S1. This correlates with varied antigenicity observed among the BCV Québec isolates when reacting with MAbs directed against the S glycoprotein of the Mebus strain. The other mutations seem to be fixed in all Québec isolates.


title: Identification of potential binders of the main protease 3CL(pro) of the COVID-19 via structure-based ligand design and molecular modeling

text: We have applied a computational strategy, using a combination of virtual screening, docking and molecular dynamics techniques, aimed at identifying possible lead compounds for the non-covalent inhibition of the main protease 3CL(pro) of the SARS-CoV2 Coronavirus. Based on the X-ray structure (PDB code: 6LU7), ligands were generated using a multimodal structure-based design and then docked to the monomer in the active state. Docking calculations show that ligand-binding is strikingly similar in SARS-CoV and SARS-CoV2 main proteases. The most potent docked ligands are found to share a common binding pattern with aromatic moieties connected by rotatable bonds in a pseudo-linear arrangement.


title: Frequency of lupus anticoagulant in Covid‐19 patients

text: We have recently published in the Journal of Thrombosis and Haemostasis the presence of lupus anticoagulant (LAC) at high frequency in Covid‐19 patients (Harzallah et al.(1)). Bowles et al.(2) and Helms et al.(3) have confirmed these results in new publications. Tang(4) has reported discordant data. He has found that very few tested covid‐19 patients had positive LAC in a small series (n=12). Bowles et al. have found that LAC were positive in 91% of patients (n=34) with high activated partial thromboplastin time (aPTT).


title: Merkel cell polyomavirus DNA in immunocompetent and immunocompromised patients with respiratory disease

text: Merkel cell polyomavirus (MCPyV) was identified originally in association with a rare but aggressive skin cancer, Merkel cell carcinoma. The virus has since been found in the respiratory tract of some patients with respiratory disease. However, the role of MCPyV in the causation of respiratory disease has not been established. To determine the prevalence of MCPyV in 305 respiratory samples from immunocompetent and immunocompromised patients and evaluate their contribution to respiratory diseases, specimens were screened for MCPyV using single, multiplex, or real‐time PCR; co‐infection with other viruses was examined. Of the 305 samples tested, 10 (3.27%) were positive for MCPyV. The virus was found in two groups of patients: in 6 (2%) nasopharyngeal aspirate samples from children aged 26 days to 7 months who were immunocompetent; and in 4 (1.3%) of nasopharyngeal aspirate samples taken from patients aged 41 to 69 years who were severely immunosuppressed from leukemia or transplant therapy. Both groups had upper or lower respiratory tract infection. Co‐infections with other viruses were found in 30% of the MCPyV positive samples. The data present a pattern of infection similar to that seen with the polyomaviruses JC and BK in which the virus is acquired during childhood, probably by the respiratory route. The viruses then establish latency and become reactivated in the event of immunosuppression. J. Med. Virol. 83:2220–2224, 2011. © 2011 Wiley Periodicals, Inc.


title: When could human challenge trials be deployed to combat emerging infectious diseases? Lessons from the case of a Zika virus human challenge trial

text: Human challenge trials (HCTs) deliberately infect participants in order to test vaccines and treatments in a controlled setting, rather than enrolling individuals with natural exposure to a disease. HCTs are therefore potentially powerful tools to prepare for future outbreaks of emerging infectious diseases. Yet when an infectious disease is emerging, there is often substantial risk and uncertainty about its complications, and few available interventions, making an HCT ethically complex. In light of the need to consider ethical issues proactively as a part of epidemic preparedness, we use the case of a Zika virus HCT to explore whether and when HCTs might be ethically justified to combat emerging infectious diseases. We conclude that emerging infectious diseases could be appropriate candidates for HCTs and we identify relevant considerations and provide a case example to illustrate when they might be ethically acceptable.


docid: ztarsxnc

title: Lithium chloride inhibits early stages of foot‐and‐mouth disease virus (FMDV) replication in vitro

text: Foot‐and‐mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven‐hoofed animals such as cattle, swine, and sheep. FMD vaccine is the traditional way to protect against the disease, which can greatly reduce its occurrence. However, the use of FMD vaccines to protect early infection is limited. Therefore, the alternative strategy of applying antiviral agents is required to control the spread of FMDV in outbreak situations. As previously reported, LiCl has obviously inhibition effects on a variety of viruses such as transmissible gastroenteritis virus (TGEV), infectious bronchitis coronavirus (IBV), and pseudorabies herpesvirus and EV‐A71 virus. In this study, our findings were the first to demonstrate that LiCl inhibition of the FMDV replication. In this study, BHK‐21 cell was dose‐dependent with LiCl at various stages of FMDV. Virus titration assay was calculated by the 50% tissue culture infected dose (TCID(50)) with the Reed and Muench method. The cytotoxicity assay of LiCl was performed by the CCK8 kit. The expression level of viral mRNA was measured by RT‐qPCR. The results revealed LiCl can inhibit FMDV replication, but it cannot affect FMDV attachment stage and entry stage in the course of FMDV life cycle. Further studies confirmed that the LiCl affect the replication stage of FMDV, especially the early stages of FMDV replication. So LiCl has potential as an effective anti‐FMDV drug. Therefore, LiCl may be an effective drug for the control of FMDV. Based on that, the mechanism of the antiviral effect of LiCl on FMDV infection is need to in‐depth research in vivo.


AHPBA Webinar about Covid-19: Lessons Learned Responding to a Pandemic


title: Current Resources for Evidence-Based Practice, May 2020

text: Abstract An extensive review of new resources to support the provision of evidence-based care for women and infants. The current column includes a discussion of a new National Academy of Medicine report on planned place of birth and implications during the SARS-CoV-2 pandemic and commentaries on reviews focused on anorectal sexually transmitted infections and feeding methods following cleft lip repair in infants.


title: Efficacy and Safety of Bortezomib in Multiple Myeloma Patients with Hepatitis B: A Multicenter Retrospective Study

text: BACKGROUND: The efficacy and safety evidence of bortezomib in multiple myeloma (MM) patients with hepatitis B is vacant. This study aimed to investigate the efficacy and safety of bortezomib in MM patients with hepatitis B in China. METHODS: From 2006 to 2011, 739 newly diagnosed MM patients were screened for serum hepatitis B virus (HBV) biomarkers. HBV-infected patients were followed for HBV reactivation by monitoring of serum alanine transaminase (ALT) and HBV DNA load. The pattern of HBV reactivation in relation to bortezomib was evaluated. Seven hundred thirty-nine MM patients were included in this study. RESULTS: The prevalence of MM patients infected with HBV was 3.4% (n = 25), of which 17 cases were treated with bortezomib. Bortezomib had no significant influence on liver function (ALT before and after treatment: 36.69 ± 8.90 U/L vs. 11.31 ± 2.74 U/L, P = 0.19) and HBV DNA of MM patients with HBV (detectable HBV DNA percentage: 5.9% vs. 11.8%, P = 0.12). CONCLUSIONS: Bortezomib can be used safely and effectively in MM patients with hepatitis B. HBV prophylaxis and surveillance are recommended during the MM treatment.


docid: ermuiujq

title: plethy: management of whole body plethysmography data in R

text: BACKGROUND: Characterization of respiratory phenotypes can enhance complex trait and genomic studies involving allergic/autoimmune and infectious diseases. Many aspects of respiration can be measured using devices known as plethysmographs that can measure thoracic movement. One such approach (the Buxco platform) performs unrestrained whole body plethysmography on mice which infers thoracic movements from pressure differences from the act of inhalation and exhalation. While proprietary software is available to perform basic statistical analysis as part of machine’s bundled software, it is desirable to be able to incorporate these analyses into high-throughput pipelines and integrate them with other data types, as well as leverage the wealth of analytic and visualization approaches provided by the R statistical computing environment. RESULTS: This manuscript describes the plethy package which is an R/Bioconductor framework for pre-processing and analysis of plethysmography data with emphasis on larger scale longitudinal experiments. The plethy package was designed to facilitate quality control and exploratory data analysis. We provide a demonstration of the features of plethy using a dataset assessing the respiratory effects over time of SARS and Influenza infection in mice. CONCLUSION: The plethy package provides functionality for users to import, perform quality assessment and exploratory data analysis in a manner that allows interoperability with existing modelling tools. Our package is implemented in R and is freely available as part of the Bioconductor project http://www.bioconductor.org/packages/release/bioc/html/plethy.html. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0547-7) contains supplementary material, which is available to authorized users.


title: Type 1 diabetes and technology at time of COVID ‐19. A case report

text: Intermittent acute illness contribute to blood glucose dysregulation in Patients with Type 1 diabetes mellitus (T1DM): systemic inflammation, insulin resistance, unpredictable eating, fever, nausea, vomiting, among other factors lead to blood glucose instability with a significant risk of hypoglycemia and represent a difficult challenge for Patients (1). Hyperglycemia (with or without diabetes) is a double edge sword : is depend on the acute illness and by itself negatively contribute to a more severe prognosis.


title: Applications of selective neutrality tests to molecular ecology

text: This paper reviews how statistical tests of neutrality have been used to address questions in molecular ecology are reviewed. The work consists of four major parts: a brief review of the current status of the neutral theory; a review of several particularly interesting examples of how statistical tests of neutrality have led to insight into ecological problems; a brief discussion of the pitfalls of assuming a strictly neutral model if it is false; and a discussion of some of the opportunities and problems that molecular ecologists face when using neutrality tests to study natural selection.


title: QSAR Studies on Andrographolide Derivatives as α-Glucosidase Inhibitors

text: Andrographolide derivatives were shown to inhibit α-glucosidase. To investigate the relationship between activities and structures of andrographolide derivatives, a training set was chosen from 25 andrographolide derivatives by the principal component analysis (PCA) method, and a quantitative structure-activity relationship (QSAR) was established by 2D and 3D QSAR methods. The cross-validation r(2) (0.731) and standard error (0.225) illustrated that the 2D-QSAR model was able to identify the important molecular fragments and the cross-validation r(2) (0.794) and standard error (0.127) demonstrated that the 3D-QSAR model was capable of exploring the spatial distribution of important fragments. The obtained results suggested that proposed combination of 2D and 3D QSAR models could be useful in predicting the α-glucosidase inhibiting activity of andrographolide derivatives.


title: Understanding community perceptions, social norms and current practice related to respiratory infection in Bangladesh during 2009: a qualitative formative study

text: BACKGROUND: Respiratory infections are the leading cause of childhood deaths in Bangladesh. Promoting respiratory hygiene may reduce infection transmission. This formative research explored community perceptions about respiratory infections. METHODS: We conducted 34 in-depth interviews and 16 focus group discussions with community members and school children to explore respiratory hygiene related perceptions, practices, and social norms in an urban and a rural setting. We conducted unstructured observations on respiratory hygiene practices in public markets. RESULTS: Informants were not familiar with the term "respiratory infection"; most named diseases that had no relation to respiratory dysfunction. Informants reported that their community identified a number of 'good behaviors' related to respiratory hygiene, but they also noted, and we observed, that very few people practiced these. All informants cited hot/cold weather changes or using cold water as causes for catching cold. They associated transmission of respiratory infections with close contact with a sick person's breath, cough droplets, or spit; sharing a sick person's utensils and food. Informants suggested that avoiding such contact was the most effective method to prevent respiratory infection. Although informants perceived that handwashing after coughing or sneezing might prevent illness, they felt this was not typically feasible or practical. CONCLUSION: Community perceptions of respiratory infections include both concerns with imbalances between hot and cold, and with person-to-person transmission. Many people were aware of measures that could prevent respiratory infection, but did not practice them. Interventions that leverage community understanding of person-to-person transmission and that encourage the practice of their identified 'good behaviors' related to respiratory hygiene may reduce respiratory disease transmission.