title: Comorbilidad y factores pronósticos al ingreso en una cohorte COVID-19 de un hospital general

text: Antecedents and Objective: To describe clinical features, comorbidity, and prognostic factors associated with in-hospital mortality in a cohort of COVID-19 admitted to a general hospital. Material and Methods: Retrospective cohort study of patients with COVID-19 admitted from 26th February, who had been discharged or died, up to 29th April, 2020. A descriptive study and an analysis of factors associated with intrahospital mortality were performed. Results: Out of the 101 patients, 96 were analysed. Of these, 79 (82%) recovered and were discharged, and 17 (18%) died in the hospital. Diagnosis of COVID-19 was confirmed by polymerase chain reaction to SARS-CoV2 in 92 (92.5%). The mean age was 63 years, and 66% were male. The most frequent comorbidities were hypertension (40%), diabetes mellitus (16%) y cardiopathy (14%). Patients who died were older (mean 77 vs 60 years), had higher prevalence of hypertension (71% vs 33%), and cardiopathy (47% vs 6%), and higher levels of lactate dehydrogenase (LDH) and reactive C protein (mean 662 vs 335 UI/L, and 193 vs 121 mg/L respectively) on admission. In a multivariant analysis the variables significantly associated to mortality were the presence of cardiopathy (CI 95% OR 2,58-67,07), levels of LDH >=345 IU/L (CI 95% OR 1,52-46,00), and age >= 65 years (CI 95% OR 1,23-44,62). Conclusions: The presence of cardiopathy, levels of LDH >=345 IU/L and age >=65 years are associated with a higher risk of death during hospital stay for COVID-19. This model should be validated in prospective cohorts.


title: Probable Secondary Infections in Households of SARS Patients in Hong Kong

text: Although severe acute respiratory syndrome (SARS) is highly infectious in clinical settings, SARS has not been well examined in household settings. The household and household member attack rates were calculated for 1,214 SARS case-patients and their household members, stratified by two phases of the epidemic. A case-control analysis identified risk factors for secondary infection. Secondary infection occurred in 14.9% (22.1% versus 11% in earlier and later phases) of all households and 8% (11.7% versus 5.9% in the earlier and later phases) of all household members. Healthcare workers’ households were less likely to be affected. Risk factors from the multivariate analysis included at-home duration before hospitalization, hospital visitation to the SARS patient (and mask use during the visit), and frequency of close contact. SARS transmission at the household level was not negligible in Hong Kong. Transmission rates may be greatly reduced with precautionary measures taken by household members of SARS patients.


title: Can COVID-19 move Myanmar in the right direction? Perspectives on older people, mental health, and local organizations

text: • Mental Health in Myanmar needs more attention, funding, and research; • Older people's mental health in Myanmar is exacerbated by economic and social effects of COVID-19; • Local community organizations are the main source of care for older people, yet in urgent need for financial support.


title: Identification of the polymerase polyprotein products p72 and p65 of the murine coronavirus MHV-JHM

text: Abstract The RNA polymerase gene of murine coronavirus MHV-JHM encodes a polyprotein of greater than 750 kDa. This polyprotein is proposed to be processed by two papain-like cysteine proteinases, PCP-1 and PCP-2, and a poliovirus 3C-like proteinase domain, 3C-pro, to generate protein products. The amino-terminal product of the MHV polymerase polyprotein, p28, is generated by cleavage of the polyprotein by PCP-1. To identify the viral products downstream of p28, we generated a fusion-protein specific antiserum directed against the region adjacent to p28 and used the antiserum to detect virus-specific proteins from MHV-JHM infected cells. When this antiserum was used to immunoprecipitate radiolabeled proteins from MHV-JHM infected cell lysates, virus-specific proteins of 72 and 65 kDa were detected. Furthermore, pulse and chase experiments demonstrated that p72 is likely a precursor to the mature protein product, p65. To investigate which viral proteinase may be responsible for generating p72 and p65, we expressed the 5′-region of the MHV-JHM RNA polymerase gene including the two papain-like cysteine proteinase domains in an in vitro transcription/translation system and analyzed the translation products for proteolytic processing. We also cloned and expressed the 72 kDa region immediately downstream from p28, and tested the ability of in vitro translated PCP-1 and PCP-2 to cleave p72 to p65 in trans. Our results indicate that neither viral proteinase domain PCP-1 nor PCP-2 is capable of cleavage of p72 to produce p65 in vitro. The role of MHV proteinases in the processing of p72 and p65 is discussed.


title: Successful establishment and global dispersal of genotype VI avian paramyxovirus serotype 1 after cross species transmission

text: Abstract The evolutionary history of avian paramyxovirus serotype 1 (PMV1), which includes the agents of Newcastle disease (ND), is characterized by a series of strain emergence events since viruses in this family were first recognized in the 1920s. Despite the importance of ND to the poultry industry, little is known about PMV1 strain emergence events and the subsequent dispersal and evolution of new strains. The genotype VI-PMV1 was first identified in the 1980s and has been named pigeon paramyxovirus-1 (PPMV1) because of unusual host specificity with Columbiformes (Collins et al., 1996); it has been responsible for panzootics in both chickens and pigeons during that time. Here, we used evolutionary analyses to characterize the emergence of this contemporary PMV1 lineage. We demonstrate that GVI-PMV1 arose through cross-species transmission events from Galliformes (i.e. chicken) to Columbiformes, and quickly established in pigeon populations. Our studies revealed a close association between the time of viral emergence and panzootic events of this virus. The virus appeared first in Southeastern Europe and quickly spread across the European continent, which became the epicenter for global virus dissemination. With new viral gene sequences, we show that GVI-PMV1 viruses currently circulating in North America resulted from multiple invasion events from Europe, one associated with an exotic European Columbiformes species, and that extant lineages have diversified locally. This study extends our understanding of successful viral emergence subsequent to cross-species transmission and dispersal patterns of newly emerged avian viruses, which may improve surveillance awareness and disease control of this and other important avian pathogens.


title: Embryo vaccination of chickens using a novel adjuvant formulation stimulates protective immunity against Eimeria maxima infection

text: Abstract Our previous study demonstrated that chickens immunized subcutaneously with an Eimeria recombinant profilin protein vaccine emulsified in a Quil A/cholesterol/DDA/Carbopol (QCDC) adjuvant developed partial protection against experimental avian coccidiosis compared with animals immunized with profilin alone. Because in ovo vaccination is presently used in commercial applications worldwide throughout the poultry industry, the current study was undertaken to investigate chicken embryo vaccination with profilin plus QCDC adjuvant. Eighteen day-old embryos were immunized with isotonic saline (control), profilin alone, QCDC alone, or profilin plus QCDC, and orally challenged with live Eimeria maxima at 7 days post-hatch. Body weight gain, fecal oocyst output, and intestinal cytokine transcript levels were assessed as measures of protective immunity. While immunization with profilin alone or QCDC alone did not alter body weight gain of infected chickens compared with the saline control group, vaccination with profilin plus QCDC increased body weight gain such that it was equal to the uninfected controls. Immunization with profilin plus QCDC also reduced fecal oocyst shedding compared with unimmunized controls, although in this case QCDC failed to provide an adjuvant effect since no difference was observed between the profilin-only and profilin/QCDC groups. Finally, increased levels of transcripts encoding IL-1β, IL-15, and IFN-γ were seen in the intestinal tissues of animals given profilin plus QCDC compared with the profilin-only or QCDC-only groups. In summary, this study demonstrates an adjuvant effect of QCDC on body weight gain and intestinal cytokine responses following in ovo vaccination of chickens with an Eimeria profilin vaccine.


title: Pneumonia, Acute Respiratory Distress Syndrome, and Early Immune-Modulator Therapy

text: Acute respiratory distress syndrome (ARDS) is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis). The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the potential stage of ARDS.


title: Spontaneous Hinge-Bending Motions of Angiotensin I Converting Enzyme: Role in Activation and Inhibition

text: The inhibition of human angiotensin I converting enzyme (ACE) has been regarded as a promising approach for the treatment of hypertension. Despite research attempts over many years, our understanding the mechanisms of activation and inhibition of ACE is still far from complete. Here, we present results of all atom molecular dynamics simulations of ACE with and without ligands. Two types of inhibitors, competitive and mixed non-competitive, were used to model the ligand bound forms. In the absence of a ligand the simulation showed spontaneous large hinge-bending motions of multiple conversions between the closed and open states of ACE, while the ligand bound forms were stable in the closed state. Our simulation results imply that the equilibrium between pre-existing backbone conformations shifts in the presence of a ligand. The hinge-bending motion of ACE is considered as an essential to the enzyme function. A mechanistic model of activation and the inhibition may provide valuable information for novel inhibitors of ACE.


title: SARS-CoV Infection Was from at Least Two Origins in the Taiwan Area

text: OBJECTIVE: Severe acute respiratory syndrome (SARS) is caused by a new coronavirus. Genomic sequence analysis will provide the molecular epidemiology and help to develop vaccines. METHODS: We developed a rapid method to amplify and sequence the whole SARS-CoV genome from clinical specimens. The technique employed one-step multiplex RT-PCR to amplify the whole SARS-CoV genome, and then nested PCR was performed to amplify a 2-kb region separately. The PCR products were sequenced. RESULTS: We sequenced the genomes of SARS-CoV from 3 clinical specimens obtained in Taiwan. The sequences were similar to those reported by other groups, except that 17 single nucleotide variations and two 2-nucleotide deletions, and a 1-nucleotide deletion were found. All the variations in the clinical specimens did not alter the amino acid sequence. Of these 17 sequenced variants, two loci (positions 26203 and 27812) were segregated together as a specific genotype-T:T or C:C. Phylogenetic analysis showed two major clusters of SARS patients in Taiwan. CONCLUSION: We developed a very economical and rapid method to sequence the whole genome of SARS-CoV, which can avoid cultural influence. From our results, SARS patients in Taiwan may be infected from two different origins.


title: Distinct Characteristics and Complex Evolution of PEDV Strains, North America, May 2013–February 2014

text: Porcine epidemic diarrhea virus (PEDV), which emerged in the United States in 2013, has spread throughout North America. Limited availability of PEDV complete genomes worldwide has impeded our understanding of PEDV introduction into the United States. To determine the relationship between the North American strains and global emerging and historic PEDV strains, we sequenced and analyzed complete genomes of 74 strains from North America; the strains clustered into 2 distinct clades. Compared with the initially reported virulent US PEDV strains, 7 (9.7%) strains from 4 states contained insertions and deletions in the spike gene (S INDELs). These S INDEL strains share 99.8%–100% nt identity with each other and 96.2%–96.7% nt identity with the initial US strains. Furthermore, the S INDEL strains form a distinct cluster within North American clade II, sharing 98.6%–100% nt identity overall. In the United States, the S INDEL and original PEDV strains are co-circulating and could have been introduced simultaneously.


title: Prospective comparison of R-mix™ shell vial system with direct antigen tests and conventional cell culture for respiratory virus detection

text: Abstract Background and objectives Conventional cell culture (CC) has limited clinical utility as a result of the extended incubation period often required for virus isolation. Alternative methodologies have been introduced in an effort to improve turnaround times. One such system, the R-mix™ shell vial is discussed herein. The study objectives were: (a) to establish R-mix™ testing parameters as compared to direct antigen testing (DAT) and CC, and (b) to assess technical aspects and cost of R-mix™ in a high volume clinical virology laboratory. Study design A prospective analysis of respiratory samples submitted to the clinical virology laboratory between November 2004 and April 2005 was performed. All specimens were inoculated onto R-mix™ shell vials (SV) and CC tubes; and a subset also underwent DAT for influenza A and B and/or RSV. A retrospective estimated cost analysis was made. Results A total of 563 samples were included in the study, which collectively revealed a total of 207 viruses. Sensitivity of R-mix™ for seven major respiratory viruses ranged from 45% to 83% compared to CC and DAT, while mean time to detection (TTD) varied from 1.1 to 1.4 days. In addition to these viruses, 23 picornaviruses, 11 CMV isolates and 5 HSV isolates were detected by CC alone. Conclusions The R-mix™ system has similar sensitivity as CC for the detection of parainfluenza 1–3 and influenza A/B while dramatically reducing the TTD. Furthermore, it is significantly more sensitive and produces more timely results for RSV than CC; yet, neither method offers a diagnostic benefit over rapid DAT for RSV detection. The sensitivity of R-mix™ for adenovirus appears to be significantly lower than that of CC. Lastly, methodologies other than R-mix™ must remain in place under circumstances where identification of other potential viral respiratory pathogens, including herpesviruses and picornaviruses, is desired.


title: Immunocapture-based ELISA to characterize and quantify exosomes in both cell culture supernatants and body fluids

text: The immunocapture-based ELISA for extracellular vesicles (EVs)/exosomes, originally described in 2009 by Logozzi and colleagues, allows to capture, detect, characterize and quantify extracellular vesicles in both human body fluids and cell culture supernatants. It is based on the use of two antibodies directed one against a typical exosomal housekeeping protein and the second against either another exosomal housekeeping protein or a potential disease marker: the first antibody is used for the capture of exosomes, the second for the quantification and characterization of the captured vesicles. In fact, with this method it is possible both to characterize and count exosomes and to detect the presence of disease, including tumor, biomarkers. This needs of course to preliminary obtain an EVs purification from the clinical sample; the most agreed method to get to an EVs purification is the repeated rounds of ultracentrifugation, that, while far to be perfect, is the methodological approach allowing to not exclude EVs subpopulation from the separation procedure and to analyze a full range of EVs from both qualitative and quantitative point of view. The immunocapture-based approach has proven to be highly useful in screening, diagnosis and prognosis of tumors, in plasma samples. One amazing information provided by this method is that cancer patients have always significantly higher levels of EVs, in particular of exosomes, independently from the histological nature of the tumor. One microenvironmental factor that is fully involved in the increased exosome release by tumors is the extracellular acidity. However, few pre-clinical data suggest that plasmatic levels of exosomes may correlate with the tumor mass. Some recent clinical reports suggest also that circulating exosomes represent the real delivery system for some known tumor markers that are presently on trial (e.g., PSA). Here we review the pros and cons of the immunocapture-based technique in quantitative and qualitative evaluation of EVs in both health and disease.


title: The yin-yang of long pentraxin PTX3 in inflammation and immunity

text: Abstract Pentraxins are a family of multimeric proteins characterized by the presence of a pentraxin signature in their C-terminus region. Based on the primary structure, pentraxins are divided into short and long pentraxin: C-reactive protein (CRP) is the prototype of the short pentraxin subfamily while pentraxin 3 (PTX3) is the prototypic long pentraxin. Despite these two molecules exert similar fundamental actions in the regulation of innate immune and inflammatory responses, several differences exist between CRP and PTX3, including gene organization, protein oligomerization and expression pattern. The pathophysiological roles of PTX3 have been investigated using genetically modified mice since PTX3 gene organization and regulation are well conserved between mouse and human. Such in vivo studies figured out that PTX3 mainly have host-protective effects, even if it could also exert negative effects under certain pathophysiologic conditions. Here we will review the general properties of CRP and PTX3, emphasizing the differences between the two molecules and the regulatory functions exerted by PTX3 in innate immunity and inflammation.


title: A highly sensitive 1-tube nested real-time RT-PCR assay using LNA-modified primers for detection of respiratory syncytial virus

text: Abstract Respiratory syncytial virus (RSV) causes serious respiratory tract infection worldwide. The relatively low RSV load makes it difficult to detect in frail, elderly, and severely immune-compromised patients. In the present study, we developed a locked nucleic acid–-based 1-tube nested real-time RT-PCR (OTNRT-PCR) assay with the advantages of extremely high sensitivity, facile operability, and less likelihood of cross-contamination. The sensitivity, specificity, and clinical performance of the OTNRT-PCR assay were compared in parallel with a conventional TaqMan probe-based real-time PCR (qRT-PCR) assay and a traditional 2-step nested RT-PCR assay. The limit of detection of the OTNRT-PCR assay was 1.02 × 10−1 TCID50/mL, equivalent to the traditional 2-step nested RT-PCR assay and 25-fold lower than the qRT-PCR assay. Of 616 nasopharyngeal aspirates tested, 143 RSV-negative samples by qRT-PCR were confirmed as positive by sequencing the OTNRT-PCR products. We therefore conclude that OTNRT-PCR is more sensitive than qRT-PCR for detection of RSV in clinical samples.


N95 respirator associated pressure ulcer amongst COVID‐19 health care workers


title: The global diabetes epidemic: what does it mean for infectious diseases in tropical countries?

text: Summary Tropical countries are experiencing a substantial rise in type 2 diabetes, which is often undiagnosed or poorly controlled. Since diabetes is a risk factor for many infectious diseases, this increase probably adds to the large infectious disease burden in tropical countries. We reviewed the literature to investigate the interface between diabetes and infections in tropical countries, including the WHO-defined neglected tropical diseases. Although solid data are sparse, patients with diabetes living in tropical countries most likely face increased risks of common and health-care-associated infections, as well as infected foot ulcers, which often lead to amputation. There is strong evidence that diabetes increases the severity of some endemic infections such as tuberculosis, melioidosis, and dengue virus infection. Some HIV and antiparasitic drugs might induce diabetes, whereas helminth infections appear to afford some protection against future diabetes. But there are no or very scarce data for most tropical infections and for possible biological mechanisms underlying associations with diabetes. The rise in diabetes and other non-communicable diseases puts a heavy toll on health systems in tropical countries. On the other hand, complications common to both diabetes and some tropical infections might provide an opportunity for shared services—for example, for eye health (trachoma and onchocerciasis), ulcer care (leprosy), or renal support (schistosomiasis). More research about the interaction of diabetes and infections in tropical countries is needed, and the infectious disease burden in these countries is another reason to step up global efforts to improve prevention and care for diabetes.


title: Containment of COVID-19 cases among healthcare workers: The role of surveillance, early detection, and outbreak management

text: OBJECTIVE: Staff surveillance is crucial during the containment phase of a pandemic to help reduce potential healthcare-associated transmission and sustain good staff morale. During an outbreak of SARS-COV-2 with community transmission, our institution used an integrated strategy for early detection and containment of COVID-19 cases among healthcare workers (HCWs). METHODS: Our strategy comprised 3 key components: (1) enforcing reporting of HCWs with acute respiratory illness (ARI) to our institution’s staff clinic for monitoring; (2) conducting ongoing syndromic surveillance to obtain early warning of potential clusters of COVID-19; and (3) outbreak investigation and management. RESULTS: Over a 16-week surveillance period, we detected 14 cases of COVID-19 among HCWs with ARI symptoms. Two of the cases were linked epidemiologically and thus constituted a COVID-19 cluster with intrahospital HCW–HCW transmission; we also detected 1 family cluster and 2 clusters among HCWs who shared accommodation. No transmission to HCWs or patients was detected after containment measures were instituted. Early detection minimized the number of HCWs requiring quarantine, hence preserving continuity of service during an ongoing pandemic. CONCLUSIONS: An integrated surveillance strategy, outbreak management, and encouraging individual responsibility were successful in early detection of clusters of COVID-19 among HCWs. With ongoing local transmission, vigilance must be maintained for intrahospital spread in nonclinical areas where social mingling of HCWs occurs. Because most individuals with COVID-19 have mild symptoms, addressing presenteeism is crucial to minimize potential staff and patient exposure.


title: Revealing −1 Programmed Ribosomal Frameshifting Mechanisms by Single-Molecule Techniques and Computational Methods

text: Programmed ribosomal frameshifting (PRF) serves as an intrinsic translational regulation mechanism employed by some viruses to control the ratio between structural and enzymatic proteins. Most viral mRNAs which use PRF adapt an H-type pseudoknot to stimulate −1 PRF. The relationship between the thermodynamic stability and the frameshifting efficiency of pseudoknots has not been fully understood. Recently, single-molecule force spectroscopy has revealed that the frequency of −1 PRF correlates with the unwinding forces required for disrupting pseudoknots, and that some of the unwinding work dissipates irreversibly due to the torsional restraint of pseudoknots. Complementary to single-molecule techniques, computational modeling provides insights into global motions of the ribosome, whose structural transitions during frameshifting have not yet been elucidated in atomic detail. Taken together, recent advances in biophysical tools may help to develop antiviral therapies that target the ubiquitous −1 PRF mechanism among viruses.


Interpreting the COVID-19 Test Results: a Guide for Physiatrists


title: Rabbit hemorrhagic disease

text: Abstract Rabbit Hemorrhagic Disease (RHD) is a rapidly lethal infectious viral disease of the European Rabbit (Oryctolagus cuniculus) characterized by high mortality rates, acute hepatic necrosis, and disseminated intravascular coagulation. Although this disease is considered enzootic in Europe and parts of Asia, it is rarely seen in the Western Hemisphere since its eradication from Mexico in 1992. In recent years, three cases of RHD have been identified in the United States. Due to the quick action of veterinarians these cases were confined and controlled before the disease could spread.


title: Political polarization at the time of the coronavirus: A Brazilian's view

text: Initially, I would like to congratulate the Editors of Oral Diseases for the initiative of grouping together different realities of our colleagues around the world, in the face of what seems to be the biggest crisis, not only in health but also in economics, politics and why not say of values, which certainly goes beyond our generation, for some with an extra component, that includes religion.


title: The Great Opportunity: Cultivating Scientific Inquiry in Medical Residency

text: Residency training is a profound experience that greatly influences the career trajectory of every trainee. Currently, residency programs focus heavily (or almost exclusively) on the acquisition of medical knowledge and fail to foster intellectual curiosity and introduce residents to careers in investigation. We share 3 programs embedded in residency training where this focus is shifted with an emphasis on prompting intellectual curiosity and exciting residents about careers in investigation to revitalize the physician-scientist workforce.


The COVID-19 Pandemic Highlights Shortcomings in US Health Care Informatics Infrastructure: A Call to Action


title: The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridiumdifficile Infection: Current Understanding and Gap Analysis

text: The leading risk factor for Clostridioides (Clostridium) difficile infection (CDI) is broad-spectrum antibiotics, which lead to low microbial diversity, or dysbiosis. Current therapeutic strategies for CDI are insufficient, as they do not address the key role of the microbiome in preventing C. difficile spore germination into toxin-producing vegetative bacteria, which leads to symptomatic disease. Fecal microbiota transplant (FMT) appears to reduce the risk of recurrent CDI through microbiome restoration. However, a wide range of efficacy rates have been reported, and few placebo-controlled trials have been conducted, limiting our understanding of FMT efficacy and safety. We discuss the current knowledge gaps driven by questions around the quality and consistency of clinical trial results, patient selection, diagnostic methodologies, use of suppressive antibiotic therapy, and methods for adverse event reporting. We provide specific recommendations for future trial designs of FMT to provide improved quality of the clinical evidence to better inform treatment guidelines.


title: Human Coronavirus OC43 RNA 4 Lacks Two Open Reading Frames Located Downstream of the S Gene of Bovine Coronavirus

text: Abstract Nucleotide sequences between the spike (S) and membrane (M) protein genes of the OC43 strain of human coronavirus were obtained from POP-amplified vital mRNAs. Sequence analysis of this region revealed the presence of two ORFs encoding proteins of 12.9 and 9.5 kDa. These two proteins were identified as putatively nonstructural (ns) due to their homology to the corresponding BCV ns gene products. Northern blot analysis indicated that each of these two genes was present on a separate mRNA (5 and 5-1, respectively). In vitro translation analyses demonstrated that the HCV-OC43 9.5-kDa protein, like its BCV counterpart, is poorly translated when situated downstream of the 12.9-kDa ORF, although immunofluorescence studies did confirm its presence in infected cells. Sequence analysis showed that a large portion of the 3′-end of the leader sequence is present within the viral genome, upstream of the 12.9-kDa ORF. In addition, two ORFs encoding potential 4.9- and 4.8-kDa ns proteins in BCV are absent in HCV-OC43, although a corresponding mRNA 4 was found at a very low level. These results demonstrate that these two putative ns proteins are not essential for virus replication, at least in HRT-18 cells.


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title: Neurological manifestations in COVID‐19 caused by SARS‐CoV‐2


Home‐visit medical care for COVID‐19 patients


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title: Panax ginseng and Panax quinquefolius: From pharmacology to toxicology

text: Abstract The use of Panax ginseng and Panax quinquefolius in traditional Chinese medicine dates back to about 5000 years ago thanks to its several beneficial and healing properties. Over the past few years, extensive preclinical and clinical evidence in the scientific literature worldwide has supported the beneficial effects of P. ginseng and P. quinquefolius in significant central nervous system, metabolic, infectious and neoplastic diseases. There has been growing research on ginseng because of its favorable pharmacokinetics, including the intestinal biotransformation which is responsible for the processing of ginsenosides - contained in the roots or extracts of ginseng - into metabolites with high pharmacological activity and how such principles act on numerous cell targets. The aim of this review is to provide a simple and extensive overview of the pharmacokinetics and pharmacodynamics of P. ginseng and P. quinquefolius, focusing on the clinical evidence which has shown particular effectiveness in specific diseases, such as dementia, diabetes mellitus, respiratory infections, and cancer. Furthermore, the review will also provide data on toxicological factors to support the favorable safety profile of these medicinal plants.


title: Benzimidazole analogs inhibit respiratory syncytial virus G protein function

text: Abstract Human respiratory syncytial virus (hRSV) is a highly contagious Paramyxovirus that infects most children by age two, generating an estimated 75,000–125,000 hospitalizations in the U.S. annually. hRSV is the most common cause of bronchiolitis and pneumonia among infants and children under 1year of age, with significant mortality among high-risk groups. A regulatory agency-approved vaccine is not available, and existing prophylaxis and therapies are limited to use in high-risk pediatric patients; thus additional therapies are sorely needed. Here, we identify a series of benzimidazole analogs that inhibit hRSV infection in vitro with high potency, using a previously-reported high-throughput screening assay. The lead compound, SRI 29365 (1-[6-(2-furyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl]methyl-1H-benzimidazole), has an EC50 of 66μM and a selectivity >50. We identified additional compounds with varying potencies by testing commercially-available chemical analogs. Time-of-addition experiments indicated that SRI 29365 effectively inhibits viral replication only if present during the early stages of viral infection. We isolated a virus with resistance to SRI 29365 and identified mutations in the transmembrane domain of the viral G protein genomic sequence that suggested that the compound inhibits G-protein mediated attachment of hRSV to cells. Additional experiments with multiple cell types indicated that SRI 29365 antiviral activity correlates with the binding of cell surface heparin by full-length G protein. Lastly, SRI 29365 did not reduce hRSV titers or morbidity/mortality in efficacy studies using a cotton rat model. Although SRI 29365 and analogs inhibit hRSV replication in vitro, this work suggests that the G-protein may not be a valid drug target in vivo.


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title: Successful clearance of human parainfluenza virus type 2 viraemia with intravenous ribavirin and immunoglobulin in a patient with acute myocarditis

text: Abstract Human parainfluenza virus (HPIV) infection as an aetiology of acute viral myocarditis is rare, with only few cases reported in the literature to date. Here we report a case of fulminant HPIV-2 myocarditis in a 47 year-old man with viraemia who was successfully treated with intravenous ribavirin and intravenous immunoglobulin (IVIG). There are currently no recommendations on the treatment of HPIV myocarditis. We are, to our knowledge, the first to report a patient with a documented HPIV-2 viraemia that subsequently cleared after the initiation of antiviral therapy. Although it is difficult to definitively attribute the patient's clinical improvement to ribavirin or IVIG alone, our case does suggest that clinicians may wish to consider initiating ribavirin and IVIG in patients with HPIV myocarditis and persistent viraemia not responding to supportive measures alone.


title: Lessons From the Polio Endgame: Overcoming the Failure to Vaccinate and the Role of Subpopulations in Maintaining Transmission

text: BACKGROUND. Recent detections of circulating serotype 2 vaccine-derived poliovirus in northern Nigeria (Borno and Sokoto states) and Pakistan (Balochistan Province) and serotype 1 wild poliovirus in Pakistan, Afghanistan, and Nigeria (Borno) represent public health emergencies that require aggressive response. METHODS. We demonstrate the importance of undervaccinated subpopulations, using an existing dynamic poliovirus transmission and oral poliovirus vaccine evolution model. We review the lessons learned during the polio endgame about the role of subpopulations in sustaining transmission, and we explore the implications of subpopulations for other vaccine-preventable disease eradication efforts. RESULTS. Relatively isolated subpopulations benefit little from high surrounding population immunity to transmission and will sustain transmission as long as they do not attain high vaccination coverage. Failing to reach such subpopulations with high coverage represents the root cause of polio eradication delays. Achieving and maintaining eradication requires addressing the weakest links, which includes immunizing populations in insecure areas and/or with disrupted or poor-performing health systems and managing the risks of individuals with primary immunodeficiencies who can excrete vaccine-derived poliovirus long-term. CONCLUSIONS. Eradication efforts for vaccine-preventable diseases need to create performance expectations for countries to immunize all people living within their borders and maintain high coverage with appropriate interventions.Keywords. Polio; eradication; transmission; heterogeneity.


title: A healthy degree of suspicion: A discussion of the implementation of transmission based precautions in the emergency department

text: Summary Background Emergency department (ED) presentations have increased significantly domestically and internationally. Swift identification and implementation of transmission based precautions (TBP) for patients known or suspected of having an epidemiologically important pathogen is important. ED staff, particularly triage nurses, are pivotal in detecting and preventing infection, including healthcare associated infections (HAI). Methods MEDLINE, CINAHL, PubMed and Ovid were searched for articles published between 2004 and 2015 using key search terms: infection control/prevention and emergency department(s), triage, and transmission based precautions and emergency department(s), and triage, to identify common themes for discussion. Systematic review/meta-analysis was not in the scope of this exploration. Findings Themes were identified relating to HAI and ED practices and grouped into: assisted detection of conditions for which TBP is required, ED and TBP, mass-causality event/bioterrorism/pandemic/epidemic, infection control not TBP and multi-resistant organisms not TBP. The literature is heavily influenced by worldwide epidemic/pandemics and bioterrorist risks resulting in increased awareness of the importance of swift identification of syndromes that require TBP, but only in these situations. Conclusion Implementation of appropriate TBP, changing triage practices, training and measures to assist decision-making could assist in preventing HAI in the ED context. A systematic quantitative review of the literature is recommended to guide practice change research.


title: Maintenance of influenza virus infectivity on the surfaces of personal protective equipment and clothing used in healthcare settings

text: OBJECTIVES: The maintenance of infectivity of influenza viruses on the surfaces of personal protective equipment and clothing is an important factor in terms of controlling viral cross-infection in the environment and preventing contact infection. The aim of this study was to determine if laboratory-grown influenza A (H1N1) virus maintained infectivity on the surfaces of personal protective equipment and clothing used in healthcare settings. METHODS: Influenza A virus (0.5 mL) was deposited on the surface of a rubber glove, an N95 particulate respirator, a surgical mask made of non-woven fabric, a gown made of Dupont Tyvek, a coated wooden desk, and stainless steel. Each sample was left for 1, 8, and 24 h, and hemagglutination (HA) and 50% tissue culture infective dose (TCID(50))/mL were measured. RESULTS: The HA titer of this influenza A virus did not decrease in any of the materials tested even after 24 h. The infectivity of influenza A virus measured by TCID(50) was maintained for 8 h on the surface of all materials, with the exception of the rubber glove for which virus infectivity was maintained for 24 h. CONCLUSIONS: Our results indicate that the replacement/renewal of personal protective equipment and clothing by healthcare professionals in cases of exposure to secretions and droplets containing viruses spread by patients is an appropriate procedure to prevent cross-infection.


title: Avian Interferon-Inducible Transmembrane Protein Family Effectively Restricts Avian Tembusu Virus Infection

text: Avian Tembusu virus (ATMUV) is a highly pathogenic flavivirus that causes significant economic losses to the Chinese poultry industry. Our previous experiments demonstrated that ATMUV infection effectively triggered host innate immune response through MDA5 and TLR3-dependent signaling pathways. However, little information is available on the role of interferon-stimulated genes (ISGs) in defending against ATMUV infection. In this study, we found that ATMUV infection induced robust expression of type I and type III interferon (IFNs) in duck tissues. Furthermore, we observed that expression of interferon-inducible transmembrane proteins (IFITMs) was significantly upregulated in DEF and DF-1 cells after infection with ATMUV. Similar results were obtained from in vivo studies using ATMUV-infected ducklings. Importantly, we showed that knockdown of endogenous IFITM1 or IFITM3 by specific shRNA markedly enhanced ATMUV replication in DF-1 cells. However, disruption of IFITM2 expression had no obvious effect on the ATMUV replication. In addition, overexpression of chicken or duck IFITM1 and IFITM3 in DF-1 cells impaired the replication of ATMUV. Taken together, these results reveal that induced expression of avian IFITM1 and IFITM3 in response to ATMUV infection can effectively restrict the virus replication, and suggest that increasing IFITM proteins in host may be a useful strategy for control of ATMUV infection.


title: Molecular Modeling of Inhibitors of Human DNA Methyltransferase with a Crystal Structure: Discovery of a Novel DNMT1 inhibitor

text: DNA methyltransferases (DNMTs) are promising epigenetic targets for the development of novel anticancer drugs and other diseases. Molecular modeling and experimental approaches are being used to identify and develop inhibitors of human DNMTs. Most of the computational efforts conducted so far with DNMT1 employ homology models of the enzyme. Recently, a crystallographic structure of the methyltransferase domain of human DNMT1 bound to unmethylated DNA was published. Following on our previous computational and experimental studies with DNMTs, we herein present molecular dynamics of the crystal structure of human DNMT1. Docking studies of established DNMT1 inhibitors with the crystal structure gave rise to a structure-based pharmacophore model that suggests key interactions of the inhibitors with the catalytic binding site. Results had a good agreement with the docking and pharmacophore models previously developed using a homology model of the catalytic domain of DNMT1. The docking protocol was able to distinguish active DNMT1 inhibitors from, for example, experimentally known inactive DNMT1 inhibitors. As part of our efforts to identify novel inhibitors of DNMT1, we conducted the experimental characterization of aurintricarboxylic acid (ATA) that in preliminary docking studies showed promising activity. ATA had a sub-micromolar inhibition (IC(50) = 0.68 μM) against DNMT1. ATA was also evaluated for Dnmt3a inhibition showing an IC(50) = 1.4 μM. This chapter illustrates the synergy from integrating molecular modeling and experimental methods for further advance the discovery of novel candidates for epigenetic therapies.


title: Evidence of prenatal toxicity of herbal based indigenous formulations for sex selection in rat models

text: Abstract Indigenous preparations(IPs) for a male child is reported from some parts of India. The present study aims to explore the effects of IPs for sex selection or sex selection drugs (SSDs) on pregnancy outcomes in rat models. SSDs contain Bryonia laciniosa, Quercus infectoria and Putranjiva roxburghii along with other ingredients. Methods An experimental design with successfully mated female rats were randomized into control and treatment groups. Phase 1 had 2 interventional arms while phase 2 had 3 interventional arms (12 rats/arm) besides control arm. In phase-1, pregnant females were dosed two SSDs(1000 mg/kg) on gestation days 1–5 whereas, in phase-2, on gestation days 6–19 to correlate the effect of the SSDs (500/1000/1500 mg/kg) consumption during different stages of pregnancy. Pregnant females were observed for clinical signs following treatment. The rats were sacrificed one day before expected day of delivery for evaluation. Pregnancy rate, gestation index, number of corpora lutea, and litter size were assessed. Foetuses were examined for sex, skeletal and soft tissue alterations. Discussion and conclusion In phase 1, no appreciable findings were there with SSD exposure. In phase 2, intrauterine growth and survival of foetuses were affected when SSDs were administered during organogenesis period. Decreased number of live foetuses and increased incidence of early and late resorption, reduced fetal growth with significant alteration in skeleton and viscera were found in treatment groups in a dose-dependent manner. This correlates well with findings from observational studies in pregnant women. However, such treatment at any dose did not effect sex differentiation.


Covid-19—The real role of NSAIDs in Italy


title: A data driven epidemic model to analyse the lockdown effect and predict the course of COVID-19 progress in India

text: We propose a data driven epidemic model using the real data on the infection, recovery and death cases for the analysis of COVID-19 progression in India. The model assumes continuation of existing control measures such as lockdown and quarantines, the suspected and confirmed cases and does not consider the scenario of 2(nd) surge of the epidemic due to any reason. The model is arrived after least square fitting of epidemic behaviour model based on theoretical formulation to the real data of cumulative infection cases reported between 24 March 2020 and 30May 2020. The predictive capability of the model has been validated with real data of infection cases reported during June 1-10, 2020. A detailed analysis of model predictions in terms of future trend of COVID-19 progress individually in 18 states of India and India as a whole has been attempted. Infection rate in India, as a whole, is continuously decreasing with time and has reached 3 times lower than the initial infection rate after 6 weeks of lock down suggesting the effectiveness of the lockdown in containing the epidemic. Results suggest that India, as a whole, could see the peak and end of the epidemic in the month of July 2020 and March 2021 respectively as per the current trend in the data. Active infected cases in India may touch 2 lakhs or little above at the peak time and total infected cases may reach over 19 lakhs as per current trend. State-wise results have been discussed in the manuscript. However, the prediction may deviate particularly for longer dates, as assumptions of model cannot be met always in a real scenario. In view of this, a real time application (COV-IND Predictor) has been developed which automatically syncs the latest data from the national COVID19 dash board on daily basis and updates the model input parameters and predictions instantaneously. This real time application can be accessed from the link: https://docs.google.com/spreadsheets/d/1fCwgnQ-dz4J0YWVDHUcbEW1423wOJjdEXm8TqJDWNAk/edit?usp=sharing and can serve as a practical tool for policy makers to track peak time and maximum active infected cases based on latest trend in data for medical readiness and taking epidemic management decisions.


docid: bcfkosyj

title: West Nile virus genome amplification requires the functional activities of the proteasome

text: Abstract The lifecycle of intracellular pathogens, especially viruses, is intimately tied to the macromolecular synthetic processes of their host cell. In the case of positive-stranded RNA viruses, the ability to translate and, thus, replicate their infecting genome is dependent upon hijacking host proteins. To identify proteins that participate in West Nile virus (WNV) replication, we tested the ability of siRNAs designed to knock-down the expression of a large subset of human genes to interfere with replication of WNV replicons. Here we report that multiple siRNAs for proteasome subunits interfered with WNV genome amplification. Specificity of the interference was shown by demonstrating that silencing proteasome subunits did not interfere with Venezuelan equine encephalitis virus replicons. Drugs that blocked proteasome activity were potent inhibitors of WNV genome amplification even if cells were treated 12 h after infection, indicating that the proteasome is required at a post-entry stage(s) of the WNV infection cycle.


title: Policy opportunities and challenges from the COVID-19 pandemic for economies with large informal sectors

text: In the developing world, the informal economy can account for as much as 80% of the population. I focus on the urban component of informality, where both informal employment and informal enterprises are especially vulnerable to the pandemic-induced economic shock. I explain the complex nature of informality, some of the reasons for its persistence and its interdependency with the formal economy, especially in the manufacturing sector, through global value chains (GVCs). Large firms (whether MNEs or domestic firms) sub-contract considerable activity to informal enterprises, but this is precarious in character. I suggest the crisis provides the circumstances for greater active engagement with informal actors, by placing informal enterprises on a par with formal firms within industrial policy. I propose integration and registration, as opposed to formalisation, and the provision of state support without taxation. The role of the state is also crucial in matchmaking, creating incentives for GVCs to engage with informal actors systematically, and to reduce the transaction costs for informal actors in such engagement. These actions are likely to provide benefits in the longer run, even if they prove costly in the short run.


title: The Change of USMLE Step 1 to Pass/Fail: Perspectives of the Surgery Program Director

text: OBJECTIVE: This study sought to evaluate the perspectives of surgical program directors regarding the change of USMLE Step 1 to pass/fail grading. DESIGN: Validated electronic survey. SETTING: Vanderbilt University Medical Center Department of Plastic Surgery. PARTICIPANTS: Program directors of all ACMGE-accredited General Surgery, Integrated Vascular Surgery, Integrated Thoracic Surgery, and Integrated Plastic Surgery residency programs. RESULTS: The overall response rate was 55.5%. Most PDs (78.1%) disagreed with the scoring change. Only 19.6% believe this change will improve medical student well-being. For 63.5% of PDs, medical school pedigree will become more important, and 52.7% believe it will place international medical graduates at a disadvantage. Only 6.2% believe Step 2 CK should also be pass/fail, while 88.7% will increase the weight of Step 2 CK and 88.4% will now require Step 2 CK score submission with the electronic residency application service. CONCLUSIONS: While well-intentioned, changing USMLE Step 1 to pass/fail may have unintended consequences and may disadvantage certain groups of applicants. The emphasis on Step 1, and resulting test-taking apprehension, will likely shift to Step 2 CK. Proponents of equitable evaluation should direct their efforts toward increasing, not decreasing, the number of objective measures available for student assessment.


Inhibitors of the renin–angiotensin system and SARS-CoV-2 infection


title: Chapter 542 Hepatitis A Virus Picornain 3C

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 800 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 540 is Hepatitis A Virus Picornain 3C. Keywords: β-barrel, β-ribbon, catalytic triad, cleavage site, hepatitis A virus, polyprotein processing, substrate specificity pocket, picornain 3C, picornavirus, viral cysteine proteinase.


docid: jaaqvzfd

title: Perceptions related to human avian influenza and their associations with anticipated psychological and behavioral responses at the onset of outbreak in the Hong Kong Chinese general population

text: BACKGROUND: Anticipated psychological responses and perceptions of risk have not been examined prior to the outbreak of an epidemic. METHODS: Using a cross-sectional, telephone survey, 805 Chinese adults in Hong Kong were interviewed anonymously in November, 2005 to examine beliefs related to H5N1 avian influenza and anticipated responses. RESULTS: Of respondents, 71.4% and 52.4%, respectively, believed that bird-to-human or human-to-human H5N1 transmission would occur in the next year. In the event of a bird-to-human or human-to-human outbreak in Hong Kong, many anticipated high fatality rates (70.5% and 74.4%, respectively), permanent physical damage (52.0% and 54.9%, respectively), inadequate vaccines (50.0% and 64.4%, respectively), insufficient medicine supplies (43.7% and 54.5%, respectively), inadequate hospital infection control (35.1% and 43.3%, respectively), high susceptibility of family members contracting H5N1 (13.9% and 24.3%, respectively), and impact on oneself/family worse than those of severe acute respiratory syndrome (21.2 and 25.0%, respectively). Most anticipated at least 1 of the 7 studied stress-related responses (e.g., panic) or the adoption of at least 1 of the 5 studied preventive behavioral measures (e.g., avoiding going out). CONCLUSION: Panic and interruption of daily routines may occur in the event of a human avian influenza outbreak. Dissemination of accurate, timely information would reduce unnecessary distress and unwanted behaviors.


title: Comparison of the anti-allergic activity of Syk inhibitors with optimized Syk siRNAs in FcεRI-activated RBL-2H3 basophilic cells

text: Abstract Spleen tyrosine kinase (Syk) binds ITAM-bearing receptors in a wide variety of cell types. One such example is the activation of mast cells, basophils and eosinophils via the stimulation of the FcεRI receptor by IgE/allergen complexes. The possible role of Syk in inflammatory signaling cascades has led to the development of pharmacological agents designed to block the Syk catalytic domain as potential novel therapeutics. Whilst the enzymatic activity of Syk lends towards the design of small-molecule inhibitors, other attention has focused on the possibility of targeting Syk expression using anti-sense oligonucleotides as an alternate means of anti-inflammatory therapy. In this study, we compared the ability of multiple optimized Syk siRNA sequences and small-molecule Syk inhibitors to block FcεRI-mediated signal transduction, degranulation and TNFα secretion in the basophilic cell line RBL-2H3. We also characterized the specificity of each siRNA sequence with regards to off-target induction of the interferon-inducible gene IFIT1. We identified a single siRNA sequence, which displayed a favorable profile of efficient Syk knockdown, blockage of FcεRI-mediated signal transduction, degranulation and TNFα secretion and a lack of IFIT1 induction. The effect of this siRNA was comparable to that of the Syk kinase domain inhibitors BAY61-3606 and R406. The identification of an active and specific Syk siRNA could be a basis for the development of therapeutic Syk siRNAs against inflammatory diseases.


title: Information theory-based algorithm for in silico prediction of PCR products with whole genomic sequences as templates

text: BACKGROUND: A new algorithm for assessing similarity between primer and template has been developed based on the hypothesis that annealing of primer to template is an information transfer process. RESULTS: Primer sequence is converted to a vector of the full potential hydrogen numbers (3 for G or C, 2 for A or T), while template sequence is converted to a vector of the actual hydrogen bond numbers formed after primer annealing. The former is considered as source information and the latter destination information. An information coefficient is calculated as a measure for fidelity of this information transfer process and thus a measure of similarity between primer and potential annealing site on template. CONCLUSION: Successful prediction of PCR products from whole genomic sequences with a computer program based on the algorithm demonstrated the potential of this new algorithm in areas like in silico PCR and gene finding.


title: Genetic characterization of novel reassortant H1N2 influenza A viruses isolated from pigs in southeastern China

text: In December 2004, three influenza H1N2 viruses were isolated from lung samples of pigs that had died from respiratory disease on a farm in southeastern China. To determine the genetic characterization and probable origin, one of the three isolates, A/Swine/Zhejiang/1/2004 (Sw/ZJ/1/2004), was genetically analyzed. Sw/ZJ/1/2004 was a reassortant with an NA gene most closely related to the corresponding gene from a human-like H3N2 virus circulating in 1995. The remaining seven genes were most closely related to those from the classical swine H1N1 virus. Sw/ZJ/1/2004 appeared to be a novel reassortant H1N2 virus that was genetically distinguishable from other H1N2 viruses found in pigs worldwide. The isolation of Sw/ZJ/1/2004 provided further evidence for pigs serving as a “mixing vessel” for the generation of new reassortant genotypes of influenza viruses and emphasizes the importance of reinforcing influenza virus surveillance in pigs in China.


title: Analysis of multiplex PCR fragments with PMMA microchip

text: Abstract Microchip electrophoresis is a promising technique for analysis of bio-molecules. It has the advantages of fast analysis, high sensitivity, high resolution and low-cost of samples. Plastic chip has the potential of mass production for clinical use for its advantages in biocompatibility and low cost. In this work, the method for fabrication of poly(methyl methacrylate) (PMMA) chip was described, and conditions for DNA separation were investigated with the chip. The PMMA microchip was used for detection of multiplex PCR products of 18 and 36 cases with SARS and hepatitis B virus infection under optimized separation conditions. Microchip electrophoresis showed higher sensitivity, higher resolution and less time consumption when compared with gel electrophoresis. The microchip electrophoresis with PMMA chip provided a rapid, sensitive and reliable method for analysis of multiplex PCR products.


title: Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development

text: Abstract Background Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19. SARS Coronavirus (SARS-CoV), MERS Coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2, are the causative agents of the SARS, MERS, and COVID-19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long-lasting virus-specific immune responses against these infectious agents are urgently needed. The coronavirus spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines for the prevention of coronavirus infection. Methods We first generated codon optimized MERS-S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. We comprehensively tested the pre-clinical immunogenicity of MERS-CoV vaccines in mice when delivered subcutaneously by traditional needle injection, or intracutaneously by dissolving microneedle arrays (MNAs) by evaluating virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays. Driven by the urgent need for COVID-19 vaccines, we utilized this strategy to rapidly develop MNA SARS-CoV-2 subunit vaccines and tested their pre-clinical immunogenicity in vivo by exploiting our substantial experience with MNA MERS-CoV vaccines. Findings Here we describe the development of MNA delivered MERS-CoV vaccines and their pre-clinical immunogenicity. Specifically, MNA delivered MERS-S1 subunit vaccines elicited strong and long-lasting antigen-specific antibody responses. Building on our ongoing efforts to develop MERS-CoV vaccines, promising immunogenicity of MNA-delivered MERS-CoV vaccines, and our experience with MNA fabrication and delivery, including clinical trials, we rapidly designed and produced clinically-translatable MNA SARS-CoV-2 subunit vaccines within 4 weeks of the identification of the SARS-CoV-2 S1 sequence. Most importantly, these MNA delivered SARS-CoV-2 S1 subunit vaccines elicited potent antigen-specific antibody responses that were evident beginning 2 weeks after immunization. Interpretation MNA delivery of coronaviruses-S1 subunit vaccines is a promising immunization strategy against coronavirus infection. Progressive scientific and technological efforts enable quicker responses to emerging pandemics. Our ongoing efforts to develop MNA-MERS-S1 subunit vaccines enabled us to rapidly design and produce MNA SARS-CoV-2 subunit vaccines capable of inducing potent virus-specific antibody responses. Collectively, our results support the clinical development of MNA delivered recombinant protein subunit vaccines against SARS, MERS, COVID-19, and other emerging infectious diseases.


title: Prevalence of depression and its association with quality of life in clinically stable patients with COVID-19

text: INTRODUCTION: : High risk of mental health problems is associated with Coronavirus Disease 2019 (COVID-19). This study explored the prevalence of depressive symptoms (depression hereafter) and its relationship with quality of life (QOL) in clinically stable patients with COVID-19. METHODS: : This was an online survey conducted in COVID-19 patients across five designated isolation hospitals for COVID-19 in Hubei province, China. Depression and QOL were assessed with standardized instruments. RESULTS: : A total of 770 participants were included. The prevalence of depression was 43.1% (95%CI: 39.6%-46.6%). Binary logistic regression analysis found that having family member infected with COVID-19 (OR=1.51, P=0.01), suffering from severe COVID-19 infection (OR=1.67, P=0.03), male gender (OR=0.53, P<0.01), and frequent social media use to obtain COVID-19 related information (OR=0.65, P<0.01) were independently associated with depression. Patients with depression had lower QOL than those without. CONCLUSION: : Depression is highly prevalent in clinically stable patients with COVID-19. Regular screening and appropriate treatment of depression are urgently warranted for this population.


title: Prediction of quaternary assembly of SARS coronavirus peplomer

text: Abstract The tertiary structures of the S1 and S2 domains of the spike protein of the coronavirus which is responsible of the severe acute respiratory syndrome (SARS) have been recently predicted. Here a molecular assembly of SARS coronavirus peplomer which accounts for the available functional data is suggested. The interaction between S1 and S2 appears to be stabilised by a large hydrophobic network of aromatic side chains present in both domains. This feature results to be common to all coronaviruses, suggesting potential targeting for drugs preventing coronavirus-related infections.


title: New classes of Gram-positive selective antibacterials: Inhibitors of MRSA and surrogates of the causative agents of anthrax and tuberculosis

text: Abstract An antimicrobial phenolic stilbene, (E)-3-hydroxy-5-methoxystilbene, 1 was recently isolated from the leaves of Comptonia peregrina (L.) Coulter and shown to possess inhibitory activity against several Gram-positive bacteria, including isolates of methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium bovis BCG, and avirulent Bacillus anthracis (Sterne strain), among others. These results prompted the design and synthesis of two new classes of compounds, phenoxystyrenes and phenothiostyrenes, as analogs of the natural antimicrobial stilbene. These and additional stilbenoid analogs were synthesized using new, efficient, copper-mediated coupling strategies. Minimum inhibitory concentration (MIC) antimicrobial assays were performed on all compounds prepared. These preliminary structure–activity relationship studies indicated that both new classes of synthetic analogs, as well as the stilbenes, show promising activity against Gram-positive bacteria when at least one phenolic moiety is present, but not when absent. The potencies of the phenolic phenoxystyrenes and phenothiostyrenes were found to be comparable to those of the phenolic stilbenes tested.


title: SARS-CoV-2 infection among patients with systemic autoimmune diseases

text: Abstract Objectives This study aimed to evaluate the prevalence of clinically overt SARS-CoV-2 infection (COVID-19) among patients with systemic autoimmune diseases residing in Tuscany, and to compare it with that observed in the general Tuscan population. Methods In this cross-sectional study, Tuscan outpatients with systemic autoimmune diseases followed at a tertiary referral centre were telephonically interviewed between April 1st-14th 2020 to collect demographic and clinical data, information on ongoing immunomodulating/immunosuppressive treatments, and on the presence of symptoms suspected of SARS-CoV-2 or of a confirmed infection. Results 458 patients were interviewed [74% female, median age 56 years (IQR 43–68)]; 56% of them were receiving corticosteroids, 44% traditional disease-modifying anti-rheumatic drugs (DMARDs), of whom 23% hydroxychloroquine, 5% colchicine, while 41% were on biologic DMARDs (of whom 9% on tocilizumab). Thirteen patients reported symptoms suggesting SARS-CoV-2 infection. Of them, 7 had undergone nasopharyngeal swab and only one was positive and developed severe SARS-CoV-2 complications. Within our cohort, the prevalence of SARS-CoV-2 infection was therefore 0.22% (0.01–1.21%), comparable to that observed in the general population of Tuscany [0.20% (0.20–0.21%), p = .597]. Conclusions Patients with systemic autoimmune diseases do not seem to carry an increased risk of SARS- CoV-2 infection as compared to the general population.


title: Towards health monitoring using remote heart rate measurement using digital camera: A feasibility study

text: The paper presents a feasibility study for heart rate measurement using a digital camera to perform health monitoring. The feasibility study investigates the reliability of the state of the art heart rate measuring methods in realistic situations. Therefore, an experiment was designed and carried out on 45 subjects to investigate the effects caused by illumination, motion, skin tone, and distance variance. The experiment was conducted for two main scenarios; human-computer interaction scenario and health monitoring scenario. The human-computer scenario investigated the effects caused by illumination variance, motion variance, and skin tone variance. The health monitoring scenario investigates the feasibility of health monitoring at public spaces (i.e. airports, subways, malls). Five state of the art heart rate measuring methods were re-implemented and tested with the feasibility study database. The results were compared with ground truth to estimate the heart rate measurement error. The heart rate measurement error was analyzed using mean error, standard deviation; root means square error and Pearson correlation coefficient. The findings of this experiment inferred promising results for health monitoring of subjects standing at a distance of 500 cm.


title: COVID-19 Impact on People with Diabetes in the South and Central America

text: Abstract Aims The present observational study aims to describe the political actions in place to fight COVID-19 in the South and Central America region (SACA) while protecting individuals with diabetes. Methods A survey with 12 questions was shared with all IDF-SACA member organizations, in 18 countries. A descriptive analysis was performed and a multivariate cluster analysis technique pam (partitioning around medoids) was applied. Results Two groups of countries were identified. The first group reported more difficulties (limitations in accessing basic or health needs) and fears (concerns regarding the impact of the pandemic), mostly countries with stricter measures to contain the spread of the virus, whereas most of the second group consisted of countries with less restrictive measures, and reported fewer difficulties. Only 37% responded that a policy was put into place to protect individuals with diabetes delivering their medicines and supplies at home (16%) or receiving at once medicine and supplies enough for 2-3 months (21%). All respondents reported as one of the main fears “be infected and do not receive adequate treatment” and/or “getting infected if going to the hospital or medical appointments”. Conclusions Most of the SACA countries lack timely implemented measures to protect individuals with diabetes, which may lead to present and future severe impact on the individuals, health system and economy.


docid: ovfqfurf

title: Emergence of medicine for mass gatherings: lessons from the Hajj

text: Summary Although definitions of mass gatherings (MG) vary greatly, they consist of large numbers of people attending an event at a specific site for a finite time. Examples of MGs include World Youth Day, the summer and winter Olympics, rock concerts, and political rallies. Some of the largest MGs are spiritual in nature. Among all MGs, the public health issues, associated with the Hajj (an annual pilgrimage to Mecca, Saudi Arabia) is clearly the best reported—probably because of its international or even intercontinental implications in terms of the spread of infectious disease. Hajj routinely attracts 2·5 million Muslims for worship. WHO's global health initiatives have converged with Saudi Arabia's efforts to ensure the wellbeing of pilgrims, contain infectious diseases, and reinforce global health security through the management of the Hajj. Both initiatives emphasise the importance of MG health policies guided by sound evidence and based on experience and the timeliness of calls for a new academic science-based specialty of MG medicine.


Human Capital in the Supply Chain of Global Firms


title: The cause of the plague of Athens: plague, typhoid, typhus, smallpox, or measles?

text: The plague of Athens raged for 4 years and resulted in the defeat of Athens. The cause of the plague of Athens continues to be debated. Infectious diseases most often cited as causes of the plague include influenza, epidemic typhus, typhoid fever, bubonic plague, smallpox, and measles. Thucydides provides the only available description of the plague of Athens. Given the nuances of the translation, bubonic plague, smallpox, and measles are the most likely causes of the plague. In my view, measles is the most likely cause of the plague of Athens.


Allergen-Immuntherapie in der aktuellen Covid-19-Pandemie(a, b, c)


title: Primary Care Accessibility Effects on Health Care Utilization among Urban Children

text: OBJECTIVES: Evidence suggests that spatial accessibility to primary care is a contributing factor to appropriate health care utilization, with limited primary care access resulting in avoidable hospitalizations and emergency department visits which are burdensome on individuals and our healthcare system. Limited research, however, has examined the effects on children. METHODS: We evaluated associations of spatial accessibility to primary care on health care utilization among a sample of 16,709 children aged 0-3 years in Philadelphia who were primarily non-White and publicly insured. Log-Poisson models with generalized estimating equations were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) while accounting for three levels of clustering (within individual, within primary care practice, within neighborhood). RESULTS: In age-adjusted models, the lowest level of spatial accessibility was associated with 7% fewer primary care visits (RR 0.93, 95% CI 0.91, 0.95), 15% more emergency department (ED) visits (RR 1.15, 95% CI 1.09, 1.22), and 18% more avoidable hospitalizations (RR 1.18, 95% CI 1.01, 1.37). After adjustment for individual- (race/ethnicity, sex, number of chronic conditions, insurance status) and neighborhood-level (racial composition and proportion of housing units with no vehicle), spatial accessibility was not significantly associated with rate of health care utilization. CONCLUSIONS: Individual-level predisposing factors, such as age, race, and need, attenuate the association between accessibility to primary care and use of primary care, emergency department visits, and avoidable hospitalization. Given the possibility of modifying access to primary care unlike immutable individual factors, a focus on spatial accessibility to primary care may promote appropriate health care utilization.


title: An unusual case of influenza-like illness after yellow fever vaccination

text: Abstract Yellow fever (YF) is an important public health concern in areas where the disease is endemic. For more than 60 years a highly effective live attenuated vaccine has been available, its widespread use resulting in a dramatic decrease in the number of cases. On rare occasions, YF vaccine can cause mild to severe disease and rare adverse vaccine-associated events have been reported. Additionally, an average viremia of 3–5 days after administration of the YF vaccine has been published. Here we present a case where YF vaccine was isolated in cell culture from a respiratory swab collected from a patient presenting with influenza-like illness. To the best of our knowledge, this is the first report finding replicating YF vaccine in the respiratory sample of a post inoculated individual.


title: Evolution of SARS-Co-2 RNA test results in a fatal Covid-19 patient: a case report

text: A 65 year-old man was hospitalized due to fever (38.6°C) and dry cough since 4 days. He visited Wuhan 8 days ago. At admission, nasopharyngeal swabs sample were taken and PCR analysis confirmed SARS-CoV-2RNA positivity. On day 9 after admission, chest CT scan showed diffuse ground-glass shadows in patient’s bilateral lungs. On day 11, his respiratory symptoms worsened. Subsequently, type 1 respiratory failure was diagnosed, coinciding with kidney injury, and subsequently, type 2 respiratory failure occurred, coupled with multi-organ failure including heart and liver. However, patient constitution worsened although SARS-CoV-2 tests were negative since day 13. He died on day 21. Lung biopsy showed areas of diffuse alveolar damage, characterized by extensive acute alveolitis with numerous intra-alveolar neutrophils, lymphocytes and macrophages infiltrations. Microthrombi were seen in the dilated pulmonary capillaries. Immunohistochemistry stainings for SARS-CoV-2-N protein was negative. Taken together, the patient died of multiorgan failure although the SARS-CoV-2 infection was cleared already, implicating that for disease worsening, no active SARS-CoV-2 infection is required.


Telemedicine algorithm for chronic wound care during COVID‐19


title: Is anaerobic digestion a reliable barrier for deactivation of pathogens in biosludge?

text: Abstract As World Health Organization advocates, the global burden of sanitation related disease and access to safely managed sanitation and safely treated wastewater should be monitored strictly. However, the spread of pathogens through various agricultural applications or direct discharge of sewage sludge generated in municipal wastewater treatment plants poses a serious challenge on the environment and public health. Anaerobic digestion (AD), the principal method of stabilizing biosolids, can efficiently and largely deactivate viable pathogens, including parasite, virus, and the pathogens harboring antibiotic resistance genes. This review aims to provide a critical overview regarding the deactivation of sludge-associated pathogens by AD, through which a serious concern on the effectiveness and rationality of AD towards sludge pathogens control was raised. Meanwhile, the underlying deactivation mechanisms and affecting factors were all discussed, with the focus on pathogen-associated modeling, engineering design and technological aspects of AD. Lastly, a matric method incorporating the operating strategy of AD with the risk assessment was proposed for evaluating the reliability of AD-based pathogen deactivation, while the research agenda forward was also outlined.


title: BST2/CD317 counteracts human coronavirus 229E productive infection by tethering virions at the cell surface

text: Abstract Bone marrow stromal antigen 2 (BST2), an interferon-inducible antiviral factor, has been shown to block the release of various enveloped viruses from cells. It has also been identified as an innate immune system component. Most enveloped viruses subject to BST2 restriction bud at the plasma membrane. Here we report our findings that (a) the production of human coronavirus 229E (HCoV-229E) progeny viruses, whose budding occurs at the ER-Golgi intermediate compartment (ERGIC), markedly decreases in the presence of BST2; and (b) BST2 knockdown expression results in enhanced HCoV-229E virion production. Electron microscopy analyses indicate that HCoV-229E virions are tethered to cell surfaces or intracellular membranes by BST2. Our results suggest that BST2 exerts a broad blocking effect against enveloped virus release, regardless of whether budding occurs at the plasma membrane or intracellular compartments.


docid: okkhmcsl

title: The Usefulness of Lung Ultrasound for the Aetiological Diagnosis of Community-Acquired Pneumonia in Children

text: The aetiology of community-acquired pneumonia (CAP) is not easy to establish. As lung ultrasound (LUS) has already proved to be an excellent diagnostic tool for CAP, we analysed its usefulness for discriminating between the aetiologically different types of CAP in children. We included 147 children hospitalized because of CAP. LUS was performed in all patients at admission, and follow-up LUS was performed in most patients. LUS-detected consolidations in viral CAP were significantly smaller, with a median diameter of 15 mm, compared to 20 mm in atypical bacterial CAP (p = 0.05) and 30 mm in bacterial CAP (p < 0.001). Multiple consolidations were detected in 65.4% of patients with viral CAP and in 17.3% of patients with bacterial CAP (p < 0.001). Bilateral consolidations were also more common in viral CAP than in bacterial CAP (51.9% vs. 8.0%, p < 0.001). At follow-up, a regression of consolidations was observed in 96.6% of patients with bacterial CAP and in 33.3% of patients with viral CAP (p < 0.001). We found LUS to be especially suitable for differentiating bacterial CAP from CAP due to other aetiologies. However, LUS must be interpreted in light of clinical and laboratory findings.


title: Diffuse alveolar hemorrhage in infants: Report of five cases

text: Diffuse alveolar hemorrhage (DAH) is a rare life-threatening condition in children. In this entity, the bleeding originates from the pulmonary microvasculature as a result of microvascular damage leading to blood leakage into the alveolar spaces. DAH can occur as an isolated medical entity or may be associated with other organ system injury or dysfunction. The classic triad of symptoms includes hemoptysis, anemia and diffuse pulmonary infiltrates. Hemoptysis is the usual presenting symptom but is not constant. A variety of diseases is associated with the development of DAH. Current classification organize the etiologies of diffuse alveolar hemorrhage based on the presence of severe immune disorders (such as systemic vasculitis and collagenosis) or non-immunodeficiency disorders (with an identified cardiac or non-cardiac origin, or idiopathic). The five cases of DAH presented in this study were all diagnosed in full-term infants, four males and one female, with normal neonatal adaptation and without family history of notable diseases. In all cases the diagnosis was made between the age of three and eighteen weeks-old. Moreover, all five patients, at the time of diagnosis, presented with hemoptysis, mild or severe dyspnea, anemia and abnormal chest X-rays. Consequently, the diagnosis of DAH was strongly suspected and, eventually, confirmed by bronchoscopy. Additional laboratory tests, as well as selected serologic and radiographic studies were performed in order to identify a specific etiology. The final diagnoses reflect a variety of causes: infections, idiopathic pulmonary hemosiderosis, accidental suffocation and Heiner syndrome. Treatment included oral corticosteroids except from one patient that received antimicrobial therapy.


docid: lpmsalux

title: Pilot use of a novel smartphone application to track traveller health behaviour and collect infectious disease data during a mass gathering: Hajj pilgrimage 2014

text: Abstract This study examines the feasibility of using a smartphone application (app) to conduct surveys among travellers during the Hajj pilgrimage, where the use of apps has not been evaluated for infectious disease surveillance. A longitudinal study was conducted among pilgrims at the Hajj 2014 using an iPhone app with separate questionnaires for three study phases covering before, during, and after Hajj. Forty-eight pilgrims from 13 countries downloaded the app. Respondents were aged between 21 and 61 (median 36) years and 58.5% (24/41) were male. Of these, 85% (41/48) completed the first phase, 52% (25/41) completed both the second and third phases, and 25 of these reported meningococcal vaccination, with 36% (9/25) receiving other vaccines. All (25) reported hand hygiene use and 64% (16/25) wore a facemask at some point during the pilgrimage. Four (6%) reported close contact with camels. Respiratory symptoms commenced from the 4th day of Hajj, with sore throat (20%) and cough (12%) being the most common. Three participants (12%) reported respiratory symptoms after returning home. Conducting a prospective survey using a smartphone app to collect data on travel-associated infections and traveller compliance to prevention is feasible at mass gatherings and can provide useful data associated with health-related behaviour.


docid: scnvnyns

title: Characterization of the bacterial gut microbiota of piglets suffering from new neonatal porcine diarrhoea

text: BACKGROUND: In recent years, new neonatal porcine diarrhoea (NNPD) of unknown aetiology has emerged in Denmark. NNPD affects piglets during the first week of life and results in impaired welfare, decreased weight gain, and in the worst-case scenario death. Commonly used preventative interventions such as vaccination or treatment with antibiotics, have a limited effect on NNPD. Previous studies have investigated the clinical manifestations, histopathology, and to some extent, microbiological findings; however, these studies were either inconclusive or suggested that Enterococci, possibly in interaction with Escherichia coli, contribute to the aetiology of NNPD. This study examined ileal and colonic luminal contents of 50 control piglets and 52 NNPD piglets by means of the qPCR-based Gut Microbiotassay and 16 samples by 454 sequencing to study the composition of the bacterial gut microbiota in relation to NNPD. RESULTS: NNPD was associated with a diminished quantity of bacteria from the phyla Actinobacteria and Firmicutes while genus Enterococcus was more than 24 times more abundant in diarrhoeic piglets. The number of bacteria from the phylum Fusobacteria was also doubled in piglets suffering from diarrhoea. With increasing age, the gut microbiota of NNPD affected piglet and control piglets became more diverse. Independent of diarrhoeic status, piglets from first parity sows (gilts) possessed significantly more bacteria from family Enterobacteriaceae and species E. coli, and fewer bacteria from phylum Firmicutes. Piglets born to gilts had 25 times higher odds of having NNPD compared with piglets born to multiparous sows. Finally, the co-occurrence of genus Enterococcus and species E. coli contributed to the risk of having NNPD. CONCLUSION: The results of this study support previous findings that points towards genus Enterococcus and species E. coli to be involved in the pathogenesis of NNPD. Moreover, the results indicate that NNPD is associated with a disturbed bacterial composition and larger variation between the diarrhoeic piglets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0419-4) contains supplementary material, which is available to authorized users.


title: Infectious and immunogenetic factors in bipolar disorder

text: OBJECTIVE: Despite the evidence supporting the association between infection and bipolar disorder (BD), the genetic vulnerability that mediates its effects has yet to be clarified. A genetic origin for the immune imbalance observed in BD, possibly involved in the mechanisms of pathogen escape, has, however, been suggested in recent studies. METHOD: Here, we present a critical review based on a systematic literature search of articles published until December 2016 on the association between BD and infectious/immunogenetic factors. RESULTS: We provide evidence suggesting that infectious insults could act as triggers of maladaptive immune responses in BD and that immunogenetic vulnerability may amplify the effects of such environmental risk factors, increasing susceptibility to subsequent environmental encounters. Quality of evidence was generally impaired by scarce attempt of replication, small sample sizes and lack of high‐quality environmental measures. CONCLUSION: Infection has emerged as a potential preventable cause of morbidity in BD, urging the need to better investigate components of the host–pathogen interaction in patients and at‐risk subjects, and thus opening the way to novel therapeutic opportunities.


OUT-OF-HOSPITAL CARDIAC ARREST AND DONATION AFTER CIRCULATORY DEATH DURING THE COVID-19 PANDEMIA


Covid-19 — The Search for Effective Therapy


title: Purified coronavirus Spike protein nanoparticles induce coronavirus neutralizing antibodies in mice

text: Development of vaccination strategies for emerging pathogens are particularly challenging because of the sudden nature of the emergence of these viruses and the long process needed for traditional vaccine development. Therefore, there is a need for development of a rapid method of vaccine development that can respond to emerging pathogens in a short time frame. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East respiratory syndrome (MERS-CoV) in late 2012 demonstrate the importance of coronaviruses as emerging pathogens. The spike glycoproteins of coronaviruses reside on the surface of the virion and are responsible for virus entry. The spike glycoprotein is the major immunodominant antigen of coronaviruses and has proven to be an excellent target for vaccine designs that seek to block coronavirus entry and promote antibody targeting of infected cells. Vaccination strategies for coronaviruses have involved live attenuated virus, recombinant viruses, non-replicative virus-like particles expressing coronavirus proteins or DNA plasmids expressing coronavirus genes. None of these strategies has progressed to an approved human coronavirus vaccine in the ten years since SARS-CoV emerged. Here we describe a novel method for generating MERS-CoV and SARS-CoV full-length spike nanoparticles, which in combination with adjuvants are able to produce high titer antibodies in mice.


title: Age and Ebola viral load correlate with mortality and survival time in 288 Ebola virus disease patients

text: Summary Background A Chinese medical team managed Ebola virus disease (EVD) patients in Sierra Leone from October 2014 to March 2015 and attended to 693 suspected patients, of whom 288 had confirmed disease. Methods A retrospective study was conducted of the 288 patients with confirmed disease. Clinical symptoms, manifestations, and serum viral load were analyzed and compared among the different groups for mortality and survival time. Results Among the 288 confirmed EVD patients (149 male and 139 female, median age 28 years, and median log viral load 6.68), 98 died, 36 recovered, and 154 were lost to follow-up. Common symptoms were fever (77.78%), fatigue (64.93%), abdominal pain (64.58%), headache (62.85%), and diarrhea (61.81%). Compared to patients aged<18 years, those who were older than 40 years had a higher probability of death (odds ratio 2.855, p =0.044). Patients with a viral load of >106 copies/ml had a higher case fatality rate than those with <106 copies/ml (odds ratio 3.095, p =0.004). Cox regression showed that age, viral load, and the presence of diarrhea correlated with mortality. Conclusion Patients with a high viral load, of older age, and with diarrhea had a higher mortality and shorter survival time.


title: Wait-time for hysterectomy and survival of women with early-stage cervical cancer: A clinical implication during the coronavirus pandemic

text: OBJECTIVE: A global pandemic caused by a novel coronavirus (Covid-19) has created unique challenges to providing timely care for cancer patients. In early-stage cervical cancer, postponing hysterectomy for 6–8 weeks is suggested as a possible option in the Covid-19 burdened hospitals. Yet, literature examining the impact of surgery wait-time on survival in early-stage cervical cancer remains scarce. This study examined the association between surgery wait-time of 8 weeks and oncologic outcome in women with early-stage cervical cancer. METHODS: This is a single institution retrospective observational study at a tertiary referral medical center examining women who underwent primary hysterectomy or trachelectomy for clinical stage IA-IIA invasive cervical cancer between 2000 and 2017 (N = 217). Wait-time from the diagnosis of invasive cervical cancer via biopsy to definitive surgery was categorized as: short wait-time (<8 weeks; n = 110) versus long wait-time (≥8 weeks; n = 107). Propensity score inverse probability of treatment weighting was used to balance the measured demographics between the two groups, and disease-free survival (DFS) and overall survival (OS) were assessed. A systematic literature review with meta-analysis was additionally performed. RESULTS: In a weighted model (median follow-up, 4.6 years), women in the long wait-time group had DFS (4.5-year rates, 91.2% versus 90.7%, hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.47–2.59, P = 0.818) and OS (95.0% versus 97.4%, HR 1.47, 95%CI 0.50–4.31, P = 0.487) similar to those in the short wait-time group. Three studies were examined for meta-analysis, and a pooled HR for surgery wait-time of ≥8 weeks on DFS was 0.96 (95%CI 0.59–1.55). CONCLUSION: Our study suggests that wait-time of 8 weeks for hysterectomy may not be associated with short-term disease recurrence in women with early-stage cervical cancer.


title: Models of infection and exacerbations in COPD

text: Despite optimal use of currently available therapy for stable COPD, acute exacerbations are common events that constitute a major health burden. The development of highly sensitive diagnostic tools highlighted the role of viral infections in inducing COPD exacerbations, with rhinoviruses being the most frequently identified virus type. So far, little is known about the mechanisms of virus-induced exacerbations. The recent development of the first human rhinovirus-induced COPD exacerbation model represents an invaluable tool towards increasing our knowledge of immunological and inflammatory mechanisms of COPD exacerbation. The model will give us the opportunity to highlight key inflammatory mediators representing possible therapeutic targets for the development of novel drugs able to treat and prevent acute episodes in COPD.


title: Readability of Online Patient Education Material for the Novel Coronavirus Disease (COVID-19): A Cross-sectional Health Literacy Study

text: Abstract Objectives The internet has become one of the most important resources for the general population when searching for health care information. However, the information available is not always suitable for all readers due to its difficult readability. We sought to assess the readability of online information regarding the novel Coronavirus disease (COVID-19) and establish whether they follow the patient educational information reading level recommendations. Study design This is a cross-sectional study. Methods We searched five key terms on Google and the first 30 results from each of the searches were considered for analysis. Five validated readability tests were utilized in order to establish the reading level for each article. Results Out of the 150 gathered articles, 61 met the inclusion criteria and were evaluated. None (0%) of the articles met the recommended 5th to 6th grade reading level (of a 11-12-year-old). The mean readability scores were: Flesch Reading Ease 44.14, Flesch-Kincaid Grade Level 12.04, Gunning-Fog Index 14.27, Simple Measure of Gobbledygook SMOG Index 10.71, and Coleman-Liau Index 12.69. Conclusions Online educational articles on COVID-19 provide information too difficult to read for the general population. The readability of articles regarding COVID-19 and other diseases needs to improve so that the general population may understand health information better and may respond adequately to protect themselves and limit the spread of infection.


title: Conservation of nucleotide sequences for molecular diagnosis of Middle East respiratory syndrome coronavirus, 2015

text: Summary Infection due to the Middle East respiratory syndrome coronavirus (MERS-CoV) is widespread. The present study was performed to assess the protocols used for the molecular diagnosis of MERS-CoV by analyzing the nucleotide sequences of viruses detected between 2012 and 2015, including sequences from the large outbreak in eastern Asia in 2015. Although the diagnostic protocols were established only 2 years ago, mismatches between the sequences of primers/probes and viruses were found for several of the assays. Such mismatches could lead to a lower sensitivity of the assay, thereby leading to false-negative diagnosis. A slight modification in the primer design is suggested. Protocols for the molecular diagnosis of viral infections should be reviewed regularly after they are established, particularly for viruses that pose a great threat to public health such as MERS-CoV.


title: Occurrence of canine parvovirus in dogs from Henan province of China in 2009–2014

text: BACKGROUND: There is no information concerning the genotype of Canine parvovirus (CPV) currently circulating in Henan province, China. Therefore, the aim of the present study was to provide insights into the epidemiology and molecular characterization of CPV circulating in Henan province from 2009 to 2014. RESULTS: Nineteen thousand nine hundred seven dogs from pet hospitals in the cities of Luoyang, Anyang, Jiaozuo, Sanmenxia, Xinxiang, Zhengzhou in Henan province between 2009 and 2014 were investigated. Over the 6-year period, 1169 CPV-positive cases were identified and the morbidity of CPV infection ranged from 4.16 to 8.06 %, although morbidity was not significant (P > 0.05) between 2009 and 2014. Factors associated with morbidity included sampling season, dog age, breed, vaccination status, and sex. CPV co-infection with coccidium (10.00 %), canine distemper virus (4.79 %), hookworm (2.40 %), canine coronavirus (1.11 %), roundworm (1.03 %), tapeworm (0.17 %) and Babesia spp. (0.09 %) were observed. The new CPV-2a variant was more prevalent than the new CPV-2b variant in Henan province. CPV 2c was not observed in this study. CONCLUSIONS: The epidemiology of CPV infection and identification of the circulating genotypes in Henan province, China from 2009 to 2014 determined that the new CPV-2a variant was more prevalent.


title: The Benefits of Transmission Dynamics Models in Understanding Emerging Infectious Diseases

text: Abstract Factors associated with the emergence and transmission of infectious diseases often do not follow the assumptions of traditional statistical models such as linearity and independence of outcomes. Transmission dynamics models are well suited to address infectious disease scenarios that do not conform to these assumptions. For example, these models easily account for changes in the incidence rates of infection as the proportions of susceptible and infectious persons change in the population. Fundamental concepts relating to these methods, such as the basic reproductive number, the effective reproductive number and the susceptible-infected-recovered compartmental models, are reviewed. In addition, comparisons and contrasts are made between the following concepts: microparasites and macroparasites, deterministic and stochastic models, difference and differential equations and homogeneous and heterogeneous mixing patterns. Finally, examples of how transmission dynamics models are being applied to factors associated with emerging infectious diseases, such as zoonotic origins, microbial adaption and change, human susceptibility and climate change, are reviewed.


title: Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplant Recipients and Patients With Hematologic Malignancies

text: BACKGROUND. The possible role of human coronavirus (HCoV) in lower respiratory tract disease (LRTD) in hematopoietic cell transplant (HCT) recipients and patients with hematologic malignancies (HM) has not been well studied. METHODS. We conducted a retrospective review of HCT/HM patients with HCoV detected in bronchoalveolar lavage (BAL). HCoV strains were identified in BAL samples using strain-specific polymerase chain reaction. Mortality rates were compared among HCT recipients with LRTD caused by HCoV, respiratory syncytial virus (RSV), influenza virus, or parainfluenza virus (PIV) by multivariable Cox regression analysis. RESULTS. We identified 35 patients (37 episodes) with HCoV LRTD. Among 23 available BAL samples, 48% were strain OC43, 22% were NL63, 17% were 229E, and 13% were HKU1. Overall, 21 patients (60%) required oxygen therapy at diagnosis and 19 (54%) died within 90 days of diagnosis. Respiratory copathogens were detected in 21 episodes (57%), including viruses (n = 12), fungi (n = 10), and bacteria (n = 8). Mortality rates were not different between patients with and without copathogens (P = .65). In multivariable models, mortality associated with HCoV LRTD was similar to that seen with RSV, influenza, and PIV LRTD in HCT recipients (adjusted hazard ratio, 1.34 [95% confidence interval, .66–2.71], P = .41 vs RSV, adjusted for cell source, cytopenia, copathogens, oxygen use, and steroid use). CONCLUSIONS. HCoV LRTD in patients with HCT or HM is associated with high rates of oxygen use and mortality. Mortality associated with HCoV LRTD in HCT recipients appears to be similar to that seen with RSV, influenza virus, and PIV.


Evaluating Potential Deceased Donor Renal Transplant Recipients for Asymptomatic COVID-19


INFLUENCIA DE LA PANDEMIA POR SARS-COV-2 EN EL MANEJO DEL CÁNCER DE MAMA