niryuu/sni-each-converted huggingface dataset:
The infiltration of immune cells in the central nervous system is a common hallmark in different neuroinflammatory conditions. Accumulating evidence indicates that resident glial cells can establish a cross-talk with infiltrated immune cells, including T-cells, regulating their recruitment, activation and function within the CNS. Although the healthy CNS has been thought to be devoid of professional dendritic cells (DCs), numerous studies have reported the presence of a population of DCs in specific locations such as the meninges, choroid plexuses and the perivascular space. Moreover, the infiltration of DC precursors during neuroinflammatory situations has been proposed, suggesting a putative role of these cells in the regulation of lymphocyte activity within the CNS. On the other hand, under specific circumstances, microglial cells are able to acquire a phenotype of DC expressing a wide range of molecules that equip these cells with all the necessary machinery for communication with T-cells. In this review, we summarize the current knowledge on the expression of molecules involved in the cross-talk with T-cells in both microglial cells and DCs and discuss the potential contribution of each of these cell populations on the control of lymphocyte function within the CNS.
Output: Are Microglial Cells the Regulators of Lymphocyte Responses in the CNS?
The primary objective of this panel discussion was to seek input on the following 3 questions from the speakers at the workshop. Comments and questions were also entertained from the members of the audience. Question 1: Considering the potential advantages of microbial decontamination of indoor air, what criteria should be used to select a given technology? Dr C. Duchaine: Technologies of interest will depend on the situation and the point source of microbial contamination, for example, a person coughing in an emergency room, a patient vomiting in a hospital ward, or a student vomiting in a classroom. The intervention of choice must be relevant for the site, for instance, a hospital versus a shopping mall. Portable indoor air decontamination devices may be used in smaller areas, such as classrooms, but devices that would allow global decontamination (eg, at a hospital or a shopping mall) would be more challenging. When possible, routine and continuous air treatment may be better than an on-site intervention. Dr Y. Li: Technologies that are effective for decontamination of circulating air in different situations would be more desirable. One example is the use of UVGI in air circulation ducts if the potentially generated ozone can be effectively removed to avoid its entry into occupied zones. The technology of choice must be safe when people are present, while also being energy efficient. Further, it must not only be effective, but also scalable to suit the site of use. The results of testing in an aerobiology chamber can be much different than those in a large area, such as a hospital or a large shopping mall, where there are on-going changes in the air quality parameters. The debate continues as to whether indoor air for breathing should be treated in the same fashion as water for drinking.
Output: Workshop on "The Role of Indoor Air as a Vehicle for Human Pathogens": A Panel Discussion
Background: We evaluated tuberculosis (TB) acquisition rate and risk factors among health care workers (HCWs) exposed to index TB patients. Methods: We performed a retrospective cohort study on exposed HCWs from August 2016 to January 2018 at a tertiary hospital in Singapore. Demographic factors and TB exposure episodes per HCW were obtained. A modified Poisson regression model was used to identify factors associated with TB infection. Results: A total of 32 TB exposure events occurred during the study period. A total of 881 HCWs with 1,536 exposure episodes were screened with QuantiFERON-TB Gold In-tube assay (QFT-GIT) at baseline and 8 weeks. A total of 129 (14.6%) HCWs had positive QFT-TB at baseline, whereas 22 (2.5%) HCWs had QFT-GIT conversion, with a latent TB infection (LTBI) rate of 1.14 cases per 100 exposure episodes per year. Foreign nationality, non-Chinese ethnicity, and age above 40 years were independently associated with baseline LTBI, whereas having >2 TB exposure episodes and working in internal medicine, medical subspecialties, and psychiatry wards were associated with QFT-GIT conversion. Discussion: The QFT-GIT conversion rate among screened HCWs is low. Foreign HCWs with LTBI likely came from countries with higher TB transmission. Targeted prevention of repeated TB exposures can reduce QFT-GIT conversion. Conclusions: The study results will guide TB contact tracing protocols in health care institutions.
Output: A retrospective review of tuberculosis exposure among health care workers in a tertiary hospital
Background: DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO 2 -powered BiojectorH device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity. Methods: Forty adults, 18-50 years, were randomly assigned to intramuscular (IM) vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8) by BiojectorH 2000 TM or needle and syringe (N/S) and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5) with N/S at 10 10 or 10 11 particle units (PU). Equal numbers per assigned schedule had low (#500) or high (.500) reciprocal titers of preexisting Ad5 neutralizing antibody. Results: 120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-c ELISpot response rates were 17/19 (89%) for BiojectorH and 13/17 (76%) for N/S delivery at Week 28 (4 weeks post rAd5 boost). The magnitude of ELISpot response was about 3-fold higher in BiojectorH compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects. Conclusions: DNA vaccination by BiojectorH was well-tolerated and compared to needle injection, primed for greater IFN-c ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting.
Output: DNA Vaccine Delivered by a Needle-Free Injection Device Improves Potency of Priming for Antibody and CD8+ T- Cell Responses after rAd5 Boost in a Randomized Clinical Trial
Nipah virus (NiV) continues to cause outbreaks of fatal human encephalitis due to spillover from its bat reservoir. We determined that a single dose of replication-defective vesicular stomatitis virus (VSV)-based vaccine vectors expressing either the NiV fusion (F) or attachment (G) glycoproteins protected hamsters from over 1000 times LD 50 NiV challenge. This highly effective single-dose protection coupled with an enhanced safety profile makes these candidates ideal for potential use in livestock and humans.
Output: Single-Dose Replication-Defective VSV-based Nipah Virus Vaccines Provide Protection from Lethal Challenge in Syrian Hamsters
ABSTRCT 29 Given the scale and rapid spread of severe acute respiratory syndrome coronavirus 2 30 (SARS-CoV-2, known as 2019-nCov) infection , the ongoing global 31 SARS-CoV-2 outbreak has become a huge public health issue. Rapid and precise 32 diagnostic methods are thus immediately needed for diagnosing COVID-19, 33 providing timely treatment and facilitating infection control. A one-step reverse 34 transcription loop-mediated isothermal amplification (RT-LAMP) coupled with 35 nanoparticles-based biosensor (NBS) assay (RT-LAMP-NBS) was successfully 36 established for rapidly and accurately diagnosing COVID-19. A simple equipment 37 (such as heating block) was required for maintaining a constant temperature (63°C) 38 for only 40 min. Using two designed LAMP primer sets, F1ab (opening reading frame 39 1a/b) and np (nucleoprotein) genes of SARS-CoV-2 were simultaneously amplified 40 and detected in a 'one-step' and 'single-tube' reaction, and the detection results were 41 easily interpreted by NBS. The sensitivity of SARS-CoV-2 RT-LAMP-NBS was 12 42 copies (each of detection target) per reaction, and no cross-reactivity was generated 43 from non-SARS-CoV-2 templates. Among clinically diagnosed COVID-19 patients, 44 the analytical sensitivity of SARS-CoV-2 was 100% (33/33) in the oropharynx swab 45 samples, and the assay's specificity was also 100% (96/96) when analyzed the clinical 46 samples collected from non-COVID-19 patients. The total diagnosis test from sample 47 collection to result interpretation only takes approximately 1 h. In sum, the 48 RT-LAMP-NBS is a promising tool for diagnosing the current SARS-CoV-2 49 infection in first line field, public health and clinical laboratories, especially for 50 resource-challenged regions. 51
Output: Title Page: 1 Reverse transcription loop-mediated isothermal amplification combined with 2 nanoparticles-based biosensor for diagnosis of COVID-19 3 4 Laboratory of Pediatric Respiratory Infection Disease, National Clinical Research
Background: Recurrent acute otitis media (rAOM, recurrent ear infection) is a common childhood disease caused by bacteria termed otopathogens, for which current treatments have limited effectiveness. Generic probiotic therapies have shown promise, but seem to lack specificity. We hypothesised that healthy children with no history of AOM carry protective commensal bacteria that could be translated into a specific probiotic therapy to break the cycle of re-infection. We characterised the nasopharyngeal microbiome of these children (controls) in comparison to children with rAOM (cases) to identify potentially protective bacteria. As some children with rAOM do not appear to carry any of the known otopathogens, we also hypothesised that characterisation of the middle ear microbiome could identify novel otopathogens, which may also guide the development of more effective therapies. Results: Middle ear fluids, middle ear rinses and ear canal swabs from the cases and nasopharyngeal swabs from both groups underwent 16S rRNA gene sequencing. The nasopharyngeal microbiomes of cases and controls were distinct. We observed a significantly higher abundance of Corynebacterium and Dolosigranulum in the nasopharynx of controls. Alloiococcus, Staphylococcus and Turicella were abundant in the middle ear and ear canal of cases, but were uncommon in the nasopharynx of both groups. Gemella and Neisseria were characteristic of the case nasopharynx, but were not prevalent in the middle ear. Conclusions: Corynebacterium and Dolosigranulum are characteristic of a healthy nasopharyngeal microbiome. Alloiococcus, Staphylococcus and Turicella are possible novel otopathogens, though their rarity in the nasopharynx and prevalence in the ear canal means that their role as normal aural flora cannot be ruled out. Gemella and Neisseria are unlikely to be novel otopathogens as they do not appear to colonise the middle ear in children with rAOM.
Output: A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera
Angiotensin converting enzyme (ACE) 2 is a negative regulator of the renin angiotensin system (RAS) through its role to degrade angiotensin II. In rats with subtotal nephrectomy (STNx), adverse cardiac remodelling occurs despite elevated cardiac ACE2 activity. We hypothesised that diminazene aceturate (DIZE), which has been described as having an off-target effect to activate ACE2, would have beneficial cardiac effects in STNx rats. STNx led to hypertension, diastolic dysfunction, left ventricular hypertrophy, cardiac fibrosis, and increased cardiac ACE, ACE2, Ang II and Ang 1-7 levels. Cardiac gene expression of ADAM17 was also increased. In STNx, two-weeks of subcutaneous DIZE (15mg/kg/d) had no effect on blood pressure but improved diastolic dysfunction and cardiac fibrosis, reduced ADAM17 mRNA and shifted the cardiac RAS balance to a cardioprotective profile with reduced ACE and Ang II. There was no change in cardiac ACE2 activity or in cardiac Ang 1-7 levels with DIZE. In conclusion, our results suggest that DIZE exerts a protective effect on the heart under the pathological condition of kidney injury. This effect was not due to improved kidney function, a fall in blood pressure or a reduction in LVH but was associated with a reduction in cardiac ACE and cardiac Ang II levels. As in vitro studies showed no direct effect of DIZE on ACE2 or ACE activity, the precise mechanism of action of DIZE remains to be determined.
Output: Diminazene Aceturate Improves Cardiac Fibrosis and Diastolic Dysfunction in Rats with Kidney Disease
Over the past few decades, global metapopulation epidemic simulations built with worldwide air-transportation data have been the main tool for studying how epidemics spread from the origin to other parts of the world (e.g., for pandemic influenza, SARS, and Ebola). However, it remains unclear how disease epidemiology and the air-transportation network structure determine epidemic arrivals for different populations around the globe. Here, we fill this knowledge gap by developing and validating an analytical framework that requires only basic analytics from stochastic processes. We apply this framework retrospectively to the 2009 influenza pandemic and 2014 Ebola epidemic to show that key epidemic parameters could be robustly estimated in real-time from public data on local and global spread at very low computational cost. Our framework not only elucidates the dynamics underlying global spread of epidemics but also advances our capability in nowcasting and forecasting epidemics.
Output: Characterizing the dynamics underlying global spread of epidemics
China is encountering formidable healthcare challenges brought about by the problem of aging. By 2050, there will be 400 million Chinese citizens aged 65+, 150 million of whom will be 80+. The undesirable consequences of the one-child policy, rural-to-urban migration, and expansion of the population of 'empty nest' elders are eroding the traditional family care of the elders, further exacerbating the burden borne by the current public healthcare system. The challenges of geriatric care demand prompt attention by proposing strategies for improvement in several key areas. Major diseases of the elderly that need more attention include chronic non-communicable diseases and mental health disorders. We suggest the establishment of a home care-dominated geriatric care system, and a proactive role for researchers on aging in reforming geriatric care through policy dialogs. We propose ideas for preparation of the impending aging burden and the creation of a nurturing environment conducive to healthy aging in China.
Output: A research agenda for aging in China in the 21st century
Sapovirus is a genus of caliciviruses that are known to cause enteric disease in humans and animals. There is considerable genetic diversity among the sapoviruses, which are classified into different genogroups based on phylogenetic analysis of the full-length capsid protein sequence. While several mammalian species, including humans, pigs, minks, and dogs, have been identified as animal hosts for sapoviruses, there were no reports of sapoviruses in bats in spite of their biological diversity. In this report, we present the results of a targeted surveillance study in different bat species in Hong Kong. Five of the 321 specimens from the bat species, Hipposideros pomona, were found to be positive for sapoviruses by RT-PCR. Complete or nearly full-length genome sequences of approximately 7.7 kb in length were obtained for three strains, which showed similar organization of the genome compared to other sapoviruses. Interestingly, they possess many genomic features atypical of most sapoviruses, like high G+C content and minimal CpG suppression. Phylogenetic analysis of the viral proteins suggested that the bat sapovirus descended from an ancestral sapovirus lineage and is most closely related to the porcine sapoviruses. Codon usage analysis showed that the bat sapovirus genome has greater codon usage bias relative to other sapovirus genomes. In summary, we report the discovery and genomic characterization of the first bat calicivirus, which appears to have evolved under different conditions after early divergence from other sapovirus lineages.
Output: Discovery and Genomic Characterization of a Novel Bat Sapovirus with Unusual Genomic Features and Phylogenetic Position
The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's endproduct. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and b-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis). Cumulatively, these data suggest that productive infection requires the mitochondrial b-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis) that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia infection, and in particular virion assembly, relies on the synthesis and mitochondrial import of fatty acids, where their b-oxidation drives robust ATP production. Citation: Greseth MD, Traktman P (2014) De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection. PLoS Pathog 10(3): e1004021.
Output: De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection
Microglia are the resident macrophage-like populations in the central nervous system (CNS). Microglia remain quiescent, unable to perform effector and antigen presentation (APC) functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS. Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calciumbinding adaptor molecule 1), which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis. During chronic inflammation (day 30 postinfection), microglia were still present within areas of demyelination. Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection. Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination.
Output: Microglia Play a Major Role in Direct Viral-Induced Demyelination
Vero E6 African green monkey kidney cells are highly susceptible to infection with the newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV), and they are permissive for rapid viral replication, with resultant cytopathic effects. We employed cDNA microarray analysis to characterize the cellular transcriptional responses of homologous human genes at 12 h post-infection. Seventy mRNA transcripts belonging to various functional classes exhibited significant alterations in gene expression. There was considerable induction of heat shock proteins that are crucial to the immune response mechanism. Modified levels of several transcripts involved in pro-inflammatory and anti-inflammatory processes exemplified the balance between opposing forces during SARS pathogenesis. Other genes displaying altered transcription included those associated with host translation, cellular metabolism, cell cycle, signal transduction, transcriptional regulation, protein trafficking, protein modulators, and cytoskeletal proteins. Alterations in the levels of several novel transcripts encoding hypothetical proteins and expressed sequence tags were also identified. In addition, transcription of apoptosis-related genes DENN and hIAP1 was upregulated in contrast to FAIM. Elevated Mx1 expression signified a strong host response to mediate antiviral resistance. Also expressed in infected cells was the C-terminal alternative splice variant of the p53 tumor suppressor gene encoding a modified truncated protein that can influence the activity of wild-type p53. We observed the interplay between various mechanisms to favor virus multiplication before full-blown apoptosis and the triggering of several pathways in host cells in an attempt to eliminate the pathogen. Microarray analysis identifies the critical hostpathogen interactions during SARS-CoV infection and provides new insights into the pathophysiology of SARS.
Output: Microarray and real-time RT-PCR analyses of differential human gene expression patterns induced by severe acute respiratory syndrome (SARS) coronavirus infection of Vero cells
Background: Hepatitis C virus (HCV) is a blood-borne flavivirus that infects many millions of people worldwide. Relatively little is known, however, concerning the stability of HCV and reliable procedures for inactivating this virus. Methods: In the current study, the thermostability of cell culture-derived HCV (HCVcc, JFH-1 strain) under different environmental temperatures (37°C, room temperature, and 4°C) and the ability of heat, UVC light irradiation, and aldehyde and detergent treatments to inactivate HCVcc were evaluated. The infectious titers of treated viral samples were determined by focus-forming unit (FFU) assay using an indirect immunofluorescence assay for HCV NS3 in hepatoma Huh7-25-CD81 cells highly permissive for HCVcc infection. MTT cytotoxicity assay was performed to determine the concentrations of aldehydes or detergents at which they were no longer cytotoxic. Results: HCVcc in culture medium was found to survive 37°C and room temperature (RT, 25 ± 2°C) for 2 and 16 days, respectively, while the virus was relatively stable at 4°C without drastic loss of infectivity for at least 6 weeks. HCVcc in culture medium was sensitive to heat and could be inactivated in 8 and 4 min when incubated at 60°C and 65°C, respectively. However, at 56°C, 40 min were required to eliminate HCVcc infectivity. Addition of normal human serum to HCVcc did not significantly alter viral stability at RT or its susceptibility to heat. UVC light irradiation (wavelength = 253.7 nm) with an intensity of 450 μW/cm 2 efficiently inactivated HCVcc within 2 min. Exposures to formaldehyde, glutaraldehyde, ionic or nonionic detergents all destroyed HCVcc infectivity effectively, regardless of whether the treatments were conducted in the presence of cell culture medium or human serum. Conclusions: The results provide quantitative evidence for the potential use of a variety of approaches for inactivating HCV. The ability of HCVcc to survive ambient temperatures warrants precautions in handling and disposing of objects and materials that may have been contaminated with HCV.
Output: Thermal stability and inactivation of hepatitis C virus grown in cell culture
Purpose To generate and characterize a specific monoclonal antibody (mAb) against recombinant human RANK receptor and to develop an antiresorptive strategy using this mAb as an osteoclast-targeting platform that selectively targets osteoclast cells whilst delivering an attached (i.e. chemically conjugated) active drug cargo. Methods Using hybridoma technology, we generated a specific monoclonal antibody (mAb) against recombinant human RANK receptor and characterized by SDS PAGE, ELISA, Western Blot and immunocytochemistry, then synthesized osteoclast-targeting bioconjugates of salmon calcitonin (sCT) using this antibody by generating thiol groups on mAb using 2-Iminothiolane and subsequently reacting them with sCT-PEG-MAL synthesised from sCT and NHS-PEG-MAL. To test the efficacy of the conjugate in vitro, osteoclasts were generated from precursor RAW 264.7 cells by dosing with the cytokines macrophagecolony-stimulating factor (M-CSF), and RANK Ligand (RANKL) and TRAP activity assay, Resorption Pit Assay, TRAP staining were performed. Cytotoxicity of the mAb-sCT conjugate was also evaluated in RAW 264.7 cells; sCT bioactivity and CTR binding potential were evaluated by in vitro intracellular cAMP stimulation assay in human T47D breast cancer cells. Results Generation of antibody against human RANK receptor was confirmed by SDS PAGE, ELISA and Western Blot. Immunocytochemistry confirmed the osteoclast targeting potential of the antibody. Successful conjugation of the antibody with sCT was confirmed by SDS PAGE and ELISA. Multinucleated osteoclast formation was confirmed by staining for tartrate-resistant acid phosphatase (TRAP). Conjugate functionality was confirmed by TRAP activity and Resorption Pit assay, showing the inhibitory effect on osteoclast differentiation. cAMP assay confirmed the retention of calcitonin bioactivity after conjugation. Conclusions Our strategy offers the potential for a "universal" osteoclast-targeting platform-one that targets the RANK receptor on osteoclast cells by simply altering the conjugated cargo in order to affect the specific regulation of osteoclast cells. KEY WORDS drug delivery system . monoclonal antibody . osteoclast . osteoporosis . post-traumatic osteoarthritis . RANK receptor . salmon calcitonin M. Newa : K. H.
Output: Antibody-Mediated "Universal" Osteoclast Targeting Platform using Calcitonin as a Model Drug
The serotonin transporter (SERT), a member of the neurotransmitter sodium symporter (NSS) family, is responsible for the reuptake of serotonin from the synaptic cleft to maintain neurotransmitter homeostasis. SERT is established as an important target in the treatment of anxiety and depression. Because a high-resolution crystal structure is not available, a computational model of SERT was built based upon the x-ray coordinates of the leucine transporter LeuT, a bacterial NSS homolog. The model was used to develop the first SERT structure-based pharmacophore. Virtual screening (VS) of a small molecule structural library using the generated SERT computational model yielded candidate ligands of diverse scaffolds. Pharmacological analysis of the VS hits identified two SERT-selective compounds, potential lead compounds for further SERT-related medication development.
Output: Discovery of Novel Selective Serotonin Reuptake Inhibitors Through Development of a Protein-Based Pharmacophore
Background: Patients with respiratory or gastrointestinal illness in emergency care settings are often not yet diagnosed but are at risk of transmitting disease. Infection control algorithms delineating a standard approach to patient management decrease risk of secondary exposure, but few articles document health care workers' (HCWs) perceptions as to their effectiveness and ease of implementation. Methods: A cross-sectional survey approach was used to explore HCWs perceptions in 2 emergency departments of the current algorithms for management of potentially infectious respiratory and gastrointestinal illnesses. Results: Surveys from 96 HCWs revealed that algorithms were perceived as invaluable in protecting staff, patients, and colleagues. Differences in self-reported compliance, clarity, and ease of implementation of the respiratory algorithm were noted between facilities, likely reflecting variation in the physical plant. Physicians scored significantly lower for compliance with the respiratory algorithm. Conclusion: Algorithms were perceived to offer a clear and consistent approach to patient management and protect HCWs in spite of environmental and resource limitations.
Output: Health care workers' perceptions of respiratory and gastrointestinal algorithms for patient management in emergency care settings
Quasispecies dynamics mediates adaptability of RNA viruses through a number of mechanisms reviewed in the present article, with emphasis on the medical implications for the hepatitis viruses. We discuss replicative and non-replicative molecular mechanisms of genome variation, modulating effects of mutant spectra, and several modes of viral evolution that can affect viral pathogenesis. Relevant evolutionary events include the generation of minority virus variants with altered functional properties, and alterations of mutant spectrum complexity that can affect disease progression or response to treatment. The widespread occurrence of resistance to antiviral drugs encourages new strategies to control hepatic viral disease such as combination therapies and lethal mutagenesis. In particular, ribavirin may be exerting in some cases its antiviral activity with participation of its mutagenic action. Despite many unanswered questions, here we document that quasispecies dynamics has provided an interpretation of the adaptability of the hepatitis viruses, with features conceptually similar to those observed with other RNA viruses, a reflection of the common underlying Darwinian principles.
Output: Quasispecies and its impact on viral hepatitis
Background: IFITM3 has been suggested to be associated with infection in some ethnic groups. Diabetes and hypercholesterolemia are also important clinical conditions that can predispose individuals to infection. The aim of this study was to investigate the association of rs12252 C polymorphism, BMI, diabetes, and hypercholesterolemia with mild flu in an Iranian population. Methods: We conducted a case-control study, including 79 mild flu and 125 flu-negative individuals attending primary care centers of three provinces of Iran (i.e, Markazi, Semnan, and Zanjan). Pharyngeal swab specimens were collected from all participants, and were subjected to RNA and DNA extractions for Real-time PCR and PCR tests. All PCR products were then sequenced to find T/C polymorphisms in the rs12252 region. Data on demographic, anthropometric, and clinical variables were collected from participants' medical records available in the primary care centers. The data was analyzed using DNASIS (v. 2.5) and Stata (v.11) software. Results: All participants were of Fars ethnic background. The allele frequency for rs12252-C was found to be 9.49% among cases and 2.40% among controls. Carriers of the rs12252 C allele (CT + CC genotypes) showed 5.92 folds increase in the risk of mild flu comparing to the T allele homozygotes (P value: 0.007). We also found a significant positive association between rs12252 C allele heterozygote and mild flu (OR: 7.62, P value: 0.008), but not in C allele homozygote group (OR: 2.71, P value: 0.406). Similarly, we did not find a significant association between mild flu and BMI (OR: 1.06, P value: 0.087), diabetes (OR: 0.61, P value: 0.392), and hypercholesterolemia (OR: 0.50, P value: 0.393) in multivariable logistic regression. Conclusions: This is the first study evaluating the association between rs12252 polymorphisms, diabetes, hypercholesterolemia, and BMI and susceptibility to mild flu in an Iranian population. Our results suggest a significant positive association between mild flu and rs12252 C allele heterozygous and carriage. Future replication of the strong association observed here between rs12252 C allele carriage and mild flu might candidate this polymorphism as a genetic marker for early screening of susceptibility to mild flu. Lack of significant association between C allele homozygous and mild flu, observed in this study, might be the result of small sample size in this group. Trial registration: IR.PII.REC.1395.3.
Output: Association of IFITM3 rs12252 polymorphisms, BMI, diabetes, and hypercholesterolemia with mild flu in an Iranian population
Pompe disease results from a defect in human acid α-glucosidase (GAA), a lysosomal enzyme 17 that cleaves terminal α1-4 and α1-6 glucose from glycogen. In Pompe disease (also known as 18 Glycogen Storage Disorder type II), the accumulation of undegraded glycogen in lysosomes 19 leads to cellular dysfunction, primarily in muscle and heart tissues. Pompe disease is an active 20 candidate of clinical research, with pharmacological chaperone therapy tested and enzyme 21 replacement therapy approved. Despite production of large amounts of recombinant GAA 22 annually, the structure of GAA has not been reported until now. Here, we describe the first 23 structure of GAA, at 1.7Å resolution. Three structures of GAA complexes reveal the molecular 24 basis for the hundreds of mutations that lead to Pompe disease and for pharmacological 25 chaperoning in the protein. The GAA structure reveals a surprising second sugar-binding site 26
Output: The molecular basis for Pompe disease 3 revealed by the structure of human acid α-glucosidase 4 5
Background: COVID-19 originated in China and has quickly spread worldwide causing a pandemic. Countries need rapid data on the prevalence of the virus in communities to enable rapid containment. However, the equipment, human and laboratory resources required for conducting individual RT-PCR is prohibitive. One technique to reduce the number of tests required is the pooling of samples for analysis by RT-PCR prior to testing. We conducted a mathematical analysis of pooling strategies for infection rate classification using group testing and for the identification of individuals by testing pooled clusters of samples. Findings: On the basis of the proposed pooled testing strategy we calculate the probability of false alarm, the probability of detection, and the average number of tests required as a function of the pool size. We find that when the sample size is 256, using a maximum pool size of 64, with only 7.3 tests on average, we can distinguish between prevalences of 1% and 5% with a probability of detection of 95% and probability of false alarm of 4%. Interpretation: The pooling of RT-PCR samples is a cost-effective technique for providing much-needed course-grained data on the prevalence of COVID-19. This is a powerful tool in providing countries with information that can facilitate a response to the pandemic that is evidence-based and saves the most lives possible with the resources available.
Output: Pooling RT-PCR or NGS samples has the potential to cost-effectively generate estimates of COVID-19 prevalence in resource limited environments
There was a pandemic of influenza A (H1N1) in 2009; in Korea, there was also an H1N1 epidemic in 2016. We aim to investigate whether survival had improved in the setting of recent advances in intensive care unit (ICU) management. We conducted a retrospective analysis of acute respiratory failure patients with H1N1 influenza pneumonia in 2016 and 2009 respectively at two tertiary referral hospitals in Korea. A total of 28 patients were treated in 2016, and 34 in 2009. There was no significant difference in SOFA scores on ICU admission day. In-hospital mortality was significantly lower in patients of 2016 compared to those of 2009 (18% vs. 44% P = 0.028). By multivariable analyses, the treatment year 2016 was associated with a greater likelihood of survival. Compared to the patients treated in 2009, those treated in 2016 were one seventh as likely to die after adjusting for other clinical variables (hazard ratio for mortality, 0.15; 95% confidence interval. 0.03-0.63, P = 0.010). Improved survival in patients who underwent extracorporeal membrane oxygenation treatment (in-hospital mortality, 17% vs. 60%, P = 0.242) and decreased tidal volumes during mechanical ventilation (median 5.4 mL/kg vs. median 9.2 mL/kg, P = 0.018) were observed in
Output: Improved survival rates in patients with H1N1 acute respiratory failure in Korea between 2009 and 2016
Feline infectious peritonitis (FIP) is an immune-mediated disease of domestic and exotic felides infected with feline coronavirus. FIP is characterized by the overexpression of an acute phase protein, the a1-acid glycoprotein (AGP). In humans, AGP is a heavily glycosylated protein that undergoes several modifications of its glycan moiety during acute and chronic inflammatory pathologies. We studied the changes in AGP glycosylation in the course of FIP. Specifically, we focussed our attention on the degree of sialylation, fucosylation and branching. This study presents a purification method for feline AGP (fAGP) from serum, using an ion exchange chromatography strategy. The glycosylation pattern was analyzed in detail by means of interaction of purified fAGP with specific lectins. In particular, Sambucus nigra agglutinin I and Maackia amurensis agglutinin lectins were used to detect sialic acid residues, Aleuria aurantia lectin was used to detect L-fucose residues and Concanavalin A was used to evaluate the branching degree. By this method we showed that fAGP did not present any L-fucose residues on its surface, and that its branching degree was very low, both in normal and in pathological conditions. In contrast, during FIP disease, fAGP underwent several modifications in the sialic acid content, including decreased expression of both a(2-6)-linked and a(2-3)-linked sialic acid (76 and 44%, respectively when compared to non-pathological feline AGP). #
Output: Decreased sialylation of the acute phase protein a1-acid glycoprotein in feline infectious peritonitis (FIP)
Automatic detection of cases of febrile illness may have potential for early detection of outbreaks of infectious disease either by identification of anomalous numbers of febrile illness or in concert with other information in diagnosing specific syndromes, such as febrile respiratory syndrome. At most institutions, febrile information is contained only in free-text clinical records. We compared the sensitivity and specificity of three fever detection algorithms for detecting fever from free-text. Keyword CC and CoCo classified patients based on triage chief complaints; Keyword HP classified patients based on dictated emergency department reports. Keyword HP was the most sensitive (sensitivity 0.98, specificity 0.89), and Keyword CC was the most specific (sensitivity 0.61, specificity 1.0). Because chief complaints are available sooner than emergency department reports, we suggest a combined application that classifies patients based on their chief complaint followed by classification based on their emergency department report, once the report becomes available.
Output: Fever detection from free-text clinical records for biosurveillance
Predicting influence of human thermal plume on the diffusion of respiration-produced particles is an important issue for improving indoor air quality through eliminating infectious microbes efficiently. In this study, the Large Eddy Simulation was utilized to predict the effects of thermal plume of different intensities on particle diffusion. Three postures of the human body model and three room temperatures were considered. The results show that the convective heat transfer coefficient on the surface of the human body varies greatly with different postures. The coefficient is the largest when the model is in sitting posture, leading to the greatest heat transfer rate. Meanwhile, the thermal plume generated by bending the thigh increases the size of the facial thermal plume in horizon direction. The increase of the difference between indoor temperature and skin temperature causes an increase of the convective heat transfer of the manikin, leading to stronger airflow in front of the face. The thicker and faster the human thermal plume is, the more difficult it is penetrated by aerosols produced by nasal breathing, finally resulting in most particles distributed within 0.2 m thick under the roof.
Output: Study on the motion law of aerosols produced by human respiration under the action of thermal plume of different intensities
Background: Domestic rabbits especially New Zealand white rabbits play an important role in biological research. The disease surveillance and quality control are essential to guarantee the results of animal experiments performed on rabbits. Rabbit hemorrhagic disease virus, rabbit rotavirus and Sendai virus are the important pathogens that needed to be eliminated. Rapid and sensitive method focus on these three viruses should be established for routine monitoring. The Luminex x-TAG assay based on multiplex PCR and fluorescent microsphere is a fast developing technology applied in high throughput detection. Specific primers modified with oligonucleotide sequence/biotin were used to amplify target fragments. The conjugation between oligonucleotide sequence of the PCR products and the MagPlex-TAG microspheres was specific without any cross-reaction, and the hybridization products could be analyzed using the Luminex 200 analyzer instrument. Recombinant plasmids were constructed to estimate the detection limit of the viruses. Furthermore, 40 clinical samples were used to evaluate the efficiency of this multiplex PCR based Luminex x-TAG assay. Results: According to the results, this new method showed high specificity and good stability. Assessed by the recombinant plasmids, the detection limit of three viruses was 100copies/μl. Among 40 clinical specimens, 18 specimens were found positive, which was completely concordant with the conventional PCR method. The new developed Luminex x-TAG assay is an accurate, high throughput method for rapid detection of three important viruses of rabbits.
Output: Rapid detection of three rabbit pathogens by use of the Luminex x-TAG assay
FIGURE 26.8 Impaction in an ostrich. The proventriculus and ventriculus are markedly distended and filled with coarse roughage-unopened (A) and opened (B). (Photos Courtesy of M. Brash, Animal Health Laboratory [AHL], University of Guelph) FIGURE 26.9 Shell abnormalities in ostrich eggs. Malformed, wrinkled egg shells. The causes of this nonspecific change are poorly understood but are postulated to include viral infection, particularly with adenovirus and Newcastle disease virus, bacterial salpingitis, nutritional deficiencies or imbalances, and other abnormalities of the oviduct.
Output: Palaeognathae: Apterygiformes, Casuariiformes, Rheiformes, Struthioniformes; Tinamiformes
Background: Chinese hamster ovary (CHO) cells are the most dependable mammalian cells for the production of recombinant proteins. Replication-incompetent retroviral vector (retrovector) is an efficient tool to generate stable cell lines. Multiple copies of integrated genes by retrovector transduction results in improved recombinant protein yield. HEK-293 and their genetic derivatives are principal cells for retrovector production. Retrovectors packaged in HEK-293 cells pose a risk of infectious agent transmission, such as viruses and mycoplasmas, from serum and packaging cells. Results: In this report, retrovectors were packaged in CHO cells cultured in chemically defined (CD) media. The retrovectors were then used to transduce CHO cells. This method can block potential transmission of infectious agents from serum and packaging cells. With this method, we generated glucagon-like protein-1 Fc fusion protein (GLP-1-Fc) stable expression CHO cell lines. Productivity of GLP-1-Fc can reach 3.15 g/L. The GLP-1-Fc protein produced by this method has comparable bioactivity to that of dulaglutide (Trulicity). These stable cell lines retain 95-100% of productivity after 40 days of continuous culture (~48-56 generations). Conclusions: Suspension CHO cells are clean, safe, and reliable cells for retrovector packaging. Retrovectors packaged from this system could be used to generate CHO stable cell lines for recombinant protein expression. How to cite: Li J, Wei S, Cao C, et al. Retrovectors packaged in CHO cells to generate GLP-1-Fc stable expression CHO cell lines. Electron J Biotechnol 2019;41. https://doi.
Output: Retrovectors packaged in CHO cells to generate GLP-1-Fc stable expression CHO cell lines-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
G-quadruplexes (G4s) are non-canonical nucleic acids secondary structures that form within guaninerich strands of regulatory genomic regions. G4s have been extensively described in the human genome, especially in telomeres and oncogene promoters; in recent years the presence of G4s in viruses has attracted increasing interest. Indeed, G4s have been reported in several viruses, including those involved in recent epidemics, such as the Zika and Ebola viruses. Viral G4s are usually located in regulatory regions of the genome and implicated in the control of key viral processes; in some cases, they have been involved also in viral latency. In this context, G4 ligands have been developed and tested both as tools to study the complexity of G4-mediated mechanisms in the viral life cycle, and as therapeutic agents. In general, G4 ligands showed promising antiviral activity, with G4-mediated mechanisms of action both at the genome and transcript level. This review aims to provide an updated close-up of the literature on G4s in viruses. The current state of the art of G4 ligands in antiviral research is also reported, with particular focus on the structural and physicochemical requirements for optimal biological activity. The achievements and the to-dos in the field are discussed.
Output: SURVEY AND SUMMARY G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy
Analyses to ensure food safety and quality are more relevant now because of rapid changes in the quantity, diversity and mobility of food. Food-contamination must be determined to maintain health and up-hold laws, as well as for ethical and cultural concerns. Real-time polymerase chain reaction (RT-PCR), a rapid and inexpensive quantitative method to detect the presence of targeted DNA-segments in samples, helps in determining both accidental and intentional adulterations of foods by biological contaminants. This review presents recent developments in theory, techniques, and applications of RT-PCR in food analyses, RT-PCR addresses the limitations of traditional food analyses in terms of sensitivity, range of analytes, multiplexing ability, cost, time, and pointof-care applications. A range of targets, including species of plants or animals which are used as food ingredients, food-borne bacteria or viruses, genetically modified organisms, and allergens, even in highly processed foods can be identified by RT-PCR, even at very low concentrations. Microfluidic RT-PCR eliminates the separate sample-processing step to create opportunities for point-of-care analyses. We also cover the challenges related to using RT-PCR for food analyses, such as the need to further improve sample handling.
Output: Trends and advances in food analysis by real-time polymerase chain reaction