PeerJ Preprints: Infectious Diseaseshttps://peerj.com/preprints/index.atom?journal=peerj&subject=5130Infectious Diseases articles published in PeerJ PreprintsDiscrete stochastic marine metapopulation disease modelhttps://peerj.com/preprints/264542019-11-282019-11-28Gorka BidegainTal Ben-Horin
Some marine microparasitic pathogens can survive several months in the water column to make contact with or to be absorbed or filtered by hosts. Once inside, pathogens invade the host if they find suitable conditions for reproduction. This transmission from the environment occurs via pathogens released from infected and dead infected animals. Some recent modeling studies concentrated on the disease dynamic imposed by this complex interaction between population and water column at the host-pathogen level in single populations. However, only when a marine disease can be understood at the metapopulation scale effective approaches to management will become routinely achievable. The discrete-time disease model in this paper investigates both spatial and temporal dynamics of hosts and waterborne pathogens in a metapopulation system of three patches. This system with a patch providing infective particles and susceptible and infected individuals by dispersal tries to imitate the effect of current forces in the ocean on the passive dispersal of organisms. The model detects behaviours that are not present in single population continuous-time and deterministic models.
Some marine microparasitic pathogens can survive several months in the water column to make contact with or to be absorbed or filtered by hosts. Once inside, pathogens invade the host if they find suitable conditions for reproduction. This transmission from the environment occurs via pathogens released from infected and dead infected animals. Some recent modeling studies concentrated on the disease dynamic imposed by this complex interaction between population and water column at the host-pathogen level in single populations. However, only when a marine disease can be understood at the metapopulation scale effective approaches to management will become routinely achievable. The discrete-time disease model in this paper investigates both spatial and temporal dynamics of hosts and waterborne pathogens in a metapopulation system of three patches. This system with a patch providing infective particles and susceptible and infected individuals by dispersal tries to imitate the effect of current forces in the ocean on the passive dispersal of organisms. The model detects behaviours that are not present in single population continuous-time and deterministic models.Bacteriophages of Klebsiella spp., their diversity and potential therapeutic useshttps://peerj.com/preprints/278902019-08-092019-08-09Warren P HerridgePreetha ShibuJessica O'SheaThomas C BrookLesley Hoyles
Klebsiella spp. are commensals of the human microbiota, and a leading cause of opportunistic nosocomial infections. The incidence of multi-drug resistant (MDR) strains of Klebsiella pneumoniae causing serious infections is increasing, and K. oxytoca is an emerging pathogen. Alternative strategies to tackle infections caused by these bacteria are required as strains become resistant to last-resort antibiotics such as colistin. Bacteriophages (phages) are viruses that can infect and kill bacteria. They and their gene products are now being considered as alternatives or adjuncts to antimicrobial therapies. Several in vitro and in vivo studies have shown the potential for lytic phages to combat MDR K. pneumoniae infections. Ready access to cheap sequencing technologies has led to a large increase in the number of genomes available for Klebsiella-infecting phages, with these phages heterogeneous at the whole-genome level. This review summarises our current knowledge on phages of Klebsiella spp. and highlights technological and biological issues relevant to the development of phage-based therapies targeting these bacteria.
Klebsiella spp. are commensals of the human microbiota, and a leading cause of opportunistic nosocomial infections. The incidence of multi-drug resistant (MDR) strains of Klebsiella pneumoniae causing serious infections is increasing, and K. oxytoca is an emerging pathogen. Alternative strategies to tackle infections caused by these bacteria are required as strains become resistant to last-resort antibiotics such as colistin. Bacteriophages (phages) are viruses that can infect and kill bacteria. They and their gene products are now being considered as alternatives or adjuncts to antimicrobial therapies. Several in vitro and in vivo studies have shown the potential for lytic phages to combat MDR K. pneumoniae infections. Ready access to cheap sequencing technologies has led to a large increase in the number of genomes available for Klebsiella-infecting phages, with these phages heterogeneous at the whole-genome level. This review summarises our current knowledge on phages of Klebsiella spp. and highlights technological and biological issues relevant to the development of phage-based therapies targeting these bacteria.Genomic analysis of prevalent Staphylococcus epidermidis multidrug-resistant strains isolated during eight years in a single children hospital in México City.https://peerj.com/preprints/276932019-08-052019-08-05Roberto Cabrera-ContrerasRosa I SantamaríaPatricia BustosIrma Martínez-FloresEnrique MeléndezRubén MorelosMartín Barbosa-AmezcuaVanessa González-CovarrubiasEugenia Silva-HerzogXavier SoberónVíctor González
Staphylococcus epidermidis is a human commensal and pathogen worldwide distributed. In this work, we surveyed for multi-resistant S. epidermidis strains in eight years at a children health-care unit in México City. Multidrug-resistant S. epidermidis were present in all years of the study. Resistance to methicillin, beta-lactams, fluoroquinolones, and macrolides were included. To understand the genetic basis of antibiotic resistance and its association with virulence and gene exchange, we sequenced the genomes of 17 S. epidermidis isolates. Whole-genome nucleotide identities between all the pairs of S. epidermidis strains were about 97% to 99%. We inferred a clonal structure and eight Multilocus Sequence Types (MLST´s) in the S. epidermidis sequenced collection. The profile of virulence includes genes involved in biofilm formation and phenol-soluble modulins (PSMs). However, half of the S. epidermidis analyzed lacked the icaoperon for biofilm formation. Likely, they are commensal S. epidermidis strains but multi-antibiotic resistant. Uneven distribution of insertion sequences, phages, and CRISPR-Cas immunity phage systems suggest frequent horizontal gene transfer. Rates of recombination between S. epidermidis strains were more prevalent than the mutation rate and affected the whole genome. Therefore, the multidrug-resistance, independently of the pathogenic traits, might explain the persistence of specific highly adapted S. epidermidis clonal lineages in nosocomial settings.
Staphylococcus epidermidis is a human commensal and pathogen worldwide distributed. In this work, we surveyed for multi-resistant S. epidermidis strains in eight years at a children health-care unit in México City. Multidrug-resistant S. epidermidis were present in all years of the study. Resistance to methicillin, beta-lactams, fluoroquinolones, and macrolides were included. To understand the genetic basis of antibiotic resistance and its association with virulence and gene exchange, we sequenced the genomes of 17 S. epidermidis isolates. Whole-genome nucleotide identities between all the pairs of S. epidermidis strains were about 97% to 99%. We inferred a clonal structure and eight Multilocus Sequence Types (MLST´s) in the S. epidermidis sequenced collection. The profile of virulence includes genes involved in biofilm formation and phenol-soluble modulins (PSMs). However, half of the S. epidermidis analyzed lacked the icaoperon for biofilm formation. Likely, they are commensal S. epidermidis strains but multi-antibiotic resistant. Uneven distribution of insertion sequences, phages, and CRISPR-Cas immunity phage systems suggest frequent horizontal gene transfer. Rates of recombination between S. epidermidis strains were more prevalent than the mutation rate and affected the whole genome. Therefore, the multidrug-resistance, independently of the pathogenic traits, might explain the persistence of specific highly adapted S. epidermidis clonal lineages in nosocomial settings.Allogenic stem cell transplant in a patient with classical Kaposi's sarcomahttps://peerj.com/preprints/482019-08-042019-08-04Richard Barchas
A 68 year old male with a history of classical Kaposi's sarcoma (KS) and precursor T-cell acute lymphoblastic leukemia (ALL) received an allogenic stem cell transplant from an unrelated donor to treat his ALL. He developed acute graft-vs.-host-disease (GVHD) which was treated by increasing immunosuppressants. KS, which had been in remission for years, then recurred aggressively. Tapering immunosuppressants to treat the KS was not possible because of GVHD. Chemotherapy could not be used because of its adverse effect on the bone marrow so soon after transplant. The only option was to use antiviral therapy (cidofovir) to lower the level of HHV-8, the virus that is a causal factor in KS. Although HHV-8 levels were significantly reduced, new KS lesions continued to appear. The patient developed acute kidney injury after the third cidofovir infusion and died from renal and respiratory failure soon afterward. Post-mortem revealed extensive internal KS lesions involving multiple organs. Based on the experience with this patient, allogenic transplant using an unrelated donor has been found to be a questionable treatment modality for classical KS patients requiring treatment for another condition such as leukemias and lymphomas. Post-transplant immunosuppression is required to prevent GVHD, and if it occurs, immunosuppression may have to be increased. Aggressive KS developed in this patient under these conditions, and could not be controlled by tapering immunosuppressants. Although the risk of GVHD is lower for an allogenic transplant using a matched sibling instead of an unrelated donor, the risk of both GVHD and aggressive KS both developing may still be unacceptably high.Alternative treatment modalities for these patients might include continuing with chemotherapy and autologous transplant. These avoid GVHD and lower the need for long term immunosuppression, but have a much higher risk of relapse of the underlying malignancy. Still, they could be preferable to an allogenic transplant for such cases.
A 68 year old male with a history of classical Kaposi's sarcoma (KS) and precursor T-cell acute lymphoblastic leukemia (ALL) received an allogenic stem cell transplant from an unrelated donor to treat his ALL. He developed acute graft-vs.-host-disease (GVHD) which was treated by increasing immunosuppressants. KS, which had been in remission for years, then recurred aggressively. Tapering immunosuppressants to treat the KS was not possible because of GVHD. Chemotherapy could not be used because of its adverse effect on the bone marrow so soon after transplant. The only option was to use antiviral therapy (cidofovir) to lower the level of HHV-8, the virus that is a causal factor in KS. Although HHV-8 levels were significantly reduced, new KS lesions continued to appear. The patient developed acute kidney injury after the third cidofovir infusion and died from renal and respiratory failure soon afterward. Post-mortem revealed extensive internal KS lesions involving multiple organs. Based on the experience with this patient, allogenic transplant using an unrelated donor has been found to be a questionable treatment modality for classical KS patients requiring treatment for another condition such as leukemias and lymphomas. Post-transplant immunosuppression is required to prevent GVHD, and if it occurs, immunosuppression may have to be increased. Aggressive KS developed in this patient under these conditions, and could not be controlled by tapering immunosuppressants. Although the risk of GVHD is lower for an allogenic transplant using a matched sibling instead of an unrelated donor, the risk of both GVHD and aggressive KS both developing may still be unacceptably high.Alternative treatment modalities for these patients might include continuing with chemotherapy and autologous transplant. These avoid GVHD and lower the need for long term immunosuppression, but have a much higher risk of relapse of the underlying malignancy. Still, they could be preferable to an allogenic transplant for such cases.Integrating the extracellular, intracellular, and intercellular metabolic processes of Escherichia coli through glucose saturation, inhibition of the acetyl-CoA carboxylase subunit accA with asRNA, and through quantifying cell to cell quorum-sensinghttps://peerj.com/preprints/274592019-07-032019-07-03Tatiana HillmanCory Tobin
The study aims to demonstrate the link between bacterial cell metabolism and virulence through integrating the environmental, genetic, and cell to cell signaling molecular processes. Dietary fiber metabolized into glucose, increases the proliferation of intestinal microflora, which augments the outputof the Short Chain Fatty Acids. Bacteria ferment the glucose, from fiber, into Short Chain Fatty Acids, which help regulate many biochemical processes and pathways. Each SCFA maintains colonic pH, promotes cell differentiation, and the apoptosis of colonocytes. To model a high-fiber diet, increasing the synthesis of Acetyl-CoA carboxylase, an enzyme that catabolizes glucose into SCFAs, Escherichia coli was cultured in Luria Broth enhanced with a high to low concentration of glucose. The 15mM, a high concentration of glucose, yielded qPCR products measured, for the target gene accA, which was 4,210ng/µL. The 7.5mM sample produced a concentration equaled to 375 ng/µL, and the 0µM sample measured an accA concentration of 196 ng/µL. The gene accA, 1 of 4 subunits for the Acetyl-CoA Carboxylase enzyme, was suppressed by asRNA, producing a qPCR concentration of 63ng/µL. Antisense RNA for accA reduced the amount of Lux-S, a vital gene needed for propagating quorum-sensing signal molecules. The Lux-S gene, responsible for releasing autoinducer 2 for cell to cell quorum sensing, was reduced by the gene inhibition of accA with asRNA. The increase in Lux-S transcription increases biofilm production for spreading virulence. The further implications of the study propose designing antibiotics that target bacterial cell metabolic processes to block bacterial antibiotic resistance.
The study aims to demonstrate the link between bacterial cell metabolism and virulence through integrating the environmental, genetic, and cell to cell signaling molecular processes. Dietary fiber metabolized into glucose, increases the proliferation of intestinal microflora, which augments the outputof the Short Chain Fatty Acids. Bacteria ferment the glucose, from fiber, into Short Chain Fatty Acids, which help regulate many biochemical processes and pathways. Each SCFA maintains colonic pH, promotes cell differentiation, and the apoptosis of colonocytes. To model a high-fiber diet, increasing the synthesis of Acetyl-CoA carboxylase, an enzyme that catabolizes glucose into SCFAs, Escherichia coli was cultured in Luria Broth enhanced with a high to low concentration of glucose. The 15mM, a high concentration of glucose, yielded qPCR products measured, for the target gene accA, which was 4,210ng/µL. The 7.5mM sample produced a concentration equaled to 375 ng/µL, and the 0µM sample measured an accA concentration of 196 ng/µL. The gene accA, 1 of 4 subunits for the Acetyl-CoA Carboxylase enzyme, was suppressed by asRNA, producing a qPCR concentration of 63ng/µL. Antisense RNA for accA reduced the amount of Lux-S, a vital gene needed for propagating quorum-sensing signal molecules. The Lux-S gene, responsible for releasing autoinducer 2 for cell to cell quorum sensing, was reduced by the gene inhibition of accA with asRNA. The increase in Lux-S transcription increases biofilm production for spreading virulence. The further implications of the study propose designing antibiotics that target bacterial cell metabolic processes to block bacterial antibiotic resistance.CRISPR-Cas9 may restore the balance of hormones affected by the frequency of DNA methylation sites and a decrease of commensal bacteriahttps://peerj.com/preprints/275092019-06-212019-06-21Tatiana Hillman
In this review, it is suggested that there are connections between hormonal changes, the frequency of DNA methylation, and disease. The commensal microbes of the gut may also affect the production of those hormones. Short Chain Fatty Acids, produced from gut microbiota glucose metabolism, like butyrate, propionate, folate, and acetate act as ligands that bind to G-coupled protein receptors. For example, folate from Bifidobacterium donates a methyl for synthesizing S-adenosylmethionine or SAM, which then donates a methyl to the enzymes of DNA methylation, acting as a substrate. The effects of hormones on DNA methylation was reviewed. Increased progesterone can produce breast cancer by lessening DNA methylation allowing progesterone molecules to bind DNA, amplifying gene expression. Through measuring the frequency of DNA methylation perhaps breast cancer can be more readily identified, diagnosed, and treated. The intended purpose for this review is to propose the possibility of applying CRISPR-Cas9 methods to correct and restore the balance of hormones through epigenetic means. In this review, 1) the effects of microbes on hormonal balance, 2) the connection between hormones and DNA Methylation, 3) cancer and DNA methylation, 4) measuring DNA methylation, and 5) applying CRISPR methods will be discussed.
In this review, it is suggested that there are connections between hormonal changes, the frequency of DNA methylation, and disease. The commensal microbes of the gut may also affect the production of those hormones. Short Chain Fatty Acids, produced from gut microbiota glucose metabolism, like butyrate, propionate, folate, and acetate act as ligands that bind to G-coupled protein receptors. For example, folate from Bifidobacterium donates a methyl for synthesizing S-adenosylmethionine or SAM, which then donates a methyl to the enzymes of DNA methylation, acting as a substrate. The effects of hormones on DNA methylation was reviewed. Increased progesterone can produce breast cancer by lessening DNA methylation allowing progesterone molecules to bind DNA, amplifying gene expression. Through measuring the frequency of DNA methylation perhaps breast cancer can be more readily identified, diagnosed, and treated. The intended purpose for this review is to propose the possibility of applying CRISPR-Cas9 methods to correct and restore the balance of hormones through epigenetic means. In this review, 1) the effects of microbes on hormonal balance, 2) the connection between hormones and DNA Methylation, 3) cancer and DNA methylation, 4) measuring DNA methylation, and 5) applying CRISPR methods will be discussed.Epidemiological scenario of Dengue in the state of Manipur during the last 3 yearshttps://peerj.com/preprints/277862019-06-062019-06-06Leimapokpam Shivadutta SinghRajkumar Manojkumar SinghHuidrom Lokhendro Singh
Background. In recent years, Dengue has been emerging as a global health problem with approximately 2.5 billion people being affected by it .In the last 50 years, the incidence of dengue infection has increased 30-fold, and the World Health Organization (WHO) has estimated that 96 million cases of dengue occur annually. The epidemiology of dengue fever (DF) is complex in the Indian subcontinent as all the four serotypes are circulating. And there is no systematic epidemiological study done on dengue cases in Manipur, a north-eastern state of India. This study is therefore done to report observations on dengue cases from a virus diagnostic and research laboratory of Manipur to present an epidemiological scenario of the state for the last three years. Method. We used the dengue data extracted from the laboratory register of Viral Research and Diagnostic Laboratory (VRDL) from 2016 to 2018. All suspected outpatient and inpatients dengue cases from public and private health services are included in the VRDL database whose informed consent were obtained. We evaluated the overall features of the data for generating seasonal pattern, geographical pattern, gender wise distribution, age wise distribution and seroprevelance pattern of dengue cases for the study period from 2016 to 2018. Results. A total of 1689 cases of suspected patients of dengue virus infection were tested for dengue ELISA test and 272(16.10%) samples were found to be seropositive. The month wise distribution of dengue cases is quite an interesting as the three years of study shows variant pattern in observation. In all the three years dengue seropositive cases were seen higher in male population. But there is no significant value to the positivity of dengue seropositive towards male than female (The chi-square statistic is 2.1314.The p-value is .344481. The result is not significant at p < .05.). Conclusion. Our study presents a comparative epidemiological study on seroprevelance of dengue in the state of Manipur from the year 2016 to 2018. The findings in the present study extend the knowledge of the geographical distribution and seroprevelance of dengue in the state of Manipur for the last three years. This is an attempt to present epidemiological dengue seroprevelance in the state of Manipur which in future would be a reference from public health concerns for taking up necessary action plan to curtail the spread of dengue.
Background. In recent years, Dengue has been emerging as a global health problem with approximately 2.5 billion people being affected by it .In the last 50 years, the incidence of dengue infection has increased 30-fold, and the World Health Organization (WHO) has estimated that 96 million cases of dengue occur annually. The epidemiology of dengue fever (DF) is complex in the Indian subcontinent as all the four serotypes are circulating. And there is no systematic epidemiological study done on dengue cases in Manipur, a north-eastern state of India. This study is therefore done to report observations on dengue cases from a virus diagnostic and research laboratory of Manipur to present an epidemiological scenario of the state for the last three years. Method. We used the dengue data extracted from the laboratory register of Viral Research and Diagnostic Laboratory (VRDL) from 2016 to 2018. All suspected outpatient and inpatients dengue cases from public and private health services are included in the VRDL database whose informed consent were obtained. We evaluated the overall features of the data for generating seasonal pattern, geographical pattern, gender wise distribution, age wise distribution and seroprevelance pattern of dengue cases for the study period from 2016 to 2018. Results. A total of 1689 cases of suspected patients of dengue virus infection were tested for dengue ELISA test and 272(16.10%) samples were found to be seropositive. The month wise distribution of dengue cases is quite an interesting as the three years of study shows variant pattern in observation. In all the three years dengue seropositive cases were seen higher in male population. But there is no significant value to the positivity of dengue seropositive towards male than female (The chi-square statistic is 2.1314.The p-value is .344481. The result is not significant at p < .05.). Conclusion. Our study presents a comparative epidemiological study on seroprevelance of dengue in the state of Manipur from the year 2016 to 2018. The findings in the present study extend the knowledge of the geographical distribution and seroprevelance of dengue in the state of Manipur for the last three years. This is an attempt to present epidemiological dengue seroprevelance in the state of Manipur which in future would be a reference from public health concerns for taking up necessary action plan to curtail the spread of dengue.Bioactivity of compounds secreted by symbiont bacteria of Nudibranchs from Indonesiahttps://peerj.com/preprints/277452019-05-202019-05-20Rhesi KristianaGilles BedouxGerard PalsI Wayan MudiantaLaure TaupinChristel MartyMeezan Ardhanu AsagabaldanDiah AyuningrumAgus TriantoNathalie BourgougnonOcky Karna RadjasaAgus Sabdono
The aim of this work was to isolate bacterial symbionts from nudibranchs and subsequently to determine anti-Methicillin resistant Staphylococcus aureus (MRSA), cytotoxicity and anti-HSV-1 activities of bio-compounds. Fifteen species of nudibranchs were collected from Karimunjawa and five species from Bali, respectively. A total of 245 bacteria isolates were obtained. The anti-MRSA activity screening activity indicated 2 isolates of active bacteria. Ethyl acetate extracts from supernatants, indicating secreted compounds, showed an inhibition zone against MRSA at concentrations of 500-1000µg/ml. DNA sequence analysis showed that the strainKJB-07 from Phyllidia coelestis was closely related to Pseudoalteromonas rubra, the strain NP31-01 from Phyllidia varicosa was closely related to Virgibacillus salarius. The extract of P. rubra was cytotoxic to Vero cells at a concentration of 75 µg/ml. The extract of V. salarius presented no cytotoxicity at concentrations of 5-1000 µg/ml. No anti-HSV-1 was observed. This is the first reported study describing research on anti-MRSA, cytotoxicity and anti-HSV-1 activity of bacterial symbionts from the viscera of nudibranch. Compounds produced and secreted byPseudoalteromonas rubra and Virgibacillus salarius, symbionts of Nudibranch, had potential anti-MRSA activity. Extracts from P. rubra showed cytotoxic effects on Vero cells, whereas extracts from V. salarius did not show cytotoxic effects. Three compounds were identified by LC/MS after purification from culture supernatant.
The aim of this work was to isolate bacterial symbionts from nudibranchs and subsequently to determine anti-Methicillin resistant Staphylococcus aureus (MRSA), cytotoxicity and anti-HSV-1 activities of bio-compounds. Fifteen species of nudibranchs were collected from Karimunjawa and five species from Bali, respectively. A total of 245 bacteria isolates were obtained. The anti-MRSA activity screening activity indicated 2 isolates of active bacteria. Ethyl acetate extracts from supernatants, indicating secreted compounds, showed an inhibition zone against MRSA at concentrations of 500-1000µg/ml. DNA sequence analysis showed that the strainKJB-07 from Phyllidia coelestis was closely related to Pseudoalteromonas rubra, the strain NP31-01 from Phyllidia varicosa was closely related to Virgibacillus salarius. The extract of P. rubra was cytotoxic to Vero cells at a concentration of 75 µg/ml. The extract of V. salarius presented no cytotoxicity at concentrations of 5-1000 µg/ml. No anti-HSV-1 was observed. This is the first reported study describing research on anti-MRSA, cytotoxicity and anti-HSV-1 activity of bacterial symbionts from the viscera of nudibranch. Compounds produced and secreted byPseudoalteromonas rubra and Virgibacillus salarius, symbionts of Nudibranch, had potential anti-MRSA activity. Extracts from P. rubra showed cytotoxic effects on Vero cells, whereas extracts from V. salarius did not show cytotoxic effects. Three compounds were identified by LC/MS after purification from culture supernatant.The key genes involved in herpes simplex virus-1 corneal infection-induced acute hepatitishttps://peerj.com/preprints/277242019-05-132019-05-13Kai HuJinlong LiXianwen Yuan
Background: Viral keratitis is mainly induced by herpes simplex virus (HSV). HSV-1 infection-induced acute hepatitis associates with immunodeficiency. Related biomarkers have not been systemically identified till now. This study was designed to explore the molecular mechanisms and potential biomarkers of HSV-1 infection-induced acute hepatitis.
Methods: Microarray dataset GSE35943, including the liver tissues infected by HSV-1 (1, 3, 5, and 7 days post infection) and the corresponding control tissues, was extracted from Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified using and were clustered using time series expression analysis. DEG-associated KEGG pathways were called using online DAVID tool. Using Cytoscape software, protein-protein interaction (PPI) network was built and significant network modules were identified.
Results: A total of 2909 DEGs grouping into 3 clusters with similar gene expression profiles were obtained. The DEGs were involved in immune-associated functional terms and pathways like natural killer cell mediated cytotoxicity and antigen processing and presentation. DEGs including PIK3R1, PIK3CD, PLCG2, PTPN6, LCK, RAC2, and PLK1 had higher degrees in the PPI network and 8 significant modules
Conclusion: PIK3R1, PIK3CD, PLCG2, PTPN6, LCK, RAC2 and PLK1 were identified to be associated with HSV-1 corneal infection-induced hepatitis, and might be potential clinical biomarkers for the diagnosis of HSV-1-induced hepatitis.
Background: Viral keratitis is mainly induced by herpes simplex virus (HSV). HSV-1 infection-induced acute hepatitis associates with immunodeficiency. Related biomarkers have not been systemically identified till now. This study was designed to explore the molecular mechanisms and potential biomarkers of HSV-1 infection-induced acute hepatitis.Methods: Microarray dataset GSE35943, including the liver tissues infected by HSV-1 (1, 3, 5, and 7 days post infection) and the corresponding control tissues, was extracted from Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified using and were clustered using time series expression analysis. DEG-associated KEGG pathways were called using online DAVID tool. Using Cytoscape software, protein-protein interaction (PPI) network was built and significant network modules were identified.Results: A total of 2909 DEGs grouping into 3 clusters with similar gene expression profiles were obtained. The DEGs were involved in immune-associated functional terms and pathways like natural killer cell mediated cytotoxicity and antigen processing and presentation. DEGs including PIK3R1, PIK3CD, PLCG2, PTPN6, LCK, RAC2, and PLK1 had higher degrees in the PPI network and 8 significant modulesConclusion: PIK3R1, PIK3CD, PLCG2, PTPN6, LCK, RAC2 and PLK1 were identified to be associated with HSV-1 corneal infection-induced hepatitis, and might be potential clinical biomarkers for the diagnosis of HSV-1-induced hepatitis.Chikungunya: time to change the paradigm of a non-fatal disease.https://peerj.com/preprints/276552019-04-162019-04-16André R R FreitasPatrick Gerardin
Since the initial description of the first human cases the chikungunya has been considered as a non-lethal virus. Since the emergence of the global virus in 2005, it has become increasingly common in the scientific literature to describe many cases of death, including in young people without preexisting diseases. In addition, it has been observed that in settings where, for some reason, death cases are not properly reported for epidemiological surveillance, it is possible to identify mortality due to chikungunya through the excess of deaths occurring during the period of chikungunya epidemics. Even so, international public health bodies still do not recognize in their official documents the importance of chikungunya as the cause of death. We believe it is necessary to review these positions and to increase investment in research to improve knowledge about the pathophysiology of severe forms and to review investment priorities in vaccines and other forms of chikungunya prevention.
Since the initial description of the first human cases the chikungunya has been considered as a non-lethal virus. Since the emergence of the global virus in 2005, it has become increasingly common in the scientific literature to describe many cases of death, including in young people without preexisting diseases. In addition, it has been observed that in settings where, for some reason, death cases are not properly reported for epidemiological surveillance, it is possible to identify mortality due to chikungunya through the excess of deaths occurring during the period of chikungunya epidemics. Even so, international public health bodies still do not recognize in their official documents the importance of chikungunya as the cause of death. We believe it is necessary to review these positions and to increase investment in research to improve knowledge about the pathophysiology of severe forms and to review investment priorities in vaccines and other forms of chikungunya prevention.