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During the acute phase of Chagas disease, Trypanosoma cruzi circulation through the bloodstream leads to high tissue parasitism in the host. In primary lymphoid organs, progenitor cell reduction paralleled transient immunosuppression. Herein we showed that acute oral infection in mice promotes diffuse parasitism in bone marrow cells at 14 and 21 days post-infection (dpi), with perivascular regions, intravascular regions, and regions near the bone being target sites of parasite replication. Phenotypic analysis of hematopoietic differentiation in the bone marrow of infected mice showed that the cell number in the tissue is decreased (lineage-negative and lineage-positive cells). Interestingly, analysis of hematopoietic branching points showed that hematopoietic stem and progenitor cells (HSPCs) were significantly increased at 14 dpi. In addition, the pool of progenitors with stem plasticity (HSC-MPP3), as well as multipotent progenitors (MPPs) such as MPP4, also showed this pattern of increase. In contrast, subsequent progenitors that arise from MPPs, such as common lymphoid progenitors (CLPs), lymphoid-primed MPPs (LMPPs), and myeloid progenitors, were not enhanced; conversely, all presented numeric decline. Annexin V staining revealed that cell death increase in the initial hematopoietic branching point probably is not linked to CLPs and that myeloid progenitors decreased at 14 and 21 dpi. In parallel, our investigation provided clues that myeloid progenitor decrease could be associated with an atypical expression of Sca-1 in this population leading to a remarkable increase on LSK-like cells at 14 dpi within the HSPC compartment. Finally, these results led us to investigate HSPC presence in the spleen as a phenomenon triggered during emergency hematopoiesis due to mobilization or expansion of these cells in extramedullary sites. Splenocyte analysis showed a progressive increase in HSPCs between 14 and 21 dpi. Altogether, our study shows that the bone marrow is a tar, Durante la fase aguda de la enfermedad de Chagas, la circulación de Trypanosoma cruzi a través del torrente sanguíneo genera una elevada parasitación tisular en el huésped. En los órganos linfoides primarios, la reducción de células progenitoras es paralela a la inmunosupresión transitoria. Aquí demostramos que la infección oral aguda en ratones promueve un parasitismo difuso en las células de la médula ósea a los 14 y 21 días post-infección (dpi), siendo las regiones perivasculares, las intravasculares y las cercanas al hueso los sitios objetivo de replicación del parásito. En conjunto, nuestro estudio muestra que la médula ósea es un tejido diana en los ratones infectados por vía oral por T. cruzi, lo que conduce a una alteración hematopoyética del número de células HSPCs que posiblemente afecta al número de progenitores mieloides. La reducción de LMPP y CLP se relaciona con un desarrollo defectuoso de los timocitos. Por último, es tentador especular que la hematopoyesis extramedular observada en el bazo es un mecanismo implicado en el mantenimiento hematológico detectado durante la fase aguda de la infección oral por T. cruzi., Coordination for the Improvement of Higher Education Personnel (CAPES), Brazilian National Research Council, Carlos Chagas Foundation for funding research in the State of Rio de Janeiro, Oswaldo Cruz Institute/Fiocruz, Mercosur Fund for Structural Convergence, Depto. de Biología Celular, Fac. de Ciencias Biológicas, TRUE, pub

BACKGROUND: Caries and periodontitis are amongst the most prevalent diseases worldwide, leading to pain and loss of oral function for those affected. Prevention relies heavily on mechanical removal of dental plaque biofilms but for populations where this is not achievable, alternative plaque control methods are required. With concerns over undesirable side-effects and potential bacterial resistance due to the use of chlorhexidine gluconate (CHX), new antimicrobial substances for oral use are greatly needed. Here we have investigated the antimicrobial effect of hypochlorous acid (HOCl), stabilized with acetic acid (HAc), on oral biofilms and compared it to that of CHX. Possible adverse effects of stabilized HOCl on hydroxyapatite surfaces were also examined. METHODS: Single- and mixed-species biofilms of six common oral bacteria (Streptococcus mutans, Streptococcus gordonii, Actinomyces odontolyticus, Veillonella parvula, Parvimonas micra and Porphyromonas gingivalis) within a flow-cell model were exposed to HOCl stabilized with 0.14% or 2% HAc, pH 4.6, as well as HOCl or HAc alone. Biofilm viability was assessed in situ using confocal laser scanning microscopy following LIVE/DEAD® BacLight™ staining. In-situ quartz crystal microbalance with dissipation (QCM-D) was used to study erosion of hydroxyapatite (HA) surfaces by stabilized HOCl. RESULTS: Low concentrations of HOCl (5 ppm), stabilized with 0.14% or 2% HAc, significantly reduced viability in multi-species biofilms representing supra- and sub-gingival oral communities, after 5 min, without causing erosion of HA surfaces. No equivalent antimicrobial effect was seen for CHX. Gram-positive and Gram-negative bacteria showed no significant differential suceptibility to stabilized HOCl. CONCLUSIONS: At low concentrations and with exposure times which could be achieved through oral rinsing, HOCl stabilized with HAc had a robust antimicrobial activity on oral biofilms, without causing erosion of HA surfaces or affectin

BACKGROUND: Caries and periodontitis are amongst the most prevalent diseases worldwide, leading to pain and loss of oral function for those affected. Prevention relies heavily on mechanical removal of dental plaque biofilms but for populations where this is not achievable, alternative plaque control methods are required. With concerns over undesirable side-effects and potential bacterial resistance due to the use of chlorhexidine gluconate (CHX), new antimicrobial substances for oral use are greatly needed. Here we have investigated the antimicrobial effect of hypochlorous acid (HOCl), stabilized with acetic acid (HAc), on oral biofilms and compared it to that of CHX. Possible adverse effects of stabilized HOCl on hydroxyapatite surfaces were also examined. METHODS: Single- and mixed-species biofilms of six common oral bacteria (Streptococcus mutans, Streptococcus gordonii, Actinomyces odontolyticus, Veillonella parvula, Parvimonas micra and Porphyromonas gingivalis) within a flow-cell model were exposed to HOCl stabilized with 0.14% or 2% HAc, pH 4.6, as well as HOCl or HAc alone. Biofilm viability was assessed in situ using confocal laser scanning microscopy following LIVE/DEAD® BacLight™ staining. In-situ quartz crystal microbalance with dissipation (QCM-D) was used to study erosion of hydroxyapatite (HA) surfaces by stabilized HOCl. RESULTS: Low concentrations of HOCl (5 ppm), stabilized with 0.14% or 2% HAc, significantly reduced viability in multi-species biofilms representing supra- and sub-gingival oral communities, after 5 min, without causing erosion of HA surfaces. No equivalent antimicrobial effect was seen for CHX. Gram-positive and Gram-negative bacteria showed no significant differential suceptibility to stabilized HOCl. CONCLUSIONS: At low concentrations and with exposure times which could be achieved through oral rinsing, HOCl stabilized with HAc had a robust antimicrobial activity on oral biofilms, without causing erosion of HA surfaces or affectin

Background: Caries and periodontitis are amongst the most prevalent diseases worldwide, leading to pain and loss of oral function for those affected. Prevention relies heavily on mechanical removal of dental plaque biofilms but for populations where this is not achievable, alternative plaque control methods are required. With concerns over undesirable side-effects and potential bacterial resistance due to the use of chlorhexidine gluconate (CHX), new antimicrobial substances for oral use are greatly needed. Here we have investigated the antimicrobial effect of hypochlorous acid (HOCl), stabilized with acetic acid (HAc), on oral biofilms and compared it to that of CHX. Possible adverse effects of stabilized HOCl on hydroxyapatite surfaces were also examined. Methods: Single- and mixed-species biofilms of six common oral bacteria (Streptococcus mutans, Streptococcus gordonii, Actinomyces odontolyticus, Veillonella parvula, Parvimonas micra and Porphyromonas gingivalis) within a flow-cell model were exposed to HOCl stabilized with 0.14% or 2% HAc, pH 4.6, as well as HOCl or HAc alone. Biofilm viability was assessed in situ using confocal laser scanning microscopy following LIVE/DEAD® BacLight™ staining. In-situ quartz crystal microbalance with dissipation (QCM-D) was used to study erosion of hydroxyapatite (HA) surfaces by stabilized HOCl. Results: Low concentrations of HOCl (5 ppm), stabilized with 0.14% or 2% HAc, significantly reduced viability in multi-species biofilms representing supra- and sub-gingival oral communities, after 5 min, without causing erosion of HA surfaces. No equivalent antimicrobial effect was seen for CHX. Gram-positive and Gram-negative bacteria showed no significant differential suceptibility to stabilized HOCl. Conclusions: At low concentrations and with exposure times which could be achieved through oral rinsing, HOCl stabilized with HAc had a robust antimicrobial activity on oral biofilms, without causing erosion of HA surfaces or affec

Background: Caries and periodontitis are amongst the most prevalent diseases worldwide, leading to pain and loss of oral function for those affected. Prevention relies heavily on mechanical removal of dental plaque biofilms but for populations where this is not achievable, alternative plaque control methods are required. With concerns over undesirable side-effects and potential bacterial resistance due to the use of chlorhexidine gluconate (CHX), new antimicrobial substances for oral use are greatly needed. Here we have investigated the antimicrobial effect of hypochlorous acid (HOCl), stabilized with acetic acid (HAc), on oral biofilms and compared it to that of CHX. Possible adverse effects of stabilized HOCl on hydroxyapatite surfaces were also examined. Methods: Single- and mixed-species biofilms of six common oral bacteria (Streptococcus mutans, Streptococcus gordonii, Actinomyces odontolyticus, Veillonella parvula, Parvimonas micra and Porphyromonas gingivalis) within a flow-cell model were exposed to HOCl stabilized with 0.14% or 2% HAc, pH 4.6, as well as HOCl or HAc alone. Biofilm viability was assessed in situ using confocal laser scanning microscopy following LIVE/DEAD® BacLight™ staining. In-situ quartz crystal microbalance with dissipation (QCM-D) was used to study erosion of hydroxyapatite (HA) surfaces by stabilized HOCl. Results: Low concentrations of HOCl (5 ppm), stabilized with 0.14% or 2% HAc, significantly reduced viability in multi-species biofilms representing supra- and sub-gingival oral communities, after 5 min, without causing erosion of HA surfaces. No equivalent antimicrobial effect was seen for CHX. Gram-positive and Gram-negative bacteria showed no significant differential suceptibility to stabilized HOCl. Conclusions: At low concentrations and with exposure times which could be achieved through oral rinsing, HOCl stabilized with HAc had a robust antimicrobial activity on oral biofilms, without causing erosion of HA surfaces or affec

Salmonella Pathogenicity Islands 19 (SPI19) encodes a type VI secretion system (T6SS). SPI19 is only present in few serovars of S. enterica, including the host-adapted serovar S. Dublin and the host-specific serovar S. Gallinarum. The role of the SPI19 encoded T6SS in virulence in these serovar is not fully understood. Here we show that during infection of mice, a SPI19/T6SS deleted strain of S. Dublin 2229 was less virulent than the wild type strain after oral challenge, but not after IP challenge. The mutant strain also competed significantly poorer than the wild type strain when co-cultured with strains of E. coli, suggesting that this T6SS plays a role in pathogenicity by killing competing bacteria in the intestine. No significant difference was found between wild type S. Gallinarum G9 and its ΔSPI19/T6SS mutant in infection, whether chicken were challenged orally or by the IP route, and the S. Gallinarum G9 ΔSPI19/T6SS strain competed equally well as the wild type strain against strains of E. coli. However, contrary to what was observed with S. Dublin, the wild type G9 strains was significantly more cytotoxic to monocyte derived primary macrophages from hens than the mutant, suggesting that SPI19/T6SS in S. Gallinarum mediates killing of eukaryotic cells. The lack of significant importance of SPI19/T6SS after oral and systemic challenge of chicken was confirmed by knocking out SPI19 in a second strain, J91. Together the results suggest that the T6SS encoded from SPI19 have different roles in the two serovars and that it is a virulence-factor after oral challenge of mice in S. Dublin, while we cannot confirm previous results that SPI19/T6SS influence virulence significantly in S. Gallinarum.

Salmonella Pathogenicity Islands 19 (SPI19) encodes a type VI secretion system (T6SS). SPI19 is only present in few serovars of S. enterica, including the host-adapted serovar S. Dublin and the host-specific serovar S. Gallinarum. The role of the SPI19 encoded T6SS in virulence in these serovar is not fully understood. Here we show that during infection of mice, a SPI19/T6SS deleted strain of S. Dublin 2229 was less virulent than the wild type strain after oral challenge, but not after IP challenge. The mutant strain also competed significantly poorer than the wild type strain when co-cultured with strains of E. coli, suggesting that this T6SS plays a role in pathogenicity by killing competing bacteria in the intestine. No significant difference was found between wild type S. Gallinarum G9 and its ΔSPI19/T6SS mutant in infection, whether chicken were challenged orally or by the IP route, and the S. Gallinarum G9 ΔSPI19/T6SS strain competed equally well as the wild type strain against strains of E. coli. However, contrary to what was observed with S. Dublin, the wild type G9 strains was significantly more cytotoxic to monocyte derived primary macrophages from hens than the mutant, suggesting that SPI19/T6SS in S. Gallinarum mediates killing of eukaryotic cells. The lack of significant importance of SPI19/T6SS after oral and systemic challenge of chicken was confirmed by knocking out SPI19 in a second strain, J91. Together the results suggest that the T6SS encoded from SPI19 have different roles in the two serovars and that it is a virulence-factor after oral challenge of mice in S. Dublin, while we cannot confirm previous results that SPI19/T6SS influence virulence significantly in S. Gallinarum.

The oral cavity is suggested as the reservoir of bacterial infection, and the oral and pharyngeal biofilms formed by oral bacterial flora, which is comprised of over 700 microbial species, have been found to be associated with systemic conditions. Almost all oral microorganisms are non-pathogenic opportunistic commensals to maintain oral health condition and defend against pathogenic microorganisms. However, oral Streptococci, the first microorganisms to colonize oral surfaces and the dominant microorganisms in the human mouth, has recently gained attention as the pathogens of various systemic diseases, such as infective endocarditis, purulent infections, brain hemorrhage, intestinal inflammation, and autoimmune diseases, as well as bacteremia. As pathogenic factors from oral Streptococci, extracellular polymeric substances, toxins, proteins and nucleic acids as well as vesicles, which secrete these components outside of bacterial cells in biofilm, have been reported. Therefore, it is necessary to consider that the relevance of these pathogenic factors to systemic diseases and also vaccine candidates to protect infectious diseases caused by Streptococci. This review article focuses on the mechanistic links among pathogenic factors from oral Streptococci, inflammation, and systemic diseases to provide the current understanding of oral biofilm infections based on biofilm and widespread systemic diseases.

Background & Aims: Chronic liver disease is a major health concern worldwide and the identification of novel modifiable risk factors may benefit subjects at risk. Few studies have analyzed periodontitis as a risk factor for liver complications. We studied whether periodontitis is associated with incident severe liver disease. Methods: The study comprised 6165 individuals without baseline liver disease who participated in the Finnish population‐based Health 2000 Survey (BRIF8901) during 2000‐2001, a nationally representative cohort. Follow‐up was until 2013 for liver‐related admissions, liver cancer and mortality from National Hospital Discharge, Finnish Cancer Registry and Causes of Death Register, Statistics Finland. Mild to moderate periodontitis was defined as ≥1 tooth with periodontal pocket ≥4 mm deep, and advanced periodontitis as ≥5 teeth with such pockets. Multiple confounders were considered. Results: A total of 79 subjects experienced a severe liver event during follow‐up. When adjusted for age, sex and number of teeth, hazards ratios by Cox regression regarding incident severe liver disease were, for mild to moderate periodontitis, 2.12 (95% CI 0.98‐4.58), and, for advanced periodontitis, 3.69 (95% CI 1.79‐7.60). These risk estimates remained stable after additionally adjusting for alcohol use, smoking, metabolic risk, serum gamma‐glutamyltransferase, dental‐care habits, lifestyle and socioeconomic status. Periodontal disease‐associated liver risk was accentuated among subjects with non‐alcoholic fatty liver disease or heavy alcohol use at baseline. Conclusions: Periodontitis was associated with incident liver disease in the general population independently of various confounders. As a preventable disease, periodontal disease might present a modifiable risk factor for chronic liver disease.

Objectives The biocompatible 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymers, which mimic a biomembrane, reduce protein adsorption and bacterial adhesion and inhibit cell attachment. The aim of this study is to clarify whether MPC-polymer can suppress the bacterial adherence in oral cavity by a crossover design. We also investigated the number of Fusobacterium nucleatum, which is the key bacterium forming dental plaque, in clinical samples. Materials and methods This study was a randomized, placebo-controlled, single-blind, crossover study, with two treatment periods separated by a 2-week washout period. We conducted clinical trial with 20 healthy subjects to evaluate the effect of 5% MPC-polymer mouthwash after 5 h on oral microflora. PBS was used as a control. The bacterial number in the gargling sample before and after intervention was counted by an electronic bacterial counter and a culture method. DNA amounts of total bacteria and F. nucleatum were examined by q-PCR. Results The numbers of total bacteria and oral streptcocci after 5 h of 5% MPC-polymer treatment significantly decreased, compared to the control group. Moreover, the DNA amounts of total bacteria and F. nucleatum significantly decreased by 5% MPC-polymer mouthwash. Conclusions We suggest that MPC-polymer coating in the oral cavity may suppress the oral bacterial adherence. Clinical relevance MPC-polymer can be a potent compound for the control of oral microflora to prevent oral infection.

Purpose. The aim of this paper is to describe epidemiology and clinical manifestations of oral infection by Human papillomavirus (HPV), with particular attention to potential malignant lesions. Materials and methods. A systematic review of the literature was conducted to describe the state of the art about HPV infection in oropharyngeal mucosa and its modalities of transmission, with particular attention to possible simultaneous infection in multiple anatomic sites. The aspects of prevention and control of infection by administering vaccines and the diffusion of sexual education campaigns are discussed also. Therapeutic protocols are also described where necessary. Results. In recent years there has been a growing interest in HPV oral medicine, suggesting a role of such a family of viruses in the development of neoplasms of the oropharyngeal district as well as of the uterine cervix. Even if the mass media have increasingly faced the problem, causing frequent alarming among patients, the dentist therefore needs a complete and up-to-date knowledge of this infectious condition that is one of the most common causes of sexually transmitted mucous membrane infections (e.g. genital, anal and oral). Conclusions. Recent studies about HPV infection are a basic requirement in order to promote the health of patients and provide them with the most exhaustive indications from dentists.

Brucellosis is a chronic, recurring disease caused by the bacterium Brucella abortus, along with other species of the genus Brucella, and is one of the most common bacterial zoonosis worldwide. The bacteria preferentially infect and reside within host macrophages, causing an undulant fever, joint pain, and other flu-like symptoms, in addition to more severe problems like hepatosplenomegaly and endocarditis. Brucella infection is most often acquired via inhalation through the respiratory route, or via consumption of unpasteurized dairy products. Although ingestion is a major route of infection, the transcriptional response of B. abortus during oral infection remains poorly characterized. In this project, RNA sequencing was used to discover genes with the greatest transcriptional changes in B. abortus subjected to deoxycholate, a host bile acid encountered by bacteria during oral infection. Gene deletion strains of B. abortus were then created and tested for susceptibility to pH and bile acid stress, along with their ability to invade and replicate within macrophages. If the genes of interest are important for the oral infection process, B. abortus strains lacking these genes will likely be more susceptible to pH and deoxycholate stress and may exhibit attenuation in the macrophage infection model. Determination of genes important for the oral infection process would further elucidate the molecular mechanisms by which B. abortus invades the host, and could help lead to future treatments and novel therapeutics.

Purpose. The aim of this paper is to describe epidemiology and clinical manifestations of oral infection by Human papillomavirus (HPV), with particular attention to potential malignant lesions. Materials and methods. A systematic review of the literature was conducted to describe the state of the art about HPV infection in oropharyngeal mucosa and its modalities of transmission, with particular attention to possible simultaneous infection in multiple anatomic sites. The aspects of prevention and control of infection by administering vaccines and the diffusion of sexual education campaigns are discussed also. Therapeutic protocols are also described where necessary. Results. In recent years there has been a growing interest in HPV oral medicine, suggesting a role of such a family of viruses in the development of neoplasms of the oropharyngeal district as well as of the uterine cervix. Even if the mass media have increasingly faced the problem, causing frequent alarming among patients, the dentist therefore needs a complete and up-to-date knowledge of this infectious condition that is one of the most common causes of sexually transmitted mucous membrane infections (e.g. genital, anal and oral). Conclusions. Recent studies about HPV infection are a basic requirement in order to promote the health of patients and provide them with the most exhaustive indications from dentists.

Trichoplusia ni insect larvae infected with vectors derived from the Autographa californica multiple nucleopolyhedrovirus (AcMNPV), are an excellent alternative to insect cells cultured in conventional bioreactors to produce recombinant proteins because productivity and cost-efficiency reasons. However, there is still a lot of work to do to reduce the manual procedures commonly required in this production platform that limit its scalability. To increase the scalability of this platform technology, a current bottleneck to be circumvented in the future is the need of injection for the inoculation of larvae with polyhedrin negative baculovirus vectors (Polh-) because of the lack of oral infectivity of these viruses, which are commonly used for production in insect cell cultures. In this work we have developed a straightforward alternative to obtain orally infective vectors derived from AcMNPV and expressing recombinant proteins that can be administered to the insect larvae (Trichoplusia ni) by feeding, formulated in the insect diet. The approach developed was based on the use of a recombinant polyhedrin protein expressed by a recombinant vector (Polh+), able to co-occlude any recombinant Polh- baculovirus vector expressing a recombinant protein. A second alternative was developed by the generation of a dual vector co-expressing the recombinant polyhedrin protein and the foreign gene of interest to obtain the occluded viruses. Additionally, by the incorporation of a reporter gene into the helper Polh+ vector, it was possible the follow-up visualization of the co-occluded viruses infection in insect larvae and will help to homogenize infection conditions. By using these methodologies, the production of recombinant proteins in per os infected larvae, without manual infection procedures, was very similar in yield to that obtained by manual injection of recombinant Polh- AcMNPV-based vectors expressing the same proteins. However, further analyses will be required for a deta

Porphyromonas gingivalis and Fusobacterium nucleatum, Gram-negative anaerobic bacteria, have been identified as major contributing pathogens in the etiology of mild to acute periodontitis. They are opportunistic pathogens that are highly adapted to colonize the oral epithelial tissues. P. gingivalis has also been associated with a variety of other chronic and inflammatory conditions including orodigestive cancers, rheumatoid arthritis, liver disease, and diabetes. Whereas, F. nucleatum has been linked to Lemierre’s syndrome and skin ulcers. Recognition and clearance of these pathogens are regulated by inflammation and host immune response. We aimed to study the mechanisms and inflammatory responses (focusing on the effect with intracellular complexes known as inflammasomes) used by P. gingivalis and F. nucleatum to survive and persist during infection in gingival epithelial cells (GECs). Our findings indicate P. gingivalis infection inhibits inflammasome activation and release of pro-inflammatory cytokines by secretion of nucleoside-diphosphate kinase (NDK) to hydrolyze extracellular ATP. By defining NDK as a key enzyme for influencing inflammation in P. gingivalis infection, therapeutic methods can be designed to possibly target NDK to prevent and treat periodontitis. On the other hand, GECs infected with F. nucleatum induce an opposite immune response of upregulated cytokine production and release as a result of inflammasome activation. In vivo studies with BALB/c and C57BL/6 mice also show pro-inflammatory response during infection. Our findings can be used as a model of invasion during F. nucleatum infection in vitro and in vivo. Expanding our understanding of host response to pathogenic bacteria is important for limiting progression of periodontitis and other emerging systematic disease linked to these bacteria.

Porphyromonas gingivalis and Fusobacterium nucleatum, Gram-negative anaerobic bacteria, have been identified as major contributing pathogens in the etiology of mild to acute periodontitis. They are opportunistic pathogens that are highly adapted to colonize the oral epithelial tissues. P. gingivalis has also been associated with a variety of other chronic and inflammatory conditions including orodigestive cancers, rheumatoid arthritis, liver disease, and diabetes. Whereas, F. nucleatum has been linked to Lemierre’s syndrome and skin ulcers. Recognition and clearance of these pathogens are regulated by inflammation and host immune response. We aimed to study the mechanisms and inflammatory responses (focusing on the effect with intracellular complexes known as inflammasomes) used by P. gingivalis and F. nucleatum to survive and persist during infection in gingival epithelial cells (GECs). Our findings indicate P. gingivalis infection inhibits inflammasome activation and release of pro-inflammatory cytokines by secretion of nucleoside-diphosphate kinase (NDK) to hydrolyze extracellular ATP. By defining NDK as a key enzyme for influencing inflammation in P. gingivalis infection, therapeutic methods can be designed to possibly target NDK to prevent and treat periodontitis. On the other hand, GECs infected with F. nucleatum induce an opposite immune response of upregulated cytokine production and release as a result of inflammasome activation. In vivo studies with BALB/c and C57BL/6 mice also show pro-inflammatory response during infection. Our findings can be used as a model of invasion during F. nucleatum infection in vitro and in vivo. Expanding our understanding of host response to pathogenic bacteria is important for limiting progression of periodontitis and other emerging systematic disease linked to these bacteria.

AimIn most infectious disease models, it is assumed that gavage needle infection is the most reliable means of pathogen delivery to the GI tract. However, this methodology can cause esophageal tearing and induces stress in experimental animals, both of which have the potential to impact early infection and the subsequent immune response.Materials & methodsC57BL/6 mice were orally infected with virulent Salmonella Typhimurium SL1344 either by intragastric gavage preceded by sodium bicarbonate, or by contamination of drinking water.ResultsWe demonstrate that water contamination delivery of Salmonella is equivalent to gavage inoculation in providing a consistent model of infection. Furthermore, exposure of mice to contaminated drinking water for as little as 4 h allowed maximal mucosal and systemic infection, suggesting an abbreviated window exists for natural intestinal entry.ConclusionTogether, these data question the need for gavage delivery for infection with oral pathogens.

Background: Aedes aegypti is the primary global vector to humans of yellow fever and dengue flaviviruses. Over the past 50 years, many population genetic studies have documented large genetic differences among global populations of this species. These studies initially used morphological polymorphisms, followed later by allozymes, and most recently various molecular genetic markers including microsatellites and mitochondrial markers. In particular, since 2000, fourteen publications and four unpublished datasets have used sequence data from the NADH dehydrogenase subunit 4 mitochondrial gene to compare Ae. aegypti collections and collectively 95 unique mtDNA haplotypes have been found. Phylogenetic analyses in these many studies consistently resolved two clades but no comprehensive study of mtDNA haplotypes have been made in Africa, the continent in which the species originated. Methods and Findings: ND4 haplotypes were sequenced in 426 Ae. aegypti s.l. from Senegal, West Africa and Kenya, East Africa. In Senegal 15 and in Kenya 7 new haplotypes were discovered. When added to the 95 published haplotypes and including 6 African Aedes species as outgroups, phylogenetic analyses showed that all but one Senegal haplotype occurred in a basal clade while most East African haplotypes occurred in a second clade arising from the basal clade. Globally distributed haplotypes occurred in both clades demonstrating that populations outside Africa consist of mixtures of mosquitoes from both clades. Conclusions: Populations of Ae. aegypti outside Africa consist of mosquitoes arising from one of two ancestral clades. One clade is basal and primarily associated with West Africa while the second arises from the first and contains primarily mosquitoes from East Africa

Background: Aedes aegypti is the primary global vector to humans of yellow fever and dengue flaviviruses. Over the past 50 years, many population genetic studies have documented large genetic differences among global populations of this species. These studies initially used morphological polymorphisms, followed later by allozymes, and most recently various molecular genetic markers including microsatellites and mitochondrial markers. In particular, since 2000, fourteen publications and four unpublished datasets have used sequence data from the NADH dehydrogenase subunit 4 mitochondrial gene to compare Ae. aegypti collections and collectively 95 unique mtDNA haplotypes have been found. Phylogenetic analyses in these many studies consistently resolved two clades but no comprehensive study of mtDNA haplotypes have been made in Africa, the continent in which the species originated. Methods and Findings: ND4 haplotypes were sequenced in 426 Ae. aegypti s.l. from Senegal, West Africa and Kenya, East Africa. In Senegal 15 and in Kenya 7 new haplotypes were discovered. When added to the 95 published haplotypes and including 6 African Aedes species as outgroups, phylogenetic analyses showed that all but one Senegal haplotype occurred in a basal clade while most East African haplotypes occurred in a second clade arising from the basal clade. Globally distributed haplotypes occurred in both clades demonstrating that populations outside Africa consist of mixtures of mosquitoes from both clades. Conclusions: Populations of Ae. aegypti outside Africa consist of mosquitoes arising from one of two ancestral clades. One clade is basal and primarily associated with West Africa while the second arises from the first and contains primarily mosquitoes from East Africa

A group of 133 primary oral squamous cell carcinomas were studied concerning a relationship between exposure factors and tumour biological parameters with a focus on the TP53 gene and p53 protein status. Tumours were evaluated using immunohistochemistry (IHC) for expression of p53, PCNA, Ki-67 and bcl-2 proteins. The TP53 gene was studied for mutations using PCR amplification of exons 5-9 and single strand conformation polymorphism (SSCP) analysis. The collected data were correlated to the exposure factors smoking, oral snuff, liquor, oral infections, dental factors, dental X-ray and iron deficiency. When compared with matched controls only oral infections, and reported HSV-infections in particular, gave statistically significant ORs (odds ratio) for all tumours (OR 8.0) as well as for the group of IHC p53 positive tumours (OR 12). No association between smoking and p53 positivity was found (OR 1.0).

Radiographic oral and maxillofacial findings were recorded in a cohort of 293 home living elderly, in Helsinki, Finland, derived from a random sample of 8035 subjects, born in 1904, 1909, and 1912, who participated in the Helsinki Ageing Study. They were 76, 81, and 86 years old at the commencement of the radiographic study. The relationships of potentially infectious findings with increased all-cause mortality over four years were studied. During the four-year follow-up, 18.5% of the subjects died. Of the 124 edentulous subjects, 17% had condylar findings, 13% radiopaque intraosseous findings, 9% retained roots, 6% maxillary sinus findings, 4% impacted teeth and 3% radiolucent findings. Edentulous women had more arthrotic condylar findings than men. The mean number of teeth in the 169 dentate subjects was 13.9, 15.5 in men and 13.2 in women. Carious teeth were found in 75%, radiolucent findings in 41%, teeth with vertical infrabony pockets in 51%, furcation lesions in 28%, calculus in 40%, and condylar findings in 25%. Periodontal attachment loss was slight in 18%, moderate in 31%, and advanced in 46%. 21% of the teeth had been endodontically treated. Periapical lesions were found in 17% of these teeth, and in 4% of the other teeth. 75% of the rootfillings were inadequate, exhibiting periapical lesions twice as often as the adequate ones. Men had more carious teeth, periapical lesions and furcation lesions than women, indicating better oral hygiene and/or utilisation of dental services in women. Compared with the previous studies carried out in Finland, slightly more teeth and less tooth-associated pathology were found in the present subjects. In contemporary Scandinavian studies, only a slightly better oral health status in the elderly has been reported. During the four-year follow-up, mortality was higher in the subjects with moderate to advanced infrabony pockets, OR 2.2, 1.0–4.7. In the previous studies, similar associations have been found in larger s

Kuruma prawns (Penaeus japonicus) were experimentally infected with Vibrio sp. PJ by the oral administration. At 3, 6, 8, 10, 12, 24, 36, and 48 h post-inoculation, prawns were sampled to determine the cell number and distribution of the pathogen in various organs by viable cell count and the enzyme-labeled antibody technique (ELAT). Vibrio sp. PJ was detected by culture method from the stomach and hemolymph at 3 h and from the hemolymph and almost all the organs sampled at 6 h post-inoculation. However, the pathogen started to disappear from all the organs from 8 h to 12 h. At 12 h, it reappeared in the hepatopancreas and lymphoid organs. Twenty-four hours after inoculation, the pathogen was detected from the hemolymph and all the organs except the stomach and gills, and at 36 h the pathogen was found distributed in all the organs. Principally the same distribution pattern of the pathogen was found by ELAT. These results seem to indicate that the process in the pathogenesis of Vibrio sp. PJ infection in orally challenged kuruma prawns consist of five stages namely, establishment of the pathogen, distribution of the pathogen, clearance of the pathogen by host prawn, secondary multiplication of the pathogen, and systemic infection. The results also suggest that the pathogen multiplied in the stomach in the establishment stage and in the hepatopancreas and lymphoid organs in the secondary multiplication stage.

Oral candidosis in neonates and children is a common infection which occurs often during the first few months after birth, but occasionally also in older children with certain predisposing factors. In neonates, oral candidosis is usually benign, although the symptoms of such an acute infection can be-disturbing to both the patient and the parents. In older children developing oral candidosis, specific predisposing factors may be present (e.g. immunodeficiency, chemotherapy, etc.). In such cases, the infection may constitute a source for further dissemination, leading to occasionally fatal Candida sepsis or to widespread chronic mucocutaneous candidosis. Treatment modalities to date include drugs with limited or no absorption from the gastrointestinal tract (e.g. nystatin and miconazole) and agents that are absorbed, combining local effect with systemic therapy (e.g. clotrimazole, ketoconazole, itraconazole and fluconazole). Overall, it appears that treatment of neonatal oral candidosis should be performed with non-absorbable drugs, while the systemically active agents should be used primarily if a risk of dissemination exists or if widespread disease is present. In general, side-effects and toxicity are not major causes of concern with non-absorbed or absorbed antifungals in children with oral candidosis, since treatment is usually of relatively short duration. When the systemically active agents are used in premature infants with suboptimal liver function, the risk of drug-induced liver toxicity may be increased.