Orally Administered Probiotics Decrease Aggregatibacter actinomycetemcomitans but Not Other Periodontal Pathogenic Bacteria Counts in the Oral Cavity: A Systematic Review and Meta-Analysis.

Introduction: At the initial part of the gastrointestinal tract, multiple tissues serve the normal function of food delivery. Periodontal structures are integral elements of these. When they deteriorate, it is extremely challenging to regenerate and reconstruct them. The conventional intervention for periodontal disease is scaling and root planning with the aim of reducing pathogenic bacteria. However, periodontal pathogens can rapidly recolonize treated areas. Probiotics have been proposed as novel tools for managing oral health by suppressing pathogenic bacteria through their anti-inflammatory effect, but the available data are controversial. Aim: Therefore, we performed a meta-analysis to study the effect of probiotics on periodontal pathogenic bacteria. Methods: The study was registered in PROSPERO under registration number CRD42018094903. A comprehensive literature search from four electronic databases (PubMed, Cochrane CENTRAL, Embase, and Web of Science) yielded nine eligible records for statistical analysis. Studies measuring bacterial counts in saliva and supra- and subgingival plaque were included. Bacterial counts were analyzed using standard mean difference (SMD) and by a random effects model with the DerSimonian-Laird estimation. Results: The results showed a significant decrease in the overall count of Aggregatibacter actinomycetemcomitans in the probiotic-treated group compared to the control at 4 weeks (SMD: -0.28; 95% CI: -0.56--0.01; p = 0.045) but not later. Analyzing the bacterial counts in subgroups, namely, in saliva and supra- and subgingival plaque, separately, yielded no significant difference. Probiotics had no significant effect on the overall count of Porphyromonas gingivalis at 4 weeks (SMD: -0.02; 95% CI: -0.35-0.31; p = 0.914) or later. Subgroup analysis also revealed no significant difference between treatment and control groups nor did probiotics significantly decrease the overall and subgroup bacterial counts of Prevotella intermedia, Tannerella forsythia, and Fusobacterium nucleatum. Conclusion: Our data support the beneficial effect of probiotics in reducing A. actinomycetemcomitans counts, but not of other key periodontal pathogenic bacteria in periodontal disease patients. However, due to the complex mechanism associated with periodontal disease and the limitations of the available studies, there is a further need for well-designed randomized clinical trials to assess the efficacy of probiotics.

Assessment of the course of acute pancreatitis in the light of aetiology: a systematic review and meta-analysis.

The main causes of acute pancreatitis (AP) are biliary disease, alcohol consumption, hypertriglyceridaemia (HTG) and endoscopic retrograde cholangiopancreatography (ERCP). The aim of this meta-analysis was to evaluate the effects of these aetiological factors on the severity and outcome of AP. Pubmed and Embase were searched between 01/01/2012 and 31/05/2020. Included articles involved adult alcoholic, biliary, HTG- or post-ERCP AP (PAP) patients. Primary outcome was severity, secondary outcomes were organ failures, intensive care unit admission, recurrence rate, pancreatic necrosis, mortality, length of hospital stay, pseudocyst, fluid collection and systematic inflammatory response syndrome. Data were analysed from 127 eligible studies. The risk for non-mild (moderately severe and severe) condition was the highest in HTG-induced AP (HTG-AP) followed by alcoholic AP (AAP), biliary AP (BAP) and PAP. Recurrence rate was significantly lower among BAP vs. HTG-AP or AAP patients (OR = 2.69 and 2.98, 95% CI 1.55-4.65 and 2.22-4.01, respectively). Mortality rate was significantly greater in HTG-AP vs. AAP or BAP (OR = 1.72 and 1.50, 95% CI 1.04-2.84 and 0.96-2.35, respectively), pancreatic necrosis occurred more frequently in AAP than BAP patients (OR = 1.58, 95% CI 1.08-2.30). Overall, there is a potential association between aetiology and the development and course of AP. HTG-AP is associated with the highest number of complications. Furthermore, AAP is likely to be more severe than BAP or PAP. Greater emphasis should be placed on determining aetiology on admission.

Foundations for Streaming Model Transformations by Complex Event Processing.

Streaming model transformations represent a novel class of transformations to manipulate models whose elements are continuously produced or modified in high volume and with rapid rate of change. Executing streaming transformations requires efficient techniques to recognize activated transformation rules over a live model and a potentially infinite stream of events. In this paper, we propose foundations of streaming model transformations by innovatively integrating incremental model query, complex event processing (CEP) and reactive (event-driven) transformation techniques. Complex event processing allows to identify relevant patterns and sequences of events over an event stream. Our approach enables event streams to include model change events which are automatically and continuously populated by incremental model queries. Furthermore, a reactive rule engine carries out transformations on identified complex event patterns. We provide an integrated domain-specific language with precise semantics for capturing complex event patterns and streaming transformations together with an execution engine, all of which is now part of the Viatra reactive transformation framework. We demonstrate the feasibility of our approach with two case studies: one in an advanced model engineering workflow; and one in the context of on-the-fly gesture recognition.

Adrenomedullin reduces vascular hyperpermeability and improves survival in rat septic shock.

OBJECTIVE: Current therapies of sepsis and septic shock require administration of a large volume of fluid to maintain hemodynamic stability. The vasoregulatory peptide adrenomedullin has been shown to prevent the transition to the fatal hypocirculatory septic state by poorly understood mechanisms. We tested the hypothesis that therapeutic administration of adrenomedullin would reduce vascular hyperpermeability, thereby contributing to improved hemodynamics and survival. DESIGN: Prospective randomized controlled animal study. SUBJECTS: Male Sprague-Dawley rats (270 g). INTERVENTIONS: We used 4.8 x 10(3) U/kg of Staphylococcus aureus alpha-toxin, a pore-forming exotoxin, to induce vascular leakage and circulatory shock in rats. The infusion rate was 24 microg/kg per hour. Adrenomedullin was started 1 h after alpha-toxin administration. MEASUREMENT AND RESULTS: Infusion of alpha-toxin in rats induced cardiocirculatory failure resulting in a 6-h mortality of 53%. alpha-Toxin provoked massive vascular hyperpermeability, which was indicated by an enrichment of Evans blue dye albumin in the tissues of lung, liver, ileum and kidney. Plasma fluid loss led to a significant hemoconcentration. Hemodynamic impairment observed after alpha-toxin infusion was closely correlated to vascular hyperpermeability. Therapeutic administration of 24 microg/kg per hour adrenomedullin reduced 6-h mortality from 53% to 7%. Stabilization of the endothelial barrier by adrenomedullin was indicated by reduced extravasation of albumin and plasma fluid and may have contributed to hemodynamic improvement. CONCLUSIONS: These data suggest that adrenomedullin-related reduction of vascular hyperpermeability might represent a novel and important mechanism contributing to the beneficial effects of this endogenous vasoregulatory peptide in sepsis and septic shock.

Adrenomedullin treatment abolishes ileal mucosal hypoperfusion induced by Staphylococcus aureus alpha-toxin--an intravital microscopic study on an isolated rat ileum.

OBJECTIVE: Disturbances of intestinal microcirculation associated with sepsis and septic shock result in diminished mucosal oxygenation. Tissue hypoxia as well as mediator formation may lead to intestinal mucosa dysfunction. As a consequence, bacteria and their products as well as gut-derived inflammatory mediators may further perpetuate septic and inflammatory events. Adrenomedullin is produced in the mucosa of the gastrointestinal tract and has been shown to improve survival in experimental sepsis. Using pore-forming Staphylococcus aureus alpha-toxin as a potent initiator of inflammatory reactions, we tested the hypothesis that exogenously added adrenomedullin improves ileal mucosal perfusion. DESIGN: Prospective, experimental study. SETTING: University laboratory. SUBJECTS: Isolated perfused ileum from male Sprague-Dawley rats INTERVENTIONS: Adrenomedullin treatment of S. aureus alpha-toxin infused ileum. MEASUREMENT AND MAIN RESULTS: An infusion of alpha-toxin (0.05 microg/mL) induced a significant decrease of red blood cell velocity in villus terminal arterioles from 1.7 to 0.7 mm/sec assessed by intravital microscopy. This was accompanied by a significant reduction of mucosal hemoglobin oxygenation from 71.8% to 17.5% and impaired oxygen uptake. At constant bulk flow and oxygen delivery, these data indicate a redistribution of blood perfusion away from mucosa. Subsequent intervention with 0.1 microM adrenomedullin redistributed blood flow back toward the mucosa, causing an improvement of mucosal hemoglobin oxygenation and of organ oxygen uptake. CONCLUSION: These data suggest that exogenously added adrenomedullin protects ileum mucosa by diminishing alpha-toxin-induced microcirculatory disturbances. Further investigations will have to clarify the therapeutic potential of adrenomedullin in sepsis-related gut dysfunction.