Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signaling

Lipopolysaccharide (LPS) of Porphyromonas gingivalis exists in at least two known forms, O-LPS and A-LPS. A-LPS shows heterogeneity in which two isoforms designated LPS1435/1449 and LPS1690 appear responsible for tissue specific immune signalingpathways activation and increased virulence. The modification of lipid A to tetra-acylated1435/1449 and/or penta-acylated1690 fatty acids indicates poor growth conditions and bioavailability of hemin. Hemin protects P. gingivalis from serum resistance and the lipid A serves as a site for its binding. The LPS1435/1449 and LPS1690 isoforms can produce opposite effects on the human Toll-like receptors (TLR) TLR 2 and TLR 4 activation. This enabless P. gingivalis to select the conditions for its entry, survival and that of its co-habiting species in the host, orchestrating its virulence to control innate immune pathway activation and biofilm dysbiosis. Thismini review describes a number of effects that LPS1435/1449 and LPS1690 can exert on the host tissues such as deregulation of the innate immune system, subversion of host cell autophagy, regulation of outer membrane vesicle production and adverse effects on pregnancy outcome. The ability to change its LPS1435/1449 and/or LPS1690 composition may enables P. gingivalis to paralyze local pro-inflammatory cytokine production, thereby gaining access to its primary location in periodontal tissue

Modelling the role of oral processing on in vivo aroma release of white rice: Conceptual model and experimental validation

A conceptual model was developed to relate oral processing parameters and aroma release of cooked white rice. The conceptual model indicates that aroma release is dependent on the increase of particle surface area, the dilution effect of saliva and the diffusion of aroma from food residues that can be trapped in the buccal-pouches in the mouth. The model was validated against in vivo retro-nasal aroma release data during the consumption of rice flavoured with two aroma compounds (2-nonanone and ethyl propanoate) by five panellists. The oral processing behaviour of each subject was characterised at four different stages during oral processing by measuring bolus particle size, saliva content and the amount of residue particles that could be washed from the mouth after bolus expectoration. The results showed that aroma release for all subjects were dependent on the particle breakdown pathways used in oral processing. Subjects who reduced the rice to smaller particle sizes, higher pasted fraction and higher bolus residues had higher aroma release as expected from the conceptual model. Accounting for the physiological variables of subjects, the physicochemical parameters of aroma compounds and using a larger number of subjects in future studies will improve the model reliability.fals

Airway "Resistotypes" and Clinical Outcomes in Bronchiectasis.

Rationale: Chronic infection and inflammation shapes the airway microbiome in bronchiectasis. Utilizing whole-genome shotgun metagenomics to analyze the airway resistome provides insight into interplay between microbes, resistance genes, and clinical outcomes. Objectives: To apply whole-genome shotgun metagenomics to the airway microbiome in bronchiectasis to highlight a diverse pool of antimicrobial resistance genes: the "resistome," the clinical significance of which remains unclear. Methods: Individuals with bronchiectasis were prospectively recruited into cross-sectional and longitudinal cohorts (n = 280), including the international multicenter cross-sectional Cohort of Asian and Matched European Bronchiectasis 2 (CAMEB 2) study (n = 251) and two independent cohorts, one describing patients experiencing acute exacerbation and a further cohort of patients undergoing Pseudomonas aeruginosa eradication treatment. Sputum was subjected to metagenomic sequencing, and the bronchiectasis resistome was evaluated in association with clinical outcomes and underlying host microbiomes. Measurements and Main Results: The bronchiectasis resistome features a unique resistance gene profile and increased counts of aminoglycoside, bicyclomycin, phenicol, triclosan, and multidrug resistance genes. Longitudinally, it exhibits within-patient stability over time and during exacerbations despite between-patient heterogeneity. Proportional differences in baseline resistome profiles, including increased macrolide and multidrug resistance genes, associate with shorter intervals to the next exacerbation, whereas distinct resistome archetypes associate with frequent exacerbations, poorer lung function, geographic origin, and the host microbiome. Unsupervised analysis of resistome profiles identified two clinically relevant "resistotypes," RT1 and RT2, the latter characterized by poor clinical outcomes, increased multidrug resistance, and P. aeruginosa. Successful targeted eradication in P. aeruginosa-colonized individuals mediated reversion from RT2 to RT1, a more clinically favorable resistome profile demonstrating reduced resistance gene diversity. Conclusions: The bronchiectasis resistome associates with clinical outcomes, geographic origin, and the underlying host microbiome. Bronchiectasis resistotypes link to clinical disease and are modifiable through targeted antimicrobial therapy

Treatment results for hypopharyngeal cancer by different treatment strategies and its secondary primary- an experience in Taiwan

<p>Abstract</p> <p>Purpose</p> <p>The aim of this study was to evaluate treatment results in our hypopharyngeal cancer patients.</p> <p>Patients and Methods</p> <p>A total of three hundred and ninety five hypopharyngeal cancer patients received radical treatment at our hospital; 96% were male. The majority were habitual smokers (88%), alcohol drinkers (73%) and/or betel quid chewers (51%). All patients received a CT scan or MRI for tumor staging before treatment. The stage distribution was stage I: 2 (0.5%); stage II: 22 (5.6%); stage III: 57 (14.4%) and stage IV: 314 (79.5%). Radical surgery was used first in 81 patients (20.5%), and the remaining patients (79.5%) received organ preservation-intended treatment (OPIT). In the OPIT group, 46 patients received radiotherapy alone, 156 patients received chemotherapy followed by radiotherapy (CT/RT) and 112 patients received concomitant chemo-radiotherapy (CCRT).</p> <p>Results</p> <p>The five-year overall survival rates for stages I/II, III and IV were 49.5%, 47.4% and 18.6%, respectively. There was no significant difference in overall and disease-specific survival rates between patients who received radical surgery first and those who received OPIT. In the OPIT group, CCRT tended to preserve the larynx better (p = 0.088), with three-year larynx preservation rates of 44.8% for CCRT and 27.2% for CT/RT. Thirty-seven patients developed a second malignancy, with an annual incidence of 4.6%.</p> <p>Conclusions</p> <p>There was no survival difference between OPIT and radical surgery in hypopharyngeal cancer patients at our hospital. CCRT may offer better laryngeal preservation than RT alone or CT/RT. However, prospective studies are still needed to confirm this finding. Additionally, second primary cancers are another important issue for hypopharyngeal cancer management.</p

Determinants of Habitat Selection by Hatchling Australian Freshwater Crocodiles

Animals almost always use habitats non-randomly, but the costs and benefits of using specific habitat types remain unknown for many types of organisms. In a large lake in northwestern Australia (Lake Argyle), most hatchling (<12-month-old) freshwater crocodiles (Crocodylus johnstoni) are found in floating vegetation mats or grassy banks rather than the more widely available open banks. Mean body sizes of young crocodiles did not differ among the three habitat types. We tested four potential explanations for non-random habitat selection: proximity to nesting sites, thermal conditions, food availability, and exposure to predation. The three alternative habitat types did not differ in proximity to nesting sites, or in thermal conditions. Habitats with higher food availability harboured more hatchlings, and feeding rates (obtained by stomach-flushing of recently-captured crocodiles) were highest in such areas. Predation risk may also differ among habitats: we were twice as likely to capture a crocodile after seeing it in open-bank sites than in the other two habitat types. Thus, habitat selection of hatchling crocodiles in this system may be driven both by prey availability and by predation risk

Vitamin d status predicts 30 day mortality in hospitalised cats

Vitamin D insufficiency, defined as low serum concentrations of the major circulating form of vitamin D, 25 hydroxyvitamin D (25(OH)D), has been associated with the development of numerous infectious, inflammatory, and neoplastic disorders in humans. In addition, vitamin D insufficiency has been found to be predictive of mortality for many disorders. However, interpretation of human studies is difficult since vitamin D status is influenced by many factors, including diet, season, latitude, and exposure to UV radiation. In contrast, domesticated cats do not produce vitamin D cutaneously, and most cats are fed a commercial diet containing a relatively standard amount of vitamin D. Consequently, domesticated cats are an attractive model system in which to examine the relationship between serum 25(OH)D and health outcomes. The hypothesis of this study was that vitamin D status would predict short term, all-cause mortality in domesticated cats. Serum concentrations of 25(OH)D, together with a wide range of other clinical, hematological, and biochemical parameters, were measured in 99 consecutively hospitalised cats. Cats which died within 30 days of initial assessment had significantly lower serum 25(OH)D concentrations than cats which survived. In a linear regression model including 12 clinical variables, serum 25(OH)D concentration in the lower tertile was significantly predictive of mortality. The odds ratio of mortality within 30 days was 8.27 (95% confidence interval 2.54-31.52) for cats with a serum 25(OH)D concentration in the lower tertile. In conclusion, this study demonstrates that low serum 25(OH)D concentration status is an independent predictor of short term mortality in cats