623 research outputs found

    Beliefs and desires in the predictive brain

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    Bayesian brain theories suggest that perception, action and cognition arise as animals minimise the mismatch between their expectations and reality. This principle could unify cognitive science with the broader natural sciences, but leave key elements of cognition and behaviour unexplained

    Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules

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    Background: Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties.<p></p> Methods: An in vitro multi-species biofilm containing <i>S. mitis, F. nucleatum, P. Gingivalis</i> and <i>A. Actinomycetemcomitans</i> was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level.<p></p> Results: CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA.<p></p> Conclusions: CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.<p></p&gt

    Obesity and pre-hypertension in family medicine: Implications for quality improvement

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    <p>Abstract</p> <p>Background.</p> <p>Prevention of pre-hypertension is an important goal for primary care patients. Obesity is a risk factor for hypertension, but has not been addressed for pre-hypertension in primary care populations. The objective of this study was to assess the degree to which obesity independently is associated with risk for pre-hypertension in family medicine patients.</p> <p>Methods.</p> <p>This study was a retrospective analysis of information abstracted from medical records of 707 adult patients. Multivariable logistic regression was used to test the relationship between body mass index (BMI) and pre-hypertension, after adjustment for comorbidity and demographic characteristics. Pre-hypertension was defined as systolic pressure between 120 and 139 mm Hg or diastolic pressure between 80 and 89 mm Hg.</p> <p>Results.</p> <p>In our sample, 42.9% of patients were pre-hypertensive. Logistic regression analysis revealed that, in comparison to patients with normal body mass, patients with BMI > 35 had higher adjusted odds of being pre-hypertensive (OR = 4.5, CI 2.55–8.11, p < .01). BMI between 30 and 35 also was significant (OR = 2.7, CI 1.61–4.63, p < 0.01) as was overweight (OR = 1.8, CI 1.14–2.92, p = 0.01).</p> <p>Conclusion.</p> <p>In our sample of family medicine patients, elevated BMI is a risk factor for pre-hypertension, especially BMI > 35. This relationship appears to be independent of age, gender, marital status and comorbidity. Weight loss intervention for obese patients, including patient education or referral to weight loss programs, might be effective for prevention of pre-hypertension and thus should be considered as a potential quality indicator.</p

    Use of dietary supplements by cardiologists, dermatologists and orthopedists: report of a survey

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    <p>Abstract</p> <p>Background</p> <p>Dietary supplements are regularly used by a majority of the American population, and usage by health professionals is also common. There is considerable interest in usage patterns within the population and in the reasons for using dietary supplements. The "Life...supplemented" Healthcare Professionals 2008 Impact Study (HCP Impact Study) surveyed usage of dietary supplements by physicians in three specialties: cardiology, dermatology, and orthopedics.</p> <p>Methods</p> <p>The HCP Impact Study was conducted online by Ipsos Public Affairs for the Council for Responsible Nutrition (CRN), a trade association of the dietary supplement industry. Respondents were 900 physicians, including 300 each from three specialties - cardiology, dermatology, and orthopedics.</p> <p>Results</p> <p>Fifty-seven percent of cardiologists said they use dietary supplements at least occasionally, as did 75% of dermatologists and 73% of orthopedists. The product most commonly reported to be used was a multivitamin, but over 25% in each specialty said they used omega-3 fatty acids and over 20% said they used some botanical supplements. Regular dietary supplement use was reported by 37% of cardiologists, 59% of dermatologists, and 50% of orthopedists. Seventy-two percent of cardiologists, 66% of dermatologists, and 91% of orthopedists reported recommending dietary supplements to their patients. The primary reason given for recommending dietary supplements to patients was for heart health or lowering cholesterol for the cardiologists; benefits for skin, hair and nails for the dermatologists; and bone and joint health for the orthopedists.</p> <p>Conclusions</p> <p>Reported dietary supplement use was relatively common in this sample of physicians, and when they recommended dietary supplements to patients, they tended to do so for reasons related to their specialty.</p

    Expression Profiling of Major Histocompatibility and Natural Killer Complex Genes Reveals Candidates for Controlling Risk of Graft versus Host Disease

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    Background: The major histocompatibility complex (MHC) is the most important genomic region that contributes to the risk of graft versus host disease (GVHD) after haematopoietic stem cell transplantation. Matching of MHC class I and II genes is essential for the success of transplantation. However, the MHC contains additional genes that also contribute to the risk of developing acute GVHD. It is difficult to identify these genes by genetic association studies alone due to linkage disequilibrium in this region. Therefore, we aimed to identify MHC genes and other genes involved in the pathophysiology of GVHD by mRNA expression profiling. Methodology/Principal Findings: To reduce the complexity of the task, we used genetically well-defined rat inbred strains and a rat skin explant assay, an in-vitro-model of the graft versus host reaction (GVHR), to analyze the expression of MHC, natural killer complex (NKC), and other genes in cutaneous GVHR. We observed a statistically significant and strong up or down regulation of 11 MHC, 6 NKC, and 168 genes encoded in other genomic regions, i.e. 4.9%, 14.0%, and 2.6% of the tested genes respectively. The regulation of 7 selected MHC and 3 NKC genes was confirmed by quantitative real-time PCR and in independent skin explant assays. In addition, similar regulations of most of the selected genes were observed in GVHD-affected skin lesions of transplanted rats and in human skin explant assays. Conclusions/Significance: We identified rat and human MHC and NKC genes that are regulated during GVHR in skin explant assays and could therefore serve as biomarkers for GVHD. Several of the respective human genes, including HLA-DMB, C2, AIF1, SPR1, UBD, and OLR1, are polymorphic. These candidates may therefore contribute to the genetic risk of GVHD in patients

    Urbanisation and incidence of acute lymphocytic leukaemia among United States children aged 0–4

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    Acute lymphocytic leukaemia (ALL) incidence among children under 5 years of age was examined, utilising data from 24 United States cancer registries. County-based incidence rates among white children were compared across four levels of urbanisation: large and small metropolitan counties, and adjacent and nonadjacent rural counties. In metropolitan areas, the incidence of ALL was lower among blacks (rate ratio (RR)=0.38, confidence interval (CI)=0.33–0.44) and among Asians/Pacific Islanders (RR=0.78, CI=0.63–0.97) than among whites. Among white children, the incidence of ALL decreased across the four strata of urbanisation, from 67 to 62 to 65 to 54 cases per million person-years at-risk (two-sided trend P=0.009), such that rates were significantly lower in the most remote rural counties than in the most populous metropolitan counties (RR=0.80, 95% CI=0.70–0.91)

    Peri-operative, functional and early oncologic outcomes of salvage robotic-assisted radical prostatectomy after high-intensity focused ultrasound partial ablation

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    BACKGROUND: Partial ablation of the prostate using high-intensity focussed ultrasound (HIFU-PA) is a treatment option for localised prostate cancer. When local recurrence occurs, salvage robot-assisted radical prostatectomy is a treatment option for selected patients, but there is a paucity of data on the peri-operative safety, functional and oncologic outcomes of sRARP.. The objective of this study was therefore to describe peri-operative safety, functional and early oncologic outcomes following salvage robot-assisted radical prostatectomy (sRARP) for local recurrence after HIFU-PA. METHODS: Retrospective analysis of a prospective database of 53 consecutive men who underwent sRARP after HIFU-PA from 2012 to 2018. Continence and erectile-function were reported pre-HIFU, pre-sRARP, 3-months post-sRARP and 12-months post-sRARP. Complications, PSMs and need for subsequent ADT/radiotherapy were assessed. RESULTS: 45 men were suitable for inclusion and had sufficient data for analyses. Median duration from HIFU to sRARP was 30.0 months and median follow-up post-sRARP was 17.7 months. Median age, PSA and ISUP group were 63.0 yrs., 7.2 ng/mL and 2; 88.9% were cT2. Median operative-console time, blood loss and hospital stay were 140 min, 200 ml and 1 day respectively. Clavien-Dindo grade 1, 2 and 3 complications 90d) complications occurred in 13.2%. At sRARP pathology, ISUP 3-5 occurred in 51.1%, pT3a/b in 64.5%, and PSMs in 44.4% (37.5% for pT2, 48.3% for pT3). Of men with > 3-months follow-up after sRARP, 26.3% underwent adjuvant radiotherapy/ADT for residual disease or adverse pathologic features; 5.3% experienced BCR requiring salvage ADT/radiotherapy. Freedom from ADT/radiotherapy was 66.7% at 12-months. Pad-free rates were 100% pre-HIFU, 95.3% post-HIFU, 29.4% 3-months post-sRARP, and 65.5% 12-months post-sRARP. Median IIEF-5 scores pre-HIFU, post-HIFU, 3- and 12-months post-sRARP were 23.5, 16, 5 and 5, respectively. Potency rates were 81.8, 65.5, 0 and 0%, respectively. Bilateral/unilateral nerve sparing were feasible in 7%/22%. CONCLUSION: Salvage RARP was safe with acceptable but sub-optimal continence and poor sexual-function and poor oncologic outcomes. One in three men required additional treatment within 12-months. This information may aid men and urologists with treatment selection and counselling regarding primary HIFU-PA vs primary RARP and when considering salvage RARP

    Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

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    The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

    Yeast : the soul of beer’s aroma—a review of flavour-active esters and higher alcohols produced by the brewing yeast

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    Among the most important factors influencing beer quality is the presence of well-adjusted amounts of higher alcohols and esters. Thus, a heavy body of literature focuses on these substances and on the parameters influencing their production by the brewing yeast. Additionally, the complex metabolic pathways involved in their synthesis require special attention. More than a century of data, mainly in genetic and proteomic fields, has built up enough information to describe in detail each step in the pathway for the synthesis of higher alcohols and their esters, but there is still place for more. Higher alcohols are formed either by anabolism or catabolism (Ehrlich pathway) of amino acids. Esters are formed by enzymatic condensation of organic acids and alcohols. The current paper reviews the up-to-date knowledge in the pathways involving the synthesis of higher alcohols and esters by brewing yeasts. Fermentation parameters affecting yeast response during biosynthesis of these aromatic substances are also fully reviewed.Eduardo Pires gratefully acknowledges the Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) for the PhD fellowship support (SFRH/BD/61777/2009). The financial contributions of the EU FP7 project Ecoefficient Biodegradable Composite Advanced Packaging (EcoBioCAP, grant agreement no. 265669) as well as of the Grant Agency of the Czech Republic (project GACR P503/12/1424) are also gratefully acknowledged. The authors thank the Ministry of Education, Youth and Sports of the Czech Republic (MSM 6046137305) for their financial support
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