The oral microbiome of denture wearers is influenced by natural dentition

Objectives: The composition of dental plaque has been well defined, whereas currently there is limited understanding of the composition of denture plaque and how it directly influences denture related stomatitis (DS). The aims of this study were to compare the microbiomes of denture wearers, and to understand the implications of these towards inter-kingdom and host-pathogen interactions within the oral cavity. Methods: Swab samples were obtained from 123 participants wearing either a complete or partial denture; the bacterial composition of each sample was determined using bar-coded illumina MiSeq sequencing of the bacterial hypervariable V4 region of 16S rDNA. Sequencing data processing was undertaken using QIIME, clustered in Operational Taxonomic Units (OTUs) and assigned to taxonomy. The dentures were sonicated to remove the microbial flora residing on the prosthesis, sonicate was then cultured using diagnostic colorex Candida media. Samples of unstimulated saliva were obtained and antimicrobial peptides (AMP) levels were measured by ELISA. Results: We have shown that dental and denture plaques are significantly distinct both in composition and diversity and that the oral microbiome composition of a denture wearer is variable and is influenced by the location within the mouth. Dentures and mucosa were predominantly made up of Bacilli and Actinobacteria. Moreover, the presence of natural teeth has a significant impact on the overall microbial composition, when compared to the fully edentulous. Furthermore, increasing levels of Candida spp. positively correlate with Lactobacillus spp. AMPs were quantified, though showed no specific correlations. Conclusions: This is the first study to provide a detailed understanding of the oral microbiome of denture wearers and has provided evidence that DS development is more complex than simply a candidal infection. Both fungal and bacterial kingdoms clearly play a role in defining the progression of DS, though we were unable to show a defined role for AMPs

Depression prevalence using the HADS-D compared to SCID major depression classification:An individual participant data meta-analysis

Objectives: Validated diagnostic interviews are required to classify depression status and estimate prevalence of disorder, but screening tools are often used instead. We used individual participant data meta-analysis to compare prevalence based on standard Hospital Anxiety and Depression Scale – depression subscale (HADS-D) cutoffs of ≥8 and ≥11 versus Structured Clinical Interview for DSM (SCID) major depression and determined if an alternative HADS-D cutoff could more accurately estimate prevalence. Methods: We searched Medline, Medline In-Process & Other Non-Indexed Citations via Ovid, PsycINFO, and Web of Science (inception-July 11, 2016) for studies comparing HADS-D scores to SCID major depression status. Pooled prevalence and pooled differences in prevalence for HADS-D cutoffs versus SCID major depression were estimated. Results: 6005 participants (689 SCID major depression cases) from 41 primary studies were included. Pooled prevalence was 24.5% (95% Confidence Interval (CI): 20.5%, 29.0%) for HADS-D ≥8, 10.7% (95% CI: 8.3%, 13.8%) for HADS-D ≥11, and 11.6% (95% CI: 9.2%, 14.6%) for SCID major depression. HADS-D ≥11 was closest to SCID major depression prevalence, but the 95% prediction interval for the difference that could be expected for HADS-D ≥11 versus SCID in a new study was −21.1% to 19.5%. Conclusions: HADS-D ≥8 substantially overestimates depression prevalence. Of all possible cutoff thresholds, HADS-D ≥11 was closest to the SCID, but there was substantial heterogeneity in the difference between HADS-D ≥11 and SCID-based estimates. HADS-D should not be used as a substitute for a validated diagnostic interview.This study was funded by the Canadian Institutes of Health Research (CIHR, KRS-144045 & PCG 155468). Ms. Neupane was supported by a G.R. Caverhill Fellowship from the Faculty of Medicine, McGill University. Drs. Levis and Wu were supported by Fonds de recherche du Québec - Santé (FRQS) Postdoctoral Training Fellowships. Mr. Bhandari was supported by a studentship from the Research Institute of the McGill University Health Centre. Ms. Rice was supported by a Vanier Canada Graduate Scholarship. Dr. Patten was supported by a Senior Health Scholar award from Alberta Innovates, Health Solutions. The primary study by Scott et al. was supported by the Cumming School of Medicine and Alberta Health Services through the Calgary Health Trust, and funding from the Hotchkiss Brain Institute. The primary study by Amoozegar et al. was supported by the Alberta Health Services, the University of Calgary Faculty of Medicine, and the Hotchkiss Brain Institute. The primary study by Cheung et al. was supported by the Waikato Clinical School, University of Auckland, the Waikato Medical Research Foundation and the Waikato Respiratory Research Fund. The primary study by Cukor et al. was supported in part by a Promoting Psychological Research and Training on Health-Disparities Issues at Ethnic Minority Serving Institutions Grants (ProDIGs) awarded to Dr. Cukor from the American Psychological Association. The primary study by De Souza et al. was supported by Birmingham and Solihull Mental Health Foundation Trust. The primary study by Honarmand et al. was supported by a grant from the Multiple Sclerosis Society of Canada. The primary study by Fischer et al. was supported as part of the RECODEHF study by the German Federal Ministry of Education and Research (01GY1150). The primary study by Gagnon et al. was supported by the Drummond Foundation and the Department of Psychiatry, University Health Network. The primary study by Akechi et al. was supported in part by a Grant-in-Aid for Cancer Research (11−2) from the Japanese Ministry of Health, Labour and Welfare and a Grant-in-Aid for Young Scientists (B) from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The primary study by Kugaya et al. was supported in part by a Grant-in-Aid for Cancer Research (9–31) and the Second-Term Comprehensive 10-year Strategy for Cancer Control from the Japanese Ministry of Health, Labour and Welfare. The primary study Ryan et al. was supported by the Irish Cancer Society (Grant CRP08GAL). The primary study by Keller et al. was supported by the Medical Faculty of the University of Heidelberg (grant no. 175/2000). The primary study by Love et al. (2004) was supported by the Kathleen Cuningham Foundation (National Breast Cancer Foundation), the Cancer Council of Victoria and the National Health and Medical Research Council. The primary study by Love et al. (2002) was supported by a grant from the Bethlehem Griffiths Research Foundation. The primary study by Löwe et al. was supported by the medical faculty of the University of Heidelberg, Germany (Project 121/2000). The primary study by Navines et al. was supported in part by the Spanish grants from the Fondo de Investigación en Salud, Instituto de Salud Carlos III (EO PI08/90869 and PSIGEN-VHC Study: FIS-E08/00268) and the support of FEDER (one way to make Europe). The primary study by O'Rourke et al. was supported by the Scottish Home and Health Department, Stroke Association, and Medical Research Council. The primary study by Sanchez-Gistau et al. was supported by a grant from the Ministry of Health of Spain (PI040418) and in part by Catalonia Government, DURSI 2009SGR1119. The primary study by Gould et al. was supported by the Transport Accident Commission Grant. The primary study by Rooney et al. was supported by the NHS Lothian Neuro-Oncology Endowment Fund. The primary study by Schwarzbold et al. was supported by PRONEX Program (NENASC Project) and PPSUS Program of Fundaçao de Amparo a esquisa e Inovacao do Estado de Santa Catarina (FAPESC) and the National Science and Technology Institute for Translational Medicine (INCT-TM). The primary study by Simard et al. was supported by IDEA grants from the Canadian Prostate Cancer Research Initiative and the Canadian Breast Cancer Research Alliance, as well as a studentship from the Canadian Institutes of Health Research. The primary study by Singer et al. (2009) was supported by a grant from the German Federal Ministry for Education and Research (no. 01ZZ0106). The primary study by Singer et al. (2008) was supported by grants from the German Federal Ministry for Education and Research (# 7DZAIQTX) and of the University of Leipzig (# formel. 1–57). The primary study by Meyer et al. was supported by the Federal Ministry of Education and Research (BMBF). The primary study by Stone et al. was supported by the Medical Research Council, UK and Chest Heart and Stroke, Scotland. The primary study by Turner et al. was supported by a bequest from Jennie Thomas through Hunter Medical Research Institute. The primary study by Walterfang et al. was supported by Melbourne Health. Drs. Benedetti and Thombs were supported by FRQS researcher salary awards. No other authors reported funding for primary studies or for their work on this study. No funder had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication

Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems

© 2008 Zafar et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background : Stage at diagnosis plays a significant role in colorectal cancer (CRC) survival. Understanding which factors contribute to a more advanced stage at diagnosis is vital to improving overall survival. Comorbidity, race, and age are known to impact receipt of cancer therapy and survival, but the relationship of these factors to stage at diagnosis of CRC is less clear. The objective of this study is to investigate how comorbidity, race and age influence stage of CRC diagnosis. Methods : Two distinct healthcare populations in the United States (US) were retrospectively studied. Using the Cancer Care Outcomes Research and Surveillance Consortium database, we identified CRC patients treated at 15 Veterans Administration (VA) hospitals from 2003–2007. We assessed metastatic CRC patients treated from 2003–2006 at 10 non-VA, fee-for-service (FFS) practices. Stage at diagnosis was dichotomized (non-metastatic, metastatic). Race was dichotomized (white, non-white). Charlson comorbidity index and age at diagnosis were calculated. Associations between stage, comorbidity, race, and age were determined by logistic regression. Results : 342 VA and 340 FFS patients were included. Populations differed by the proportion of patients with metastatic CRC at diagnosis (VA 27% and FFS 77%) reflecting differences in eligibility criteria for inclusion. VA patients were mean (standard deviation; SD) age 67 (11), Charlson index 2.0 (1.0), and were 63% white. FFS patients were mean age 61 (13), Charlson index 1.6 (1.0), and were 73% white. In the VA cohort, higher comorbidity was associated with earlier stage at diagnosis after adjusting for age and race (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.58–1.00; p = 0.045); no such significant relationship was identified in the FFS cohort (OR 1.09, 95% CI 0.82–1.44; p = 0.57). In both cohorts, no association was found between stage at diagnosis and either age or race. Conclusion : Higher comorbidity may lead to earlier stage of CRC diagnosis. Multiple factors, perhaps including increased interactions with the healthcare system due to comorbidity, might contribute to this finding. Such increased interactions are seen among patients within a healthcare system like the VA system in the US versus sporadic interactions which may be seen with FFS healthcare

Changes in weight loss, body composition and cardiovascular disease risk after altering macronutrient distributions during a regular exercise program in obese women

<p>Abstract</p> <p>Background</p> <p>This study's purpose investigated the impact of different macronutrient distributions and varying caloric intakes along with regular exercise for metabolic and physiological changes related to weight loss.</p> <p>Methods</p> <p>One hundred forty-one sedentary, obese women (38.7 ± 8.0 yrs, 163.3 ± 6.9 cm, 93.2 ± 16.5 kg, 35.0 ± 6.2 kg•m^-2, 44.8 ± 4.2% fat) were randomized to either no diet + no exercise control group (CON) a no diet + exercise control (ND), or one of four diet + exercise groups (high-energy diet [HED], very low carbohydrate, high protein diet [VLCHP], low carbohydrate, moderate protein diet [LCMP] and high carbohydrate, low protein [HCLP]) in addition to beginning a 3x•week^-1supervised resistance training program. After 0, 1, 10 and 14 weeks, all participants completed testing sessions which included anthropometric, body composition, energy expenditure, fasting blood samples, aerobic and muscular fitness assessments. Data were analyzed using repeated measures ANOVA with an alpha of 0.05 with LSD post-hoc analysis when appropriate.</p> <p>Results</p> <p>All dieting groups exhibited adequate compliance to their prescribed diet regimen as energy and macronutrient amounts and distributions were close to prescribed amounts. Those groups that followed a diet and exercise program reported significantly greater anthropometric (waist circumference and body mass) and body composition via DXA (fat mass and % fat) changes. Caloric restriction initially reduced energy expenditure, but successfully returned to baseline values after 10 weeks of dieting and exercising. Significant fitness improvements (aerobic capacity and maximal strength) occurred in all exercising groups. No significant changes occurred in lipid panel constituents, but serum insulin and HOMA-IR values decreased in the VLCHP group. Significant reductions in serum leptin occurred in all caloric restriction + exercise groups after 14 weeks, which were unchanged in other non-diet/non-exercise groups.</p> <p>Conclusions</p> <p>Overall and over the entire test period, all diet groups which restricted their caloric intake and exercised experienced similar responses to each other. Regular exercise and modest caloric restriction successfully promoted anthropometric and body composition improvements along with various markers of muscular fitness. Significant increases in relative energy expenditure and reductions in circulating leptin were found in response to all exercise and diet groups. Macronutrient distribution may impact circulating levels of insulin and overall ability to improve strength levels in obese women who follow regular exercise.</p

Morphology of the earliest reconstructable tetrapod Parmastega aelidae.

The known diversity of tetrapods of the Devonian period has increased markedly in recent decades, but their fossil record consists mostly of tantalizing fragments1-15. The framework for interpreting the morphology and palaeobiology of Devonian tetrapods is dominated by the near complete fossils of Ichthyostega and Acanthostega; the less complete, but partly reconstructable, Ventastega and Tulerpeton have supporting roles2,4,16-34. All four of these genera date to the late Famennian age (about 365-359 million years ago)-they are 10 million years younger than the earliest known tetrapod fragments5,10, and nearly 30 million years younger than the oldest known tetrapod footprints35. Here we describe Parmastega aelidae gen. et sp. nov., a tetrapod from Russia dated to the earliest Famennian age (about 372 million years ago), represented by three-dimensional material that enables the reconstruction of the skull and shoulder girdle. The raised orbits, lateral line canals and weakly ossified postcranial skeleton of P. aelidae suggest a largely aquatic, surface-cruising animal. In Bayesian and parsimony-based phylogenetic analyses, the majority of trees place Parmastega as a sister group to all other tetrapods

Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies

CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.</p

Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies

CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.</p

Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes. An Individual-Participant Data Meta-Analysis

IMPORTANCE: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. OBJECTIVE: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. DESIGN, SETTING, AND PARTICIPANTS: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. EXPOSURES: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). MAIN OUTCOMES AND MEASURES: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. RESULTS: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). CONCLUSIONS AND RELEVANCE: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations

A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPreviously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.info:eu-repo/grantAgreement/EC/FP7/21807

Creative destruction in science

Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents\u2019 reasoning about day care options, and gender discrimination in hiring decisions. Significance statement It is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void\u2014 reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building. Scientific transparency statement The materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article