Circulating miRNAs as Epigenetic Mediators of Periodontitis and Preeclampsia Association.

Objective: Periodontal disease has been associated with pregnancy complications including preeclampsia. This bioinformatic study is aimed at investigating the possible role of circulating microRNAs (miRNAs) as mediators of the association between maternal periodontal disease and preeclampsia. Methods: Peripheral blood miRNA profiles of periodontitis and controls were sought from Gene Expression Omnibus (GEO), and differential expression analysis was performed. Experimentally validated circulating miRNAs associated with preeclampsia were determined from the Human MicroRNA Disease Database (HMDD v3.0). Venn diagrams were drawn to identify shared circulating differential miRNAs (DEmiRNAs). Significantly enriched target genes, KEGG pathways, and Gene Ontology (GO) terms for the set of shared DEmiRNA were predicted using miRNA enrichment analysis and annotation tool (miEAA v 2.0). Additionally, the shared DEmiRNA-enriched target genes were analyzed for enriched WikiPathways, BioCarta metabolic pathways, and tissue proteins in the human proteome map. Results: Among 183 circulating DEmiRNA in periodontitis and 60 experimentally validated miRNA in preeclampsia, 9 shared DEmiRNA were identified. The top among 32 overrepresented target genes included MAFB, PSAP, and CDK5RAP2, top among 14 enriched KEGG pathways were renin-angiotensin system and graft-versus-host disease, and that among enriched 44 GO profiles included "positive regulation of epidermal growth factor-activated receptor activity" and "sequestering of calcium ion." In the overrepresented target gene set, among 10 enriched WikiPathways, the top included "NAD metabolism, sirtuins, and aging" and "regulation of Wnt/B-catenin signaling by small molecule compounds" and PPAR-related mechanisms was top among 13 enriched BioCarta metabolic pathways. Conclusion: A circulating 9-DEmiRNA set was significantly linked to both periodontitis and preeclampsia. Enrichment analysis identified specific genes, pathways, and functional mechanisms, which may be epigenetically altered and thereby mediate the biological association of periodontitis and preeclampsia.

Long noncoding RNA TUG1 promotes osteogenic differentiation of human periodontal ligament stem cell through sponging microRNA-222-3p to negatively regulate Smad2/7.

OBJECTIVE: To scrutinize the function of long non-coding RNA TUG1 on the osteogenic differentiation of human periodontal ligament stem cells in periodontitis and its specific mechanism. METHODS: Human periodontal ligament stem cells were extracted from human periodontium, followed by induction of osteogenic differentiation with osteogenic medium. Knockdown or overexpression of TUG1, microRNA-222-3p or Smad2/7 were performed in human periodontal ligament stem cells to observe their effect on expressions of osteogenic differentiation markers (Runx2, ALP, and OCN), and on calcium nodule formation by Alizarin red staining. Starbase software was utilized for prediction of the binding sites of TUG1 and microRNA-222-3p in addition to microRNA-222-3p and Smad2/7. Then dual-luciferase reporter gene assay was adopted to inspect the binding relationships between microRNA-222-3p and TUG1 or Smad2/7. RESULTS: Highly expressed TUG1 and lowly expressed microRNA-222-3p were found in human periodontal ligament stem cells during osteogenic differentiation. After measuring the expression of Runx2, ALP, and OCN as well as the formation of calcium nodules, we discovered that TUG1 can facilitate osteogenic differentiation of human periodontal ligament stem cells, while microRNA-222-3p had a reverse effect. Subsequently, knockdown of TUG1 and Smad2/7 or overexpression of microRNA-222-3p inhibited the osteogenic differentiation of human periodontal ligament stem cells. MicroRNA-222-3p is a target gene of TUG1, while microRNA-222-3p can negatively regulate Smad2/7. CONCLUSION: LncRNA TUG1 accelerates the osteogenic differentiation of human periodontal ligament stem cells by sponging microRNA-222-3p to regulate Smad2/7.

Berberine reduces inflammation of human dental pulp fibroblast via miR-21/KBTBD7 axis.

OBJECTIVE: This study is to investigate the effect and underlying mechanisms of berberine (BBR) on the proliferation and inflammatory levels of lipopolysaccharide induced human dental pulp fibroblast (LPS-HDPF). METHODS: Different concentrations of LPS were used to induce inflammatory response of HDPF. Cell proliferation was observed in BBR treated HDPF after transfection of miR-21 mimic, miR-21 inhibitor or sh-kBTBD7 plasmids and their negative controls. ELISA was employed to detect the expressions of inflammation related cytokines. Real-time quantitative RT-PCR was applied to estimate the expressions of miR-21 and KBTBD7. KBTBD7 expression was detected by Immunocytochemistry. Western blot analysis showed the protein levels of KBTBD7, Phospho-IKKα/ß, IKKß, Phospho-NF-κB p65, NF-κB p65, and IκBα. Luciferase reporter gene assay was used to determine the interaction between miR-21 and KBTBD7. RESULTS: LPS could promote inflammatory response in HDPF. Down-regulated miR-21 and up-regulated KBTBD7 were found in LPS-HDPF. BBR (25 uM) treatment in LPS-HDPF could ameliorate cell inflammatory response, presented by reduced expressions of IL-1ß, IL-6 and TNF-α, as well as enhanced cell proliferation and miR-21 expression. Moreover, miR-21 negatively targets KBTBD7. Over-expression of miR-21 or silencing of KBTBD7 could enhance the protective role of BBR on LPS-HDPF by inhibiting inflammatory response and promoting cell proliferation. Transfection of miR-21 overexpression or KBTBD7 silencing in BBR treated LPS-HDPF could inhibit activation of NF-κB signal pathway. CONCLUSION: Evidence in this study suggested that BBR mediates LPS induced inflammation in HDPF via miR-21/KBTBD7 axis to regulate NF-κB signal pathway, which may provide theoretical basis for BBR in prevention of pulpitis.

Berberine Promotes Osteogenic Differentiation of Human Dental Pulp Stem Cells Through Activating EGFR-MAPK-Runx2 Pathways.

Similar to the mesenchymal stem cells (MSCs), dental pulp stem cells (DPSCs) also have pluripotent differentiation characteristic and may be more ideal for tissue regeneration, especially in tooth regeneration engineering. However, bacterial infection may be a powerful obstacle. Berberine (BBR), known with antibacterial effects, was recently found to play functions in bone formation through promoting osteogenic differentiation from pluripotent stem cells. However, whether BBR also function in DPSCs osteogenic differentiation has not yet been reported. Primary DPSCs were isolated from dental pulp tissues extracted from human impacted mandibular third molars, and identified by flow cytometry for cell surface antigen molecules. A dexamethasone osteogenic medium was used to induce DPSCs osteogenic differentiation. BBR (1 µM and 5 µM) was pre-added to into medium, and then cell proliferation, spheroid formation and osteogenic differentiation capacities of DPSCs were analyzed, as well as the underlying molecules modulation mechanism. Flow cytometry identified that CD44, CD90, CD81 and CD105 positively expressed in the isolated hDPSCs, with CD34 and CD45 negetively expressed. BBR enhanced the cell proliferation of hDPSCs in a dose-dependent pattern, and promoted dexamethasone-induced osteogenic differentiation via enhancing Runx2 transcription factor activity followed by upregulating osteogenesis markers expression, whereas the adipogenic differentiation of hDPSCs was suppressed dramatically by BBR. The EGFR and MAPK pathways were activated by BBR, and inhibitors for these pathways significantly suppressed the osteogenic differentiation promotion of BBR. These results have revealed a novel mechanism that berberine might promote hDPSCs osteogenic differentiation through activating EGFR-MAPK-Runx2 signaling pathways.

An investigation of factors predicting the type of bladder antimuscarinics initiated in Medicare nursing homes residents.

BACKGROUND: To examine factors predicting type of bladder antimuscarinics (BAM) initiated in nursing home (NH) residents. METHODS: Incident BAM initiators following NH admission were identified by constructing a retrospective cohort from Medicare files and Minimum Data Set (MDS). Participants included all residents 65 years and older admitted in Medicare-certified NH between January 1, 2007 and December 31, 2008 who were prescribed BAM and had continuous Medicare (Part A, B, and D) enrollment. Patient characteristics, medications, and comorbidities were derived from Medicare enrollment and claims. NH characteristics and health status were derived from MDS assessments. The outcome was defined as type of BAM initiated after admission (selective, non-selective extended release, non-selective immediate release). Multinomial logistic regression using generalized estimating equation methodology determined which factors predicted the type of BAM initiated. RESULTS: Twelve thousand eight hundred ninety-nine NH residents initiating BAM therapy were identified; 13.38% of new users were prescribed selective BAM, 45.56% non-selective extended release, and 41.07% non-selective immediate release medications. In both sexes, significant predictors of BAM included region of nursing home, body mass index, cognitive performance score, frailty measures, activities of daily living, and measures of bladder continence. In women, history of fracture and fall-related injuries were significant predictors of type of BAM use, while race and indicators of balance were significant predictors of type of BAM use in men. Non-pharmacological continence management strategies were not predictive of type of BAM initiation. CONCLUSIONS: Several factors are important in predicting type of BAM initiation in both women and men, but other factors are sex-specific. Some observed factors predicting the type of BAM initiated, such as other medications use, body mass index, or provider-related factors are potentially modifiable and could be used in targeted interventions to help optimize BAM use in this population. TRIAL REGISTRATION: Not applicable.

Bladder antimuscarinics and cognitive decline in elderly patients.

INTRODUCTION: The evidence on the impact of bladder antimuscarinics initiation on cognitive function in older adults is inconsistent. METHODS: A retrospective analysis of data from the National Alzheimer's Coordinating Center (NACC) on enrollees 65 years and older evaluated the association between antimuscarinic initiation and cognitive decline. We defined decline from baseline (yes/no) for cognitive assessments included in the NACC Uniform Data Set 2.0 battery. New users were matched on year of enrollment and time in the cohort to randomly selected nonusers. Analyses were conducted using inverse probability of treatment weights based on baseline propensity scores. RESULTS: Our analyses included 698 new users and 7037 nonusers. The odds ratio (OR) and 95% confidence interval for cognitive decline in users as compared to nonusers was 1.4 (1.19-1.65) for Mini-Mental State Examination (MMSE), and 1.21 (1.03-1.42) for Clinical Dementia Rating; in addition, the odds of decline were 20% higher in users compared to nonusers for semantic memory/language and executive function. The effect estimate for MMSE was 1.94 (1.3-2.91) for those with mild cognitive impairment, 1.26 (0.99-1.62) in those with normal cognition, and 1.44 (1.04-1.99) in those with dementia at baseline. DISCUSSION: Our results show that antimuscarinic initiation is associated with cognitive decline and raise questions about their use, especially in those with impaired cognition.

A Comparison of Sex Differences in Psychotropic Medication Use in Older People with Alzheimer's Disease in the US and Finland.

AIMS: Given the high prevalence of psychotropic medication use in people with dementia and the potential for different prescribing practices in men and women, our study aimed to investigate sex differences in psychotropic medication use in older adults with Alzheimer's disease (AD) living in the US and Finland. METHODS: We used data collected between 2005 and 2011 as part of the National Alzheimer's Coordinating Center (NACC) in the US, and Medication use and Alzheimer's disease (MEDALZ) cohorts in Finland. We evaluated psychotropic medication use (antidepressant, antipsychotic, anxiolytic, sedative, or hypnotic) in participants aged 65 years or older. We employed multivariable logistic regression adjusted for demographics, co-morbidities, and other medications to estimate the magnitude of the association (adjusted odds ratio [aOR] with 95% confidence intervals [CIs]) according to sex. RESULTS: We included 1099 NACC participants (502 [45.68%] men, 597 [54.32%] women), and 67,049 participants from the MEDALZ cohort (22,961 [34.24%] men, 44,088 [65.75%] women). Women were more likely than men to use psychotropic medications: US, 46.2% vs. 33.1%, p < 0.001; Finland, 45.3% vs. 36.1%, p < 0.001; aOR was 2.06 (95% CI 1.58-2.70) in the US cohort and 1.38 (95% CI 1.33-1.43) in the Finnish cohort. Similarly, of the different psychotropic medications, women were more likely to use antidepressants (aOR-US: 2.16 [1.44-3.25], Finland: 1.52 [1.45-1.58]) and anxiolytics (aOR-US: 2.16 [1.83-3.96], Finland: 1.17 [1.13-1.23]) than men. CONCLUSION: Older women with AD are more likely to use psychotropic medications than older men, regardless of study population and country. Approaches to mitigate psychotropic medication use need to consider different prescribing habits observed in older women vs. men with AD.

Public and personal depression stigma in a rural American female sample.

We examined public and personal stigma among a community sample of 1,000 women living in primarily rural counties of Western Kentucky. Data on demographics, depression, stigma, health information sources, and availability of health services were collected via a random digit dial survey. The prevalence of depression was 15.7%. The majority of respondents (82.2%) reported congruent levels of stigma with 11.6% reporting high public and high personal stigma. However, 17.8% of respondents reported incongruent public and personal stigma. The 7.5% of women with low public and high personal stigma were older and less educated, preferred anonymous sources of health information, and reported better availability of health services. The 10.3% of women with high public and low personal stigma were younger and more educated, preferred interpersonal sources of health information, and reported poorer availability of health services. In multivariate analyses, depression and lower education were associated with any incongruent stigma, while rural residence and White race/ethnicity was associated with high personal and public stigma. Psychiatric nurses should develop community-based and targeted, point-of-care interventions to reduce public and personal stigma among rural women.

Sources of health information among rural women in Western Kentucky.

OBJECTIVE: To identify sources of general and mental health information for rural women to inform the development of public health nursing interventions that consider preferences for obtaining information. DESIGN AND SAMPLE: One thousand women (mean age = 57 years; 96.9% White) living in primarily nonmetropolitan areas of Western Kentucky participated via a random-digit-dial survey. MEASURES: Data were collected on demographics, sources of health information, depression, and stigma. RESULTS: Most participants preferred anonymous versus interpersonal sources for both general (68.1%) and mental health (69.4%) information. All participants reported at least one source of general health information, but 20.8% indicated not seeking or not knowing where to seek mental health information. The Internet was the most preferred anonymous source. Few women cited health professionals as the primary information source for general (11.4%) or mental (9.9%) health. Public stigma was associated with preferring anonymous sources and not seeking information. CONCLUSIONS: Public health nurses should understand the high utilization of anonymous sources, particularly for mental health information, and focus efforts on helping individuals to navigate resources to ensure they obtain accurate information about symptoms, effective treatments, and obtaining care. Reducing stigma should remain a central focus of prevention and education in rural areas.

Developmental-behavioral pediatric teaching of medical students: a national COMSEP survey.

BACKGROUND: The Council on Medical Student Education in Pediatrics (COMSEP) pediatric clerkship curriculum is widely followed. To date, there are no known studies on clerkship instruction related to developmental-behavioral pediatric (DBP) curricular elements. PURPOSES: The goals of this study are to examine pediatric clerkships' current DBP teaching methods and to identify barriers and solutions to recommended curriculum implementation. METHODS: Electronic survey was conducted with COMSEP-member pediatric clerkship directors. Descriptive statistics and qualitative data analysis was conducted. RESULTS: Response rate was 66%. General Pediatricians (87.1%) were mostly responsible for clerkship DBP teaching. Around 18% of directors reported not assessing DBP competencies. Most clerkship directors report time constraints (61.8%) as a barrier to implementing the curriculum, along with faculty availability and resources. Suggested solutions included DBP faculty collaboration and resources. CONCLUSIONS: General pediatricians should collaborate with DBP faculty for instructional content creation, and community-based observational opportunities and web-based shared resources could help clerkship directors achieve the COMSEP DBP curriculum competencies.

Prevalence of human immunodeficiency virus testing and associated risk factors in college students.

OBJECTIVE: This study documents the prevalence of human immunodeficiency virus (HIV) testing in a sample of college students and examines associated demographic and behavioral characteristics. PARTICIPANTS: College students aged 18 or older were randomly selected to participate in a health behavior survey at a southeastern university in September 2011. METHODS: Only sexually active students were included (N = 905). Relationships between demographic and sexual behavior characteristics were explored using logistic regression and classification regression tree (p ≤.05). RESULTS: Only 36.2% reported having been tested for HIV. Age was the most significant factor associated with testing. Factors associated with those least likely to be tested were race and anal sexual activity. Unsafe sexual behaviors were also associated with lower rates of HIV testing. CONCLUSIONS: Findings support the need for targeted HIV interventions on college campuses. Such interventions need to be tailored for at-risk students and take into consideration factors likely to contribute to HIV testing.