Metformin prevents against oxidative stress-induced senescence in human periodontal ligament cells.

Periodontitis is a chronic infectious disease involving periodontal tissues. Periodontal ligament cells (PDLCs) play an important role in the regeneration of periodontal tissue. However, senescent PDLCs have an impeded regenerative potential. Metformin has been reported to prevent senescence at both the cellular and individual levels. The objectives of the present study were to evaluate the effects of metformin on cellular senescence in human PDLCs (hPDLCs) under oxidative stress. hPDLCs were pretreated with metformin, followed by H2O2 exposure. The cell viability, oxidative damage, cellular senescence and osteogenic potential were detected. To inhibit autophagy, hPDLCs were treated with 3-methyladenine before metformin treatment. The present study revealed that H2O2 exposure inhibits proliferation, increased lysosomal ß-galactosidase activity, augments reactive oxidative species (ROS) accumulation, elevates the oxidative damage, stimulates the expression of senescence-related genes and impedes the activity of the osteogenic differentiation of hPDLCs. Metformin pretreatment could partly reverse the detrimental influences of H2O2 on hPDLCs. Moreover, metformin could stimulate autophagy, whereas the inhibition of autophagy with 3-methyladenine reversed the anti-senescence effects of metformin on hPDLCs under oxidative stress. The present study manifested that metformin could alleviate oxidative stress-induced senescence via stimulating autophagy and could partially recover the osteogenic potential of hPDLCs, possibly providing a reference for the discovery of periodontal treatment from the perspective of antisenescence.

Comparative evaluation of the vertical fracture resistance of endodontically treated roots filled with Gutta-percha and Resilon: a meta-analysis of in vitro studies.

BACKGROUND: Teeth treated endodontically are more susceptible to vertical root fracture (VRF). Some studies have suggested that obturating the root canals with Gutta-percha or Resilon can reinforce endodontically treated teeth, but a few others have presented conflicting results. These inconsistent results cannot guide clinicians in determining clinical approaches. The objective of this meta-analysis is to evaluate and compare the vertical fracture resistance of endodontically treated root canals obturated with Gutta-percha/AH plus and the Resilon system. METHODS: Comprehensive literature searches were performed in the PubMed, Cochrane Library, ScienceDirect, Web of Science and Embase databases. The titles and abstracts of all of the retrieved articles were independently assessed by two authors according to predefined selection criteria. Data in the included articles were independently extracted. Statistical analyses were conducted using Review Manager 5.3 and Stata 12.0 software. The pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for the outcome indicators. The level of statistical significance was set at p < 0.05. The Cochran Q test (I2 test) was used to test for heterogeneity among studies. RESULTS: Fourteen randomized controlled in vitro trials were included in the meta-analysis. The results demonstrated that the vertical root fracture resistance of unprepared and unfilled roots was significantly higher than that of roots obturated with Gutta-percha/AH plus (SMD = - 0.69, 95% CI = - 1.34 to - 0.04, p = 0.04) or the Resilon system (SMD = - 0.54, 95% CI = - 1.07 to - 0.00, p = 0.05). The differences in fracture resistance between the roots filled with Gutta-percha/AH plus and the prepared unfilled root canals was not significant (SMD = 0.59, 95% CI = - 0.02 to 1.21, p = 0.06). Roots obturated with Resilon had higher fracture resistance than instrumented unfilled roots (SMD = 0.83, 95% CI = 0.44 to 1.22, p < 0.0001) or roots filled with Gutta-percha/AH plus (SMD = 0.62, 95% CI = 0.01 to 1.23, p = 0.05). CONCLUSIONS: The present study suggests that filling with Gutta-percha/AH plus dose not reinforce endodontically treated roots, whereas obturating with the Resilon system can increase vertical root fracture resistance of prepared roots. As this meta-analysis was based on in vitro studies, it should be careful to extrapolate its conclusion to the clinical context.

Religiosity, dietary habit, intake of fruit and vegetable, and vegetarian status among Seventh-Day Adventists in West Malaysia.

Religion has been shown to be salutary on health, and a possible link between religion and positive health outcomes is diet. Research has shown that religiosity is associated with better diet but most studies were conducted in a multi-denominational context, which might be confounded with theological differences. This study examined the relationship between religiosity and diet within a homogenous group of believers. Data from survey of 574 Seventh-Day Adventists residing in West Malaysia, aged 18-80, were analyzed using multiple regressions. While none of the religious variables were significantly associated with fruit and vegetable intake, a higher level of religiosity was associated with a better dietary habit and vegetarian status. The mixed relationship between religiosity and diet suggest that further research is needed to explore how religion might influence the diet of adherents.

The Association of Self-Perception of Aging and Quality of Life in Older Adults: A Systematic Review.

BACKGROUND AND OBJECTIVES: Self-perception of aging is an important psychosocial factor that can influence quality of life in older age. This review aimed to synthesize findings on the association between self-perception of aging and quality of life among older adults aged 60 and above. RESEARCH DESIGN AND METHODS: A systematic search was conducted in 4 electronic databases (Ovid Medline, PsycInfo, CINAHL, and Web of Science). Studies conducted in English and including measures on the perception of aging and quality of life were included in this review. A total of 32 observational studies (21 cross-sectional, 8 longitudinal, 2 mixed-method, and 1 qualitative) met the inclusion criteria. Outcomes reported in the included studies were quality of life, physical health and functioning, psychological health, mental health, and general well-being. RESULTS: Overall, 20 quantitative studies indicated a strong association between positive perception of aging and increased quality of life. Similarly, 9 quantitative studies demonstrated that negative perception of aging is associated with lower quality of life. Results of the mixed-method and qualitative studies indicated that older adults with higher morale and good physical capability had more positive perceptions of health. DISCUSSION AND IMPLICATIONS: These results suggest that promoting a positive perception of aging and a self-care attitude would help to enhance older adults' quality of life and should be incorporated into future health promotions and interventions.

Erratum: Low-intensity Pulsed Ultrasound regulates alveolar bone homeostasis in experimental Periodontitis by diminishing Oxidative Stress: Erratum.

[This corrects the article DOI: 10.7150/thno.42508.].

Cultural Responses to Covid-19 Pandemic: Religions, Illness Perception, and Perceived Stress.

Many psychological researchers have proven the deteriorating effects of the coronavirus disease 2019 (Covid-19) pandemic on public mental health. In Malaysia, various Covid-19 clusters were associated with religious gatherings. From a cultural psychology perspective, how ethno-religious groups respond to this crisis originating from their unique rationality and ecological systems. Therefore, this study aimed to explore the illness perceptions of major religious groups (Christian, Muslim, and Buddhist) in Malaysia toward the Covid-19 pandemic, their stress levels, and the relationship between illness perception, stress, and forms of religious expression during the lockdown period. Through an online survey method, 608 Malaysian religious believers were included in this mixed-method empirical study, which adapted standardized instruments [Duke University Religion Index (DUREL), Brief Illness Perception Questionnaire (BIPQ), and Perceived Stress Scale (PSS)]. Statistical analysis showed that all three groups reported moderate levels of stress in average without any significant difference after controlling for age. Both internal and external forms of religious expression had a significant negative relationship with stress levels. Personal control, comprehension, and emotions domains of illness perception accounted for a significant variance in the stress level. Furthermore, religious expression significantly moderated the relationship between some illness perception domains and stress. Qualitative coding revealed that most participants perceived human behavior and attitudes, sociopolitical, and sociological factors as causal factors to the current pandemic. These findings confirmed the relationship between religious expression, illness belief, and stress regulation during the pandemic lockdown. Incidental findings of age as a potential protective factor for Malaysian believers warrants further study. In the conclusion, implications for public health policymakers and religious communities on pandemic prevention and well-being promotion were discussed.

Low-intensity Pulsed Ultrasound regulates alveolar bone homeostasis in experimental Periodontitis by diminishing Oxidative Stress.

Periodontitis is a widespread oral disease that results in the loss of alveolar bone. Low-intensity pulsed ultrasound (LIPUS), which is a new therapeutic option, promotes alveolar bone regeneration in periodontal bone injury models. This study investigated the protective effect of LIPUS on oxidative stress in periodontitis and the mechanism underlying this process. Methods: An experimental periodontitis model was induced by administering a ligature. Immunohistochemistry was performed to detect the expression levels of oxidative stress, osteogenic, and osteoclastogenic markers in vivo. Cell viability and osteogenic differentiation were analyzed using the Cell Counting Kit-8, alkaline phosphatase, and Alizarin Red staining assays. A reactive oxygen species assay kit, lipid peroxidation MDA assay kit, and western blotting were used to determine oxidative stress status in vitro. To verify the role of nuclear factor erythroid 2-related factor 2 (Nrf2), an oxidative regulator, during LIPUS treatment, the siRNA technique and Nrf2-/- mice were used. The PI3K/Akt inhibitor LY294002 was utilized to identify the effects of the PI3K-Akt/Nrf2 signaling pathway. Results: Alveolar bone resorption, which was experimentally induced by periodontitis in vivo, was alleviated by LIPUS via activation of Nrf2. Oxidative stress, induced via H2O2 treatment in vitro, inhibited cell viability and suppressed osteogenic differentiation. These effects were also alleviated by LIPUS treatment via Nrf2 activation. Nrf2 silencing blocked the antioxidant effect of LIPUS by diminishing heme oxygenase-1 expression. Nrf2-/- mice were susceptible to ligature-induced periodontitis, and the protective effect of LIPUS on alveolar bone dysfunction was weaker in these mice. Activation of Nrf2 by LIPUS was accompanied by activation of the PI3K/Akt pathway. The oxidative defense function of LIPUS was inhibited by exposure to LY294002 in vitro. Conclusions: These results demonstrated that LIPUS regulates alveolar bone homeostasis in periodontitis by attenuating oxidative stress via the regulation of PI3K-Akt/Nrf2 signaling. Thus, Nrf2 plays a pivotal role in the protective effect exerted by LIPUS against ligature-induced experimental periodontitis.

Low-intensity pulsed ultrasound upregulates osteogenesis under inflammatory conditions in periodontal ligament stem cells through unfolded protein response.

BACKGROUND: In periodontal tissue engineering, periodontal ligament stem cells derived from patients with periodontitis (P-PDLSCs) are among the most promising and accessible stem cells for repairing disrupted alveolar bone and other connective tissues around the teeth. However, the inflammatory environment influences the osteogenic differentiation ability of P-PDLSCs. We examined low-intensity pulsed ultrasound (LIPUS) in P-PDLSCs in vitro and in rats with experimental periodontitis to determine whether LIPUS can enhance the osteogenic differentiation of stem cells. MATERIALS AND METHODS: P-PDLSCs were harvested and isolated from the periodontal tissues around the teeth of periodontitis patients, and healthy PDLSCs (H-PDLSCs) were obtained from tissues around healthy teeth. After validation by flow cytometry analysis, the P-PDLSCs were cultured in osteogenic medium either pretreated with the endoplasmic reticulum stress (ERS) inhibitor 4-phenyl butyric acid (4-PBA) or not pretreated and then treated with or without LIPUS (90 mW/cm2, 1.5 MHz) for 30 min per day. Cell viability, ERS marker expression, and osteogenic potential were determined between the different treatment groups. LPS-induced H-PDLSCs were used to mimic the inflammatory environment. In addition, we established a model of experimental periodontitis in rats and used LIPUS and 4-PBA as treatment methods. Then, the maxillary bone was collected, and micro-CT and histology staining methods were used to detect the absorption of alveolar bone. RESULTS: Our data showed that the P-PDLSCs derived from periodontitis tissues were in a more pronounced ERS state than were the H-PDLSCs, which resulted in the former being associated with increased inflammation and decreased osteogenic ability. LIPUS can alleviate ERS and inflammation while increasing the bone formation capacity of P-PDLSCs in vivo and in vitro. CONCLUSIONS: LIPUS may be an effective method to enhance the outcome of periodontal tissue engineering treatments of periodontitis by suppressing inflammation and increasing the osteogenic differentiation of P-PDLSCs through the unfolded protein response pathway, and more detailed studies are needed in the future.

European polygenic risk score for prediction of breast cancer shows similar performance in Asian women.

Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.

Evaluation of Cancer-Based Criteria for Use in Mainstream BRCA1 and BRCA2 Genetic Testing in Patients With Breast Cancer.

Importance: Increasing BRCA1 and BRCA2 (collectively termed herein as BRCA) gene testing is required to improve cancer management and prevent BRCA-related cancers. Objective: To evaluate mainstream genetic testing using cancer-based criteria in patients with cancer. Design, Setting, and Participants: A quality improvement study and cost-effectiveness analysis of different BRCA testing selection criteria and access procedures to evaluate feasibility, acceptability, and mutation detection performance was conducted at the Royal Marsden National Health Service Foundation Trust as part of the Mainstreaming Cancer Genetics (MCG) Programme. Participants included 1184 patients with cancer who were undergoing genetic testing between September 1, 2013, and February 28, 2017. Main Outcomes and Measures: Mutation rates, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were the primary outcomes. Results: Of the 1184 patients (1158 women [97.8%]) meeting simple cancer-based criteria, 117 had a BRCA mutation (9.9%). The mutation rate was similar in retrospective United Kingdom (10.2% [235 of 2294]) and prospective Malaysian (9.7% [103 of 1061]) breast cancer studies. If traditional family history criteria had been used, more than 50% of the mutation-positive individuals would have been missed. Of the 117 mutation-positive individuals, 115 people (98.3%) attended their genetics appointment and cascade to relatives is underway in all appropriate families (85 of 85). Combining with the equivalent ovarian cancer study provides 5 simple cancer-based criteria for BRCA testing with a 10% mutation rate: (1) ovarian cancer; (2) breast cancer diagnosed when patients are 45 years or younger; (3) 2 primary breast cancers, both diagnosed when patients are 60 years or younger; (4) triple-negative breast cancer; and (5) male breast cancer. A sixth criterion-breast cancer plus a parent, sibling, or child with any of the other criteria-can be added to address family history. Criteria 1 through 5 are considered the MCG criteria, and criteria 1 through 6 are considered the MCGplus criteria. Testing using MCG or MCGplus criteria is cost-effective with cost-effectiveness ratios of $1330 per discounted QALYs and $1225 per discounted QALYs, respectively, and appears to lead to cancer and mortality reductions (MCG: 804 cancers, 161 deaths; MCGplus: 1020 cancers, 204 deaths per year over 50 years). Use of MCG or MCGplus criteria might allow detection of all BRCA mutations in patients with breast cancer in the United Kingdom through testing one-third of patients. Feedback questionnaires from 259 patients and 23 cancer team members (12 oncologists, 8 surgeons, and 3 nurse specialists) showed acceptability of the process with 100% of patients pleased they had genetic testing and 100% of cancer team members confident to approve patients for genetic testing. Use of MCGplus criteria also appeared to be time and resource efficient, requiring 95% fewer genetic consultations than the traditional process. Conclusions and Relevance: This study suggests that mainstream testing using simple, cancer-based criteria might be able to efficiently deliver consistent, cost-effective, patient-centered BRCA testing.

A case-control study of breast cancer risk factors in 7,663 women in Malaysia.

BACKGROUND: Breast cancer risk factors have been examined extensively in Western setting and more developed Asian cities/countries. However, there are limited data on developing Asian countries. The purpose of this study was to examine breast cancer risk factors and the change of selected risk factors across birth cohorts in Malaysian women. METHODS: An unmatched hospital based case-control study was conducted from October 2002 to December 2016 in Selangor, Malaysia. A total of 3,683 cases and 3,980 controls were included in this study. Unconditional logistic regressions, adjusted for potential confounding factors, were conducted. The breast cancer risk factors were compared across four birth cohorts by ethnicity. RESULTS: Ever breastfed, longer breastfeeding duration, a higher soymilk and soy product intake, and a higher level of physical activity were associated with lower risk of breast cancer. Chinese had the lowest breastfeeding rate, shortest breastfeeding duration, lowest parity and highest age of first full term pregnancy. CONCLUSIONS: Our study shows that breastfeeding, soy intake and physical activity are modifiable risk factors for breast cancer. With the increasing incidence of breast cancer there is an urgent need to educate the women about lifestyle intervention they can take to reduce their breast cancer risk.

The application of multi-baseline digital close-range photogrammetry in three-dimensional imaging and measurement of dental casts.

OBJECTIVE: To explore a new technique for reconstructing and measuring three-dimensional (3D) models of orthodontic plaster casts using multi-baseline digital close-range photogrammetry (MBDCRP) with a single-lens reflex camera. STUDY DESIGN: Thirty sets of orthodontic plaster casts that do not exhibit severe horizontal overlap (>2 mm) between any two teeth were recorded by a single-lens reflex camera with 72 pictures taken in different directions. The 3D models of these casts were reconstructed and measured using the open source software MeshLab. These parameters, including mesio-distal crown diameter, arch width, and arch perimeter, were recorded six times on both the 3D digital models and on plaster casts by two examiners. Statistical analysis was carried out using the Bland-Altman method to measure agreement between the novel method and the traditional calliper method by calculating the differences between mean values. RESULTS: The average differences between the measurements of the photogrammetric 3D models and the plaster casts were 0.011-0.402mm. The mean differences between measurements obtained by the photogrammetric 3D models and the dental casts were not significant except for the lower arch perimeter (P>0.05), and all the differences were regarded as clinically acceptable (<0.5 mm). CONCLUSIONS: Measurements obtained by MBDCRP are compared well with those obtained from plaster casts, indicating that MBDCRP is an alternate way to store and measure dental plaster casts without severe horizontal overlap between any two teeth.

Religiosity and spirituality and the intake of fruit, vegetable, and fat: a systematic review.

Objectives. To systematically review articles investigating the relationship between religion and spirituality (R/S) and fruit, vegetable, and fat intake. Methods. PubMed, CINAHL, and PsycInfo were searched for studies published in English prior to March 2013. The studies were divided into two categories: denominational studies and degree of R/S studies. The degree of R/S studies was further analyzed to (1) determine the categories of R/S measures and their relationship with fruit, vegetable, and fat intake, (2) evaluate the quality of the R/S measures and the research design, and (3) determine the categories of reported relationship. Results. Thirty-nine studies were identified. There were 14 denominational studies and 21 degree of R/S studies, and 4 studies were a combination of both. Only 20% of the studies reported validity and 52% reported reliability of the R/S measures used. All studies were cross-sectional, and only one attempted mediation analysis. Most studies showed a positive association with fruit and vegetable intake and a mixed association with fat intake. Conclusion. The positive association between R/S and fruit and vegetable intake may be one possible link between R/S and positive health outcome. However, the association with fat intake was mixed, and recommendations for future research are made.