Dental treatment procedures for periodontal disease and the subsequent risk of ischaemic stroke: A retrospective population-based cohort study.

AIM: To investigate the association between specific dental therapy for periodontal disease and the risk of ischaemic stroke. MATERIALS AND METHODS: We conducted a population-based cohort study that used data from the Taiwan National Health Insurance Research Database 2005 for the period of 2000-2013. Our observations focused on patients with the diagnoses of gingivitis or periodontitis with and without specific treatment and subsequent incidence of ischaemic stroke. Dental care services include dental scaling, intensive treatment (subgingival curettage and root planing) and tooth extraction. Multivariate Cox regression analysis was used to estimate the hazard ratios and corresponding 95% confidence intervals (95% CI). RESULTS: Compared with those in the gingivitis cohort, patients with periodontitis have a higher risk of ischaemic stroke and a lower survival rate of stroke over the 10-year follow-up period. After integrative dental care, both dental scaling and intensive treatment, the risk was reduced, especially in patients with periodontitis, while patients with periodontal disease may have an increased risk of stroke after tooth extraction therapy. CONCLUSIONS: Our study showed that periodontitis is a risk factor for ischaemic stroke. Both dental scaling and intensive treatment for periodontal disease are associated with a lower risk of further ischaemic stroke events.

Human breast cancer cell metastasis is attenuated by lysyl oxidase inhibitors through down-regulation of focal adhesion kinase and the paxillin-signaling pathway.

The extracellular matrix (ECM) plays a critical role in the development and invasion of primary breast tumors. Lysyl oxidase (LOX), which is an ECM remodeling enzyme, appears to play roles in promoting cancer cell motility and invasion. To ascertain whether LOX overexpression in breast tumor tissues from Asian patients is associated with decreases in metastasis-free and overall survival in breast cancer patients, the mRNA levels of LOX were examined in paired tumor/normal tissue samples using real-time RT-PCR analysis (n = 246 pair-matched samples). To test whether specifically targeting LOX by inhibiting its activity (using beta-aminopropionitrile (ß-APN), a LOX inhibitor), mRNA expression (using siRNA), or protein expression (using 25 µM magnolol) attenuates the invasion of MDA-MB-231 breast cancer cells, a cancer cell migration assay was performed. Interestingly, only 78.5% (n = 193) of the breast cancer tumors displayed detectable LOX expression. Nearly 60% (n = 120) of the cases fell into Group 1 (tumor > normal, T > N); in this group, the mean LOX expression in the tumor cells was 20.2-fold greater than in normal cells. However, in Group 2 (normal > tumor, N > T), the LOX expression level in most of the normal tissues examined (80%, 59/73) was less than fivefold greater than in the tumor tissues. The increased level of active LOX in the invasive breast cancer cell line MDA-MB-231 was accompanied by the increased phosphorylation of focal adhesion kinase at Tyr-576 and of paxillin at Tyr-118. We also found that the addition of ß-APN (300 µM) and magnolol (25 µM), synergistically inhibited the migration and invasion of MDA-MB-231 cells. In this article, we describe, for the first time, higher expression of a LOX protein in breast tumors compared with normal tissues from Asian patients. Moreover, the results indicate that the inhibition of LOX using magnolol may represent a more desirable strategy for breast cancer therapy than the use of ß-APN.

Inhibition of Anchorage-Independent Proliferation and G0/G1 Cell-Cycle Regulation in Human Colorectal Carcinoma Cells by 4,7-Dimethoxy-5-Methyl-l,3-Benzodioxole Isolated from the Fruiting Body of Antrodia camphorate.

In this study, 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1) was isolated from three different sources of dried fruiting bodies of Antrodia camphorate (AC). AC is a medicinal mushroom that grows on the inner heartwood wall of Cinnamomum kanehirai Hay (Lauraceae), an endemic species that is used in Chinese medicine for its anti-tumor and immunomodulatory properties. In this study, we demonstrated that SY-1 profoundly decreased the proliferation of human colon cancer cells (COLO 205) through G0/G1 cell-cycle arrest (50-150 µM) and induction of apoptosis (>150 µM). Cell-cycle arrest induced by SY-1 was associated with a significant increase in levels of p53, p21/Cip1 and p27/Kip1, and a decrease in cyclins D1, D3 and A. In contrast, SY-1 treatment did not induce significant changes in G0/G1 phase cell-cycle regulatory proteins in normal human colonic epithelial cells (FHC). The cells were cultured in soft agar to evaluate anchorage-independent colony formation, and we found that the number of transformed colonies was significantly reduced in the SY-1-treated COLO 205 cells. These findings demonstrate for the first time that SY-1 inhibits human colon cancer cell proliferation through inhibition of cell growth and anchorage-independent colony formation in soft agar. However, the detailed mechanisms of these processes remain unclear and will require further investigation.

Deep-Learning Approach to Predict Survival Outcomes Using Wearable Actigraphy Device Among End-Stage Cancer Patients.

Survival prediction is highly valued in end-of-life care clinical practice, and patient performance status evaluation stands as a predominant component in survival prognostication. While current performance status evaluation tools are limited to their subjective nature, the advent of wearable technology enables continual recordings of patients' activity and has the potential to measure performance status objectively. We hypothesize that wristband actigraphy monitoring devices can predict in-hospital death of end-stage cancer patients during the time of their hospital admissions. The objective of this study was to train and validate a long short-term memory (LSTM) deep-learning prediction model based on activity data of wearable actigraphy devices. The study recruited 60 end-stage cancer patients in a hospice care unit, with 28 deaths and 32 discharged in stable condition at the end of their hospital stay. The standard Karnofsky Performance Status score had an overall prognostic accuracy of 0.83. The LSTM prediction model based on patients' continual actigraphy monitoring had an overall prognostic accuracy of 0.83. Furthermore, the model performance improved with longer input data length up to 48 h. In conclusion, our research suggests the potential feasibility of wristband actigraphy to predict end-of-life admission outcomes in palliative care for end-stage cancer patients. Clinical Trial Registration: The study protocol was registered on ClinicalTrials.gov (ID: NCT04883879).

Increased expression of enolase alpha in human breast cancer confers tamoxifen resistance in human breast cancer cells.

Enolase-alpha (ENO-1) is a key glycolytic enzyme that has been used as a diagnostic marker to identify human lung cancers. To investigate the role of ENO-1 in breast cancer diagnosis and therapy, the mRNA levels of ENO-1 in 244 tumor and normal paired tissue samples and 20 laser capture-microdissected cell clusters were examined by quantitative real-time PCR analysis. Increased ENO-1 mRNA expression was preferentially detected in estrogen receptor-positive (ER+) tumors (tumor/normal ratio >90-fold) when compared to ER-negative (tumor/normal ratio >20-fold) tumor tissues. The data presented here demonstrate that those patients whose tumors highly expressed ENO-1 had a poor prognosis with greater tumor size (>2 cm, *P = .017), poor nodal status (N > 3, *P = .018), and a shorter disease-free interval (<==1 year, *P < .009). We also found that higher-expressing ENO-1 tumors confer longer distance relapse (tumor/normal ratio = 82.8-92.4-fold) when compared to locoregional relapse (tumor/normal ratio = 43.4-fold) in postsurgical 4-hydroxy-tamoxifen (4-OHT)-treated ER+ patients (*P = .014). These data imply that changes in tumor ENO-1 levels are related to clinical 4-OHT therapeutic outcome. In vitro studies demonstrated that decreasing ENO-1 expression using small interfering RNA (siRNA) significantly augmented 4-OHT (100 nM)-induced cytotoxicity in tamoxifen-resistant (Tam-R) breast cancer cells. These results suggest that downregulation of ENO-1 could be utilized as a novel pharmacological approach for overcoming 4-OHT resistance in breast cancer therapy.

The lived experiences of spiritual suffering and the healing process among Taiwanese patients with terminal cancer.

AIMS AND OBJECTIVES: The purposes of this study were to explore the lived experiences of spiritual suffering and the change mechanism in healing processes among Taiwanese patients with terminal cancer. METHODS: The approach to this study was phenomenological-hermeneutic. Twenty-one patients with terminal cancer were invited to participate in a semi-structured interview that dealt with their experiences of spiritual suffering and the healing process. This study was conducted in the inpatient unit of the oncology department in two general hospitals. The interviews were recorded, transcribed and later analysed using the approach of narrative analysis. RESULTS: According to the results of case narration, the causes of spiritual suffering included cancer, known as a life-threatening illness, physical pain, treatment complications, uncertain illness progression, disability problems and lack of support. Patients turned to internal resources (including regarding the suffering as a life challenge, volunteering to help other cancer patients and searching for life wisdoms) and external resources (including peer support groups and family support) as they endured spiritual suffering. Taiwanese patients turned to Eastern and Western philosophies of Taoism, Confucianism, Buddhism and Christianity as methods to interpret their spiritual suffering. CONCLUSION: Patients' positive views of misfortune because of cancer and sufficient social supports were the key elements of the healing process to alleviate spiritual suffering. RELEVANCE TO CLINICAL PRACTICE: Nurses who learn to participate in suffering assessment are better able to understand spiritual needs of cancer patients. Cancer patients' views on the change mechanism in healing processes could provide essential information for nurses in developing an effective intervention programme. If nurses consider cultural factors that shape patients' experiences of spiritual suffering and the healing process, they could learn how to meet the needs of patients better from different cultural backgrounds.