Protective Effect of Alpha-Linolenic Acid on Human Oral Squamous Cell Carcinoma Metastasis and Apoptotic Cell Death.

Oral cancer ranks sixth among Taiwan's top 10 cancers and most patients with poor prognosis acquire metastases. The essential fatty acid alpha-linolenic acid (ALA) has been found to diminish many cancer properties. However, the anti-cancer activity of ALA in oral cancer has yet to be determined. We examined the mechanisms underlying ALA inhibition of metastasis and induction of apoptotic cell death in oral squamous cell carcinoma (OSCC). Migration and invasion assays confirmed the cancer cells' EMT capabilities, whereas flow cytometry and Western blotting identified molecular pathways in OSCC. ALA dramatically reduced cell growth in a concentration-dependent manner according to the findings. Low concentrations of ALA (100 or 200 µM) inhibit colony formation, the expression of Twist and EMT-related proteins, the expression of MMP2/-9 proteins, and enzyme activity, as well as cell migration and invasion. Treatment with high concentrations of ALA (200 or 400 µM) greatly increases JNK phosphorylation and c-jun nuclear accumulation and then upregulates the FasL/caspase8/caspase3 and Bid/cytochrome c/caspase9/caspase3 pathways, leading to cell death. Low concentrations of ALA inhibit SAS and GNM cell migration and invasion by suppressing Twist and downregulating EMT-related proteins or by decreasing the protein expression and enzyme activity of MMP-2/-9, whereas high concentrations of ALA promote apoptosis by activating the JNK/FasL/caspase 8/caspase 3-extrinsic pathway and the Bid/cytochrome c/caspase 9 pathway. ALA demonstrates potential as a treatment for OSCC patients.

Temporal Events Detector for Pregnancy Care (TED-PC): A rule-based algorithm to infer gestational age and delivery date from electronic health records of pregnant women with and without COVID-19.

OBJECTIVE: Identifying the time of SARS-CoV-2 viral infection relative to specific gestational weeks is critical for delineating the role of viral infection timing in adverse pregnancy outcomes. However, this task is difficult when it comes to Electronic Health Records (EHR). In combating the COVID-19 pandemic for maternal health, we sought to develop and validate a clinical information extraction algorithm to detect the time of clinical events relative to gestational weeks. MATERIALS AND METHODS: We used EHR from the National COVID Cohort Collaborative (N3C), in which the EHR are normalized by the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). We performed EHR phenotyping, resulting in 270,897 pregnant women (June 1st, 2018 to May 31st, 2021). We developed a rule-based algorithm and performed a multi-level evaluation to test content validity and clinical validity, and extreme length of gestation (<150 or >300). RESULTS: The algorithm identified 296,194 pregnancies (16,659 COVID-19, 174,744 without COVID-19) in 270,897 pregnant women. For inferring gestational age, 95% cases (n = 40) have moderate-high accuracy (Cohen's Kappa = 0.62); 100% cases (n = 40) have moderate-high granularity of temporal information (Cohen's Kappa = 1). For inferring delivery dates, the accuracy is 100% (Cohen's Kappa = 1). The accuracy of gestational age detection for the extreme length of gestation is 93.3% (Cohen's Kappa = 1). Mothers with COVID-19 showed higher prevalence in obesity or overweight (35.1% vs. 29.5%), diabetes (17.8% vs. 17.0%), chronic obstructive pulmonary disease (0.2% vs. 0.1%), respiratory distress syndrome or acute respiratory failure (1.8% vs. 0.2%). DISCUSSION: We explored the characteristics of pregnant women by different gestational weeks of SARS-CoV-2 infection with our algorithm. TED-PC is the first to infer the exact gestational week linked with every clinical event from EHR and detect the timing of SARS-CoV-2 infection in pregnant women. CONCLUSION: The algorithm shows excellent clinical validity in inferring gestational age and delivery dates, which supports multiple EHR cohorts on N3C studying the impact of COVID-19 on pregnancy.

By-Products of the Black Soybean Sauce Manufacturing Process as Potential Antioxidant and Anti-Inflammatory Materials for Use as Functional Foods.

To assess the potential of by-products of the black bean fermented soybean sauce manufacturing process as new functional food materials, we prepared black bean steamed liquid lyophilized product (BBSLP) and analysed its antioxidant effects in vitro. RAW264.7 macrophages were cultured and treated with BBSLP for 24 h, and 1 µg/mL lipopolysaccharide (LPS) was then used for another 24 h to induce inflammation. The cellular antioxidant capacity and inflammatory response were then analysed. Activation of nuclear factor kappa B (NF-κB) signaling in RAW264.7 macrophages was also analysed. Results showed BBSLP had 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium (ABTS+) radical-scavenging abilities and reducing power in vitro. The levels of both reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) were reduced after RAW264.7 macrophages were treated with BBSLP after LPS induction. After RAW264.7 macrophage treatment with BBSLP and induction by LPS, the levels of inflammatory molecules, including nitric oxide (NO), prostaglandin E2 (PGE2), IL-1α, IL-6 and TNF-α, decreased. NF-κB signaling activity was inhibited by reductions in IκB phosphorylation and NF-κB DNA-binding activity after RAW264.7 macrophages were treated with BBSLP after LPS induction. In conclusion, BBSLP has antioxidant and anti-inflammatory capabilities and can be a supplement material for functional food.

Suicide Prevention Programs Across U.S. Outpatient Mental Health Care Settings: Differences by Facility Ownership.

OBJECTIVE: This study aimed to examine whether facility ownership (public, private nonprofit, private for-profit ownership) was associated with provision of suicide prevention programs. METHODS: A retrospective cross-sectional study identified self-reported suicide prevention program status across 7,597 mental health facilities with outpatient settings by using data from the 2019 Substance Abuse and Mental Health Services Administration Behavioral Health Treatment Services Locator. Multivariable logistic regression models examined whether facility ownership was associated with availability of these programs. RESULTS: In 2019, only 61.2% of facilities provided outpatient suicide prevention programs. Higher odds of program provision were associated with public ownership (adjusted odds ratio [AOR]=1.64, 95% confidence interval [CI]=1.37-1.97, p<0.001), facilities serving young adults (AOR=2.16, 95% CI=1.66-2.82, p<0.001) or serving seniors (AOR=1.44, 95% CI=1.27-1.63, p<0.001), and facilities accepting Medicare (AOR=1.34, 95% CI=1.16-1.53, p<0.001), compared with their counterparts, with significant differences across facility ownership types by rurality of locations. Facilities accepting uninsured patients (AOR=0.81, 95% CI=0.68-0.98, p=0.027) or Medicaid patients (AOR=0.76, 95% CI=0.62-0.92, p=0.006) had lower odds of providing these programs. CONCLUSIONS: Facility ownership contributed to significantly different decisions on provision of outpatient suicide prevention programs. Maldistribution of these services should raise concerns, given nationwide efforts to prevent suicide and weak ownership regulations for mental health facilities. Understanding barriers and facilitators for deployment of these programs may improve access to suicide prevention services for all, especially for eligible patients in rural areas.

Changes in community mental health services availability and suicide mortality in the US: a retrospective study.

BACKGROUND: Despite the fact that the overwhelming majority of mental health services are delivered in outpatient settings, the effect of changes in non-hospital-based mental health care on increased suicide rates is largely unknown. This study examines the association between changes in community mental health center (CMHC) supply and suicide mortality in the United States. METHODS: Retrospective analysis was performed using data from National Mental Health Services Survey (N-MHSS) and the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) (2014-2017). Population-weighted multiple linear regressions were used to examine within-state associations between CMHCs per capita and suicide mortality. Models controlled for state-level characteristics (i.e., number of hospital psychiatric units per capita, number of mental health professionals per capita, age, race, and percent low-income), year and state. RESULTS: From 2014 to 2017, the number of CMHCs decreased by 14% nationally (from 3406 to 2920). Suicide increased by 9.7% (from 15.4 to 16.9 per 100,000) in the same time period. We find a small but negative association between the number of CMHCs and suicide deaths (- 0.52, 95% CI - 1.08 to 0.03; p = 0.066). Declines in the number of CMHCs from 2014 to 2017 may be associated with approximately 6% of the national increase in suicide, representing 263 additional suicide deaths. CONCLUSIONS: State governments should avoid the declining number of CMHCs and the services these facilities provide, which may be an important component of suicide prevention efforts.