Cytotoxicity and Apoptotic Mechanism of 2-Hydroxyethyl Methacrylate via Genotoxicity and the Mitochondrial-Dependent Intrinsic Caspase Pathway and Intracellular Reactive Oxygen Species Accumulation in Macrophages.

Macrophages are mainly active cells of the immune system and play a role in the defense of pathogens. However, the overactivation of macrophages by fatal pathogens can result in toxic responses. 2-hydroxyethyl methacrylate (HEMA), which is a hydrophilic monomer, is used in dental adhesive reagents and composite resins as well as biocompatible hydrogels. The mechanisms underlying the genotoxicity engendered by HEMA-induced apoptosis that leads to cytotoxicity remain unclear. Accordingly, this study was conducted to clarify such mechanisms. The results showed that HEMA induced cell toxicity in RAW264.7 macrophages depending on the concentration. A higher HEMA concentration was associated with a higher level of apoptosis and genotoxicity. Moreover, HEMA induced a concentration-dependent increase in mitochondrial dysfunction and the intrinsic caspase pathway, including the activation of caspase-3 and caspase-9. HEMA was also found to upregulate intracellular reactive oxygen species generation and to decrease the activity of antioxidant enzymes, including superoxide dismutase and catalase. Taken together, the mitochondrial-dependent intrinsic caspase pathway and intracellular reactive oxygen species accumulation were found to mediate HEMA-induced genotoxicity and apoptosis, leading to cytotoxicity in RAW264.7 macrophages.

High BRCA1 gene expression increases the risk of early distant metastasis in ER+ breast cancers.

Although the function of the BRCA1 gene has been extensively studied, the relationship between BRCA1 gene expression and tumor aggressiveness remains controversial in sporadic breast cancers. Because the BRCA1 protein is known to regulate estrogen signaling, we selected microarray data of ER+ breast cancers from the GEO public repository to resolve previous conflicting findings. The BRCA1 gene expression level in highly proliferative luminal B tumors was shown to be higher than that in luminal A tumors. Survival analysis using a cure model indicated that patients of early ER+ breast cancers with high BRCA1 expression developed rapid distant metastasis. In addition, the proliferation marker genes MKI67 and PCNA, which are characteristic of aggressive tumors, were also highly expressed in patients with high BRCA1 expression. The associations among high BRCA1 expression, high proliferation marker expression, and high risk of distant metastasis emerged in independent datasets, regardless of tamoxifen treatment. Tamoxifen therapy could improve the metastasis-free fraction of high BRCA1 expression patients. Our findings link BRCA1 expression with proliferation and possibly distant metastasis via the ER signaling pathway. We propose a testable hypothesis based on these consistent results and offer an interpretation for our reported associations.

Change in Activities of Daily Living in the Year Following a Stroke: A Latent Growth Curve Analysis.

BACKGROUND: Early prediction of future functional capability is crucial for stroke survivors' care management. OBJECTIVES: The purposes of this study were to test the trajectory of change across time in activities of daily living (ADLs) and to determine whether the National Institutes of Health Stroke Scale (NIHSS) score within 24 hours poststroke, gender, and age predict ADLs at 1, 3, 6, and 12 months poststroke. METHODS: A prospective cohort design was used. Baseline characteristics and neurological deficits were measured in 1,021 stroke survivors. The 13-item NIHSS was used to examine neurological status within 24 hours poststroke. ADLs were measured with the Barthel index at 1, 3, 6, and 12 months poststroke. A latent growth curve model was used to analyze how the dynamic changes in ADLs were related to NIHSS score, gender, and age. RESULTS: The latent growth curve model analyses revealed that, as the time following a stroke increases, survivors tend to gradually improve with regard to ADLs. In addition, lower levels of initial ADLs were associated with higher growth in ADLs over time. However, after 6 months poststroke, further gains in ADLs slowed. Based on further analysis, the findings indicate that a lower NIHSS score, being male, and a young age at time of stroke were associated with higher initial levels of ADLs. Having a higher NIHSS score, being female, and a young age at time of stroke predicted an increase in ADLs over time. DISCUSSION: To promote ADLs of stroke patients, NIHSS score at admission, gender, and age should be included as important predictors of stroke care management. The results highlight that the rehabilitation of stroke patients should be focused more on ADLs at 1-6 months poststroke.

The Efficacy of 24-Month Metformin for Improving Menses, Hormones, and Metabolic Profiles in Polycystic Ovary Syndrome.

Context: The long-term effects of metformin in women with polycystic ovarian syndrome (PCOS) are inadequately studied. Objective: The effects of metformin on women with PCOS during 24 months with respect to menses, hormones, and metabolic profiles are assessed. Design: Prospective cohort. Setting: A reproductive endocrinology clinic in a university-affiliated medical center. Patients: One hundred nineteen women with PCOS, defined by the Rotterdam criteria, were enrolled. Intervention: Metformin was given daily for 24 months. Main Outcome Measures: The primary outcome was the proportion of patients with regular menstruation during treatment. Changes in anthropometric, hormonal, and metabolic parameters were also assessed. Analyses were performed using segmented regression analysis with a generalized estimating equation methodology. Outcomes are expressed as magnitude of change from the baseline. Results: Both overweight (OW) and normal-weight (NW) women with PCOS had increased menstrual frequency and decreased body mass index (BMI), testosterone, and luteinizing hormone levels in the first 6 months. Further stratification showed that NW women exhibiting elevated testosterone at baseline had the largest magnitude of improvement at 6 months [odds ratio (OR), 7.21; 95% confidence interval (CI), 2.35 to 22.17], whereas OW patients with normal testosterone were most likely to achieve normal menses at 12 months (OR, 0.63; 95% CI, 0.47 to 0.77). Conclusions: Metformin was associated with improvements in the menstrual cycle and most hormonal profiles in OW and NW women with PCOS during 24 months of treatment. Most parameters reached maximal response and steady-state after 6 months. Phenotypic differences in baseline BMI and testosterone level can be used as patient selection criteria or treatment prognostics.

Comparing effects between music intervention and aromatherapy on anxiety of patients undergoing mechanical ventilation in the intensive care unit: a randomized controlled trial.

PURPOSE: Using patient-reported outcomes and physiological indicators to test the effects of music intervention and aromatherapy on reducing anxiety for intensive care unit (ICU) patients undergoing mechanical ventilation. METHODS: Patients with ICU admission duration >24 h were randomly assigned to a Music intervention group (n = 41), Aromatherapy group (n = 47), or Control group (rest only; n = 44). Each patient in the Music group listened to music; each patient in the Aromatherapy group received lavender essential oil massage on his/her back for 5 min; each patient in the Control group wore noise-canceling headphones. Anxiety was measured using the Chinese version of the Stage-Trait Anxiety Inventory (C-STAI) and the Visual Analogue Scale for Anxiety (VAS-A) at baseline, post-test, and 30-min follow-up. Heart rate, breathing rate, and blood pressure were measured every 10 min from baseline to the 30-min follow-up. RESULTS: The Music group had significantly better post-test VAS-A and C-STAI scores, and had lower heart rate and blood pressure than the Control group. The Aromatherapy group had significantly better VAS-A score and lower heart rate than the Control group. The 30-min follow-up showed that both Music and Aromatherapy groups had lower heart rate and blood pressure than the Control group. CONCLUSIONS: Music and aromatherapy interventions were both effective for ICU patients. The effects of music intervention were greater than that of aromatherapy; both interventions maintained the effects for at least 30 min.