Hepatic and Systemic Inflammation for Left Ventricular Mass in Physically Fit Adults: CHIEF Heart Study.

BACKGROUND: Both low-grade systemic and hepatic inflammation could result in increased left ventricular mass (LVM) in the general population. However, the associations, which might be modified by exercise, have not been clarified in physically active young adults. METHODS: The study included 2,004 military males aged 18-43 years in eastern Taiwan. Systemic and hepatic inflammation was defined by the upper tertiles of blood white blood cell (WBC) counts (7.51-11.00 x 103/µL) and serum alanine aminotransferase (ALT: 30-120 U/L), respectively. LVM indexed for the body height ≥49 g/m2.7 was defined as left ventricular hypertrophy (LVH) based on echocardiography. Multiple logistic regression analysis adjusting for age, smoking, alcohol intake, physical fitness, and metabolic syndrome was utilized to determine the associations. RESULTS: As compared to the lower WBC/lower ALT group, there tended to have an increased risk of LVH with the higher WBC/lower ALT group, the lower WBC/higher ALT group, and the higher WBC/higher ALT group [odds ratios: 0.89 (95% confidence intervals (CI): 0.41-1.94), 1.90 (95% CI: 0.86-4.22) and 2.48 (95% CI: 1.04-5.92); p-value for trend = 0.01]. CONCLUSION: Our study suggested that in physically active males, those with hepatic inflammation rather than low-grade systemic inflammation had a higher risk of LVH. Hepatic injury might be relevant to LVH as an early sign of end-organ damage regardless of physical fitness in young adults.

High-dose copper activates p53-independent apoptosis through the induction of nucleolar stress in human cell lines.

Copper is an essential micronutrient involved in many redox reactions in human cells. However, a high concentration of copper, intake from the environment or abnormal accumulation within cells because of genetic mutation, leads to cell toxicity. This is attributable to oxidative damage, altered gene expression, and functional impairment of the mitochondria. Copper stress also alters the morphology of the nucleolus, but the process has not been fully elucidated. In this study, cells were treated with copper sulfate at 3-9 ppm and examined if a high dose of copper would block ribosome biogenesis. With the incorrect distribution of nucleolar proteins nucleophosmin and fibrillarin to the nucleoplasm, ribosomal RNA (rRNA) processing was impaired; 34S rRNA from an abnormal A2 cut increased, and downstream pre-rRNAs decreased. The under-accumulation of 60S subunits was detected using sucrose gradients. From transcriptome analysis, ribosome synthesis-related genes were misregulated. Blockage in ribosome synthesis under copper-treatment induced nucleolar stress and triggered p53-independent apoptosis pathways. Thus, nucleolar stress is one cause of cell death under copper exposure.

The Association Between Medicare Low-Income Subsidy and Anticancer Treatment Uptake in Advanced Lung Cancer.

BACKGROUND: High out-of-pocket costs may impact anticancer treatment uptake. The Low-Income Subsidy (LIS) program can reduce patient out-of-pocket cost for Medicare Part D-covered treatments. We examined whether the LIS increased uptake and reduced time to initiate orally administered anticancer drugs in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Using Surveillance, Epidemiology and End Results (SEER)-Medicare data, we identified older adults (aged 65 years and older) diagnosed with advanced NSCLC from 2007 through 2013 and categorized them as full LIS, partial LIS, or non-LIS. We used propensity-score weighted (IPTW) Cox proportional hazards regression to assess the likelihood of and time to initiate Part D treatments. Part B medication uptake was our negative control because supplemental insurance reduces out-of-pocket costs for those drugs. All statistical tests were two-sided. RESULTS: Among 19 746 advanced NSCLC patients, approximately 10% initiated Part D treatments. Patients with partial or no LIS were less likely to initiate Part D treatments than were those with full subsidies (partial LIS vs full LIS HRIPTW = 0.77, 95% confidence interval = 0.62 to 0.97; non-LIS vs full LIS HRIPTW = 0.87, 95% confidence interval = 0.79 to 0.95). Time to initiate Part D treatments was also slightly shorter among full-LIS patients (full LIS mean [SD] = 10.8 [0.04] months; partial LIS mean [SD] = 11.3 [0.08] months; and non-LIS mean [SD] = 11.1 [0.03] months, P < .001). Conversely, patients with partial or no LIS had shorter time to initiation of Part B drugs. CONCLUSIONS: Patients receiving the full LIS had higher orally administered anticancer treatment uptake than patients without LIS. Notably, patients with partial LIS had the lowest treatment uptake, likely because of their low incomes combined with high expected out-of-pocket spending. High out-of-pocket costs for Part D medications may be a barrier to treatment use for patients without full LIS.

Thallium(I) treatment induces nucleolar stress to stop protein synthesis and cell growth.

Thallium is considered as an emergent contaminant owing to its potential use in the superconductor alloys. The monovalent thallium, Tl(I), is highly toxic to the animals as it can affect numerous metabolic processes. Here we observed that Tl(I) decreased protein synthesis and phosphorylated eukaryotic initiation factor 2α. Although Tl(I) has been shown to interact with the sulfhydryl groups of proteins and cause the accumulation of reactive oxygen species, it did not activate endoplasmic reticulum stress. Notably, the level of 60S ribosomal subunit showed significant under-accumulation after the Tl(I) treatment. Given that Tl(I) shares similarities with potassium in terms of the ionic charge and atomic radius, we proposed that Tl(I) occupies certain K+-binding sites and inactivates the ribosomal function. However, we observed neither activation of ribophagy nor acceleration of the proteasomal degradation of 60S subunits. On the contrary, the ribosome synthesis pathway was severely blocked, i.e., the impairment of rRNA processing, deformed nucleoli, and accumulation of 60S subunits in the nucleus were observed. Although p53 remained inactivated, the decreased c-Myc and increased p21 levels indicated the activation of nucleolar stress. Therefore, we proposed that Tl(I) interfered the ribosome synthesis, thus resulting in cell growth inhibition and lethality.

Assessing disruptions in adherence to antidepressant treatments after breast cancer diagnosis.

PURPOSE: Long-term treatment with antidepressants can lessen the symptoms of depression, but health-related crises-such as a cancer diagnosis-may disrupt ongoing depression care. The study aims to estimate the effect of receiving a breast cancer diagnosis on antidepressant adherence among women with depression. METHODS: Using SEER-Medicare administrative claims, we identified women aged 65+ with newly diagnosed breast cancer between 2008 and 2011, who were diagnosed with depression and used antidepressants during the year before pre-diagnosis year. We compared antidepressant adherence among women with breast cancer to similar women without cancer using generalized estimation equations. Antidepressant adherence was estimated using the proportion of days covered 1 year before and after the index date. RESULTS: We included 1142 women with breast cancer and pre-existing depression and 1142 matched non-cancer patients with pre-existing depression. Mean antidepressant adherence was similar for both groups in the year before and after the index date (all around 0.71); adherence decreased by approximately 0.01 following breast cancer diagnosis in cancer group, with similar reductions among non-cancer group (p = 0.19). However, substantial proportion of patients had inadequate adherence to antidepressants in the post-diagnosis period, and almost 40% of patients in each group discontinued antidepressants over the study period. CONCLUSIONS: Antidepressant adherence was not associated with receiving a breast cancer diagnosis beyond what would have been expected in a similar cohort of women without cancer; however, adherence was poor among both groups. Ensuring adequate ongoing depression care is important to improve cancer care and patient quality of life in the long term. Copyright © 2017 John Wiley & Sons, Ltd.

Decreased Power but Preserved Bursting Features of Subthalamic Neuronal Signals in Advanced Parkinson's Patients under Controlled Desflurane Inhalation Anesthesia.

Deep brain stimulation (DBS) surgery of the subthalamic nucleus (STN) under general anesthesia (GA) had been used in Parkinson's disease (PD) patients who are unable tolerate awake surgery. The effect of anesthetics on intraoperative microelectrode recording (MER) remains unclear. Understanding the effect of anesthetics on MER is important in performing STN DBS surgery with general anesthesia. In this study, we retrospectively performed qualitive and quantitative analysis of STN MER in PD patients received STN DBS with controlled desflurane anesthesia or LA and compared their clinical outcome. From January 2005 to March 2006, 19 consecutive PD patients received bilateral STN DBS surgery in Hualien Tzu-Chi hospital under either desflurane GA (n = 10) or LA (n = 9). We used spike analysis (frequency and modified burst index [MBI]) and the Hilbert transform to obtain signal power measurements for background and spikes, and compared the characterizations of intraoperative microelectrode signals between the two groups. Additionally, STN firing pattern characteristics were determined using a combined approach based on the autocorrelogram and power spectral analysis, which was employed to investigate differences in the oscillatory activities between the groups. Clinical outcomes were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) before and after surgery. The results revealed burst firing was observed in both groups. The firing frequencies were greater in the LA group and MBI was comparable in both groups. Both the background and spikes were of significantly greater power in the LA group. The power spectra of the autocorrelograms were significantly higher in the GA group between 4 and 8 Hz. Clinical outcomes based on the UPDRS were comparable in both groups before and after DBS surgery. Under controlled light desflurane GA, burst features of the neuronal firing patterns are preserved in the STN, but power is reduced. Enhanced low-frequency (4-8 Hz) oscillations in the MERs for the GA group could be a characteristic signature of desflurane's effect on neurons in the STN.