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PurposeThe Epworth sleepiness scale (ESS) is a widely used tool which has been validated as a measure of sleepiness. However, the scores within individual patients referred for clinical sleep services vary considerably which may limit the clinical use of the ESS. We sought to determine the test-retest reliability of the ESS if scores were classified as either normal or sleepy.MethodsWe measured the ESS in patients presenting to our sleep center at a clinical visit and again when a sleep study was done. Demographic and clinical information was extracted from the electronic medical record.ResultsAverage ESS scores were similar on 2 administrations, mean (SD) of 9.8 (5.4) and 10.2 (6.2). Bland-Altman analysis showed upper and lower limits of agreement of 7.5 and − 6.7, respectively. No demographic or clinical variables were identified which contributed to the intra-individual variability. Of the patients who presented with an initial ESS < 11, 80% had a second ESS < 11. Of the patients who presented with an initial ESS ≥ 11, 89% had a second ESS ≥ 11. Cohen’s kappa for the two administrations of the ESS was 0.67 (95% CI of 0.51–0.83). Using previously published reports, we calculated Cohen’s kappa for polysomnographic determination of the apnea-hypopnea index (AHI) with values ranging from 0.26 to 0.69.ConclusionsIndividual ESS scores varied considerably within individual patients, but with classification into either normal or sleepy, the test-retest reliability was substantial and in line with other clinical measures including polysomnographic determination of the AHI.

Phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme of serine synthesis, is frequently overexpressed in human cancer. PHGDH overexpression activates serine synthesis to promote cancer progression. Currently, PHGDH regulation in normal cells and cancer is not well understood. Parkin, an E3 ubiquitin ligase involved in Parkinson's disease, is a tumor suppressor. Parkin expression is frequently downregulated in many types of cancer, and its tumor-suppressive mechanism is poorly defined. Here, we show that PHGDH is a substrate for Parkin-mediated ubiquitination and degradation. Parkin interacted with PHGDH and ubiquitinated PHGDH at lysine 330, leading to PHGDH degradation to suppress serine synthesis. Parkin deficiency in cancer cells stabilized PHGDH and activated serine synthesis to promote cell proliferation and tumorigenesis, which was largely abolished by targeting PHGDH with RNA interference, CRISPR/Cas9 KO, or small-molecule PHGDH inhibitors. Furthermore, Parkin expression was inversely correlated with PHGDH expression in human breast cancer and lung cancer. Our results revealed PHGDH ubiquitination by Parkin as a crucial mechanism for PHGDH regulation that contributes to the tumor-suppressive function of Parkin and identified Parkin downregulation as a critical mechanism underlying PHGDH overexpression in cancer.

Unprecedented pollution control actions during the Beijing Olympics provided a quasi-experimental opportunity to examine biologic responses to drastic changes in air pollution levels. To determine whether changes in levels of biomarkers reflecting pulmonary inflammation and pulmonary and systemic oxidative stress were associated with changes in air pollution levels in healthy young adults. We measured fractional exhaled nitric oxide, a number of exhaled breath condensate markers (H(+), nitrite, nitrate, and 8-isoprostane), and urinary 8-hydroxy-2-deoxyguanosine in 125 participants twice in each of the pre- (high pollution), during- (low pollution), and post-Olympic (high pollution) periods. We measured concentrations of air pollutants near where the participants lived and worked. We used mixed-effects models to estimate changes in biomarker levels across the three periods and to examine whether changes in biomarker levels were associated with changes in pollutant concentrations, adjusting for meteorologic parameters. From the pre- to the during-Olympic period, we observed significant and often large decreases (ranging from -4.5% to -72.5%) in levels of all the biomarkers. From the during-Olympic to the post-Olympic period, we observed significant and larger increases (48-360%) in levels of these same biomarkers. Moreover, increased pollutant concentrations were consistently associated with statistically significant increases in biomarker levels. These findings support the important role of oxidative stress and that of pulmonary inflammation in mediating air pollution health effects. The findings demonstrate the utility of novel and noninvasive biomarkers in the general population consisting largely of healthy individuals.

Background And Objectives: Epidemiologie studies have attributed adverse health effects to air pollution; however, controversy remains regarding the relationship between ambient oxidante [ozone (O₃) and nitrogen dioxide (NO₂)] and mortality, especially in Asia. We conducted a fourcity time-series study to investigate acute effects of O₃ and NO₂ in the Pearl River Delta (PRD) of southern China, using data from 2006 through 2008. Methods: We used generalized linear models with Poisson regression incorporating natural spline functions to analyze acute mortality in association with O₃ and NO₂, with PM₁₀ (paniculate matter ≤ 10 μm in diameter) included as a major confounder. Effect estimates were determined for individual cities and for the four cities as a whole. We stratified the analysis according to high-and low-exposure periods for O₃. Results: We found consistent positive associations between ambient oxidants and daily mortality across the PRD cities. Overall, 10-μg/m³ increases in average O₃ and NO₂ concentrations over the previous 2 days were associated with 0.81% [95% confidence interval (CI): 0.63%, 1.00%] and 1.95% (95% CI: 1.62%, 2.29%) increases in total mortality, respectively, with stronger estimated effects for cardiovascular and respiratory mortality. After adjusting for PM₁₀, estimated effects of O₃ on total and cardiovascular mortality were stronger for exposure during high-exposure months (September through November), whereas respiratory mortality was associated with O3 exposure during nonpeak exposure months only. Conclusions: Our findings suggest significant acute mortality effects of O₃ and NO₂ in the PRD and strengthen the rationale for further limiting the ambient pollution levels in the area.

Background: The mutual maintenance model proposes that post-traumatic stress disorder (PTSD) symptoms and chronic physical symptoms have a bi-directional temporal relationship. Despite widespread support for this model, there are relatively few empirical tests of the model and these have primarily examined patients with a traumatic physical injury. Objective: To extend the assessment of this model, we examined the temporal relationship between PTSD and physical symptoms for military personnel deployed to combat (i.e., facing the risk of death) who were not evacuated for traumatic injury. Methods: The current study used a prospective, longitudinal design to understand the cross-lagged relationships between PTSD and physical symptoms before, immediately after, 3 months after, and 1 year after combat deployment. Results: The cross-lagged results showed physical symptoms at every time point were consistently related to greater PTSD symptoms at the subsequent time point. PTSD symptoms were related to subsequent physical symptoms, but only at one time-point with immediate post-deployment PTSD symptoms related to physical symptoms at three months after deployment. Conclusion: The findings extend prior work by providing evidence that PTSD and physical symptoms may be mutually maintaining even when there is not a severe traumatic physical injury. * We followed soldiers from before to after combat and found a high comorbidity of PTSD and physical symptoms.* PTSD and physical symptoms were mutually maintaining among soldiers who did not experience a traumatic injury resulting in hospitalization.

Objectives: Extreme weather events require extensive tree removal and disposal, tasks associated with severe injury risks among workers and residents. To help understand the risks of such activities, we evaluated the impact of a large and destructive storm (Hurricane Sandy in 2012) on the incidence of tree-related injuries. Methods: We searched chief-complaint text fields for patients aged 18-65 from 2011-2014 emergency department visit records submitted by New Jersey hospitals through the state-based syndromic surveillance system. Tree-related keywords (eg, saw, branch, wood chip, woodchip, tree) identified possible injuries that we then reviewed to exclude unrelated cases and classify mechanisms of tree-related injury. We used Poisson regression analysis to evaluate changes in the rates of probable tree-related injuries, adjusting for total emergency department visits and seasonal variation. Results: We identified 698 probable tree-related injuries from 2011-2014 among patients aged 18-65, including 104 (14.9%) falls, 241 (34.5%) machine-related injuries, 311 (44.6%) struck-by injuries, and 42 (6.0%) other tree-related injuries. Tree-related injuries increased significantly in the quarter immediately after Hurricane Sandy (November 2012–January 2013) compared with the same quarter the year before (rate ratio [RR] = 1.67; 95% confidence interval [CI], 1.13-2.47) and the year after (RR = 2.47; 95% CI, 1.62-3.78) Hurricane Sandy, especially for struck-by injuries compared with the year before (RR = 2.74; 95% CI, 1.47-5.12) and the year after (RR = 4.17; 95% CI, 2.09-8.32) Hurricane Sandy. More than one-third of the injuries (33.4%) involved chainsaws. Conclusions: A major hurricane was associated with an increase in tree-related injuries in emergency departments, especially for mechanisms consistent with handling downed and damaged trees. Further research should confirm these findings and evaluate opportunities for preventing tree-related injuries.

Background Pre‐clinical studies suggest that metformin and statins may delay prostate cancer (PCa) metastases; however, data in humans are limited. To the best of our knowledge, this is the first human study aimed to quantify the individual and joint effects of statin and metformin use among patients with high‐risk PCa. Methods This population‐based retrospective cohort study identified patients from the Surveillance, Epidemiology, and End Results (SEER)‐Medicare linked database. Exposure to metformin and statins was ascertained from Medicare Prescription Drug Event files. The association with all‐cause and PCa mortality were evaluated using Cox proportional hazard model with competing causes of death, where propensity scores were used to adjusted imbalances in covariates across groups. Results Based on 12 700 patients with high‐risk PCa, statin alone or in combination with metformin was significantly associated with reduced all‐cause mortality (Hazard Ratio [HR]: 0.89; 95% Confidence Interval [CI]: 0.83, 0.96; and HR: 0.75; 95% CI, 0.67‐0.83, respectively) and PCa mortality (HR, 0.80; 95% CI: 0.69, 0.92) and 0.64; 95% CI, d 0.51‐0.81, respectively. The effects were more pronounced in post‐diagnostic users: combination use of metformin/statins was associated with a 32% reduction in all‐cause mortality (95% CI, 0.57‐0.80), and 54% reduction in PCa mortality (95% CI, 0.30‐0.69). No significant association of metformin alone was observed with either all‐cause mortality or PCa mortality. Conclusions Statin use alone or in combination with metformin was associated with lower all‐cause and PCa mortality among high‐risk patients, particularly in post‐diagnostic settings; further studies are warranted. In this population‐based cohort study of 12 700 high‐risk prostate cancer patients, statin use alone or combined with metformin was significantly associated with lower all‐cause mortality, particularly in post‐diagnostic settings. Randomized clinical trials are warranted to confirm these findings.

Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p<0.0001) and were not linear (from lag 0 to lag 3: p = 0.0629, from lag 3 to lag 6: p = 0.0005). These findings suggest that, among this healthy young adult population, the pulmonary inflammation and oxidative stress pathway is the first to respond to ambient air pollution exposure (within 24 hours) and the hemostasis pathway responds gradually over a 2-3 day period. The initial pulmonary response may contribute to the more gradual systemic changes that likely ultimately involve the cardiovascular system.

Underlying mechanisms by which air pollutants adversely affect human health remain poorly understood. Oxidative stress has been considered as a potential mechanism that may promote lipid peroxidation by reactive oxygen species, leading to the formation of malondialdehyde (MDA) that is excreted in biofluids (e.g., urine and exhaled breath condensate (EBC)). A panel study was conducted to examine whether concentrations of MDA in EBC and urine were associated, respectively, with changes in air pollution levels brought by the Beijing Olympic air pollution control measures. EBC and urine samples from 125 healthy adults were collected twice in each of the pre-, during-, and post-Olympic periods. Period-specific means of MDA and changes in MDA levels associated with increases in 24-h average pollutant concentrations were estimated using linear mixed-effects models. From the pre- to the during-Olympic period, when concentrations of most pollutants decreased, EBC MDA and urinary MDA significantly decreased by 24% ( P <0.0001) and 28% ( P =0.0002), respectively. From the during-Olympic to the post-Olympic period, when concentrations of most pollutants increased, EBC MDA and urinary MDA increased by 28% ( P =0.094) and 55% ( P =0.046), respectively. Furthermore, the largest increases in EBC MDA associated with one interquartile range (IQR) increases in all pollutants but ozone ranged from 10% (95% CI: 2%, 18%) to 19% (95% CI: 14%, 25%). The largest increases in urinary MDA associated with IQR increases in pollutant concentration ranged from 9% (95%: 0.3%, 19%) to 15% (95% CI: 3%, 28%). These findings support the utility of EBC MDA as a biomarker of oxidative stress in the respiratory tract and urinary MDA as a biomarker of systemic oxidative stress in relation to air pollution exposure in healthy young adults. Both EBC and urine samples can be collected noninvasively in the general population.

Oxidative stress is one of the key mechanisms linking ambient particulate matter (PM) exposure with various adverse health effects. The oxidative potential of PM has been used to characterize the ability of PM induced oxidative stress. Hydroxyl radical (•OH) is the most destructive radical produced by PM. However, there is currently no high-throughput approach which can rapidly measure PM-induced •OH for a large number of samples with an automated system. This study evaluated four existing molecular probes (disodium terephthalate, 3′-p-(aminophenyl)fluorescein, coumarin-3-carboxylic acid, and sodium benzoate) for their applicability to measure •OH induced by PM in a high-throughput cell-free system using fluorescence techniques, based on both our experiments and on an assessment of the physicochemical properties of the probes reported in the literature. Disodium terephthalate (TPT) was the most applicable molecular probe to measure •OH induced by PM, due to its high solubility, high stability of the corresponding fluorescent product (i.e., 2-hydroxyterephthalic acid), high yield compared with the other molecular probes, and stable fluorescence intensity in a wide range of pH environments. TPT was applied in a high-throughput format to measure PM (NIST 1648a)-induced •OH, in phosphate buffered saline. The formed fluorescent product was measured at designated time points up to 2 h. The fluorescent product of TPT had a detection limit of 17.59 nM. The soluble fraction of PM contributed approximately 76.9% of the •OH induced by total PM, and the soluble metal ions of PM contributed 57.4% of the overall •OH formation. This study provides a promising cost-effective high-throughput method to measure •OH induced by PM on a routine basis.