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In contrast, EGFR activity was necessary for the increase in cell speed, as it was reversed with an EGFR inhibitor, AG1478, but was not necessary to enhance persistence and protrusion length. From these data, we were able to isolate both EGFR-dependent and -independent features of cell migration that were enhanced by chronic arsenic exposure.

The critical role of long non-coding RNAs (lncRNAs) has been implicated in prostate cancer (PCa). As one of them, LINC00992 (LNC992) has been revealed by bioinformatics prediction to be significantly overexpressed in PCa. However, the underlying mechanism of LNC992 in PCa has not been well investigated.

First, gene expression microarrays of prostate adenocarcinoma (PRAD) were downloaded from the GEO database, and differentially expressed genes were analyzed. Subsequently, we assessed the LNC992 expression in PCa patients. PCa cells with overexpression or low expression of LNC992 were generated, followed by the examination of proliferation, invasion and migration in vitro and in vivo. The differentially expressed genes were analyzed by microarrays after altering LNC992 expression in PCa cells, and the downstream regulatory mechanisms of LNC992 were analyzed by bioinformatics analysis and validated by RIP and RNA pull-down assays.

LNC992 was highly expressed in the PRAD database and in cancer tissues from PCa patients, serving as a poor prognostic factor for PCa patients. Knockdown of LNC992 significantly inhibited PCa cell growth, metastasis, and angiogenesis in vitro and in vivo. Moreover, we found that knockdown of LNC992 significantly suppressed SOX4 expression in cells and that LNC992 could bind to EIF4A3 and promote the translation of SOX4. Inhibition of either EIF4A3 or SOX4 significantly suppressed the growth and metastasis of PCa cells.

LNC992 elevates SOX4 expression by binding to SOX4 mRNA and recruiting translation initiation factor EIF4A3, thereby promoting the growth and metastasis of PCa cells in vitro and in vivo.

LNC992 elevates SOX4 expression by binding to SOX4 mRNA and recruiting translation initiation factor EIF4A3, thereby promoting the growth and metastasis of PCa cells in vitro and in vivo.Although body mass index (BMI) is considered a key determinant of high blood pressure, its importance may differ over time and by age group. We utilised separate data sources to investigate temporal changes in this association 23 independent (newly sampled), repeated cross-sectional studies (Health Survey for England (HSE)) at ≥25 years (1994-2018; N = 126,742); and three British birth cohorts at 43-46 years (born 1946, 1958, and 1970; N = 18,657). In HSE, associations were weaker in more recent years, with this trend most pronounced amongst older adults. After adjustment for sex, anti-hypertensive treatment and education, the mean difference in systolic blood pressure (SBP) per 1 kg/m2 increase in BMI amongst adults ≥55 years was 0.75 mmHg (95%CI 0.60-0.90) in 1994, 0.66 mmHg (0.46-0.85) in 2003, and 0.53 mmHg (0.35-0.71) in 2018. In the 1958 and 1970 cohorts, BMI and SBP associations were of similar magnitude yet weaker in the 1946 cohort, potentially due to differences in blood pressure measurement device. Quantile regression analyses suggested that associations between BMI and SBP were present both below and above the hypertension threshold. A weaker association between BMI and blood pressure may partly offset the public health impacts of increasing obesity prevalence. However, despite sizable increases in use of antihypertensive medication, BMI remains positively associated with SBP in all ages. Our findings highlight the need to tackle non-medical factors such as population diet which influence both BMI and blood pressure, and the utility of using multiple datasets to obtain robust inferences on trends in risk factor-outcome associations across time.Prevalence of multimorbidity (i.e., ≥2 chronic conditions), chronic diseases, and obesity is increasing in low- and middle-income countries (LMICs), posing a potential threat to the health of older adults living in these areas. This study hence investigates the unexplored association between obesity and multimorbidity among older adults from LMICs. Cross-sectional, community-based data from the WHO Study on global Ageing and adult health (SAGE) were analysed. The sample consisted of 20,198 individuals aged ≥60 years [Mean age (SD) = 69.3 (13.1) years; 54.1% female] from China, India, Ghana, Mexico, Russia, South Africa. Twelve chronic conditions were assessed. Multivariable logistic regression was conducted to assess the association between BMI ≥ 30 kg/m2, high waist circumference (WC, cut-points > 102 cm for males and > 88 cm for females) and multimorbidity. After adjusting for potential confounders, overall, BMI ≥ 30 kg/m2 was associated with 1.43 (95%CI = 1.21-1.69) times higher odds for multimorbidity, while this estimate for high WC was 1.50 (95%CI = 1.21-1.86). Significant associations emerged between obesity measures and five out of twelve chronic conditions. Results from this study underline the need to reduce obesity among older adults in areas where its prevalence is increasing, as it is associated with increased odds for multimorbidity. Future longitudinal research in this setting is required to assess the impact of obesity reduction on multimorbidity incidence.Firearm access is a risk factor for firearm suicide; substance use may confer additional risk. In this retrospective cohort study, we estimated the associations between prior alcohol and drug charges at the time of handgun purchase and subsequent suicide among men in California. The sample comprised all men who legally purchased a handgun in California in 2001 and who were age ≥ 21 at the time of acquisition (N = 101,377), identified in the California Department of Justice (CA DOJ) Dealer's Record of Sale database. Exposures included alcohol and drug criminal charges and convictions accrued January 1, 1990 until the first ('index') handgun acquisition in 2001, recorded in the CA DOJ Criminal History Information System. Outcomes included suicide and firearm suicide occurring after the index purchase and before January 1, 2016. A total of 1907 purchasers had alcohol charges, 1248 had drug charges, and 304 had both; 594 purchasers died by suicide (516 by firearm suicide). Compared with those with neither alcohol nor drug charges, those with alcohol charges had 2.20 times the hazard of suicide (95% confidence interval [CI], 1.39-3.46) and 2.22 times the hazard of firearm suicide (95% CI, 1.36-3.62). Risk was most elevated among those with more recent charges and those with 2 or more charges, and in the time period closest to the purchase. The associations for drug charges and the combination of alcohol and drug charges were not distinguishable from the null. Firearm owners with alcohol offenses may benefit from intervention to reduce firearm access and alcohol use.Carotid intima-media thickness (cIMT), plaque quantification and coronary artery calcium (CAC) scoring have been suggested to improve risk prediction of cardiovascular disease (CVD), particularly for asymptomatic individuals classified as low-to-intermediate risk. We aimed to compare the predictive value of cIMT, carotid plaque identification, and CAC scoring for identifying sub-clinical atherosclerosis and assessing future risk of CVD in asymptomatic, low-to-intermediate risk individuals. We conducted a comprehensive search of Ovid (Embase and Medline), Cochrane Central Register of Controlled Trials (CENTRAL) and Medline complete (EBSCO health). A total of 30 papers were selected and data were extracted. Comparisons were made according to the cIMT measurement (mean, maximum), carotid plaque evaluation (presence or area), and CAC scoring. CVD event rates, hazard ratios (HR), net reclassification index (NRI), and c-statistic of the markers were compared. There were 27 studies that reported cIMT, 24 reported carotid plaque, and 6 reported CAC scoring. Inclusion of CAC scores yielded the highest HR ranging from 1.45 (95% CI, 1.11-1.88, p = 0.006) to 3.95 (95% CI, 2.97-5.27, p less then 0.001), followed by maximum cIMT (HR 1.08; 95% CI, 1.06-1.11, p less then 0.001 to 2.58; 95% CI, 1.83-3.62, p less then 0.001) and carotid plaque presence (HR 1.21; 95% CI, 0.5-1.2, p = 0.39 to 2.43; 95% CI, 1.7-3.47, p less then 0.001). The c-statistic enhanced predictive value by a minimum increase of 0.7. Finally, the NRI ranked higher with CAC (≥11.2%), followed by carotid plaque (≥2%) and cIMT (3%). CAC scoring was superior compared to carotid plaque and cIMT measurements in asymptomatic individuals classified as being at low-to-intermediate risk.Despite the benefits of factorial designs in quantifying the relative benefits of different school-based approaches to prevent unhealthy weight gain among students, few have been undertaken. The aims of this 2 × 2 cluster randomized factorial trial was to evaluate the impact of a physical activity and nutrition intervention on child weight status and quality of life. Twelve primary schools in New South Wales, Australia randomly allocated to one of four groups (i.) physical activity (150 min of planned in-school physical activity); (ii.) nutrition (a healthy school lunch-box); (iii.) combined physical activity and nutrition; or (iv.) control. Outcome data assessing child weight and quality of life were collected at baseline and 9-months post-baseline. Within Grades 4-6 in participating schools, 742 students participated in anthropometric measurements, including child body mass index (BMI) and waist circumference, at baseline and follow-up. Findings indicated that students that received the nutrition intervention had higher odds of being classified in the BMI category of underweight/healthy weight (OR 1.64 95%CI 1.07, 2.50; p = 0.0220), while those who received the physical activity intervention reported a lower waist circumference (mean difference - 1.86 95%CI -3.55, -0.18; p = 0.030). There were no significant effects of the nutrition or physical activity intervention on child BMI scores or child quality of life, and no significant synergistic effects of the two interventions combined. Future research assessing the longer-term impact of both intervention strategies, alone and combined, is warranted to better understand their potential impact on child health. TRIAL REGISTRATION Australian Clinical Trials Registry ACTRN ACTRN12616001228471.The coronavirus disease 2019 (COVID-19) pandemic has been associated with a declining volume of patients seen in the emergency department. this website Despite the need for seeking urgent care for conditions such as myocardial infarction, many people may not seek treatment. This study seeks to measure associations between the COVID-19 pandemic and location of death among individuals who died from ischemic heart disease (IHD). Data obtained from death certificates from the Arkansas Department of Health was used to conduct a difference-in-difference analysis to assess whether decedents of IHD were more likely to die at home during the pandemic (March 2020 through September 2020). The analysis compared location of death for decedents of IHD pre and during the pandemic to location of death for decedents from non-natural causes. Before the pandemic, 50.0% of decedents of IHD died at home compared to 57.9% dying at home during (through September 2020) the pandemic study period (p less then .001). There was no difference in the proportion of decedents who died at home from non-natural causes before and during the pandemic study period (55.