Using Mendelian randomization provides genetic insights into potential targets for sepsis treatment.

Sepsis is recognized as a major contributor to the global disease burden, but there is a lack of specific and effective therapeutic agents. Utilizing Mendelian randomization (MR) methods alongside evidence of causal genetics presents a chance to discover novel targets for therapeutic intervention. MR approach was employed to investigate potential drug targets for sepsis. Pooled statistics from IEU-B-4980 comprising 11,643 cases and 474,841 controls were initially utilized, and the findings were subsequently replicated in the IEU-B-69 (10,154 cases and 454,764 controls). Causal associations were then validated through colocalization. Furthermore, a range of sensitivity analyses, including MR-Egger intercept tests and Cochran's Q tests, were conducted to evaluate the outcomes of the MR analyses. Three drug targets (PSMA4, IFNAR2, and LY9) exhibited noteworthy MR outcomes in two separate datasets. Notably, PSMA4 demonstrated not only an elevated susceptibility to sepsis (OR 1.32, 95% CI 1.20-1.45, p = 1.66E-08) but also exhibited a robust colocalization with sepsis (PPH4 = 0.74). According to the present MR analysis, PSMA4 emerges as a highly encouraging pharmaceutical target for addressing sepsis. Suppression of PSMA4 could potentially decrease the likelihood of sepsis.

Understanding China's industrialization driven water pollution stress in 2002-2015-A multi-pollutant based net gray water footprint analysis.

China produces a large amount of industrial effluent with multiple pollutants contained, along with a flourishing economy. This study aims to examine the dynamics between China's industrialization and accompanying environmental pressure based on the gray water footprint (GWF) concept. A newly proposed net GWF (NetGWF) and the decoupling index (DI) are applied to evaluate China's industrial activities during 2002-2015 in different modes considering typical, all, and individual pollutants. The NetGWF dynamics are further quantitatively decomposed into 17 effects of not only commonly assessed drivers but also industrial fixed capital formation, inventory variation, and import, using an advanced dynamic decomposition analysis approach. Results show NetGWF is an effective indicator measuring domestic water pollution stress from industrialization, with NetGWF-AllPlt (estimated using all pollutants) validated to be more reliable and sensitive than NetGWF-COD&NH3N (estimated using Chemical oxygen demand and Ammonia nitrogen). An overall decoupling between China's industrialization and wastewater pollution is identified with most of DIs less than 1.0 caused mainly by decreased (by around 40%) industrial NetGWFs for 2002-2015. Industrial fixed capital formation and export have caused main components of China's industrial GWF, with proportions of 37.3% and 30.8%, respectively, followed by urban household consumption (16.8%). Volatile phenol, Petroleum, and Ammonia nitrogen are recognized as three decisive contaminants to the industrial NetGWFs. Technological development is the dominant contributor (-50%) to decreasing China's industrial NetGWFs, while fixed capital formation (18%) and export (16%) are principal drivers increasing the NetGWFs. Based on these, we expect to provide informative findings for building a pollution-decoupled industrialization.

Epigenetic Age Acceleration and Cognitive Function in African American Adults in Midlife: The Atherosclerosis Risk in Communities Study.

Methylation levels measured at defined sites across the genome have recently been shown to be correlated with an individual's chronological age. Age acceleration, or the difference between age estimated from DNA methylation status and chronological age, has been proposed as a novel biomarker of aging. In this study, the cross-sectional association between two different measures of age acceleration and cognitive function was investigated using whole blood samples from 2,157 African American participants 47-70 years of age in the population-based Atherosclerosis Risk in Communities (ARIC) Study. Cognition was evaluated using three domain-specific tests. A significant inverse association between a 1-year increase in age acceleration calculated using a blood-based age predictor and scores on the Word Fluency Test was found using a general linear model adjusted for chronological age, gender, and years of education (ß = -0.140 words; p = .001) and after adding other potential confounding variables (ß = -0.104 words, p = .023). The results were replicated in 1,670 European participants in the Generation Scotland: Scottish Family Health Study (fully adjusted model: ß = -0.199 words; p = .034). A significant association was also identified in a trans-ethnic meta-analysis across cohorts that included an additional 708 European American ARIC study participants (fully adjusted model: ß = -0.110 words, p = .003). There were no associations found using an estimate of age acceleration derived from multiple tissues. These findings provide evidence that age acceleration is a correlate of performance on a test of verbal fluency in middle-aged adults.

Assessment of older adults' satisfaction with adult protective services investigation and assistance.

This study examined elder self-neglect client satisfaction with services provided by an Adult Protective Services (APS) program. A total of 77 community-dwelling older adults with APS-substantiated self-neglect responded to the standardized and widely used 8-item Client Satisfaction Questionnaire. Approximately 75% of the participants reported being satisfied with the overall services. They felt that the services provided were responsive to their need(s) and helped them deal with their problem(s). Greater than 80% responded that they would refer a friend, would utilize APS in the future if necessary, and were at least satisfied with the amount of help received. The extent to which their needs were met received the lowest satisfaction scores. Future studies are needed to examine elder self-neglect client satisfaction in relation to specific services.

Mesenchymal Stem Cells Combined with Hepatocyte Growth Factor Therapy for Attenuating Ischaemic Myocardial Fibrosis: Assessment using Multimodal Molecular Imaging.

Clinically, myocardial fibrosis is increasingly being recognized as a new therapeutic target for ischaemic heart diseases. The aim of this study was to investigate whether noninvasive multimodal molecular imaging could be used to dynamically assess whether the combination of bone marrow mesenchymal stem cells (BMSCs) and hepatocyte growth factor (HGF) therapy can synergistically attenuate myocardial fibrosis after myocardial infarction (MI). MI was induced in 28 rats by coronary ligation with subsequent injection of BMSCs/HGF, BMSCs, HGF, or saline into the border zone under echocardiography guidance. The therapeutic procedure and treatment effects were tracked and assessed using bioluminescence imaging (BLI) and cardiac magnetic resonance (MR) imaging. Four weeks after transplantation therapy, cardiac MR imaging demonstrated that BMSC/HGF-treated animals showed better ejection fractions (p < 0.001) and smaller scar sizes (p < 0.001) than those treated with BMSCs or HGF alone. Histopathological and immunohistochemical results showed less collagen deposition, increased microvessel densities and more regenerative cardiomyocytes in the BMSC/HGF-treated animals than in those receiving HGF or BMSCs alone (all p < 0.05). Multimodal molecular imaging allows a specific and timely strategy to be established for dynamically tracking treatment and noninvasively assessing the therapeutic effects. Under echocardiography guidance, intramyocardial injection of transfected HGF with BMSCs can enhance cell survival, improve cardiac function, stimulate angiogenesis, and reduce myocardial fibrosis in a post-MI rat model.

Assessment of myocardial edema and area at risk in a rat model of myocardial infarction with a faster T2 mapping method.

BACKGROUND: The common T2 mapping is not suitable for the use in rat heart with high heart rate, unless data are acquired in multiple cardiac cycles. PURPOSE: To evaluate a simplified T2 mapping method for faster assessment of myocardial edema and area at risk in a rat model of myocardial infarction. MATERIAL AND METHODS: The simplified T2 mapping method (TR/TE, 1500 ms/10, 20, 30 ms) was implemented at a 7.0T MRI system. The accuracy of T2 mapping was compared with a standard T2 mapping method (TR, 2500 ms, 16 TEs equally spaced from 11 ms to 176 ms) in thigh muscles in rats (n = 6) and a phantom. This method was further evaluated in normal rats (n = 8) and rats with myocardial infarction (n = 8). Late gadolinium enhancement images were also acquired in the rats with myocardial infarction. RESULTS: T2 values of simplified T2 mapping in the muscles and phantom were 27.3 ± 2 ms and 26.5 ± 1.1 ms, which were similar to the T2 values obtained by the standard T2 mapping method (28.1 ± 1.4 ms, P > 0.05; 26.9 ± 1.7 ms). No significant difference in T2 distribution (different segments and slices from base to apex) in the whole heart was found in normal rats (25.6 ± 3.3 ms, P > 0.05). The mean T2 value in the myocardial edema regions of myocardial infarction rats (37 ± 4.9 ms) was significantly higher than that of the normal rats (25.6 ± 3.3 ms, P < 0.001). The T2 value in the myocardial infarction core of myocardial infarction rats (39.9 ± 3.6 ms) was significantly higher than that of area at risk (34.7 ± 2.9 ms, P < 0.001). CONCLUSION: The simplified myocardial T2 mapping is technically feasible and accurate, and can readily detect myocardial edema and area at risk in rats with high heart rate.

Racial disparities in the use of hospice services according to geographic residence and socioeconomic status in an elderly cohort with nonsmall cell lung cancer.

BACKGROUND: The authors investigated whether there were racial disparities in the receipt of hospice services within geographic residence and socioeconomic status (SES) levels. METHODS: In total, 117,894 patients aged ≥66 years with nonsmall cell lung cancer (NSCLC) were identified from the Surveillance, Epidemiology, and End Results-Medicare linked database who had received hospice services in the last 6 months before death and who died between January 1, 1991 and December 31, 2005. Multivariate odds ratios (ORs) with 95% confidence intervals (CIs) using mixed-effects logistic regression models were used to describe relations. RESULTS: In urban areas, there were significant disparity trends in age/sex-adjusted rates for blacks and Asians/Pacific Islanders compared with whites (P = .003 and P = .036, respectively). Blacks (OR, 0.79; 95% CI, 0.75-0.82), Asians/Pacific Islanders (OR, 0.42; 95% CI, 0.39-0.46), and Hispanics (OR, 0.81; 95% CI, 0.73-0.91) were less likely to receive hospice services. In rural areas, blacks were 21% less likely to receive hospice services (OR, 0.79; 95% CI, 0.63-0.98). Patients in the poorest socioeconomic status (SES) quartile were 7% less likely to receive hospice services (OR, 0.93; 95% CI, 0.86-1.00). Moreover, within stratified SES quartiles, blacks and Asians/Pacific Islanders had lower receipt of hospice services, and Asians/Pacific Islanders were the least likely to receive hospice services, particularly those in the poorest SES quartile. In general, older patients and women were more likely to receive hospice services. CONCLUSIONS: There were substantial disparities in the receipt of hospice services among ethnic minorities within urban and rural areas and within SES levels. The results indicated that efforts are needed to identify barriers, enhance support, and educate patients on the benefits of hospice services.

Racial disparities and survival for nonsmall-cell lung cancer in a large cohort of black and white elderly patients.

BACKGROUND: This study aimed to examine disparities in survival and associated factors for patients with nonsmall-cell lung cancer (NSCLC) and to determine whether racial disparities varied over time (1991-1995, 1996-1999, and 2000-2002). METHODS: The authors studied 70,901 patients aged>or=65 years with stage I-IV NSCLC identified from Surveillance, Epidemiology, and End Results/Medicare data. Multivariate time-to-event survival analyses were completed using Cox proportional regression modeling. RESULTS: The 5-year observed lung cancer-specific survival rates were 52.7% for whites and 47.5% for blacks with stage I-II disease, and 17.7% and 19.6% for whites and blacks, respectively at stages III-IV. After controlling for standard treatment, socioeconomic status (SES), and other factors, there were no significant differences in all-cause mortality, or lung cancer-specific mortality between black and white patients with stage I-II or III-IV lung cancer. However, blacks had an increased risk for overall all-cause mortality at stage I-IV (hazard ratio [HR], 1.24; 95% confidence interval, 1.13-1.35), and during 2000-2002 at stage III-IV for all-cause mortality (HR, 1.22; 95% CI, 1.02-1.47) and lung cancer-specific mortality (HR, 1.24; 95% CI,1.01-1.53). Standard treatment was significantly associated with increased survival, whereas poor SES was associated with increased mortality. CONCLUSIONS: There were no significant differences in survival between blacks and whites with NSCLC within stage stratifications after adjusting for covariates, except for black patients at overall stage for all-cause mortality and at stage III-IV diagnosed in 2000-2002. Receiving stage-specific evidence-based standard therapy was associated with significantly increased survival.

Racial disparities and treatment trends in a large cohort of elderly African Americans and Caucasians with colorectal cancer, 1991 to 2002.

BACKGROUND: Racial differences have been demonstrated in patients who receive treatment for colorectal cancer. However, little is known about whether these disparities have changed over time. The objective of this study was to determine whether racial disparities in receiving standard therapy have declined between 1991 and 2002. METHODS: The study population consisted of 59,803 Caucasians and African Americans aged > or =65 years who were diagnosed with colorectal cancer (American Joint Committee on Cancer stages I, II, and III) between 1991 and 2002 and were identified from the Surveillance, Epidemiology, and End Results Program/Medicare-linked database. Standard therapy for colorectal cancer was defined based on the Physician Data Query guidelines from the National Cancer Institute. The crude and age- and sex-adjusted percentages and the odds ratios (ORs) of receiving standard therapy were reported. RESULTS: From 1991 to 2002, the percentage of patients who did not receive standard therapy for colorectal cancer decreased for both Caucasians (from 24.5% to 22.4%) and African Americans (from 30.4% to 26.4%). Overall, African Americans were 16% less likely to receive standard therapy for colorectal cancer (OR, 0.84; 95% confidence interval [CI], 0.78-0.90) than Caucasians, but the difference was not significant after the analysis was adjusted for other factors (OR, 0.96; 95% CI, 0.88-1.05). The gap for not receiving standard therapy was relatively stable, peaked in 1997 (7.2%), and decreased from 1999 to 2002 (from 7.1% to 4%). CONCLUSIONS: The percentage of patients receiving standard therapy for colorectal cancer increased over time, but disparities remained and decreased in recent years. Future studies should include other ethnic groups and should incorporate provider and system factors that may contribute to treatment disparities.