Lipid Metabolism-Related Gene Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Advanced Gastric Cancer.

Objective: Abnormal lipid metabolism is known to influence the malignant behavior of gastric cancer. However, the underlying mechanism remains elusive. In this study, we comprehensively analyzed the biological significance of genes involved in lipid metabolism in advanced gastric cancer (AGC). Methods: We obtained gene expression profiles from The Cancer Genome Atlas (TCGA) database for early and advanced gastric cancer samples and performed differential expression analysis to identify specific lipid metabolism-related genes in AGC. We then used consensus cluster analysis to classify AGC patients into molecular subtypes based on lipid metabolism and constructed a diagnostic model using least absolute shrinkage and selection operator- (LASSO-) Cox regression analysis and Gene Set Enrichment Analysis (GSEA). We evaluated the discriminative ability and clinical significance of the model using the Kaplan-Meier (KM) curve, ROC curve, DCA curve, and nomogram. We also estimated immune levels based on immune microenvironment expression, immune checkpoints, and immune cell infiltration and obtained hub genes by weighted gene co-expression network analysis (WGCNA) of differential genes from the two molecular subtypes. Results: We identified 6 lipid metabolism genes that were associated with the prognosis of AGC and used consistent clustering to classify AGC patients into two subgroups with significantly different overall survival and immune microenvironment. Our risk model successfully classified patients in the training and validation sets into high-risk and low-risk groups. The high-risk score predicted poor prognosis and indicated low degree of immune infiltration. Subgroup analysis showed that the risk model was an independent predictor of prognosis in AGC. Furthermore, our results indicated that most chemotherapeutic agents are more effective for AGC patients in the low-risk group than in the high-risk group, and risk scores for AGC are strongly correlated with drug sensitivity. Finally, we performed qRT-PCR experiments to verify the relevant results. Conclusion: Our findings suggest that lipid metabolism-related genes play an important role in predicting the prognosis of AGC and regulating immune invasion. These results have important implications for the development of targeted therapies for AGC patients.

Sediment nickel bioavailability and toxicity to estuarine crustaceans of contrasting bioturbative behaviors--an evaluation of the SEM-AVS paradigm.

Robust sediment quality criteria require chemistry and toxicity data predictive of concentrations where population/community response should occur under known geochemical conditions. Understanding kinetic and geochemical effects on toxicant bioavailability is key, and these are influenced by infaunal sediment bioturbation. This study used fine-scale sediment and porewater measurement of contrasting infaunal effects on carbon-normalized SEM-AVS to evaluate safe or potentially toxic nickel concentrations in a high-binding Spartina saltmarsh sediment (4%TOC; 35-45 µmol-S2-·g(-1)). Two crustaceans producing sharply contrasting bioturbation--the copepod Amphiascus tenuiremis and amphipod Leptocheirus plumulosus--were cultured in oxic to anoxic sediments with SEM[Ni]-AVS, TOC, porewater [Ni], and porewater DOC measured weekly. From 180 to 750 µg-Ni·g(-1) sediment, amphipod bioturbation reduced [AVS] and enhanced porewater [Ni]. Significant amphipod uptake, mortality, and growth-depression occurred at the higher sediment [Ni] even when [SEM-AVS]/foc suggested acceptable risk. Less bioturbative copepods produced higher AVS and porewater DOC but exhibited net population growth despite porewater [Ni] 1.3-1.7× their aqueous [Ni] LOEC. Copepod aqueous tests with/without dissolved organic matter showed significant aqueous DOC protection, which suggests porewater DOC attenuates sediment Ni toxicity. The SEM[Ni]-AVS relationship was predictive of acceptable risk for copepods at the important population-growth level.

Self-reported alcohol and drug use six months after brief intervention: do changes in reported use vary by mental-health status?

BACKGROUND: Although brief intervention (BI) for alcohol and other drug problems has been associated with subsequent decreased levels of self-reported substance use, there is little information in the extant literature as to whether individuals with co-occurring hazardous substance use and mental illness would benefit from BI to the same extent as those without mental illness. This is an important question, as mental illness is estimated to co-occur in 37% of individuals with an alcohol use disorder and in more than 50% of individuals with a drug use disorder. The goal of this study was to explore differences in self-reported alcohol and/or drug use in patients with and without mental illness diagnoses six months after receiving BI in a hospital emergency department (ED). METHODS: This study took advantage of a naturalistic situation where a screening, brief intervention, and referral to treatment (SBIRT) program had been implemented in nine large EDs in the US state of Washington as part of a national SBIRT initiative. A subset of patients who received BI was interviewed six months later about current alcohol and drug use. Linear regression was used to assess whether change in substance use measures differed among patients with a mental illness diagnosis compared with those without. Data were analyzed for both a statewide (n = 828) and single-hospital (n = 536) sample. RESULTS: No significant differences were found between mentally ill and non-mentally ill subgroups in either sample with regard to self-reported hazardous substance use at six-month follow-up. CONCLUSION: These results suggest that BI may not have a differing impact based on the presence of a mental illness diagnosis. Given the high prevalence of mental illness among individuals with alcohol and other drug problems, this finding may have important public health implications.

Reaction of N-acylhomoserine lactones with hydroxyl radicals: rates, products, and effects on signaling activity.

Chemical communication in bacteria, sometimes called quorum sensing, is a fundamental microbial process that is based on the exchange of molecular signals between cells. The signaling molecules involved in this process are thermodynamically unstable in some environments and their degradation affects microbial communication. This work reports the oxidation of a series of substituted N-acylhomoserine lactones (AHLs, a class of quorum sensing signals) by hydroxyl radicals. The corresponding bimolecular rate constants were obtained and correlated positively with the length of the acyl side chain (C, in numbers of carbon atoms) ranging from 2.4 × 10(9) M(-1) s(-1) to 9.4 × 10(9) M(-1) s(-1) (C4- to C10-AHL), 2.4 × 10(8) M(-1) s(-1) for 3-oxo C6-AHL, and 2.94 × 10(9) M(-1) s(-1) for 3-oxo C8-AHL. Liquid chromatography-mass spectrometric techniques were applied to qualify the identity and quantify the yields of the hydroxyl radical oxidation products of C6-AHL (aldo, keto, and hydroxylated C6-analogues identified). The biological activity of C6-AHL and associated products was determined using the Vibrio harveyi bioluminescence bioassay. Oxidation resulted in a net increase in assay response indexed against the starting AHL. This result suggested that the application of HO• based technologies such as advanced oxidation processes for biofilm control may result in unintended quorum sensing responses by microbial communities.

The use of administrative data as a substitute for individual screening scores in observational studies related to problematic alcohol or drug use.

Administrative data provide a rich resource for improving our understanding of individuals with substance use disorders. The validation of administrative proxies for moderate or high risk alcohol or drug (AOD) use could enhance the ability to carry out rigorous observational research (for example, for use in the construction of comparison groups). This study used receiver operating characteristic (ROC) curve techniques to assess how well AOD-related administrative indicators predicted self-reported AOD use obtained from AUDIT/DAST screening scores. An administrative AOD indicator, derived from a combination of medical encounter and billing data, arrest records, and publicly funded AOD-related services data, demonstrated discrimination in the acceptable range (AUC: 0.72-0.78) for identifying self-reported AOD use consistent with potential need for either (1) any AOD-related intervention, or (2) intensive AOD-related intervention or treatment. These findings held up in two distinct samples: a statewide Medicaid-only sample and a single-site mixed-payer sample that included the uninsured. Our findings suggest that indicators of AOD-related problems derived from administrative data can be useful for identifying moderate or high risk AOD use in a research context. The findings further suggest that proxies for substance use disorders, such as those evaluated here, can enhance future observational studies intended to improve health care for this population.

Impact of brief interventions and brief treatment on admissions to chemical dependency treatment.

This study examined two issues. One, whether individuals with possible substance use disorders were more likely to be admitted to specialized chemical dependency (CD) treatment after receiving a brief intervention (BI) - either alone or in combination with other services - than similar individuals who did not receive a BI. Two, whether participation in brief treatment (BT) following a BI was helpful in facilitating admission to CD treatment. The study took place in the emergency department (ED) of a large urban safety-net hospital where CD professionals screened patients for alcohol/drug problems and provided BI, BT, and referral to specialized CD treatment when appropriate (SBIRT). Substance use disorders were indicated by alcohol/drug problems noted in administrative records. Hospital records were used to match patients with likely substance use disorders who received BI with similar ED patients who had not been screened. Admission to publicly funded CD treatment was determined by matching patient identifiers to state administrative records of CD treatment. Results indicated that individuals with a likely substance use disorder who received a BI (regardless of subsequent participation in BT) were significantly more likely to enter specialized CD treatment in the subsequent year than similar individuals who did not receive a BI. This result was particularly pronounced for patients with no CD treatment in the past two years. Results also indicated that participation in BT facilitated admission into CD treatment. The results suggest that SBIRT programs could serve an important role in increasing entry to specialized treatment for individuals with substance use disorders.

Evaluation of the Washington state screening, brief intervention, and referral to treatment project: cost outcomes for Medicaid patients screened in hospital emergency departments.

BACKGROUND: Substance abuse is a major determinant of morbidity, mortality, and health care resource consumption. We evaluated a screening, brief intervention, and referral to treatment (SBIRT) program, implemented in 9 hospital emergency departments (ED) in Washington State. METHODS: Working-age, disabled Medicaid patients who were screened and received a brief intervention (BI) from April 12, 2004 through September 30, 2006 were included in the study's intervention group (N = 1557). The comparison group (N = 1557), constructed using (one-to-one) propensity score matching, consisted of Medicaid patients who received care in one of the counties in which an intervention hospital ED was located but who did not receive a BI. We estimated difference-in-difference (DiD) regression models to assess the effects of the SBIRT program for different patient groups. RESULTS: The SBIRT program was associated with an estimated reduction in Medicaid costs per member per month of $366 (P = 0.05) for all patients, including patients who received a referral for chemical dependency (CD) treatment. For patients who received a BI only and had no CD treatment in the year before or the year after the ED visit, the estimated reduction in Medicaid per member per month costs was $542 (P = 0.06). The SBIRT program was also associated with decreased inpatient utilization (P = 0.04). CONCLUSION: SBIRT programs have potential to limit resource consumption among working-age, disabled Medicaid patients. The hospital ED seems especially well suited for SBIRT programs given the large number of injured patients treated in the ED and the fact that many conditions treated are related to substance abuse.

Autoinducers extracted from microbial mats reveal a surprising diversity of N-acylhomoserine lactones (AHLs) and abundance changes that may relate to diel pH.

Microbial mats are highly structured and diverse communities, and one of the earliest-known life assemblages. Mat bacteria interact within an environment marked by strong geochemical gradients and fluctuations. We examined natural mat systems for the presence of autoinducers involved in quorum sensing, a form of cell-cell communication. Our results revealed that a diverse array of N-acylhomoserine lactones (AHLs) including C(4)- to C(14)-AHLs, were identified from mat extracts using mass spectrometry (MS), with further confirmation by MS/MS-collision-induced dissociation (CID), and additions of external standards. Microelectrode measurements showed that mats exhibited diel pH fluctuations, ranging from alkaline (pH 9.4) during daytime (net photosynthesis) to acidic (pH 6.8) during darkness (net respiration/fermentation). Under laboratory conditions, AHLs having shorter acyl-chains were degraded within the time frame that daily alkaline pH (> 8.2) conditions exist in mats. Intensive sampling of mats after full day- or night-time incubations revealed that accumulations of extractable shorter-chain AHLs (e.g. C(8)- and C(10)-AHLs) were significantly (P < 0.001) diminished during daytime. Our study offers evidence that stabilities of AHLs under natural conditions may be influenced by the proximal extracellular environment. We further propose that the ancient periodicity of photosynthesis/respiration in mats may potentially drive a mechanism for diel differences in activities of certain autoinducers, and hence bacterial activities mediated through quorum sensing.

Risk assessment of the National Institute of Standards and Technology petroleum crude oil standard water accommodated fraction: further application of a copepod-based, full life-cycle bioassay.

The U.S. National Institute of Standards and Technology (NIST) petroleum crude oil was used to generate NIST water-accommodated hydrocarbon fractions (WAFs) for standardized assessment of crude oil effects on the copepod Amphiascus tenuiremis. Effects were assessed using a 96-well microplate, full life-cycle test. Briefly, nauplii (age, 24 h) were reared individually to adults (n > or =120 nauplii/treatment) in microplate wells containing 200 microl of treatment solution (seawater control [0%] or 10, 30, 50, or 100% NIST-WAF). Nauplii were monitored through development to adulthood, and mature virgin male:female pairs mated in wells containing original treatments (<30 d). A second bioassay using 0, 10, 30, and 50% WAFs (n > or =60 nauplii/treatment) was conducted to assess the effects of ultraviolet (UV) light on naupliar endpoints (<16 d). In the first experiment, nauplius-to-copepodite survival in exposures to 100% WAF was 27% +/- 6% lower than in controls (92% +/- 1%), but copepodite-to-adult survival was greater than 90% across all treatments. Analysis of development curves showed that nauplii in the 10% WAF developed into copepodites 25% faster, whereas nauplii in the 50 and 100% WAFs developed 17% slower, than controls. Copepodite development into male and female copepods was significantly delayed (2 and 4 d, respectively) in the 100% WAF compared to controls. Although none of the WAF exposures had significant effects on fertilization success or total viable production (p > 0.05), embryo hatching in the 100% WAF was significantly less (70.0% +/- 21.2%) than that in controls (87.0% +/- 19.4%). Results from the UV bioassay showed that relatively short exposures (<14 d) to 30 and 50% WAFs in the presence of UV light caused negative effects on copepod survival and development. Naupliar-stage survival and developmental endpoints were the most sensitive indicators of exposure to the NIST crude oil WAF

Treatment readmissions and criminal recidivism in youth following participation in chemical dependency treatment.

The purpose of this study was to use administrative records of admissions to substance abuse treatment to construct episodes of care for publicly funded adolescent clients in Washington State, and then to analyze two important outcomes after an index episode: readmissions to treatment and criminal convictions (including felony convictions and any conviction). The study population was youth, ages 14 to 17, who began and ended an index episode in 1997 and 1998 (n=5903). The youth were followed for 18 months after the end of their episode, and survival analysis techniques were used to determine the treatment correlates of the outcomes. Clients who completed treatment, compared to those who did not, had significantly lower risks of each outcome, while those with treatment episodes longer than 90 days had lower risks of readmission and felony convictions.