Quaternary ammonium compounds (QACs) are among the most commonly used disinfectants. There has been concern that their widespread use will lead to the development of resistant organisms, and it has ...been suggested that limits should be place on their use. While increases in tolerance to QACs have been observed, there is no clear evidence to support the development of resistance to QACs. Since efflux pumps are believe to account for at least some of the increased tolerance found in bacteria, there has been concern that this will enhance the resistance of bacteria to certain antibiotics. QACs are membrane-active agents interacting with the cytoplasmic membrane of bacteria and lipids of viruses. The wide variety of chemical structures possible has seen an evolution in their effectiveness and expansion of applications over the last century, including non-lipid-containing viruses (i.e., noroviruses). Selection of formulations and methods of application have been shown to affect the efficacy of QACs. While numerous laboratory studies on the efficacy of QACs are available, relatively few studies have been conducted to assess their efficacy in practice. Better standardized tests for assessing and defining the differences between increases in tolerance versus resistance are needed. The ecological dynamics of microbial communities where QACs are a main line of defense against exposure to pathogens need to be better understood in terms of sublethal doses and antibiotic resistance.
Extended-release naltrexone, a sustained-release monthly injectable formulation of the full mu-opioid receptor antagonist, is effective for the prevention of relapse to opioid dependence. Data ...supporting its effectiveness in U.S. criminal justice populations are limited.
In this five-site, open-label, randomized trial, we compared a 24-week course of extended-release naltrexone (Vivitrol) with usual treatment, consisting of brief counseling and referrals for community treatment programs, for the prevention of opioid relapse among adult criminal justice offenders (i.e., persons involved in the U.S. criminal justice system) who had a history of opioid dependence and a preference for opioid-free rather than opioid maintenance treatments and who were abstinent from opioids at the time of randomization. The primary outcome was the time to an opioid-relapse event, which was defined as 10 or more days of opioid use in a 28-day period as assessed by self-report or by testing of urine samples obtained every 2 weeks; a positive or missing sample was computed as 5 days of opioid use. Post-treatment follow-up occurred at weeks 27, 52, and 78.
A total of 153 participants were assigned to extended-release naltrexone and 155 to usual treatment. During the 24-week treatment phase, participants assigned to extended-release naltrexone had a longer median time to relapse than did those assigned to usual treatment (10.5 vs. 5.0 weeks, P<0.001; hazard ratio, 0.49; 95% confidence interval CI, 0.36 to 0.68), a lower rate of relapse (43% vs. 64% of participants, P<0.001; odds ratio, 0.43; 95% CI, 0.28 to 0.65), and a higher rate of opioid-negative urine samples (74% vs. 56%, P<0.001; odds ratio, 2.30; 95% CI, 1.48 to 3.54). At week 78 (approximately 1 year after the end of the treatment phase), rates of opioid-negative urine samples were equal (46% in each group, P=0.91). The rates of other prespecified secondary outcome measures--self-reported cocaine, alcohol, and intravenous drug use, unsafe sex, and reincarceration--were not significantly lower with extended-release naltrexone than with usual treatment. Over the total 78 weeks observed, there were no overdose events in the extended-release naltrexone group and seven in the usual-treatment group (P=0.02).
In this trial involving criminal justice offenders, extended-release naltrexone was associated with a rate of opioid relapse that was lower than that with usual treatment. Opioid-use prevention effects waned after treatment discontinuation. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00781898.).
Since DSM-IV was published in 1994, its approach to substance use disorders has come under scrutiny. Strengths were identified (notably, reliability and validity of dependence), but concerns have ...also arisen. The DSM-5 Substance-Related Disorders Work Group considered these issues and recommended revisions for DSM-5. General concerns included whether to retain the division into two main disorders (dependence and abuse), whether substance use disorder criteria should be added or removed, and whether an appropriate substance use disorder severity indicator could be identified. Specific issues included possible addition of withdrawal syndromes for several substances, alignment of nicotine criteria with those for other substances, addition of biomarkers, and inclusion of nonsubstance, behavioral addictions.This article presents the major issues and evidence considered by the work group, which included literature reviews and extensive new data analyses. The work group recommendations for DSM-5 revisions included combining abuse and dependence criteria into a single substance use disorder based on consistent findings from over 200,000 study participants, dropping legal problems and adding craving as criteria, adding cannabis and caffeine withdrawal syndromes, aligning tobacco use disorder criteria with other substance use disorders, and moving gambling disorders to the chapter formerly reserved for substance-related disorders. The proposed changes overcome many problems, while further studies will be needed to address issues for which less data were available.
Superconductivity Poole, Charles P., Jr; Farach, Horacio A; Creswick, Richard J ...
2007, 2010-07-20
eBook
Superconductivity, 2E is an encyclopedic treatment of all aspects of the subject, from classic materials to fullerenes. Emphasis is on balanced coverage, with a comprehensive reference list and ...significant graphicsfrom all areas of the published literature. Widely used theoretical approaches are explained in detail. Topics of special interest include high temperature superconductors, spectroscopy, critical states, transport properties, and tunneling.This book covers the whole field of superconductivity from both the theoretical and the experimental point of view.
- Comprehensive coverage of the field of superconductivity- Very up-to date on magnetic properties, fluxons, anisotropies, etc.- Over 2500 references to the literature - Long lists of data on the various types of superconductors
Mood and substance use disorders commonly co-occur, yet there is little evidence-based research to guide the pharmacologic management of these comorbid disorders. The authors review the existing ...empirical findings, some of which may call into question current clinical pharmacotherapy practices for treating co-occurring mood and substance use disorders. The authors also highlight knowledge gaps that can serve as a basis for future research. The specific mood disorders reviewed are bipolar and major depressive disorders (either one co-occurring with a substance use disorder). Overall, findings from the relatively small amount of available data indicate that pharmacotherapy for managing mood symptoms can be effective in patients with substance dependence, although results have not been consistent across all studies. Also, in most studies, medications for managing mood symptoms did not appear to have an impact on the substance use disorder. In a recent trial for comorbid major depression and alcohol dependence, combination treatment with a medication for depression and another for alcohol dependence was found to reduce depressive symptoms and excessive drinking simultaneously. However, research has only begun to address optimal pharmacologic management of co-occurring disorders. In addition, current clinical treatment for alcohol and drug dependence often excludes new pharmacotherapies approved by the U.S. Food and Drug Administration for treating certain types of addiction. With new data becoming available, it appears that we need to revisit current practice in the pharmacological management of co-occurring mood and substance use disorders.
OBJECTIVE: Some preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study ...examining the association between pioglitazone therapy and the risk of bladder cancer in patients with diabetes. RESEARCH DESIGN AND METHODS: This study includes 193,099 patients in the Kaiser Permanente Northern California diabetes registry who were ≥40 years of age between 1997 and 2002. Those with prior bladder cancer were excluded. Ever use of each diabetes medication (defined as two or more prescriptions within 6 months) was treated as a time-dependent variable. Cox regression-generated hazard ratios (HRs) compared pioglitazone use with nonpioglitazone use adjusted for age, sex, race/ethnicity, diabetes medications, A1C, heart failure, household income, renal function, other bladder conditions, and smoking. RESULTS: The group treated with pioglitazone comprised 30,173 patients. There were 90 cases of bladder cancer among pioglitazone users and 791 cases of bladder cancer among nonpioglitazone users. Overall, ever use of pioglitazone was not associated with risk of bladder cancer (HR 1.2 95% CI 0.9-1.5), with similar results in men and women (test for interaction P = 0.8). However, in the a priori category of >24 months of therapy, there was an increased risk (1.4 1.03-2.0). Ninety-five percent of cancers diagnosed among pioglitazone users were detected at early stage. CONCLUSIONS: In this cohort of patients with diabetes, short-term use of pioglitazone was not associated with an increased incidence of bladder cancer, but use for more than 2 years was weakly associated with increased risk.
The spread of multiple myeloma (MM) involves (re)circulation into the peripheral blood and (re)entrance or homing of MM cells into new sites of the BM. Hypoxia in solid tumors was shown to promote ...metastasis through activation of proteins involved in the epithelial-mesenchymal transition (EMT) process. We hypothesized that MM-associated hypoxic conditions activate EMT-related proteins and promote metastasis of MM cells. In the present study, we have shown that hypoxia activates EMT-related machinery in MM cells, decreases the expression of E-cadherin, and, consequently, decreases the adhesion of MM cells to the BM and enhances egress of MM cells to the circulation. In parallel, hypoxia increased the expression of CXCR4, consequently increasing the migration and homing of circulating MM cells to new BM niches. Further studies to manipulate hypoxia to regulate tumor dissemination as a therapeutic strategy are warranted.
Lesbian, gay, bisexual, and transgender (LGBT) populations experience significant health disparities, theorized to result from LGBT specific minority stressors. The fully conceptualized Minority ...Stress Model was published more than 15 years ago. Minority stressors include external conditions and events, such as discrimination and victimization. Internal minority stressors include expectations of rejection and discrimination, concealment of minority identity, and internalizations of negative dominant cultural attitudes, beliefs, stereotypes, and values. Connection to sexual and gender minority communities is theorized to moderate the effects of minority stressors. In this integrative review, I examine two decades of research on minority stress. Based on this review, I highlight strengths and limitations of the model, and suggest next steps for moving minority stress research forward.
Endospores formed by Bacillus, Clostridia, and related genera are encased in a protein shell called the coat. In many species, including B. subtilis, the coat is the outermost spore structure, and in ...other species, such as the pathogenic organisms B. anthracis and B. cereus, the spore is encased in an additional layer called the exosporium. Both the coat and the exosporium have roles in protection of the spore and in its environmental interactions. Assembly of both structures is a function of the mother cell, one of two cellular compartments of the developing sporangium. Studies in B. subtilis have revealed that the timing of coat protein production, the guiding role of a small group of morphogenetic proteins, and several types of posttranslational modifications are essential for the fidelity of the assembly process. Assembly of the exosporium requires a set of novel proteins as well as homologues of proteins found in the outermost layers of the coat and of some of the coat morphogenetic factors, suggesting that the exosporium is a more specialized structure of a multifunctional coat. These and other insights into the molecular details of spore surface morphogenesis provide avenues for exploitation of the spore surface layers in applications for biotechnology and medicine.
Abstract Introduction Reducing racial/ethnic disparities is a primary objective of the National Alzheimer's Plan (NAPA), yet direct comparisons within large samples representing diversity of the ...United States are lacking. Methods Dementia incidence from January 1, 2000 to December 31, 2013 and a 25-year cumulative risk in 274,283 health care members aged 64+ (n = 18,778 African-American, n = 4543 American Indian/Alaska Native AIAN, n = 21,000 Latino, n = 440 Pacific Islander, n = 206,490 white, n = 23,032 Asian-Americans). Cox proportional hazard models were adjusted for age, sex, medical utilization, and comorbidities. Results Dementia incidence (n = 59,555) was highest for African-Americans (26.6/1000 person-years) and AIANs (22.2/1000 person-years); intermediate for Latinos (19.6/1000 person-years), Pacific Islanders (19.6/1000 person-years), and whites (19.3/1000 person-years) and lowest among Asian-Americans (15.2/1000 person-years). Risk was 65% greater for African-Americans (hazard ratio = 1.65; 95% confidence interval = 1.58–1.72) versus Asian-Americans. Cumulative 25-year risk at age 65 was as follows: 38% African-Americans, 35% AIANs, 32% Latino, 25% Pacific Islanders, 30% white, and 28% Asian-Americans. Discussion Dementia rates varied over 60% between groups, providing a comprehensive benchmark for the NAPA goal of reducing disparities.
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