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Objective: To explore the feasibility and utility of a tolerance break (T-Break) guide on young adults' cannabis use. Participants: Young adults aged 18-29 (n = 125) who were current cannabis users. Methods: Participants recruited through posters and listservs at various universities were offered the T-Break Guide-daily activities, advice, and encouragement-to help complete a 21-day cannabis break. Bivariate analyses examined associations between Guide use and follow-up measures. Results: Compared to non-Guide users, participants who used the Guide "a lot" were more likely to complete the 21-day abstinence break (84% vs. 57%), revise their personal definition of balance to mean less cannabis (84% vs. 62%), and plan a future break (32% vs. 11%). Conclusion: Use of this self-directed T-Break Guide may help young adults take a break from cannabis use and reduce future use. Further research using more rigorous designs to test the Guide's efficacy and assess longer-term maintenance of effects is needed.

Introduction: Considering recent and proposed bans on menthol cigarettes, methods are needed to understand the substitutability of potential menthol cigarette alternatives (MCAs) for menthol cigarettes. This study examined the prospective relationship between behavioral economic demand indices and subjective effects of usual brand menthol cigarettes (UBMC) and preferred MCAs with subsequent performance on a laboratory-based concurrent-choice task comparing UBMC and MCAs., Methods: Eighty participants who typically smoked menthol cigarettes completed this clinical laboratory study. After sampling each product, participants completed the cigarette purchase task (CPT) and modified cigarette evaluation questionnaire (mCEQ). Following 1 week of substituting their preferred MCA for their UBMC, participants completed a 90-minute concurrent-choice self-administration (SA) task comparing their UBMC and preferred MCA. Linear regression models explored associations between CPT demand indices and mCEQ subjective effects in the laboratory with subsequent response effort for UBMCs on the concurrent-choice task., Results: Three demand indices for UBMC were positively associated with UBMC response effort: essential value (EV; p = .02), Omax (p = .02), and breakpoint (p = .04). Four CPT demand indices for the preferred MCA significantly corresponded with UBMC response effort: EV (p = .03), price associated with maximal expenditure (Pmax) (p = .04), maximal expenditure (Omax) (p = .03), and breakpoint (p = .03). Subjective effects captured by the mCEQ were not associated with response effort., Conclusions: Demand indices reflecting Persistence (ie, sensitivity to escalating price) predicted effort to obtain UBMC puffs on the concurrent-choice task. Among this sample, the CPT captured information on the relative reinforcing value (ie, addiction potential) of combustible tobacco products similar to the longer SA task., Implications: In an ever-changing product market, assessing the reinforcing efficacy of menthol cigarettes and putative substitutes quickly and with validity is an important methodological tool for understanding abuse liability. Results suggest that behavioral economic demand indices of CPT efficiently capture information on the relative reinforcing value of UBMC and plausible alternative tobacco products, similar to a 90-minute in-laboratory SA task., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Disability is identified in surveys using various question sets, with little understanding of reliability across these measures, nor how these estimates may vary across age groups, including adolescents and young adults (AYA). The purpose of this study was to assess AYA prevalence of disability using two disability question sets and reliability of these measures., Methods: AYA participants in the Policy and Communication Evaluation (PACE) Vermont Study completed a single-item disability question used in the National Survey on Health and Disability (NSHD) and Urban Institute's Health Reform Monitoring Survey (HRMS) and a six-item set on functioning (Washington Group-Short Set, WG-SS) from the National Health Interview Survey (NHIS) and National Survey on Drug Use and Health (NSDUH) in 2021. Prevalence was estimated for any disability and each disability domain in adolescents (ages 12-17) and young adults (ages 18-25) and compared with U.S. national estimates in NHIS and NSDUH., Results: Using the WG-SS, the prevalence of any disability was 17.0 % in PACE Vermont adolescents and 22.0 % in young adults, consistent with the national prevalence of adolescents in NSDUH (17.9 %) but higher than estimates of young adults in NHIS (3.9 %) and NSDUH (12.9 %). The single-item question provided lower estimates of disability (adolescents: 6.9 %; young adults: 18.5 %) than the WG-SS, with low positive agreement between measures., Discussion: The prevalence of disability in AYAs varies depending on measures used. To improve disability surveillance, it may be necessary to validate new disability questions, including among AYAs, to capture a broader range of disability domains., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors have no conflicts of interest to disclose. Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R21DA051943. Effort of the authors was also provided by the National Institute on Drug Abuse of the National Institutes of Health under Award Numbers U54DA036114 (JAS, JCW) and by grant #90IFRE0050 from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) within the Administration on Community Living, Department of Health and Human Services. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or HHS. The NIH had no role in study design, data collection or analysis, or preparation and submission of the manuscript., (© 2024 The Author(s).)

Background: Nicotine vaping is more prevalent among U.S. adults with disabilities compared to those without disabilities. However, less is known about nicotine vaping among adolescents (12-17 years) and young adults (18-25 years) by disability status., Methods: Using data from a sample of 24,722 adolescents and young adults (AYAs) from the 2021 National Survey on Drug Use and Health, we conducted descriptive and multivariable analyses to estimate the national prevalence of nicotine vaping by disability type and examined major depressive episodes (MDEs) as a risk factor for nicotine vaping., Results: A greater proportion of AYAs with disabilities engaged in past-month nicotine vaping compared to those without a disability (13.9 % vs 9.6 %, p = 0.0001). Also, when MDE was excluded from the model, AYAs with any disability had higher odds of nicotine vaping (AOR = 1.41; 95 % CI 1.15, 1.74) than those without a disability. However, disability status was no longer significant when MDE was included (AOR = 1.16; 95 % CI 0.91, 1.46) in the model., Conclusions: The higher prevalence of nicotine vaping among AYAs with disabilities suggests that tailored messages may be needed to communicate health risks and adverse outcomes of e-cigarette use. Also, MDE is associated with nicotine vaping among AYA populations. This information can be helpful to school nurses, counselors, and mental health professionals in their screening of major depression as a risk factor for e-cigarette use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To estimate the national prevalence of tobacco, marijuana, and alcohol use among U.S. adolescents (age 12-17) and young adults (aged 18-25; adolescents and young adults [AYAs]) with a disability and examine associations between disability and substance use from 2015 to 2019., Methods: Data from the 2015-2019 National Survey on Drug Use and Health were used to estimate the prevalence of tobacco, marijuana, and alcohol use among AYAs with disabilities. Modified Poisson regression models evaluated linear time trends in past-month substance use and estimated adjusted prevalence ratios (aPRs) for past-month cigarette, any tobacco, alcohol, and marijuana use., Results: Adolescents with any disability had a higher prevalence of past-month cigarette (aPR = 1.87; 95% CI 1.67-2.09), alcohol (aPR = 1.21; 95% CI 1.11-1.31), and marijuana use (aPR = 1.47; 95% CI 1.36-1.60) compared to those without disabilities. Cigarette smoking among adolescents decreased over this time period; however, the decline among adolescents without a disability was greater than those with any disability. Young adults with any disability had a higher prevalence of past-month cigarette (aPR = 1.42; 95% CI 1.35-1.48) and marijuana use (aPR = 1.39; 95% CI 1.34-1.45), but a lower prevalence of past-month alcohol use (aPR = 0.93; 95% CI 0.90-0.95) than those without disabilities. Alcohol use remained constant among young adults with any disability but decreased for those without disabilities., Discussion: Population-level disparities in cigarette and marijuana use exist in AYAs with disabilities. Future studies should identify strategies tailored to AYAs with disabilities to encourage smoking cessation and prevent cannabis use disorder., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The Food and Drug Administration (FDA) has issued proposed product standards banning menthol as a characterising flavour in cigarettes and cigars. The public health benefits of these product standards may be attenuated by the role of plausible substitutes in the marketplace. Therefore, the present study examined the addiction potential of plausible combustible menthol alternatives compared with usual brand menthol cigarettes (UBMC)., Methods: Ninety-eight adult menthol cigarette smokers completed four visits, smoking their UBMC at the first session and three menthol cigarette alternatives in random order at the subsequent visits: (1) a preassembled menthol roll-your-own (mRYO) cigarette using menthol pipe tobacco and mentholated cigarette tube, (2) a menthol filtered little cigar (mFLC) and (3) a non-menthol cigarette (NMC). Measures of smoking topography, exhaled carbon monoxide (CO), craving and withdrawal, subjective effects and behavioural economic demand indices were assessed., Results: Compared with UBMC, menthol cigarette alternatives resulted in different puffing topography and CO exposure (except mRYO), and lower levels of positive subjective experience and behavioural economic demand indices. Among the alternative products, participants reported the highest level of positive subjective experience and higher demand for mRYO, compared with mFLC and NMC. Similarly, participants were significantly more likely to want to try again, purchase and use the mRYO product regularly compared with mFLC and NMC., Conclusions and Relevance: mRYO cigarettes were the most highly rated cigarette alternative among study products, suggesting their potential appeal as a menthol cigarette substitute and needed inclusion of menthol pipe tobacco and cigarette tubes in FDA's proposed ban., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: People with disabilities disproportionately use tobacco products. However, little is known about cessation interventions tailored for people with disabilities. The objective of this study was to conduct a systematic review of smoking cessation interventions for adults with disabilities., Methods: Six electronic databases (Cochrane, CINAHL Plus [EBSCOhost], Embase [Ovid], Medline [Ovid], PsycINFO [Ovid], and Web of Science) were searched to identify eligible interventions for people with disabilities (e.g., vision, hearing, mobility, communication, cognition, self-care) through July 2023. Two independent coders evaluated the records and extracted data from studies that met inclusion criteria. Qualitative synthesis was conducted on the included studies in 2023., Results: One randomized controlled trial and one nonrandomized study met the inclusion criteria. Both studies used mindfulness-based procedures to reduce cigarette use in adults with mild intellectual disability. The outcome was defined as self-reported cigarette use at follow-up, which ranged from 1 year to 3 years. Limited information was provided on how the interventions were tailored to meet the unique needs of people with disabilities in either study., Conclusion: Two interventions conducted in adults with mild intellectual disability showed promising results using mindfulness-based procedures; however, the studies did not address barriers reported by people with disabilities, nor tailor the interventions to meet the needs of the target population. Research is needed to address tobacco use disparities among people with a range of disabilities. Current cessation interventions would be enhanced by integrating disability identifiers alongside other demographic information in future studies and reporting subgroup analyses in adults with disabilities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ACV was supported by P30CA072720-5931 and the Rutgers Cancer Institute of New Jersey. SDR was supported by grants from the National Institute on Drug Abuse (T32DA035200) of the National Institutes of Health. We acknowledge support from the Center of Biomedical Research Excellence Award (P20 GM103644) from the National Institute of General Medical Sciences. The funding agency had no role in study design, data collection or analysis, or preparation and submission of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Cigarette smoking is disproportionately high among lesbian, gay, and bisexual (LGB) adults. Yet, collapsing these identities into a monolith can disguise important within group disparities (e.g., lesbian/gay versus bisexual female). The purpose of this study is to report recent national prevalence estimates and trends of cigarette smoking behaviors and nicotine dependence by sexual identity and sex., Methods: Data were from the 2015-2019 National Survey on Drug Use and Health (n = 210,392; adults 18+), a nationally representative, repeated cross-sectional study of substance use and mental health in the U.S. We examined bivariate and multivariable associations between sexual identity and cigarette smoking measures (i.e., former smoking, lifetime smoking, current smoking, current daily smoking, nicotine dependence) by sex. We also examined linear time trends in current and former smoking. Covariates included age, race/ethnicity, education, annual household income, and survey year., Results: Bisexual women had the highest unadjusted prevalence of current smoking (31 %) and lowest of former smoking (25 %). LGB females and males had higher adjusted prevalence of current smoking, daily smoking, and nicotine dependence than heterosexual adults. Bisexual females and gay and bisexual males had lower adjusted prevalence of former smoking (adjusted prevalence ratio range: 0.78-0.85) than heterosexual counterparts., Discussion: This is the first study to identify disproportionately low prevalence of former smoking among bisexual females. Paired with findings of high prevalence of current cigarette smoking and nicotine dependence, these data suggest that tobacco control interventions targeted toward bisexual females are urgently needed to reduce the burden of cigarette smoking among these individuals., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction: This study assessed the substitutability of plausible combustible menthol cigarette alternatives (MCAs) for usual brand menthol cigarettes (UBMCs) in adults who smoke menthol cigarettes., Methods: Following three in-lab sampling sessions, 80 adults aged 21-50 who smoke menthol cigarettes chose their preferred MCA: (1) a menthol roll-your-own cigarette (mRYO), (2) a menthol filtered little cigar (mFLC) or (3) a non-menthol cigarette (NMC). Participants were instructed to completely substitute their preferred MCA for their UBMC for 1 week and complete daily diaries documenting adherence and subjective effects. At the final lab visit, participants completed concurrent choice and cross-price elasticity tasks with their substitute product and UBMC as the comparator., Results: Most (65%) participants chose mRYO as their preferred product, followed by NMC and mFLC. Adherence to MCA was high for all products across the week (range: 63%-88%). Positive subjective effects for mRYO decreased over time but remained numerically higher than the other MCA products; craving reduction also decreased for NMC across phases. In the progressive ratio task, participants chose their UBMC in 61.7% of choices; this did not differ by preferred MCA, although the median breakpoint was highest for mRYO and similar for mFLC and NMC. Cross-price elasticity comparing UBMC and the preferred product indicated high substitutability of each MCA at phase 3 ( I values -0.70 to -0.82)., Conclusions and Relevance: mRYOs were the most preferred MCA among the study products, but all MCAs were acceptable substitutes for UBMC using behavioural and economic measures in a short-term trial period. Trial registration number NCT04844762., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The drug efflux transporters ABCB1 and ABCG2 at the blood-brain barrier limit the delivery of drugs into the brain. Strategies to overcome ABCB1/ABCG2 have been largely unsuccessful, which poses a tremendous clinical problem to successfully treat central nervous system (CNS) diseases. Understanding basic transporter biology, including intracellular regulation mechanisms that control these transporters, is critical to solving this clinical problem.In this comprehensive review, we summarize current knowledge on signaling pathways that regulate ABCB1/ABCG2 at the blood-brain barrier. In Section I, we give a historical overview on blood-brain barrier research and introduce the role that ABCB1 and ABCG2 play in this context. In Section II, we summarize the most important strategies that have been tested to overcome the ABCB1/ABCG2 efflux system at the blood-brain barrier. In Section III, the main component of this review, we provide detailed information on the signaling pathways that have been identified to control ABCB1/ABCG2 at the blood-brain barrier and their potential clinical relevance. This is followed by Section IV, where we explain the clinical implications of ABCB1/ABCG2 regulation in the context of CNS disease. Lastly, in Section V, we conclude by highlighting examples of how transporter regulation could be targeted for therapeutic purposes in the clinic. SIGNIFICANCE STATEMENT: The ABCB1/ABCG2 drug efflux system at the blood-brain barrier poses a significant problem to successful drug delivery to the brain. The article reviews signaling pathways that regulate blood-brain barrier ABCB1/ABCG2 and could potentially be targeted for therapeutic purposes., (Copyright © 2023 by The Author(s).)

According to the free drug hypothesis (FDH), only free, unbound drug is available to interact with biological targets. This hypothesis is the fundamental principle that continues to explain the vast majority of all pharmacokinetic and pharmacodynamic processes. Under the FDH, the free drug concentration at the target site is considered the driver of pharmacodynamic activity and pharmacokinetic processes. However, deviations from the FDH are observed in hepatic uptake and clearance predictions, where observed unbound intrinsic hepatic clearance (CL int,u ) is larger than expected. Such deviations are commonly observed when plasma proteins are present and form the basis of the so-called plasma protein-mediated uptake effect (PMUE). This review will discuss the basis of plasma protein binding as it pertains to hepatic clearance based on the FDH, as well as several hypotheses that may explain the underlying mechanisms of PMUE. Notably, some, but not all, potential mechanisms remained aligned with the FDH. Finally, we will outline possible experimental strategies to elucidate PMUE mechanisms. Understanding the mechanisms of PMUE and its potential contribution to clearance underprediction is vital to improving the drug development process.

RNA-sequencing has been proposed as a valuable technique to develop individualized therapy concepts for cancer patients based on their tumor-specific mutational profiles. Here, we aimed to identify drugs and inhibitors in an individualized therapy-based drug repurposing approach focusing on missense mutations for 35 biopsies of cancer patients. The missense mutations belonged to 9 categories (ABC transporter, apoptosis, angiogenesis, cell cycle, DNA damage, kinase, protease, transcription factor, tumor suppressor). The highest percentages of missense mutations were observed in transcription factor genes. The mutational profiles of all 35 tumors were subjected to hierarchical heatmap clustering. All 7 leukemia biopsies clustered together and were separated from solid tumors. Based on these individual mutation profiles, two strategies for the identification of possible drug candidates were applied: Firstly, virtual screening of FDA-approved drugs based on the protein structures carrying particular missense mutations. Secondly, we mined the Drug Gene Interaction (DGI) database (https://www.dgidb.org/) to identify approved or experimental inhibitors for missense mutated proteins in our dataset of 35 tumors. In conclusion, our approach based on virtual drug screening of FDA-approved drugs and DGI-based inhibitor selection may provide new, individual treatment options for patients with otherwise refractory tumors that do not respond anymore to standard chemotherapy., Competing Interests: Declaration of competing interest H.J.G. and T.E. are inventors of patent #EP18211231. The other authors do not have any potential conflict of interest in relation to this study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: People with disabilities have a higher prevalence of cigarette smoking than people without disabilities. However, little information exists on smoking cessation interventions tailored to address the unique needs of people with disabilities. This paper describes a systematic review protocol to identify and evaluate tobacco smoking cessation interventions designed to improve outcomes for people with disabilities., Methods and Analysis: We will conduct a systematic review of the literature using the procedures outlined by Cochrane. We will search four electronic databases (CINAHL Plus (EBSCO), Embase (Ovid), Medline (Ovid) and PsycINFO (Ovid)) with no date restriction to identify tobacco cessation interventions tailored to meet the needs of people with disabilities. We will extract data and assess risk of bias using the RoB2 and ROBINS-I for included studies using Covidence systematic review software. Quantitative and qualitative syntheses will summarise key study characteristics and outcomes with text, tables and forest plots; a meta-analysis will be conducted, if appropriate., Ethics and Dissemination: Ethical approval is not required as there are no primary data associated with the study. Data will be disseminated through a peer-reviewed articles and conference presentations., Prospero Registration Number: CRD42022337434., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The prevalence of current cigarette smoking is higher in people with disabilities compared to those without. However, little is known about smoking status and trends in smoking by disability functioning domain., Methods: Data from the 2015-2019 National Surveys on Drug Use and Health were used to estimate the prevalence of past-month and daily cigarette smoking, former smoking, and nicotine dependence for people with any disability and six disability functioning domains. Logistic regression models estimated the odds of each outcome by disability domain compared to no disability, adjusting for sociodemographic factors., Results: From 2015-2019, the overall prevalence of current cigarette smoking (23.3% vs. 16.7%) and the proportion of those with nicotine dependence (14.6% vs 8.0%) was higher in people with any disability compared to those without (ps < 0.001). The prevalence of current cigarette smoking decreased while the prevalence of former cigarette smoking increased from 2015 to 2019 (ps < 0.05). People with any disability had higher odds of current smoking (AOR=1.20; 95% CI 1.16, 1.25) and similar odds of former smoking (AOR=1.00; 95% CI 0.95, 1.06) compared to people without disabilities. Odds of current and former smoking varied by domain., Conclusion: The prevalence of cigarette smoking among people with any disability decreased over time but remained higher than those without. People with any disability had similar odds of former smoking, though differences existed by disability domain. Future research should explore additional smoking and quit behaviors by disability functioning domain., Competing Interests: Conflict of Interest No conflict declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: People with disabilities report a higher prevalence of cigarette use than people without disabilities. However, evidence is limited on the relationships between disability type, degree of functional difficulty, and other tobacco product use., Methods: Data from the 2019 U.S. National Health Interview Survey were used to estimate the prevalence and odds of tobacco product use for 6 disability types and degree of functional difficulty. Bivariate and multivariable analyses conducted in 2021 examined the associations between tobacco product use and disability type., Results: Compared to adults who reported no difficulty, current cigarette use prevalence was higher for adults who reported a lot of difficulty/cannot do at all to vision (21.5% vs 13.1%), hearing (19.6% vs 13.6%), mobility (20.0% vs 12.9%), and cognitive (25.4% vs 12.9%) disability questions. The odds of current cigarette (AOR=1.32), pipe (AOR=1.85), and smokeless tobacco (AOR=1.57) use were significantly higher for adults who reported a lot of difficulty/cannot do at all to any disability question and significantly higher for current cigarette (AOR=1.24), e-cigarette (AOR=1.33), pipe (AOR=1.45), and smokeless tobacco (AOR=1.29) use for adults who reported some difficulty to any disability question than those who reported no difficulty. Pipe use was correlated with mobility difficulty (AOR=1.68), and smokeless tobacco use was correlated with hearing difficulty (AOR=1.95)., Conclusions: People who reported difficulty with vision, hearing, mobility, or cognition had a higher cigarette use prevalence than people without disabilities. Other tobacco use differed by disability type. Future research should tailor tobacco interventions to reduce these disparities., (Copyright © 2022 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Glioblastoma (GBM) is one of the deadliest cancers. Treatment options are limited, and median patient survival is only several months. Translation of new therapies is hindered by a lack of GBM models that fully recapitulate disease heterogeneity. Here, we characterize two human GBM models (U87-luc2, U251-RedFLuc). In vitro, both cell lines express similar levels of luciferase and show comparable sensitivity to temozolomide and lapatinib exposure. In vivo, however, the two GBM models recapitulate different aspects of the disease. U87-luc2 cells quickly grow into large, well-demarcated tumors; U251-RedFLuc cells form small, highly invasive tumors. Using a new method to assess GBM invasiveness based on detecting tumor-specific anti-luciferase staining in brain slices, we found that U251-RedFLuc cells are more invasive than U87-luc2 cells. Lastly, we determined expression levels of ABC transporters in both models. Our findings indicate that U87-luc2 and U251-RedFLuc GBM models recapitulate different aspects of GBM heterogeneity that need to be considered in preclinical research., (© 2022. The Author(s).)

Background: Independent Living (IL) involves having choice and control over where and with whom one lives. People with disabilities are less likely to live independently than their peers without disabilities., Objective: The purpose of this study was to understand the perceptions of young adults with mobility disabilities regarding IL, how they define IL, and what advice they would give others considering living a more independent life., Method: Semi-structured interviews were conducted with six young adults with mobility disabilities who had successfully transitioned to living independently. A content analysis was used to identify emergent themes from the interviews., Results: Results indicate that participants had individualized perceptions of the definition of IL. Participants identified many barriers and facilitators to IL, including the physical layout of housing, available amenities, and social support. They recommended preparing for IL in advance and taking advantage of outside resources to enable a successful transition., Conclusion: Young adults with mobility disabilities define IL in various ways, which may have an impact on whether they consider their transition to IL successful. Findings can be used to guide recommendations for young people with disabilities to use to ensure a successful transition to IL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: The COVID-19 pandemic and subsequent mandates upended community participation in the United States. People with disabilities were often more vulnerable to the adverse effects of the pandemic. Some areas of community participation affected for this population include employment, access to transportation, and social engagement and connection to others., Objectives: The purpose of this study was to explore the effects of the COVID-19 pandemic for people with mobility disabilities across a variety of topics related to community engagement including social interactions with family and friends, and access to caregivers, groceries, transportation, and employment., Methods: A survey was administered to participants with mobility disabilities (N = 39). Participants were asked to elaborate on topic areas that they identified as being affected by the COVID-19 pandemic. Data analysis included descriptive statistics and a content analysis in search of themes from open-ended responses., Results: Results indicate that access to family and friends was the most negatively affected topic related to participation, followed by access to food and groceries, transportation, employment, living independently, caring for others, and participating in the community in general. In response to these pandemic-related challenges, participants reported utilizing technology to connect with others and to get essential items delivered., Conclusions: Findings from this rapid research emphasize the need for emergency preparedness strategies, accessible and reliable resources related to technology use (e.g., Internet), and continued access to services for people with disabilities to maintain various aspects of community participation throughout the COVID-19 pandemic and in the future., (Copyright © 2021. Published by Elsevier Inc.)

Recent police brutality and related violence against Black people, coupled with the COVID-19 pandemic, has further evidenced the disproportionate impact of systemic racism in our institutions and across society. In the United States, the alarming mortality rates for Black people due to police violence and COVID-19 related deaths are clear demonstrations of inequities within a long history of disparate outcomes. In understanding systemic racism, it is essential to consider how it is embedded within society and across socio-ecological levels. The Social-Ecological Model (SEM) is used to examine conditions within the environment that maintain systemic racism, including within our field and discipline. A behavioral-community approach for examining racism aids in determining points of intervention across multiple ecological levels that may contribute to behavior change, including with behaviorists. The science of behavior is well-suited to help examine the contingencies governing behaviors within and across systems, which is pivotal for addressing operant behaviors to influence long-term behavior change. This paper calls on the behavioral community to address systemic racism within our environments and systems of influence to contribute to a more equitable community. Systemic racism, including within the context of anti-Blackness, is examined by considering behavior change strategies that can be supported by behaviorists across socio-ecological levels. Tools for collaborative action are provided to support behaviorists in demonstrating the skills needed across a continuum of behaviors from allyship to anti-racism to actively address systemic racism., Competing Interests: Conflicts of interestThe authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (© The Author(s) 2022.)

Background: People with mobility disabilities frequently have unmet needs in their home environment, which can lead to difficulties completing daily living activities. Therefore, it is important that homes are not just accessible, but rather useable, meaning that the home complements an individual's functional, social, and psychological needs. Although previous research has shown the importance of home usability for people with mobility disabilities on health outcomes, this research explores the relationship between home usability and community participation both inside and outside the home., Objective: The objective of this study was to understand the perception of people with mobility disabilities on the relationship between community participation and home usability., Method: Twelve participants completed in-person semi-structured interviews to answer questions related to home usability and community participation. A content analysis was used to identify emergent themes., Results: Results indicate that personal, social, and environment factors influence home usability and one's ability to participate in the community., Conclusion: Home usability is a complex concept that is intertwined with a person's ability to participate in their community. Useable homes can facilitate community participation, both inside and outside the home. In fact, home usability is a critical component of community participation, as homes are not only located in the community but are sites from which people access community. Further research is needed to understand the significance of this interaction and the impact of changing home usability on one's ability to participate in the community., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Approximately one in eight visits to the Emergency Department (ED) in the United States are due to a behavioral health crisis. A Midwest community created an Integrated Crisis Team (ICT) as part of its county-wide effort to improve quality of care for people with mental health and/or substance use disorders. This ICT, which is embedded in the ED, ensured trained crisis clinicians were available in the ED, among other strategies. Semi-structured interviews were conducted with 15 staff members and a thematic analysis was used to assess ED staff members' perceptions of the impact of the ICT on staff and patient experience, and to identify barriers to implementation. Results indicated that the ICT facilitated a collaborative team effort in the ED and improved patient care in the ED. This evaluation informs key stakeholders about the importance of integrating a crisis team within an ED to better serve behavioral health patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Objective: To review the use, care, and fitting of pessaries., Target Population: Women requiring the use of vaginal pessaries for pelvic organ prolapse and/or stress urinary incontinence. Use may also be indicated for women with certain pregnancy-related clinical scenarios, including incarcerated uterus., Options: Pessaries are an option for women presenting with prolapse and/or stress urinary incontinence. In addition, certain types of pessaries can be considered for patients with cervical insufficiency or incarcerated uterus., Outcomes: Most women with prolapse or stress urinary incontinence can be successfully fitted with a pessary and experience excellent symptom relief, high satisfaction rates, and minimal complications., Benefits, Harms, and Costs: Women with pelvic organ prolapse and/or stress urinary incontinence may choose to use a pessary to manage their symptoms rather than surgery or while waiting for surgery. Major complications have been seen only when pessaries are neglected. Minor complications such as vaginal discharge, odour, and erosions can usually be successfully treated., Evidence: Medline was searched for relevant articles up to December 2018. This is an update of the SOGC technical update published in 2013, which was the first internationally published guidance on pessary use. Subsequently, an Australian guideline on the use of pessaries for the treatment of prolapse was published later in 2013., Validation Methods: The authors rated the quality of evidence and strength of recommendations using the approach of the Canadian Task Force on Preventive Health Care (Appendix A)., Intended Audience: Gynaecologists, obstetricians, family physicians, physiotherapists, residents, and fellows., Summary Statements: RECOMMENDATION., (Copyright © 2020 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: This study sought to evaluate the use of the Edmonton Obesity Staging System (EOSS) in predicting cesarean delivery among term, nulliparous, singleton pregnancies in women with overweight or obesity who are undergoing an induction of labour., Methods: A prospective cohort study was performed in Edmonton, Alberta. Women undergoing an induction of labour at term were recruited to either a sample cohort, including women with a body mass index of ≥25 kg/m 2 at first antenatal visit, or a control cohort with a body mass index of 18.5 to 24.9 kg/m 2 . Participating women provided a self-reported health history and consented to review of their medical records allowing allocation into EOSS categories. The primary outcome was the rate of cesarean delivery based on EOSS category. Secondary outcomes consisted of a summary score of adverse maternal, delivery, and neonatal events (Canadian Task Force Classification II-2)., Results: Overall, 345 women were recruited, with a participation rate of 93.7%. The sample cohort consisted of 276 women with overweight or obesity, whereas the control cohort included 69 normal-weight women. The overall rate of cesarean delivery was 30.4% for the control cohort and 35.8%, 29.9%, 43.2%, and 90.5% for women assigned an EOSS category 0, 1, 2, and 3, respectively (P < 0.001). A summary score was not indicative of overall rate of adverse maternal, delivery, and neonatal events (P = 0.22)., Conclusion: The EOSS may help predict the chance of cesarean delivery in a high-risk group of nulliparous women with overweight or obesity who are undergoing an induction of labour at term., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: Urinary incontinence and pelvic organ prolapse are highly prevalent in women and have a significant impact on quality of life. Pessaries are devices that are used as a conservative management option. Many women use pessaries, which avoid surgical intervention with its associated morbidity and cost. However, not all women are good candidates for pessary use. The objective of this study was to determine clinical factors leading to persistent pessary use for incontinence or pelvic organ prolapse in a tertiary care centre at 12 months. Studying patient characteristics for long-term pessary use will contribute to better patient counselling, management, and health resource distribution., Methods: This study was a retrospective outpatient chart review of new pessary fittings in patients in a tertiary care urogynaecology clinic between January and June 2014. Any woman over 18 years of age fitted with a pessary at that time was included in the study. All statistical analyses were performed using IBM SPSS Statistics version. 24 (IBM Corp., Armonk, NY) (Canadian Task Force Classification II-3)., Results: A total of 152 women were fitted with pessaries. A multivariable logistic regression analysis found that a patient's diagnosis of prolapse or incontinence (P = 0.01) and a lack of complications (P < 0.0001) were statistically significant for persistent pessary use at 12 months. Patients with prolapse had 7.7 times higher odds (95% CI 1.51-39.35) of using a pessary at 12 months than did patients with incontinence. Patients without complications had 250 times higher odds (95% CI 18.52-2500) of pessary use. Patients who tried two to three pessaries had 16 times higher odds (95% CI 1.80-137.00) of persistent use than patients who trialed just one., Conclusion: This study has found that a lack of complications, the number of pessaries tried, and a primary diagnosis of prolapse are significant factors for continued pessary use at 12 months., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Understanding blood-brain barrier function under physiological and pathophysiological conditions is critical for the development of new therapeutic strategies that hold the promise to enhance brain drug delivery, improve brain protection, and treat brain disorders. However, studying the human blood-brain barrier function is challenging. Thus, there is a critical need for appropriate models. In this regard, brain capillaries isolated from human brain tissue represent a unique tool to study barrier function as close to the human in vivo situation as possible. Here, we describe an optimized protocol to isolate capillaries from human brain tissue at a high yield and with consistent quality and purity. Capillaries are isolated from fresh human brain tissue using mechanical homogenization, density-gradient centrifugation, and filtration. After the isolation, the human brain capillaries can be used for various applications including leakage assays, live cell imaging, and immune-based assays to study protein expression and function, enzyme activity, or intracellular signaling. Isolated human brain capillaries are a unique model to elucidate the regulation of the human blood-brain barrier function. This model can provide insights into central nervous system (CNS) pathogenesis, which will help the development of therapeutic strategies for treating CNS disorders.

Background: Cashews are the third most-consumed tree nut in the United States and are abundant with monounsaturated fatty acids and polyunsaturated fatty acids, which are associated with reduced cardiovascular disease risk. Although a qualified Food and Drug Administration health claim exists for nuts and heart health, cashews have been exempt from its use because cashews exceed the disqualifying amount of saturated fatty acids. Approximately one-third of the saturated fat in cashews is stearic acid, which is relatively neutral on blood lipids, thereby suggesting that cashews could have effects that are similar to those of other nuts. However, clinical data on cashews and blood lipids have been limited. Objective: We investigated the effect of reasonable intakes of cashews on serum lipids in adults with or at risk of high LDL cholesterol. Design: In a randomized, crossover, isocaloric, controlled-feeding study, 51 men and women (aged 21-73 y) with a median LDL-cholesterol concentration of 159 mg/dL (95% CI: 146, 165 mg/dL) at screening consumed typical American diets with cashews (28-64 g/d; 50% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 32% of kilocalories from total fat) or potato chips (control; 54% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 29% of kilocalories from total fat) for 28 d with a ≥2-wk washout period. Results: Consumption of the cashew diet resulted in a significantly greater median change from baseline (compared with the control, all P < 0.05) in total cholesterol [-3.9% (95% CI: -9.3%, 1.7%) compared with 0.8% (95% CI: -1.5%, 4.5%), respectively], LDL cholesterol [-4.8% (95% CI: -12.6%, 3.1%) compared with 1.2% (95% CI: -2.3%, 7.8%), respectively], non-HDL cholesterol [-5.3% (95% CI: -8.6%, 2.1%) compared with 1.7% (95% CI: -0.9%, 5.6%), respectively], and the total-cholesterol:HDL-cholesterol ratio [-0.0% (95% CI: -4.3%, 4.8%) compared with 3.4% (95% CI: 0.6%, 5.2%), respectively]. There were no significant differences between diets for HDL cholesterol and triglyceride. Conclusions: In comparison with a control diet, the incorporation of cashews into typical American diets decreases total cholesterol and LDL cholesterol. Results from this study provide support that the daily consumption of cashews, when substituted for a high-carbohydrate snack, may be a simple dietary strategy to help manage total cholesterol and LDL cholesterol. This study was registered at clinicaltrials.gov as NCT02769741., (© 2017 American Society for Nutrition.)

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

Objective: Midurethral slings have become the standard of care for women with stress urinary incontinence; prolapse repair is often also required. The primary objective of our study was to compare voiding dysfunction rates and the need for reoperation between patients having midurethral sling procedures alone versus those having midurethral sling procedures with concomitant prolapse repair., Methods: We performed a retrospective chart review over a two-year period in a tertiary urogynaecology clinic. Of 108 charts, 93 had complete data for analysis., Results: Patients having concomitant prolapse repair had a longer operating time, a longer hospital stay, and a longer time to resume normal voiding in the immediate postoperative period., Conclusion: Although tension-free vaginal tape or transobturator tape procedures with concomitant prolapse repair have a higher incidence of voiding dysfunction in the immediate postoperative period, we found that this did not persist to the six-week follow-up visit. There appeared to be no greater risk of lasting voiding dysfunction or need for reoperation after concomitant procedures.

Objective: The purpose of this study was to determine the effectiveness of a teaching module using simulation for the tension-free vaginal tape (TVT) procedure on procedural knowledge and skill., Methods: Twenty-five gynecology residents participated in a teaching module about the TVT procedure and urinary incontinence, which included a simulated insertion on a training model. Questionnaires using 10-point scales for self-rated competence and knowledge and a written examination were administered before and after the module. A simulated TVT insertion was evaluated at an examination at 7 weeks and at 7 months., Results: A significant median improvement of 44% on the written examination and at least one point on each of the self-rated competence and knowledge scales were observed after the teaching module. Residents performed the insertion well at both examinations (89% and 90%), regardless of surgical experience. More than 94% agreed the module was useful and improved their understanding of the procedure., Conclusion: A short teaching module and simulation session can effectively teach residents and improve their perceived competence with the TVT procedure.

Genital prolapse is common among ageing women. Urinary obstruction and hydronephrosis have been reported as one of the most severe and fortunately uncommon complications. An 82-year-old multiparous woman with symptomatic pelvic organ prolapse quantification stage 4 genital procidentia fails multiple trials of pessary and abandons the trials due to significant side effects. She chooses to pursue conservative management with estrogen cream and tight underwear. However, she fails to follow up as planned. Two years later, she presents with acute abdomen and renal failure due to renal calyceal rupture and perirenal urinary extravasation from complete procidentia. She is treated promptly with urinary catheter, manual prolapse reduction, and Gellhorn pessary which relieves anuria and stabilizes her condition. She then receives definitive surgical treatment 2 weeks later. Her renal failure and abdominal pain resolve post-operatively.

Background: Multidisciplinary team care is becoming more popular for complex health issues, including pelvic floor dysfunction., Methods: We conducted a retrospective review of the records of 207 patients attending a multidisciplinary pelvic floor dysfunction clinic. A telephone survey was also conducted. The outcomes investigated included conservative versus surgical management, comorbidities, number of specialists seen, and subjective patient feedback., Results: The average patient was 59.9 years old and travelled an average distance of 128.6 km to attend the clinic. Common clinical presentations were urge urinary incontinence (58.9%) and stress urinary incontinence (54.6%). Ninety-three of 178 patients (52.2%) presented with at least two comorbidities. At the time of data collection, 52.2% of patients had opted for surgical management, 27.5% had chosen conservative management, and the remainder remained undecided. One hundred sixty-five women participated in the telephone survey and their responses were grouped into major themes: (1) wait times, (2) multidisciplinary clinic feedback, and (3) parking, patient education, and information distribution., Conclusion: Based on feedback, the majority of patients were accepting of a multidisciplinary approach to pelvic floor dysfunction and were satisfied with that approach.

Tension-free vaginal tape (TVT) is increasingly being used as the gold standard to treat stress urinary incontinence. Previously reported complications include peritoneal perforation with acute bowel injury. A thin, petite 51-year-old woman with stress urinary incontinence underwent uneventful TVT placement. Three years later, she presented to hospital with de novo small-bowel obstruction. Laparotomy revealed TVT tape violating the peritoneum and causing the distal ileum to adhere to the pelvic sidewall. The compromised bowel was resected and primary anastomosis performed. Delayed, adhesion-related small-bowel obstruction can be a complication of TVT.

Objective: Symptoms of urinary incontinence often do not correlate well with the diagnosis provided by urodynamic investigations. Video urodynamics has been described as the "gold standard" investigation for patients with lower urinary tract symptoms. The aim of our study was to determine the concordance of diagnoses made on multi-channel and video urodynamics in women presenting with urinary incontinence to a tertiary care urogynaecology unit., Materials and Methods: We performed a retrospective chart review of 38 women who had video urodynamics and a multi-channel study completed within a one-year period. All patients had a complete history and pelvic floor assessment. The investigators completing each study were blinded to the clinical diagnoses, the physical findings, and the other urodynamics diagnoses. International Continence Society standards were followed for completion of all urodynamics investigations. Multi-channel studies were completed with the patient lying supine and video studies were performed with the patient sitting on a commode. The level of agreement of the diagnoses was calculated using a kappa (kappa) statistic with 95% confidence intervals (CI)., Results: The median age of subjects was 61 years (range 14-79), with a median duration of lower urinary tract symptoms of 6.0 years (range 0.5-41). Patients had had a median of two previous bladder surgeries (range 0-5). The level of concordance of the two diagnoses gave a kappa of 0.16 (95% CI 0.06-0.26)., Conclusions: There was poor concordance between the diagnoses made on multi-channel and video urodynamics when the two tests were performed on the same patient. Prospective studies are required to evaluate the reproducibility of diagnoses made on cystometry.

Objective: To determine the prevalence of and risk factors for urinary and fecal incontinence four months after vaginal delivery., Methods: All patients who had vaginal deliveries at a tertiary care hospital over a three-month period were approached during their postpartum hospital stay regarding participation in the study. Participants underwent a telephone interview at four months after their delivery to determine the presence and type of any incontinence., Results: Of 632 patients, 145 (23%) had stress incontinence, 77 (12%) had urge incontinence, 181 (29%) had any urinary incontinence and 23 (4%) had fecal incontinence. In univariate analysis, stress incontinence was found to be increased in patients>or=30 years of age (26.2%) compared with patients<30 years of age (19.3%) (RR 1.4; 95% CI 1.0-1.8, P=0.05). Urge incontinence was increased in patients who had a forceps delivery (21%) compared with no forceps delivery (9%) (RR 2.2; 95% CI 1.4-3.6, P=0.005), an episiotomy (32.4%) compared with no episiotomy (18.7%) (RR 1.9; 95% CI 1.2-2.9, P<0.01) and a longer second stage of labour (108 min vs. 77 min, P=0.01). The prevalence of any urinary incontinence was increased with forceps delivery (15.5%) compared with no forceps delivery (8.7%) (RR 1.5; 95% CI 1.1-2.1, P=0.01) and maternal age of >or=30 years (34.1%) compared to <30 years (23.5%) (RR 1.5; 95% CI 1.1-1.9, P=0.003). In multivariate analysis, the two variables that remained significant for any urinary incontinence were maternal age>or=30 years (P<0.01) and forceps delivery (P<0.01). There were no identified risk factors for fecal incontinence., Conclusion: Urinary incontinence is common in women at four months post partum. Fecal incontinence is less common. Maternal age and forceps assisted delivery were risk factors for urinary incontinence.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

Objective: To assess the overall success of sling procedures and surgical sling release in achieving urinary continence and voiding function in women with stress urinary incontinence., Methods: We reviewed the charts of 107 patients with stress urinary incontinence who had a two-team abdominal-vaginal fascial sling procedure performed between January 2000 and December 2003. Data reviewed included the patients' medical history, demographic data, findings on physical examination, urodynamic studies, operative report, and findings at visits 6 weeks, 6 months, and 12 months after surgery. Patients with sling releases were followed up to assess pelvic organ prolapse, uroflowmetry, and post-void residual urine volume, and to complete the quality of life questionnaire IIQ-7., Results: At one year after pubovaginal sling surgery, 82.1% of patients were cured of stress urinary incontinence. The majority (85.1%) of patients did not develop postoperative voiding dysfunction. Only 5.6% of those who did develop postoperative voiding dysfunction required surgical sling release. Sling release resolved the post-sling voiding dysfunction in three out of five patients., Conclusion: Pubovaginal sling surgery is a highly successful strategy for the management of stress urinary incontinence and has a low rate of postoperative voiding dysfunction. Surgical sling release may resolve post-sling voiding dysfunction.

Objectives: We sought to identify the structure of academic protected time curriculum and to determine interest in a knowledge-sharing, web-based initiative., Methods: We undertook a survey of the 16 obstetrics and gynaecology program directors in Canada., Results: The response rate was 88%. Seventy-one percent of the responding program directors are responsible for developing protected time curriculum. Seventy-eight percent use a template based on a two-year rotation of topics, 64% use lectures as the main educational format, and 50% have incorporated professional competencies into academic time. The largest barrier to curriculum development is time constraints. Seventy-eight percent of program directors are interested in a network for sharing ideas., Conclusions: In most programs, the curriculum for academic protected time is developed by program directors, who are dependent upon lectures and limited by time constraints. Programs therefore have difficulty integrating professional competencies into the academic curriculum. This educational environment could prove fertile ground for establishing a collaborative curriculum initiative.

Objective: An aging population has resulted in higher prevalence of urinary incontinence (UI) and pelvic organ prolapse (POP). This study examines a nurse-run clinic and analyzes the factors contributing to successful pessary use., Study Design: A retrospective chart review of 1,216 patients was completed. History, pelvic examination and pessary fitting was done. Data was analyzed utilizing a categorical model of maximum-likelihood estimation to investigate relationships., Results: Median patient age was 63 years. Median number of pessaries tried was two. Eighty-five percent of post-menopausal women were on hormone replacement therapy (HRT) prior to fitting. Highest success rate of 78% was in the group on both systemic and local HRT. Success rates ranged from 58% for urge incontinence to 83% for uterine prolapse. Prior vaginal surgery was a factor impacting success. In our series highest success rates for fitting were obtained with ring pessaries, ring with support, and gellhorns., Conclusions: This model is a viable, option for the conservative management of UI and POP. Local HRT plays an important role in successful pessary fitting. Complications are rare.

The purpose of our study was to compare the two standard routes of urethral bulking injection in a prospective randomized trial. Forty women with genuine stress incontinence (n = 36), or mixed incontinence with a minor and controlled urge component (n = 4), participated in a urethral bulking agent trial. All patients had a standardized preoperative evaluation which included history, physical examination, assignment of incontinence status on a Stamey grading scale, postvoid residual (PVR) determination, Valsalva leak-point pressure, maximal urethral closure pressure, functional urethral length, Q-tip excursion angle, quantitative pad test, and completion of a quality of life questionnaire. On the day of injection they were randomly assigned to a periurethral or transurethral route of injection based on a computer-generated block randomization scheme. An ultrasound-determined PVR was obtained on all patients after injection. If self-catheterization was necessary, and the PVR was > 200 ml, urinary retention was diagnosed. Postoperative assessment included a patient interview, subjective assessment of improvement, PVR, voiding diary, and assignment of incontinence grade. At the screening visit there were no significant differences between the groups for any variables except type of stress incontinence. With short-term follow-up both transurethral and periurethral routes of injection seem to be equally efficacious. In the periurethral injection group there was a higher rate of postoperative retention; this group had a significantly higher volume of injectable agent used. There was no significant difference in risk of urinary tract infections between the two groups. We conclude that both periurethral and transurethral methods of bulking agent injection for stress urinary incontinence are equally efficacious, with minimal morbidity.

At least half of all women who have given birth experience pelvic organ prolapse, a condition where pelvic organs protrude through the vagina. Because of the presentation of the different aspects of prolapse, treatment had become compartmentalized in line with pelvic involvement, with urologists, gynecologists, colorectal surgeons, and gastroenterologists each addressing their field of expertise. In addition, urinary or fecal incontinence, urinary retention, and urinary tract infections often are associated with pelvic organ prolapse. Both pelvic organ prolapse and incontinence have a significant impact on the quality of life. New training programs in urogynecology and reconstructive pelvic surgery are producing clinicians who are better equipped to treat pelvic organ prolapse, as well as related urinary and fecal incontinence. This article provides an overview of the various aspects of pelvic organ prolapse for all clinicians involved in assessment, treatment, and potential prevention of this condition.

The aim of this study was to determine whether water perfusion maximum urethral closure pressure (MUCP) correlates with Valsalva leak-point pressure (LPP), and which of these best correlates with subjective and objective incontinence severity measures. Fifty-two women with previously diagnosed genuine stress incontinence (n = 46), or mixed incontinence with a minor and controlled urge component (n = 6), were assigned an incontinence status grade based on interview and diary review. These women then completed visually observed standing LPPs at 250 ml bladder capacity, supine water perfusion MUCP determinations, pad tests and quality of life questionnaires. The urodynamic and severity measures were compared with correlation analysis or analysis of variance. A modest correlation exists between LPP and MUCP (r = 0.50-0.62, P < 0.001). Both MUCP and LPP demonstrated significant decreases (P < 0.01) with increasing severity of assigned incontinence grade. A very low and insignificant correlation existed for these urodynamic parameters and pad loss or quality of life measures. MUCP and LPP correlate modestly with each other and both are comparable in predicting incontinence severity. Either can be used as the urodynamic measure to assess intrinsic sphincter deficiency.

Recurrent stress urinary incontinence is a distressing problem. Its causes are multifactorial and the literature continually provides suggestions for changes to the surgical approach. Over 200 surgical procedures exist for the treatment of stress urinary incontinence, and this leaves the practising surgeon with an overwhelming range of choice. This article will review current available techniques for the surgical treatment of recurrent stress urinary incontinence.

When the coat protein of the small icosahedral virus, brome mosaic virus, reassembles into capsids, the ultrasonic absorption of the solution greatly increases. Submitting the solution to an ultrasonic field thus appears to reveal spontaneous molecular motions within a protein assembly. Confirmatory evidence of a dynamics of a protein shell comes from measurements on brome mosaic virus at various degrees of swelling and on tomato bushy stunt virus treated with the crosslinking agent glutaraldehyde. The detected fluctuations may be related either with cooperative deformational motion in the capsid or with more localized structural changes. Such structural changes may help liberate the RNA at an early stage of viral infection.

Competitive inhibition of prostaglandin synthetase by 8-cis-12-trans-14-cis-eicosatrienoic acid has been reported to occur in vitro. No in vivo effects were observed, possibly due to rapid metabolic degradation of this fatty acid by beta-oxidation. The present study involved the evaluation of this compound in vivo, and the preparation and evaluation in vivo of its alpha and beta methyl-substituted analogs which retain the carbon skeleton of the parent compound, and which might be expected to be resistant to beta-oxidation. Using a newly developed radioimmunoassay for the total urinary metabolites of prostaglandin E, data were obtained that indicates that both the parent compound and its 2-methyl analog are prostaglandin synthetase inhibitors in vivo. The 2-methyl analog exhibited an unusually long duration of activity as compared to both indomethacin and the parent compound. The lengthened duration of action of the 2-methyl analog may be explained both by its possible resistance to beta-oxidation, and to possible alteration in rates of either fatty acid transport, or incorporation/release from triglycerides (acylation/deacylation of triglycerides).

The structural fluctuations specific to self-assembled biological systems have been investigated further with ultrasonic techniques by using two strains of tobacco mosaic virus (TMV), as well as the helical aggregate of the common strain protein and subassemblies of it. We confirmed our earlier conclusion that protein assemblies exhibit specific structural fluctuations detected in ultrasonic experiments. As in spherical viruses, the fluctuations exhibited by the protein aggregates having a quaternary structure similar to that of the virion were modified in the virus by interaction with the RNA strand. It is unlikely that the origin for the observed effect is due either to: (1) the difference in local mobility of the segment 89 to 113 of the polypeptide chain in TMV and in the helical aggregate on the one hand, and in smaller aggregates, on the other hand; or (2) a local fluctuation associated with proton transfer reactions or ion-pair interactions. The most remarkable feature in the TMV system is the fact that the two-ring disk showed no excess of ultrasonic absorption with respect to the A-protein oligomer, while a large increase of ultrasonic absorption was observed in the rod-like aggregate that had undergone the disk-helix transition.