How Membrane Phospholipids Containing Long-Chain Polyunsaturated Fatty Acids and Their Oxidation Products Orchestrate Lipid Raft Dynamics to Control Inflammation.

BACKGROUND: Long-chain PUFA (LC-PUFA) influence varying aspects of inflammation. One mechanism by which they regulate inflammation is by controlling the size and molecular composition of lipid rafts. Lipid rafts are sphingolipid/cholesterol-enriched plasma membrane microdomains that compartmentalize signaling proteins and thereby control downstream inflammatory gene expression and cytokine production. OBJECTIVES: This review summarizes developments in our understanding of how LC-PUFA acyl chains of phospholipids, in addition to oxidized derivatives of LC-PUFAs such as oxidized 1-palmitoyl-2-arachidonyl-phosphatidylcholine (oxPAPC), manipulate formation of lipid rafts and thereby inflammation. METHODS: We reviewed the literature, largely from the past 2 decades, on the impact of LC-PUFA acyl chains and oxidized products of LC-PUFAs on lipid raft biophysical organization of myeloid and lymphoid cells. The majority of the studies are based on rodent or cellular experiments with supporting mechanistic studies using biomimetic membranes and molecular dynamic simulations. These studies have focused largely on the LC-PUFA docosahexaenoic acid, with some studies addressing eicosapentaenoic acid. A few studies have investigated the role of oxidized phospholipids on rafts. RESULTS: The biophysical literature suggests a model in which n-3 LC-PUFAs, in addition to oxPAPC, localize predominately to nonraft regions and impart a disordering effect in this environment. Rafts become larger because of the ensuing increase in the difference in order between raft and nonrafts. Biochemical studies suggest that some n-3 LC-PUFAs can be found within rafts. This deviation from homeostasis is a potential trigger for controlling aspects of innate and adaptive immunity. CONCLUSION: Overall, select LC-PUFA acyl chains and oxidized acyl chains of phospholipids control lipid raft dynamics and downstream inflammation. Gaps in knowledge remain, particularly on underlying molecular mechanisms by which plasma membrane receptor organization is controlled in response to oxidized LC-PUFA acyl chains of membrane phospholipids. Validation in humans is also an area for future study.

Incorporating sex, gender and vulnerable populations in a large multisite health research programme: The Ontario Pharmacy Evidence Network as a case study.

BACKGROUND: Funders now frequently require that sex and gender be considered in research programmes, but provide little guidance about how this can be accomplished, especially in large research programmes. The purpose of this study is to present and evaluate a model for promoting sex- and gender-based analysis (SGBA) in a large health service research programme, the Ontario Pharmacy Evidence Network (OPEN). METHODS: A mixed method study incorporating (1) team members' critical reflection, (2) surveys (n = 37) and interviews (n = 23) at programme midpoint, and (3) an end-of-study survey in 2016 with OPEN research project teams (n = 6). RESULTS: Incorporating gender and vulnerable populations (GVP) as a cross-cutting theme, with a dedicated team and resources to promote GVP research across the programme, was effective and well received. Team members felt their knowledge was improved, and the programme produced several sex- and gender-related research outputs. Not all resources were well used, however, and better communication of the purposes and roles of the team could increase effectiveness. CONCLUSIONS: The experience of OPEN suggests that dedicating resources for sex and gender research can be effective in promoting SGBA research, but that research programmes should also focus on communicating the importance of SGBA to their members.

Increasing patient recall of nurse leader rounding.

Nursing staff in a medical/surgical acute care 34-bed hospital unit were challenged by low percentages of patients able to recall nurse leader rounding activity (NLR). NLR occurred daily for all patients, yet many did not recall visits by nursing leaders when surveyed at discharge. Care giver credibility suffered as non-nursing executives questioned if NLR consistently occurred. Several mechanisms were used to facilitate patient NLR recall: scripted NLR verbiage/keywords, nursing uniform leadership insignia and white lab coats, sharing of business cards, handwritten notes on patient communication white boards, multimedia leadership insignia on leader e-tablets, and visits with family members: patient NLR recall did not improve. Nurses designed low effort, active learning, spaced repetition exchanges using the hospital nurse call system in reverse to distinguish NLR from other care-related activity. A pilot study saw NLR recall climb from a baseline measurement of 37.5% (n=88) to 88% (n=93) following implementation. Mann-Whitney U confirmed significant findings (U=2018.5, p<0.001). Patient age and cognitive impairment were confirmed as confounding factors. Binary logistic regression analysis confirmed intervention effects exceeded confounding effects. Findings were consistent with subsequent patient survey results provided by a third party.

Triethysilyl Enol Ethers in the Synthesis of Carbapenem Precursors.

A diastereoselective process for the formation of intermediates suitable for the preparation of C1 substituted carbapenems was developed. The process is readily scalable and does not involve organometallics or strong bases such as LDA.

Temperate functional niche availability not resident-invader competition shapes tropicalisation in reef fishes.

Temperate reefs are at the forefront of warming-induced community alterations resulting from poleward range shifts. This tropicalisation is exemplified and amplified by tropical species' invasions of temperate herbivory functions. However, whether other temperate ecosystem functions are similarly invaded by tropical species, and by what drivers, remains unclear. We examine tropicalisation footprints in nine reef fish functional groups using trait-based analyses and biomass of 550 fish species across tropical to temperate gradients in Japan and Australia. We discover that functional niches in transitional communities are asynchronously invaded by tropical species, but with congruent invasion schedules for functional groups across the two hemispheres. These differences in functional group tropicalisation point to habitat availability as a key determinant of multi-species range shifts, as in the majority of functional groups tropical and temperate species share functional niche space in suitable habitat. Competition among species from different thermal guilds played little part in limiting tropicalisation, rather available functional space occupied by temperate species indicates that tropical species can invade. Characterising these drivers of reef tropicalisation is pivotal to understanding, predicting, and managing marine community transformation.

Coral assemblages at higher latitudes favor short-term potential over long-term performance.

The persistent exposure of coral assemblages to more variable abiotic regimes is assumed to augment their resilience to future climatic variability. Yet, while the determinants of coral population resilience across species remain unknown, we are unable to predict the winners and losers across reef ecosystems exposed to increasingly variable conditions. Using annual surveys of 3171 coral individuals across Australia and Japan (2016-2019), we explore spatial variation across the short- and long-term dynamics of competitive, stress-tolerant, and weedy assemblages to evaluate how abiotic variability mediates the structural composition of coral assemblages. We illustrate how, by promoting short-term potential over long-term performance, coral assemblages can reduce their vulnerability to stochastic environments. However, compared to stress-tolerant, and weedy assemblages, competitive coral taxa display a reduced capacity for elevating their short-term potential. Accordingly, future climatic shifts threaten the structural complexity of coral assemblages in variable environments, emulating the degradation expected across global tropical reefs.

A community and functional comparison of coral and reef fish assemblages between four decades of coastal urbanisation and thermal stress.

Urbanized coral reefs experience anthropogenic disturbances caused by coastal development, pollution, and nutrient runoff, resulting in turbid, marginal conditions in which only certain species can persist. Mortality effects are exacerbated by increasingly regular thermal stress events, leading to shifts towards novel communities dominated by habitat generalists and species with low structural complexity.There is limited data on the turnover processes that occur due to this convergence of anthropogenic stressors, and how novel urban ecosystems are structured both at the community and functional levels. As such, it is unclear how they will respond to future disturbance events.Here, we examine the patterns of coral reef community change and determine whether ecosystem functions provided by specialist species are lost post-disturbance. We present a comparison of community and functional trait-based changes for scleractinian coral genera and reef fish species assemblages subject to coastal development, coastal modification, and mass bleaching between two time periods, 1975-1976 and 2018, in Nakagusuku Bay, Okinawa, Japan.We observed an increase in fish habitat generalists, a dominance shift from branching to massive/sub-massive corals and increasing site-based coral genera richness between years. Fish and coral communities significantly reassembled, but functional trait-based multivariate space remained constant, indicating a turnover of species with similar traits. A compression of coral habitat occurred, with shallow (<5 m) and deep (>8 m) coral genera shifting towards the mid-depths (5-8 m).We show that although reef species assemblages altered post disturbance, new communities retained similar ecosystem functions. This result could be linked to the stressors experienced by urban reefs, which reflect those that will occur at an increasing frequency globally in the near future. Yet, even after shifts to disturbed communities, these fully functioning reef systems may maintain high conservation value.

Study design and participant characteristics of a randomized controlled trial of directly administered antiretroviral therapy in opioid treatment programs.

BACKGROUND: HIV-infected drug users are at higher risk of non-adherence and poor treatment outcomes than HIV-infected non-drug users. Prior work from our group and others suggests that directly administered antiretroviral therapy (DAART) delivered in opioid treatment programs (OTPs) may increase rates of viral suppression. METHODS/DESIGN: We are conducting a randomized trial comparing DAART to self-administered therapy (SAT) in 5 OTPs in Baltimore, Maryland. Participants and investigators are aware of treatment assignments. The DAART intervention is 12 months. The primary outcome is HIV RNA < 50 copies/mL at 3, 6, and 12 months. To assess persistence of any study arm differences that emerge during the active intervention, we are conducting an 18-month visit (6 months after the intervention concludes). We are collecting electronic adherence data for 2 months in both study arms. Of 457 individuals screened, a total of 107 participants were enrolled, with 56 and 51 randomly assigned to DAART and SAT, respectively. Participants were predominantly African American, approximately half were women, and the median age was 47 years. Active use of cocaine and other drugs was common at baseline. HIV disease stage was advanced in most participants. The median CD4 count at enrollment was 207 cells/mm3, 66 (62%) had a history of an AIDS-defining opportunistic condition, and 21 (20%) were antiretroviral naïve. CONCLUSIONS: This paper describes the rationale, methods, and baseline characteristics of subjects enrolled in a randomized clinical trial comparing DAART to SAT in opioid treatment programs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00279110.

Clinic-based treatment of opioid-dependent HIV-infected patients versus referral to an opioid treatment program: A randomized trial.

BACKGROUND: Opioid dependence is common in HIV clinics. Buprenorphine-naloxone (BUP) is an effective treatment of opioid dependence that may be used in routine medical settings. OBJECTIVE: To compare clinic-based treatment with BUP (clinic-based BUP) with case management and referral to an opioid treatment program (referred treatment). DESIGN: Single-center, 12-month randomized trial. Participants and investigators were aware of treatment assignments. (ClinicalTrials.gov registration number: NCT00130819) SETTING: HIV clinic in Baltimore, Maryland. PATIENTS: 93 HIV-infected, opioid-dependent participants who were not receiving opioid agonist therapy and were not dependent on alcohol or benzodiazepines. INTERVENTION: Clinic-based BUP included BUP induction and dose titration, urine drug testing, and individual counseling. Referred treatment included case management and referral to an opioid-treatment program. MEASUREMENTS: Initiation and long-term receipt of opioid agonist therapy, urine drug test results, visit attendance with primary HIV care providers, use of antiretroviral therapy, and changes in HIV RNA levels and CD4 cell counts. RESULTS: The average estimated participation in opioid agonist therapy was 74% (95% CI, 61% to 84%) for clinic-based BUP and 41% (CI, 29% to 53%) for referred treatment (P < 0.001). Positive test results for opioids and cocaine were significantly less frequent in clinic-based BUP than in referred treatment, and study participants receiving clinic-based BUP attended significantly more HIV primary care visits than those receiving referred treatment. Use of antiretroviral therapy and changes in HIV RNA levels and CD4 cell counts did not differ between the 2 groups. LIMITATION: This was a small single-center study, follow-up was only moderate, and the study groups were unbalanced in terms of recent drug injections at baseline. CONCLUSION: Management of HIV-infected, opioid-dependent patients with a clinic-based BUP strategy facilitates access to opioid agonist therapy and improves outcomes of substance abuse treatment. PRIMARY FUNDING SOURCE: Health Resources and Services Administration Special Projects of National Significance program.

Sex and gender-based analysis in pharmacy practice research: A scoping review.

BACKGROUND: Recognizing the potential effect of sex and gender on health outcomes, there is a shift toward conducting sex and gender-based analysis (SGBA) within health research. However, little is known about the extent to which SGBA has been incorporated into pharmacy practice research. OBJECTIVES: To understand the extent to which SGBA is included in pharmacy practice research. METHOD: Scoping review of English-language studies identified through MEDLINE, Embase, International Pharmacy Abstracts (IPA), and CINAHL (inception to Jan 2014). Two raters independently screened citations to identify titles and abstracts that included key words related to sex or gender and studies that could be categorized as pharmacy practice research. One author extracted data from included studies related to study design, population, intervention/exposure and outcomes, with results reviewed by another. All authors reviewed eligible articles to categorize them based on a previously-developed typology, and to assess four criteria: 1) the inclusion of sex or gender in research objectives, 2) the depth of sex/gender analysis incorporated into study designs and reporting, 3) the inclusion of sex or gender considerations in interpretation of study results, 4) the intentional and accurate use of sex/gender language. RESULTS: Of 458 unique search results, only six articles met the inclusion criteria. Two of these six publications included sex/gender considerations in a model consistent with sex/gender based analysis as described by Hammarström. Three of the six studies inaccurately applied sex and gender terminology, whereas the two studies that featured sex or gender in their primary research question did use these terms appropriately. CONCLUSION: Despite increasing attention on the need for considering sex and gender, there was a paucity of pharmacy practice research publications that conducted SGBA. This presents an opportunity to explore sex, gender and intersectionality when pursuing studies that explore the impact of pharmacists interventions on patient outcomes.

Complicating the coming out narrative: becoming oneself in a heterosexist and cissexist world.

Traditional stage models of LGBTQ identity development have conceptualized coming out as a linear process from "closeted" to "out" that all queer/trans individuals must follow if they are to be considered healthy and well adjusted. These stage models have been critiqued for their rigidity and absence of a dynamic understanding of the coming out process. In this article we explore the findings from a qualitative photovoice study with 15 LGBTQ youths in a small urban center in Ontario that supports these critiques. We explore the efficacy of the photovoice technique in investigating questions of sexual and gender identity. This article identifies some contextual factors that are important in understanding coming out as a social (rather than internal) process; it also identifies some of the ways in which these youths' experiences challenge normative understandings of the "good, out queer."

Directly administered antiretroviral therapy for HIV-infected individuals in opioid treatment programs: results from a randomized clinical trial.

BACKGROUND: Data regarding the efficacy of directly administered antiretroviral therapy (DAART) are mixed. Opioid treatment programs (OTPs) provide a convenient framework for DAART. In a randomized controlled trial, we compared DAART and self-administered therapy (SAT) among HIV-infected subjects attending five OTPs in Baltimore, MD. METHODS: HIV-infected individuals attending OTPs were eligible if they were not taking antiretroviral therapy (ART) or were virologically failing ART at last clinical assessment. In subjects assigned to DAART, we observed one ART dose per weekday at the OTP for up to 12 months. SAT subjects administered ART at home. The primary efficacy comparison was the between-arm difference in the average proportions with HIV RNA <50 copies/mL during the intervention phase (3-, 6-, and 12-month study visits), using a logistic regression model accounting for intra-person correlation due to repeated observations. Adherence was measured with electronic monitors in both arms. RESULTS: We randomized 55 and 52 subjects from five Baltimore OTPs to DAART and SAT, respectively. The average proportions with HIV RNA <50 copies/mL during the intervention phase were 0.51 in DAART and 0.40 in SAT (difference 0.11, 95% CI: -0.020 to 0.24). There were no significant differences between arms in electronically-measured adherence, average CD4 cell increase from baseline, average change in log10 HIV RNA from baseline, opportunistic conditions, hospitalizations, mortality, or the development of new drug resistance mutations. CONCLUSIONS: In this randomized trial, we found little evidence that DAART provided clinical benefits compared to SAT among HIV-infected subjects attending OTPs. TRIAL REGISTRATION: ClinicalTrials.gov NCT00279110 NCT00279110?term = NCT00279110&rank = 1.

The Impact of Choice and Control on Women's Childbirth Experiences.

Women's choice and control impact birthing experiences. This study used a qualitative, descriptive approach to explore how women develop their initial birth plan and how changes made to the plan affect overall birth experiences. Narrative, semistructured interviews were conducted with 15 women who had given birth in Waterloo Region, Ontario, Canada, and data were analyzed using a phenomenological approach. Findings showed that women relied on many resources when planning a birth and that changes made to a woman's initial birth plan affected her recollection of the birth experience. Conclusions are that women's positive and negative recollections of their birth experiences are related more to feelings and exertion of choice and control than to specific details of the birth experience.

A single case design evaluation of a software and tutor intervention addressing emotion recognition and social interaction in four boys with ASD.

Many students with Autism Spectrum Disorders (ASD) have delays learning to recognize emotions. Social behavior is also challenging, including initiating interactions, responding to others, developing peer relationships, and so forth. In this single case design study we investigated the relationship between use of computer software (Mind Reading: The Interactive Guide to Emotions) and emotion recognition (ER) and social behavior change. After using Mind Reading for 7 to 10 weeks with a tutor, four boys with ASD improved ER scores and social interactions with peers. However, observed behavior changes were not strong enough to claim a causal relationship between variables. Findings, practice implications, and future research are discussed.

Linking molecular and population stress responses in Daphnia magna exposed to cadmium.

DNA microarrays can be used to measure environmental stress responses. If they are to be predictive of environmental impact, we need to determine if altered gene expression translates into negative impacts on individuals and populations. A large cDNA microarray (14000 spots) was created to measure molecular stress responses to cadmium in Daphnia magna,the mostwidely used aquatic indicator species, and relate responses to population growth rate (pgr). We used the array to detect differences in the transcription of genes in juvenile D. magna (24 h old) after 24 h exposure to a control and three cadmium concentrations (6, 20, and 37 microg Cd2+ L(-1)). Stress responses at the population level were estimated following a further 8 days exposure. Pgr was approximately linear negative with increasing cadmium concentration over this range. The microarray profile of gene expression in response to acute cadmium exposure begins to provide an overview of the molecular responses of D. magna, especially in relation to growth and development. Of the responding genes, 29% were involved with metabolism including carbohydrate, fat and peptide metabolism, and energy production, 31% were involved with transcription/translation, while 40% of responding genes were associated with cellular processes like growth and moulting, ion transport, and general stress responses (which included oxidative stress). Our production and application of a large Daphnia magna microarray has shown that measured gene responses can be logically linked to the impact of a toxicant such as cadmium on somatic growth and development, and consequently pgr.