Trajectories of sexual well-being and links with grief after a recent pregnancy loss: a dyadic longitudinal study.

BACKGROUND: Pregnancy loss affects 1 in 4 women and is linked with poorer overall health and relationship outcomes. Despite sexual well-being's importance to health, how sexual well-being changes across time after a pregnancy loss and what might predict such changes, like perinatal grief, have never been examined, leaving practitioners and couples without knowledge of what to expect. AIM: We aimed to examine (1) how sexual satisfaction, sexual desire, sexual distress, and perinatal grief change from 10 to 25 weeks postloss for both couple members; and (2) if perinatal grief levels at 10 weeks postloss predict sexual well-being trajectories. METHODS: Women and gender-diverse individuals who were pregnant when a pregnancy loss occurred (within the last 4 months) and men, women, and gender-diverse partners who were not pregnant (N = 132 couples) independently completed 4 monthly assessments of sexual well-being and perinatal grief. OUTCOMES: Outcomes included sexual satisfaction (Global Measure of Sexual Satisfaction), sexual desire (Sexual Desire Inventory), sexual distress (Sexual Distress Scale-Short Form), perinatal grief (Perinatal Grief Scale). RESULTS: Dyadic growth curve modeling indicated that, from 10 to 25 weeks postloss, both couple members' sexual satisfaction increased, and their sexual desire remained stable; sexual distress decreased for partners but remained stable for individuals who were pregnant; and both couple members' perinatal grief decreased. Perinatal grief levels at 10 weeks postloss did not predict sexual well-being trajectories over time. CLINICAL IMPLICATIONS: Given sexual well-being's dynamic nature, clinicians should regularly discuss sexuality with both couple members after pregnancy loss. During such discussions, clinicians could reassure couples about their sexual relationship's recovery by sharing that, on average, sexual satisfaction, sexual desire, and sexual distress tend to improve or stay the same (rather than worsen) from 10 to 25 weeks postloss. They can also share that perinatal grief tends to decrease during this time and is unrelated to trajectories of sexual satisfaction, sexual desire, and sexual distress. STRENGTHS AND LIMITATIONS: This is the first study, to our knowledge, to examine how sexual well-being changes across time after a pregnancy loss and perinatal grief's role in such changes. The results may not generalize broadly, as most couples were in mixed-gender/sex relationships, identified as White, and were relatively affluent. CONCLUSION: From 10 to 25 weeks postloss, both couple members tend to experience improvements in their overall sexual well-being and declines in their perinatal grief. Early perinatal grief levels and subsequent sexual well-being trajectories are seemingly unrelated.

What Does a Pregnancy Loss Mean for Sex? Comparing Sexual Well-Being Between Couples With and Without a Recent Loss.

It is unclear whether sexual well-being, which is an important part of individual and relational health, may be at risk for declines after a pregnancy loss given the limits of prior work. Accordingly, in a cross-sectional study, we used structural equation modeling to (1) compare sexual well-being levels-satisfaction, desire, function, distress, and frequency-of both partners in couples who had experienced a pregnancy loss in the past four months (N = 103 couples) to their counterparts in a control sample of couples with no history of pregnancy loss (N = 120 couples), and (2) compare sexual well-being levels of each member of a couple to one another. We found that gestational individuals and their partners in the pregnancy loss sample were less sexually satisfied than their control counterparts but did not differ in sexual desire, problems with sexual function, nor sexual frequency. Surprisingly, we found that partners of gestational individuals had less sexual distress than their control counterparts. In the pregnancy loss sample, gestational individuals had lower levels of sexual desire post-loss than their partners but did not differ in sexual satisfaction, problems with sexual function, nor sexual distress. Our results provide evidence that a recent pregnancy loss is associated with lower sexual satisfaction and greater differences between partners in sexual desire, which may be useful information for clinicians working with couples post-loss. Practitioners can share these findings with couples who may find it reassuring that we did not find many aspects of sexual well-being to be related to pregnancy loss at about three months post-loss.

A novel peptide-based tau aggregation inhibitor as a potential therapeutic for Alzheimer's disease and other tauopathies.

INTRODUCTION: As aggregation underpins Tau toxicity, aggregation inhibitor peptides may have disease-modifying potential. They are therefore currently being designed and target either the 306VQIVYK311 aggregation-promoting hotspot found in all Tau isoforms or the 275VQIINK280 aggregation-promoting hotspot found in 4R isoforms. However, for any Tau aggregation inhibitor to potentially be clinically relevant for other tauopathies, it should target both hotspots to suppress aggregation of Tau isoforms, be stable, cross the blood-brain barrier, and rescue aggregation-dependent Tau phenotypes in vivo. METHODS: We developed a retro-inverso, stable D-amino peptide, RI-AG03 [Ac-rrrrrrrrGpkyk(ac)iqvGr-NH2], based on the 306VQIVYK311 hotspots which exhibit these disease-relevant attributes. RESULTS: Unlike other aggregation inhibitors, RI-AG03 effectively suppresses aggregation of multiple Tau species containing both hotspots in vitro and in vivo, is non-toxic, and suppresses aggregation-dependent neurodegenerative and behavioral phenotypes. DISCUSSION: RI-AG03 therefore meets many clinically relevant requirements for an anti-aggregation Tau therapeutic and should be explored further for its disease-modifying potential for Tauopathies. HIGHLIGHTS: Our manuscript describes the development of a novel peptide inhibitor of Tau aggregation, a retro-inverso, stable D-amino peptide called RI-AG03 that displays many clinically relevant attributes. We show its efficacy in preventing Tau aggregation in both in vitro and in vivo experimental models while being non-toxic to cells. RI-AG03 also rescues a biosensor cell line that stably expresses Tau repeat domains with the P301S mutation fused to Cer/Clo and rescues aggregation-dependent phenotypes in vivo, suppressing neurodegeneration and extending lifespan. Collectively our data describe several properties and attributes of RI-AG03 that make it a promising disease-modifying candidate to explore for reducing pathogenic Tau aggregation in Tauopathies such as Alzheimer's disease. Given the real interest in reducing Tau aggregation and the potential clinical benefit of using such agents in clinical practice, RI-AG03 should be investigated further for the treatment of Tauopathies after validation in mammalian models. Tau aggregation inhibitors are the obvious first choice as Tau-based therapies as much of Tau-mediated toxicity is aggregation dependent. Indeed, there are many research efforts focusing on this therapeutic strategy with aggregation inhibitors being designed against one of the two aggregation-promoting hotspots of the Tau protein. To our knowledge, RI-AG03 is the only peptide aggregation inhibitor that inhibits aggregation of Tau by targeting both aggregation-promoting hotspot motifs simultaneously. As such, we believe that our study will have a significant impact on drug discovery efforts in this arena.

Sexual growth and destiny beliefs: Longitudinal associations with dyadic coping among couples seeking medically assisted reproduction.

BACKGROUND: Medically assisted reproduction is a vulnerable time for couples' sexual health. Believing that sexual challenges can be worked through (i.e., sexual growth beliefs) or that these challenges indicate incompatibility (i.e., sexual destiny beliefs) may be related to dyadic coping-the strategies couples use to cope-with the physical and psychological stressors of medically assisted reproduction. AIM: In the current study we aimed to examine the longitudinal associations between typical (i.e., average) levels of sexual growth and destiny beliefs and positive and negative facets of dyadic coping and how greater than typical levels of these constructs predicted each other across time. METHODS: Couples (n = 219) seeking medically assisted reproduction were recruited for an online longitudinal, dyadic study. OUTCOMES: Couples completed online measures of sexual growth and destiny beliefs and positive and negative dyadic coping at baseline, 6-and 12-months. RESULTS: Random intercept cross-lagged panel models demonstrated that at the within-person level, reporting higher sexual growth beliefs at baseline, relative to their average across time points, was associated with lower negative dyadic coping at 6 months. Higher negative dyadic coping at 6 months, relative to their average, was linked to lower sexual growth beliefs at 12-months. When individuals reported higher sexual destiny beliefs at 6-months, relative to their average, they and their partners reported higher negative dyadic coping at 12 -months. At the between-person level, higher overall levels of sexual destiny beliefs were related to higher overall levels of negative dyadic coping. No associations with positive dyadic coping were identified. CLINICAL IMPLICATIONS: Couples may benefit from identifying and reducing unhelpful beliefs about sex and negative dyadic coping. STRENGTHS AND LIMITATIONS: Strengths of this study include our large, inclusive sample, engagement of community partners, and novel analytical approach to assess change over time. However, following couples in 6-month increments and not using questionnaires specific to medically assisted reproduction may have limited our ability to detect nuanced changes that couples experience during this time. CONCLUSION: Lower sexual growth and higher sexual destiny beliefs may promote couples' engagement in less adaptive coping behaviors as they seek medically assisted reproduction.

Change in 21 Sexual Concerns of New Parents From Three to Twelve Months Postpartum: Similarities and Differences between Mothers and Partners.

BACKGROUND: Postpartum sexual concerns are associated with depressive symptoms, distress, and lower relationship satisfaction, and are commonly reported by both mothers and their partners. Previous studies have examined changes in postpartum sexual concern using aggregate scores and have not examined patterns of change for unique concerns, thus ignoring that the initial levels and trajectories of a variety of distinct, postpartum sexual concerns may differ from one another and may differ between mothers and partners. AIMS: The aims of the current study were to (i) examine how a variety of postpartum sexual concerns change from 3 to 12 months postpartum for mothers and their partners using a sample of first-time parents, and (ii) examine how mothers and their partners may differ in their initial levels and subsequent changes in postpartum sexual concerns. METHODS: First-time mothers and their partners (N = 203 couples) independently completed a measure of 21 postpartum sexual concerns at 3, 6, 9, and 12 months postpartum. OUTCOMES: Postpartum Sexual Concerns Questionnaire RESULTS: Growth modeling indicated that twelve of mothers' and 6 of partners' postpartum sexual concerns declined over time from 3 to 12 months postpartum, only one concern of mothers' and none of partners' concerns increased over time, and the remaining 8 and 15 concerns were stable for mothers and partners, respectively. At 3 months postpartum, mothers had higher levels of 11 postpartum sexual concerns than partners, while partners had higher levels than mothers on 4 concerns. Compared to partners, from 3 to 12 months postpartum, mothers showed both steeper decreases in concern about body image changes and steeper increases in concern about returning to work. CLINICAL IMPLICATIONS: Various postpartum sexual concerns do not all follow the same pattern of change over time, and mothers and their partners share similarities and differences in these patterns. Clinicians should use a checklist to discuss a range of postpartum sexual concerns with both new mothers and their partners. STRENGTHS AND LIMITATIONS: This is the first study, to our knowledge, to examine how a variety of postpartum sexual concerns change over time and how mothers and partners both differ and are similar in their experiences. Most couples were in mixed-sex relationships, identified as White, and were relatively affluent; results may not generalize. CONCLUSION: A variety of postpartum sexual concerns follow different patterns of change from 3 to 12 months postpartum, and mothers and partners share similarities and differences in these patterns. Allsop DB, Impett EA, Vannier SA, et al. Change in 21 Sexual Concerns of New Parents From Three to Twelve Months Postpartum: Similarities and Differences between Mothers and Partners. J Sex Med 2022;19:1366-1377.

How Gender Differences in Emotional Cutoff and Reactivity Influence Couple's Sexual and Relational Outcomes.

We evaluated gender differences in differentiation of self, specifically addressing aspects of emotional cutoff (EC) and emotional reactivity (ER), and their association with relational and sexual satisfaction and sexual desire. Midlife U.S. men and women (N = 334 married heterosexual couples; 50% female; 85% Caucasian, mean age 47.4 years) completed online surveys. Men reported higher levels of EC compared to women after accounting for control variables-a medium effect (Cohen's d = .48) which negatively predicted their own relationship and sexual satisfaction as well as partner relationship satisfaction. Women's EC was also negatively associated with their own relationship satisfaction. Women reported higher levels of ER compared to men after accounting for control variables-a small effect (Cohen's d = .18). No associations with ER and outcome variables were found and no other partner effects were found. For couples in which the woman was higher on ER, the association between women's T1 emotional reactivity and men's T2 sexual desire was positive and significant (B = .31, p < .05). These findings underscore the influence of emotional cutoff on relationship satisfaction and sexual desire and the importance of staying engaged even through relational conflict.

Forgiveness and Gratitude: Links Between Couples' Mindfulness and Sexual and Relational Satisfaction in New Cisgender Heterosexual Marriages.

The association of mindfulness with couples' relational and sexual satisfaction may be mediated by forgiveness and gratitude. Although forgiveness and gratitude have individually been shown to play a role in couples' relational and sexual satisfaction, we use an integrated model. This study included 1,360 couples recruited through a nationwide two-stage cluster stratification. Using an actor-partner interdependence model, we found significant indirect effects (ß = 0.01, 0.08, p < .01), indicating that forgiveness and gratitude mediated many of the associations between couples' mindfulness and their sexual and relational satisfaction. This may provide useful information for clinicians and therapists when addressing marital issues.

How Empathy Moderates Associations Between Sexual and Relational Satisfaction.

Those with low sexual satisfaction tend to have low relational satisfaction. However, literature provides examples of those who maintain satisfying relationships despite low sexual satisfaction yet provides few clues as to what factors protect these individuals. Using U.S. nationally representative data from 1569 newlywed couples, we investigated if empathy for one's partner buffers individuals and couples from low relational satisfaction due to low sexual satisfaction. The positive connection between sexual satisfaction and relational satisfaction was weak for those reporting high empathy but was strong for those reporting low empathy. Empathy may protect against poor relational satisfaction when sexual satisfaction is low.

Mindfulness and Sexual Mindfulness as Moderators Between Conflict Resolution and Sexual and Relationship Satisfaction.

Mindfulness has shown positive links with conflict resolution. Additionally, couples skilled in conflict resolution report greater sexual and relationship satisfaction. However, no research has examined the moderating effect of mindfulness, specifically sexual mindfulness, between conflict resolution and sexual and relationship satisfaction. We used 1,627 couples from wave III of the Couple Relationships and Transition Experiences (CREATE) study. Sexual mindfulness moderated the association between conflict resolution and sexual satisfaction, even after controlling for attachment. Wives higher in sexual mindful awareness may rely less on conflict resolution for their sexual satisfaction. Karremans and colleagues' (2017) model of mindfulness and romantic relationships provides a framework for testing whether, when, and how mindfulness increases positive romantic relationship processes and outcomes. Under this framework, mindfulness may provide a mechanism to help couples achieve sexual and relationship satisfaction. Mindfulness and sexual mindfulness may provide a useful mechanism for therapists, educators, social workers, and couples to enhance satisfaction within the romantic and sexual relationship even without partner buy-in.

Perspectives from Highly Religious Families on Boundaries and Rules About Sex.

We investigated the intersection of religion and boundaries placed around sex using qualitative data from 198 highly religious Muslim, Christian, and Jewish families. Coding performed by two researchers resulted in six core themes that provide insight into the connection between these two domains. Frequency counts of the core themes, participant quotes, and implications are presented-including the benefits of practitioners inquiring into how clients' faith affects sexual behavior and scripts, how fidelity and vows might serve a protective function for the relationships of highly religious couples, and how religion may empower women in terms of sexual boundary setting.

Differential diagnosis of Alzheimer's disease using spectrochemical analysis of blood.

The progressive aging of the world's population makes a higher prevalence of neurodegenerative diseases inevitable. The necessity for an accurate, but at the same time, inexpensive and minimally invasive, diagnostic test is urgently required, not only to confirm the presence of the disease but also to discriminate between different types of dementia to provide the appropriate management and treatment. In this study, attenuated total reflection FTIR (ATR-FTIR) spectroscopy combined with chemometric techniques were used to analyze blood plasma samples from our cohort. Blood samples are easily collected by conventional venepuncture, permitting repeated measurements from the same individuals to monitor their progression throughout the years or evaluate any tested drugs. We included 549 individuals: 347 with various neurodegenerative diseases and 202 age-matched healthy individuals. Alzheimer's disease (AD; n = 164) was identified with 70% sensitivity and specificity, which after the incorporation of apolipoprotein ε4 genotype (APOE ε4) information, increased to 86% when individuals carried one or two alleles of ε4, and to 72% sensitivity and 77% specificity when individuals did not carry ε4 alleles. Early AD cases (n = 14) were identified with 80% sensitivity and 74% specificity. Segregation of AD from dementia with Lewy bodies (DLB; n = 34) was achieved with 90% sensitivity and specificity. Other neurodegenerative diseases, such as frontotemporal dementia (FTD; n = 30), Parkinson's disease (PD; n = 32), and progressive supranuclear palsy (PSP; n = 31), were included in our cohort for diagnostic purposes. Our method allows for both rapid and robust diagnosis of neurodegeneration and segregation between different dementias.

Associations of mindfulness with adolescent outcomes and sexuality.

INTRODUCTION: Using an online survey, we evaluated how adolescent trait and state mindfulness was associated with positive adolescent outcomes in non-sexually active and sexually active adolescents. Additionally, we evaluated a newly developed measure, the Sexual Mindfulness Measure (SMM), with adolescents. METHODS: We asked 2000 U.S. adolescents (half boys/girls; 1/3 low, medium, and high incomes) aged 13-18 (one group 13-15, another 16-18) about trait mindfulness, sexual state mindfulness, and adolescent outcomes. Using Confirmatory Factor Analysis and structured equation modeling, we evaluated the reliability and validity of the SMM and its associations with adolescent outcomes. RESULTS: Using a trait mindfulness measure, we found that mindful adolescents with no sexual experience, showed positive associations with self-efficacy, body-esteem, and disclosure with both fathers and mothers. Evaluating adolescents who were sexually active, we confirmed that the SMM had a two-factor structure and demonstrated acceptable reliability for both male and female adolescents. We found that the SMM was associated with positive sexual attitudes, body image, self-efficacy, and disclosure to parents above and beyond trait mindfulness. CONCLUSIONS: Trait mindfulness was associated with positive self-assessments and parental disclosure. The SMM provided an important assessment of how sexually active adolescents' ability to remain aware and non-judgmental during sexual experiences may be positively associated with outcomes such as sexual consent, positive body image, self-efficacy, disclosure to parents, and negatively associated with sexual shame and sexual anxiety above and beyond trait mindfulness.

Magnetite pollution nanoparticles in the human brain.

Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683-7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <∼200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.

Blood-based near-infrared spectroscopy for the rapid low-cost detection of Alzheimer's disease.

Alzheimer's disease (AD) is currently under-diagnosed and is predicted to affect a great number of people in the future, due to the unrestrained aging of the population. An accurate diagnosis of AD at an early stage, prior to (severe) symptomatology, is of crucial importance as it would allow the subscription of effective palliative care and/or enrolment into specific clinical trials. Today, new analytical methods and research initiatives are being developed for the on-time diagnosis of this devastating disorder. During the last decade, spectroscopic techniques have shown great promise in the robust diagnosis of various pathologies, including neurodegenerative diseases and dementia. In the current study, blood plasma samples were analysed with near-infrared (NIR) spectroscopy as a minimally-invasive method to distinguish patients with AD (n = 111) from non-demented volunteers (n = 173). After applying multivariate classification models (principal component analysis with quadratic discriminant analysis - PCA-QDA), AD individuals were correctly identified with 92.8% accuracy, 87.5% sensitivity and 96.1% specificity. Our results show the potential of NIR spectroscopy as a simple and cost-effective diagnostic tool for AD. Robust and early diagnosis may be a first step towards tackling this disease by allowing timely intervention.

Medicinal cannabis in Australia, 2016: the Cannabis as Medicine Survey (CAMS-16).

OBJECTIVE: To explore patterns of cannabis use for medical purposes in Australia immediately prior to the 2016 legislation for frameworks for medical cannabis use. Design, setting: Anonymous online survey with convenience sample, April-October 2016. Participants were recruited through online media and at professional and consumer forums. PARTICIPANTS: Adults (at least 18 years of age) who reported using a cannabis product for self-identified medical or therapeutic reasons during the preceding 12 months. MAIN OUTCOME MEASURES: Consumer characteristics; indications and patterns of medical cannabis use; perceived benefits and harms; views on appropriate availability of medical cannabis. RESULTS: Most of the 1748 participants were men (68.1%) and employed (56.6%), with a mean age of 37.9 years (SD, 13.4 years) and mean reported period of medical cannabis use of 9.8 years (SD, 12.5 years). The most frequent reasons for medical cannabis use were anxiety (50.7%), back pain (50.0%), depression (49.3%), and sleep problems (43.5%). Respondents had used medical cannabis on a mean of 19.9 of the previous 28 days (SD, 10.0 days), spending a mean $68.60 (SD, $85.00) per week, and 83.4% had inhaled the substance. Participants reported high levels of clinical effectiveness and frequent side effects, including drowsiness, ocular irritation, lethargy and memory impairment; 17% met DSM-5 criteria for moderate or severe cannabis use disorder. Many reported harms or concerns related to the illicit status of cannabis. Participants believed that medical cannabis should be integrated into mainstream health care, and that products should be required to meet consistency and safety standards. CONCLUSION: Illicitly sourced cannabis is used to treat a broad range of medical conditions in Australia. Future models of prescribed medical cannabis take consumer patterns of use and demand into consideration.

Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol.

BACKGROUND: The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches. METHODS/DESIGN: A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment. Four specialist drug and alcohol outpatient clinics in New South Wales, Australia. One hundred forty-two treatment seeking cannabis dependent adults, with no significant medical, psychiatric or other substance use disorders. Nabiximols is an oromucosal spray prescribed on a flexible dose regimen to a maximum daily dose of 32 sprays; 8 sprays (total 21.6 mg tetrahydrocannabinol (THC) and 20 mg cannabidiol (CBD)) four times a day, or matching placebo, dispensed weekly. All participants will receive six-sessions of individual cognitive behavioural therapy (CBT) and weekly clinical reviews. Primary endpoints are use of non-prescribed cannabis (self-reported cannabis use days, urine toxicology), safety measures (adverse events and abuse liability), and cost effectiveness (incremental cost effectiveness in achieving additional Quality Adjusted Life Years). Secondary outcomes include, improvement in physical and mental health parameters, substance use other than cannabis, cognitive functioning and patient satisfaction measures. DISCUSSION: This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with this population and more generally on other agonist replacement treatments (e.g. nicotine, opioids). TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12616000103460 (Registered 1st February 2016).

An Australian nationwide survey on medicinal cannabis use for epilepsy: History of antiepileptic drug treatment predicts medicinal cannabis use.

Epilepsy Action Australia conducted an Australian nationwide online survey seeking opinions on and experiences with the use of cannabis-based products for the treatment of epilepsy. The survey was promoted via the Epilepsy Action Australia's main website, on their Facebook page, and by word of mouth. The survey consisted of 39 questions assessing demographics, clinical factors, including diagnosis and seizure types, and experiences with and opinions towards cannabis use in epilepsy. A total of 976 responses met the inclusion criteria. Results show that 15% of adults with epilepsy and 13% of parents/guardians of children with epilepsy were currently using, or had previously used, cannabis products to treat epilepsy. Of those with a history of cannabis product use, 90% of adults and 71% of parents reported success in reducing seizure frequency after commencing cannabis products. The main reasons for medicinal cannabis use were to manage treatment-resistant epilepsy and to obtain a more favorable side-effect profile compared to standard antiepileptic drugs. The number of past antiepileptic drugs tried was a significant predictor of medicinal cannabis use in both adults and children with epilepsy. Fifty-six percent of adults with epilepsy and 62% of parents/guardians of children with epilepsy expressed willingness to participate in clinical trials of cannabinoids. This survey provides insight into the use of cannabis products for epilepsy, in particular some of the likely factors influencing use, as well as novel insights into the experiences of and attitudes towards medicinal cannabis in people with epilepsy in the Australian community. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy".

Retro-inverso peptide inhibitor nanoparticles as potent inhibitors of aggregation of the Alzheimer's Aß peptide.

Aggregation of amyloid-ß peptide (Aß) is a key event in the pathogenesis of Alzheimer's disease (AD). We investigated the effects of nanoliposomes decorated with the retro-inverso peptide RI-OR2-TAT (Ac-rGffvlkGrrrrqrrkkrGy-NH2) on the aggregation and toxicity of Aß. Remarkably low concentrations of these peptide inhibitor nanoparticles (PINPs) were required to inhibit the formation of Aß oligomers and fibrils in vitro, with 50% inhibition occurring at a molar ratio of ~1:2000 of liposome-bound RI-OR2-TAT to Aß. PINPs also bound to Aß with high affinity (Kd=13.2-50 nM), rescued SHSY-5Y cells from the toxic effect of pre-aggregated Aß, crossed an in vitro blood-brain barrier model (hCMEC/D3 cell monolayer), entered the brains of C57 BL/6 mice, and protected against memory loss in APPSWE transgenic mice in a novel object recognition test. As the most potent aggregation inhibitor that we have tested so far, we propose to develop PINPs as a potential disease-modifying treatment for AD.

Rapid elimination of Carboxy-THC in a cohort of chronic cannabis users.

Urinary 11-nor-Δ(9)-tetrahydrocannabinol-9-carboxylic acid (Carboxy-THC) concentrations, normalised to creatinine output, have been demonstrated to be a useful tool in the interpretation of the results of a series of urine tests for cannabis. These tests, often termed historical data, can be used to identify potential chronic cannabis users who may present occupational health and safety risks within the workplace. Conversely, the data can also be used to support employee claims of previous regular, rather than recent, cannabis use. This study aimed at examining the mean elimination of Carboxy-THC in 37 chronic users undergoing voluntary abstinence over a 2-week period. Urine specimens were collected prior to the study and after 1 and 2 weeks of abstinence. Carboxy-THC levels in urine were measured by gas chromatography-mass spectrometry (GC-MS) following alkaline hydrolysis, organic solvent extraction and derivatisation to form its pentafluoropropionic derivative. The creatinine-normalised Carboxy-THC concentrations declined rapidly over the 2 weeks of abstinence period and the majority of chronic cannabis users (73%) reduced their urinary Carboxy-THC levels to below the 15-µg/L confirmatory cutoff within that time. The study further highlights the value of historical urinary Carboxy-THC data as a means of identifying potential occupational health and safety risks among chronic cannabis users.