A phase III multisite randomised controlled trial to compare the efficacy of cannabidiol to placebo in the treatment of cannabis use disorder: the CBD-CUD study protocol.

BACKGROUND: Cannabis use disorder (CUD) is increasingly common and contributes to a range of health and social problems. Cannabidiol (CBD) is a non-intoxicating cannabinoid recognised for its anticonvulsant, anxiolytic and antipsychotic effects with no habit-forming qualities. Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people with CUD. This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD. METHODS/DESIGN: A phase III multi-site, randomised, double-blinded, placebo controlled parallel design of a 12-week course of CBD to placebo, with follow-up at 24 weeks after enrolment. Two hundred and fifty adults with moderate-to-severe CUD (target 20% Aboriginal), with no significant medical, psychiatric or other substance use disorders from seven drug and alcohol clinics across NSW and VIC, Australia will be enrolled. Participants will be administered a daily dose of either 4 mL (100 mg/mL) of CBD or a placebo dispensed every 3-weeks. All participants will receive four-sessions of Cognitive Behavioural Therapy (CBT) based counselling. Primary endpoints are self-reported cannabis use days and analysis of cannabis metabolites in urine. Secondary endpoints include severity of CUD, withdrawal severity, cravings, quantity of use, motivation to stop and abstinence, medication safety, quality of life, physical/mental health, cognitive functioning, and patient treatment satisfaction. Qualitative research interviews will be conducted with Aboriginal participants to explore their perspectives on treatment. DISCUSSION: Current psychosocial and behavioural treatments for CUD indicate that over 80% of patients relapse within 1-6 months of treatment. Pharmacological treatments are highly effective with other substance use disorders but there are no approved pharmacological treatments for CUD. CBD is a promising candidate for CUD treatment due to its potential efficacy for this indication and excellent safety profile. The anxiolytic, antipsychotic and neuroprotective effects of CBD may have added benefits by reducing many of the mental health and cognitive impairments reported in people with regular cannabis use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12623000526673 (Registered 19 May 2023).

Antenatal care is associated with adherence to iron supplementation among pregnant women in selected low-middle-income-countries of Asia, Africa, and Latin America & the Caribbean regions: Insights from Demographic and Health Surveys.

Anaemia is a global public health problem affecting 800 million women and children globally. Anaemia is associated with perinatal mortality, child morbidity and mortality, mental development, immune competence, susceptibility to lead poisoning and performance at work. The objective of this article is to identify whether antenatal care-seeking was associated with the uptake of iron supplementation among pregnant women, adjusting for a range of covariates. This article used data from the cross-sectional recent Demographic and Health Surveys (DHS) of 12 countries in Asia, Africa and Latin America & the Caribbean regions. The individual-level data from 273,144 women of reproductive age (15-49 years) were analysed from multi-country DHS. Multiple Logistic regression analyses were conducted using Predictive Analytics Software for Windows (PASW), Release 18.0. Receiving at least four antenatal care visits was significantly associated with the consumption of 90 or more iron-containing supplements in 12 low and middle income countries across three regions after adjusting for different household and respondent characteristics, while mass media exposure was found to be a significant predictor in India and Indonesia. Antenatal care seems to be the most important predictor of adherence to iron intake in the selected countries across Africa, Asia, Latin America and Caribbean regions.

Shifts in predator behaviour following climate induced disturbance on coral reefs.

Coral reefs are increasingly ecologically destabilized across the globe due to climate change. Behavioural plasticity in corallivore behaviour and short-term trophic ecology in response to bleaching events may influence the extent and severity of coral bleaching and subsequent recovery potential, yet our understanding of these interactions in situ remains unclear. Here, we investigated interactions between corallivory and coral bleaching during a severe high thermal event (10.3-degree heating weeks) in Belize. We found that parrotfish changed their grazing behaviour in response to bleaching by selectively avoiding bleached Orbicella spp. colonies regardless of bleaching severity or coral size. For bleached corals, we hypothesize that this short-term respite from corallivory may temporarily buffer coral energy budgets by not redirecting energetic resources to wound healing, and may therefore enable compensatory nutrient acquisition. However, colonies that had previously been heavily grazed were also more susceptible to bleaching, which is likely to increase mortality risk. Thus, short-term respite from corallivory during bleaching may not be sufficient to functionally rescue corals during prolonged bleaching. Such pairwise interactions and behavioural shifts in response to disturbance may appear small scale and short term, but have the potential to fundamentally alter ecological outcomes, especially in already-degraded ecosystems that are vulnerable and sensitive to change.

'Omics' approaches in developing combined drought and heat tolerance in food crops.

Global climate change will significantly increase the intensity and frequency of hot, dry days. The simultaneous occurrence of drought and heat stress is also likely to increase, influencing various agronomic characteristics, such as biomass and other growth traits, phenology, and yield-contributing traits, of various crops. At the same time, vital physiological traits will be seriously disrupted, including leaf water content, canopy temperature depression, membrane stability, photosynthesis, and related attributes such as chlorophyll content, stomatal conductance, and chlorophyll fluorescence. Several metabolic processes contributing to general growth and development will be restricted, along with the production of reactive oxygen species (ROS) that negatively affect cellular homeostasis. Plants have adaptive defense strategies, such as ROS-scavenging mechanisms, osmolyte production, secondary metabolite modulation, and different phytohormones, which can help distinguish tolerant crop genotypes. Understanding plant responses to combined drought/heat stress at various organizational levels is vital for developing stress-resilient crops. Elucidating the genomic, proteomic, and metabolic responses of various crops, particularly tolerant genotypes, to identify tolerance mechanisms will markedly enhance the continuing efforts to introduce combined drought/heat stress tolerance. Besides agronomic management, genetic engineering and molecular breeding approaches have great potential in this direction.

Heat Priming of Lentil (Lens culinaris Medik.) Seeds and Foliar Treatment with γ-Aminobutyric Acid (GABA), Confers Protection to Reproductive Function and Yield Traits under High-Temperature Stress Environments.

Gradually increasing temperatures at global and local scales are causing heat stress for cool and summer-season food legumes, such as lentil (Lens culinaris Medik.), which is highly susceptible to heat stress, especially during its reproductive stages of development. Hence, suitable strategies are needed to develop heat tolerance in this legume. In the present study, we tested the effectiveness of heat priming (HPr; 6 h at 35 °C) the lentil seeds and a foliar treatment of γ-aminobutyric acid (GABA; 1 mM; applied twice at different times), singly or in combination (HPr+GABA), under heat stress (32/20 °C) in two heat-tolerant (HT; IG2507, IG3263) and two heat-sensitive (HS; IG2821, IG2849) genotypes to mitigate heat stress. The three treatments significantly reduced heat injury to leaves and flowers, particularly when applied in combination, including leaf damage assessed as membrane injury, cellular oxidizing ability, leaf water status, and stomatal conductance. The combined HPr+GABA treatment significantly improved the photosynthetic function, measured as photosynthetic efficiency, chlorophyll concentration, and sucrose synthesis; and significantly reduced the oxidative damage, which was associated with a marked up-regulation in the activities of enzymatic antioxidants. The combined treatment also facilitated the synthesis of osmolytes, such as proline and glycine betaine, by upregulating the expression of their biosynthesizing enzymes (pyrroline-5-carboxylate synthase; betaine aldehyde dehydrogenase) under heat stress. The HPr+GABA treatment caused a considerable enhancement in endogenous levels of GABA in leaves, more so in the two heat-sensitive genotypes. The reproductive function, measured as germination and viability of pollen grains, receptivity of stigma, and viability of ovules, was significantly improved with combined treatment, resulting in enhanced pod number (21-23% in HT and 35-38% in HS genotypes, compared to heat stress alone) and seed yield per plant (22-24% in HT and 37-40% in HS genotypes, in comparison to heat stress alone). The combined treatment (HPr+GABA) was more effective and pronounced in heat-sensitive than heat-tolerant genotypes for all the traits tested. This study offers a potential solution for tackling and protecting heat stress injury in lentil plants.

Family influences on health and nutrition practices of pregnant adolescents in Bangladesh.

Adolescent pregnancy can result in serious risks to the mother and her baby; yet, adolescents are among the least likely to access healthcare. Specific nutrition or antenatal care (ANC) guidelines for supporting pregnant adolescents are not available. To understand experiences and decision-making of pregnant adolescents in Bangladesh related to ANC and nutrition practices, peer interviewers were trained to conduct qualitative interviews in Dhaka and Rangpur with pregnant adolescents (n = 48), adolescent mothers (n = 48), adolescents' family members (n = 64) and health service providers (n = 32). Key themes explored included perception and support of adolescent pregnancy, experiences in seeking ANC, dietary practices, sources of information and roles of male and female family members. Spheres of influence on adolescent pregnancy were identified through analytical framework informed by the socio-ecological model. Respondents felt that adolescent pregnancy is risky and that adolescents require support and guidance through this experience. Families were highly influential on the care seeking, health and nutrition of pregnant adolescents, and mothers/mothers-in-law primarily took on the decision-making roles, with husbands actively participating. Adolescents valued family support but felt a loss of autonomy and agency upon becoming pregnant. Financial constraints were the greatest perceived barrier to appropriate nutrition and healthcare; yet, both were valued. There is sometimes discord of health and nutrition beliefs between families and health service providers; more research is needed to understand this further. It is essential to engage family members and adolescents in initiatives to increase access to quality ANC for pregnant adolescents, improve dietary practices and support the ability to delay pregnancy.

Nitric oxide secures reproductive efficiency in heat-stressed lentil (Lens culinaris Medik.) plants by enhancing the photosynthetic ability to improve yield traits.

Rising temperatures, globally and locally, would be detrimental for cool- and summer-season food legumes, such as lentil (Lens culinaris Medik.). Lentil is highly sensitive to supra-optimal temperatures (> 30 °C), particularly during reproductive growth, resulting in flower and pod losses. Thus, suitable strategies are needed to introduce heat tolerance in this legume. Here, we evaluated the efficacy of nitric oxide (NO)-applied as foliar treatment of 1 mM sodium nitroprusside (SNP), twice (one day before final exposure to high temperature, and again five days later)-on heat-stressed (32/20 °C) lentil genotypes, differing in heat sensitivity. As a result of heat stress, endogenous NO increased significantly in heat-tolerant genotypes (46-62% in leaves and 66-68% in anthers, relative to the respective controls), while it decreased in heat-sensitive (HS) genotypes (27-30% in leaves and 28-33% in anthers, relative to the respective controls). Foliar supplementation with SNP markedly increased endogenous NO in leaves and anthers of both the control and heat-treated plants. Heat stress significantly accelerated phenology, damaged membranes, chlorophyll, chlorophyll fluorescence, cellular viability, and decreased leaf water status, carbon fixing and assimilating ability, less so in plants treated with SNP. Heat stress plus SNP significantly improved carbon fixation (as RuBisCo activity) and assimilation ability, (as sucrose concentration (in leaves and anthers), sucrose synthase and vacuolar acid invertase activity, reducing sugars), as well as osmolyte accumulation (proline and glycine betaine) in leaves and anthers. Moreover, SNP-treated plants had significantly less oxidative damage-measured as malondialdehyde and hydrogen peroxide concentrations-in leaves and anthers, relative to the respective control. Reproductive function-assessed as pollen grain germination and viability, stigma receptivity, and ovular viability-decreased markedly in plants exposed to heat stress alone, more so in HS genotypes, but increased significantly with SNP treatment as a consequence of improved leaf and anther function, to significantly increase the pod and seed numbers in heat-stressed lentil plants, relative to heat-stress alone.

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).

Non-AIDS complexity amongst patients living with HIV in Sydney: risk factors and health outcomes.

OBJECTIVE: To assess the prevalence of non-AIDS co-morbidities (NACs) and predictors of adverse health outcomes amongst people living with HIV in order to identify health needs and potential gaps in patient management. DESIGN: Retrospective, non-consecutive medical record audit of patients attending a publicly funded HIV clinic in metropolitan Sydney analysed for predictors of adverse health outcomes. We developed a scoring system based on the validated Charlson score method for NACs, mental health and social issues and confounders were selected using directed acyclic graph theory under the principles of causal inference. RESULTS: 211 patient files were audited non-consecutively over 6 weeks. 89.5% were male; 41.8% culturally and linguistically diverse and 4.1% were of Aboriginal/Torres Strait Islander origin. Half of patients had no general practitioner and 25% were ineligible for Medicare subsidised care. The most common NACs were: cardiovascular disease (25%), hepatic disease (21%), and endocrinopathies (20%). One-third of patients had clinical anxiety, one-third major depression and almost half of patients had a lifetime history of tobacco smoking. Five predictors of poor health outcomes were identified: (1) co-morbidity score was associated with hospitalisation (odds ratio, OR 1.58; 95% CI 1.01-2.46; p = 0.044); (2) mental health score was associated with hospitalisation (OR 1.79; 95% CI 1.22-2.62; p = 0.003) and poor adherence to ART (OR 2.34; 95% CI 1.52-3.59; p = 0.001); (3) social issues score was associated with genotypic resistance (OR 2.61; 95% CI 1.48-4.59; p = 0.001), co-morbidity score (OR 1.69; 95% CI 1.24-2.3; p = 0.001) and hospitalisation (OR 1.72; 95% CI 1.1-2.7; p = 0.018); (4) body mass index < 20 was associated with genotypic resistance (OR 6.25; 95% CI 1.49-26.24; p = 0.012); and (5) Medicare eligibility was associated with co-morbidity score (OR 2.21; 95% CI 1.24-3.95; p = 0.007). CONCLUSION: Most HIV patients are healthy due to effective antiretroviral therapy; however, NACs and social/mental health issues are adding to patient complexity. The current findings underpin the need for multidisciplinary management beyond routine viral load and CD4 count monitoring.

Social networks of adults with an intellectual disability from South Asian and White communities in the United Kingdom: A comparison.

BACKGROUND: Little research exists comparing the social networks of people with intellectual disability (ID) from South Asian and White backgrounds. This UK study reports on the barriers that South Asian people with intellectual disability face in relation to social inclusion compared to their White counterparts. MATERIALS AND METHODS: A mixed-methods research design was adopted to explore the social lives of 27 men (15 White; 12 South Asian) and 20 women (10 White; 10 South Asian with intellectual disability). Descriptive and parametric tests were used to analyse the quantitative data. RESULTS: The average network size of the whole group was 32 members. South Asian participants had more family members whilst White participants had more service users and staff in their networks; 96% network members from White intellectual disability group were also of White background, whilst the South Asian group had mixed ethnic network members. CONCLUSIONS: Social networks of individuals with intellectual disability in this study were found to be larger overall in comparison with previous studies, whilst network structure differed between the White and South Asian population. These differences have implications relating to future service planning and appropriateness of available facilities.

Advancements in CRISPR-Based Therapies for Genetic Modulation in Neurodegenerative Disorders.

: Neurodegenerative disorders pose significant challenges in the realm of healthcare, as these conditions manifest in complex, multifaceted ways, often attributed to genetic anomalies. With the emergence of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology, a new frontier has been unveiled in the quest for targeted, precise genetic manipulation. This abstract explores the recent advancements and potential applications of CRISPR-based therapies in addressing genetic components contributing to various neurodegenerative disorders. The review delves into the foundational principles of CRISPR technology, highlighting its unparalleled ability to edit genetic sequences with unprecedented precision. In addition, it talks about the latest progress in using CRISPR to target specific genetic mutations linked to neurodegenerative diseases like Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. It talks about the most important studies and trials that show how well and safely CRISPR-based therapies work. This shows how this technology can change genetic variants that cause diseases. Notably, the discussion emphasizes the challenges and ethical considerations associated with the implementation of CRISPR in clinical settings, including off-target effects, delivery methods, and long-term implications. Furthermore, the article explores the prospects and potential hurdles in the widespread application of CRISPR technology for treating neurodegenerative disorders. It touches upon the need for continued research, improved delivery mechanisms, and ethical frameworks to ensure responsible and equitable access to these groundbreaking therapies.

Dementia in people with intellectual disability: insights and challenges in epidemiological research with an at-risk population.

The population with intellectual disability (ID) is ageing, but age-related health concerns such as dementia have received little research attention thus far. We review evidence regarding the prevalence and incidence of dementia in people with ID, and discuss some possible explanations for an increased risk, such as shared genetic risk factors, co-morbid physical and mental disorders, lifestyle factors, trauma, and lowered brain reserve. We discuss practical and theoretical challenges facing researchers in this field, before highlighting the implications of findings to date for future research and clinical care. Research on dementia in this at-risk population has the potential to help us understand dementia in general and to improve services for this group of vulnerable individuals.

Investigating the influence of elevated temperature on nutritional and yield characteristics of mung bean (Vigna radiata L.) genotypes during seed filling in a controlled environment.

Rising temperatures impact different developmental stages of summer crops like mung bean, particularly during the crucial seed-filling stage. This study focused on two mung bean genotypes, categorized as heat-tolerant [HT] or heat-sensitive [HS]. These genotypes were grown in pots in an outdoor natural environment (average day/night temperature 36°C/24.3°C) until the onset of podding (40 days after sowing) and subsequently relocated to controlled-environment walk-in growth chambers for exposure to heat stress (42°C/30°C) or control conditions (35°C/25°C) until maturity. For all measured attributes, heat stress had a more pronounced effect on the HS genotype than on the HT genotype. Heat-stressed plants exhibited severe leaf damage, including membrane damage, reduced chlorophyll content, diminished chlorophyll fluorescence, and decreased leaf water content. Heat stress impeded the seed-filling rate and duration, decreasing starch, protein, fat, and mineral contents, with a notable decline in storage proteins. Heat stress disrupted the activities of several seed enzymes, inhibiting starch and sucrose accumulation and consequently decreasing individual seed weights and seed weight plant-1. This study revealed that heat stress during seed filling severely impaired mung bean seed yield and nutritional quality due to its impact on various stress-related traits in leaves and enzyme activities in seeds. Moreover, this research identified potential mechanisms related to heat tolerance in genotypes with contrasting heat sensitivity.

Vertebrate growth plasticity in response to variation in a mutualistic interaction.

Vertebrate growth can be phenotypically plastic in response to predator-prey and competitive interactions. It is unknown however, if it can be plastic in response to mutualistic interactions. Here we investigate plasticity of vertebrate growth in response to variation in mutualistic interactions, using clown anemonefish and their anemone hosts. In the wild, there is a positive correlation between the size of the fish and the size of the anemone, but the cause of this correlation is unknown. Plausible hypotheses are that fish exhibit growth plasticity in response to variation in food or space provided by the host. In the lab, we pair individuals with real anemones of various sizes and show that fish on larger anemones grow faster than fish on smaller anemones. By feeding the fish a constant food ration, we exclude variation in food availability as a cause. By pairing juveniles with artificial anemones of various sizes, we exclude variation in space availability as a single cause. We argue that variation in space availability in conjunction with host cues cause the variability in fish growth. By adjusting their growth, anemonefish likely maximize their reproductive value given their anemone context. More generally, we demonstrate vertebrate growth plasticity in response to variation in mutualistic interactions.

Cannabis use in patients 3 months after ceasing nabiximols for the treatment of cannabis dependence: Results from a placebo-controlled randomised trial.

INTRODUCTION AND AIMS: Previous studies suggest cannabinoid agonist treatment is effective in reducing cannabis use in dependent treatment seekers, however few studies have reported on post-treatment outcomes. We examine cannabis use outcomes 12 weeks after cessation of treatment from a randomised placebo-controlled trial of nabiximols for the treatment of cannabis dependence. METHOD: 128 participants received either nabiximols (n = 61) or placebo (n = 67) for 12 weeks, in combination with psychosocial interventions. Self-reported number of days of cannabis use in the previous 28 days was measured at baseline, 4, 8, and 12 weeks (end of treatment) and again at 24 weeks (3 months after treatment ceased). Urinalysis was used to confirm self-report data at Week 24 interview. RESULTS: A factorial mixed-effects model for repeated measures regression revealed that the nabiximols group used cannabis on 6.8 fewer days in the previous 28 days at week 12 (end of treatment) than the placebo group (p = 0.002, CI: 2.1,11.4), and 6.7 fewer days in the previous 28 days at the week-24 follow-up than the placebo group (p = 0.006, CI: 1.4,12.1). A significantly higher proportion of the nabiximols group (14/61; 23 %) than the placebo group (6/67; 9%) reported abstinence from cannabis in the previous 28 days at the week-24 research interview OR=3.0, CI: 1.1, 9.1; p=0.035, NNT=8, CI: 4, 71). DISCUSSIONS AND CONCLUSIONS: The benefits of treatment incorporating nabiximols with psychosocial interventions in reducing cannabis use appears to persist for up to 3 months after the cessation of treatment. A stepped care model of treatment is proposed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12616000103460) https://www.anzctr.org.au.

Identification and Characterization of Contrasting Genotypes/Cultivars for Developing Heat Tolerance in Agricultural Crops: Current Status and Prospects.

Rising global temperatures due to climate change are affecting crop performance in several regions of the world. High temperatures affect plants at various organizational levels, primarily accelerating phenology to limit biomass production and shortening reproductive phase to curtail flower and fruit numbers, thus resulting in severe yield losses. Besides, heat stress also disrupts normal growth, development, cellular metabolism, and gene expression, which alters shoot and root structures, branching patterns, leaf surface and orientation, and anatomical, structural, and functional aspects of leaves and flowers. The reproductive growth stage is crucial in plants' life cycle, and susceptible to high temperatures, as reproductive processes are negatively impacted thus reducing crop yield. Genetic variation exists among genotypes of various crops to resist impacts of heat stress. Several screening studies have successfully phenotyped large populations of various crops to distinguish heat-tolerant and heat-sensitive genotypes using various traits, related to shoots (including leaves), flowers, fruits (pods, spikes, spikelets), and seeds (or grains), which have led to direct release of heat-tolerant cultivars in some cases (such as chickpea). In the present review, we discuss examples of contrasting genotypes for heat tolerance in different crops, involving many traits related to thermotolerance in leaves (membrane thermostability, photosynthetic efficiency, chlorophyll content, chlorophyll fluorescence, stomatal activity), flowers (pollen viability, pollen germination, fertilization, ovule viability), roots (architecture), biomolecules (antioxidants, osmolytes, phytohormones, heat-shock proteins, other stress proteins), and "omics" (phenomics, transcriptomics, genomics) approaches. The traits linked to heat tolerance can be introgressed into high yielding but heat-sensitive genotypes of crops to enhance their thermotolerance. Involving these traits will be useful for screening contrasting genotypes and would pave the way for characterizing the underlying molecular mechanisms, which could be valuable for engineering plants with enhanced thermotolerance. Wherever possible, we discussed breeding and biotechnological approaches for using these traits to develop heat-tolerant genotypes of various food crops.

Nabiximols for the Treatment of Cannabis Dependence: A Randomized Clinical Trial.

IMPORTANCE: There are no effective medications for treating dependence on cannabis. OBJECTIVE: To examine the safety and efficacy of nabiximols in the treatment of patients with cannabis dependence. DESIGN, SETTING, AND PARTICIPANTS: This parallel double-blind randomized clinical trial comparing nabiximols with placebo in a 12-week, multisite outpatient study recruited participants from February 3, 2016, to June 14, 2017, at 4 outpatient specialist alcohol and drug treatment services in New South Wales, Australia. Participants had cannabis dependence (as defined by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and were seeking treatment, were nonresponsive to prior treatment attempts, were 18 to 64 years of age, had no other substance use disorder, had no severe medical or psychiatric conditions, were not pregnant, were not mandated by a court to undergo treatment, and provided informed consent. Results for primary efficacy measures and all secondary outcomes were obtained using a modified intention-to-treat data set. INTERVENTIONS: Participants received 12-week treatment involving weekly clinical reviews, structured counseling, and flexible medication doses-up to 32 sprays daily (tetrahydrocannabinol, 86.4 mg, and cannabidiol, 80 mg), dispensed weekly. MAIN OUTCOMES AND MEASURES: Primary outcome was self-reported number of days using illicit cannabis during the 12-week period. Other outcomes included alternate cannabis use parameters (periods of abstinence, withdrawal, cravings, and problems), safety parameters (adverse events and aberrant medication use), health status, other substance use, and treatment retention. RESULTS: A total of 128 participants (30 women and 98 men; mean [SD] age, 35.0 [10.9] years) were randomized and received at least 1 dose of study medication. Participants had used a mean (SD) of 2.3 (2.1) g of cannabis on a mean (SD) of 25.7 (4.5) days in the past 28 days. Treatment retention was comparable for the 2 groups (placebo, 30 of 67 participants [44.8%]; nabiximols, 30 of 61 participants [49.2%]), and both groups used similar mean (SD) doses (placebo, 18.5 [9.5] sprays daily; nabiximols, 17.6 [9.5] sprays daily, equivalent to a mean [SD] of 47.5 [25.7] mg of tetrahydrocannabinol and 44.0 [23.8] mg of cannabidiol). For the primary end point, the placebo group reported significantly more days using cannabis during the 12 weeks (mean [SD], 53.1 [33.0] days) than the nabiximols group (mean [SD], 35.0 [32.4] days; estimated difference, 18.6 days; 95% CI, 3.5-33.7 days; P = .02). Both groups showed comparable improvements in health status, with no substantial changes in other substance use. Medication was well tolerated with few adverse events. CONCLUSIONS AND RELEVANCE: This study demonstrates that cannabinoid agonist treatment, in this case using nabiximols, in combination with psychosocial interventions is a safe approach for reducing cannabis use among individuals with cannabis dependence who are seeking treatment. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12616000103460.

Family caring of older adults with intellectual disability and coping according to loci of responsibility.

BACKGROUND: A complex interplay of factors is evident in the response of family caring for older adults with intellectual disability (ID). The aim of this study was to explore the interaction of these factors. METHODS: Quantitative data on health and wellbeing, and coping strategies were obtained for carers and their adult children with ID. Qualitative data were from three focus groups conducted with 19 main family carers. RESULTS: Carers varied in their health and wellbeing. Four overarching themes emerged from an initial interpretative phenomenological analysis of the qualitative data: loci of responsibility, impacts of caring and responses to it on health and wellbeing, transitioning care responsibilities, and interrelationships around the caring role. Further interrogation of data according to carers' coping strategies revealed three loci of responsibility, providing a point of convergence that related to carer experiences, plans for transition, and relationships within families. These loci of responsibility were having sole responsibility because there was no-one else, having sole responsibility because no-one could do it better, and sharing responsibility. CONCLUSION: The loci of responsibility provide a means to understand carers' appraisal of their role and the degree of control they have over it, and may account for varied coping strategies adopted.