Complex epistatic interactions between ELF3, PRR9, and PRR7 regulate the circadian clock and plant physiology.

Circadian clocks are endogenous timekeeping mechanisms that coordinate internal physiological responses with the external environment. EARLY FLOWERING3 (ELF3), PSEUDO RESPONSE REGULATOR (PRR9), and PRR7 are essential components of the plant circadian clock and facilitate entrainment of the clock to internal and external stimuli. Previous studies have highlighted a critical role for ELF3 in repressing the expression of PRR9 and PRR7. However, the functional significance of activity in regulating circadian clock dynamics and plant development is unknown. To explore this regulatory dynamic further, we first employed mathematical modeling to simulate the effect of the prr9/prr7 mutation on the elf3 circadian phenotype. These simulations suggested that simultaneous mutations in prr9/prr7 could rescue the elf3 circadian arrhythmia. Following these simulations, we generated all Arabidopsis elf3/prr9/prr7 mutant combinations and investigated their circadian and developmental phenotypes. Although these assays could not replicate the results from the mathematical modeling, our results have revealed a complex epistatic relationship between ELF3 and PRR9/7 in regulating different aspects of plant development. ELF3 was essential for hypocotyl development under ambient and warm temperatures, while PRR9 was critical for root thermomorphogenesis. Finally, mutations in prr9 and prr7 rescued the photoperiod-insensitive flowering phenotype of the elf3 mutant. Together, our results highlight the importance of investigating the genetic relationship among plant circadian genes.

Life-Course Brain Health as a Determinant of Late-Life Mental Health: American Association for Geriatric Psychiatry Expert Panel Recommendations.

This position statement of the Expert Panel on Brain Health of the American Association for Geriatric Psychiatry (AAGP) emphasizes the critical role of life course brain health in shaping mental well-being during the later stages of life. Evidence posits that maintaining optimal brain health earlier in life is crucial for preventing and managing brain aging-related disorders such as dementia/cognitive decline, depression, stroke, and anxiety. We advocate for a holistic approach that integrates medical, psychological, and social frameworks with culturally tailored interventions across the lifespan to promote brain health and overall mental well-being in aging adults across all communities. Furthermore, our statement underscores the significance of prevention, early detection, and intervention in identifying cognitive decline, mood changes, and related mental illness. Action should also be taken to understand and address the needs of communities that traditionally have unequal access to preventive health information and services. By implementing culturally relevant and tailored evidence-based practices and advancing research in geriatric psychiatry, behavioral neurology, and geroscience, we can enhance the quality of life for older adults facing the unique challenges of aging. This position statement emphasizes the intrinsic link between brain health and mental health in aging, urging healthcare professionals, policymakers, and a broader society to prioritize comprehensive strategies that safeguard and promote brain health from birth through later years across all communities. The AAGP Expert Panel has the goal of launching further activities in the coming months and years.

Factors associated with return of home oral fluid kits by suspected cases of measles, cohort study, London and South East of England, 2016-2018.

A testing rate for measles above 80% is required by the WHO European Region Measles Elimination strategy to verify elimination. To comply with this rate, we explored factors associated with the return of oral fluid kits (OFK) by suspected measles cases. We described the cases and conducted a mixed-effects analysis to assess the relationship between socio-demographic and public health management characteristics and the likelihood of returning an OFK to the reference laboratory. Of 3,929 cases who were sent a postal OFK, 2,513 (67%) returned the kit. Adjusting for confounding, registration with a general practitioner (GP) (aOR:1.48, 95%CI:1.23-1.76) and living in a less deprived area (aOR:1.35, 95%CI:1.04-1.74) were associated with an increased likelihood of returning the OFK. The odds of returning the OFK also increased if the HPT contacted the parents/guardians of all cases prior to sending the kit and confirmed their address (aOR:2.01, 95%CI:1.17-3.42). Cases notified by a hospital (aOR:1.94, 95%CI:1.31-2.87) or GP (aOR:1.52; 95%CI:1.06-2.16) also had higher odds of returning the OFK. HPTs may want to consider these factors when managing suspected cases of measles since this may help in increasing the testing rates to the WHO-recommended level.

Influenza in carehome residents: applying a conceptual framework to describe barriers to the implementation of guidance on treatment and prophylaxis.

BACKGROUND: The European Centre for Disease Prevention and Control, National Institute for Health and Care Excellence and Public Health England have all endorsed the use of antivirals for the treatment and prophylaxis of influenza for care home residents. However, implementing these guidelines in practice is often challenging. This article aims to explore what factors impact the management of care home flu outbreaks in England according to national guidelines and highlight opportunities for change. METHODS: Qualitative data from notified outbreaks between September 2017 to April 2018 in the South East of England were analyzed, applying the Greenhalgh framework for barriers to guideline implementation. Summary statistics on outbreak characteristics were generated. Stakeholders were mapped out using Eden and Ackermann's grid of interest and influence. A process map was developed to describe operational pathways. RESULTS: There was often a delay in notifying potential outbreaks to Public Health England. Clinicians cited a lack of robust evidence for the use of antivirals and the available guidelines being too unwieldy as reasons for not implementing prescribing guidance. Many high interests and high influence stakeholders are involved in the sometimes complex care pathway, requiring coordinated work and agreement before antivirals can be prescribed. CONCLUSIONS: Our findings highlight points in the care pathway that stakeholders can target to improve quality of care and increase the likelihood of national guidance being implemented. The principles described in this article can also be applied to other challenges of translating evidence into practice and cross-organisational working.

Lifestyle Choices and Brain Health.

This article is largely based on the recommendations of the AARP's Global Council on Brain Health (GCBH) and aims to provide an overview of evidence from current literature and expert opinion on key elements known to be relevant in preserving brain health as people age. Although we realize that there may be other lifestyle choices of importance to brain health, the GCBH has decided to initially focus on the issues below based on the preferences and concerns of its members. The areas to be discussed are: mental well-being, exercise, cognitively stimulating activities, sleep, nutrition, and social connectedness. Our review concluded that each of these areas offer opportunities for aging individuals to make lifestyle adjustments to positively impact brain health.

CDC Grand Rounds: Promoting Well-Being and Independence in Older Adults.

Healthy aging is not merely the absence of disease or disability, but requires physical and mental health and ongoing social engagement (1). As the average U.S. life expectancy increases, recognition that public health can play a vital role in promoting healthy, successful aging even in the face of increased prevalence of chronic diseases, including types of dementia, among older adults (i.e., aged ≥65 years) has grown. Furthermore, actively engaging adults in prevention and wellness along with involving their caregivers (i.e., the family and friends of older adults who provide them with unpaid and informal support and services) can serve to prevent or delay the onset of physical disabilities and cognitive decline. Adults often are reluctant to discuss their concerns about worsening memory with their health care providers although such discussions can lead to earlier diagnosis and better care, planning, and support. As advances in public health and health care have helped increase life expectancy, public health professionals and health care providers have the opportunity to improve the quality of life for older adults and their caregivers and reduce the burdens associated with aging.

Synthesis, Characterization, and Bioactivity of the Photoisomerizable Tubulin Polymerization Inhibitor azo-Combretastatin A4.

Combretastatin A4 is a stilbenoid tubulin binding mitotic inhibitor whose conformation greatly influences its potency, making it an excellent candidate for adaptation as a photoactivatable tool. Herein we report a novel synthesis, the facile isomerization with commercial grade equipment, and biological activity of azo-combretastatin A4 in vitro and in human cancer cells. Photoisomerized azo-combretestatin A4 is at least 200-fold more potent in cellular culture, making it a promising phototherapeutic and biomedical research tool.

Secondary stressors and extreme events and disasters: a systematic review of primary research from 2010-2011.

Introduction Extreme events and disasters, such as earthquakes and floods, cause distress and are associated with some people developing mental disorders. Primary stressors inherent in many disasters can include injuries sustained or watching someone die. The literature recognises the distress which primary stressors cause and their association with mental disorders. Secondary stressors such as a lack of financial assistance, the gruelling process of submitting an insurance claim, parents' worries about their children, and continued lack of infrastructure can manifest their effects shortly after a disaster and persist for extended periods of time. Secondary stressors, and their roles in affecting people's longer-term mental health, should not be overlooked. We draw attention in this review to the nature of secondary stressors that are commonly identified in the literature, assess how they are measured, and develop a typology of these stressors that often affect people after extreme events. Methods We searched for relevant papers from 2010 and 2011 using MEDLINE®, Embase and PsycINFO®. We selected primary research papers that evaluated the associations between secondary stressors and distress or mental disorders following extreme events, and were published in English. We extracted information on which secondary stressors were assessed, and used thematic analysis to group the secondary stressors into a typology. Results Thirty-two relevant articles published in 2010 and 2011 were identified. Many secondary stressors were poorly defined and difficult to differentiate from primary stressors or other life events. We identified 11 categories of secondary stressors, though some extend over more than one category. The categories include: economic stressors such as problems with compensation, recovery of and rebuilding homes; loss of physical possessions and resources; health-related stressors; stress relating to education and schooling; stress arising from media reporting; family and social stressors; stress arising from loss of leisure and recreation; and stress related to changes in people's views of the world or themselves. Limitations in this review include its focus on studies published in 2010 and 2011, which may have led to some secondary stressors being excluded. Assumptions have been made about whether certain items are secondary stressors, if unclear definitions made it difficult to differentiate them from primary stressors. Conclusions This is the first review, to our knowledge, that has developed a typology of secondary stressors that occur following extreme events. We discuss the differing natures of these stressors and the criteria that should be used to differentiate primary and secondary stressors. Some secondary stressors, for example, are entities in themselves, while others are persisting primary stressors that exert their effects through failure of societal responses to disasters to mitigate their immediate impacts. Future research should aim to define secondary stressors and investigate the interactions between stressors. This is essential if we are to identify which secondary stressors are amenable to interventions which might reduce their impacts on the psychosocial resilience and mental health of people who are affected by disasters. Corresponding Author: Dr Sarah Lock, Extreme Events and Health Protection, London, 151 Buckingham Palace Road, London, SW1W 9SZ. E-mail: sarah.lock@hpa.org.uk.

Interaction-focused intervention for acquired language disorders: facilitating mutual adaptation in couples where one partner has aphasia.

This paper discusses the implementation and evaluation of an interaction-focused intervention single case study for a couple where one partner has aphasia. Drawing on conversation analytic research, naturally occurring conversations of the couple at home pre- and post-intervention were collected and analysed. Analysis of the speaker with aphasia's topic initiating turns in the pre-intervention conversation showed that in each case a feature of the attempt was that the speaker had difficulty in getting the topic initiation accepted and established. Drawing on conversation analytic work on topic initiations in normal conversation, intervention focused on training the couple to co-produce these topic initiating turns of the speaker with aphasia in a collaborative and step-by-step manner. Post-intervention, there was evidence that the couple were now using this new method, albeit in a slightly different way to that worked on in the intervention sessions. Drawing on work into adaptation by speakers with aphasia and their conversation partners, these results are discussed in terms of a process of mutual adaptation by the couple.

Integration of mental health into primary care in Kenya.

Integration of mental health into primary care is essential in Kenya, where there are only 75 psychiatrists for 38 million population, of whom 21 are in the universities and 28 in private practice. A partnership between the Ministry of Health, the Kenya Psychiatric Association and the World Health Organization (WHO) Collaborating Centre, Institute of Psychiatry, Kings College London was funded by Nuffield Foundation to train 3,000 of the 5,000 primary health care staff in the public health system across Kenya, using a sustainable general health system approach. The content of training was closely aligned to the generic tasks of the health workers. The training delivery was integrated into the normal national training delivery system, and accompanied by capacity building courses for district and provincial level staff to encourage the inclusion of mental health in the district and provincial annual operational plans, and to promote the coordination and supervision of mental health services in primary care by district psychiatric nurses and district public health nurses. The project trained 41 trainers, who have so far trained 1671 primary care staff, achieving a mean change in knowledge score of 42% to 77%. Qualitative observations of subsequent clinical practice have demonstrated improvements in assessment, diagnosis, management, record keeping, medicine supply, intersectoral liaison and public education. Around 200 supervisors (psychiatrists, psychiatric nurses and district public health nurses) have also been trained. The project experience may be useful for other countries also wishing to conduct similar sustainable training and supervision programmes.

Integration of mental health into primary care and community health working in Kenya: context, rationale, coverage and sustainability.

Integration of mental health into primary care is essential to meet population needs yet faces many challenges if such projects are to achieve impact and be sustainable in low income countries alongside other competing priorities. This paper describes the rationale and progress of a collaborative project in Kenya to train primary care and community health workers about mental health and integrate mental health into their routine work, Within a health systems strengthening approach. So far 1877 health workers have been trained. The paper describes the multiple challenges faced by the project, and reviews the mechanisms deployed which have strengthened its impact and sustainability to date.