Hormonal contraception and risk for cognitive impairment or Alzheimer's disease and related dementias in young women: a scoping review of the evidence.

Introduction: Women are significantly more likely to develop Alzheimer's disease and related dementias (ADRD) than men. Suggestions to explain the sex differences in dementia incidence have included the influence of sex hormones with little attention paid to date as to the effect of hormonal contraception on brain health. The aim of this scoping review is to evaluate the current evidence base for associations between hormonal contraceptive use by women and non-binary people in early adulthood and brain health outcomes. Methods: A literature search was conducted using EMBASE, Medline and Google Scholar, using the keywords "hormonal contraception" OR "contraception" OR "contraceptive" AND "Alzheimer*" OR "Brain Health" OR "Dementia". Results: Eleven papers were identified for inclusion in the narrative synthesis. Studies recruited participants from the UK, USA, China, South Korea and Indonesia. Studies included data from women who were post-menopausal with retrospective data collection, with only one study contemporaneously collecting data from participants during the period of hormonal contraceptive use. Studies reported associations between hormonal contraceptive use and a lower risk of ADRD, particularly Alzheimer's disease (AD), better cognition and larger grey matter volume. Some studies reported stronger associations with longer duration of hormonal contraceptive use, however, results were inconsistent. Four studies reported no significant associations between hormonal contraceptive use and measures of brain health, including brain age on MRI scans and risk of AD diagnosis. Discussion: Further research is needed on young adults taking hormonal contraceptives, on different types of hormonal contraceptives (other than oral) and to explore intersections between sex, gender, race and ethnicity. Systematic Review Registration: https://doi.org/10.17605/OSF.IO/MVX63, identifier: OSF.io: 10.17605/OSF.IO/MVX63.

Mental health in autistic adults: A rapid review of prevalence of psychiatric disorders and umbrella review of the effectiveness of interventions within a neurodiversity informed perspective.

BACKGROUND: Autistic adults have high risk of mental ill-health and some available interventions have been associated with increased psychiatric diagnoses. Understanding prevalence of psychiatric diagnoses is important to inform the development of individualised treatment and support for autistic adults which have been identified as a research priority by the autistic community. Interventions require to be evaluated both in terms of effectiveness and regarding their acceptability to the autistic community. OBJECTIVE: This rapid review identified the prevalence of psychiatric disorders in autistic adults, then systematic reviews of interventions aimed at supporting autistic adults were examined. A rapid review of prevalence studies was completed concurrently with an umbrella review of interventions. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed, including protocol registration (PROSPERO#CRD42021283570). DATA SOURCES: MEDLINE, CINAHL, PsycINFO, and Cochrane Database of Systematic Reviews. STUDY ELIGIBILITY CRITERIA: English language; published 2011-2022; primary studies describing prevalence of psychiatric conditions in autistic adults; or systematic reviews evaluating interventions for autistic adults. APPRAISAL AND SYNTHESIS: Bias was assessed using the Prevalence Critical Appraisal Instrument and AMSTAR2. Prevalence was grouped according to psychiatric diagnosis. Interventions were grouped into pharmacological, employment, psychological or mixed therapies. Strength of evidence for interventions was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Autistic researchers within the team supported interpretation. RESULTS: Twenty prevalence studies were identified. Many included small sample sizes or failed to compare their sample group with the general population reducing validity. Prevalence of psychiatric diagnoses was variable with prevalence of any psychiatric diagnosis ranging from 15.4% to 79%. Heterogeneity was associated with age, diagnosis method, sampling methods, and country. Thirty-two systematic reviews of interventions were identified. Four reviews were high quality, four were moderate, five were low and nineteen critically low, indicating bias. Following synthesis, no intervention was rated as 'evidence based.' Acceptability of interventions to autistic adults and priorities of autistic adults were often not considered. CONCLUSIONS: There is some understanding of the scope of mental ill-health in autism, but interventions are not tailored to the needs of autistic adults, not evidence based, and may focus on promoting neurotypical behaviours rather than the priorities of autistic people.

Inequity in exercise-based interventions for adults with rheumatoid arthritis: a systematic review.

Objectives: This systematic review describes the extent to which PROGRESS-Plus equity factors were considered in the eligibility criteria of trials of exercise interventions for adults with RA. Methods: Electronic databases were searched for published (Cinahl, Embase, Medline, Physiotherapy Evidence Database), unpublished (Opengrey) and registered ongoing (International Standard Randomized Controlled Trial Number registry) randomized controlled trials (RCTs) of exercise interventions for adults with RA. Two authors independently performed study selection and quality assessment (Cochrane risk of bias tool). Results: A total of 9696 records were identified. After screening, 50 trials were included. All trials had either some concerns or high risk of bias and reported at least one PROGRESS-Plus equity factor within the eligibility criteria; this included place of residence, personal characteristics (age and disability), language, sex, social capital, time-dependent factors or features of relationship factors. Where reported, this equated to exclusion of 457 of 1337 potential participants (34%) based on equity factors. Conclusion: This review identified the exclusion of potential participants within exercise-based interventions for people with RA based on equity factors that might affect health-care opportunities and outcomes. This limits the generalizability of results, and yet this evidence is used to inform management and service design. Trials need to optimize participation, particularly for people with cardiovascular conditions, older adults and those with cognitive impairments. Reasons for exclusions need to be justified. Further research needs to address health inequalities to improve treatment accessibility and the generalizability of research findings. PROSPERO registration: CRD42021260941.

Comparison of Informational and Educational Resource Provision for Individuals Living With Traumatic Brain Injury Based on Language, Nativity, and Neighborhood.

OBJECTIVE: To examine a resource provision program for individuals living with moderate-to-severe traumatic brain injury (TBI), using a comparison of the resources provided across social differences of language, nativity, and neighborhood. SETTING: The Rusk Rehabilitation TBI Model System (RRTBIMS) collects data longitudinally on individuals from their associated private and public hospitals, located in New York City. PARTICIPANTS: A total of 143 individuals with TBI or their family members. DESIGN: An observational study of relative frequency of resource provision across variables of language, nativity, and neighborhood, using related-samples nonparametric analyses via Cochran's Q test. MAIN MEASURES: Variables examined were language, place of birth, residence classification as medically underserved area/population (MUA), and resource categories. RESULTS: Results indicate that US-born persons with TBI and those living in medically underserved communities are provided more resources than those who are born outside the United States or reside in communities identified as adequately medically served. Language was not found to be a factor. CONCLUSION: Lessons learned from this research support the development of this resource provision program, as well as guide future programs addressing the gaps in health information resources for groups negatively impacted by social determinants of health (SDoH). An approach with immigrant participants should take steps to elicit questions and requests, or offer resources explicitly. We recommend research looking at what interpreter strategies are most effective and research on SDoH in relation to the dynamic interaction of variables in the neighborhood setting.

Frailty trajectories and associated factors in the years prior to death: evidence from 14 countries in the Survey of Health, Aging and Retirement in Europe.

BACKGROUND: Age-related changes in frailty have been documented in the literature. However, the evidence regarding changes in frailty prior to death is scarce. Understanding patterns of frailty progression as individuals approach death could inform care and potentially lead to interventions to improve individual's well-being at the end of life. In this paper, we estimate the progression of frailty in the years prior to death. METHODS: Using data from 8,317 deceased participants of the Survey of Health, Ageing, and Retirement in Europe, we derived a 56-item Frailty Index. In a coordinated analysis of repeated measures of the frailty index in 14 countries, we fitted growth curve models to estimate trajectories of frailty as a function of distance to death controlling both the level and rate of frailty progression for age, sex, years to death and dementia diagnosis. RESULTS: Across all countries, frailty before death progressed linearly. In 12 of the 14 countries included in our analyses, women had higher levels of frailty close to the time of death, although they progressed at a slower rate than men (e.g. Switzerland (-0.008, SE = 0.003) and Spain (-0.004, SE = 0.002)). Older age at the time of death and incident dementia were associated with higher levels and increased rate of change in frailty, whilst higher education was associated with lower levels of frailty in the year preceding death (e.g. Denmark (0.000, SE = 0.001)). CONCLUSION: The progression of frailty before death was linear. Our results suggest that interventions aimed at slowing frailty progression may need to be different for men and women. Further longitudinal research on individual patterns and changes of frailty is warranted to support the development of personalized care pathways at the end of life.

Interactions between apolipoprotein E, sex, and amyloid-beta on cerebrospinal fluid p-tau levels in the European prevention of Alzheimer's dementia longitudinal cohort study (EPAD LCS).

BACKGROUND: Alzheimer's Disease, the leading cause of dementia, is over-represented in females. The apolipoprotein E (APOE)ε4 allele is the strongest genetic risk factor for late-onset AD and is associated with aberrant cerebrospinal fluid levels (CSF) of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-ß (Aß). There is some evidence that sex may mediate the relationship between APOE status and CSF tau, however, evidence is mixed. METHODS: We aimed to examine the interaction between sex, APOE ε4 status, CSF Aß on t-tau and p-tau in 1599 mid-to-late life individuals without a diagnosis of dementia in the European Prevention of Alzheimer's Dementia (EPAD) longitudinal cohort study. FINDINGS: We found a significant interaction between APOE status, sex, and CSF Aß on CSF p-tau levels (ß = 0·18, p = 0·04). Specifically, there was a stronger association between APOE status and CSF Aß42 on CSF p-tau in males compared to females. Further, in females with high Aß levels (reflecting less cortical deposition), ε4 carriers had significantly elevated p-tau levels relative to non-carriers (W = 39663, p = 0·01). However, there were no significant differences in p-tau between male ε4 carriers and non-carriers with high Aß (W = 23523, p = 0·64). INTERPRETATION: An interaction between sex and cerebrospinal fluid Aß may mediate the relationship between APOE status and CSF p-tau. These data suggest tau accumulation may be independent of Aß in females, but not males. FUNDING: Innovative Medicines Initiative, Swedish Research Council, Alzheimer Drug Discovery Foundation, Swedish Alzheimer Foundation, the Swedish state under the agreement between the Swedish government and the County Councils: the ALF-agreement, and the Alzheimer's Association 2021 Zenith Award.

Treating sleep disorders following traumatic brain injury in adults: Time for renewed effort?

Traumatic brain injury (TBI) disrupts normal brain function and can lead to chronic symptoms of sleep disturbance, pain, irritability, and depression. Sleep disorders occur in 30-70% of individuals who have experienced TBI. Disturbed sleep impairs the recovery process and may exacerbate other issues that arise because of brain injury (e.g., headaches, depression). Noticeable benefits have been reported when sleep problems due to TBI are addressed and treated; for instance, treating post-TBI insomnia reduces the expression of inflammatory genes, potentially reducing ongoing neurological damage. In this review, we discuss twenty-four randomised clinical trials (RCT) published to date (August 2021), exploring interventions for sleep disturbances resulting from TBI. Treatment effects were observed for insomnia, circadian rhythm disorders, hypersomnia, and general sleep disturbance. However, the evidence remains limited and significant methodological issues are discussed with a recommendation for further research.

Trajectories of Frailty With Aging: Coordinated Analysis of Five Longitudinal Studies.

BACKGROUND AND OBJECTIVES: There is an urgent need to better understand frailty and its predisposing factors. Although numerous cross-sectional studies have identified various risk and protective factors of frailty, there is a limited understanding of longitudinal frailty progression. Furthermore, discrepancies in the methodologies of these studies hamper comparability of results. Here, we use a coordinated analytical approach in 5 independent cohorts to evaluate longitudinal trajectories of frailty and the effect of 3 previously identified critical risk factors: sex, age, and education. RESEARCH DESIGN AND METHODS: We derived a frailty index (FI) for 5 cohorts based on the accumulation of deficits approach. Four linear and quadratic growth curve models were fit in each cohort independently. Models were adjusted for sex/gender, age, years of education, and a sex/gender-by-age interaction term. RESULTS: Models describing linear progression of frailty best fit the data. Annual increases in FI ranged from 0.002 in the Invecchiare in Chianti cohort to 0.009 in the Longitudinal Aging Study Amsterdam (LASA). Women had consistently higher levels of frailty than men in all cohorts, ranging from an increase in the mean FI in women from 0.014 in the Health and Retirement Study cohort to 0.046 in the LASA cohort. However, the associations between sex/gender and rate of frailty progression were mixed. There was significant heterogeneity in within-person trajectories of frailty about the mean curves. DISCUSSION AND IMPLICATIONS: Our findings of linear longitudinal increases in frailty highlight important avenues for future research. Specifically, we encourage further research to identify potential effect modifiers or groups that would benefit from targeted or personalized interventions.

Macrostructural brain alterations at midlife are connected to cardiovascular and not inherited risk of future dementia: the PREVENT-Dementia study.

BACKGROUND: Macrostructural brain alterations in the form of brain atrophy or cortical thinning typically occur during the prodromal Alzheimer's disease stage. Mixed findings largely dependent on the age of the examined cohorts have been reported during the preclinical, asymptomatic disease stage. In the present study, our aim was to examine the association of midlife dementia risk with brain macrostructural alterations. METHODS: Structural 3T MRI scans were acquired for 647 cognitively normal middle-aged (40-59 years old) participants in the PREVENT-Dementia study. Cortical thickness, volumes of subcortical structures, the hippocampus and hippocampal subfields were quantified using Freesurfer version 7.1. The clarity of the hippocampal molecular layer was evaluated based on T2-weighted hippocampal scans. Associations of structural measures with apolipoprotein ε4 (APOE4) genotype and dementia family history (FHD), were investigated using linear regression. Correlations between the CAIDE dementia risk score (incorporating information about blood pressure, cholesterol, physical activity, body mass index, education, age and sex) and structural measures were further investigated. RESULTS: A higher CAIDE score was associated with thinner cortex and a larger hippocampal fissure. APOE4 genotype was associated with reduced molecular layer clarity. CONCLUSIONS: Our findings suggest that a higher CAIDE score is associated with widespread cortical thinning. Conversely, APOE4 carriers and participants with FHD do not demonstrate prominent macrostructural alterations at this age range. These findings indicate that cardiovascular and not inherited risk factors for dementia are associated with macrostructural brain alterations at midlife.

Reliability of Telephone and Videoconference Methods of Cognitive Assessment in Older Adults with and without Dementia.

BACKGROUND: Telephone and videoconference administration of cognitive tests introduce additional sources of variance compared to in-person testing. Reviews of test-retest reliability have included mixed neurocognitive and psychiatric populations with limited consideration of methodological and statistical contributions. OBJECTIVE: We reviewed reliability estimates from comparison studies of older adults with and without dementia, considering test-retest analyses and study methods. METHODS: Medline, Embase, PsycINFO, and Web of Science were systematically searched from 1 January 2000 to 9 June 2020 for original articles comparing telephone or videoconference administered cognitive instruments to in-person administration in older adults with and without dementia or mild cognitive impairment. RESULTS: Of 4,125 articles, 23 were included: 11 telephone (N = 2 dementia cohorts) and 12 videoconference (N = 4 dementia cohorts). Telephone administered subtest scores trended in the same direction as in-person with comparable means. Person-level data were scarce. Data on dementia was only available for MMSE, with resulting subtle modality bias. MMSE, SMMSE, Letter Fluency, and HVLT-R in healthy to mild-moderate Alzheimer's disease were particularly reliable for videoconference administration. Other tests show promise but require more observations and comprehensive analyses. Most studies used high-speed stable videoconferencing hardware resulting in a lack of ecological validity for home administration. CONCLUSION: Remote administration is often consistent with in-person administration but variable and limited at the person/test level. Improved statistical design and inclusion of dementia related cohorts in telephone studies is recommended. Reliability evidence is stronger for videoconferencing but with limited applicability to home administration and severe dementia. Improved reporting of administrative procedures is recommended.

A Systematic Review of Frailty Trajectories: Their Shape and Influencing Factors.

BACKGROUND AND OBJECTIVES: Frailty describes an increased vulnerability to adverse events such as disease or injury. Combating this state remains a major challenge for geriatric research. By exploring how and why frailty changes throughout later life we will be better positioned to improve ways of identifying and treating those at high risk. RESEARCH DESIGN AND METHODS: We systematically reviewed publications that captured rate of frailty progression over time and established any associated risk or protective factors that affected this progression. We included longitudinal observational studies which quantified frailty trajectories in adults aged 50+ using any validated continuous frailty measurement tool. RESULTS: After screening 8,318 publications, 25 met our criteria. Findings show that despite a great degree of heterogeneity in the literature, progression of frailty is unquestionably affected by numerous risk and protective factors, with particular influence exhibited by social demographics, brain pathology, and physical comorbidities. DISCUSSION AND IMPLICATIONS: Findings that the gradient of frailty progression is affected by various influencing factors are valuable to clinicians and policymakers as they will help identify those at highest frailty risk and inform prevention strategies. However, the heterogeneous methodological approaches of the publications included in this review highlight the need for consensus within the field to promote more coordinated research. Improved consistency of methods will enable further data synthesis and facilitate a greater understanding of the shape of frailty over time and the influencing factors contributing to change, the results of which could have crucial implications for frailty risk reduction.

Reproductive Health in Women with Physical Disability: A Conceptual Framework for the Development of New Patient-Reported Outcome Measures.

Background: Barriers in the built environment, enduring stereotypes and biases, and limited disability competency of health care providers compromise access to and quality of reproductive health care for women with physical disabilities. One way to improve our understanding of critical factors that drive reproductive health inequity and its impact on access to care is to use patient-reported outcome measures (PROMs) that capture relevant and meaningful information about experience. In this study, we developed a conceptual framework as the foundation for relevant and clinically meaningful patient-reported outcome measures targeting the interface of disability and reproductive health. Materials and Methods: We conducted semistructured focus groups and interviews to assess women's experiences around their reproductive health and contextual factors related to disability. We used deductive and inductive qualitative coding approaches to develop the conceptual framework. Results: Eighty-one women between the ages of 16 and 50 with a self-reported physical disability, defined by an impairment of mobility, participated in 13 focus groups (N = 64) and 17 individual interviews. Five major themes characterized the conceptual framework that emerged-knowledge about reproductive health, communication about reproductive health, relationships, the reproductive health care environment, and self-advocacy/identity-all of which had some relationship with five major reproductive health issues-pregnancy and labor/delivery, periods and menstrual management, contraception, sexuality and sexual functioning, and pelvic examinations. Conclusions: This conceptual framework will serve as a foundation for PROM and guide intervention development to reduce reproductive health inequity and improve reproductive health outcomes of women with physical disabilities.

Prescreening for European Prevention of Alzheimer Dementia (EPAD) trial-ready cohort: impact of AD risk factors and recruitment settings.

BACKGROUND: Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings. METHODS: We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry (n = 16,877; mean ± SD age = 64 ± 8 years). These included a clinical cohort, a research in-person cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level, APOE status, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status. RESULTS: A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS (n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95-0.99]), high education (OR = 1.64 [1.23-2.17]), male sex (OR = 1.56 [1.19-2.04]), and positive family history of dementia (OR = 1.66 [1.19-2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02-1.10]) and APOE ɛ4 allele carriership (OR = 2.99 [1.81-4.94]). These results were similar across prescreen settings. CONCLUSIONS: Numbers needed to prescreen varied greatly between settings. Understanding how common AD risk factors link to study participation and amyloid positivity is informative for recruitment strategy of studies on secondary prevention of AD.

Systematic Review of Pulmonary Function and Cognition in Aging.

BACKGROUND: Substantial research is dedicated to understanding the aging-related dynamics among individual differences in level, change, and variation across physical and cognitive abilities. Evaluating replicability and synthesizing findings has been limited by differences in measurements, samples, study design, and statistical analyses that confound between-person differences with within-person changes. Here, we systematically reviewed longitudinal results on the aging-related dynamics linking pulmonary function and cognitive performance. METHODS: Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were used to systematically review longitudinal studies of pulmonary function and cognition. RESULTS: Only four studies thoroughly investigating cognitive and pulmonary longitudinal associations (three or more measurement occasions) were identified. Expanded review criteria identified three studies reporting two measurement occasions, and seven studies reporting one measurement of pulmonary function or cognition and two or more measurements of the other. We identified numerous methodological quality and risk for bias issues across studies. CONCLUSIONS: Despite documented correlational associations between pulmonary function and cognition, these results show there is very limited research thoroughly investigating their longitudinal associations. This highlights the need for longitudinal data, rigorous methodological design including key covariates, and clear communication of methods and analyses to facilitate replication across an array of samples. We recommend systematic study of outcome measures and covariates, inclusion of multiple measures (e.g., peak expiratory flow, forced expiratory volume in 1 s, and forced vital capacity), as well as application of the same analytic approach across multiple datasets.

Investigation of Fumed Silica/Aqueous NaCl Superdielectric Material.

A constant current charge/discharge protocol which showed fumed silica filled to the point of incipient wetness with aqueous NaCl solution to have dielectric constants >108 over the full range of dielectric thicknesses of 0.38-3.9 mm and discharge times of 0.25->100 s was studied, making this material another example of a superdielectric. The dielectric constant was impacted by both frequency and thickness. For time to discharge greater than 10 s the dielectric constant for all thicknesses needed to be fairly constant, always >108, although trending higher with increasing thickness. At shorter discharge times the dielectric constant consistently decreased, with decreasing time to discharge. Hence, it is reasonable to suggest that for time to discharge >10 s the dielectric constant at all thicknesses will be greater than 108. This in turn implies an energy density for a 5 micron thick dielectric layer in the order of 350 J/cm³ for discharge times greater than 10 s.

Materials for Paediatric Dentistry. Part 1: Background to the Treatment of Carious Primary Teeth.

Dental caries is a disease that affects many people, including children, and presents numerous challenges to healthcare providers. As clinicians it is important that we consider the advantages and disadvantages of treating carious primary teeth, and make an informed decision about when it is appropriate or not. This paper describes the background to the treatment of carious primary teeth, looking at the differences between primary and permanent teeth, and the relevance of this. It also suggests points to consider when looking at restoration survival studies, as the ability to appraise the literature critically is important for us all in this 'evidence-based' age. CPD/Clinical Relevance: Our early life experiences have the ability to shape our future attitudes and behaviour. Children with carious teeth require careful management so that pain and suffering is minimized, and positive attitudes towards dentistry are fostered.

Materials for Paediatric Dentistry. Part 2: The Evidence.

Which materials should be used to restore primary teeth? The second part in this series summarizes the current evidence base relating to this question, and describes the biological approach to caries management. CPD/Clinical Relevance: Our decisions regarding material choices should be based, where possible, on up-to-date evidence. This will help to ensure that the appropriate material is placed in the appropriate clinical scenario.

Base- and Co(II)-catalyzed ring-opening reactions of perhydrooxireno[2,3-d][1,2]dioxines: an efficient route to 4-hydroxy-2,3-epoxy-ketones.

A series of 3,4,6-substituted 3,6-dihydro-1,2-dioxines were epoxidized with m-chloroperbenzoic acid to furnish perhydrooxireno[2,3-d][1,2]dioxines (epoxy-1,2-dioxines) in yields ranging from 51% to 93% with de's from 26% to 100%. Unsymmetrical epoxy-1,2-dioxines were ring-opened using triethylamine to yield 4-hydroxy-2,3-epoxy-ketones quantitatively, and meso-epoxy-1,2-dioxines were ring-opened using Co(II) salen complexes to afford 4-hydroxy-2,3-epoxy-ketones in 77-98% yield. The first reported examples of the catalytic asymmetric ring-opening of meso-epoxy-1,2-dioxines using a range of chiral Co(II) salen and beta-ketoiminato complexes to afford highly enantio-enriched 4-hydroxy-2,3-epoxy-ketones are also presented.

First examples of the catalytic asymmetric ring-opening of meso 1,2-dioxines utilising cobalt(II) complexes with optically active tetradentate Schiff base ligands: formation of enantio-enriched cyclopropanes.

The combination of chiral cobalt beta-ketoiminato or cobalt salen complexes and meso 1,2-dioxines leads to catalytic asymmetric ring-opening affording enantio-enriched cis gamma-hydroxy enones; subsequent capture by an ylide affords enantio-enriched cyclopropanes.