The role of governance in shaping health system reform: a case study of the design and implementation of new health regions in Ireland, 2018-2023.

BACKGROUND: Effective governance arrangements are central to the successful functioning of health systems. While the significance of governance as a concept is acknowledged within health systems research, its interplay with health system reform initiatives remains underexplored in the literature. This study focuses on the development of new regional health structures in Ireland in the period 2018-2023, one part of a broader health system reform programme aimed at greater universalism, in order to scrutinise how aspects of governance impact on the reform process, from policy design through to implementation. METHODS: This qualitative, multi-method study draws on document analysis of official documents relevant to the reform process, as well as twelve semi-structured interviews with key informants from across the health sector. Interviews were analysed according to thematic analysis methodology. Conceiving governance as comprising five domains (Transparency, Accountability, Participation, Integrity, Capacity) the research uses the TAPIC framework for health governance as a conceptual starting point and as initial, deductive analytic categories for data analysis. RESULTS: The analysis reveals important lessons for policymakers across the five TAPIC domains of governance. These include deficiencies in accountability arrangements, poor transparency within the system and vis-à-vis external stakeholders and the public, and periods during which a lack of clarity in terms of roles and responsibilities for various process and key decisions related to the reform were identified. Inadequate resourcing of implementation capacity, competing policy visions and changing decision-making arrangements, among others, were found to have originated in and continuously reproduced a lack of trust between key institutional actors. The findings highlight how these challenges can be addressed through strengthening governance arrangements and processes. Importantly, the research reveals the interwoven nature of the five TAPIC dimensions of governance and the need to engage with the complexity and relationality of health system reform processes. CONCLUSIONS: Large scale health system reform is a complex process and its governance presents distinct challenges and opportunities for stakeholders. To understand and be able to address these, and to move beyond formulaic prescriptions, critical analysis of the historical context surrounding the policy reform and the institutional relationships at its core are needed.

Temporal Considerations in Brain Metastases Radiation Therapy: The Intersection of Chronobiology and Patient Profiles.

The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assessed circadian timing's impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. The aim of the study was to evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes and to identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities. An IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017-2021), receiving over 80% of treatments in the morning or afternoon, was performed. Survival analyses utilized Kaplan-Meier curves. This was a single-institution study involving patients receiving whole-brain radiotherapy. Demographic, disease, and socioeconomic parameters from electronic medical records were collected. Morning treatment (n = 158) showed a trend toward improved overall survival vs. afternoon (n = 79); the median survival was 158 vs. 79 days (p = 0.20, HR = 0.84, CI95% 0.84-0.91). Subgroup benefits for morning treatment in females (p = 0.04) and trends in controlled primary disease (p = 0.11) and breast cancer metastases (p = 0.08) were observed. Black patients exhibited diminished circadian influence. The present study emphasized chronobiological factors' relevance in brain metastases radiation therapy. Morning treatment correlated with improved survival, particularly in specific subgroups. Potential circadian influence disparities were identified, laying a foundation for personalized cancer therapy and interventions synchronizing circadian rhythms for enhanced treatment efficacy.

States' investment in recovery support services: An exploratory analysis.

INTRODUCTION: Recovery support services (RSS), while not yet precisely defined, nevertheless have a longstanding role in managing chronic illnesses including substance use disorders (SUDs). This exploratory study is the first to identify the amounts of money that states invest from Substance Abuse and Mental Health Services Administration (SAMHSA) Block Grants; SAMHSA discretionary grant and state-appropriated sources; the types of organizations from which RSS are purchased; and the non-financial supports states provide for RSS. METHODS: The study is a mixed method exploratory analysis, based on three data sources: content analysis of all 51 (Washington, D.C. included) Substance Abuse Block Grant (SABG) state applications; in-depth interviews with a purposive sample of ten states and one territory; and a structured electronic survey sent to all SABG recipients. Forty states and 2 territories returned a total of 42 questionnaires from 56 possible states and territories (75%). Thirty-two of the responding states provided complete FY2022 financial data. RESULTS: States reporting financial data spent $412 million from SABG, SAMHSA discretionary grants, and state appropriations for RSS. An estimate based on extrapolating regionally grouped per capita spending averages to non-responding state populations projected $775 million spent from these sources for all states. The study also calculated per capita and SUD prevalent population expenditures from these sources for each state. States purchase services from recovery community organizations and SUD treatment organizations in equal proportions, as well as from statewide recovery support organizations, educational institutions, hospitals, community health centers, and justice system organizations. Purchased services are not uniformly defined, but include community centers, peer staff, housing, and other support services. States provide non-financial support in forms that include technical assistance, community engagement, practice guidelines, and regulatory frameworks. CONCLUSIONS: This first report of states' investments establishes a baseline to serve as a reference point for future analysis of these expenditures, as well as a foundation to which other sources of RSS funding such as Medicaid and other state and federal (e.g. HRSA, CDC, DOJ) dollars may be added. Uniform definitions for RSS will be necessary to support future reporting, accountability, and research. Finally, newly formed peer-based provider organizations need particular attention in order to be sustainable.

Comparison of daily step count between the Fitbit Inspire 3 and the activPAL 3 in adults with transtibial amputation.

Introduction: Physical activity has significant positive effects on health. Accelerometers can be used to track daily physical activity. The Fitbit Inspire 3 is a commercially available health and fitness tracker, but its validity for tracking steps among individuals with transtibial amputation has not been examined. Therefore, the purpose of this study was to evaluate the concurrent validity of the Fitbit Inspire 3 for assessing free-living daily steps in adults with transtibial amputation. Methods: Participants (n = 79) completed a general health survey and were provided with a Fitbit Inspire 3 and activPAL 3 accelerometer to wear concurrently for seven days in their home environment. Relationships between the activPAL and Fitbit Inspire 3 were examined using Pearson's Correlation. Paired samples t-tests, mean difference, mean absolute difference, and equivalence testing were used to compared daily step counts between Fitbit Inspire 3 and activPAL 3. Results: Average step counts were 5,768 ± 3,750 (mean ± SD) and 4,674 ± 3,081 by the Fitbit Inspire 3 and activPAL, respectively. A high correlation (r = 0.93) but significant mean difference was found between the activPAL 3 and Fitbit Inspire 3 (p < 0.001). The mean absolute difference between the devices was 1,347 ± 1,184 steps. On average, the Fitbit Inspire 3 counted 1,094 ± 1,423 more daily steps than the activPAL 3. Equivalency could not be claimed between the devices. Discussion: The Fitbit Inspire 3 counted more steps compared to the activPAL. Because of the significant mean differences and the large mean absolute difference between the devices, the activPAL 3 and Fitbit Inspire 3 are not interchangeable for estimating physical activity in individuals with transtibial amputation. However, due to the high correlation, the devices will produce similar classification rankings based on step counts.

How and why do financial incentives contribute to helping people stop smoking? A realist review.

BACKGROUND: Tobacco smoking remains a key cause of preventable illness and death globally. In response, many countries provide extensive services to help people to stop smoking by offering a variety of effective behavioural and pharmacological therapies. However, many people who wish to stop smoking do not have access to or use stop smoking supports, and new modes of support, including the use of financial incentives, are needed to address this issue. A realist review of published international literature was undertaken to understand how, why, for whom, and in which circumstances financial incentives contribute to success in stopping smoking for general population groups and among pregnant women. METHODS: Systematic searches were undertaken from inception to February 2022 of five academic databases: MEDLINE (ovid), Embase.com, CIHAHL, Scopus and PsycINFO. Study selection was inclusive of all study designs. Twenty-two studies were included. Using Pawson and Tilley's iterative realist review approach, data collected were screened, selected, coded, analysed, and synthesised into a set of explanatory theoretical findings. RESULTS: Data were synthesised into six Context-Mechanism-Outcome Configurations and one overarching programme theory after iterative rounds of analysis, team discussion, and expert panel feedback. Our programme theory shows that financial incentives are particularly useful to help people stop smoking if they have a financial need, are pregnant or recently post-partum, have a high threshold for behaviour change, and/or respond well to external rewards. The incentives work through a number of mechanisms including the role their direct monetary value can play in a person's life and through a process of reinforcement where they can help build confidence and self-esteem. CONCLUSION: This is the first realist review to synthesise how, why, and for whom financial incentives work among those attempting to stop smoking, adding to the existing evidence demonstrating their efficacy. The findings will support the implementation of current knowledge into effective programmes which can enhance the impact of stop smoking care. PROSPERO REGISTRATION NUMBER: CRD42022298941.

MetaVision3D: Automated Framework for the Generation of Spatial Metabolome Atlas in 3D.

High-resolution spatial imaging is transforming our understanding of foundational biology. Spatial metabolomics is an emerging field that enables the dissection of the complex metabolic landscape and heterogeneity from a thin tissue section. Currently, spatial metabolism highlights the remarkable complexity in two-dimensional space and is poised to be extended into the three-dimensional world of biology. Here, we introduce MetaVision3D, a novel pipeline driven by computer vision techniques for the transformation of serial 2D MALDI mass spectrometry imaging sections into a high-resolution 3D spatial metabolome. Our framework employs advanced algorithms for image registration, normalization, and interpolation to enable the integration of serial 2D tissue sections, thereby generating a comprehensive 3D model of unique diverse metabolites across host tissues at mesoscale. As a proof of principle, MetaVision3D was utilized to generate the mouse brain 3D metabolome atlas (available at https://metavision3d.rc.ufl.edu/ ) as an interactive online database and web server to further advance brain metabolism and related research.

A long-term ketogenic diet in young and aged rats has dissociable effects on prelimbic cortex and CA3 ensemble activity.

Introduction: Age-related cognitive decline has been linked to distinct patterns of cellular dysfunction in the prelimbic cortex (PL) and the CA3 subregion of the hippocampus. Because higher cognitive functions require both structures, selectively targeting a neurobiological change in one region, at the expense of the other, is not likely to restore normal behavior in older animals. One change with age that both the PL and CA3 share, however, is a reduced ability to utilize glucose, which can produce aberrant neural activity patterns. Methods: The current study used a ketogenic diet (KD) intervention, which reduces the brain's reliance on glucose, and has been shown to improve cognition, as a metabolic treatment for restoring neural ensemble dynamics in aged rats. Expression of the immediate-early genes Arc and Homer1a were used to quantify the neural ensembles that were active in the home cage prior to behavior, during a working memory/biconditional association task, and a continuous spatial alternation task. Results: Aged rats on the control diet had increased activity in CA3 and less ensemble overlap in PL between different task conditions than did the young animals. In the PL, the KD was associated with increased activation of neurons in the superficial cortical layers, establishing a clear link between dietary macronutrient content and frontal cortical activity. The KD did not lead to any significant changes in CA3 activity. Discussion: These observations suggest that the availability of ketone bodies may permit the engagement of compensatory mechanisms in the frontal cortices that produce better cognitive outcomes.

How do health system factors (funding and performance) impact on access to healthcare for populations experiencing homelessness: a realist evaluation.

BACKGROUND: People experiencing long-term homelessness face significant difficulties accessing appropriate healthcare at the right time and place. This study explores how and why healthcare performance management and funding arrangements contribute to healthcare accessibility or the lack thereof using long-term homeless adults as an example of a population experiencing social exclusion. METHODS: A realist evaluation was undertaken. Thirteen realist interviews were conducted after which data were transcribed, coded, and analysed. RESULTS: Fourteen CMOCs were created based on analysis of the data collected. These were then consolidated into four higher-level CMOCs. They show that health systems characterised by fragmentation are designed to meet their own needs above the needs of patients, and they rely on practitioners with a special interest and specialised services to fill the gaps in the system. Key contexts identified in the study include: health system fragmentation; health service fragmentation; bio-medical, one problem at a time model; responsive specialised services; unresponsive mainstream services; national strategy; short health system funding cycles; and short-term goals. CONCLUSION: When health services are fragmented and complex, the needs of socially excluded populations such as those experiencing homelessness are not met. Health systems focus on their own metrics and rely on separate actors such as independent NGOs to fill gaps when certain people are not accommodated in the mainstream health system. As a result, health systems lack a comprehensive understanding of the needs of all population groups and fail to plan adequately, which maintains fragmentation. Policy makers must set policy and plan health services based on a full understanding of needs of all population groups.

Gys1 Antisense Therapy Prevents Disease-Driving Aggregates and Epileptiform Discharges in a Lafora Disease Mouse Model.

Patients with Lafora disease have a mutation in EPM2A or EPM2B, resulting in dysregulation of glycogen metabolism throughout the body and aberrant glycogen molecules that aggregate into Lafora bodies. Lafora bodies are particularly damaging in the brain, where the aggregation drives seizures with increasing severity and frequency, coupled with neurodegeneration. Previous work employed mouse genetic models to reduce glycogen synthesis by approximately 50%, and this strategy significantly reduced Lafora body formation and disease phenotypes. Therefore, an antisense oligonucleotide (ASO) was developed to reduce glycogen synthesis in the brain by targeting glycogen synthase 1 (Gys1). To test the distribution and efficacy of this drug, the Gys1-ASO was administered to Epm2b-/- mice via intracerebroventricular administration at 4, 7, and 10 months. The mice were then sacrificed at 13 months and their brains analyzed for Gys1 expression, glycogen aggregation, and neuronal excitability. The mice treated with Gys1-ASO exhibited decreased Gys1 protein levels, decreased glycogen aggregation, and reduced epileptiform discharges compared to untreated Epm2b-/- mice. This work provides proof of concept that a Gys1-ASO halts disease progression of EPM2B mutations of Lafora disease.

Spatial Metabolome Lipidome and Glycome from a Single brain Section.

Metabolites, lipids, and glycans are fundamental biomolecules involved in complex biological systems. They are metabolically channeled through a myriad of pathways and molecular processes that define the physiology and pathology of an organism. Here, we present a blueprint for the simultaneous analysis of spatial metabolome, lipidome, and glycome from a single tissue section using mass spectrometry imaging. Complimenting an original experimental protocol, our workflow includes a computational framework called Spatial Augmented Multiomics Interface (Sami) that offers multiomics integration, high dimensionality clustering, spatial anatomical mapping with matched multiomics features, and metabolic pathway enrichment to providing unprecedented insights into the spatial distribution and interaction of these biomolecules in mammalian tissue biology.

How International Health System Austerity Responses to the 2008 Financial Crisis Impacted Health System and Workforce Resilience - A Realist Review.

BACKGROUND: The Great Recession, following the 2008 financial crisis, led many governments to adopt programmes of austerity. This had a lasting impact on health system functionality, resources, staff (numbers, motivation and morale) and patient outcomes. This study aimed to understand how health system resilience was impacted and how this affects readiness for subsequent shocks. METHODS: A realist review identified legacies associated with austerity (proximal outcomes) and how these impact the distal outcome of health system resilience. EMBASE, CINAHL, MEDLINE, EconLit and Web of Science were searched (2007-May 2021), resulting in 1081 articles. Further theory-driven searches resulted in an additional 60 studies. Descriptive, inductive, deductive and retroductive realist analysis (utilising excel and Nvivo) aided the development of context-mechanism-outcome configurations (CMOCs), alongside stakeholder engagement to confirm or refute emerging results. Causal pathways, and the interplay between context and mechanisms that led to proximal and distal outcomes, were revealed. The refined CMOCs and policy recommendations focused primarily on workforce resilience. RESULTS: Five CMOCs demonstrated how austerity-driven policy decisions can impact health systems when driven by the priorities of external agents. This created a real or perceived shift away from the values and interests of health professionals, a distrust in decision-making processes and resistance to change. Their values were at odds with the realities of implementing such policy decisions within sustained restrictive working conditions (rationing of staff, consumables, treatment options). A diminished view of the profession and an inability to provide high-quality, equitable, and needs-led care, alongside stagnant or degraded working conditions, led to moral distress. This can forge legacies that may adversely impact resilience when faced with future shocks. CONCLUSION: This review reveals the importance of transparent, open communication, in addition to co-produced policies in order to avoid scenarios that can be detrimental to workforce and health system resilience.

Visual cortical LFP in relation to the hippocampal theta rhythm in track running rats.

Theta oscillations in the primary visual cortex (VC) have been observed during running tasks, but the mechanism behind their generation is not well understood. Some studies have suggested that theta in the VC is locally generated, while others have proposed that it is volume conducted from the hippocampus. The present study aimed to investigate the relationship between hippocampal and VC LFP dynamics. Analysis of power spectral density revealed that LFP in the VC was similar to that in the hippocampus, but with lower overall magnitude. As running velocity increased, both the power and frequency of theta and its harmonics increased in the VC, similarly to what is observed in the hippocampus. Current source density analysis triggered to theta did not identify distinct current sources and sinks in the VC, supporting the idea that theta in the VC is conducted from the adjacent hippocampus. Phase coupling between theta, its harmonics, and gamma is a notable feature in the hippocampus, particularly in the lacunosum moleculare. While some evidence of coupling between theta and its harmonics in the VC was found, bicoherence estimates did not reveal significant phase coupling between theta and gamma. Similar results were seen in the cross-region bicoherence analysis, where theta showed strong coupling with its harmonics with increasing velocity. Thus, theta oscillations observed in the VC during running tasks are likely due to volume conduction from the hippocampus.

Muscimol inactivation of dorsal striatum in young and aged male rats does not affect paired associates learning performance.

Improving cognitive health for older adults requires understanding the neurobiology of age-related cognitive decline and the mechanisms underlying preserved cognition in old age. During spatial learning tasks, aged humans and rodents shift navigation preferences in favor of a stimulus-response learning strategy. This has been hypothesized to result from competitive interactions of the caudate nucleus/dorsal striatum (DS) memory system with the hippocampus (HPC)-dependent spatial/allocentric memory system. In support of this hypothesis, a recent study reported that inactivation of the DS in aged rodents rescued HPC-dependent spatial learning on a T-maze (Gardner, Gold, & Korol, 2020). Currently, it is unclear whether a shift from HPC-dependent to DS-dependent behavior also contributes to age-related cognitive decline outside of spatial learning and memory. To test the hypothesis that inactivation of the DS can restore age-related cognitive function outside of spatial behavior, the present study bilaterally inactivated the DS of young (n = 8) and aged (n = 7) rats during visuospatial paired associates learning (PAL). This study found that inactivation of the DS did not alter PAL performance in young or aged rats, but did alter a positive control, DS-dependent spatial navigation task. This observation suggests that elevated DS activity does not play a role in the decline of HPC-dependent PAL performance in aged male rats. Given the persistent tendencies of aged rodents toward DS-dependent learning, it will be worthwhile to explore further the coordination dynamics between the HPC and DS that may contribute to age-related cognitive decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Public attitudes to implementing financial incentives in stopsmoking services in Ireland.

INTRODUCTION: Financial incentives improve stop-smoking service outcomes. Views on acceptability can influence implementation success. To inform implementation planning in Ireland, public attitudes on financial incentives to stop smoking were measured. METHODS: A cross-sectional telephone survey was administered to 1000 people in Ireland aged ≥15 years in 2022, sampled through random digit dialing. The questionnaire included items on support for financial incentives under different conditions. Prevalence of support was calculated with 95% Confidence Intervals (CIs) and multiple logistic regression identified associated factors using adjusted odds ratios (AORs) with 95% CIs. RESULTS: Almost half (47.0%, 95% CI: 43.9-50.1) of the participants supported at least one type of financial incentive to stop smoking, with support more prevalent for shopping vouchers (43.3%, 95% CI: 40.3-46.5) than cash payments (32.1%, 95% CI: 29.2-35.0). Support was similar for universal and income-restricted schemes. Of those who supported financial incentives, the majority (60.6%) believed the maximum amount given on proof of stopping smoking should be under €250 (median=100, range: 1-7000). Compared to their counterparts, those of lower education level (AOR=1.49; 95% CI: 1.10-2.03, p=0.010) and tobacco/e-cigarette users (AOR=1.43; 95% CI: 1.02-2.03, p=0.041) were significantly more likely to support either financial incentive type, as were younger people. CONCLUSIONS: While views on financial incentives to stop smoking in Ireland were mixed, the intervention is more acceptable in groups experiencing the heaviest burden of smoking-related harm and most capacity to benefit. Engagement and communication must be integral to planning for successful implementation to improve stop-smoking service outcomes.

Nonlinear Theta-Gamma Coupling between the Anterior Thalamus and Hippocampus Increases as a Function of Running Speed.

The hippocampal theta rhythm strongly correlates to awake behavior leading to theories that it represents a cognitive state of the brain. As theta has been observed in other regions of the Papez circuit, it has been theorized that activity propagates in a reentrant manner. These observations complement the energy cascade hypothesis in which large-amplitude, slow-frequency oscillations reflect activity propagating across a large population of neurons. Higher frequency oscillations, such as gamma, are related to the speed with which inhibitory and excitatory neurons interact and distribute activity on the local level. The energy cascade hypothesis suggests that the larger anatomic loops, maintaining theta, drive the smaller loops. As hippocampal theta increases in power with running speed, so does the power and frequency of the gamma rhythm. If theta is propagated through the circuit, it stands to reason that the local field potential (LFP) recorded in other regions would be coupled to the hippocampal theta, with the coupling increasing with running speed. We explored this hypothesis using open-source simultaneous recorded data from the CA1 region of the hippocampus and the anterior dorsal and anterior ventral thalamus. Cross-regional theta coupling increased with running speed. Although the power of the gamma rhythm was lower in the anterior thalamus, there was an increase in the coupling of hippocampal theta to anterior thalamic gamma. Broadly, the data support models of how activity moves across the nervous system, suggesting that the brain uses large-scale volleys of activity to support higher cognitive processes.

How to not revert to type: Complexity-informed learnings from the pandemic response for health system reform and universal access to integrated care.

This article is part of the Research Topic 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict'. Background: COVID-19 has highlighted existing health inequalities and health system deficiencies both in Ireland and internationally; however, understanding of the critical opportunities for health system change that have arisen during the pandemic is still emerging and largely descriptive. This research is situated in the Irish health reform context of Sláintecare, the reform programme which aims to deliver universal healthcare by strengthening public health, primary and community healthcare functions as well as tackling system and societal health inequities. Aims and objectives: This study set out to advance understanding of how and to what extent COVID-19 has highlighted opportunities for change that enabled better access to universal, integrated care in Ireland, with a view to informing universal health system reform and implementation. Methods: The study, which is qualitative, was underpinned by a co-production approach with Irish health system leadership. Semi-structured interviews were conducted with sixteen health system professionals (including managers and frontline workers) from a range of responses to explore their experiences and interpretations of social processes of change that enabled (or hindered) better access to universal integrated care during the pandemic. A complexity-informed approach was mobilized to theorize the processes that impacted on access to universal, integrated care in Ireland in the COVID-19 context. Findings: A range of circumstances, strategies and mechanisms that created favorable system conditions in which new integrated care trajectories emerged during the crisis. Three key learnings from the pandemic response are presented: (1) nurturing whole-system thinking through a clear, common goal and shared information base; (2) harnessing, sharing and supporting innovation; and (3) prioritizing trust and relationship-building in a social, human-centered health system. Policy and practice implications for health reform are discussed.

A long-term ketogenic diet in young and aged rats has dissociable effects on prelimbic cortex and CA3 ensemble activity.

Age-related cognitive decline has been linked to distinct patterns of cellular dysfunction in the prelimbic cortex (PL) and the CA3 subregion of the hippocampus. Because higher cognitive functions require both structures, selectively targeting a neurobiological change in one region, at the expense of the other, is not likely to restore normal behavior in older animals. One change with age that both the PL and CA3 share, however, is a reduced ability to utilize glucose, which can produce aberrant neural activity patterns. The current study used a ketogenic diet (KD) intervention, which reduces the brain’s reliance on glucose, and has been shown to improve cognition, as a metabolic treatment for restoring neural ensemble dynamics in aged rats. Expression of the immediate-early genes Arc and Homer 1a were used to quantify the neural ensembles that were active in the home cage prior to behavior, during a working memory/biconditional association task, and a continuous spatial alternation task. Aged rats on the control diet had increased activity in CA3 and less ensemble overlap in PL between different task conditions than did the young animals. In the PL, the KD was associated with increased activation of neurons in the superficial cortical layers. The KD did not lead to any significant changes in CA3 activity. These observations suggest that the KD does not restore neuron activation patterns in aged animals, but rather the availability of ketone bodies in the frontal cortices may permit the engagement of compensatory mechanisms that produce better cognitive outcomes. Significance Statement: This study extends understanding of how a ketogenic diet (KD) intervention may improve cognitive function in older adults. Young and aged rats were given 3 months of a KD or a calorie-match control diet and then expression of the immediate-early genes Arc and Homer 1a were measured to examine neural ensemble dynamics during cognitive testing. The KD diet was associated with increased activation of neurons in the superficial layers of the PL, but there were no changes in CA3. These observations are significant because they suggest that compensatory mechanisms for improving cognition are engaged in the presence of elevated ketone bodies. This metabolic shift away from glycolysis can meet the energetic needs of the frontal cortices when glucose utilization is compromised.

Touchscreen-Based Cognitive Training Alters Functional Connectivity Patterns in Aged But Not Young Male Rats.

Age-related cognitive decline is related to cellular and systems-level disruptions across multiple brain regions. Because age-related cellular changes within different structures do not show the same patterns of dysfunction, interventions aimed at optimizing function of large-scale brain networks may show greater efficacy at improving cognitive outcomes in older adults than traditional pharmacotherapies. The current study aimed to leverage a preclinical rat model of aging to determine whether cognitive training in young and aged male rats with a computerized paired-associates learning (PAL) task resulted in changes in global resting-state functional connectivity. Moreover, seed-based functional connectivity was used to examine resting state connectivity of cortical areas involved in object-location associative memory and vulnerable in old age, namely the medial temporal lobe (MTL; hippocampal cortex and perirhinal cortex), retrosplenial cortex (RSC), and frontal cortical areas (prelimbic and infralimbic cortices). There was an age-related increase in global functional connectivity between baseline and post-training resting state scans in aged, cognitively trained rats. This change in connectivity following cognitive training was not observed in young animals, or rats that traversed a track for a reward between scan sessions. Relatedly, an increase in connectivity between perirhinal and prelimbic cortices, as well as reduced reciprocal connectivity within the RSC, was found in aged rats that underwent cognitive training, but not the other groups. Subnetwork activation was associated with task performance across age groups. Greater global functional connectivity and connectivity between task-relevant brain regions may elucidate compensatory mechanisms that can be engaged by cognitive training.

Work like a Doc: A comparison of regulations on residents' working hours in 14 high-income countries.

BACKGROUND: Medical residents work long, continuous hours. Working in conditions of extreme fatigue has adverse effects on the quality and safety of care, and on residents' quality of life. Many countries have attempted to regulate residents' work hours. OBJECTIVES: We aimed to review residents' work hours regulations in different countries with an emphasis on night shifts. METHODS: Standardized qualitative data on residents' working hours were collected with the assistance of experts from 14 high-income countries through a questionnaire. An international comparative analysis was performed. RESULTS: All countries reviewed limit the weekly working hours; North-American countries limit to 60-80 h, European countries limit to 48 h. In most countries, residents work 24 or 26 consecutive hours, but the number of long overnight shifts varies, ranging from two to ten. Many European countries face difficulties in complying with the weekly hour limit and allow opt-out contracts to exceed it. CONCLUSIONS: In the countries analyzed, residents still work long hours. Attempts to limit the shift length or the weekly working hours resulted in modest improvements in residents' quality of life with mixed effects on quality of care and residents' education.

Gendered Anti-Bisexual Bias: Heterosexual, Bisexual, and Gay/Lesbian People's Willingness to Date Sexual Orientation Ingroup and Outgroup Members.

Bisexual people may appear to have more potential romantic partners than people only attracted to one gender (e.g., heterosexual, gay, lesbian people). However, bisexual people's dating choices are limited by non-bisexual people's reluctance to date bisexual people. Studies have indicated that some heterosexual, gay, and lesbian people are reluctant to date bisexual people, particularly bisexual men. We extend current understandings of gendered anti-bisexual bias through investigating heterosexual, bisexual, gay, and lesbian people's reported willingness to date within and outside of their sexual orientation groups. Participants (n = 1823) varying in sexual orientation completed measures regarding their willingness to engage in a romantic relationship with heterosexual, bisexual, gay, and lesbian individuals. Heterosexual and gay/lesbian people were less willing to date bisexual people than bisexual people were to date them, consistent with anti-bisexual bias rather than mere in-group preference. Preferences against dating bisexual men appeared particularly strong, even among bisexual women.