The effects of Tai Chi on standing balance control in older adults may be attributed to the improvement of sensory reweighting and complexity rather than reduced sway velocity or amplitude.

Introduction: Tai Chi has proved to be an effective therapy for balance performance and cognition. However, non-consistency exists in the results of the effect of Tai Chi training on standing balance control in older adults. This study aimed to use traditional and non-traditional methods to investigate the effect of Tai Chi on standing balance in older adults. Methods: Thirty-six Tai Chi practitioners (TC group) and thirty-six older adults with no Tai Chi practice (control group) were recruited in this study. A Nintendo Wii Balance Board was used to record the center of pressure (COP) during standing balance over 20 s in the condition of eyes closed with three repetitions. The wavelet analysis, multiscale entropy, recurrence quantification analysis, and traditional methods were used to evaluate the standing balance control in the anterior-posterior (AP) and mediolateral (ML) directions. Results: (1) Greater sway mean velocity in the AP direction and sway Path length were found in the TC group compared with the control group; (2) lower Very-low frequency band (0.10-0.39 Hz) and higher Moderate frequency band (1.56-6.25 Hz) in the AP and ML directions were found in the TC group compared with the control group; (3) greater complexity index (CI) and lower determinism (DET) in the AP and ML directions were observed in the TC group compared with control group; (4) greater path length linked with smaller Very-low frequency band in the AP and ML directions and higher Moderate frequency band in the AP direction in both groups; (5) greater path length linked with lower DET and higher CI in the AP direction only in the TC group. Conclusion: Long-term Tai Chi practice improved sensory reweighting (more reliance on the proprioception system and less reliance on the vestibular system) and complexity of standing balance control in older adults. In addition, greater sway velocity may be as an exploratory role in standing balance control of TC older adults, which correlated with greater complexity, but no such significant relationship in the control group. Therefore, the effects of Tai Chi practice on standing balance control in older adults may be attributed to the improvement of sensory reweighting and complexity rather than reduced sway velocity or amplitude.

Patterns of comorbidities in patients with atrial fibrillation and impact on management and long-term prognosis: an analysis from the Prospective Global GLORIA-AF Registry.

BACKGROUND: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes. METHODS: From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed. RESULTS: 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49-2.09] and 1.57 [1.35-1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13-1.67] and 1.47 [1.24-1.75], respectively). CONCLUSIONS: Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.

The clinical complexity among patients with systemic, chronic diseases.

OBJECTIVES: This study aimed to assess the clinical complexity of patients with chronic systemic diseases (systemic lupus erythematosus [SLE] and ANCA-associated vasculitis [AAV]) using the INTERMED Self-Assessment questionnaire (IMSA) to determine the most important factors responsible for this phenomenon in these patients. METHODS: This was a cross-sectional, observational study. Questionnaires were used to evaluate biopsychosocial complexity (IMSA), quality of life (Short Form Survey [SF-36]), mental state (General Health Questionnaire - 28 [GHQ-28] and Hospital Anxiety and Depression Scale [HADS]), and acceptance of illness (Acceptance of Illness Scale [AIS]). RESULTS: The final analysis included 81 patients. There was a moderate correlation between clinical complexity (total IMSA score) and quality of life related to mental health (SF-36) and mental state (GHQ-28) in patients with SLE. However, in patients with AAV, clinical complexity had a strong relationship with physical health-related quality of life and a moderate relationship with mental health-related quality of life. Stepwise regression analysis showed that low mental health-related quality of life is a predictor of higher complexity in SLE. The predictors of high clinical complexity in AAV were low physical and mental health-related quality of life and aggravated depressive symptoms (HADS). Other principal factors of clinical complexity were employment status, place of residence, social functioning, and illness duration. CONCLUSION: This study confirmed the importance of holistic attitudes and complex healthcare among patients with chronic diseases.

The effect of different types of cognitive tasks on postural sway fluctuations in older and younger adults: A nonlinear study.

BACKGROUND: There are numerous types of cognitive tasks classified as mental tracking (MT), working memory (WM), reaction time (RT), discrimination and decision-making and verbal fluency (VF). However, limited studies have investigated the effects of cognitive task type on postural control in older adults. PURPOSE: s: The aim of this study was to investigate the effect of aging and several types of cognitive tasks on postural control in terms of nonlinear analysis. METHOD: Postural control was investigated under 6 conditions (single task and dual-task with RT; easy and difficult VF; easy and difficult WM; easy and difficult MT. Outcome measurements were the max Lyapunov, entropy, and correlation dimension at anteroposterior (AP) and mediolateral (ML) directions. RESULTS: The results revealed that within the older group, the AP & ML max Lyapunov at dual-task with difficult WM and MT was significantly higher than all other conditions. In addition, the older group had lower AP entropy at dual-task with easy VF, difficult WM, and easy as well as difficult MT. CONCLUSION: The results can be useful to understand the postural control mechanisms and to detect the alterations following aging and applying different types of cognitive tasks. In addition, the investigated parameters can be a basis for identifying postural control deficiencies.

Approaches to Design an Efficient, Predictable Global Post-approval Change Management System that Facilitates Continual Improvement and Drug Product Availability.

The complexity and inter-connectedness of operating in a global world for drug product supply has become an undeniable reality, further underscored by the COVID-19 pandemic. For Post-Approval Changes (PACs) that are an inevitable part of a product's commercial life, the impact of the growing global regulatory complexity and related drug shortages has brought the Global PAC Management System to an inflection point in particular for companies that have their products marketed in many countries.This paper illustrates through data analyzed for the first time from 145,000 + PACs for 156 countries, collected by 18 global pharma companies over a 3-year period (2019-2021), how severe the problem of global regulatory complexity is. Only PACs requiring national regulatory agency (NRA) approval prior to implementation were included in the data set. 1 of the 156 country NRAs approved all submitted PACs within a period of 6 months. The 6-month timeline was chosen because it is the recommended review timeline for major changes in the WHO guidance for vaccines and biotherapeutic products. 10 out of the 156 (6%) countries had no more than 10% of the PACs reviewed and approved in > 6 months. In 33 (22%) countries more than half of the PACs took > 6 months for approval. It is rare that the same PAC is approved globally within 6 months as individual NRAs take from a few months to years (in some cases > 5 years) for their review.The global PAC management complexity has steadily grown over the past 20 years. Attempts thus far to solve this problem have not made any meaningful difference. Senior leaders and decision-makers across the interdependent components of the complex Global PAC Management System (industry and regulators) must come together and collaboratively manage the problem holistically with the objective of ensuring global drug product availability instead of continuing with distinct stakeholder or country-focused solutions, which can tend to worsen the problem.In this paper, the Chief Quality Officers (CQOs) from 18 of the largest innovator pharma companies (see Acknowledgements) are speaking with One-Voice-of-Quality for PACs (1VQ for PACs Initiative). They are recommending a set of 8 approaches to activate a holistic transformation of the Global PAC Management System. This article presents their view on the problem of global regulatory complexity for managing PACs, it's impact on continual improvement and the risk to drug product supply, as well as approaches that can help alleviate the problem.

Caring for children with medical complexity at home: An integrative review.

PROBLEM: Despite reporting significant systemic barriers to providing care, burden among parental caregivers of children with medical complexity (CMC) is often attributed to stressors related to disease management. The relationship between parental caregiver burden and systemic barriers within the healthcare bureaucracy, as defined by Ray's Theory of Bureaucratic Caring (BCT), has not been explored. The purpose of this integrative review was to examine which elements of the bureaucratic healthcare system are contributing to burden among parental caregivers of CMC living at home. ELIGIBILITY CRITERIA: Refereed research articles related to the experiences of parental caregivers of CMC living in the United States published after 2014. SAMPLE: 1967 articles were obtained on initial literature search. Using the PRISMA algorithm, ten articles published between 2018 and 2022 were ultimately selected for appraisal. RESULTS: Parental caregiver burden was consistently attributed to barriers and gaps among social-cultural, physical, political, legal, economic, technological, and educational elements of the bureaucratic healthcare system. CONCLUSIONS: Weaknesses across the bureaucratic elements of the healthcare system prevent CMC from consistently receiving necessary care which in turn, contribute to feelings of burden among their parental caregivers. Efforts to alleviate burden experienced by parental caregivers should focus on addressing gaps within the healthcare bureaucracy. IMPLICATIONS: Nurses are well-positioned to address these gaps through clinical work, advocacy, and research. Future research should further examine the appropriateness of using BCT to better understand the implications of systems-level weaknesses on parental caregiver burden. Parental caregivers of CMC should be closely involved in this process.

Mindfulness meditation styles differently modulate source-level MEG microstate dynamics and complexity.

Background: The investigation of mindfulness meditation practice, classically divided into focused attention meditation (FAM), and open monitoring meditation (OMM) styles, has seen a long tradition of theoretical, affective, neurophysiological and clinical studies. In particular, the high temporal resolution of magnetoencephalography (MEG) or electroencephalography (EEG) has been exploited to fill the gap between the personal experience of meditation practice and its neural correlates. Mounting evidence, in fact, shows that human brain activity is highly dynamic, transiting between different brain states (microstates). In this study, we aimed at exploring MEG microstates at source-level during FAM, OMM and in the resting state, as well as the complexity and criticality of dynamic transitions between microstates. Methods: Ten right-handed Theravada Buddhist monks with a meditative expertise of minimum 2,265 h participated in the experiment. MEG data were acquired during a randomized block design task (6 min FAM, 6 min OMM, with each meditative block preceded and followed by 3 min resting state). Source reconstruction was performed using eLORETA on individual cortical space, and then parcellated according to the Human Connect Project atlas. Microstate analysis was then applied to parcel level signals in order to derive microstate topographies and indices. In addition, from microstate sequences, the Hurst exponent and the Lempel-Ziv complexity (LZC) were computed. Results: Our results show that the coverage and occurrence of specific microstates are modulated either by being in a meditative state or by performing a specific meditation style. Hurst exponent values in both meditation conditions are reduced with respect to the value observed during rest, LZC shows significant differences between OMM, FAM, and REST, with a progressive increase from REST to FAM to OMM. Discussion: Importantly, we report changes in brain criticality indices during meditation and between meditation styles, in line with a state-like effect of meditation on cognitive performance. In line with previous reports, we suggest that the change in cognitive state experienced in meditation is paralleled by a shift with respect to critical points in brain dynamics.

Exploring settings as social complex adaptive systems in setting-based health research: a scoping review.

Since launching health health-promoting settings approach to health by WHO, valuable progress has happened in implementing its holistic concepts in settings such as cities, schools, workplaces, hospitals and healthcare services. However, significant knowledge-intention-success gaps still exist in creating sustainable health-promoting changes in settings. The complexity of the task of bridging this gap has contributed to the call for a complexity-informed paradigm shift to health as well as settings, followed by increasing consultation of relevant complexity theories, frameworks and tools in health research. This paper provides a critical scoping review of the application of complex adaptive system (CAS) theory in settings-based health promotion research. We included 14 papers, mostly qualitative studies, reporting on planning or implementation of change initiatives, less on its evaluation. CAS theory application was often incomplete thereby reducing the potential benefit of using this lens to understand change management. We suggest some recommendations how to comprehensively apply the CAS theory in setting-based health research and to report on all CAS characteristics to enhance the understanding of settings as adaptive health-promoting settings.

Fortalezas sistémicas y necesidades en atención paliativa domiciliaria: explorando la complejidad / Systemic strengths and needs in palliative home care: exploring complexity

Objetivo Nos proponemos investigar la relación entre las fortalezas sistémicas y el lugar de muerte en atención domiciliaria de pacientes en final de vida. Método Estudio cuantitativo descriptivo longitudinal de pacientes atendidos por un equipo domiciliario de cuidados paliativos. Se analizó la ubicación de la muerte en relación con la complejidad detectada tras la primera valoración domiciliaria usando el modelo de complejidad HexCom. Para la comparación de proporciones utilizamos la prueba de ji cuadrado de Pearson. Resultados Participaron 464 pacientes (74,4% oncológicos), edad media 76,2años (DE: 13,2). El 53% presentaban dependencia funcional total o severa, el 30,8% estaban ya encamados en la primera valoración y el 59,7% fallecieron en domicilio. Las fortalezas influyen en el lugar de muerte, sobre todo la fortaleza del exosistema (equipo) (OR: 4,07 [1,92-8,63]), la del microsistema (tanto la fortaleza del paciente (0,51 [0,28-0,94]) como de cuidador (OR: 3,90 [1,48-10,25]), y la del cronosistema, relativo a la previsión de un curso progresivo (OR: 2,22 [1,37-3,60]). Conclusiones Para mejorar la asistencia a los pacientes en situación de final de vida y sus familias es necesaria una mirada sistémica del morir y de la muerte que incluya tanto necesidades como fortalezas. En este sentido, el marco sistémico propuesto por Bonfrenbrenner puede ser de utilidad para la práctica clínica. (AU)

Objective We aimed to investigate the relationship between systemic strengths and complexity in home care of end-of-life patients. Methods Quantitative descriptive longitudinal study of patients cared for at home by a palliative care team. Place of death was analyzed in relation to complexity, as determined by the HexCom complexity model after the initial home assessment. We used Pearson's chi-square test to analyze the comparison of proportions. Results Forty-six hundred patients (74.4% oncologic) with a mean age of 76.2years (SD 13.2) participated. Fifty-three percent had complete or severe functional dependence, 30.8% were already bedridden in the first assessment, and 59.7% died at home. Strengths influenced place of death, specifically exosystem (team) strength (OR: 4.07 [1.92-8.63]), microsystem (both patient 0.51 [0.28-0.94]) and caregiver (OR: 3.90 [1.48-10.25]), and chronosystem, related to prediction of progressive course (OR: 2.22 [1.37-3.60]). Conclusions To improve care for end-of-life patients and their families, a systemic view of dying and death that includes both needs and strengths is necessary. In this sense, the systemic framework proposed by Bonfrenbrenner can be useful for clinical practice. (AU)

Complexity of STG signals and linguistic rhythm: a methodological study for EEG data.

The superior temporal and the Heschl's gyri of the human brain play a fundamental role in speech processing. Neurons synchronize their activity to the amplitude envelope of the speech signal to extract acoustic and linguistic features, a process known as neural tracking/entrainment. Electroencephalography has been extensively used in language-related research due to its high temporal resolution and reduced cost, but it does not allow for a precise source localization. Motivated by the lack of a unified methodology for the interpretation of source reconstructed signals, we propose a method based on modularity and signal complexity. The procedure was tested on data from an experiment in which we investigated the impact of native language on tracking to linguistic rhythms in two groups: English natives and Spanish natives. In the experiment, we found no effect of native language but an effect of language rhythm. Here, we compare source projected signals in the auditory areas of both hemispheres for the different conditions using nonparametric permutation tests, modularity, and a dynamical complexity measure. We found increasing values of complexity for decreased regularity in the stimuli, giving us the possibility to conclude that languages with less complex rhythms are easier to track by the auditory cortex.

Metalloproteinases as Biomarkers and Sociomarkers in Human Health and Disease.

Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of this review are to analyze a specific family of MPs, the matrix metalloproteinases (MMPs), in the most common chronic and complex diseases that affect patients' social lives and to better understand the nature of the associations between MMPs and the psychosocial environment. In accordance with the PRISMA extension for a scoping review, an examination was carried out. A collection of 24 studies was analyzed, focusing on the molecular mechanisms of MMP and their connection to the manifestation of social aspects in human disease. The complexity of the relationship between MMP and social problems is presented via an interdisciplinary approach based on complexity paradigm as a new approach for conceptualizing knowledge in health research. Finally, two implications emerge from the study: first, the psychosocial states of individuals have a profound impact on their overall health and disease conditions, which implies the importance of adopting a holistic perspective on human well-being, encompassing both physical and psychosocial aspects. Second, the use of MPs as biomarkers may provide physicians with valuable tools for a better understanding of disease when used in conjunction with "sociomarkers" to develop mathematical predictive models.

Improving patient-centered care for HIV and mental illness: exploring hospital and community integration through education.

Current models of care delivery are failing patients with complexity, like those living with HIV, mental illness and other psychosocial challenges. These patients often require resource-intensive personalized care across hospital and community settings, but available supports can be fragmented and challenging to access and navigate. To improve this, the authors created a program to enhance integrated, trauma-informed care through an innovative educational role for a HIV community caseworker embedded in an academic HIV Psychiatry clinic, called the Mental Health Clinical Fellowship. Through qualitative interviews with 21 participants (patients, physicians, clinicians and Mental Health Clinical Fellows) from October 2020-March 2023, the authors explore how implementation of this program affects patient experiences and satisfaction with care. Patients described their care experiences as less stigmatizing, more accessible, holistic and coordinated. They often attributed this to the integration between fellow and psychiatrist, and specifically the accessible stance of community organizations embedded within a hospital, which helped build trust. Interchangeable and integrated support by caseworker and psychiatrist improved patient engagement in psychiatric management and patient satisfaction with their care. Cross-context and cross-disciplinary care provision that includes providers from community and hospital working directly together to deliver care can improve care for patients with significant complexity.

Metastasis Models: Thermodynamics and Complexity.

The thermodynamic formalism of nonequilibrium systems together with the theory of complex systems and systems biology offer an appropriate theoretical framework to explain the complexity observed at the macroscopic level in physiological phenomena. In turn, they allow the establishment of an appropriate conceptual and operational framework to address the study of phenomena such as the emergence and evolution of cancer.This chapter is organized as follows: In Subheading 1, an integrated vision of these disciplines is offered for the characterization of the emergence and evolution of cancer, seen as a nonlinear dynamic system, temporally and spatially self-organized out of thermodynamic equilibrium. The development of the various mathematical models and different techniques and approaches used in the characterization of cancer metastasis is presented in Subheading 2. Subheading 3 is devoted to the time course of cancer metastasis, with particular emphasis on the epithelial-mesenchymal transition (EMT henceforth) as well as chronotherapeutic treatments. In Subheading 4, models of the spatial evolution of cancer metastasis are presented. Finally, in Subheading 5, some conclusions and remarks are presented.

Palliative Care in Children with Inherited Metabolic Diseases: Why does it matter?

BACKGROUND: Inherited metabolic diseases (IMD) bring considerable burden on the child and family. Challenging areas for health care include the identification of distressing symptoms, prognostic uncertainty, and bereavement. Literature regarding the impact of paediatric palliative care (PPC) is scarce. OBJECTIVE: This study aims to evaluate children with IMD referred to a PPC team (PPCT) and to analyse its impact on home care, decision to limit treatment (DLT), use of hospital resources (emergency department admissions - EDA, hospital admissions - HA, intensive care admissions - ICA) and end of life support. METHODS: Retrospective cohort study of children with IMD referred to a specialized PPCT (2016-2022). We assessed clinical data: symptoms control, time of referral and length of the follow-up period, DLT, device dependency, use of hospital resources prior to and after referral, place of death and end-of-life support. RESULTS: Fifteen children with IMD were referred to PPCT (8% of total referrals), with median age of 7 years (4 months - 17 years); 53% female. All children were non or pre-verbal. Most prevalent symptoms were neurologic and motor impairment (100%), respiratory and gastrointestinal (75%). 80% had tube feeding, 90% had some respiratory device (non-invasive ventilation in 23%). All children had multidrug use, with a mean of 6 drugs per child (2-9). 73% had home PPC and 80% had DLT planned. Nine children died (78% in hospital), after a mean of 17 months of follow-up (2 months to 4 years), all with DLT planned. 67% had support from PPCT at the end of life. All these families received emotional support. Decrease in EDA (10 vs 2) was noticed before and after PPCT. No impact was seen in HA and ICA (6 vs 5 and 1 vs 1, respectively) and there was a longer mean of hospitalisation stay (15 vs 32 days). CONCLUSION: Our cohort includes a group of children with severe, complex and neurodegenerative IMD. They need multiple medications for symptoms control, are highly dependent on medical devices and consume significant healthcare resources. Communication impairment adds complexity being a major barrier to symptom assessment. PPCT referral allowed home support, anticipated care plans development with end of life and bereavement support, as well as a tendency towards a reduction in EDA. These findings reinforce the need for holistic approach to identify and address the PPC needs of children with IMD.

Dendritogenic Potential of the Ethanol Extract from Lippia alba Leaves in Rat Cortical Neurons.

A reduced dendritic complexity, especially in regions such as the hippocampus and the prefrontal cortex, has been linked to the pathophysiology of some neuropsychiatric disorders, in which synaptic plasticity and functions such as emotional and cognitive processing are compromised. For this reason, the identification of new therapeutic strategies would be enriched by the search for metabolites that promote structural plasticity. The present study evaluated the dendritogenic potential of the ethanol extract of Lippia alba, an aromatic plant rich in flavonoids and terpenes, which has been widely used in traditional medicine for its presumed analgesic, anxiolytic, and antidepressant potential. An in vitro model of rat cortical neurons was used to determine the kinetics of the plant's effect at different time intervals. Changes in morphological parameters of the neurons were determined, as well as the dendritic complexity, by Sholl analysis. The extract promotes the outgrowth of dendritic branching in a rapid and sustained fashion, without being cytotoxic to the cells. We found that this effect could be mediated by the phosphatidylinositol 3-kinase pathway, which is involved in mechanisms of neuronal plasticity, differentiation, and survival. The evidence presented in this study provides a basis for further research that, through in vivo models, can delve into the plant's therapeutic potential.

Exploring the Impact of ECHO Ontario Integrated Mental and Physical Health on Participants' Approach and Attitude Toward the Care of Patients With Complex Needs.

OBJECTIVE: To examine how project Extension for Community Healthcare Outcomes-Integrated Mental and Physical Health (ECHO-IMPH) influences the attitudes and approaches of primary care providers and other participants towards patients. METHODS: An exploratory qualitative approach was undertaken using semistructured interviews conducted between August 2020 and March 2021. One hundred and sixty-four individuals from two cycles of ECHO-IMPH were invited to participate, and 22 (n = 22) agreed to participate. Data were analyzed using the Braun and Clarke method for thematic analysis. RESULTS: Three major themes were identified: 1) enhanced knowledge and skills; 2) changes in attitude and approach; 3) space for reflection and exploration. When participants were asked about areas for improvement, suggestions were focused on the structure of the sessions. Participants identified that ECHO-IMPH helped them to view patients more holistically, which led to greater patient-centered care in their practice. Additionally, skills gained in ECHO-IMPH gave participants the concrete tools needed to have more empathetic interactions with patients with complex needs. CONCLUSIONS: ECHO-IMPH created a safe space for participants to reflect on their practice with patients with complex needs. Participants applied newly acquired knowledge and skills to provide more empathetic and patient-centered care for patients with complex needs. Based on the shift in perspectives described by participants, transformative learning theory was proposed as a model for how ECHO-IMPH created change in participants' practice.

Targeted health and social care interventions for women and infants who are disproportionately impacted by health inequalities in high-income countries: a systematic review.

BACKGROUND: Disadvantaged populations (such as women from minority ethnic groups and those with social complexity) are at an increased risk of poor outcomes and experiences. Inequalities in health outcomes include preterm birth, maternal and perinatal morbidity and mortality, and poor-quality care. The impact of interventions is unclear for this population, in high-income countries (HIC). The review aimed to identify and evaluate the current evidence related to targeted health and social care service interventions in HICs which can improve health inequalities experienced by childbearing women and infants at disproportionate risk of poor outcomes and experiences. METHODS: Twelve databases searched for studies across all HICs, from any methodological design. The search concluded on 8/11/22. The inclusion criteria included interventions that targeted disadvantaged populations which provided a component of clinical care that differed from standard maternity care. RESULTS: Forty six index studies were included. Countries included Australia, Canada, Chile, Hong Kong, UK and USA. A narrative synthesis was undertaken, and results showed three intervention types: midwifery models of care, interdisciplinary care, and community-centred services. These intervention types have been delivered singularly but also in combination of each other demonstrating overlapping features. Overall, results show interventions had positive associations with primary (maternal, perinatal, and infant mortality) and secondary outcomes (experiences and satisfaction, antenatal care coverage, access to care, quality of care, mode of delivery, analgesia use in labour, preterm birth, low birth weight, breastfeeding, family planning, immunisations) however significance and impact vary. Midwifery models of care took an interpersonal and holistic approach as they focused on continuity of carer, home visiting, culturally and linguistically appropriate care and accessibility. Interdisciplinary care took a structural approach, to coordinate care for women requiring multi-agency health and social services. Community-centred services took a place-based approach with interventions that suited the need of its community and their norms. CONCLUSION: Targeted interventions exist in HICs, but these vary according to the context and infrastructure of standard maternity care. Multi-interventional approaches could enhance a targeted approach for at risk populations, in particular combining midwifery models of care with community-centred approaches, to enhance accessibility, earlier engagement, and increased attendance. TRIAL REGISTRATION: PROSPERO Registration number: CRD42020218357.

DESIGNER fraction concept unmasks minor bioactive constituents in red clover (Trifolium pratense L.).

In botanical extracts, highly abundant constituents can mask or dilute the effects of other, and often, more relevant biologically active compounds. To facilitate the rational chemical and biological assessment of these natural products with wide usage in human health, we introduced the DESIGNER approach of Depleting and Enriching Selective Ingredients to Generate Normalized Extract Resources. The present study applied this concept to clinical Red Clover Extract (RCE) and combined phytochemical and biological methodology to help rationalize the utility of RCE supplements for symptom management in postmenopausal women. Previous work has demonstrated that RCE reduces estrogen detoxification pathways in breast cancer cells (MCF-7) and, thus, may serve to negatively affect estrogen metabolism-induced chemical carcinogenesis. Clinical RCE contains ca. 30% of biochanin A and formononetin, which potentially mask activities of less abundant compounds. These two isoflavonoids are aryl hydrocarbon receptor (AhR) agonists that activate P450 1A1, responsible for estrogen detoxification, and P450 1B1, producing genotoxic estrogen metabolites in female breast cells. Clinical RCE also contains the potent phytoestrogen, genistein, that downregulates P450 1A1, thereby reducing estrogen detoxification. To identify less abundant bioactive constituents, countercurrent separation (CCS) of a clinical RCE yielded selective lipophilic to hydrophilic metabolites in six enriched DESIGNER fractions (DFs 01-06). Unlike solid-phase chromatography, CCS prevented any potential loss of minor constituents or residual complexity (RC) and enabled the polarity-based enrichment of certain constituents. Systematic analysis of estrogen detoxification pathways (ERα-degradation, AhR activation, CYP1A1/CYP1B1 induction and activity) of the DFs uncovered masked bioactivity of minor/less abundant constituents including irilone. These data will allow the optimization of RCE with respect to estrogen detoxification properties. The DFs revealed distinct biological activities between less abundant bioactives. The present results can inspire future carefully designed extracts with phytochemical profiles that are optimized to increase in estrogen detoxification pathways and, thereby, promote resilience in women with high-risk for breast cancer. The DESIGNER approach helps to establish links between complex chemical makeup, botanical safety and possible efficacy parameters, yields candidate DFs for (pre)clinical studies, and reveals the contribution of minor phytoconstituents to the overall safety and bioactivity of botanicals, such as resilience promoting activities relevant to women's health.

Cortico-thalamo-cortical interactions modulate electrically evoked EEG responses in mice.

Perturbational complexity analysis predicts the presence of consciousness in volunteers and patients by stimulating the brain with brief pulses, recording EEG responses, and computing their spatiotemporal complexity. We examined the underlying neural circuits in mice by directly stimulating cortex while recording with EEG and Neuropixels probes during wakefulness and isoflurane anesthesia. When mice are awake, stimulation of deep cortical layers reliably evokes locally a brief pulse of excitation, followed by a biphasic sequence of 120 ms profound off period and a rebound excitation. A similar pattern, partially attributed to burst spiking, is seen in thalamic nuclei and is associated with a pronounced late component in the evoked EEG. We infer that cortico-thalamo-cortical interactions drive the long-lasting evoked EEG signals elicited by deep cortical stimulation during the awake state. The cortical and thalamic off period and rebound excitation, and the late component in the EEG, are reduced during running and absent during anesthesia.

Embracing Complexity-the Role of Cancer Rehabilitation in Restoring and Maintaining Function and Quality of Life in Cancer Survivors with Radiation Fibrosis Syndrome.

Purpose of Review: Despite more than 6 decades of growth and transformation, the field of cancer rehabilitation has considerable room to evolve if it is to live up to its full potential. This article will discuss the importance of this evolution in the context of radiation late effects and serve as a call for the clinical and operational expansion of the field so that it can become a key component of comprehensive cancer care. Recent Findings: The clinical and operational challenges inherent in cancer survivors with radiation late effects necessitate different thinking with respect to how rehabilitation professionals evaluate and manage patients as well as how our institutions equip these professionals to practice at the highest possible level. Summary: To achieve its promise, the field of cancer rehabilitation must evolve to embrace fully the scope, scale, and complexity of issues faced by cancer survivors with radiation late effects. Better engagement and coordination of the care team are needed to deliver this care and ensure our programs are robust, sustainable, and flexible.