Structural Maintenance of Chromosomes Complexes.

The Structural Maintenance of Chromosomes (SMC) protein complexes are DNA-binding molecular machines required to shape chromosomes into functional units and to safeguard the genome through cell division. These ring-shaped multi-subunit protein complexes, which are present in all kingdoms of life, achieve this by organizing chromosomes in three-dimensional space. Mechanistically, the SMC complexes hydrolyze ATP to either stably entrap DNA molecules within their lumen, or rapidly reel DNA into large loops, which allow them to link two stretches of DNA in cis or trans. In this chapter, the canonical structure of the SMC complexes is first introduced, followed by a description of the composition and general functions of the main types of eukaryotic and prokaryotic SMC complexes. Thereafter, the current model for how SMC complexes perform in vitro DNA loop extrusion is presented. Lastly, chromosome loop formation by SMC complexes is introduced, and how the DNA loop extrusion mechanism contributes to chromosome looping by SMC complexes in cells is discussed.

CWL-Based Analysis Pipeline for Hi-C Data: From FASTQ Files to Matrices.

Over a decade has passed since the development of the Hi-C method for genome-wide analysis of 3D genome organization. Hi-C utilizes next-generation sequencing (NGS) technology to generate large-scale chromatin interaction data, which has accumulated across a diverse range of species and cell types, particularly in eukaryotes. There is thus a growing need to streamline the process of Hi-C data analysis to utilize these data sets effectively. Hi-C generates data that are much larger compared to other NGS techniques such as chromatin immunoprecipitation sequencing (ChIP-seq) or RNA-seq, making the data reanalysis process computationally expensive. In an effort to bridge this resource gap, the 4D Nucleome (4DN) Data Portal has reanalyzed approximately 600 Hi-C data sets, allowing users to access and utilize the analyzed data. In this chapter, we provide detailed instructions for the implementation of the common workflow language (CWL)-based Hi-C analysis pipeline adopted by the 4DN Data Portal ecosystem. This reproducible and portable pipeline generates standard Hi-C contact matrices in formats such as .hic or .mcool from FASTQ files. It enables users to output their own Hi-C data in the same format as those registered in the 4DN Data portal, facilitating comparative analysis using data registered in the portal. Our custom-made scripts are available on GitHub at https://github.com/kuzobuta/4dn_cwl_pipeline .

Three-Dimensional Simulation of Whole-Genome Structuring Through the Transition from Anaphase to Interphase.

In order to analyze the three-dimensional genome architecture, it is important to simulate how the genome is structured through the cell cycle progression. In this chapter, we present the usage of our computation codes for simulating how the human genome is formed as the cell transforms from anaphase to interphase. We do not use the global Hi-C data as an input into the genome simulation but represent all chromosomes as linear polymers annotated by the neighboring region contact index (NCI), which classifies the A/B type of each local chromatin region. The simulated mitotic chromosomes heterogeneously expand upon entry to the G1 phase, which induces phase separation of A and B chromatin regions, establishing chromosome territories, compartments, and lamina and nucleolus associations in the interphase nucleus. When the appropriate one-dimensional chromosomal annotation is possible, using the protocol of this chapter, one can quantitatively simulate the three-dimensional genome structure and dynamics of human cells of interest.

Cooperators or competitors? The interactions between WHO and the World Bank in global health governance.

Interactions between International Organisations (IOs) within a regime complex often manifest themselves through competition and cooperation. Current research has examined the factors that promote inter-organisational competition and cooperation, yet the precise timing of when such competition or cooperation commences remains unclear. This paper focuses on two pivotal IOs in global health governance, the World Health Organization (WHO) and the World Bank, to explore the timing and onset of competition and cooperation within a regime complex, as well as the driving factors in the evolution of their inter-organisational relationships. By looking into the interactions between the WHO and the World Bank in norm-setting and resource mobilising, the paper sheds light on how their relationships have transitioned from competitors to cooperators. It systematically presents the mechanisms and processes of policy transformation in inter-organisational interactions. As a new agenda arises, IOs within a regime complex often compete for dominance, with ideational differences driving them to propose and implement distinct governance strategies. They will compete for resources and mainstream of their strategy. The negative spillover effects of competitive policies consequently undermine the effectiveness of IOs' policy, thereby undercut their legitimacy. To surmount these challenges, the international community should promote inter-institutional coordination in global governance.

Reconsolidation of Traumatic Memories in the Treatment of Complex Post-traumatic Stress Disorder (CPTSD): A Case Study.

This case study explores the memory reconsolidation-based technique of reconsolidation of traumatic memories (RTM) to address complex post-traumatic stress disorder (CPTSD). Using the framework of CPTSD and the components of International Trauma Questionnaire (ITQ), several presenting symptoms and the history of childhood trauma (adverse childhood experiences assessment) were assessed. The individual, based on the trauma-informed care approach, went through a total of eight sessions after the initial consultation that included RTM on index trauma events, reframing, and self-regulation techniques. CPTSD and several internalizing symptoms were measured before and after the intervention. The findings suggest that memory reconsolidation-based RTM protocol, coupled with the constructs of CPTSD using ITQ and index trauma, could provide benefits for individuals with symptoms from prolonged exposure to trauma during childhood.

Cortical surface area profile mediates effects of childhood disadvantage on later-life general cognitive ability.

OBJECTIVES: Childhood disadvantage is associated with lower general cognitive ability (GCA) and brain structural differences in midlife and older adulthood. However, the neuroanatomical mechanisms underlying childhood disadvantage effects on later-life GCA remain poorly understood. Although total surface area (SA) has been linked to lifespan GCA differences, total SA does not capture the non-uniform nature of childhood disadvantage effects on neuroanatomy, which varies across unimodal and transmodal cortices. Here, we examined whether cortical SA profile-the extent to which the spatial patterning of SA deviates from the normative unimodal-transmodal cortical organization-is a mediator of childhood disadvantage effects on later-life GCA. METHOD: In 477 community-dwelling men aged 56-72 years old, childhood disadvantage index (CDI) was derived from four indicators of disadvantages and GCA was assessed using a standardized test. Cortical SA was obtained from structural magnetic resonance imaging. For cortical SA profile, we calculated the spatial similarity between maps of individual cortical SA and MRI-derived principal gradient (i.e., unimodal-transmodal organization). Mediation analyses were conducted to examine the indirect effects of CDI through cortical SA profile on GCA. RESULTS: Around 1.31% of CDI effects on later-life GCA were mediated by cortical SA profile, whereas total SA did not. Higher CDI was associated with more deviation of the cortical SA spatial patterning from the principal gradient, which in turn related to lower later-life GCA. DISCUSSION: Childhood disadvantage may contribute to later-life GCA differences partly by influencing the spatial patterning of cortical SA in a way that deviates from the normative cortical organizational principle.

The perceptual and mnemonic effects of ensemble representation on individual size representation.

Our visual world consists of multiple objects, necessitating the identification of individual objects. Nevertheless, the representation of visual objects often exerts influence on each other. Even when we selectively attend to a subset of visual objects, the representations of surrounding items are encoded and influence the processing of the attended item(s). However, it remains unclear whether the effect of group ensemble representation on individual item representation occurs at the perceptual encoding phase, during the memory maintenance period, or both. Therefore, the current study conducted visual psychophysics experiments to investigate the contributions of perceptual and mnemonic bias on the observed effect of ensemble representation on individual size representation. Across five experiments, we found a consistent pattern of repulsive ensemble bias, such that the size of an individual target circle was consistently reported to be smaller than it actually was when presented alongside other circles with larger mean size, and vice versa. There was a perceptual component to the bias, but mnemonic factors also influenced its magnitude. Specifically, the repulsion bias was strongest with a short retention period (0-50 ms), then reduced within a second to a weaker magnitude that remained stable for a longer retention period (5,000 ms). Such patterns of results persisted when we facilitated the processing of ensemble representation by increasing the set size (Experiment 1B) or post-cueing the target circle so that attention was distributed across all items (Experiment 2B).

Economic evaluation of the prevention of falls resulting from missed care in polish hospitals.

Objectives: Falls are associated with increased morbidity, mortality, prolonged hospitalization and an increase in the cost of treatment in hospitals. They contribute to the deterioration of fitness and quality of life, especially among older patients, thus posing a serious social and economic problem. They increase the risk of premature death. Falls are adverse, costly, and potentially preventable. The aim of the study was to analyze the cost-effectiveness of avoiding one fall by nurse care provided by the nurses with higher education, from the perspective of the health service provider. Methods: The economic analysis included and compared only the cost of nurse intervention measured by the hours of care provided with higher education in non-surgical departments (40.5%) with higher time spend by nurses with higher education level an increase in the number of hours by 10% (50.5%) to avoid one fall. The time horizon for the study is 1 year (2021). Cost-effectiveness and Cost-benefit analysis were performed. All registered falls of all hospitalized patients were included in the study. Results: In the analyzed was based on the case control study where, 7,305 patients were hospitalized, which amounted to 41,762 patient care days. Care was provided by 100 nurses, including 40 nurses with bachelor's degrees and nurses with Master of Science in Nursing. Increasing the hours number of high-educated nurses care by 10% in non-surgical departments decreased the chance for falls by 9%; however, this dependence was statistically insignificant (OR = 1.09; 95% CI: 0.72-1.65; p = 0.65). After the intervention (a 10% increase in Bachelor's Degrees/Master of Science in Nursing hours), the number of additional Bachelor's Degrees/Master of Science hours was 6100.5, and the cost was USD 7630.4. The intervention eliminated four falls. The cost of preventing one fall is CER = USD 1697.1. Conclusion: The results of these studies broaden the understanding of the relationship among nursing education, falls, and the economic outcomes of hospital care. According to the authors, the proposed intervention has an economic justification.

Beyond the Badge: A Scoping Review Among Police Personnel in South India Exploring the Impact of Yoga and Health Education on Cardiovascular Health.

Communicable diseases have been the primary cause of morbidity and mortality, affecting populations for decades. However, in recent times, noncommunicable diseases (NCDs) have emerged as the primary cause of illness and premature death due to factors such as urbanization, longer life expectancy, and unhealthy lifestyles. In recent years, noncommunicable illnesses have emerged as the primary cause of morbidity and premature mortality, replacing infectious diseases as the leading cause of illness and death. Among the top five causes of NCD, cardiovascular disease (CVD) is the most important factor, comprising the major diseases with maximum mortality and morbidity. The burden of CVD is greatly increased by modifiable risk factors, such as smoking, high blood pressure, type 2 diabetes, low-density lipoprotein cholesterol, and excess body weight. CVD occurs particularly in certain occupational risk groups, such as doctors, police personnel, and persons working for prolonged hours, predisposing them to unhealthy dietary practices, improper sleeping patterns, and increased psychological stress. As members of this occupational group, police personnel are particularly at risk for cardiovascular diseases, making it imperative to implement preventive measures to reduce the burden of these diseases in this population. The primary objective was to assess the impact of yoga and health education interventions on cardiovascular health outcomes among police personnel in South India, and the secondary objective was to examine the changes in blood pressure levels and lipid profiles following yoga and health education programs among police personnel.

Making health inequality analysis accessible: WHO tools and resources using Microsoft Excel.

Addressing health inequity is a central component of the Sustainable Development Goals and a priority of the World Health Organization (WHO). WHO supports countries in strengthening their health information systems in order to better collect, analyze and report health inequality data. Improving information and research about health inequality is crucial to identify and address the inequalities that lead to poorer health outcomes. Building analytical capacities of individuals, particularly in low-resource areas, empowers them to build a stronger evidence-base, leading to more informed policy and programme decision-making. However, health inequality analysis requires a unique set of skills and knowledge. This paper describes three resources developed by WHO to support the analysis of inequality data by non-statistical users using Microsoft Excel, a widely used and accessible software programme. The resources include a practical eLearning course, which trains learners in the preparation and reporting of disaggregated data using Excel, an Excel workbook that takes users step-by-step through the calculation of 21 summary measures of health inequality, and a workbook that automatically calculates these measures with the user's disaggregated dataset. The utility of the resources is demonstrated through an empirical example.

Role and promise of health policy and systems research in integrating rehabilitation into the health systems.

Despite recognized need and reasonable demand, health systems and rehabilitation communities keep working in silos, independently with minimal recognition to the issues of those who require rehabilitation services. Consolidated effort by health systems and rehabilitation parties, recognizing the value, power and promise of each other, is a need of the hour to address this growing issue of public health importance. In this paper, the importance and the need for integration of rehabilitation into health system is emphasized. The efforts being made to integrate rehabilitation into health systems and the potential challenges in integration of these efforts were discussed. Finally, the strategies and benefits of integrating rehabilitation in health systems worldwide is proposed. Health policy and systems research (HPSR) brings a number of assets that may assist in addressing the obstacles discussed above to universal coverage of rehabilitation. It seeks to understand and improve how societies organize themselves to achieve collective health goals; considers links between health systems and social determinants of health; and how different actors interact in policy and implementation processes. This multidisciplinary lens is essential for evidence and learning that might overcome the obstacles to the provision of rehabilitation services, including integration into health systems. Health systems around the world can no longer afford to ignore rehabilitation needs of their populations and the World Health Assembly (WHA) resolution marked a global call to this effect. Therefore, national governments and global health community must invest in setting a priority research agenda and promote the integration of rehabilitation into health systems. The context-specific, need-based and policy-relevant knowledge about this must be made available globally, especially in low- and middle-income countries. This could help integrate and implement rehabilitation in health systems of countries worldwide and also help achieve the targets of Rehabilitation 2030, universal health coverage and Sustainable Development Goals.

How online healthcare team evolve into organization: A social network analysis.

Objective: The rapid development of online healthcare has greatly promoted the transformation of healthcare service. The effectiveness of online healthcare is enhanced by the team that supports the doctor-patient connection. However, extant researches lack the comprehensive analysis of social networks within online healthcare team. In this study, we aim to clarify the characteristics and models of online healthcare team. Method: This study focuses on the online healthcare context and collects data from online healthcare team. Using social network analysis, the social networks of online healthcare members are also developed as part of the research. Result: This study uncovers the different modes of online healthcare teams from individual, team and organizational levels. These results shed light on the characteristics of an online healthcare team and show that such teams are capable of restructuring social networks. In addition, collaboration between teams allows for the development of multilevel relationships and the potential for the online healthcare team to evolve into a large-scale online healthcare organization. Conclusion: Through social network analysis, this study offers a fresh viewpoint on online healthcare and its implications for management, team construction, and organizational restruction. By examining the characteristics and models of online healthcare team, this research offers valuable insights for improving the overall effectiveness of online healthcare.

Exploring Lived Experiences of Vulnerability in Nursing Management during the Coronavirus Disease 2019 Pandemic: A Phenomenological Study of Nurse Managers and Nurses.

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic placed enormous pressure on healthcare systems around the world, but it also provided valuable insights for healthcare organizations during this challenging period. Objective: This study aimed to explore nurses' lived experiences of vulnerability in hospital nursing management during the COVID-19 pandemic, and reflect on the lessons learned. Methods: In this phenomenological study, 14 participants, including nurse managers at different levels and staff nurses, were selected by purposive sampling from one center university hospital. Data collection was done through in-depth individual semistructured interviews with participants and a review of weekly reports of crisis management meetings at the university hospital. Interviews were analyzed using Colaizzi's method in seven phases by MAXQDA software Version 10. Results: One overarching theme, four themes, and 15 subthemes were obtained from analyses of interviews. Four themes of "nurses' attrition," "distrust of society to the organization," "fragility in the organization's performance," and "intensified inequalities" were extracted as threats to nursing management at the hospital. Subsequently, the weekly reports of crisis management meetings at the university hospital were analyzed to extract the solutions and lessons. Conclusion: The unpreparedness of the healthcare system against a crisis can led to the loss of organizational assets, including medical staff and the credibility of the healthcare system. Limitations of the infrastructure at hospital became more obvious during the pandemic and caused serious threats to the healthcare system. Despite severe challenges along with the pandemic, it offered four valuable lessons in nursing management.

Complex PTSD symptoms predict positive symptoms of psychosis in the flow of daily life.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been shown to predict psychotic symptomology. However, few studies have examined the relative contribution of PTSD compared to broader post-traumatic sequelae in maintaining psychosis. Complex PTSD (cPTSD), operationalized using ICD-11 criteria, includes core PTSD (intrusions, avoidance, hyperarousal) as well as additional "disturbances of self-organisation" (DSO; emotional dysregulation, interpersonal difficulties, negative self-concept) symptoms, more likely to be associated with complex trauma histories. It was hypothesized that DSOs would be associated with positive psychotic symptoms (paranoia, voices, and visions) in daily life, over and above core PTSD symptoms. METHODS: This study (N = 153) employed a baseline subsample of the Study of Trauma And Recovery (STAR), a clinical sample of participants with comorbid post-traumatic stress and psychosis symptoms. Core PTSD, DSO and psychosis symptoms were assessed up to 10 times per day at quasi-random intervals over six consecutive days using Experience Sampling Methodology. RESULTS: DSOs within the preceding 90 min predicted paranoia, voices, and visions at subsequent moments. These relationships persisted when controlling for core PTSD symptoms within this timeframe, which were themselves significant. The associations between DSOs and paranoia but not voices or visions, were significantly stronger than those between psychosis and core PTSD symptoms. CONCLUSIONS: Consistent with an affective pathway to psychosis, the findings suggest that DSOs may be more important than core PTSD symptoms in maintaining psychotic experiences in daily life among people with comorbid psychosis and cPTSD, and indicate the potential importance of addressing broad post-traumatic sequelae in trauma-focused psychosis interventions.

Comparison of orientation encoding across layers within single columns of primate V1 revealed by high-density recordings.

Primary visual cortex (V1) has been the focus of extensive neurophysiological investigations, with its laminar organization serving as a crucial model for understanding the functional logic of neocortical microcircuits. Utilizing newly developed high-density, Neuropixels probes, we measured visual responses from large populations of simultaneously recorded neurons distributed across layers of macaque V1. Within single recordings, myriad differences in the functional properties of neuronal subpopulations could be observed. Notably, while standard measurements of orientation selectivity showed only minor differences between laminar compartments, decoding stimulus orientation from layer 4C responses outperformed both superficial and deep layers within the same cortical column. The superior orientation discrimination within layer 4C was associated with greater response reliability of individual neurons rather than lower correlated activity within neuronal populations. Our results underscore the efficacy of high-density electrophysiology in revealing the functional organization and network properties of neocortical microcircuits within single experiments.

Impact of caring leadership on nurses' work engagement: examining the chain mediating effect of calling and affective organization commitment.

BACKGROUND: Previous studies have established a positive link between nurse managers' caring leadership and nurses' work engagement, but the processes and conditions through which this leadership style influences positive work behaviors remain largely unexplored. To address this gap and contribute to the existing body of knowledge, we developed a chain-mediated effects model to elucidate the impact of caring leadership on nurses' work engagement and the underlying mechanisms. In this model, we identified professional mission and affective organizational commitment as the mediating variables, offering a novel perspective on the relationship between caring leadership and work engagement. METHODS: A robust multi-center and large-sample cross-sectional survey was conducted, involving 2502 first-line nurses from six general tertiary hospitals across the eastern, central, and western regions of China. The data collection instruments included a comprehensive questionnaire covering demographic information, the caring leadership scale, the Chinese calling scale, the affective organizational commitment scale, and the Utrecht work engagement scale. Data were meticulously screened and analyzed, employing descriptive analysis to summarize the demographic information, correlation analysis to test the relationship among the variables, stepwise regression analysis to explore the mediating role of calling and affective organization commitment, and the bootstrap method to test the chain mediating effect. This rigorous methodology not only ensures the reliability and validity of research findings but also instills confidence in the robustness of this research. RESULTS: The results indicated a positive relationship among caring leadership, calling, affective organizational commitment, and nurses' work engagement (p < 0.001). Specifically, caring leadership was significantly associated with nurses' calling (ß = 0.55, p < 0.001), affective organizational commitment (ß = 0.21, p < 0.001), and work engagement (ß = 0.05, p < 0.001). And the analysis further revealed that calling and affective organizational commitment mediate the process between caring leadership and work engagement(Effect: 0.17, 0.03, 0.05), with a relative effect size of 89.3% for the total indirect effect. These findings highlight the crucial role of these factors in enhancing nurses' work engagement, providing valuable insights for healthcare leaders and policymakers. CONCLUSION: Caring leadership positively predicts nurses' work engagement and indirectly mediates calling and affective organizational commitment. The results of this study revealed that the mechanisms of caring leadership influence nurses' work engagement, which provides a new approach to strengthening nurses' work engagement and improving patient healthcare outcomes and organizational performance. Healthcare organizations face continuous challenges; this study embodies the significance of caring leadership in improving nurses' work experience and increasing their work engagement. Nursing managers should enhance their knowledge of caring leadership and receive caring leadership training, thus actively improving their leadership behaviors in nurse management, enhancing leadership effectiveness, and creating more possibilities for developing healthcare organizations.

Factors associated with facility childbirth and skilled birth attendance in Migori County, Kenya and the effect of Lwala Community Alliance intervention: a cross-sectional assessment from the 2019 and 2021 Lwala household surveys.

Background: Despite evidence of the beneficial effects of skilled birth attendance (SBA) on maternal health and childbirth outcomes, there are disparities in access across counties in Kenya. These include Migori County which has historically recorded high maternal mortality rates. In 2007, the Lwala Community Alliance was founded to improve health outcomes in this county. The objective of this study is to provide a baseline status of facility childbirth and SBA in Migori and to characterize the effect of Lwala intervention on these outcomes. Methods: A cross-sectional household survey was designed for a 10-year study to evaluate the effectiveness of Lwala initiatives. The 2019 and 2021 household surveys were conducted in Lwala intervention wards and in comparison wards with sample sizes of 3,846 and 5,928 mothers, respectively. The survey captured demographic, health, and socioeconomic data at each household, data on SBA and facility childbirth, and explanatory variables. A generalized linear model was used to determine factors associated with SBA. A secondary trend analysis was conducted to determine change over time in the explanatory variables and SBA. To determine the change in SBA rate due to Lwala intervention, controlling for background temporal trends, a difference-in-differences (DiD) model compared SBA rates in intervention wards and comparison wards. Results: SBA increased in all surveyed wards and across all explanatory variables from 2019 to 2021. The DiD analysis showed that the SBA rate increased more in Lwala intervention wards than in comparison wards (Adjusted Prevalence Rate Ratio 1.05, p < 0.001, 95%CI 1.03-1.08). The 2021 survey found the highest rates of both facility childbirths (97.9%, 95%CI 96.5-98.7) and SBA (98.2%, 95%CI 97.0-99.0) in North Kamagambo, the oldest ward of Lwala intervention. Higher educational status, four or more ANC visits, marriage/cohabitation, and wealth were significantly associated with increased SBA. Conclusions: We provide the first quasi-experimental evidence that Lwala interventions are significantly improving SBA which may inform related initiatives in similar settings. The household-survey data provides a baseline for continued evaluation of Lwala programs, and the breakdown by ward allows for development of specific programmatic targets.

An RNA-centric view of transcription and genome organization.

Foundational models of transcriptional regulation involve the assembly of protein complexes at DNA elements associated with specific genes. These assemblies, which can include transcription factors, cofactors, RNA polymerase, and various chromatin regulators, form dynamic spatial compartments that contribute to both gene regulation and local genome architecture. This DNA-protein-centric view has been modified with recent evidence that RNA molecules have important roles to play in gene regulation and genome structure. Here, we discuss evidence that gene regulation by RNA occurs at multiple levels that include assembly of transcriptional complexes and genome compartments, feedback regulation of active genes, silencing of genes, and control of protein kinases. We thus provide an RNA-centric view of transcriptional regulation that must reside alongside the more traditional DNA-protein-centric perspectives on gene regulation and genome architecture.