Somatic stem cells mediate tissue maintenance for the lifetime of an organism. Despite the well-established longevity that is a prerequisite for such function, accumulating data argue for compromised ...stem cell function with age. Identifying the mechanisms underlying age-dependent stem cell dysfunction is therefore key to understanding the aging process. Here, using a model carrying a proofreading-defective mitochondrial DNA polymerase, we demonstrate hematopoietic defects reminiscent of premature HSC aging, including anemia, lymphopenia, and myeloid lineage skewing. However, in contrast to physiological stem cell aging, rapidly accumulating mitochondrial DNA mutations had little functional effect on the hematopoietic stem cell pool, and instead caused distinct differentiation blocks and/or disappearance of downstream progenitors. These results show that intact mitochondrial function is required for appropriate multilineage stem cell differentiation, but argue against mitochondrial DNA mutations per se being a primary driver of somatic stem cell aging.
► Mitochondria numbers change in a stage- and lineage-specific manner upon early HSC differentiation ► Mitochondria DNA (mtDNA) mutations compromise development of distinct hematopoietic lineages ► Physiological HSC aging is molecularly distinct from the premature aging of accelerated mtDNA mutations ► HSCs can efficiently self-renew even in the face of severe mtDNA mutations
Artificial intelligence (AI) is often heralded as a potential disruptor that will transform the practice of medicine. The amount of data collected and available in health care, coupled with advances ...in computational power, has contributed to advances in AI and an exponential growth of publications. However, the development of AI applications does not guarantee their adoption into routine practice. There is a risk that despite the resources invested, benefits for patients, staff, and society will not be realized if AI implementation is not better understood. The aim of this study was to explore how the implementation of AI in health care practice has been described and researched in the literature by answering 3 questions: What are the characteristics of research on implementation of AI in practice? What types and applications of AI systems are described? What characteristics of the implementation process for AI systems are discernible? A scoping review was conducted of MEDLINE (PubMed), Scopus, Web of Science, CINAHL, and PsycINFO databases to identify empirical studies of AI implementation in health care since 2011, in addition to snowball sampling of selected reference lists. Using Rayyan software, we screened titles and abstracts and selected full-text articles. Data from the included articles were charted and summarized. Of the 9218 records retrieved, 45 (0.49%) articles were included. The articles cover diverse clinical settings and disciplines; most (32/45, 71%) were published recently, were from high-income countries (33/45, 73%), and were intended for care providers (25/45, 56%). AI systems are predominantly intended for clinical care, particularly clinical care pertaining to patient-provider encounters. More than half (24/45, 53%) possess no action autonomy but rather support human decision-making. The focus of most research was on establishing the effectiveness of interventions (16/45, 35%) or related to technical and computational aspects of AI systems (11/45, 24%). Focus on the specifics of implementation processes does not yet seem to be a priority in research, and the use of frameworks to guide implementation is rare. Our current empirical knowledge derives from implementations of AI systems with low action autonomy and approaches common to implementations of other types of information systems. To develop a specific and empirically based implementation framework, further research is needed on the more disruptive types of AI systems being implemented in routine care and on aspects unique to AI implementation in health care, such as building trust, addressing transparency issues, developing explainable and interpretable solutions, and addressing ethical concerns around privacy and data protection.
Abstract
Background
Artificial intelligence (AI) for healthcare presents potential solutions to some of the challenges faced by health systems around the world. However, it is well established in ...implementation and innovation research that novel technologies are often resisted by healthcare leaders, which contributes to their slow and variable uptake. Although research on various stakeholders’ perspectives on AI implementation has been undertaken, very few studies have investigated leaders’ perspectives on the issue of AI implementation in healthcare. It is essential to understand the perspectives of healthcare leaders, because they have a key role in the implementation process of new technologies in healthcare. The aim of this study was to explore challenges perceived by leaders in a regional Swedish healthcare setting concerning the implementation of AI in healthcare.
Methods
The study takes an explorative qualitative approach. Individual, semi-structured interviews were conducted from October 2020 to May 2021 with 26 healthcare leaders. The analysis was performed using qualitative content analysis, with an inductive approach.
Results
The analysis yielded three categories, representing three types of challenge perceived to be linked with the implementation of AI in healthcare: 1) Conditions external to the healthcare system; 2) Capacity for strategic change management; 3) Transformation of healthcare professions and healthcare practice.
Conclusions
In conclusion, healthcare leaders highlighted several implementation challenges in relation to AI within and beyond the healthcare system in general and their organisations in particular. The challenges comprised conditions external to the healthcare system, internal capacity for strategic change management, along with transformation of healthcare professions and healthcare practice. The results point to the need to develop implementation strategies across healthcare organisations to address challenges to AI-specific capacity building. Laws and policies are needed to regulate the design and execution of effective AI implementation strategies. There is a need to invest time and resources in implementation processes, with collaboration across healthcare, county councils, and industry partnerships.
Greater interest is being shown in participatory approaches, especially in research on interventions that concern children and young people's health and well-being. Although participatory approaches ...have user involvement in common, they differ in terms of the explicit guidance on how to actually involve and engage children and young people in health research. The aim of this scoping review was to systematically map recent research involving children and young people in the development of interventions targeting issues of health and well-being.
An interpretative scoping literature review based on: a scientific literature search in (health and social science) databases, reference lists, a manual search in key journals and contact with existing networks was conducted. A total of 4458 references were identified through the literature search, of which 41 studies published between 2000 and 2017 were included in the review. The target population was children and young people under 25 years old. Level of participation was categorized according to Shier's Pathways to Participation Model.
The review showed that participatory approaches were most often used in the development of interventions in school settings and in community and healthcare settings and on issues concerning support in lifestyle or in managing illness or disease. The level of participation varied from children and young people taking part just as active informants, through stages of greater participation both in quantitative and qualitative terms, to children and young people becoming an active agent involved as a co-researcher where the research process was shaped by views of a higher level of mutuality. Most of the studies were categorised at a medium level and only three studies were judged to involve the children and young people at the highest level.
This scoping review showed that work remains in enabling children and young people to influence the development of interventions targeting health and well-being. In relation to level of sustainability in the interventions, it is relevant that goals, strategies and processes are formulated by those who can gain from the interventions. Participatory approaches aiming for a higher level of participation where children and young people work together with the researchers in partnerships are thus warranted.
The improvement in treatment of pediatric acute lymphatic leukemia (ALL) has introduced new challenges for pediatric oncology care in understanding and handling long-term treatment-related ...complications later in adult life. The aim of this study was to describe health related quality of life (HRQoL) and the relation to buffering factors among young adult (YA) pediatric ALL survivors and their siblings.
This cross-sectional study was performed among 227 adults, treated for pediatric ALL in Sweden between 1985 and 1997 and their siblings (n = 70). Group means of HRQoL (SF-36) were compared between YA ALL survivors and the siblings, as well as to normative values from the general population. Self-efficacy (GSES) and social support (SS-13 subscale AVSI) was considering potential buffering factors for HRQoL and mental health. Associations between HRQoL and mental health respectively and self-efficacy and social support was analyzed.
The YA ALL survivors scored significantly lower on the HRQoL parameters general health (69.6 vs. 78.4, p = 0.004) and role emotional (77.1 vs. 88.1, p = 0.014), than the siblings. Further, they reported significantly lower general health (69.6 vs. 75.8), vitality (56.9 vs. 68.8), social functioning (84.5 vs. 88.6), role emotional (77.1 vs. 85.7) and mental health (71.3 vs. 80.9) compared with Swedish norms. Both YA ALL survivors and the siblings reported lower vitality and worse mental health than the general population. The HRQoL parameters, depression, stress and anxiety were all associated with both self-efficacy and social support among the YA ALL survivors. Among the siblings however, only general health, vitality, role emotional, mental health and depression were associated with social support, and only general health and mental health were associated with general self-efficacy.
The results from this study show that buffering factors, like social support and self-efficacy, may play an important role for psychosocial outcomes and HRQoL among YA ALL survivors later in life. The results suggest that this group could benefit from continuous support in adult life to handle consequences of their pediatric disease.
•IgG antibodies are detectable six months after Covid-19.•IgG antibodies avidity index increases after Covid-19.•Avidity index is not suitable to differentiate between acute and previous covid-19 ...infection.
A potentially important aspect of the humoral immune response to Covid-19 is avidity, the overall binding strength between antibody and antigen. As low avidity is associated with a risk of re- infection in several viral infections, avidity might be of value to predict risk for reinfection with covid-19.
The purpose of this study was to describe the maturation of IgG avidity and the antibody-levels over time in patients with PCR-confirmed non-severe covid-19.
Prospective longitudinal cohort study including patients with RT-PCR confirmed covid-19. Blood samples were drawn 1, 3 and 6 months after infection. Antibody levels and IgG-avidity were analysed.
The majority had detectable s- and n-antibodies (88,1%, 89,1%, N = 75). The level of total n-antibodies significantly increased from 1 to 3 months (median value 28,3 vs 39,3 s/co, p<0.001) and significantly decreased from 3 to 6 months (median value 39,3 vs 17,1 s/co, p<0.001). A significant decrease in the IgG anti-spike levels (median value 37,6, 24,1 and 18,2 RU/ml, p<0.001) as well as a significant increase in the IgG-avidity index (median values 51,6, 66,0 and 71,0%, p<0.001) were seen from 1 to 3 to 6 months.
We found a significant ongoing increase in avidity maturation after Covid-19 whilst the levels of antibodies were declining, suggesting a possible aspect of long-term immunity.
Cellular replacement therapy has emerged as a novel strategy for the treatment of heart failure. The aim of our study was to determine the fate of injected mesenchymal stem cells (MSCs) and whole ...bone marrow (BM) cells in the infarcted heart. MSCs were purified from BM of transgenic mice and characterized using flow cytometry and in vitro differentiation assays. Myocardial infarctions were generated in mice and different cell populations including transgenic MSCs, unfractionated BM cells, or purified hematopoietic progenitors were injected. Encapsulated structures were found in the infarcted areas of a large fraction of hearts after injecting MSCs (22 of 43, 51.2%) and unfractionated BM cells (6 of 46, 13.0%). These formations contained calcifications and/or ossifications. In contrast, no pathological abnormalities were found after injection of purified hematopoietic progenitors (0 of 5, 0.0%), fibroblasts (0 of 5, 0.0%), vehicle only (0 of 30, 0.0%), or cytokine-induced mobilization of BM cells (0 of 35, 0.0%). We conclude that the developmental fate of BM-derived cells is not restricted by the surrounding tissue after myocardial infarction and that the MSC fraction underlies the extended bone formation in the infarcted myocardium. These findings seriously question the biologic basis and clinical safety of using whole BM and in particular MSCs to treat nonhematopoietic disorders.
Recent reports of increasing prevalence of frequent health complaints and mental health problems among adolescents call for directing more attention on determinants of adolescent health. The ...relationship between health and social capital has gained increased attention since the early 2000's and research at review level confirms the importance of social capital for health outcomes, despite methodological heterogeneity. The aim of this study was to identify distinct profiles of family, school and peer social capital in a nationally representative sample of adolescents and to explore health outcomes in those profiles.
Cross-sectional data from the Swedish Health Behaviour of School-aged Children 2013/14 was used for this study. The analytical sample consisted of 7,804 adolescents aged 11-, 13- and 15-years. Items representing sense of belonging and emotional support were assessed in three contexts; family, school and among peers. Latent profile analyses (LPA) were run to determine social capital profiles. Health outcomes included frequent health complaints and life satisfaction, while socioeconomic status and genders were included as predictors.
The results show that five distinct profiles best represent the data for 11- and 15-year olds, while a four-profile model was optimal for 13-year olds. Some profiles were recurrent between age groups but unique profiles were also found. Health outcomes were significantly different between profiles depending on levels of social capital in the different contexts.
This study provides novel insight into how social capital co-occurs among adolescents within the contexts of family, school and peers and how this translates into differences in health outcomes. The national representativeness of the sample increases the implications of the results and contributes to meaningful insights that help explain the interactions of social capital in multiple contexts, complementing what is previously known about the relationship with adolescent health.
To translate and culturally adapt the Children's Sleep Habits Questionnaire (CSHQ) to a Swedish version, CSHQ-SWE, and to assess its validity and reliability for use with children with attention ...deficit hyperactivity disorder (ADHD).
A total of 84 children with ADHD (51 boys and 33 girls; 6-12 years) and parents (7 men and 77 women; 28-51 years) were included in the study. CSHQ was translated and culturally adapted to Swedish, and assessed for concurrent validity with sleep actigraphy (analyzed by Kendall's Tau) and for reliability by internal consistency (analyzed by McDonald's Omega H). Face and content validity was evaluated by parents (n = 4) and healthcare professionals (n = 6) qualitatively (comprehensiveness, relevance, and comprehensibility assessed by interviews and analyzed by thematic analysis) and quantitatively (analyzed by content validity ratio and content validity index for 33 items and four non-scored inquiries).
Parent-reported sleep problems (CSHQ-SWE total score) were moderately correlated with less "Sleep Efficiency" (Tau = -0.305; p < 0.001) measured by sleep actigraphy. Parent-reported problems with "Sleep Onset Delay" was moderately correlated with measured time for "Sleep Onset Latency" (Tau = 0.433; p < 0.001). Parent-reported problems with "Night Wakings" were weakly correlated with measured time for "Wake After Sleep Onset" (Tau = 0.282; p < 0.001). Parents estimation of "Total daily sleep duration" was moderately correlated with measured "Total Sleep Time" (Tau = 0.386; p < 0.001). Five of the seven subscales reached an acceptable level for internal consistency (McDonald's Omega H > 0.700). Comprehensiveness, relevance, and comprehensibility of CSHQ-SWE were satisfactory overall. Content validity ratio was 0.80 to 1.00 for six items, 0.00 to 0.60 for 22 items, and < 0.00 for nine items. Content validity index was 0.22.
CSHQ-SWE demonstrated acceptable concurrent validity with objectively measured sleep and internal consistency, whereas the overall results of face and content validity assessment varied. The instrument needs to be further evaluated regarding construct validity, responsiveness, test-retest reliability, and its generalization to other populations.
Recent studies have suggested that bone marrow cells might possess a much broader differentiation potential than previously appreciated. In most cases, the reported efficiency of such plasticity has ...been rather low and, at least in some instances, is a consequence of cell fusion. After myocardial infarction, however, bone marrow cells have been suggested to extensively regenerate cardiomyocytes through transdifferentiation. Although bone marrow-derived cells are already being used in clinical trials, the exact identity, longevity and fate of these cells in infarcted myocardium have yet to be investigated in detail. Here we use various approaches to induce acute myocardial injury and deliver transgenically marked bone marrow cells to the injured myocardium. We show that unfractionated bone marrow cells and a purified population of hematopoietic stem and progenitor cells efficiently engraft within the infarcted myocardium. Engraftment was transient, however, and hematopoietic in nature. In contrast, bone marrow-derived cardiomyocytes were observed outside the infarcted myocardium at a low frequency and were derived exclusively through cell fusion.
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