Deciphering the roadmap of in vivo reprogramming toward pluripotency

Differentiated cells can be converted into pluripotent stem cells by expressing the transcription factors OCT4, SOX2, KLF4, and MYC (OSKM) in a process known as reprogramming. Here, using single-cell RNA sequencing of pancreas undergoing reprogramming, we identify markers along the trajectory from acinar cell identity to pluripotency. These markers allow direct in situ visualization of cells undergoing dedifferentiation and acquiring features of early and advanced intermediate reprogramming. We also find that a fraction of cells do not dedifferentiate upon OSKM expression and are characterized by stress markers of the REG3 and AP-1 families. Importantly, most markers of intermediate reprogramming in the pancreas are also observed in stomach, colon, and cultured fibroblasts expressing OSKM. Among them is LY6A, a protein characteristic of progenitor cells and generally upregulated during tissue repair. Our roadmap defines intermediate reprogramming states that could be functionally relevant for tissue regeneration and rejuvenation.Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved

Patterns of impact resulting from a 'sit less, move more' web-based program in sedentary office employees.

PURPOSE: Encouraging office workers to 'sit less and move more' encompasses two public health priorities. However, there is little evidence on the effectiveness of workplace interventions for reducing sitting, even less about the longer term effects of such interventions and still less on dual-focused interventions. This study assessed the short and mid-term impacts of a workplace web-based intervention (Walk@WorkSpain, W@WS; 2010-11) on self-reported sitting time, step counts and physical risk factors (waist circumference, BMI, blood pressure) for chronic disease. METHODS: Employees at six Spanish university campuses (n=264; 42±10 years; 171 female) were randomly assigned by worksite and campus to an Intervention (used W@WS; n=129; 87 female) or a Comparison group (maintained normal behavior; n=135; 84 female). This phased, 19-week program aimed to decrease occupational sitting time through increased incidental movement and short walks. A linear mixed model assessed changes in outcome measures between the baseline, ramping (8 weeks), maintenance (11 weeks) and follow-up (two months) phases for Intervention versus Comparison groups. RESULTS: A significant 2 (group) × 2 (program phases) interaction was found for self-reported occupational sitting (F[3]=7.97, p=0.046), daily step counts (F[3]=15.68, p=0.0013) and waist circumference (F[3]=11.67, p=0.0086). The Intervention group decreased minutes of daily occupational sitting while also increasing step counts from baseline (446±126; 8,862±2,475) through ramping (+425±120; 9,345±2,435), maintenance (+422±123; 9,638±3,131) and follow-up (+414±129; 9,786±3,205). In the Comparison group, compared to baseline (404±106), sitting time remained unchanged through ramping and maintenance, but decreased at follow-up (-388±120), while step counts diminished across all phases. The Intervention group significantly reduced waist circumference by 2.1cms from baseline to follow-up while the Comparison group reduced waist circumference by 1.3cms over the same period. CONCLUSIONS: W@WS is a feasible and effective evidence-based intervention that can be successfully deployed with sedentary employees to elicit sustained changes on "sitting less and moving more"

Uptake and factors that influence the use of ‘sit less, move more’ occupational intervention strategies in Spanish office employees

Background Little is known about the types of ‘sit less, move more’ strategies that appeal to office employees, or what factors influence their use. This study assessed the uptake of strategies in Spanish university office employees engaged in an intervention, and those factors that enabled or limited strategy uptake. Methods The study used a mixed method design. Semi-structured interviews were conducted with academics and administrators (n = 12; 44 ± 12 mean SD age; 6 women) at three points across the five-month intervention, and data used to identify factors that influenced the uptake of strategies. Employees who finished the intervention then completed a survey rating (n = 88; 42 ± 8 mean SD age; 51 women) the extent to which strategies were used [never (1) to usually (4)]; additional survey items (generated from interviewee data) rated the impact of factors that enabled or limited strategy uptake [no influence (1) to very strong influence (4)]. Survey score distributions and averages were calculated and findings triangulated with interview data. Results Relative to baseline, 67% of the sample increased step counts post intervention (n = 59); 60% decreased occupational sitting (n = 53). ‘Active work tasks’ and ‘increases in walking intensity’ were the strategies most frequently used by employees (89% and 94% sometimes or usually utilised these strategies); ‘walk-talk meetings’ and ‘lunchtime walking groups’ were the least used (80% and 96% hardly ever or never utilised these strategies). ‘Sitting time and step count logging’ was the most important enabler of behaviour change (mean survey score of 3.1 ± 0.8); interviewees highlighted the motivational value of being able to view logged data through visual graphics in a dedicated website, and gain feedback on progress against set goals. ‘Screen based work’ (mean survey score of 3.2 ± 0.8) was the most significant barrier limiting the uptake of strategies. Inherent time pressures and cultural norms that dictated sedentary work practices limited the adoption of ‘walk-talk meetings’ and ‘lunch time walking groups’. Conclusions The findings provide practical insights into which strategies and influences practitioners need to target to maximise the impact of ‘sit less, move more’ occupational intervention strategies

High genetic diversity at the extreme range edge: nucleotide variation at nuclear loci in Scots pine (Pinus sylvestris L.) in Scotland

Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations across an environmental gradient in Scotland, to evaluate the impacts of demographic history and selection on genetic diversity. At eight loci, diversity patterns were compared between Scottish and continental European populations. At these loci, a similar level of diversity (θsil=~0.01) was found in Scottish vs mainland European populations, contrary to expectations for recent colonization, however, less rapid decay of linkage disequilibrium was observed in the former (ρ=0.0086±0.0009, ρ=0.0245±0.0022, respectively). Scottish populations also showed a deficit of rare nucleotide variants (multi-locus Tajima's D=0.316 vs D=−0.379) and differed significantly from mainland populations in allelic frequency and/or haplotype structure at several loci. Within Scotland, western populations showed slightly reduced nucleotide diversity (πtot=0.0068) compared with those from the south and east (0.0079 and 0.0083, respectively) and about three times higher recombination to diversity ratio (ρ/θ=0.71 vs 0.15 and 0.18, respectively). By comparison with results from coalescent simulations, the observed allelic frequency spectrum in the western populations was compatible with a relatively recent bottleneck (0.00175 × 4Ne generations) that reduced the population to about 2% of the present size. However, heterogeneity in the allelic frequency distribution among geographical regions in Scotland suggests that subsequent admixture of populations with different demographic histories may also have played a role

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

Relation between health literacy, self-care and adherence to treatment with oral anticoagulants in adults: a narrative systematic review.

Background Oral anticoagulants (OAC) are widely used in patients with cardiovascular diseases. However, for optimal OAC self-care patients must have skills, among which health literacy (HL) is highlighted. We aimed to describe the relation between HL and self-care in cardiovascular patients on OAC treatment. Methods Electronic searches were carried out in the PubMed, Scopus, Embase, CINAHL, Web of Science, Cochrane Library, SciELO, IME-Biomedicina, CUIDEN Plus and LILACS databases, limited to Spanish and English language and between January 2000-December 2016. Papers reported on adults older than 18 years, taking OAC by themselves for at least three months. PRISMA guidelines were used for paper selection. Results We identified 142 articles and finally included 10; almost all of them about warfarin. Our results suggest that in patients taking OAC treatments there is a positive relationship between HL and the level of knowledge. In addition, a small percentage of participants on the selected papers recognized the side effects and complications associated with OAC treatment. Lower HL level was associated with greater knowledge deficits and less adherence to treatment. Conclusion There is a paucity of research evaluating the effect of HL on diverse aspects of OAC treatments. There is a need to expand the evidence base regarding appropriate HL screening tools, determinants of adequate knowledge and optimal behaviours related to OAC self-management

Independent and combined influence of healthy lifestyle factors on academic performance in adolescents: DADOS Study

BACKGROUND. Few studies have analyzed the combined effect of lifestyle factors on academic performance (AP) in adolescents. The aim of this study was to analyze the independent and combined effects of weight status, screen time, sleep quality, daily meal frequency, cardiorespiratory fitness and physical activity (PA) on AP in adolescents. METHODS. A total of 262 adolescents (13.9±0.3 years) from the DADOS study were included in the analysis. Weight status was assessed through body mass index (kg/m 2 ). Participants completed questionnaires to evaluate screen time, sleep quality and daily meal frequency. Cardiorespiratory fitness was assessed by the 20-m shuttle run test. PA was evaluated by a wrist-worn GENEActiv accelerometer. AP was assessed through the final academic grades and a validated questionnaire. RESULTS. Non-overweight status, low screen time, good sleep quality and proper meal frequency showed independent, positive influence on AP. Moreover, adolescents achieving at least 3 healthy lifestyles were more likely to be in the high-performance group for academic grades than those achieving ≤ 1 (math OR: 3.02-9.51, language OR: 3.51-6.76 and grade point average OR: 4.22-9.36). CONCLUSIONS. Although individual healthy lifestyles are independently and positively associated with AP, the cumulative effect of multiple healthy lifestyles have a stronger impact

Clinical inertia in poorly controlled elderly hypertensive patients: a cross-sectional study in Spanish physicians to ascertain reasons for not intensifying treatment

Background Clinical inertia, the failure of physicians to initiate or intensify therapy when indicated, is a major problem in the management of hypertension and may be more prevalent in elderly patients. Overcoming clinical inertia requires understanding its causes and evaluating certain factors, particularly those related to physicians. Objective The objective of our study was to determine the rate of clinical inertia and the physician-reported rea- sons for it. Conclusion Physicians provided reasons for not intensi- fying treatment in poorly controlled patients in only 30 % of instances. Main reasons for not intensifying treatment were borderline BP values, co-morbidity, suspected white coat effect, or perceived difficulty achieving target. nJCI was associated with high borderline BP values and car- diovascular diseas

Prolonged Sitting Time: Barriers, Facilitators and Views on Change among Primary Healthcare Patients Who Are Overweight or Moderately Obese

Background and Objectives Prolonged sitting time has negative consequences on health, although the population is not well aware of these harmful effects. We explored opinions expressed by primary care patients diagnosed as overweight or moderately obese concerning their time spent sitting, willingness to change, and barriers, facilitators, goals and expectations related to limiting this behaviour. Methods A descriptive-interpretive qualitative study was carried out at three healthcare centres in Barcelona, Spain, and included 23 patients with overweight or moderate obesity, aged 25 to 65 years, who reported sitting for at least 6 hours a day. Exclusion criteria were inability to sit down or stand up from a chair without help and language barriers that precluded interview participation. Ten in-depth, semi-structured interviews (5 group, 5 individual) were audio recorded from January to July 2012 and transcribed. The interview script included questions about time spent sitting, willingness to change, barriers and facilitators, and the prospect of assistance from primary healthcare professionals. An analysis of thematic content was made using ATLAS.Ti and triangulation of analysts. Results The most frequent sedentary activities were computer use, watching television, and motorized journeys. There was a lack of awareness of the amount of time spent sitting and its negative consequences on health. Barriers to reducing sedentary time included work and family routines, lack of time and willpower, age and sociocultural limitations. Facilitators identified were sociocultural change, free time and active work, and family surroundings. Participants recognized the abilities of health professionals to provide help and advice, and reported a preference for patient-centred or group interventions. Conclusions Findings from this study have implications for reducing sedentary behaviour. Patient insights were used to design an intervention to reduce sitting time within the frame of the SEDESTACTIV clinical trial

Impact of a workplace 'sit less, move more' program on efficiency-related outcomes of office employees.

BACKGROUND: Few studies have examined the impact of 'sit less, move more' interventions on workplace performance. This study assessed the short and mid-term impacts of and patterns of change within, a 19-week workplace web-based intervention (Walk@WorkSpain; W@WS; 2010-11) on employees´ presenteeism, mental well-being and lost work performance. METHODS: A site randomised control trial recruited employees at six Spanish university campuses (n = 264; 42 ± 10 years; 171 female), assigned by worksite and campus to an Intervention (IG; used W@WS; n = 129; 87 female) or an active Comparison group (A-CG; pedometer, paper diary and self-reported sitting time; n = 135; 84 female). A linear mixed model assessed changes between the baseline, ramping (8 weeks), maintenance (11 weeks) and follow-up (two months) phases for the IG versus A-CG on (i) % of lost work productivity (Work Limitations Questionnaire; WLQ); (ii) three scales for presenteeism (WLQ) assessing difficulty meeting scheduling demands (Time), performing cognitive and inter-personal tasks (Mental-Interpersonal) and decrements in meeting the quantity, quality and timeliness of completed work (Output); and (iii) mental well-being (Warwick-Edinburgh Mental Well-being Scale). T-tests assessed differences between groups for changes on the main outcomes. In the IG, a multivariate logistic regression model identified patterns of response according to baseline socio-demographic variables, physical activity and sitting time. RESULTS: There was a significant 2 (group) × 2 (program time points) interaction for the Time (F [3]=8.69, p = 0.005), Mental-Interpersonal (F [3]=10.01, p = 0.0185), Output scales for presenteeism (F [3]=8.56, p = 0.0357), and for % of lost work performance (F [3]=10.31, p = 0.0161). Presenteeism and lost performance rose significantly in both groups across all study time points; after baseline performance was consistently better in the IG than in the A-CG. Better performance was linked to employees being more active (Time, p = 0.041) and younger (Mental-interpersonal, p = 0.057; Output, p = 0.017). Higher total sitting time during nonworking days (Mental-interpersonal, p = 0.019) and lower sitting time during workdays (WLQ Index, p = 0.013) also improved performance. CONCLUSION: Versus an active comparison condition, a 'sit less, move more` workplace intervention effectively reduced an array of markers of lost workday productivity. TRIAL REGISTRATION: NCT02960750 ; Date of registration: 07/11/2016