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Nature Communications Apr 2024In tissue formation and repair, the epithelium undergoes complex patterns of motion driven by the active forces produced by each cell. Although the principles governing...
In tissue formation and repair, the epithelium undergoes complex patterns of motion driven by the active forces produced by each cell. Although the principles governing how the forces evolve in time are not yet clear, it is often assumed that the contractile stresses within the cell layer align with the axis defined by the body of each cell. Here, we simultaneously measured the orientations of the cell shape and the cell-generated contractile stresses, observing correlated, dynamic domains in which the stresses were systematically misaligned with the cell body. We developed a continuum model that decouples the orientations of contractile stress and cell body. The model recovered the spatial and temporal dynamics of the regions of misalignment in the experiments. These findings reveal that the cell controls its contractile forces independently from its shape, suggesting that the physical rules relating cell forces and cell shape are more flexible than previously thought.
Topics: Stress, Mechanical; Animals; Cell Shape; Models, Biological; Biomechanical Phenomena; Madin Darby Canine Kidney Cells; Dogs; Epithelial Cells
PubMed: 38684651
DOI: 10.1038/s41467-024-47702-w -
The Journal of Cell Biology Jun 2022Errors in mitosis that cause chromosome missegregation lead to aneuploidy and micronucleus formation, which are associated with cancer. Accurate segregation requires the...
Errors in mitosis that cause chromosome missegregation lead to aneuploidy and micronucleus formation, which are associated with cancer. Accurate segregation requires the alignment of all chromosomes by the mitotic spindle at the metaphase plate, and any misalignment must be corrected before anaphase is triggered. The spindle is situated in a membrane-free "exclusion zone"; beyond this zone, endomembranes (mainly endoplasmic reticulum) are densely packed. We investigated what happens to misaligned chromosomes localized beyond the exclusion zone. Here we show that such chromosomes become ensheathed in multiple layers of endomembranes. Chromosome ensheathing delays mitosis and increases the frequency of chromosome missegregation and micronucleus formation. We use an induced organelle relocalization strategy in live cells to show that clearance of endomembranes allows for the rescue of chromosomes that were destined for missegregation. Our findings indicate that endomembranes promote the missegregation of misaligned chromosomes that are outside the exclusion zone and therefore constitute a risk factor for aneuploidy.
Topics: Anaphase; Aneuploidy; Cell Membrane; Chromosome Segregation; Chromosomes; Endoplasmic Reticulum; Humans; Metaphase; Mitosis; Spindle Apparatus
PubMed: 35486148
DOI: 10.1083/jcb.202203021 -
Mixed messages: most spinal pain and osteoarthritis observational research is unclear or misaligned.Journal of Clinical Epidemiology Mar 2023We assessed authors' language and methods to determine alignment between reported aims, methods, intent, and interpretations in observational studies in spinal pain or... (Review)
Review
OBJECTIVES
We assessed authors' language and methods to determine alignment between reported aims, methods, intent, and interpretations in observational studies in spinal pain or osteoarthritis.
STUDY DESIGN AND SETTING
We searched five databases for observational studies that included people with spinal pain or osteoarthritis published in the last 5 years. We randomized 100 eligible studies, and classified study intent (aims and methods) and interpretations as causal, non-causal, unclear, or misaligned.
RESULTS
Overall, 38% of studies were aligned regarding their intent and interpretation (either causally (22%) or non-causally (16%)). 29% of studies' aims and 29% of study methods were unclear. Intent was misaligned in 16% of studies (where aim differed to method) and 23% of studies had misaligned interpretations (where there were multiple conflicting claims). The most common kind of aim was non-causal (38%), and the most common type of method (39%), intent (38%), and interpretations (35%) was causal.
CONCLUSIONS
Misalignment and mixed messages are common in observational research of spinal pain and osteoarthritis. More than 6 in 10 observational studies may be uninterpretable, because study intent and interpretations do not align. While causal methods and intent are most common in observational research, authors commonly shroud causal intent in non-causal terminology.
Topics: Humans; Osteoarthritis; Pain; Language
PubMed: 36736708
DOI: 10.1016/j.jclinepi.2023.01.005 -
Sensors (Basel, Switzerland) Dec 2022This study aims to report on the capability of microscope-based augmented reality (AR) to evaluate registration and navigation accuracy with extracranial and...
This study aims to report on the capability of microscope-based augmented reality (AR) to evaluate registration and navigation accuracy with extracranial and intracranial landmarks and to elaborate on its opportunities and obstacles in compensation for navigation inaccuracies. In a consecutive single surgeon series of 293 patients, automatic intraoperative computed tomography-based registration was performed delivering a high initial registration accuracy with a mean target registration error of 0.84 ± 0.36 mm. Navigation accuracy is evaluated by overlaying a maximum intensity projection or pre-segmented object outlines within the recent focal plane onto the in situ patient anatomy and compensated for by translational and/or rotational in-plane transformations. Using bony landmarks (85 cases), there was two cases where a mismatch was seen. Cortical vascular structures (242 cases) showed a mismatch in 43 cases and cortex representations (40 cases) revealed two inaccurate cases. In all cases, with detected misalignment, a successful spatial compensation was performed (mean correction: bone (6.27 ± 7.31 mm), vascular (3.00 ± 1.93 mm, 0.38° ± 1.06°), and cortex (5.31 ± 1.57 mm, 1.75° ± 2.47°)) increasing navigation accuracy. AR support allows for intermediate and straightforward monitoring of accuracy, enables compensation of spatial misalignments, and thereby provides additional safety by increasing overall accuracy.
Topics: Humans; Augmented Reality; Surgery, Computer-Assisted; Tomography, X-Ray Computed; Imaging, Three-Dimensional
PubMed: 36559961
DOI: 10.3390/s22249591 -
Journal of Sleep Research Apr 2023Decision-making has been shown to suffer when circadian preference is misaligned with time of assessment; however, little is known about how misalignment between sleep...
Decision-making has been shown to suffer when circadian preference is misaligned with time of assessment; however, little is known about how misalignment between sleep timing and the central circadian clock impacts decision-making. This study captured naturally occurring variation in circadian alignment (i.e., alignment of sleep-wake timing with the central circadian clock) to examine if greater misalignment predicts worse decision-making. Over the course of 2 weeks, 32 late adolescent drinkers (aged 18-22 years; 61% female; 69% White) continuously wore actigraphs and completed two overnight in-laboratory visits (Thursday and Sunday) in which both dim-light melatonin onset (DLMO) and behavioural decision-making (risk taking, framing, and strategic reasoning tasks) were assessed. Sleep-wake timing was assessed by actigraphic midsleep from the 2 nights prior to each in-laboratory visit. Alignment was operationalised as the phase angle (interval) between average DLMO and average midsleep. Multilevel modelling was used to predict performance on decision-making tasks from circadian alignment during each in-laboratory visit; non-linear associations were also examined. Shorter DLMO-midsleep phase angle predicted greater risk-taking under conditions of potential loss (B = -0.11, p = 0.06), but less risk-taking under conditions of potential reward (B = 0.14, p = 0.03) in a curvilinear fashion. Misalignment did not predict outcomes in the framing and strategic reasoning tasks. Findings suggest that shorter alignment in timing of sleep with the central circadian clock (e.g., phase-delayed misalignment) may impact risky decision-making, further extending accumulating evidence that sleep/circadian factors are tied to risk-taking. Future studies will need to replicate findings and experimentally probe whether manipulating alignment influences decision-making.
Topics: Adolescent; Humans; Female; Male; Circadian Rhythm; Sleep; Circadian Clocks; Time Factors; Melatonin; Risk-Taking
PubMed: 36122900
DOI: 10.1111/jsr.13728 -
Nutrition & Dietetics: the Journal of... Jul 2021Internal coherence in research refers to the alignment between ontology (nature of reality), epistemology (nature of knowledge), axiology (values), methodology and... (Review)
Review
AIM
Internal coherence in research refers to the alignment between ontology (nature of reality), epistemology (nature of knowledge), axiology (values), methodology and methods and is an important but often overlooked element of research quality. We therefore aimed to illustrate the concept of internal coherence in nutrition and dietetics research, and its importance beyond individual elements of study quality.
METHOD
A targeted literature search in Nutrition and Dietetics was used to identify research illustrating one example of three main approaches to research (scientific, interpretive and critical inquiry) published between November 2017 and November 2020. Studies were included if they related to education research based on the expertise of the authors, and illustrated diverse points about internal coherence. The authors independently critiqued included studies for internal coherence and synthesised their findings.
RESULTS
From 76 manuscripts, 14 were identified as describing education research. Of the three selected studies that were critiqued, all had elements of internal coherence, in particular alignment between epistemology and methodology. However, each had elements of misalignment too, specifically between epistemology, axiology and method. The results point to the profession's historical groundings privileging the scientific approach, showing how this can yield misalignments, particularly when describing the limitations of interpretive and critical inquiry approaches.
CONCLUSION
This review demonstrates the importance of internal coherence as a marker of quality, over and above existing quality assessment checklists for qualitative and quantitative methodologies. As such, it can help authors, reviewers and editors to improve the quality of nutrition and dietetics research and its reporting.
Topics: Dietetics; Humans; Nutritional Status; Research Design
PubMed: 34151511
DOI: 10.1111/1747-0080.12680 -
Frontiers in Behavioral Neuroscience 2022Steroids are lipid hormones that reach bodily tissues through the systemic circulation, and play a major role in reproduction, metabolism, and homeostasis. All of these... (Review)
Review
BACKGROUND
Steroids are lipid hormones that reach bodily tissues through the systemic circulation, and play a major role in reproduction, metabolism, and homeostasis. All of these functions and steroids themselves are under the regulation of the circadian timing system (CTS) and its cellular/molecular underpinnings. In health, cells throughout the body coordinate their daily activities to optimize responses to signals from the CTS and steroids. Misalignment of responses to these signals produces dysfunction and underlies many pathologies.
QUESTIONS ADDRESSED
To explore relationships between the CTS and circulating steroids, we examine the brain clock located in the suprachiasmatic nucleus (SCN), the daily fluctuations in plasma steroids, the mechanisms producing regularly recurring fluctuations, and the actions of steroids on their receptors within the SCN. The goal is to understand the relationship between temporal control of steroid secretion and how rhythmic changes in steroids impact the SCN, which in turn modulate behavior and physiology.
EVIDENCE SURVEYED
The CTS is a multi-level organization producing recurrent feedback loops that operate on several time scales. We review the evidence showing that the CTS modulates the timing of secretions from the level of the hypothalamus to the steroidogenic gonadal and adrenal glands, and at specific sites within steroidogenic pathways. The SCN determines the timing of steroid hormones that then act on their cognate receptors within the brain clock. In addition, some compartments of the body-wide CTS are impacted by signals derived from food, stress, exercise etc. These in turn act on steroidogenesis to either align or misalign CTS oscillators. Finally this review provides a comprehensive exploration of the broad contribution of steroid receptors in the SCN and how these receptors in turn impact peripheral responses.
CONCLUSION
The hypothesis emerging from the recognition of steroid receptors in the SCN is that mutual shaping of responses occurs between the brain clock and fluctuating plasma steroid levels.
PubMed: 35722187
DOI: 10.3389/fnbeh.2022.877256 -
Clinical Rheumatology Sep 2017The main objective of the present study is to evaluate the misalignment between psoriatic arthritis (PsA) patient- and physician-reported satisfaction with PsA control....
The main objective of the present study is to evaluate the misalignment between psoriatic arthritis (PsA) patient- and physician-reported satisfaction with PsA control. Data came from the Adelphi Rheumatology Disease Specific Programme, a retrospective, cross-sectional survey of US-based rheumatologists and patients. Physicians provided satisfaction and clinical characteristics on tender joint count, swollen joint count, and percent body surface area (BSA) affected by psoriasis. Patients provided data on satisfaction, the Work Productivity Activity Impairment and Health Assessment Questionnaire-Disability Index (HAQ-DI) questionnaires. Based on their satisfaction response, patient-physician pairs were classified into aligned (both satisfied or dissatisfied) or misaligned (rated satisfaction differently) groups. Multivariate analysis evaluated association of characteristics with misalignment. Among 305 paired patient-physician records analyzed, 23.6% were misaligned and 76.4% were aligned. The misaligned group had shorter disease duration (mean years, 5.2 vs. 6.4), used fewer biologic disease-modifying antirheumatic drugs (49.3 vs. 62.9%), had more swollen (mean, 3.7 vs. 1.9, P = 0.0002) and tender joints (mean, 5.6 vs. 2.9, P < 0.0001), greater proportion of patients with comorbidities (72.2 vs. 63.1%), and >3% BSA affected by psoriatic skin lesions (64.2 vs. 55.1%). Misaligned patients reported greater work impairment (mean, 38.7 vs. 21.4, P = 0.0004), daily activities (mean, 38.7 vs. 22.3, P < 0.0001), and higher disease burden (mean HAQ-DI; 0.56 vs. 0.37, P = 0.0001). Multivariate analysis found the number of swollen joints (P = 0.02) and HAQ-DI score (P = 0.03) was significantly associated with misalignment among all patients; however, not in the subgroup of employed patients. Patient-physician misalignment is associated with increased disease activity and disability among patients with PsA.
Topics: Adult; Antirheumatic Agents; Arthritis, Psoriatic; Comorbidity; Cross-Sectional Studies; Female; Humans; Joints; Logistic Models; Male; Middle Aged; Multivariate Analysis; Patient Satisfaction; Physician-Patient Relations; Retrospective Studies; Skin; Surveys and Questionnaires; United States
PubMed: 28238086
DOI: 10.1007/s10067-017-3578-9 -
Journal of Biological Rhythms Apr 2017Shift work is a risk factor for inflammation, hypertension, and cardiovascular disease. This increased risk cannot be fully explained by classical risk factors. Shift...
Shift work is a risk factor for inflammation, hypertension, and cardiovascular disease. This increased risk cannot be fully explained by classical risk factors. Shift workers' behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in shift workers, independent of differences in work stress, food quality, and other factors that are likely to differ between night and day shifts. Thus, our objectives were to determine the independent effect of circadian misalignment on 24-h high-sensitivity C-reactive protein (hs-CRP; a marker of systemic inflammation) and blood pressure levels-cardiovascular disease risk factors-in chronic shift workers. Chronic shift workers undertook two 3-day laboratory protocols that simulated night work, comprising 12-hour inverted behavioral and environmental cycles (circadian misalignment) or simulated day work (circadian alignment), using a randomized, crossover design. Circadian misalignment increased 24-h hs-CRP by 11% ( p < 0.0001). Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 1.4 mmHg and 0.8 mmHg, respectively (both p ≤ 0.038). The misalignment-mediated increase in 24-h SBP was primarily explained by an increase in SBP during the wake period (+1.7 mmHg; p = 0.017), whereas the misalignment-mediated increase in 24-h DBP was primarily explained by an increase in DBP during the sleep opportunity (+1.8 mmHg; p = 0.005). Circadian misalignment per se increases hs-CRP and blood pressure in shift workers. This may help explain the increased inflammation, hypertension, and cardiovascular disease risk in shift workers.
Topics: Adult; Biomarkers; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Chronobiology Disorders; Circadian Rhythm; Female; Humans; Hypertension; Inflammation; Male; Middle Aged; Risk Factors; Shift Work Schedule; Sleep; Work Schedule Tolerance; Young Adult
PubMed: 28347188
DOI: 10.1177/0748730417697537 -
Health Policy and Planning Jan 2024Development assistance is a major source of financing for health in least developed countries. However, persistent aid fragmentation has led to inefficiencies and health... (Review)
Review
Development assistance is a major source of financing for health in least developed countries. However, persistent aid fragmentation has led to inefficiencies and health inequities and constrained progress towards Universal Health Coverage (UHC). Malawi is a case study for this global challenge, with 55% of total health expenditure funded by donors and fragmentation across 166 financing sources and 265 implementing partners. This often leads to poor coordination and misalignment between government priorities and donor projects. To address these challenges, the Malawi Ministry of Health (MoH) has developed and implemented an architecture of aid coordination tools and processes. Using a case study approach, we documented the iterative development, implementation and institutionalization of these tools, which was led by the MoH with technical assistance from the Clinton Health Access Initiative. We reviewed the grey literature, including relevant policy documents, planning tools and databases of government/partner funding commitments, and drew upon the authors' experiences in designing, implementing and scaling up these tools. Overall, the iterative use and revision of these tools by the Government of Malawi across the national and subnational levels, including integration with the government's public financial management system, was critical to successful uptake. The tools are used to inform government and partner resource allocation decisions, assess financing and gaps for national and district plans and inform donor grant applications. As Malawi has launched the Health Sector Strategic Plan 2023-2030, these tools are being adapted for the 'One Plan, One Budget and One Report' approach. However, while the tools are an incremental mechanism to strengthen aid alignment, success has been constrained by the larger context of power imbalances and misaligned incentives between the donor community and the Government of Malawi. Reform of the aid architecture is therefore critical to ensure that these tools achieve maximum impact in Malawi's journey towards UHC.
Topics: Humans; Malawi; Universal Health Insurance; Budgets; Databases, Factual; Developing Countries
PubMed: 38253443
DOI: 10.1093/heapol/czad102