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Stem Cell Reviews and Reports Jan 2024Tissue homeostasis is crucial for multicellular organisms, wherein the loss of cells is compensated by generating new cells with the capacity for proliferation and... (Review)
Review
Tissue homeostasis is crucial for multicellular organisms, wherein the loss of cells is compensated by generating new cells with the capacity for proliferation and differentiation. At the origin of these populations are the stem cells, which have the potential to give rise to cells with both capabilities, and persevere for a long time through the self-renewal and quiescence. Since the discovery of stem cells, an enormous effort has been focused on learning about their functions and the molecular regulation behind them. Wnt signaling is widely recognized as essential for normal and cancer stem cell. Moreover, β-catenin-dependent Wnt pathway, referred to as canonical, has gained attention, while β-catenin-independent Wnt pathways, known as non-canonical, have remained conspicuously less explored. However, recent evidence about non-canonical Wnt pathways in stem cells begins to lay the foundations of a conceivably vast field, and on which we aim to explain this in the present review. In this regard, we addressed the different aspects in which non-canonical Wnt pathways impact the properties of stem cells, both under normal conditions and also under disease, specifically in cancer.
Topics: Humans; Wnt Signaling Pathway; beta Catenin; Neoplastic Stem Cells; Neoplasms; Cell Differentiation
PubMed: 37804416
DOI: 10.1007/s12015-023-10610-5 -
Biological Psychiatry Global Open... Jan 2024The nature of cognitive flexibility deficits in obsessive-compulsive disorder (OCD), which historically have been tested with probabilistic reversal learning tasks,...
BACKGROUND
The nature of cognitive flexibility deficits in obsessive-compulsive disorder (OCD), which historically have been tested with probabilistic reversal learning tasks, remains elusive. Here, a novel deterministic reversal task and inclusion of unmedicated patients in the study sample illuminated the role of fixed versus uncertain rules/contingencies and of serotonergic medication. Additionally, our understanding of probabilistic reversal was enhanced through theoretical computational modeling of cognitive flexibility in OCD.
METHODS
We recruited 49 patients with OCD, 21 of whom were unmedicated, and 43 healthy control participants matched for age, IQ, and gender. Participants were tested on 2 tasks: a novel visuomotor deterministic reversal learning task with 3 reversals (feedback rewarding/punishing/neutral) measuring accuracy/perseveration and a 2-choice visual probabilistic reversal learning task with uncertain feedback and a single reversal measuring win-stay and lose-shift. Bayesian computational modeling provided measures of learning rate, reinforcement sensitivity, and stimulus stickiness.
RESULTS
Unmedicated patients with OCD were impaired on the deterministic reversal task under punishment only at the first and third reversals compared with both control participants and medicated patients with OCD, who had no deficit. Perseverative errors were correlated with OCD severity. On the probabilistic reversal task, unmedicated patients were only impaired at reversal, whereas medicated patients were impaired at both the learning and reversal stages. Computational modeling showed that the overall change was reduced feedback sensitivity in both OCD groups.
CONCLUSIONS
Both perseveration and increased shifting can be observed in OCD, depending on test conditions including the predictability of reinforcement. Perseveration was related to clinical severity and remediated by serotonergic medication.
PubMed: 38298803
DOI: 10.1016/j.bpsgos.2023.06.004 -
JAMA Network Open Aug 2023Little is known about temporal trends in children's well-being and how the COVID-19 pandemic may have influenced the well-being of young Australians. Certain demographic...
IMPORTANCE
Little is known about temporal trends in children's well-being and how the COVID-19 pandemic may have influenced the well-being of young Australians. Certain demographic groups may be more vulnerable to experiencing declines in well-being.
OBJECTIVE
To examine well-being trends over 6 consecutive years among South Australian students and explore the influence of sociodemographic characteristics.
DESIGN, SETTING, AND PARTICIPANTS
Longitudinal analyses of annual (2017 to 2022) cross-sectional data of students in grades 4 through 9 (n = 40 392 to 56 897 per year) attending South Australian government schools from the Well-being and Engagement Collection (WEC) census.
EXPOSURES
Calendar year (2017-2022) and sociodemographic characteristics (sex, school grade, parental education, language spoken at home, residential region) from school enrollment records.
MAIN OUTCOMES AND MEASURES
Students self-reported life satisfaction, optimism, happiness, cognitive engagement, emotional regulation, perseverance, worry, and sadness.
RESULTS
Over 6 years (2017 to 2022), a total of 119 033 students (mean [SD] age, 12.1 y; 51.4% male) participated in this study. Most well-being measures declined over time, with consistent worsening of well-being from 2020 onward. For example, compared with 2017, sadness was 0.26 (95% CI, 0.25-0.27) points higher in 2020 (standardized mean difference [SMD], 0.27) and remained elevated by more than 0.26 points (SMD, 0.27) in 2021 and 2022. At almost every time point, greatest well-being was reported by students of male sex (except cognitive engagement and perseverance), in earlier school grades, with highest parental education, speaking a language other than English at home, and residing in outer regional and remote settings (for satisfaction, optimism, and emotional regulation). Sociodemographic differences in well-being were generally consistent over time; however, sex differences widened from 2020 for all indicators except cognitive engagement and perseverance. For example, between 2017 and 2022, sadness increased by 0.27 (95% CI, 0.25-0.29) more points among females than males (SMD, 0.28).
CONCLUSIONS AND RELEVANCE
In this longitudinal analysis of annual census data, there were downward trends in students' well-being, especially since 2020. The largest sociodemographic disparities were observed for students of female sex, those in later school grades, and those with lowest parental education. Urgent and equitable support for the well-being of all young people, particularly those facing disparity, is imperative.
Topics: Child; Female; Adolescent; Male; Humans; Australia; Cross-Sectional Studies; Pandemics; COVID-19; South Australia
PubMed: 37606925
DOI: 10.1001/jamanetworkopen.2023.30098 -
Brain : a Journal of Neurology Apr 2024Apathy is a common and disabling complication of Parkinson's disease characterized by reduced goal-directed behaviour. Several studies have reported dysfunction within...
Apathy is a common and disabling complication of Parkinson's disease characterized by reduced goal-directed behaviour. Several studies have reported dysfunction within prefrontal cortical regions and projections from brainstem nuclei whose neuromodulators include dopamine, serotonin and noradrenaline. Work in animal and human neuroscience have confirmed contributions of these neuromodulators on aspects of motivated decision-making. Specifically, these neuromodulators have overlapping contributions to encoding the value of decisions, and influence whether to explore alternative courses of action or persist in an existing strategy to achieve a rewarding goal. Building upon this work, we hypothesized that apathy in Parkinson's disease should be associated with an impairment in value-based learning. Using a four-armed restless bandit reinforcement learning task, we studied decision-making in 75 volunteers; 53 patients with Parkinson's disease, with and without clinical apathy, and 22 age-matched healthy control subjects. Patients with apathy exhibited impaired ability to choose the highest value bandit. Task performance predicted an individual patient's apathy severity measured using the Lille Apathy Rating Scale (R = -0.46, P < 0.001). Computational modelling of the patient's choices confirmed the apathy group made decisions that were indifferent to the learnt value of the options, consistent with previous reports of reward insensitivity. Further analysis demonstrated a shift away from exploiting the highest value option and a reduction in perseveration, which also correlated with apathy scores (R = -0.5, P < 0.001). We went on to acquire functional MRI in 59 volunteers; a group of 19 patients with and 20 without apathy and 20 age-matched controls performing the Restless Bandit Task. Analysis of the functional MRI signal at the point of reward feedback confirmed diminished signal within ventromedial prefrontal cortex in Parkinson's disease, which was more marked in apathy, but not predictive of their individual apathy severity. Using a model-based categorization of choice type, decisions to explore lower value bandits in the apathy group activated prefrontal cortex to a similar degree to the age-matched controls. In contrast, Parkinson's patients without apathy demonstrated significantly increased activation across a distributed thalamo-cortical network. Enhanced activity in the thalamus predicted individual apathy severity across both patient groups and exhibited functional connectivity with dorsal anterior cingulate cortex and anterior insula. Given that task performance in patients without apathy was no different to the age-matched control subjects, we interpret the recruitment of this network as a possible compensatory mechanism, which compensates against symptomatic manifestation of apathy in Parkinson's disease.
Topics: Humans; Parkinson Disease; Apathy; Dopamine; Motivation; Neurotransmitter Agents
PubMed: 38305691
DOI: 10.1093/brain/awae025 -
Arquivos de Neuro-psiquiatria Oct 2023Frontal ataxia, originally described by Bruns, is characterized by the presence of signs of frontal lobe dysfunction, such as perseveration, paratonia, frontal release...
Frontal ataxia, originally described by Bruns, is characterized by the presence of signs of frontal lobe dysfunction, such as perseveration, paratonia, frontal release signs, cognitive changes, and urinary difficulty, associated with imbalance, slow gait, broad-based, the presence of postural instability and falls, retropulsion, and bradykinesia in the lower limbs. The goal of the present study is to recall the historical aspects of this condition, to draw attention to the importance of this clinical finding for the differential diagnosis of ataxias and to review the main semiological differences between primary ataxias (frontal, cerebellar, and sensory ataxia).
Topics: Humans; Ataxia; Cerebellum; Diagnosis, Differential; Frontal Lobe; Gait
PubMed: 37899045
DOI: 10.1055/s-0043-1775886 -
Scientific Reports Jun 2023Irritability, anger, and impulsivity have important associations with psychological well-being. However, studying the internal relationships between such emotional...
Irritability, anger, and impulsivity have important associations with psychological well-being. However, studying the internal relationships between such emotional constructs is challenging, largely because of the lack of precise operational definitions and extensively validated measurement tools. The aim of this study was to examine relationships between the above emotional constructs and how they relate to satisfaction with life and perceived negative impact on different life domains. Participants (N = 471) completed a self-report questionnaire online. Correlational analyses showed that higher levels of irritability and trait anger were associated with lower life satisfaction. Impulsivity displayed complex relationships with life satisfaction, with some aspects (sensation seeking) showing a positive relationship and others (urgency, lack of perseverance) showing a negative relationship. A two-factor Confirmatory Factor Analysis treating irritability and anger as separate constructs showed a better fit compared with a one-factor model, indicating that irritability and anger should be treated as separate constructs. An exploratory moderation analysis showed that higher irritability predicted increased anger only for participants scoring average to high on urgency (a facet of impulsivity). Our findings increase the understanding of the relationship between these dispositional constructs and supports the conceptualization of irritability and anger as related but distinct constructs.
Topics: Humans; Anger; Impulsive Behavior; Irritable Mood; Surveys and Questionnaires; Self Report
PubMed: 37369760
DOI: 10.1038/s41598-023-37557-4 -
Medicina (Kaunas, Lithuania) Oct 2023The history of esophagectomy reflects a journey of dedication, collaboration, and technical innovation, with ongoing endeavors aimed at optimizing outcomes and reducing... (Review)
Review
The history of esophagectomy reflects a journey of dedication, collaboration, and technical innovation, with ongoing endeavors aimed at optimizing outcomes and reducing complications. From its early attempts to modern minimally invasive approaches, the journey has been marked by perseverance and innovation. Franz J. A. Torek's 1913 successful esophageal resection marked a milestone, demonstrating the feasibility of transthoracic esophagectomy and the potential for esophageal cancer cure. However, its high mortality rate posed challenges, and it took almost two decades for similar successes to emerge. Surgical techniques evolved with the left thoracotomy, right thoracotomy, and transhiatal approaches, expanding the indications for resection. Mechanical staplers introduced in the early 20th century transformed anastomosis, reducing complications. The advent of minimally invasive techniques in the 1990s aimed to minimize complications while maintaining oncological efficacy. Robot-assisted esophagectomy further pushed the boundaries of minimally invasive surgery. Collaborative efforts, particularly from the Worldwide Esophageal Cancer Collaboration and the Esophageal Complications Consensus Group, standardized reporting and advanced the understanding of outcomes. The introduction of risk prediction models aids in making informed decisions. Despite significant improvements in survival rates and postoperative mortality, anastomotic leaks remain a concern, with recent rates showing an increase. Prevention strategies include microvascular anastomosis and ischemic preconditioning, yet challenges persist.
Topics: Humans; Esophagectomy; Postoperative Complications; Esophageal Neoplasms; Anastomotic Leak; Robotic Surgical Procedures; Treatment Outcome
PubMed: 37893504
DOI: 10.3390/medicina59101786 -
Frontiers in Psychology 2023Recent years have witnessed increasing attention to personality strength (grit) due to its merit in goal-seeking language learning processes. Two facets of grit, namely... (Review)
Review
Recent years have witnessed increasing attention to personality strength (grit) due to its merit in goal-seeking language learning processes. Two facets of grit, namely perseverance of effort (PE) and consistency of interest (CI), play a critical role in overcoming learning difficulties and strengthening willpower to pursue learning goals. The current review seeks to explore various issues related to grit, including its factor structure, the relationship between grit and frequently associated factors, as well as the utility of PE and CI in facilitating language learning. This exploration is based on the findings of 32 empirical articles published between 2017 and 2022 from three databases. The results indicate that although research which examines the role of grit has entered a fast growth phase since 2020, there is still a need for expansion and diversification in scopes, participants, research methods, and language contexts. Moreover, previous studies have not adequately addressed the critical issue of grit's conceptualization and factor structure. Finally, this study suggests that future researchers should impartially assess the factor structure and nature of PE and CI, to provide more robust evidence to clarify the relationship between grit and diverse emotions and positive institutions, in order to advance understanding of grit in second language learning.
PubMed: 37727745
DOI: 10.3389/fpsyg.2023.1238788 -
Journal of Affective Disorders Oct 2023The affective, cognitive, and behavioral aspects of impulsivity involved in suicide-related outcomes can be investigated through the UPPS model, which conceptualizes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The affective, cognitive, and behavioral aspects of impulsivity involved in suicide-related outcomes can be investigated through the UPPS model, which conceptualizes these facets in multidimensional terms related to negative and positive urgency, lack of premeditation and perseverance, and sensation seeking. This systematic review and meta-analysis provided a comprehensive understanding of the role of all facets of impulsivity in the development of suicidal ideation and behaviors.
METHODS
We conducted a systematic search on six databases (PsycINFO, PsycARTICLES, PubMed, MEDLINE, Scopus, and Web of Science) until May 5,2023. Overall, 49 studies met the criteria for systematic review, of which 37 were included in a meta-analysis of data from 17.898 individuals. Additional moderation analyses included age, gender, sample status, country of study conduct, assessment instruments, type of suicide-related outcome, study quality, and research design.
RESULTS
We found significant relationships between aspects of impulsivity and suicide-related outcomes. Specially, affective facets related to impulsivity showed a stronger association with suicidal ideations and attempts than cognitive and behavioral dimensions, recommending the main involvement of emotional aspects-positive and negative-in suicide-related dimensions.
LIMITATIONS
The limited number of studies may have negatively impacted the power of moderation analyses. In addition, for most dimensions of impulsivity, the limited number of longitudinal studies did not allow to test the moderating role of research design.
CONCLUSIONS
This study supports the role of impulsivity in suicidal ideation and behavior, identifying the affective component of impulsivity as the most involved, providing a significant contribution from a clinical and diagnostic point of view.
Topics: Humans; Suicide; Impulsive Behavior; Suicidal Ideation; Longitudinal Studies
PubMed: 37459976
DOI: 10.1016/j.jad.2023.07.086 -
Cureus Jul 2023The journey of heart transplantation in the United Kingdom (UK) has been marked by challenges and triumphs. Following a series of unsuccessful transplant attempts in...
The journey of heart transplantation in the United Kingdom (UK) has been marked by challenges and triumphs. Following a series of unsuccessful transplant attempts in 1968, a moratorium was imposed on the procedure. However, in 1979, Sir Terence English broke the national ban, by performing the UK's first successful heart transplant at Papworth Hospital. This achievement opened doors for advancements in heart and lung transplantation and established the Papworth programme as a world leader in the field. Sir Terence's legacy stands as a testament to the transformative power of determination, perseverance and teamwork in overcoming the moratorium, lack of financial support, difficult colleagues and the failure of his first transplant attempt. Through a comprehensive review of the literature, qualitative interviews and Sir Terence's personal contributions, this article provides an account of his trials and tribulations, aiming to inspire and encourage physicians, surgeons and scientists in their pursuit of innovation in the field of medicine.
PubMed: 37602124
DOI: 10.7759/cureus.42051