-
PLoS Biology Jun 2024In the highly regulative embryo of the sea urchin Paracentrotus lividus, establishment of the dorsal-ventral (D/V) axis critically depends on the zygotic expression of...
In the highly regulative embryo of the sea urchin Paracentrotus lividus, establishment of the dorsal-ventral (D/V) axis critically depends on the zygotic expression of the TGF-β nodal in the ventral ectoderm. nodal expression is first induced ubiquitously in the 32-cell embryo and becomes progressively restricted to the presumptive ventral ectoderm by the early blastula stage. This early spatial restriction of nodal expression is independent of Lefty, and instead relies on the activity of Panda, a maternally expressed TGF-β ligand related to Lefty and Inhibins, which is required maternally for D/V axis specification. However, the mechanism by which Panda restricts the early nodal expression has remained enigmatic and it is not known if Panda works like a BMP ligand by opposing Nodal and antagonizing Smad2/3 signaling, or if it works like Lefty by sequestering an essential component of the Nodal signaling pathway. In this study, we report that Panda functions as an antagonist of the TGF-β type II receptor ACVRII (Activin receptor type II), which is the only type II receptor for Nodal signaling in the sea urchin and is also a type II receptor for BMP ligands. Inhibiting translation of acvrII mRNA disrupted D/V patterning across all 3 germ layers and caused acvrII morphants to develop with a typical Nodal loss-of-function phenotype. In contrast, embryos overexpressing acvrII displayed strong ectopic Smad1/5/8 signaling at blastula stages and developed as dorsalized larvae, a phenotype very similar to that caused by over activation of BMP signaling. Remarkably, embryos co-injected with acvrII mRNA and panda mRNA did not show ectopic Smad1/5/8 signaling and developed with a largely normal dorsal-ventral polarity. Furthermore, using an axis induction assay, we found that Panda blocks the ability of ACVRII to orient the D/V axis when overexpressed locally. Using co-immunoprecipitation, we showed that Panda physically interacts with ACVRII, as well as with the Nodal co-receptor Cripto, and with TBR3 (Betaglycan), which is a non-signaling receptor for Inhibins in mammals. At the molecular level, we have traced back the antagonistic activity of Panda to the presence of a single proline residue, conserved with all the Lefty factors, in the ACVRII binding motif of Panda, instead of a serine as in most of TGF-β ligands. Conversion of this proline to a serine converted Panda from an antagonist that opposed Nodal signaling and promoted dorsalization to an agonist that promoted Nodal signaling and triggered ventralization when overexpressed. Finally, using phylogenomics, we analyzed the emergence of the agonist and antagonist form of Panda in the course of evolution. Our data are consistent with the idea that the presence of a serine at that position, like in most TGF-β, was the ancestral condition and that the initial function of Panda was possibly in promoting and not in antagonizing Nodal signaling. These results highlight the existence of key functional and structural elements conserved between Panda and Lefty, allow to draw an intriguing parallel between sea urchin Panda and mammalian Inhibin α and raise the unexpected possibility that the original function of Panda may have been in activation of the Nodal pathway rather than in its inhibition.
PubMed: 38913712
DOI: 10.1371/journal.pbio.3002701 -
EClinicalMedicine Jul 2024Mobile health (mHealth) systems are a promising alternative for rehabilitation of hip fracture, addressing constrained healthcare resources. Half of older adults fails...
Effects of the ActiveHip+ mHealth intervention on the recovery of older adults with hip fracture and their family caregivers: a multicentre open-label randomised controlled trial.
BACKGROUND
Mobile health (mHealth) systems are a promising alternative for rehabilitation of hip fracture, addressing constrained healthcare resources. Half of older adults fails to recover their pre-fracture routines, which imposes a burden on caregivers. We aimed to test the effectiveness of the 3-month ActiveHip + mHealth intervention on physical and psychological outcomes of older adults with hip fracture and their family caregivers.
METHODS
In a multicentre open-label randomised controlled trial conducted across 3 hospitals in Andalusia (Spain), patients older than 65 with a hip fracture, who were previously independent and lacked cognitive impairment were recruited alongside with their caregivers. Participants were randomly allocated (1:1) to the intervention group (ActiveHip+) or control (usual care) group. The intervention group underwent a 12-week health education and tele-rehabilitation programme through the ActiveHip + mHealth intervention. The primary outcome, physical performance, was assessed using the Short Physical Performance Battery at three time points: at hospital discharge (baseline), 3-month after surgery (post intervention) and 1-year after surgery follow-up. Primary analyses of primary outcomes and safety data followed an intention-to-treat approach. This study is registered at ClinicalTrials.gov, NCT04859309.
FINDINGS
Between June 1st, 2021 and June 30th, 2022 data from 105 patients and their caregivers were analysed. Patients engaged in the ActiveHip + mHealth intervention (mean 7.11 points, SE 0.33) showed higher physical performance compared with patients allocated in the control group (mean 5.71 points, SE 0.32) at 3 months after surgery (mean difference in change from baseline 1.40 points, SE 0.36; puncorrected = 0.00011). These benefits were not maintained at 1-year after surgery follow-up (mean difference in change from baseline 0.19 points, SE 0.47; puncorrected = 0.68). No adverse events, including falls and refractures, were reported during the tele-rehabilitation sessions. At 3-months, the intervention group had 2 falls, compared to 4 in the control group, with no observed refractures. At the 1-year follow-up, the intervention group experienced 7 falls and 1 refracture, while the control group had 13 falls and 2 refractures.
INTERPRETATION
This study suggests that the ActiveHip + mHealth intervention may be effective for recovering physical performance in older adults with hip fracture. Importantly, the implementation of ActiveHip + into daily clinical practice may be feasible and has already been adopted in 18 hospitals, mostly in Spain but also in Belgium and Portugal. Thus, ActiveHip + could offer a promising solution when rehabilitation resources are limited. However, its dependence on caregiver support and the exclusion of participants with cognitive impairment makes it necessary to be cautious about its applicability. In addition, the non-maintenance of the effectiveness at 1-year follow-up highlights the need of refinement the ActiveHip + intervention to promote long-lasting behavioural changes.
FUNDING
EIT Health and the Ramón y Cajal 2021 Excellence Research Grant action from the Spanish Ministry of Science and Innovation.
PubMed: 38911836
DOI: 10.1016/j.eclinm.2024.102677 -
SAGE Open Medicine 2024Ambulatory mobility aids are several devices the elderly may use in order to improve their walking pattern, balance, or safety while mobilizing independently.
INTRODUCTION
Ambulatory mobility aids are several devices the elderly may use in order to improve their walking pattern, balance, or safety while mobilizing independently.
OBJECTIVES
To assess the effect of ambulatory mobility aid devices on cardiovascular parameters, walking speed, perceived exertion, and balance of older adult men.
METHODS
A sample of 156 old men was studied. Data were obtained through measurement of the participants' walking speed (distance covered/second), cardiovascular parameters (blood pressure), perceived exertion (difficulty or ease in breathing), and balance (ease in standing) after walking with and without the selected walking aid devices. Analysis was done to compare the effect of the walking aid devices on the selected dependent variables.
RESULTS
Results showed ambulation with mobility aid devices resulted in increase in the heart rate and blood pressure with the greatest increase observed when walking with Zimmer frame. Ambulation with mobility aid devices resulted in decrease of the walking speed of the participants when compared to ambulation without devices. Perceived exertion of participants after using Zimmer frame and walking cane was within 4.06 ± 1.35 and 3.98 ± 1.26, respectively, as opposed to 3.08 ± 0.73 after ambulation without aid. Use of Zimmer frame provided enough balance for participants.
CONCLUSION
Ambulatory mobility devices caused difference in cardiovascular parameters when compared to ambulation at rest and without aid. It was recommended that selection of ambulatory mobility aid devices should depend on objective mobility assessments and periodical re-evaluation to ensure that it suits a person's functional requirements and physical capabilities.
PubMed: 38911443
DOI: 10.1177/20503121241262250 -
Frontiers in Pharmacology 2024Tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, is indicated for chronic weight...
BACKGROUND
Tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, is indicated for chronic weight management in adults with obesity or overweight as an adjunct to a reduced-calorie diet and increased physical activity. However, the safety profile of Tirzepatide-associated adverse events requires comprehensive evaluation.
METHODS
The AE reports from the first quarter of 2022 to the third quarter of 2023 were selected by exploring the FDA Adverse Event Reporting System (FAERS) database. The new and unexpected potenial AE signals were detected using the disproportionality analysis, including reporting odds ratio(ROR), the proportional reporting ratio (PRR) the Bayesian confidence propagation neural network (BCPNN) and the empirical Bayes geometric mean(EBGM). Then the MedDRA was used to systematically classify the results.
RESULTS
A total of 1,904,481 case reports were obtained from 2022Q2 to 2023Q3. Forty-sixth tirzepatide-induced ADRs at the preferred terms (PTs) level are associated with 8 system organ class In addition, this study uncovered multiple anticipated ADRs, such as gastrooesophageal reflux disease, dyspepsia, and vomiting, in line with the drug labels. Moreover, unexpected and significant ADRs at PTs level, such as incorrect dose administered, injection site haemorrhage, and increased appetite, were discovered and linked to Injury, poisoning, and procedural complications, General disorders and administration site conditions, and Metabolism and nutrition disorders at the System Organ Class level.
CONCLUSION
This study offered new perspectives on the monitoring, surveillance, and management of adverse drug reactions related to tirzepatide. The outcomes of severe adverse events and their respective detection signals, along with unexpected significant adverse event signals, are important to consider in efforts to enhance clinical medication safety when using tirzepatide.
PubMed: 38910884
DOI: 10.3389/fphar.2024.1397029 -
Acta Oncologica (Stockholm, Sweden) Jun 2024As many as one in four adults with cancer have children under 18 years. Balancing parenting and cancer is challenging and can be a source of psychological distress. This...
Parenting under pressure: a cross-sectional questionnaire study of psychological distress, parenting concerns, self-efficacy, and emotion regulation in parents with cancer.
BACKGROUND AND PURPOSE
As many as one in four adults with cancer have children under 18 years. Balancing parenting and cancer is challenging and can be a source of psychological distress. This study aimed to examine psychological distress in parents with cancer and its associations with parenting concerns, self-efficacy, and emotion regulation.
MATERIALS AND METHODS
This was a cross-sectional questionnaire study of 406 parents (aged 25-60 years) diagnosed with cancer within the last 5 years, with at least one dependent child (≤ 18 years). Parents completed questionnaires on psychological distress (DASS-21), parenting concerns (PCQ), self-efficacy (GSE), emotion regulation (ERQ), mental and physical health, and sociodemographics. Data were analysed using multiple logistic regressions on depression (yes/no), anxiety (yes/no), and stress (yes/no).
RESULTS
Higher parenting concerns were associated with greater odds of depression (OR = 2.33, 95% CI: 1.64-3.31), anxiety (OR = 2.30, 95% CI: 1.64-3.20), and stress (OR = 3.21, 95% CI: 2.20-4.69) when adjusting for health and sociodemographic factors. Poorer self-efficacy was associated with increased odds of anxiety (OR = 0.94, 95% CI: 0.89-0.99, p < 0.05), whereas lower use of cognitive reappraisal and higher use of expressive suppression increased the odds of depression (OR = 0.76, 95% CI: 0.59-0.98 | OR = 1.46, 95% CI: 1.18-1.80).
INTERPRETATION
The findings highlight the complexity of parental well-being in relation to parenthood and cancer, stressing the need for interventions that address relevant psychological factors to improve overall mental health in this population.
Topics: Humans; Cross-Sectional Studies; Self Efficacy; Female; Adult; Male; Parenting; Neoplasms; Middle Aged; Surveys and Questionnaires; Psychological Distress; Parents; Emotional Regulation; Anxiety; Depression; Stress, Psychological; Adolescent; Child
PubMed: 38910314
DOI: 10.2340/1651-226X.2024.40404 -
International Journal of Cardiology Jun 2024Background and aims of the study A functionally single ventricle (FSV) refers to a group of congenital heart defects that are not amenable for biventricular correction....
UNLABELLED
Background and aims of the study A functionally single ventricle (FSV) refers to a group of congenital heart defects that are not amenable for biventricular correction. The Fontan operation is utilized as surgical treatment for most of FSV patients. The evaluation of FSV function is extremely difficult due to its unique pathophysiology. This study aimed to explore the efficacy of speckle tracking echocardiography (STE) parameters measured at rest and during exercise for comprehensive assessment of univentricular heart.
METHODS
We enrolled 37 patients with a functionally single ventricle after the Fontan operation, hospitalized in the Department of Congenital Heart Defects between years 2019 and 2021.The echocardiographic stress tests were performed in the Echocardiography Laboratory of the Congenital Heart Defects Department. The study was conducted on a bicycle ergometer in a semi-recumbent position. The parameters obtained by speckle tracking echocardiography (STE): the longitudinal strain of the FSV free wall (Ɛ) and the longitudinal strain of myocardial layers: subendocardial, medial and subepicardial were analyzed. A transmural longitudinal strain gradient (TG) was calculated as the difference between longitudinal deformation of the subendocardial and subepicardial layers. Current results of cardiac magnetic resonance imaging (CMR) and cardio-pulmonary test (CPET) were also incorporated. Demographic data, past interventions, pharmacological treatment and comorbidities were extracted from medical records.
RESULTS
Ɛ at rest and during exercise were not related to the parameters of physical capacity obtained on CPET nor to the CMR results. The transmural strain gradient was dependent on physical performance parameter- peak oxygen uptake- and related to the FSV ejection fraction calculated by magnetic resonance imaging.
CONCLUSIONS
The transmural strain gradient and FSV free wall strain are readily measurable and suitable for evaluating single ventricle function. The TG is positively correlated with peak oxygen uptake during the cardiopulmonary test and with the ejection fraction derived from cardiac magnetic resonance imaging. The applicability of these findings in patients undergoing the Fontan procedure warrants further exploration.
PubMed: 38908552
DOI: 10.1016/j.ijcard.2024.132286 -
Lancet (London, England) Jun 2024Recurrence of low back pain is common and a substantial contributor to the disease and economic burden of low back pain. Exercise is recommended to prevent recurrence,...
Effectiveness and cost-effectiveness of an individualised, progressive walking and education intervention for the prevention of low back pain recurrence in Australia (WalkBack): a randomised controlled trial.
BACKGROUND
Recurrence of low back pain is common and a substantial contributor to the disease and economic burden of low back pain. Exercise is recommended to prevent recurrence, but the effectiveness and cost-effectiveness of an accessible and low-cost intervention, such as walking, is yet to be established. We aimed to investigate the clinical effectiveness and cost-effectiveness of an individualised, progressive walking and education intervention to prevent the recurrence of low back pain.
METHODS
WalkBack was a two-armed, randomised controlled trial, which recruited adults (aged 18 years or older) from across Australia who had recently recovered from an episode of non-specific low back pain that was not attributed to a specific diagnosis, and which lasted for at least 24 h. Participants were randomly assigned to an individualised, progressive walking and education intervention facilitated by six sessions with a physiotherapist across 6 months or to a no treatment control group (1:1). The randomisation schedule comprised randomly permuted blocks of 4, 6, and 8 and was stratified by history of more than two previous episodes of low back pain and referral method. Physiotherapists and participants were not masked to allocation. Participants were followed for a minimum of 12 months and a maximum of 36 months, depending on the date of enrolment. The primary outcome was days to the first recurrence of an activity-limiting episode of low back pain, collected in the intention-to-treat population via monthly self-report. Cost-effectiveness was evaluated from the societal perspective and expressed as incremental cost per quality-adjusted life-year (QALY) gained. The trial was prospectively registered (ACTRN12619001134112).
FINDINGS
Between Sept 23, 2019, and June 10, 2022, 3206 potential participants were screened for eligibility, 2505 (78%) were excluded, and 701 were randomly assigned (351 to the intervention group and 350 to the no treatment control group). Most participants were female (565 [81%] of 701) and the mean age of participants was 54 years (SD 12). The intervention was effective in preventing an episode of activity-limiting low back pain (hazard ratio 0·72 [95% CI 0·60-0·85], p=0·0002). The median days to a recurrence was 208 days (95% CI 149-295) in the intervention group and 112 days (89-140) in the control group. The incremental cost per QALY gained was AU$7802, giving a 94% probability that the intervention was cost-effective at a willingness-to-pay threshold of $28 000. Although the total number of participants experiencing at least one adverse event over 12 months was similar between the intervention and control groups (183 [52%] of 351 and 190 [54%] of 350, respectively, p=0·60), there was a greater number of adverse events related to the lower extremities in the intervention group than in the control group (100 in the intervention group and 54 in the control group).
INTERPRETATION
An individualised, progressive walking and education intervention significantly reduced low back pain recurrence. This accessible, scalable, and safe intervention could affect how low back pain is managed.
FUNDING
National Health and Medical Research Council, Australia.
PubMed: 38908392
DOI: 10.1016/S0140-6736(24)00755-4 -
Biomedicine & Pharmacotherapy =... Jun 2024Sarcopenia is an aging-related skeletal disease characterized by decreased muscle mass, strength, and physical function, severely affecting the quality of life (QoL) of... (Review)
Review
Sarcopenia is an aging-related skeletal disease characterized by decreased muscle mass, strength, and physical function, severely affecting the quality of life (QoL) of the elderly population. Sirtuin 1 (SIRT1), as a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, has been reported to participate in various aging-related signaling pathways and exert protective effect on many human diseases. SIRT1 functioned as an important role in the occurrence and progression of sarcopenia through regulating key pathways related to protein homeostasis, apoptosis, mitochondrial dysfunction, insulin resistance and autophagy in skeletal muscle, including SIRT1/Forkhead Box O (FoxO), AMP-activated protein kinase (AMPK)/SIRT1/nuclear factor κB (NF-κB), SIRT1/p53, AMPK/SIRT1/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and SIRT1/live kinase B1 (LKB1)/AMPK pathways. However, the specific mechanisms of these processes have not been fully illuminated. Currently, several SIRT1-mediated interventions on sarcopenia have been preliminarily developed, such as SIRT1 activator polyphenolic compounds, exercising and calorie restriction. In this review, we summarized the predominant mechanisms of SIRT1 involved in sarcopenia and therapeutic modalities targeting the SIRT1 signaling pathways for the prevention and prognosis of sarcopenia.
PubMed: 38908209
DOI: 10.1016/j.biopha.2024.116917 -
Journal of Anesthesia, Analgesia and... Jun 2024Burnout is a maladaptive response to chronic stress, particularly prevalent among clinicians. Anesthesiologists are at risk of burnout, but the role of maladaptive...
BACKGROUND
Burnout is a maladaptive response to chronic stress, particularly prevalent among clinicians. Anesthesiologists are at risk of burnout, but the role of maladaptive traits in their vulnerability to burnout remains understudied.
METHODS
A secondary analysis was performed on data from the Italian Association of Hospital Anesthesiologists, Pain Medicine Specialists, Critical Care, and Emergency (AAROI-EMAC) physicians. The survey included demographic data, burnout assessment using the Maslach Burnout Inventory (MBI) and subscales (emotional exhaustion, MBI-EE; depersonalization, MBI-DP; personal accomplishment, MBI-PA), and evaluation of personality disorders (PDs) based on DSM-IV (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition) criteria using the assessment of DSM-IV PDs (ADP-IV). We investigated the aggregated scores of maladaptive personality traits as predictor variables of burnout. Subsequently, the components of personality traits were individually assessed.
RESULTS
Out of 310 respondents, 300 (96.77%) provided complete information. The maladaptive personality traits global score was associated with the MBI-EE and MBI-DP components. There was a significant negative correlation with the MBI-PA component. Significant positive correlations were found between the MBI-EE subscale and the paranoid (r = 0.42), borderline (r = 0.39), and dependent (r = 0.39) maladaptive personality traits. MBI-DP was significantly associated with the passive-aggressive (r = 0.35), borderline (r = 0.33), and avoidant (r = 0.32) traits. Moreover, MBI-PA was negatively associated with dependent (r = - 0.26) and avoidant (r = - 0.25) maladaptive personality features.
CONCLUSIONS
There is a significant association between different maladaptive personality traits and the risk of experiencing burnout among anesthesiologists. This underscores the importance of understanding and addressing personality traits in healthcare professionals to promote their well-being and prevent this serious emotional, mental, and physical exhaustion state.
PubMed: 38907360
DOI: 10.1186/s44158-024-00171-5 -
NPJ Microgravity Jun 2024Cognitive impairments have been reported in astronauts during spaceflights and documented in ground-based models of simulated microgravity (SMG) in animals. However, the...
Cognitive impairments have been reported in astronauts during spaceflights and documented in ground-based models of simulated microgravity (SMG) in animals. However, the neuronal causes of these behavioral effects remain largely unknown. We explored whether adult neurogenesis, known to be a crucial plasticity mechanism supporting memory processes, is altered by SMG. Adult male Long-Evans rats were submitted to the hindlimb unloading model of SMG. We studied the proliferation, survival and maturation of newborn cells in the following neurogenic niches: the subventricular zone (SVZ)/olfactory bulb (OB) and the dentate gyrus (DG) of the hippocampus, at different delays following various periods of SMG. SMG exposure for 7 days, but not shorter periods of 6 or 24 h, resulted in a decrease of newborn cell proliferation restricted to the DG. SMG also induced a decrease in short-term (7 days), but not long-term (21 days), survival of newborn cells in the SVZ/OB and DG. Physical exercise, used as a countermeasure, was able to reverse the decrease in newborn cell survival observed in the SVZ and DG. In addition, depending on the duration of SMG periods, transcriptomic analysis revealed modifications in gene expression involved in neurogenesis. These findings highlight the sensitivity of adult neurogenesis to gravitational environmental factors during a transient period, suggesting that there is a period of adaptation of physiological systems to this new environment.
PubMed: 38906877
DOI: 10.1038/s41526-024-00411-6