Physiotherapy in acute geriatrics wards: What (de)motivates patients? A qualitative study based on self-determination theory.

BACKGROUND: While the benefits of physiotherapy for hospitalized older patients (HOPs) are well established, these patients are often considered demotivated by healthcare team members (HTMs), which is perceived as a hindrance to their rehabilitation. The quantitative data currently available on the lack of involvement of HOPs are mainly measures of mobility. Motivation as such has, to our knowledge, never been measured. Therefore, this study aims to quantify for the first time the motivation levels of HOPs in their participation in activities of daily living (ADLs) and physiotherapy, and to explore the motivating factors behind their participation in physiotherapy. METHODS: The motivation of 60 older patients hospitalized in an acute geriatrics ward was quantified using the Scale of Demotivation Assessment (SDA). Out of these participants, 14 were interrogated through individual semi-structured face-to-face interviews. After transcription, data were analyzed according to Self-Determination Theory, which has been proven effective in the understanding of motivational mechanisms. RESULTS: The prevalence of demotivation was 47% (95% CI: [0.34;0.6]) for ADLs and 35% (95% CI: [0.23;0.48]) for physiotherapy. The main demotivating factors were the feeling of external control (lack of autonomy) and dependance experienced by HOPs, as well as the limited availability of staff during hospitalization. Conversely, feelings of competence, security, respect for limits, and commitment from the HTMs were important motivating factors. CONCLUSION: A large number of relational factors have an impact on the motivation of HOPs regarding their participation in ADLs and in physiotherapy sessions. Appropriate time and space organizing and the provision of suitable equipment, combined with a genuine caring and respectful attitude from the HTMs, could considerably encourage the expression of intrinsic motivation and thus the involvement of HOPs in their own care program.

Hallmarks of anticancer and antimicrobial activities of corroles.

Corroles provide a remarkable opportunity for the development of cancer theranostic agents among other porphyrinoids. While most transition metal corrole complexes are only therapeutic, post-transition metallocorroles also find their applications in bioimaging. Moreover, corroles exhibit excellent photo-physicochemical properties, which can be harnessed for antitumor and antimicrobial interventions. Nevertheless, these intriguing, yet distinct properties of corroles, have not attained sufficient momentum in cancer research. The current review provides a comprehensive summary of various cancer-relevant features of corroles ranging from their structural and photophysical properties, chelation, protein/corrole interactions, to DNA intercalation. Another aspect of the paper deals with the studies of corroles conducted in vitro and in vivo with an emphasis on medical imaging (optical and magnetic resonance), photo/sonodynamic therapies, and photodynamic inactivation. Special attention is also given to a most recent finding that shows the development of pH-responsive phosphorus corrole as a potent antitumor drug for organelle selective antitumor cytotoxicity in preclinical studies. Another biomedical application of corroles is also highlighted, signifying the application of water-soluble and completely lipophilic corroles in the photodynamic inactivation of microorganisms. We strongly believe that future studies will offer a greater possibility of utilizing advanced corroles for selective tumor targeting and antitumor cytotoxicity. In the line with future developments, an ideal pipeline is envisioned on grounds of cancer targeting nanoparticle systems upon decoration with tumor-specific ligands. Hence, we envision that a bright future lies ahead of corrole anticancer research and therapeutics.

MR-guided focused ultrasound in pediatric neurosurgery: current insights, technical challenges, and lessons learned from 45 treatments at Children's National Hospital.

OBJECTIVE: MR-guided focused ultrasound (MRgFUS) is an evolving technology with numerous present and potential applications in pediatric neurosurgery. The aim of this study was to describe the use of MRgFUS, technical challenges, complications, and lessons learned at a single children's hospital. METHODS: A retrospective analysis was performed of a prospectively collected database of all pediatric patients undergoing investigational use of MRgFUS for treatment of various neurosurgical pathologies at Children's National Hospital. Treatment details, clinical workflow, and standard operating procedures are described. Patient demographics, procedure duration, and complications were obtained through a chart review of anesthesia and operative reports. RESULTS: In total, 45 MRgFUS procedures were performed on 14 patients for treatment of diffuse intrinsic pontine glioma (n = 12), low-grade glioma (n = 1), or secondary dystonia (n = 1) between January 2022 and April 2024. The mean age at treatment was 9 (range 5-22) years, and 64% of the patients were male. With increased experience, the total anesthesia time, sonication time, and change in core body temperature during treatment all significantly decreased. Complications affected 4.4% of patients, including 1 case of scalp edema and 1 patient with a postprocedure epidural hematoma. Device malfunction requiring abortion of the procedure occurred in 1 case (2.2%). Technical challenges related to transducer malfunction and sonication errors occurred in 6.7% and 11.1% of cases, respectively, all overcome by subsequent user modifications. CONCLUSIONS: The authors describe the largest series on MRgFUS technical aspects in pediatric neurosurgery at a single institution, comprising 45 total treatments. This study emphasizes potential technical challenges and provides valuable insights into the nuances of its application in pediatric patients.

Workplace Causality Orientations Moderate Impostorism and Burnout: New Insights for Wellness Interventions in Graduate Medical Education.

Theory: Impostor phenomenon (IP) is strongly linked to physician burnout, but the nature of this association is not well understood. A better grasp of the mechanism between these constructs could shed new light on ways to mitigate physician IP and burnout. Grounded in self-determination theory (SDT), the present study explores whether and how residents' general causality orientations at work-impersonal, controlled, and autonomous-each moderate the effect of IP on physician burnout. Hypotheses: We theorized that the autonomous orientation would buffer the facilitative effect of IP on burnout, while the controlled and impersonal orientations would each enhance it to varying degrees. Method: Two hundred forty-three residents from the Universities of Saskatchewan, Calgary, and Alberta, across various programs, specialties, and years of training, completed a survey containing demographic questions and three previously validated instruments: the Clance Impostor Phenomenon Scale, Causality Orientations at Work Scale, and Oldenburg Burnout Inventory. We used partial correlation analyses to test our moderation hypotheses. Results: In line with what we expected, the autonomous causality orientation buffered the facilitative effect of IP on burnout, while the controlled and impersonal causality orientations each enhanced it. Conclusions: Results suggest that possessing a stronger autonomous causality orientation (and creating learning/work environments that prime it) will dampen the effect of IP on burnout, while possessing a stronger controlled or impersonal causality orientation (and creating learning/work environments that prime them) will each augment it. Findings and their implications are discussed in terms of instigating theory-informed, system-level wellness interventions in graduate medical education.

Promoting motivation and reducing stress in medical students by utilizing self-determination theory - a randomized controlled trial in practical psychiatry courses.

BACKGROUND: Medical students experience high levels of stress and related mental health problems. Students' autonomous and controlled motivation and their mental well-being are interconnected. This study aimed to investigate whether an innovative teaching concept based on self-determination theory (SDT) could improve students' motivation and thereby reduce their stress levels, ultimately providing a healthier framework for learning. METHODS: In a week-long practical psychiatry course for medical students, a new didactic concept was implemented in half the groups (n = 73) and compared with the preexisting concept (n = 75) as a randomized controlled trial (RCT). To promote the SDT-target factors of perceived autonomy, competence, and relatedness, the methods used included team building, exclusively positive feedback, group discussions, and choice in task distribution. Significant group differences in motivation, stress, performance, and their relationships were analyzed through t-tests, multiple linear regression analyses, mediation analyses, and hierarchical linear modeling (HLM) using questionnaires collected before (t0) and after (t1) the course, and students' exam results (t2). RESULTS: In the innovation group (n = 53), intrinsic motivation/interest (d = 0.41; p = .019) and perceived choice/autonomy (d = 0.33; p = .048) were greater than in the control group (n = 52). While autonomous regulation remained stable, the innovation group showed reduced controlled regulation (d = -0.36; p = .033) and reported significantly lower stress (d = -0.55; p = .003). The observed changes in motivation collectively mediated the stress reduction. However, students in the innovation group achieved lower exam scores, which seemed to result from the absence of critical feedback, but not from the observed differences in motivation or stress. CONCLUSIONS: This study demonstrated that enhancing intrinsic motivation through SDT-based teaching can effectively reduce stress in medical students. Exclusively strengths-based positive feedback may have hindered exam performance, but optimizing educational concepts to promote motivation and reduce stress will be a valuable step toward improving medical students' mental well-being.

Biomimetic Nanovesicle with Mitochondria-Synthesized Sonosensitizer and Mitophagy Inhibition for Cancer Sono-Immunotherapy.

Mitochondria are crucial for both sonodynamic therapy and antitumor immunity. However, how to accurately damage mitochondria and meanwhile prevent the mitophagy and immune checkpoint inhibition is still a great challenge. Herein, hexyl 5-aminolevulinate hydrochloride (HAL) and 3-methyladenine (3MA) are loaded into the tumor cell-derived microparticle (X-MP), which can direct the target delivery of the prepared HAL/3MA@X-MP to the tumor cells. HAL induces the confined biosynthesis and accumulation of sonosensitizer PpIX in mitochondria, leading to the localized generation of reactive oxygen species (ROS) upon ultrasound irradiation and, thus, the efficient mitochondrial damage. Meanwhile, 3MA not only inhibits mitophagy but also down-regulates the PD-L1 expression, promoting the immunogenic cell death (ICD) while blocking the immune checkpoint recognition. The smart synergism of precise mitochondrial damage, mitophagy inhibition and antitumor immunity results in potent therapeutic efficacy without obvious side effects.

Oxygen-Vacancy-Engineered W18 O49-x Nanobrush with a Suitable Band Structure for Highly Efficient Sonodynamic Therapy.

With the rapid development of external minimally invasive or noninvasive therapeutic modalities, ultrasound-based sonodynamic therapy (SDT) is a new alternative for treating deep tumors. However, inadequate sonosensitizer efficiency and poor biosecurity limit clinical applications. In this study, we prepared an oxygen-vacancy-engineered W18 O49-x nanobrush with a band gap of 2.79 eV for highly efficient SDT using a simple solvothermal method. The suitable band structures of the W18 O49-x nanobrush endows it with the potential to simultaneously produce singlet oxygen (1 O2 ), superoxide anions (⋅O2 - ), and hydroxyl radicals (⋅OH) under ultrasound irradiation. Additionally, abundant oxygen vacancies that serve as further charge traps that inhibit electron-hole recombination are incidentally introduced through one-step thermal reduction. Collectively, the in vitro and in vivo results demonstrate that the oxygen-vacancy-engineered W18 O49-x nanobrush delivers highly efficient reactive oxygen species (ROS) for SDT in a very biosafe manner. Overall, this study provides a new avenue for discovering and designing inorganic nanosonosensitizers with enhanced therapeutic efficiencies for use in SDT.

PtMo-Au Metalloenzymes Regulated Tumor Microenvironment for Enhanced Sonodynamic/Chemodynamic/Starvation Synergistic Therapy.

The clinical application of sonodynamic therapy (SDT) is greatly limited by the low quantum yield of sonosensitizers and tumor microenvironment (TME). Herein, PtMo-Au metalloenzyme sonosensitizer is synthesized by modulating energy band structure of PtMo with Au nanoparticles. The surface deposition of Au simultaneously solves the carrier recombination and facilitates the separation of electrons (e- ) and holes (h+ ), effectively improving the reactive oxygen species (ROS) quantum yield under ultrasound (US). The catalase-like activity of PtMo-Au metalloenzymes alleviates hypoxia TME, thus enhancing the SDT-induced ROS generation. More importantly, tumor overexpressed glutathione (GSH) can serve as the hole scavenger, which is accompanied by a persistent depletion of the GSH, thus inactivating GPX4 for the accumulation of lipid peroxides. The distinctly facilitated SDT-induced ROS production is coupled with chemodynamic therapy (CDT)-induced hydroxyl radicals (•OH) to exacerbate ferroptosis. Furthermore, Au with glucose oxidase mimic activity can not only inhibit intracellular adenosine triphosphate (ATP) production and induce tumor cell starvation but also generate H2 O2 to facilitate CDT. In general, this PtMo-Au metalloenzyme sonosensitizer optimizes the defects of conventional sonosensitizers through surface deposition of Au to regulate TME, providing a novel perspective for US-based tumor multimodal therapy.

A Comprehensive Review of Inorganic Sonosensitizers for Sonodynamic Therapy.

Sonodynamic therapy (SDT) is an emerging non-invasive cancer treatment method in the field of nanomedicine, which has the advantages of deep penetration, good therapeutic efficacy, and minimal damage to normal tissues. Sonosensitizers play a crucial role in the process of SDT, as their structure and properties directly determine the treatment outcome. Inorganic sonosensitizers, with their high stability and longer circulation time in the human body, have great potential in SDT. In this review, the possible mechanisms of SDT including the ultrasonic cavitation, reactive oxygen species generation, and activation of immunity are briefly discussed. Then, the latest research progress on inorganic sonosensitizers is systematically summarized. Subsequently, strategies for optimizing treatment efficacy are introduced, including combination therapy and image-guided therapy. The challenges and future prospects of sonodynamic therapy are discussed. It is hoped that this review will provide some guidance for the screening of inorganic sonosensitizers.

A qualitative study on parents of autistic adolescents' experience of OT-ParentShip: A family-centred intervention.

BACKGROUND: OT-ParentShip intervention addresses the needs of autistic adolescents and the physical and emotional burden associated with parental caregiving. AIM: This article describes the qualitative findings of a mixed-method, single-group, pre-test-post-test pilot study to determine whether this intervention has adequate potential for further, large-scale testing. METHOD: The qualitative study sought to understand 14 parents' (N = 4 couples, N = 6 mothers) experiences in the intervention, examine their satisfaction, and receive their suggestions for improvement, using a grounded approach, with the aim of conceptualising a theoretical understanding of the data gathered. RESULTS: A total of five key themes and 14 sub-themes describe parents' experiences. The key themes that were identified were parent-therapist relationship, parent-adolescent relationship, reframing, benefit for family, and parental resilience. Emerging themes shed light on the therapeutic components and change mechanisms of the intervention. CONCLUSION: Self-determination theory was found to be an adequate theoretical framework to map these components and help in understanding their contribution to treatment outcomes. OT-Parentship directly enforces parents' basic psychological needs, who, in turn, support their adolescent child's need for relatedness, competence, and autonomy. An occupational therapy intervention that satisfies these basic needs has the potential to lead to therapeutic alliance and internalisation of goals, thus increasing therapy engagement and outcomes.

Nature, implications and determinants of academic motivation profiles among upper elementary and secondary students.

The present study sought to contribute to self-determination theory by examining the nature of adolescents' academic motivation profiles defined while considering its global and specific nature. The construct validity of these profiles was examined by considering their replicability across samples of upper elementary (n = 781) and secondary (n = 467) school students, as well as their associations with predictors (perceived parental need nurturing behaviors) and outcomes (academic achievement and expectations of success). Latent profile analyses revealed four profiles (Non-Motivated, Identified, Amotivated, and Strongly Motivated) characterized by differing levels of global and specific levels of academic motivation. These profiles were fully replicated across educational levels. Most profiles differed from one another in terms of outcomes, although differences in terms of outcomes associations were observed across educational levels. Finally, profile membership was predicted by global levels of need nurturing and by some of the specific need nurturing behaviors in a way that replicated across educational levels. Our results suggest that the specific qualities of academic motivation and the global levels of self-determination are equally important in the identification of academic motivation profiles. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04687-x.

Effectiveness of a novel traction device in endoscopic submucosal dissection for colorectal lesions.

BACKGROUND: Among all types of superficial gastrointestinal (GI) neoplasms, colorectal lesions are recognized as one of the most difficult locations to operate, due to the limited operation space, physiological bends, poor visualization of the submucosal dissection plane sheltered by colorectal crinkle wall, and the thin intestinal mucosa layer which is easy to perforation. The purpose of this prospective study is to evaluate the feasibility, efficacy, and safety of a novel endoscopic traction technique in assisting the endoscopic submucosal dissection (ESD) procedure in colorectal lesions. METHOD: A total of 117 patients with colonic lesions who underwent endoscopic treatment were enrolled between August 2020 and January 2021 at the endoscopic center of Beijing Chao-yang Hospital of Capital Medical University. Based on whether traction device was used during the operation, 60 and 57 patients were assigned to the conventional ESD group and clips and rubber band triangle traction-assisted ESD group (CRT-ESD, in which three clips and a rubber band were used to form an elastic triangular traction device), respectively. The total procedure time (TPT), submucosal dissection time (SDT), submucosal dissection speed (SDS), and rate of adverse events of the two groups were analyzed. RESULTS: After excluding patients who did not undergo treatment (conventional ESD, 1; CRT-ESD, 4), 112 patients were included in the study (conventional ESD, 59; CRT-ESD, 53). The baseline characteristics of the patients were well balanced between the two groups. The TPT (58.71 ± 26.22 min vs 33.58 ± 9.88 min, p < 0.001) and SDT (49.24 ± 23.75 min vs 26.34 ± 8.75 min, p < 0.001) were significantly different between the conventional ESD group and CRT-ESD group. The CRT-ESD group had significantly higher SDS than that of the traditional ESD group (0.54 ± 0.42 cm2/min vs 0.89 ± 0.40 cm2/min, p < 0.001). There were 4 (6.8%) cases of perforation in the traditional ESD group, and no perforation occurred in traction-assisted ESD. CONCLUSIONS: Compared with traditional ESD, CRT-ESD with clip and rubber band is both safer and more effective in the treatment of colorectal lesions.

Salt loading with unilateral nephrectomy accelerates decline in glomerular filtration rate in the hypertensive, obese, type 2 diabetic SDT fatty rat model of diabetic kidney disease.

For the evaluation of novel therapeutic agents for diabetic kidney disease (DKD), it is desirable to examine their efficacy in animal models by using the glomerular filtration rate (GFR) as an index. For this purpose, animal models that demonstrate a short-term GFR decline because of disease progression are required. Therefore, we aimed to develop such an animal model of DKD by using obese type 2 diabetic spontaneously diabetic Torii (SDT) fatty rats treated with salt loading by drinking water containing sodium chloride with or without unilateral nephrectomy. As a result, we have found that 0.3% salt loading with unilateral nephrectomy or 0.8% salt loading alone caused a rapid GFR decline, hypertension and rapid development of tubulointerstitial fibrosis. Moreover, the addition of losartan to a mixed diet suppressed the GFR decline in SDT fatty rats treated with 0.3% salt loading with unilateral nephrectomy. These results suggest that the model of SDT fatty rats treated with 0.3% salt loading and unilateral nephrectomy could be used as a hypertensive DKD model for evaluating therapeutic agents based on suppression of GFR decline.

Sonodynamic Therapy Promotes Efferocytosis via CD47 Down-Regulation in Advanced Atherosclerotic Plaque.

Atherosclerotic cerebrocardiovascular disease is the major cause of acute ischemic diseases in humans. Impaired efferocytosis contributes to the progression of atherosclerosis. Pathological and apoptotic cells fail to undergo effective phagocytic clearance, leading to increased inflammation and necrotic core formation. Previously, we reported that 5-aminolevulinic acid-mediated sonodynamic therapy (SDT) promotes apoptotic cell efferocytosis via ATP release in atherosclerotic plaques. However, the exact signaling molecule involved in this process is still unknown. In the present study, sinoporphyrin sodium-mediated SDT (DVDMS-SDT) was applied to balloon-denuded rabbits in vivo to observe changes in the composition of atherosclerotic lesions. Cultured human THP-1-derived and mouse peritoneal macrophage-derived foam cells were used for in vitro mechanistic studies. Three days after DVDMS-SDT treatment, macrophage efferocytosis was significantly enhanced whereas local inflammation was attenuated in rabbit atherosclerotic lesions. At days 7 and 28, the histopathological analysis showed that DVDMS-SDT inhibited the progression of atherosclerosis, reduced the macrophage content, and increased the smooth muscle cell content in a time-dependent manner. Mechanistically, DVDMS-SDT activated mitochondria-caspase apoptosis in foam cells. Interestingly, activated by DVDMS-SDT, caspase-3 a key factor of apoptosis, reduced the expression of the anti-phagocytic molecule CD47 in foam cells. Of great importance, the promotion of macrophage efferocytosis by DVDMS-SDT can be eliminated by the overexpression of CD47. Overall, these results demonstrated that DVDMS-SDT effectively boosted efferocytosis via deactivation of CD47 expression, thereby reducing inflammation in advanced atherosclerotic plaques.

The sphingosine-1-phosphate receptor modulator, FTY720, prevents the incidence of diabetes in Spontaneously Diabetic Torii rats.

The sphingosine-1-phosphate (S1P) receptor modulator regulates lymphocyte trafficking, resulting in its depletion from circulation, which ultimately causes immunosuppression. In this study, we investigated the preventive effect of fingolimod (FTY720) in the non-obese type 2 diabetic model, Spontaneously Diabetic Torii (SDT) rats. The S1P receptor modulator, FTY720 (0.3 mg/kg p.o.), was administered for 12 weeks to SDT rats from 5 to 17 weeks of age. Based on our findings, FTY720 could suppress the incidence of diabetes in SDT rats. Further, glucose intolerance was improved in FTY720-treated SDT rats at 14 weeks of age. Based on the haematological and histological analyses performed at 17 to 18 weeks of age, a decrease in lymphocytes and monocytes in the peripheral blood and a decrease in lymphocyte and atrophy in spleen occurred in the FTY720-treated SDT rats. Furthermore, the pancreatic changes, such as inflammation, atrophy, and fibrosis in islets observed in SDT rats were improved by FTY720 treatment. These findings suggest that the immunomodulatory effects of FTY720 reduced the pancreatic lesion in SDT rats, thereby demonstrating its preventive effect against diabetes. The development of diabetes in SDT rats is related to disorders of the immune system. However, the S1P receptor modulator may be useful for treating type 2 diabetes.

The Impact of Gamification-Induced Users' Feelings on the Continued Use of mHealth Apps: A Structural Equation Model With the Self-Determination Theory Approach.

BACKGROUND: Continued use of mHealth apps can achieve better effects in health management. Gamification is an important factor in promoting users' intention to continue using mHealth apps. Past research has rarely explored the factors underlying the continued use of mobile health (mHealth) apps and gamification's impact mechanism or path on continued use. OBJECTIVE: This study aimed to explore the factors influencing mHealth app users' intention to continue using mHealth apps and the impact mechanism and path of users' feelings induced by gamification on continued mHealth app use. METHODS: First, based on the expectation confirmation model of information system continuance, we built a theoretical model for continued use of mHealth apps based on users' feelings toward gamification. We used self-determination theory to analyze gamification's impact on user perceptions and set the resulting feelings (competence, autonomy, and relatedness) as constructs in the model. Second, we used the survey method to validate the research model, and we used partial least squares to analyze the data. RESULTS: A total of 2988 responses were collected from mHealth app users, and 307 responses were included in the structural equation model after passing the acceptance criteria. The intrinsic motivation for using mHealth apps is significantly affected by autonomy (ß=.312; P<.001), competence (ß=.346; P<.001), and relatedness (ß=.165; P=.004) induced by gamification. The intrinsic motivation for using mHealth apps has a significant impact on satisfaction (ß=.311, P<.001) and continuance intention (ß=.142; P=.045); furthermore, satisfaction impacts continuance intention significantly (ß=.415; P<.001). Confirmation has a significant impact on perceived usefulness (ß=.859; P<.001) and satisfaction (ß=.391; P<.001), and perceived usefulness has a significant impact on satisfaction (ß=.269; P<.001) and continuance intention (ß=.273; P=.001). The mediating effect analysis showed that in the impact path of the intrinsic motivation for using the mHealth apps on continuance intention, satisfaction plays a partial mediating role (ß=.129; P<.001), with a variance accounted for of 0.466. CONCLUSIONS: This study explored the impact path of users' feelings induced by gamification on the intention of continued mHealth app use. We confirmed that perceived usefulness, confirmation, and satisfaction in the classical continued use theory for nonmedical information systems positively affect continuance intention. We also found that the path and mechanism of users' feelings regarding autonomy, competence, and relatedness generated during interactions with different gamification elements promote the continued use of mHealth apps.

American Heterosexual Emerging Adults' Reasoning about the Fairness of Household Labor.

This study investigated American heterosexual emerging adults' evaluations and reasoning about the fairness of their parents' gendered division of household labor, their future expectations of their own division, and in a third-party situation. A total of 161 American heterosexual (88.20% European American; 50.93% cisgender women), emerging adults (M = 20.60, SD = 1.21) participated in this study. The majority of participants evaluated their parents' and future expected division to be fair. On the other hand, participants were less likely to consider a hypothetical gendered division fair. Equality justification usage, as well as reported parental childcare division predicted differences in fairness evaluations. The present study highlights the importance of employing methods that can capture the complex and multi-faceted nature of fairness evaluations and reasoning about the gendered division of household labor.

Phosphorylation potential of Drosophila E-Cadherin intracellular domain is essential for development and adherens junction biosynthetic dynamics regulation.

Phosphorylation of a highly conserved serine cluster in the intracellular domain of E-Cadherin is essential for binding to ß-Catenin in vitro In cultured cells, phosphorylation of specific serine residues within the cluster is also required for regulation of adherens junction (AJ) stability and dynamics. However, much less is known about how such phosphorylation of E-Cadherin regulates AJ formation and dynamics in vivo In this report, we generated an extensive array of Drosophila E-Cadherin (DE-Cad) endogenous knock-in alleles that carry mutations targeting this highly conserved serine cluster. Analyses of these mutations suggest that the overall phosphorylation potential, rather than the potential site-specific phosphorylation, of the serine cluster enhances the recruitment of ß-Catenin by DE-Cad in vivo Moreover, phosphorylation potential of the serine cluster only moderately increases the level of ß-Catenin in AJs and is in fact dispensable for AJ formation in vivo Nonetheless, phosphorylation-dependent recruitment of ß-Catenin is essential for development, probably by enhancing the interactions between DE-Cad and α-Catenin. In addition, several phospho-mutations dramatically reduced the biosynthetic turnover rate of DE-Cad during apical-basal polarization, and such biosynthetically stable DE-Cad mutants specifically rescued the polarity defects in embryonic epithelia lacking the polarity proteins Stardust and Crumbs.

Analysis of haemodynamics and angiogenic response to ischaemia in the obese type 2 diabetic model Spontaneously Diabetic Torii Leprfa (SDT fatty) rats.

Peripheral artery disease (PAD) is defined as peripheral blood flow impairment, especially in the legs, caused by atherosclerotic stenosis. The disease decreases quality of life because of intermittent claudication or necrosis of the leg. The hindlimb ischaemia model, in which ischaemia is induced by femoral artery ligation, is often utilized as a PAD model. In the hindlimb ischaemia model, nonmetabolic syndrome animals are mainly used. In this study, we investigated the usefulness of Spontaneously Diabetic Torii Leprfa (SDT fatty) rats, a new model for obese type 2 diabetes, as a new PAD animal model. We found that hindlimb blood flow in SDT fatty rats was significantly lower than that in Sprague-Dawley (SD) rats under nonischaemic conditions. Furthermore, SDT fatty rats showed a significantly higher plasma nitrogen oxide level, shorter prothrombin time, and shorter activated partial thromboplastin time than SD rats. In addition, we found that the change in blood flow 7 days after induction of hindlimb ischaemia and the number of Von Willebrand factor-positive vessels in gastrocnemius muscles were significantly lower in SDT fatty rats than in SD rats. These results suggest that excess production of reactive oxygen species and coagulation activation could be involved in lower blood flow in non-ischaemic rats and that decreased angiogenesis could be involved in the poor recovery of blood flow in SDT fatty rats with hindlimb ischaemia. Taken together, our results suggest that SDT fatty rats might be useful as a new model for PAD with metabolic syndrome.

Predictors and outcomes of core and peripheral sport motivation profiles: A person-centered study.

While previous studies highlighted the importance of the different motivations for doing sports as proposed by self-determination theory, less emphasis has been put on the simultaneous presence of multiple motivations within the same individual. Therefore, the present study aimed to investigate the complex interaction of sport motivations and to identify core (common) and peripheral (uncommon) profiles of people engaged in sports based on a combination of motivations. To achieve this goal, latent profile analysis, a person-centered approach, was performed on responses from 506 participants engaged in sports. For better understanding the extracted profiles, basic psychological need fulfillment was included as profile predictor, while subjective vitality and various engagement-related indicators as outcomes. Four core and peripheral profiles were identified: Moderately Motivated, Highly Motivated, Amotivated, and Poorly Motivated. Contrary to theory, introjected regulation clustered more closely with self-determined motivations. Profile membership was significantly predicted by global need fulfillment, autonomy satisfaction as well as, to a smaller extent, autonomy, relatedness, and competence frustration. The four profiles differed along vitality and some, but not all, engagement-related outcomes.