Alternative molecular mechanisms for force transmission at adherens junctions via ß-catenin-vinculin interaction.

Force transmission through adherens junctions (AJs) is crucial for multicellular organization, wound healing and tissue regeneration. Recent studies shed light on the molecular mechanisms of mechanotransduction at the AJs. However, the canonical model fails to explain force transmission when essential proteins of the mechanotransduction module are mutated or missing. Here, we demonstrate that, in absence of α-catenin, ß-catenin can directly and functionally interact with vinculin in its open conformation, bearing physiological forces. Furthermore, we found that ß-catenin can prevent vinculin autoinhibition in the presence of α-catenin by occupying vinculin´s head-tail interaction site, thus preserving force transmission capability. Taken together, our findings suggest a multi-step force transmission process at AJs, where α-catenin and ß-catenin can alternatively and cooperatively interact with vinculin. This can explain the graded responses needed to maintain tissue mechanical homeostasis and, importantly, unveils a force-bearing mechanism involving ß-catenin and extended vinculin that can potentially explain the underlying process enabling collective invasion of metastatic cells lacking α-catenin.

Reflective supervision and consultation and its impact within early childhood-serving programs: A systematic review.

Reflective supervision and consultation (RS/C) is regarded as best practice within the infant/early childhood mental health field. Benefits of RS/C on the early childhood workforce and children and families have been demonstrated through case studies, conceptual pieces, and individual research studies. However, findings across studies have not been summarized using gold-standard methodology, thus the state of existing empirical support for RS/C is unclear. This systematic review examined the collective evidence for RS/C across diverse early childhood-serving programs. Electronic databases were searched to identify studies investigating associations between RS/C and professionals' reflective capacity and well-being, child/family outcomes, and implementation factors. Twenty-eight papers were identified. Studies showed positive associations between RS/C and early childhood-serving professionals' reflective capacity and well-being, with qualitative studies reporting more consistent results than studies using quantitative methods. Many methodological limitations were identified, including incomplete reporting of study designs and participant characteristics, variability in outcome measures, and lack of randomization and comparison groups. Furthermore, few studies examined child and family outcomes. Therefore, while RS/C shows great promise, it was difficult to ascertain its overall effectiveness from an empirical standpoint. Establishing RS/C as an empirically supported approach will be possible with more rigorous research.

A la consulta y supervisión con reflexión (RS/C) se le considera como práctica óptima dentro del campo de la salud mental infantil y la temprana niñez. Los beneficios de RS/C en la fuerza laboral de la temprana niñez, así como en niños y familias, han quedado demostrados a través de estudios de casos, componentes conceptuales y estudios individuales de investigación. Sin embargo, los resultados en la gama de estudios no han sido resumidos usando una metodología arquetípica; por tanto, el estado del apoyo empírico existente para RS/C no está claro. Esta sistemática revisión examinó la evidencia colectiva de RS/C a lo largo de los diversos programas que se dedican a la temprana niñez. Se investigaron bancos electrónicos de datos para identificar estudios que investigaron las asociaciones entre RS/C y la capacidad de reflexión y bienestar de profesionales, los resultados en niño y familia, así como los factores de implementación. Se identificaron veintiocho artículos. Los estudios mostraron asociaciones positivas entre RS/C y la capacidad de reflexión y bienestar de profesionales que prestan servicios en al campo de la temprana niñez, con estudios cualitativos que reportaron resultados más consistentes que los estudios que usaron métodos cuantitativos. Se identificaron muchas limitaciones metodológicas, incluyendo un incompleto reporte de los diseños del estudio y las características de los participantes, la variabilidad en las medidas para los resultados, así como una falta de aleatorización y grupos de comparación. Es más, pocos estudios examinaron los resultados en el niño y la familia. Por tanto, mientras que RS/C muestra gran promesa, fue difícil cerciorarse de su efectividad en términos generales desde un punto de vista empírico. Establecer RS/C como un acercamiento empíricamente apoyado será posible con una investigación más rigurosa.

La supervision et la conversation par réflexion (RS/C) est considérée comme étant la meilleure pratique dans le domaine de la santé mentale du nourrisson et de la petite enfance. Les bénéfices de la RS/C sur les effectifs de la petite enfance et les enfants et leurs familles ont été prouvés au travers d'études de cas, de travaux conceptuels et d'études individuelles de recherche. Cependant les résultats au travers des études n'ont pas été résumés au moyen d'une méthodologie de référence et par conséquent l'état du soutien empirique existent pour le RS/C n'est pas clair. Cette revue systématique a examiné les preuves collectives de la RS/C au travers de divers programmes servant la petite enfance. Les bases de données électroniques ont été utilisées afin d'identifier des études se penchant sur les liens entre la RS/C et la capacité de réflexion des professionnels ainsi que leur bien-être, les résultats pour l'enfant/la famille et les facteurs de mise en place. Vingt-huit études ont été identifiées. Les études ont démontré des liens positifs entre la RS/C et la capacité de réflexion et le bien-être de professionnels de la petite enfance, avec des études qualitatives faisant état de résultats plus constants que les études utilisant des méthodes quantitatives. Plusieurs limitations méthodologiques ont été identifiées, y compris le fait de rapporter de manière incomplète les méthodologies des études et les caractéristiques des participants, la variabilité des mesures des résultats, et le manque de de groupes de randomisation et de contrôle. De plus, peu d'études ont examiné les résultats de l'enfant et de la famille. En conclusion, bien que la RS/C soit promettante, il était difficile de vérifier son efficacité générale d'un point de vue empirique. L'établissement de la RS/C en tant qu'approche soutenue empiriquement sera possible avec des recherches plus rigoureuses.

Co-designing Community Out-of-hours Palliative Care Services: A systematic literature search and review.

BACKGROUND: In order to provide responsive, individualised and personalised care, there is now greater engagement with patients, families and carers in designing health services. Out-of-hours care is an essential component of community palliative care. However, little is known about how patients, families and carers have been involved in the planning and design of these services. AIM: To systematically search and review the research literature that reports on how out-of-hours palliative care services are provided in the community and to identify the extent to which the principles of co-design have been used to inform the planning and design of these services. DESIGN: Systematic literature search and review. DATA SOURCES: A systematic search for published research papers from seven databases was conducted in MEDLINE, PsycINFO, Embase, Emcare, PubMed, CINAHL and Web of Science, from January 2010 and December 2021. Reference list searches of included papers were undertaken to source additional relevant literature. A manifest content analysis was used to analyse the data. RESULTS: A total of 77 papers were included. The majority of out-of-hours services in the community were provided by primary care services. The review found little evidence that patients, families or carers were involved in the planning or development of out-of-hours services. CONCLUSION: Incorporating patients, families and carers priorities and preferences in the planning and designing of out-of-hours palliative care service is needed for service providers to deliver care that is more patient-centred. Adopting the principles of co-design may improve how out-of-hours care scan be delivered.

The use of telehealth in the provision of after-hours palliative care services in rural and remote Australia: A scoping review.

BACKGROUND: Accessing quality palliative care, especially at the end of life is vital in reducing physical and emotional distress and optimising quality of life. For people living in rural and remote Australia, telehealth services can be effective in providing access to after-hours palliative care. OBJECTIVE: To review and map the available evidence on the use of telehealth in providing after-hours palliative care services in rural and remote Australia. METHOD: Scoping review using Arksey and O'Malley methodological framework. Findings are reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Scopus, Web of Science, CINAHL Complete, Embase via Ovid, Emcare via Ovid, and Medline via Ovid databases were searched. Peer-reviewed studies and grey literature published in English from 2000 to May 2021 were included. RESULTS: Twelve studies were included in the review. Four main themes were identified: 1) Stakeholder perceptions of service; 2) benefits to services and users; 3) service challenges; and 4) recommendations for service improvement. CONCLUSION: Telehealth can connect patients and families with healthcare professionals and enable patients to continue receiving care at home. However, challenges relating to patients, service, staff skills, and experience need to be overcome to ensure the success and sustainability of this service. Improved communication and care coordination, better access to patient records, and ongoing healthcare professional education are required. IMPLICATIONS: Protocols, comprehensive policy documents and standardized operating procedures to guide healthcare professionals to provide after-hours palliative care is needed. Ongoing education and training for staff is crucial in managing patients' symptoms. Existing service gaps need to be explored and alternative models of after-hours palliative care need to be tested.

Self-supervised classification of subcellular morphometric phenotypes reveals extracellular matrix-specific morphological responses.

Cell morphology is profoundly influenced by cellular interactions with microenvironmental factors such as the extracellular matrix (ECM). Upon adhesion to specific ECM, various cell types are known to exhibit different but distinctive morphologies, suggesting that ECM-dependent cell morphological responses may harbour rich information on cellular signalling states. However, the inherent morphological complexity of cellular and subcellular structures has posed an ongoing challenge for automated quantitative analysis. Since multi-channel fluorescence microscopy provides robust molecular specificity important for the biological interpretations of observed cellular architecture, here we develop a deep learning-based analysis pipeline for the classification of cell morphometric phenotypes from multi-channel fluorescence micrographs, termed SE-RNN (residual neural network with squeeze-and-excite blocks). We demonstrate SERNN-based classification of distinct morphological signatures observed when fibroblasts or epithelial cells are presented with different ECM. Our results underscore how cell shapes are non-random and established the framework for classifying cell shapes into distinct morphological signature in a cell-type and ECM-specific manner.

Use of telehealth in the provision of after-hours palliative care services in rural and remote Australia: A scoping review protocol.

INTRODUCTION: After-hours services are essential in ensuring patients with life limiting illness and their caregivers are supported to enable continuity of care. Telehealth is a valuable approach to meeting after-hours support needs of people living with life-limiting illness, their families, and caregivers in rural and remote communities. It is important to explore the provision of after-hours palliative care services using telehealth to understand the reach of these services in rural and remote Australia. A preliminary search of databases failed to reveal any scoping or systematic reviews of telehealth in after-hours palliative care services in rural or remote Australia. AIM: To review and map the available evidence about the use of telehealth in providing after-hours palliative care services in Australian rural and remote communities. METHODS: The proposed scoping review will be conducted using the Arksey and O'Malley methodological framework and in accordance with the Joanna Briggs Institute methodology for scoping reviews. The reporting of the scoping review will be guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). This review will consider research and evaluation of after-hours services using telehealth for palliative care stakeholders in rural and remote Australia. Peer reviewed studies and grey literature published in English from 2000 to May 2021 will be included. Scopus, Web of Science, CINAHL Complete, Embase via Ovid, PsycINFO via Ovid, Emcare via Ovid, Medline via Ovid, and grey literature will be searched for relevant articles. Titles and abstracts will be screened by two independent reviewers for assessment against the inclusion criteria. Data will be extracted and analysed by two reviewers using an adapted data extraction tool and thematic analysis techniques. Diagrams, tables, and summary narratives will be used to map, summarise and thematically group the characteristics of palliative care telehealth services in rural and remote Australia, including stakeholders' perceptions and benefits and challenges of the services.

The Performance and Trajectory of Medical Students With Disabilities: Results From a Multisite, Multicohort Study.

PURPOSE: To conduct a post-Americans with Disabilities Act Amendments Act of 2008 multisite, multicohort study called the Pathways Project to assess the performance and trajectory of medical students with disabilities (SWDs). METHOD: From June to December 2020, the authors conducted a matched cohort study of SWDs and nondisabled controls from 2 graduating cohorts (2018 and 2019) across 11 U.S. MD-granting medical schools. Each SWD was matched with 2 controls, one from their institution and, whenever possible, one from their cohort for Medical College Admission Test score and self-reported gender. Outcome measures included final attempt Step 1 and Step 2 Clinical Knowledge scores, time to graduation, leave of absence, matching on first attempt, and matching to primary care. RESULTS: A total of 171 SWDs and 341 controls were included; the majority of SWDs had cognitive/learning disabilities (118/171, 69.0%). Compared with controls, SWDs with physical/sensory disabilities had similar times to graduation (88.6%, 95% confidence interval [CI]: 77.0, 100.0 vs 95.1%, 95% CI: 90.3, 99.8; P = .20), Step 1 scores (229.6 vs 233.4; P = .118), and match on first attempt (93.9%, 95% CI: 86.9, 100.0 vs 94.6%, 95% CI: 91.8, 97.4; P = .842), while SWDs with cognitive/learning disabilities had lower Step 1 scores (219.4; P < .001) and were less likely to graduate on time (81.2%, 95% CI: 69.2, 93.2; P = .003) and match on first attempt (85.3%, 95% CI: 78.0, 92.7; P = .009). Accommodated SWDs had Step 1 scores that were 5.9 points higher than nonaccommodated SWDs (95% CI: -0.7, 12.5; P = .08). CONCLUSIONS: Structural barriers remain for SWDs with cognitive/learning disabilities, which could be partially mitigated by accommodations on high-stakes exams.

Investigating the Impact of the Bit Depth of Fluorescence-Stained Images on the Performance of Deep Learning-Based Nuclei Instance Segmentation.

Nuclei instance segmentation can be considered as a key point in the computer-mediated analysis of histological fluorescence-stained (FS) images. Many computer-assisted approaches have been proposed for this task, and among them, supervised deep learning (DL) methods deliver the best performances. An important criterion that can affect the DL-based nuclei instance segmentation performance of FS images is the utilised image bit depth, but to our knowledge, no study has been conducted so far to investigate this impact. In this work, we released a fully annotated FS histological image dataset of nuclei at different image magnifications and from five different mouse organs. Moreover, by different pre-processing techniques and using one of the state-of-the-art DL-based methods, we investigated the impact of image bit depth (i.e., eight bits vs. sixteen bits) on the nuclei instance segmentation performance. The results obtained from our dataset and another publicly available dataset showed very competitive nuclei instance segmentation performances for the models trained with 8 bit and 16 bit images. This suggested that processing 8 bit images is sufficient for nuclei instance segmentation of FS images in most cases. The dataset including the raw image patches, as well as the corresponding segmentation masks is publicly available in the published GitHub repository.

CryoNuSeg: A dataset for nuclei instance segmentation of cryosectioned H&E-stained histological images.

Nuclei instance segmentation plays an important role in the analysis of hematoxylin and eosin (H&E)-stained images. While supervised deep learning (DL)-based approaches represent the state-of-the-art in automatic nuclei instance segmentation, annotated datasets are required to train these models. There are two main types of tissue processing protocols resulting in formalin-fixed paraffin-embedded samples (FFPE) and frozen tissue samples (FS), respectively. Although FFPE-derived H&E stained tissue sections are the most widely used samples, H&E staining of frozen sections derived from FS samples is a relevant method in intra-operative surgical sessions as it can be performed more rapidly. Due to differences in the preparation of these two types of samples, the derived images and in particular the nuclei appearance may be different in the acquired whole slide images. Analysis of FS-derived H&E stained images can be more challenging as rapid preparation, staining, and scanning of FS sections may lead to deterioration in image quality. In this paper, we introduce CryoNuSeg, the first fully annotated FS-derived cryosectioned and H&E-stained nuclei instance segmentation dataset. The dataset contains images from 10 human organs that were not exploited in other publicly available datasets, and is provided with three manual mark-ups to allow measuring intra-observer and inter-observer variabilities. Moreover, we investigate the effects of tissue fixation/embedding protocol (i.e., FS or FFPE) on the automatic nuclei instance segmentation performance and provide a baseline segmentation benchmark for the dataset that can be used in future research. A step-by-step guide to generate the dataset as well as the full dataset and other detailed information are made available to fellow researchers at https://github.com/masih4/CryoNuSeg.

Rapid high resolution 3D imaging of expanded biological specimens with lattice light sheet microscopy.

Expansion microscopy was invented to surpass the optical diffraction limit by physically expanding biological specimens with swellable polymers. Due to the large sizes of expanded specimens, 3D imaging techniques that are capable to acquire large volumetric data rapidly at high spatial resolution are therefore required for expansion microscopy. Lattice light sheet microscopy (LLSM) was developed to image biological specimens rapidly at high 3D spatial resolution by using a thin lattice light sheet for sample illumination. However, due to the current limitations of LLSM mechanism and the optical design of LLS microscopes, it is challenging to image large expanded specimens at isotropic high spatial resolution using LLSM. To address the problem, we first optimized the sample preparation and expansion procedure for LLSM. Then, we implement a tiling lattice light sheet method to minimize sample translation during imaging and achieve much faster 3D imaging speed at high spatial resolution with more isotropic performance. Taken together, we report a general and improved 3D super-resolution imaging method for expanded samples.

MEASURING REFLECTIVE SUPERVISION WITHIN HOME VISITING: CHANGES IN SUPERVISORS' SELF-PERCEPTION OVER TIME.

Despite widespread belief in the early childhood field of the benefits of reflective supervision, there has been limited empirical evidence to support the effectiveness of reflective supervision for home visitors and the children and families they serve. The present study examined the psychometric properties of four adapted self-report measures assessing supervisors' reflective supervision capacities; the study also investigated whether these measures captured change in reflective capacity over time as supervisors participated in professional development activities focused on reflective supervision. Results from 33 participants (home visiting supervisors and program managers) suggested that three of the four measures demonstrated acceptable internal consistency, and these three measures were correlated with each other. Two of these measures also captured significant change over time. Finally, there was some evidence that those with less education demonstrated more substantial improvement in their reflective supervision capacities than did those with an advanced degree. Findings provide initial evidence for reliable, efficient, and cost-effective supervisor self-report measures that could be used in research and program evaluation to assess change in supervisor reflective capacity over time.

Vibrator and PI4KIIIα govern neuroblast polarity by anchoring non-muscle myosin II.

A central feature of most stem cells is the ability to self-renew and undergo differentiation via asymmetric division. However, during asymmetric division the role of phosphatidylinositol (PI) lipids and their regulators is not well established. Here, we show that the sole type I PI transfer protein, Vibrator, controls asymmetric division of Drosophilaneural stem cells (NSCs) by physically anchoring myosin II regulatory light chain, Sqh, to the NSC cortex. Depletion of vib or disruption of its lipid binding and transfer activities disrupts NSC polarity. We propose that Vib stimulates PI4KIIIα to promote synthesis of a plasma membrane pool of phosphatidylinositol 4-phosphate [PI(4)P] that, in turn, binds and anchors myosin to the NSC cortex. Remarkably, Sqh also binds to PI(4)P in vitro and both Vib and Sqh mediate plasma membrane localization of PI(4)P in NSCs. Thus, reciprocal regulation between Myosin and PI(4)P likely governs asymmetric division of NSCs.

Good choices, great future: an applied theatre prevention program to reduce alcohol-related risky behaviours during Schoolies.

INTRODUCTION AND AIMS: The contextual and temporal factors of post-school celebratory events ('Schoolies') place young people at elevated risk of excessive drinking compared with other social occasions. This study investigates the impact of an applied theatre prevention program 'Choices' in reducing the risk of drinking and other risk behaviours during Schoolies celebrations. DESIGN AND METHODS: Choices was delivered in the last term of Year 12 across 28 North Queensland schools. A total of 352 school leavers (43.1% male, mean age = 17.14 years) completed a questionnaire at Whitsunday Schoolies, Queensland, Australia on 23-24 November 2010. Nearly 49% of respondents had attended Choices. The survey included measures of alcohol use, illicit drug use and associated problems during Schoolies and a month prior to Schoolies. RESULTS: After controlling for gender and pre-Schoolies drinking, school leavers who attended Choices were significantly less likely to report illicit drug use (OR = 0.51, P < 0.05) and problem behaviours (OR = 0.40, P < 0.01) than those who did not attend Choices. There was, however, no intervention effect in risky drinking (i.e. drank on 5 or more days, typical amount five or more standard drink and binge drank on 3 or more days) at Schoolies (OR = 0.92, P = 0.80). DISCUSSION AND CONCLUSIONS: Delivery of a youth-specific applied theatre prevention program employing a harm minimisation framework may be effective in reducing high-risk behaviours associated with alcohol consumption at celebratory events, even if young people expect to engage in excessive alcohol consumption.

Chaotic living conditions and sleep problems associated with children's responses to academic challenge.

The ecology of economic disadvantage includes chaotic living conditions that may disrupt children's regulatory functioning and undermine mastery oriented responses to challenge. The present study examined chaotic living conditions, sleep problems, and responses to academic challenge for 96 economically disadvantaged children enrolled in a Head Start preschool. Caregiver interviews provided information regarding chaotic living conditions of residential crowding, noise, and family instability, as well as child sleep problems. Tasks individually administered to children provided measures of responses to academic challenge. Chaotic living conditions statistically predicted helpless/hopeless responses to academic challenge, and sleep problems partially mediated this relationship. Implications concern pathways of ecological risk and diversity in the school functioning of economically disadvantaged children.

Forensic child abuse evaluation: a review.

This review discusses the forensic medical and psychological assessments of children and adolescents suspected of being victims of sexual or physical abuse/neglect. Evaluation of the whole child and the need to minimize trauma during the investigative and assessment processes are stressed. The forensic medical examination is reviewed, including the specifics of the pediatric anogenital examination. The key components of the forensic medical examination in sexual assault cases are also reviewed, with particular attention to maintaining the integrity of the process. Special emphasis is placed on the forensic interview in child sexual abuse cases, the best evidence available and areas in need of further research.

Friendship jealousy in young adolescents: individual differences and links to sex, self-esteem, aggression, and social adjustment.

Children's vulnerability to jealousy surrounding their best friends was explored in 2 studies. Study 1 involved 94 adolescents who reported on their friendship jealousy on a newly created measure. Results indicated that the jealousy measure had sound psychometric properties and produced individual differences that were robust over time and free from socially desirable responding. As expected, girls and adolescents with low self-worth reported the greatest friendship jealousy. Study 2 involved 399 young adolescents and extended the measurement of self-report jealousy to a broader age range. In addition, Study 2 included assessments of jealousy provided by friends and other peers. Self- and peer-reported jealousy were only modestly associated and had somewhat distinct correlates. Structural modeling revealed that young adolescents' reputation for friendship jealousy was linked to behaving aggressively and to broader peer adjustment difficulties. Both self- and peer-reported jealousy contributed to loneliness.