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1.
Sex Reprod Healthc ; 40: 100982, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38795653

ABSTRACT

OBJECTIVE: To investigate how fathers or partners perceive their roles as new parents when confronted with early breastfeeding challenges, how they navigate these difficulties, and the specific type of support they seek from the Child Health Care Centre (CHCC). METHOD: In-depth, individual interviews conducted with 12 partners of women for whom breastfeeding was difficult. Reflexive thematic analysis was applied on the interview data. RESULTS: Interviews resulted in three themes: 1) 'It is a revolutionary time to be a new father' represented a tumultuous time when fathers wanted to be involved in all decisions and part of a strong team with their partners. 2) 'When a breastfeeding problem arose'; fathers questioned the sovereignty of breast milk and began to seek more knowledge. They experienced a strong social norm about breastfeeding that led to feelings of guilt for their partners. They felt helpless when their partners suffered and lacked support. 3) 'Child Health Care Centre's duty'; was instrumental, as knowledge and competence were found to be important for trust. The fathers wanted concrete solutions to breastfeeding problems and more conversations of support with the CHCC nurse. CONCLUSION: Well-educated fathers desire to protect their partners as they experience suffering due to a robust social norm telling them that breastfeeding is best. This can result in them starting to question the sovereignty of breast milk. Fathers need support to help their partners successfully during breastfeeding. They want counselling to strengthen their role as parents and help them build trusting teams with their partners.


Subject(s)
Breast Feeding , Fathers , Humans , Fathers/psychology , Breast Feeding/psychology , Male , Female , Adult , Social Support , Qualitative Research , Role , Interviews as Topic , Spouses/psychology
2.
Br J Dermatol ; 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38234043

ABSTRACT

BACKGROUND: Use of artificial intelligence, or machine learning, to assess dermoscopic images of skin lesions to detect melanoma has in several retrospective studies shown high levels of diagnostic accuracy on par with, or even outperforming, experienced dermatologists. However, the enthusiasm around these algorithms has not yet been matched by prospective clinical trials performed in authentic clinical settings. In several European countries, including Sweden, the initial clinical assessment of suspected skin cancer is principally conducted in the primary health care setting by primary care physicians; with or without access to teledermoscopic support from dermatology clinics. OBJECTIVE: To determine the diagnostic performance of an artificial intelligence-based clinical decision support tool for cutaneous melanoma detection, operated by a smartphone application (app), when used prospectively by primary care physicians to assess skin lesions of concern due to some degree of melanoma suspicion. METHODS: This prospective, multicentre, clinical trial was conducted at 36 primary care centres in Sweden. The physicians used the smartphone app on skin lesions of concern by photographing them dermoscopically, which resulted in a dichotomous decision support text regarding evidence for melanoma. Regardless of the app outcome, all lesions underwent standard diagnostic procedure, by surgical excision or referral to dermatologist. After completed investigation, lesion diagnoses were collected from the patients' medical records and compared to app outcome and other lesion data. RESULTS: In total, 253 lesions of concern in 228 patients were included, of which 21 proved to be melanomas, with 11 thin invasive melanomas and 10 melanomas in situ. The app's accuracy (95% confidence interval) in identifying melanomas was reflected in an area under the receiver operating characteristic (AUROC) curve of 0.960 (0.928-0.980), corresponding to a maximum sensitivity and specificity of 95.2% and 84.5%, respectively. For invasive melanomas alone, the AUROC was 0.988 (0.965-0.997), corresponding to a maximum sensitivity and specificity of 100% and 92.6%, respectively. CONCLUSIONS: The clinical decision support tool evaluated in this investigation showed high diagnostic accuracy when used prospectively on primary care patients, which could add significant clinical value for primary care physicians in assessing skin lesions to detect melanoma. ClinicalTrials.gov Identifier: NCT05172232.

3.
Scand J Prim Health Care ; 42(1): 51-60, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37982736

ABSTRACT

Objective: Skin examination to detect cutaneous melanomas is commonly performed in primary care. In recent years, clinical decision support systems (CDSS) based on artificial intelligence (AI) have been introduced within several diagnostic fields.Setting: This study employs a variety of qualitative and quantitative methodologies to investigate the feasibility of an AI-based CDSS to detect cutaneous melanoma in primary care.Subjects and Design: Fifteen primary care physicians (PCPs) underwent near-live simulations using the CDSS on a simulated patient, and subsequent individual semi-structured interviews were explored with a hybrid thematic analysis approach. Additionally, twenty-five PCPs performed a reader study (diagnostic assessment on the basis of image interpretation) of 18 dermoscopic images, both with and without help from AI, investigating the value of adding AI support to a PCPs decision. Perceived instrument usability was rated on the System Usability Scale (SUS).Results: From the interviews, the importance of trust in the CDSS emerged as a central concern. Scientific evidence supporting sufficient diagnostic accuracy of the CDSS was expressed as an important factor that could increase trust. Access to AI decision support when evaluating dermoscopic images proved valuable as it formally increased the physician's diagnostic accuracy. A mean SUS score of 84.8, corresponding to 'good' usability, was measured.Conclusion: AI-based CDSS might play an important future role in cutaneous melanoma diagnostics, provided sufficient evidence of diagnostic accuracy and usability supporting its trustworthiness among the users.


Effective primary care is important for discovering cutaneous melanoma, the deadliest and an increasingly prevalent form of skin cancer. 'Trust', 'usability and user experience', and 'the clinical context' are the qualitative themes that emerged from the qualitative analysis. These areas need to be considered for the successful adoption of AI assisted decision support tools by PCPs.The AI CDSS tool was rated by the PCPs at grade B (average 84.8) on the System Usability Scale (SUS), which is equivalent to 'good' usability.A reader study, (diagnostic assessment on the basis of image interpretation) with 25 PCPs rating dermoscopic images, showed increased value of adding an AI decision support to their clinical assessment.


Subject(s)
Decision Support Systems, Clinical , Melanoma , Skin Neoplasms , Humans , Melanoma/diagnosis , Skin Neoplasms/diagnosis , Artificial Intelligence , Feasibility Studies , Primary Health Care/methods
4.
Sensors (Basel) ; 23(22)2023 Nov 16.
Article in English | MEDLINE | ID: mdl-38005593

ABSTRACT

The development of smart wearable solutions for monitoring daily life health status is increasingly popular, with chest straps and wristbands being predominant. This study introduces a novel sensorized T-shirt design with textile electrodes connected via a knitting technique to a Movesense device. We aimed to investigate the impact of stationary and movement actions on electrocardiography (ECG) and heart rate (HR) measurements using our sensorized T-shirt. Various activities of daily living (ADLs), including sitting, standing, walking, and mopping, were evaluated by comparing our T-shirt with a commercial chest strap. Our findings demonstrate measurement equivalence across ADLs, regardless of the sensing approach. By comparing ECG and HR measurements, we gained valuable insights into the influence of physical activity on sensorized T-shirt development for monitoring. Notably, the ECG signals exhibited remarkable similarity between our sensorized T-shirt and the chest strap, with closely aligned HR distributions during both stationary and movement actions. The average mean absolute percentage error was below 3%, affirming the agreement between the two solutions. These findings underscore the robustness and accuracy of our sensorized T-shirt in monitoring ECG and HR during diverse ADLs, emphasizing the significance of considering physical activity in cardiovascular monitoring research and the development of personal health applications.


Subject(s)
Activities of Daily Living , Textiles , Humans , Heart Rate/physiology , Electrocardiography , Monitoring, Physiologic/methods
5.
Stud Health Technol Inform ; 309: 8-12, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37869796

ABSTRACT

Patient involvement in research has been highlighted as a major requirement for the development of products and services that cover actual patients' needs. However, there has not been an agreement on a commonly used standard for patient involvement in research, at least not in the EU, partially because of lack of common terminology and implementation methodology. Within the standardization activities of "LifeChamps: A Collective Intelligent Platform To Support Cancer Champions", this qualitative study was developed to discover patients' views for their engagement in research. This is an ongoing qualitative study of semi-structured interviews of cancer survivors aged over 65 years of age, exiting the feasibility studies of the LifeChamps project in Stockholm and Thessaloniki. Findings from the thematic analysis of this study are expected to indicate requirements for involvement of patients in research studies as participants.


Subject(s)
Cancer Survivors , Neoplasms , Humans , Aged , Qualitative Research , Patient Participation/methods , Patients
6.
J Med Internet Res ; 25: e41294, 2023 07 27.
Article in English | MEDLINE | ID: mdl-37498644

ABSTRACT

BACKGROUND: Cyber threats are increasing across all business sectors, with health care being a prominent domain. In response to the ever-increasing threats, health care organizations (HOs) are enhancing the technical measures with the use of cybersecurity controls and other advanced solutions for further protection. Despite the need for technical controls, humans are evidently the weakest link in the cybersecurity posture of HOs. This suggests that addressing the human aspects of cybersecurity is a key step toward managing cyber-physical risks. In practice, HOs are required to apply general cybersecurity and data privacy guidelines that focus on human factors. However, there is limited literature on the methodologies and procedures that can assist in successfully mapping these guidelines to specific controls (interventions), including awareness activities and training programs, with a measurable impact on personnel. To this end, tools and structured methodologies for assisting higher management in selecting the minimum number of required controls that will be most effective on the health care workforce are highly desirable. OBJECTIVE: This study aimed to introduce a cyber hygiene (CH) methodology that uses a unique survey-based risk assessment approach for raising the cybersecurity and data privacy awareness of different employee groups in HOs. The main objective was to identify the most effective strategy for managing cybersecurity and data privacy risks and recommend targeted human-centric controls that are tailored to organization-specific needs. METHODS: The CH methodology relied on a cross-sectional, exploratory survey study followed by a proposed risk-based survey data analysis approach. First, survey data were collected from 4 different employee groups across 3 European HOs, covering 7 categories of cybersecurity and data privacy risks. Next, survey data were transcribed and fitted into a proposed risk-based approach matrix that translated risk levels to strategies for managing the risks. RESULTS: A list of human-centric controls and implementation levels was created. These controls were associated with risk categories, mapped to risk strategies for managing the risks related to all employee groups. Our mapping empowered the computation and subsequent recommendation of subsets of human-centric controls to implement the identified strategy for managing the overall risk of the HOs. An indicative example demonstrated the application of the CH methodology in a simple scenario. Finally, by applying the CH methodology in the health care sector, we obtained results in the form of risk markings; identified strategies to manage the risks; and recommended controls for each of the 3 HOs, each employee group, and each risk category. CONCLUSIONS: The proposed CH methodology improves the CH perception and behavior of personnel in the health care sector and provides risk strategies together with a list of recommended human-centric controls for managing a wide range of cybersecurity and data privacy risks related to health care employees.


Subject(s)
Delivery of Health Care , Privacy , Humans , Cross-Sectional Studies , Computer Security , Organizations
7.
Semin Oncol Nurs ; 39(3): 151437, 2023 06.
Article in English | MEDLINE | ID: mdl-37149438

ABSTRACT

OBJECTIVES: LifeChamps is an EU Horizon 2020 project that aims to create a digital platform to enable monitoring of health-related quality of life and frailty in patients with cancer over the age of 65. Our primary objective is to assess feasibility, usability, acceptability, fidelity, adherence, and safety parameters when implementing LifeChamps in routine cancer care. Secondary objectives involve evaluating preliminary signals of efficacy and cost-effectiveness indicators. DATA SOURCES: This will be a mixed-methods exploratory project, involving four study sites in Greece, Spain, Sweden, and the United Kingdom. The quantitative component of LifeChamps (single-group, pre-post feasibility study) will integrate digital technologies, home-based motion sensors, self-administered questionnaires, and the electronic health record to (1) enable multimodal, real-world data collection, (2) provide patients with a coaching mobile app interface, and (3) equip healthcare professionals with an interactive, patient-monitoring dashboard. The qualitative component will determine end-user usability and acceptability via end-of-study surveys and interviews. CONCLUSION: The first patient was enrolled in the study in January 2023. Recruitment will be ongoing until the project finishes before the end of 2023. IMPLICATIONS FOR NURSING PRACTICE: LifeChamps provides a comprehensive digital health platform to enable continuous monitoring of frailty indicators and health-related quality of life determinants in geriatric cancer care. Real-world data collection will generate "big data" sets to enable development of predictive algorithms to enable patient risk classification, identification of patients in need for a comprehensive geriatric assessment, and subsequently personalized care.


Subject(s)
Frailty , Neoplasms , Humans , Aged , Feasibility Studies , Quality of Life , Surveys and Questionnaires
8.
BMC Prim Care ; 24(1): 67, 2023 03 13.
Article in English | MEDLINE | ID: mdl-36907875

ABSTRACT

BACKGROUND: There is a need to accelerate digital transformation in healthcare to meet increasing needs and demands. The accuracy of medical digital diagnosis tools is improving. The introduction of new technology in healthcare can however be challenging and it is unclear how it should be done to reach desired results. The aim of this study was to explore perceptions and experiences of introducing new Information Technology (IT) in a primary healthcare organisation, exemplified with a Clinical Decision Support System (CDSS) for malignant melanoma. METHODS: A qualitative interview-based study was performed in Region Stockholm, Sweden, with fifteen medical doctors representing three different organisational levels - primary care physician, primary healthcare centre manager, and regional manager/chief medical officer. In addition, one software provider was included. Interview data were analysed according to content analysis. RESULTS: One central theme "Introduction of digital CDSS in primary healthcare requires a multidimensional perspective and handling" along with seven main categories and thirty-three subcategories emerged from the analysis. Digital transformation showed to be key for current healthcare providers to stay relevant and competitive. However, healthcare represents a closed community, very capable but with lack of time, fostered to be sceptical to new why change needs to bring true value and be inspired by people with medical background to motivate the powerful frontline. CONCLUSIONS: This qualitative study revealed structured information of what goes wrong and right and what needs to be considered when driving digital change in primary care organisations. The task shows to be complex and the importance of listening to the voice of healthcare is valuable for understanding the conditions that need to be fulfilled when adopting new technology into a healthcare organization. By considering the findings of this study upcoming digital transformations can improve their success-rate. The information may also be used in developing a holistic approach or framework model, adapted to primary health care, that can support and accelerate the needed digitalization in healthcare as such.


Subject(s)
Delivery of Health Care , Health Personnel , Humans , Qualitative Research , Health Facilities , Sweden
9.
J Cancer Surviv ; 17(4): 1094-1110, 2023 08.
Article in English | MEDLINE | ID: mdl-36367615

ABSTRACT

PURPOSE: This study is to evaluate healthcare needs, preferences, and expectations in supportive cancer care as perceived by cancer survivors, family caregivers, and healthcare professionals. METHODS: Key stakeholders consisted of cancer survivors diagnosed with breast cancer, prostate cancer, or melanoma; adult family caregivers; and healthcare professionals involved in oncology. Recruitment was via several routes, and data were collected via either online surveys or telephone interviews in Greece, Spain, Sweden, and the UK. Framework analysis was applied to the dataset. RESULTS: One hundred and fifty-five stakeholders participated: 70 cancer survivors, 23 family caregivers, and 62 healthcare professionals (13 clinical roles). Cancer survivors and family caregivers' needs included information and support on practical/daily living, as frustration was apparent with the lack of follow-up services. Healthcare professionals agreed on a multidisciplinary health service with a "focus on the patient" and availability closer to home. Most healthcare professionals acknowledged that patient-reported outcomes may provide "better individualised care". Cancer survivors and family caregivers generally felt that the digital platform would be useful for timely personalised support and aided communication. Healthcare professionals were supportive of the "proactive" functionality of the platform and the expected advantages. Anticipated challenges were integration obstacles such as workload/infrastructure and training/support in using the new technology. CONCLUSIONS: Obtaining key stakeholders' insights provided a foundation for action to further co-create the LifeChamps digital platform to meet needs and priorities and deliver enhanced supportive care to "older" cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Co-creation provided insight into gaps where digital support may enhance health and well-being.


Subject(s)
Breast Neoplasms , Cancer Survivors , Adult , Male , Humans , Motivation , Caregivers , Delivery of Health Care
10.
Sensors (Basel) ; 21(15)2021 Jul 28.
Article in English | MEDLINE | ID: mdl-34372354

ABSTRACT

Background: Cybersecurity is increasingly becoming a prominent concern among healthcare providers in adopting digital technologies for improving the quality of care delivered to patients. The recent reports on cyber attacks, such as ransomware and WannaCry, have brought to life the destructive nature of such attacks upon healthcare. In complement to cyberattacks, which have been targeted against the vulnerabilities of information technology (IT) infrastructures, a new form of cyber attack aims to exploit human vulnerabilities; such attacks are categorised as social engineering attacks. Following an increase in the frequency and ingenuity of attacks launched against hospitals and clinical environments with the intention of causing service disruption, there is a strong need to study the level of awareness programmes and training activities offered to the staff by healthcare organisations. Objective: The objective of this systematic review is to identify commonly encountered factors that cybersecurity postures of a healthcare organisation, resulting from the ignorance of cyber threat to healthcare. The systematic review aims to consolidate the current literature being reported upon human behaviour resulting in security gaps that mitigate the cyber defence strategy adopted by healthcare organisations. Additionally, the paper also reviews the organisational risk assessment methodology implemented and the policies being adopted to strengthen cybersecurity. Methods: The topic of cybersecurity within healthcare and the clinical environment has attracted the interest of several researchers, resulting in a broad range of literature. The inclusion criteria for the articles in the review stem from the scope of the five research questions identified. To this end, we conducted seven search queries across three repositories, namely (i) PubMed®/MED-LINE; (ii) Cumulative Index to Nursing and Allied Health Literature (CINAHL); and (iii) Web of Science (WoS), using key words related to cybersecurity awareness, training, organisation risk assessment methodologies, policies and recommendations adopted as counter measures within health care. These were restricted to around the last 12 years. Results: A total of 70 articles were selected to be included in the review, which addresses the complexity of cybersecurity measures adopted within the healthcare and clinical environments. The articles included in the review highlight the evolving nature of cybersecurity threats stemming from exploiting IT infrastructures to more advanced attacks launched with the intent of exploiting human vulnerability. A steady increase in the literature on the threat of phishing attacks evidences the growing threat of social engineering attacks. As a countermeasure, through the review, we identified articles that provide methodologies resulting from case studies to promote cybersecurity awareness among stakeholders. The articles included highlight the need to adopt cyber hygiene practices among healthcare professionals while accessing social media platforms, which forms an ideal test bed for the attackers to gain insight into the life of healthcare professionals. Additionally, the review also includes articles that present strategies adopted by healthcare organisations in countering the impact of social engineering attacks. The evaluation of the cybersecurity risk assessment of an organisation is another key area of study reported in the literature that recommends the organisation of European and international standards in countering social engineering attacks. Lastly, the review includes articles reporting on national case studies with an overview of the economic and societal impact of service disruptions encountered due to cyberattacks. Discussion: One of the limitations of the review is the subjective ranking of the authors associated to the relevance of literature to each of the research questions identified. We also acknowledge the limited amount of literature that focuses on human factors of cybersecurity in health care in general; therefore, the search queries were formulated using well-established cybersecurity related topics categorised according to the threats, risk assessment and organisational strategies reported in the literature.


Subject(s)
Computer Security , Social Media , Delivery of Health Care , Hospitals , Humans
11.
BMC Cancer ; 16: 259, 2016 Mar 31.
Article in English | MEDLINE | ID: mdl-27036398

ABSTRACT

BACKGROUND: The non-canonical Wnt/Planar cell polarity (PCP) signaling pathway is a major player in cell migration during embryonal development and has recently been implicated in tumorigenesis. METHODS: Transfections with cDNA plasmids or siRNA were used to increase and suppress Prickle1 and Vangl2 expression in neuroblastoma cells and in non-tumorigenic cells. Cell viability was measured by trypan blue exclusion and protein expression was determined with western blotting. Transcriptional activity was studied with luciferase reporter assay and mRNA expression with real-time RT-PCR. Immunofluorescence stainings were used to study the effects of Vangl2 overexpression in non-tumorigenic embryonic cells. Statistical significance was tested with t-test or one-way ANOVA. RESULTS: Here we show that high expression of the PCP core genes Prickle1 and Vangl2 is associated with low-risk neuroblastoma, suppression of neuroblastoma cell growth and decreased Wnt/ß-catenin signaling. Inhibition of Rho-associated kinases (ROCKs) that are important in mediating non-canonical Wnt signaling resulted in increased expression of Prickle1 and inhibition of ß-catenin activity in neuroblastoma cells. In contrast, overexpression of Vangl2 in MYC immortalized neural stem cells induced accumulation of active ß-catenin and decreased the neural differentiation marker Tuj1. Similarly, genetically modified mice with forced overexpression of Vangl2 in nestin-positive cells showed decreased Tuj1 differentiation marker during embryonal development. CONCLUSIONS: Our experimental data demonstrate that high expression of Prickle1 and Vangl2 reduce the growth of neuroblastoma cells and indicate different roles of PCP proteins in tumorigenic cells compared to normal cells. These results suggest that the activity of the non-canonical Wnt/PCP signaling pathway is important for neuroblastoma development and that manipulation of the Wnt/PCP pathway provides a possible therapy for neuroblastoma.


Subject(s)
Carcinogenesis/genetics , Intracellular Signaling Peptides and Proteins/biosynthesis , LIM Domain Proteins/biosynthesis , Membrane Proteins/biosynthesis , Neuroblastoma/genetics , Tumor Suppressor Proteins/biosynthesis , Animals , Cell Movement/genetics , Cell Polarity/genetics , Cell Survival/genetics , Gene Expression Regulation, Neoplastic , Humans , Intracellular Signaling Peptides and Proteins/genetics , LIM Domain Proteins/genetics , Membrane Proteins/genetics , Mice , Neuroblastoma/pathology , Tumor Suppressor Proteins/genetics , Wnt Signaling Pathway/genetics , beta Catenin/genetics , rho-Associated Kinases/genetics
12.
Brain Res ; 1576: 27-34, 2014 Aug 12.
Article in English | MEDLINE | ID: mdl-24953933

ABSTRACT

Wnt/beta-catenin signaling plays an important role in neural development, instructing both progenitor cell division and differentiation. During early corticogenesis, Wnt7b is expressed in a restricted expression pattern in the ventricular zone progenitor cells. However, its influence on progenitor cell behavior has not been fully studied. We report that transgenic overexpression of Wnt7b in neural progenitor cells impairs neuronal differentiation and the development of forebrain structures at embryonic day 10.5 (E10.5). This was accompanied by a decreased expression of T-domain transcription factors Tbr1 and Tbr2, in both progenitor cells and post-mitotic neurons. However, proliferation, apoptosis and the overall proportion of pax6(+) neural progenitor cells were similar to wild-type litter mates. These results suggest that Wnt signaling may affect early neural progenitor differentiation by regulating the expression of pro-neural transcription factors.


Subject(s)
DNA-Binding Proteins/biosynthesis , Neurogenesis/physiology , Prosencephalon/metabolism , Proto-Oncogene Proteins/physiology , T-Box Domain Proteins/biosynthesis , Wnt Proteins/physiology , Animals , Cell Movement/physiology , Central Nervous System/embryology , Central Nervous System/metabolism , Cytoskeleton/ultrastructure , DNA-Binding Proteins/genetics , Down-Regulation , Enhancer Elements, Genetic/genetics , Genes, Synthetic , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , Microinjections , Nerve Tissue Proteins/analysis , Nerve Tissue Proteins/physiology , Nestin/genetics , Neural Stem Cells/metabolism , Neural Tube/ultrastructure , Neurons/metabolism , Prosencephalon/embryology , Proto-Oncogene Proteins/biosynthesis , Proto-Oncogene Proteins/genetics , T-Box Domain Proteins/genetics , Tubulin/analysis , Wnt Proteins/biosynthesis , Wnt Proteins/genetics , Zygote
13.
J Cell Sci ; 123(Pt 3): 472-83, 2010 Feb 01.
Article in English | MEDLINE | ID: mdl-20067994

ABSTRACT

The Wnt planar cell polarity (Wnt/PCP) pathway signals through small Rho-like GTPases to regulate the cytoskeleton. The core PCP proteins have been mapped to the Wnt/PCP pathway genetically, but the molecular mechanism of their action remains unknown. Here, we investigate the function of the mammalian PCP protein Vang-like protein 2 (Vangl2). RNAi knockdown of Vangl2 impaired cell-cell adhesion and cytoskeletal integrity in the epithelial cell lines HEK293T and MDCK. Similar effects were observed when Vangl2 was overexpressed in HEK293T, MDCK or C17.2 cells. The effects of Vangl2 overexpression could be blocked by knockdown of the small GTPase Rac1 or by dominant-negative Rac1. In itself, knockdown of Rac1 impaired cytoskeletal integrity and reduced cell-cell adhesion. We found that Vangl2 bound and re-distributed Rac1 within the cells but did not alter Rac1 activity. Moreover, both transgenic mouse embryos overexpressing Vangl2 in neural stem cells and loop-tail Vangl2 loss-of-function embryos displayed impaired adherens junctions, a cytoskeletal unit essential for neural tube rigidity and neural tube closure. In vivo, Rac1 was re-distributed within the cells in a similar way to that observed by us in vitro. We propose that Vangl2 affects cell adhesion and the cytoskeleton by recruiting Rac1 and targeting its activity in the cell to adherens junctions.


Subject(s)
Adherens Junctions/metabolism , Membrane Proteins/metabolism , rac1 GTP-Binding Protein/metabolism , Adherens Junctions/genetics , Animals , Cell Line , Dogs , Humans , Immunohistochemistry , Immunoprecipitation , In Situ Hybridization , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/genetics , Mice , Mice, Transgenic , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Protein Binding/genetics , Protein Binding/physiology , Reverse Transcriptase Polymerase Chain Reaction , rac1 GTP-Binding Protein/genetics
14.
Brain Res ; 1130(1): 67-72, 2007 Jan 26.
Article in English | MEDLINE | ID: mdl-17174942

ABSTRACT

Wnt7a and HA-tagged Wnt7a have previously been shown to promote or delay neuronal differentiation respectively. In this study, we show that embryonic days 9.5 and 10.5 transgenic mouse embryos overexpressing Wnt7a specifically in nestin-positive neural stem/progenitor cells displayed a delay in neuronal differentiation, assayed by beta-tubulin III expression. Our results corroborate previous studies using HA-Wnt7a, and suggest a critical role for Wnt7a in control of neuronal progenitor maturation.


Subject(s)
Gene Expression Regulation, Developmental/physiology , Neurons/metabolism , Proto-Oncogene Proteins/metabolism , Stem Cells/metabolism , Tubulin/metabolism , Wnt Proteins/metabolism , Animals , Brain/cytology , Brain/embryology , Brain/metabolism , Cell Differentiation , Intermediate Filament Proteins/metabolism , Mice , Mice, Transgenic , Nerve Tissue Proteins/metabolism , Nestin , Neurons/cytology , Proto-Oncogene Proteins/genetics , Stem Cells/cytology , Wnt Proteins/genetics
15.
Mol Cell Neurosci ; 30(3): 437-51, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16154760

ABSTRACT

Wnt7a has been reported to signal via the canonical pathway, but also in non-canonical pathways acting on the cytoskeleton. Since Wnt7a is expressed after neurulation, we set to investigate the effects of Wnt7a on brain regionalization. We engineered transgenic mouse embryos that, under control of the nestin second intron, overexpressed Wnt7a in neural stem/progenitor cells. Surprisingly, transgenic embryos failed to complete cranial neurulation due to reduced levels and an impaired distribution of actin microfilaments, beta-catenin, and N-cadherin at the neural tube adherens junctions. These transgenic embryos expressed high levels of Vangl2, an essential component of non-canonical Wnt signaling. In agreement with a disregulation of this pathway, aberrant spinal neurulation was detected in the transgenic embryos, revealing a novel function regulated by Wnts. Thus, our findings suggest that Wnt7a overexpression disrupts normal Wnt signaling in the neural tube, resulting in defective adherens junctions and neurulation.


Subject(s)
Adherens Junctions/metabolism , Central Nervous System/embryology , Central Nervous System/metabolism , Neurons/metabolism , Proto-Oncogene Proteins/metabolism , Stem Cells/metabolism , Wnt Proteins/metabolism , Actin Cytoskeleton/metabolism , Animals , Cadherins/metabolism , Cell Adhesion/genetics , Cell Communication/genetics , Cell Differentiation/genetics , Central Nervous System/cytology , Gene Expression Regulation, Developmental/genetics , Mice , Mice, Transgenic , Nerve Tissue Proteins/metabolism , Neural Tube Defects/genetics , Neural Tube Defects/metabolism , Neurons/cytology , Proto-Oncogene Proteins/genetics , Signal Transduction/physiology , Stem Cells/cytology , Up-Regulation/genetics , Wnt Proteins/genetics , beta Catenin/metabolism
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