Programs Promoting Virtual Social Connections and Friendships for Youth with Disabilities: A Scoping Review.

AIMS: This scoping review explores what is known about programs that support youth with physical and developmental disabilities to create virtual social connections as a means toward friendships. METHODS: Peer-reviewed studies were searched in six electronic databases: CINAHL, EMBASE, ERIC, MEDLINE, PsycINFO, and Scopus. Two reviewers screened articles that described programs in which participants, ages 8-20, interacted with others online, and reported outcomes related to virtual social connections and friendships in their personal social networks. Data extraction involved program characteristics (e.g., duration, group members, online platform) plus qualitative description outlining access and participation experiences. RESULTS: After screening 12,605 articles, 9 were determined eligible. Programs followed two approaches: (1) training youth to use the internet and technology to access virtual spaces independently; and (2) designing virtual opportunities and activities that encourage youth interaction and collaboration. Each approach was grounded in the principles of fostering privacy and independence (i.e., socializing with peers without relying on caregivers), safety and self-expression (i.e., communicating authentically), plus confidence and capability (i.e., trying new skills). CONCLUSIONS: This scoping review provides guidance on enhancing access and participation of youth with disabilities in virtual spaces where they can develop social connections that increase chances for friendships.

'I Didn't Know What to Expect': Describing Parents' Expectations in Children's Rehabilitation Services.

Aims: The aim of this paper is to provide a holistic description of the nature, formation and impact of parents' therapy related expectations.Methods: This qualitative descriptive study drew from initial and follow up interviews with 20 parents of children ≤ 6 years who had a developmental disability or delay and used therapy services at a children's treatment center in Ontario, Canada. Conventional content analysis was used to inductively generate themes and investigator triangulation was completed.Results: Parent's child related expectations focused on whether the child would receive a diagnosis and what they might achieve. Parents held expectations about the availability of service and how it would be offered. Parents' expectations of service providers included their knowledge, skills, relationships and communication with the children and parents. Parents held expectations of themselves related to attendance and roles in therapy sessions and home practice. These expectations are described according to how they are shaped and changed them over time. The impact of matched/mismatched expectations is explored.Conclusion: Service providers can improve family-centred care and collaboration with parents by explicitly discussing parents' expectations when beginning, and throughout, therapy. Parent satisfaction and therapy engagement may improve if parents and service providers negotiate and agree upon expectations.

Generating Expectations: What Pediatric Rehabilitation Can Learn From Mental Health Literature.

Family-Centered Care (FCC) represents the ideal service delivery approach in pediatric rehabilitation. Nonetheless, implementing FCC as intended in clinical settings continues to be hindered by knowledge gaps. One overlooked gap is our understanding of clients' therapy expectations. This perspective article synthesizes knowledge from the mental health services literature on strategies recommended to service providers for generating transparent and congruent therapy expectations with clients, and applies this knowledge to the pediatric rehabilitation literature, where this topic has been researched significantly less, for the purpose of improving FCC implementation. Dimensions of the Measure of Processes of Care, an assessment tool that measures clients' perceptions of the extent a service is family-centered, inform the organization of therapy expectation-generating strategies: (1) Providing Respectful and Supportive Care (assessing and validating clients' expectations); (2) General and Specific Information (foreshadowing therapy journeys, explaining treatment rationale, and conveying service provider qualifications); (3) Coordinated and Comprehensive Care (socializing clients to roles and reflecting on past socialization); and (4) Enabling and Partnership (applying a negotiation framework and fostering spaces safe to critique). Strategies can help pediatric rehabilitation service providers work with families to reframe unrealistic expectations, establish congruent beliefs supporting effective partnerships, and prevent possible disillusionment with therapy over time.

Facilitating virtual social connections for youth with disabilities: lessons for post-COVID-19 programming.

PURPOSE: Social connections are essential for the development of life skills for youth. Youth with disabilities have long faced barriers to meaningful social connections. The onset of COVID-19 increased barriers to social connections for all youth, and also led to enhanced use of virtual platforms in paediatric rehabilitation programming. Harnessing this opportunity, service providers created a suite of online programs to foster social connections and friendships. The current study explores participant and service provider experiences of such programs. METHODS: This qualitative descriptive study used interviews and focus groups to explore how youth with disabilities (n = 8), their parents (n = 7), and service providers (n = 13) involved in program development and delivery experienced the programs, the accessibility of the virtual platforms, and their social connections in relation to program participation. RESULTS: Participants were satisfied with the programs' content, accessibility and ability to meet their social needs. Qualitative themes included facilitating social connections, accessibility of virtual spaces, and recommendations for future virtual programming. DISCUSSION: For youth with disabilities who have been historically marginalized in social spheres, the newly ubiquitous infrastructure regarding virtual programming must be supported and enhanced. A hybrid approach involving virtual/in-person options in future programming is recommended.

Youth with disabilities can benefit from social connections on virtual platforms in terms of physical access to social spaces and opportunities to communicate in alternative waysFor some youth with disabilities, virtual social connections can be the only feasible and readily available option for reducing social isolation due to physical barriers to accessWhen offering virtual program options, service providers should consider the various benefits of connecting with the physical, communication-based, interaction-based, access-based and other barriers to virtual connection.

Social participation interventions targeting relational outcomes for young people with physical and developmental disabilities: an umbrella review and narrative synthesis.

PURPOSE: To synthesize knowledge about social participation interventions targeting relational outcomes for young people with physical and developmental disabilities. METHOD: An umbrella review with a narrative synthesis was conducted to integrate findings of review articles examining social participation interventions targeting relational outcomes (e.g., peer interaction and friendships). Six databases were searched to identify reviews published between 2010 and 2021. RESULTS: Five reviews were identified, examining participation interventions, social/community integration interventions, recreational sport programs, online peer mentorship programs, and augmentative and alternative communication interventions to promote social interaction with peers. Interventions associated with improvements in relational outcomes included group-based programs, programs involving personalized goals, arts-based programs, and multi-component social communication interventions. Recommendations for future research included better description of interventions to identify active ingredients and key mechanisms, measurement of participants' experiences, and the need for interventions to be aligned with the nature of the outcomes examined. Preliminary intervention principles are proposed to guide the design of social participation interventions: individualizing, contextualizing, and immersion in social settings. CONCLUSIONS: There are multiple pathways by which to influence the relational outcomes of young people with disabilities. There are implications for the design of social participation interventions based on an ecological/experiential and relational perspective. IMPLICATIONS FOR REHABILITATIONImprovements in relational outcomes are associated with participation in group-based programs, programs involving personalized goals, arts-based programs, and multi-component social communication interventions.Three evidence-informed principles can help guide the design of social participation interventions: (1) personalizing, (2) contextualizing, and (3) immersion in social settings.Greater attention to aligning the nature of intervention with desired outcomes is needed to more effectively measure and promote relational outcomes.

"What their expectations could be": a narrative study of mothers and service providers in paediatric rehabilitation.

PURPOSE: To better understand and visualise how and why mothers' and service providers' expectations for therapy can change over time spanning their journeys and careers in the paediatric rehabilitation system. METHODS: Narrative analysis was used to construct two parallel collective stories that illustrate and explain phases and turning points of developing expectations. Five mothers and nine service providers participated in interviews discussing their expectations when new and more experienced with therapy. RESULTS: Each collective story had five chapters illustrating how expectations became more relational, controllable, and informed. For mothers, the chapters were: (1) expecting therapy to be a saviour; (2) being turned away and alone; (3) expecting to advocate from necessity; (4) finding new solutions in the environment; and (5) expecting to combine mother and service provider expertise. For service providers, the chapters were: (1) expecting to rescue and fix; (2) searching for an alternative sense of professional worth; (3) expecting to lose control; (4) being the authentic self before expected self; and (5) expecting the unexpected. CONCLUSIONS: Mothers' experiences with feeling alone and learning ways to modify their child's environments, and service providers' experiences with feeling inadequate and embracing authenticity, were essential to the developmental trajectories of expectations.Implications for Rehabilitation:Mapping expectations for therapy on a line graph shaped as a wave shows promise in reflecting the developmental trajectory of mothers' and service providers' expectations over time.Service providers should become aware of how to work with three distinct groups of mothers as determined by the phase of expectations for therapy they are currently experiencing (i.e., hyped, disillusioned, or enlightened).Therapy programmes can optimise expectations for therapy through redesigns that emphasise elements of networking, self-compassion, ethics, and authenticity.

Negotiating expectations for therapy between mothers and service providers: a narrative analysis.

PURPOSE: To use stories about mothers and service providers negotiating expectations for therapy to illuminate processes contributing to power differences within partnerships. METHODS: This narrative study presented stories from three mothers and three service providers. Stories were co-constructed between participants and researchers and analyzed using narrative analysis. Building on An and Palisano's (2014) Model of Family-Professional Collaboration, stories were organized into the stages of goal setting, planning, and doing therapy. RESULTS: Each story illuminated a process unique to that story that can redistribute power between mothers, service providers, and therapy environments while negotiating expectations: protecting sacred issues, facilitating knowledge exposure, filling voids/vacuums, recognizing cultural conditioning, re-discovering eclipsed roles, and connecting relay teams. We propose including three additional strategies to An and Palisano's model to increase the readiness of mothers and service providers to negotiate expectations for therapy and collaborate fully as the model intends: 1) exploring power-sharing conversations; 2) looking for social context clues; and 3) adopting a humility stance. CONCLUSION: Information on the six illuminated processes can help structure a client story grounded in optimal negotiation of expectations and equal partnerships.Implications for RehabilitationKnowledge of diverse stories about mothers and service providers negotiating expectations for therapy can be a resource to guide actions in related situations.Leaving the topic of expectations for therapy implicit or unchallenged increases the risks that negotiations remain unbalanced and unproductive.Service providers may enhance collaboration with mothers in paediatric rehabilitation by exploring power-sharing conversations, looking for social context clues, and adopting a humility stance.

Lipid rafts, caveolae and GPI-linked proteins.

Lipid rafts and caveolae are specialized membrane microdomains enriched in sphingolipids and cholesterol. They function in a variety of cellular processes including but not limited to endocytosis, transcytosis, signal transduction and receptor recycling. Here, we outline the similarities and differences between lipid rafts and caveolae as well as discuss important components and functions of each.

Expectations for therapy in pediatric rehabilitation: reframing meaning through metaphor.

PURPOSE: To propose a holistic approach and an accompanying tool to facilitate conversations about expectations of therapy in pediatric rehabilitation based on meanings generated through metaphor. METHODS: In this study, five parents and nine service providers took part in narrative interviews. Topics included the content and development of expectations over time. Participants reviewed written summaries of their interviews and provided feedback. Data analysis was grounded in a narrative methodological approach. Multiple levels of meaning from participant experiences were constructed through a parallel thematic analysis and metaphor analysis, revealing meaning participants attributed to expectations directly, and inferred indirectly. RESULTS: The thematic analysis produced three themes related to the difficult to define characteristics and mixed value of expectations. The metaphor analysis produced four metaphorical concepts related to how expectations affect the therapy process by adding a sense of Force (i.e., therapy momentum), Appreciation (i.e., understanding of the client), Illumination (i.e., envisioning new therapy activities), and Relationship (i.e., therapeutic rapport). CONCLUSIONS: We propose the "F.A.I.R." approach and tool comprising terminology that can help reframe the meaning of expectations away from focusing on binary realistic or unrealistic outcomes, and toward focusing on a plurality of optimal therapy processes.Implications for RehabilitationMeaningful conversations about expectations for therapy between parents and service providers in pediatric rehabilitation can be challenging, one-sided, or missed.Attention to metaphors used to describe expectations for therapy introduces additional terminology parents and service providers may use to help facilitate conversations.Service providers are encouraged to use a resource proposed here to learn about parents' expectations for therapy through a collaborative process involving shared questioning, observation, and reflection.

The complexities and synergies of engagement: an ethnographic study of engagement in outpatient pediatric rehabilitation sessions.

PURPOSE: To investigate client (youth/caregiver) and service provider engagement in outpatient pediatric rehabilitation therapy sessions. METHODS: In an ethnographic study, five research assistants attended 28 outpatient sessions, mostly delivered by occupational, physical, and speech-language therapists, and rated signs of client, provider, and relational engagement using the Pediatric Rehabilitation Intervention Measure of Engagement - Observation version. Post-session interviews were conducted individually with 13 youth, 15 caregivers, and 26 providers. RESULTS: Overall, there was a moderate to great extent of engagement. Provider engagement was rated as higher than client engagement, particularly in sessions with activities focusing on body structure/function. The interviews indicated associations among engagement-related constructs: (a) expectations influenced engagement/disengagement and therapy progress, (b) engagement was associated with positive affect and relationships, and (c) engagement was strongly associated with relationships and collaboration. CONCLUSIONS: Engagement is a central process within a complex system of psychosocial constructs operating in therapy. Engagement is emergent, synergistic, and change-inducing - it emanates from, involves, and influences multiple aspects of therapy. Notably, engagement ties two pivotal elements - positive expectations and positive affect - to positive relationships, collaboration, and therapy progress. Implications for practice include an understanding of how providers manage the therapeutic context and work to foster engagement.Implications for rehabilitationEngagement, and its various elements, plays a central role in shaping how clients, parents, and clinicians value therapeutic encounters.Optimal therapy is often thought to include engagement, relationships, and collaboration; the importance of therapy expectations, positive affect, and perceptions of progress are frequently overlooked.Engagement and motivation may be maximized when youth and caregivers are asked explicitly about how they view their engagement in therapy.In addition to clarifying and aligning expectations with youth and caregivers, service providers can enhance engagement and motivation by intentionally creating enjoyable and meaningful interactions, developing relationships, negotiating consensus on goals and plans, and demonstrating therapy progress.Service providers can harness engagement and the system of related constructs by listening and communicating effectively, by entering the world of the client and family, and by being aware of, anticipating, and responding to engagement and disengagement.

Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic endothelial cells isolated from caveolin-1 deficient mice.

Exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), is a risk factor for the development of cardiovascular diseases such as atherosclerosis. Vascular cell adhesion molecule-1 (VCAM-1) is a critical mediator for adhesion and uptake of monocytes across the endothelium in the early stages of atherosclerosis development. The upregulation of VCAM-1 by PCBs may be dependent on functional membrane domains called caveolae. Caveolae are particularly abundant in endothelial cell membranes and involved in trafficking and signal transduction. The objective of this study was to investigate the role of caveolae in PCB-induced endothelial cell dysfunction. Primary mouse aortic endothelial cells (MAECs) isolated from caveolin-1-deficient mice and background C57BL/6 mice were treated with coplanar PCBs, such as PCB77 and PCB126. In addition, siRNA gene silencing technique was used to knockdown caveolin-1 in porcine vascular endothelial cells. In MAECs with functional caveolae, VCAM-1 protein levels were increased after exposure to both coplanar PCBs, whereas expression levels of VCAM-1 were not significantly altered in cells deficient of caveolin-1. Furthermore, PCB-induced monocyte adhesion was attenuated in caveolin-1-deficient MAECs. Similarly, siRNA silencing of caveolin-1 in porcine endothelial cells confirmed the caveolin-1-dependent VCAM-1 expression. Treatment of cells with PCB77 and PCB126 resulted in phosphorylation of extracellular signal-regulated kinase-1/2 (ERK1/2), and pharmacological inhibition of ERK1/2 diminished the observed PCB-induced increase in monocyte adhesion. These findings suggest that coplanar PCBs induce adhesion molecule expression, such as VCAM-1, in endothelial cells, and that this response is regulated by caveolin-1 and functional caveolae. Our data demonstrate a critical role of functional caveolae in the activation and dysfunction of endothelial cells by coplanar PCBs.

Thiol oxidative stress induced by metabolic disorders amplifies macrophage chemotactic responses and accelerates atherogenesis and kidney injury in LDL receptor-deficient mice.

BACKGROUND: Strengthening the macrophage glutathione redox buffer reduces macrophage content and decreases the severity of atherosclerotic lesions in LDL receptor-deficient (LDLR(-/-)) mice, but the underlying mechanisms were not clear. This study examined the effect of metabolic stress on the thiol redox state, chemotactic activity in vivo, and the recruitment of macrophages into atherosclerotic lesions and kidneys of LDL-R(-/-) mice in response to mild, moderate, and severe metabolic stress. METHODS AND RESULTS: Reduced glutathione (GSH) and glutathione disulfide (GSSG) levels in peritoneal macrophages isolated from mildly, moderately, and severe metabolically-stressed LDL-R(-/-) mice were measured by HPLC, and the glutathione reduction potential (E(h)) was calculated. Macrophage E(h) correlated with the macrophage content in both atherosclerotic (r(2)=0.346, P=0.004) and renal lesions (r(2)=0.480, P=0.001) in these mice as well as the extent of both atherosclerosis (r(2)=0.414, P=0.001) and kidney injury (r(2)=0.480, P=0.001). Compared to LDL-R(-/-) mice exposed to mild metabolic stress, macrophage recruitment into MCP-1-loaded Matrigel plugs injected into LDL-R(-/-) mice increased 2.6-fold in moderately metabolically-stressed mice and 9.8-fold in severely metabolically-stressed mice. The macrophage E(h) was a strong predictor of macrophage chemotaxis (r(2)=0.554, P<0.001). CONCLUSIONS: Thiol oxidative stress enhances macrophage recruitment into vascular and renal lesions by increasing the responsiveness of macrophages to chemoattractants. This novel mechanism contributes at least in part to accelerated atherosclerosis and kidney injury associated with dyslipidemia and diabetes in mice.

Performance and visual arts-based programs for children with disabilities: a scoping review focusing on psychosocial outcomes.

Purpose: There is a growing movement in pediatric rehabilitation to understand how approaches addressing aspects beyond body function contribute to enhanced psychosocial well-being. Among such approaches is the use of creative arts. A scoping review was undertaken to synthesize the current literature on performance and visual arts-based programs and outcomes for children with disabilities.Methods: Data sources included CINAHL, MEDLINE, and PsycINFO. Eligible articles described programs involving performing or visual art activities in community and ambulatory care settings, delivered to children between 6 and 18 years with physical or developmental disabilities, and reported on at least one psychosocial outcome. Domains of interest included emotional, social, behavioral, physical, cognitive, and/or communicative functioning, which are known to impact well-being and participation. No limits were applied to study design.Results: Twelve articles using primarily case study and quasi-experimental designs were identified, encompassing an 11-year period. Most programs focused on theater as the central modality. A majority of papers addressed changes in physical, cognitive, and communicative function (n = 8), followed by social function (n = 6), emotional function (n = 5), and finally, behavioral function (n = 3). Across individual papers, diverse study designs, measures, and outcomes were examined with positive qualitative and/or quantitative findings noted across all domains.Conclusions: Within an emerging evidence base, arts-based programs show potential to positively impact psychosocial well-being and warrant further investigation with broader populations of children with physical and developmental disabilities. A greater emphasis on programmatic approaches and enhanced methodological rigor to establishing benefits is needed to advance understanding.Implications for rehabilitationPediatric therapists may wish to consider recommending arts-based programs for children with ASD, TBI, and other developmental disabilities given their potential in achieving psychosocial outcomesArts-based programs in rehabilitation provide creative ideas (e.g., drawing, painting) and techniques (e.g., modeling, role-play), which may be incorporated into individualized or group-based therapy to promote psychosocial well-beingProgram evaluators and researchers are encouraged to adopt a programmatic approach to further explore how art activities facilitate psychosocial outcomes.

The Nature, Value, and Experience of Engagement in Pediatric Rehabilitation: Perspectives of Youth, Caregivers, and Service Providers.

Purpose: To conduct a qualitative investigation of engagement in pediatric rehabilitation therapy.Methods: Interviews were conducted with 10 youth, 10 caregivers, and 10 service providers. Transcripts were analyzed thematically using an inductive approach.Results: Themes illustrated three perspectives: engagement as a connection with components of the therapy process, engagement as working together, and engagement as an affective and motivational process. Engagement created valued connections with therapy components and forward momentum for therapy.Conclusions: The themes supported a view of engagement as complex, transactional, and multidimensional. Participants focused on different, yet not discrepant, aspects of engagement. Youth focused on having fun and personal connection with service providers. Caregivers provided a more complex perspective encompassing both their own and their child's engagement, with an emphasis on relationship, understanding what is taking place, and feeling valued in the process. Service providers highlighted goal attainment and the value of engagement in bringing about outcomes.

Caveolin-1 regulates human immunodeficiency virus-1 Tat-induced alterations of tight junction protein expression via modulation of the Ras signaling.

The blood-brain barrier (BBB) is the critical structure for preventing human immunodeficiency virus (HIV) trafficking into the brain. Specific HIV proteins, such as Tat protein, can contribute to the dysfunction of tight junctions at the BBB and HIV entry into the brain. Tat is released by HIV-1-infected cells and can interact with a variety of cell surface receptors activating several signal transduction pathways, including those localized in caveolae. The present study focused on the mechanisms of Tat-induced caveolae-associated Ras signaling at the level of the BBB. Treatment with Tat activated the Ras pathway in human brain microvascular endothelial cells (HBMECs). However, caveolin-1 silencing markedly attenuated these effects. Because the integrity of the brain endothelium is regulated by intercellular tight junctions, these structural elements of the BBB were also evaluated in the present study. Exposure to Tat diminished the expression of several tight junction proteins, namely, occludin, zonula occludens (ZO)-1, and ZO-2 in the caveolar fraction of HBMECs. These effects were effectively protected by pharmacological inhibition of the Ras signaling and by silencing of caveolin-1. The present data indicate the importance of caveolae-associated signaling in the disruption of tight junctions on Tat exposure. They also demonstrate that caveolin-1 may constitute an early and critical modulator that controls signaling pathways leading to the disruption of tight junction proteins. Thus, caveolin-1 may provide an effective target to protect against Tat-induced HBMEC dysfunction and the disruption of the BBB in HIV-1-infected patients.

Up-regulation of endothelial monocyte chemoattractant protein-1 by coplanar PCB77 is caveolin-1-dependent.

Atherosclerosis, the primary cause of heart disease and stroke is initiated in the vascular endothelium, and risk factors for its development include environmental exposure to persistent organic pollutants. Caveolae are membrane microdomains involved in regulation of many signaling pathways, and in particular in endothelial cells. We tested the hypothesis that intact caveolae are required for coplanar PCB77-induced up-regulation of monocyte chemoattractant protein-1 (MCP-1), an endothelium-derived chemokine that attracts monocytes into sub-endothelial space in early stages of the atherosclerosis development. Atherosclerosis-prone LDL-R(-/-) mice (control) or caveolin-1(-/-)/LDL-R(-/-) mice were treated with PCB77. PCB77 induced aortic mRNA expression and plasma protein levels of MCP-1 in control, but not caveolin-1(-/-)/LDL-R(-/-) mice. To study the mechanism of this effect, primary endothelial cells were used. PCB77 increased MCP-1 levels in endothelial cells in a time- and concentration-dependent manner. This effect was abolished by caveolin-1 silencing using siRNA. Also, MCP-1 up-regulation by PCB77 was prevented by inhibiting p38 and c-Jun N-terminal kinase (JNK), but not ERK1/2, suggesting regulatory functions via p38 and JNK MAPK pathways. Finally, pre-treatment of endothelial cells with the aryl hydrocarbon receptor (AhR) inhibitor alpha-naphthoflavone (alpha-NF) partially blocked MCP-1 up-regulation. Thus, our data demonstrate that coplanar PCB77 can induce MCP-1 expression by endothelial cells and that this effect is mediated by AhR, as well as p 38 and JNK MAPK pathways. Intact caveolae are required for these processes both in vivo and in vitro. This further supports a key role for caveolae in vascular inflammation induced by persistent organic pollutants.

Salt inactivates endothelial nitric oxide synthase in endothelial cells.

There is a 1-4 mmol/L rise in plasma sodium concentrations in individuals with high salt intake and in patients with essential hypertension. In this study, we used 3 independent assays to determine whether such a small increase in sodium concentrations per se alters endothelial nitric oxide synthase (eNOS) function and contributes to hypertension. By directly measuring NOS activity in living bovine aortic endothelial cells, we demonstrated that a 5-mmol/L increase in salt concentration (from 137 to 142 mmol/L) caused a 25% decrease in NOS activity. Importantly, the decrease in NOS activity was in a salt concentration-dependent manner. The NOS activity was decreased by 25, 45, and 70%, with the increase of 5, 10, and 20 mmol/L of NaCl, respectively. Using Chinese hamster ovary cells stably expressing eNOS, we confirmed the inhibitory effects of salt on eNOS activity. The eNOS activity was unaffected in the presence of equal milliosmol of mannitol, which excludes an osmotic effect. Using an ex vivo aortic angiogenesis assay, we demonstrated that salt attenuated the nitric oxide (NO)-dependent proliferation of endothelial cells. By directly monitoring blood pressure changes in response to salt infusion, we found that in vivo infusion of salt induced an acute increase in blood pressure in a salt concentration-dependent manner. In conclusion, our findings demonstrated that eNOS is sensitive to changes in salt concentration. A 5-mmol/L rise in salt concentration, within the range observed in essential hypertension patients or in individuals with high salt intake, could significantly suppress eNOS activity. This salt-induced reduction in NO generation in endothelial cells may contribute to the development of hypertension.

Role of caveolin-1 in EGCG-mediated protection against linoleic-acid-induced endothelial cell activation.

Flavonoids can protect against inflammatory diseases such as atherosclerosis by decreasing vascular endothelial cell activation. Plasma microdomains called caveolae may be critical in regulating endothelial activation. Caveolae are particularly abundant in endothelial cells and play a major role in endothelial trafficking and the regulation of signaling pathways associated with the pathology of vascular diseases. We hypothesize that flavonoids can down-regulate endothelial inflammatory parameters by modulating caveolae-regulated cell signaling. We focused on the role of caveolae and its major protein, caveolin-1, in mechanisms of linoleic-acid-induced endothelial cell activation and protection by the catechin epigallocatechin-3-gallate (EGCG). Exposure to linoleic acid for 6 h induced expression of both caveolin-1 and cyclooxygenase (COX)-2. Pretreatment with EGCG blocked fatty-acid-induced caveolin-1 and COX-2 expression in a time- and concentration-dependent manner. Similar results were observed with nuclear factor-kappa B DNA binding activity, which was also reduced by caveolin-1 silencing. Exposure to linoleic acid rapidly increased phosphorylation of several kinases, including p38 MAPK, extracellular signal regulated kinase 1/2 (ERK1/2) and amino kinase terminal (Akt), with maximal induction at about 10 min. Inhibitors of ERK1/2 and Akt down-regulated the linoleic-acid-induced increase in COX-2 protein, which also occurred after pretreatment with EGCG. Caveolin-1 silencing blocked linoleic-acid-induced phosphorylation of ERK1/2 and protein expression of COX-2, suggesting that specific MAPK signaling is caveolae dependent. Our data provide evidence that caveolae may play a critical role in regulating vascular endothelial cell activation and protection by flavonoids such as EGCG.

Glucagon-like peptide 1 and pancreatic polypeptide responses to feeding in normal weight and overweight children.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) and pancreatic polypeptide (PP) are intestinal hormones that are involved in the post-prandial satiety response. We sought to assess meal-related changes in these hormones in young children and determine whether differences exist between normal weight (NW) and overweight (OW) children. METHODS: Seven to 11-year-old healthy NW (n=20) and OW (n=12) volunteers were given a standardized breakfast and lunch following an overnight fast and had measurements of GLP-1 and PP over 9 hours. We characterized whether GLP-1 and PP changed from the pre-prandial to the post-prandial state and whether the serum levels corresponded to reported appetite. RESULTS: GLP-1 did not increase after eating, did not decline prior to the next meal, and did not correspond to satiety ratings in either group. PP increased post-prandially in OW children after both breakfast and lunch, but in the NW group PP only increased after breakfast. PP levels did not decline in either group as the next meal approached. CONCLUSIONS: In our study of school-age children, feeding had little effect on GLP-1 secretion and a variable effect on serum PP levels. Observed differences in the GLP-1 and PP responses between the NW and OW groups do not suggest there is an intrinsic abnormality in their secretion that causes weight gain.