Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1.

BACKGROUND: Narcolepsy type 1 is caused by severe loss or lack of brain orexin neuropeptides. METHODS: We conducted a phase 2, randomized, placebo-controlled trial of TAK-994, an oral orexin receptor 2-selective agonist, in patients with narcolepsy type 1. Patients with confirmed narcolepsy type 1 according to clinical criteria were randomly assigned to receive twice-daily oral TAK-994 (30 mg, 90 mg, or 180 mg) or placebo. The primary end point was the mean change from baseline to week 8 in average sleep latency (the time it takes to fall asleep) on the Maintenance of Wakefulness Test (range, 0 to 40 minutes; normal ability to stay awake, ≥20 minutes). Secondary end points included the change in the Epworth Sleepiness Scale (ESS) score (range, 0 to 24, with higher scores indicating greater daytime sleepiness; normal, <10) and the weekly cataplexy rate. RESULTS: Of the 73 patients, 17 received TAK-994 at a dose of 30 mg twice daily, 20 received 90 mg twice daily, 19 received 180 mg twice daily, and 17 received placebo. The phase 2 trial and an extension trial were terminated early owing to hepatic adverse events. Primary end-point data were available for 41 patients (56%); the main reason for missing data was early trial termination. Least-squares mean changes to week 8 in average sleep latency on the MWT were 23.9 minutes in the 30-mg group, 27.4 minutes in the 90-mg group, 32.6 minutes in the 180-mg group, and -2.5 minutes in the placebo group (difference vs. placebo, 26.4 minutes in the 30-mg group, 29.9 minutes in the 90-mg group, and 35.0 minutes the 180-mg group; P<0.001 for all comparisons). Least-squares mean changes to week 8 in the ESS score were -12.2 in the 30-mg group, -13.5 in the 90-mg group, -15.1 in the 180-mg group, and -2.1 in the placebo group (difference vs. placebo, -10.1 in the 30-mg group, -11.4 in the 90-mg group, and -13.0 in the 180-mg group). Weekly incidences of cataplexy at week 8 were 0.27 in the 30-mg group, 1.14 in the 90-mg group, 0.88 in the 180-mg group, and 5.83 in the placebo group (rate ratio vs. placebo, 0.05 in the 30-mg group, 0.20 in the 90-mg group, and 0.15 in the 180-mg group). A total of 44 of 56 patients (79%) receiving TAK-994 had adverse events, most commonly urinary urgency or frequency. Clinically important elevations in liver-enzyme levels occurred in 5 patients, and drug-induced liver injury meeting Hy's law criteria occurred in 3 patients. CONCLUSIONS: In a phase 2 trial involving patients with narcolepsy type 1, an orexin receptor 2 agonist resulted in greater improvements on measures of sleepiness and cataplexy than placebo over a period of 8 weeks but was associated with hepatotoxic effects. (Funded by Takeda Development Center Americas; TAK-994-1501 and TAK-994-1504 ClinicalTrials.gov numbers, NCT04096560 and NCT04820842.).

Disseminated Tuberculosis with Cutaneous Findings in an Immunocompetent Patient: A Case Report.

BACKGROUND: Tuberculosis (TB) is one of the leading causes of infectious disease, and emergency medicine providers are often the first physicians to encounter patients with untreated or undiagnosed disease. CASE REPORT: We present the case of a 30-year old man with disseminated TB with multiple musculoskeletal and subcutaneous tubercular abscesses. The diagnosis was suspected in the Emergency Department, but his inpatient treatment was complicated by various social issues. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights uncommon examination findings of TB and illustrates the importance of considering this disease when treating patients who present with atypical manifestations of it.

The co-design of an online support programme with and for informal carers of people with heart failure: A methodological paper.

AIM: To describe the co-designing process of an online support programme with and for informal carers of people with heart failure. DESIGN: A co-design process built on core concepts and ideas embedded in co-design methodology. DATA SOURCES: Our co-design process included three phases involving 32 informal caregivers and 25 content creators; (1) Identification of topics and content through literature searches, focus group interviews and user group sessions; (2) Development of the online support programme and; (3) Refinement and finalization which included testing a paper prototype followed by testing the online version and testing and approval of the final version of the support programme. OUTCOMES: The co-design process resulted in a support programme consisting of 15 different modules relevant to informal carers, delivered on a National Health Portal. CONCLUSION: Co-design is an explorative process where researchers need to balance a range of potentially conflicting factors and to ensure that the end users are genuinely included in the process. RELEVANCE TO CLINICAL PRACTICE: Emphasizing equal involvement of end users (e.g. carers or patients) in the design and development of healthcare interventions aligns with contemporary ideas of person-centred care and provides a valuable learning opportunity for those involved. Furthermore, a co-designed online support programme has the capacity to be both accessible and meet end users' information and support needs, thereby optimizing their self-care abilities. Additionally, an online support programme provides the opportunity to address current challenges regarding scarce resources and the lack of healthcare personnel. REPORTING METHODS: Consolidated criteria for reporting qualitative research (COREQ). PATIENT OR PUBLIC CONTRIBUTION: Both informal carers and content creators were involved in developing the support programme.

A balance between putting on the researcher's hat and being a fellow human being: a researcher perspective on informal carer involvement in health and social care research.

BACKGROUND: Public involvement in health and social care research is increasingly prioritized by policy-makers and research funders. Often, the impact of the involvement is described in terms of how it has contributed to the research outcomes and how it has affected the involved members of the public. There is a dearth of studies reporting from the perspective of researchers themselves of having involved members of the public in their research. Nevertheless, there is a general expectation for researchers to accept and embrace public involvement in research. This study aims to explore researchers' views of involving informal carers in health and social care research. METHODS: Eleven individual in-depth interviews with researchers in the fields of social work, caring science, health science and medical science constituted the dataset of this qualitative study, inspired by discourse psychology. RESULTS: The qualitative data analysis resulted in two interpretative repertoires describing researchers' views of involving informal carers in research, "Philosophy of Science" and "Personal relationships and growth". Both repertoires need to be recognized; however, as of today, the Philosophy of Science repertoire is more acknowledged, while the second repertoire describing empathy, relationships and emotions may be viewed as the researcher being "unprofessional". Further, the findings highlighted the dual perspective of being a researcher and a carer as creating opportunities for growth on the part of the researcher, on both a professional and a personal level. CONCLUSIONS: Researchers and their research work would benefit from acknowledging, discussing and reporting both interpretative repertoires in their publications, as well as recognizing the benefit of dialectal positions, for example, having a dual perspective as both a researcher and an informal carer.

To teach or not to teach? Assessing medical school faculty motivation to teach in the era of curriculum reform.

BACKGROUND: Medical schools have undergone a period of continual curricular change in recent years, particularly with regard to pre-clinical education. While these changes have many benefits for students, the impact on faculty is less clear. METHODS: In this study, faculty motivation to teach in the pre-clinical medical curriculum was examined using self-determination theory (SDT) as a framework. Basic science and clinical faculty were surveyed on factors impacting their motivation to teach using validated scales of motivation as well as open-ended questions which were coded using self-determination theory (SDT) as a guiding framework. RESULTS: Faculty reported that teaching activities often meet their basic psychological needs of competence, autonomy, and relatedness. Professors were more likely than associate professors to report that teaching met their need for autonomy. Faculty were more motivated by intrinsic as compared to external factors, although basic science faculty were more likely than clinical faculty to be motivated by external factors. Motivating and de-motivating factors fell into the themes Resources, Recognition and Rewards, Student Factors, Self-Efficacy, Curriculum, Contribution, and Enjoyment. The majority of factors tied to the faculty's need for relatedness. Based on these findings, a conceptual model for understanding medical school faculty motivation to teach was developed. CONCLUSIONS: Assessing faculty motivation to teach provided valuable insights into how faculty relate to their teaching roles and what factors influence them to continue in those roles. This information may be useful in guiding future faculty development and research efforts.

A comparison of spouse and non-spouse carers of people with dementia: a descriptive analysis of Swedish national survey data.

BACKGROUND: Being an informal carer of a person with dementia (PwD) can have a negative effect on the carer's health and quality of life, and spouse carers have been found to be especially vulnerable. Yet relatively little is known about the care provided and support received by spouse carers. This study compares spouse carers to other informal carers of PwDs regarding their care provision, the support received and the psychosocial impact of care. METHODS: The study was a cross-sectional questionnaire-based survey of a stratified random sample of the Swedish population aged 18 or over. The questionnaire explored how much care the respondent provided, the support received, and the psychosocial impact of providing care. Of 30,009 people sampled, 11,168 (37.7 %) responded, of whom 330 (2.95 %) were informal carers of a PwD. RESULTS: In comparison to non-spouse carers, spouse carers provided more care more frequently, did so with less support from family or the local authority, while more frequently experiencing negative impacts on their social life and psychological and physical health. Spouse carers also received more carer support and more frequently experienced a closeness in their relationship with the care-recipient. CONCLUSIONS: Spouse carers of PwD differed from non-spouse carers on virtually all aspects of their care situation. Policy and practice must be more sensitive to how the carer-care-recipient relationship shapes the experience of care, so that support is based on an understanding of the individual carer's actual needs and preferences rather than on preconceptions drawn from a generalised support model.

Cost analysis of informal care: estimates from a national cross-sectional survey in Sweden.

BACKGROUND: Over the past decades, informal care has increased in most OECD-countries. Informal care is costly to caregivers and to society in the form of lost income and direct costs of providing care. Existing evidence suggests that providing informal care affects caregivers' overall health. However, estimates of the social costs of informal care based on national data on individuals are currently scarce. OBJECTIVE: This study contributes to the existing evidence on the costs of informal care by estimating the direct and indirect costs to caregivers using a purposive national household survey from Sweden. METHODS: Adopting a bottom-up, prevalence approach, the direct and indirect costs are estimated using the survey data and the value of working time and leisure time from existing sources. RESULTS: The results suggest that around 15% of the adult population of Sweden provide informal care and that such care costs around SEK 152 billion per year (around 3% of GDP; USD 16,3 billion; EUR 14,5 billion), or SEK 128000 per caregiver. Around 55% of costs are in the form of income loss to caregivers. The largest cost items are reduced work hours and direct costs of providing informal care. Replacing informal caregivers with professional care providers would be costly at around SEK 193,6 billion per year. CONCLUSIONS: Findings indicate that, even in a country with a relatively generous welfare system, significant resources are allocated toward providing informal care. The costing analysis suggests that effective support initiatives to ease the burden of informal caregivers may be cost-effective.

Tonic Activation of GluN2C/GluN2D-Containing NMDA Receptors by Ambient Glutamate Facilitates Cortical Interneuron Maturation.

Developing cortical GABAergic interneurons rely on genetic programs, neuronal activity, and environmental cues to construct inhibitory circuits during early postnatal development. Disruption of these events can cause long-term changes in cortical inhibition and may be involved in neurological disorders associated with inhibitory circuit dysfunction. We hypothesized that tonic glutamate signaling in the neonatal cortex contributes to, and is necessary for, the maturation of cortical interneurons. To test this hypothesis, we used mice of both sexes to quantify extracellular glutamate concentrations in the cortex during development, measure ambient glutamate-mediated activation of developing cortical interneurons, and manipulate tonic glutamate signaling using subtype-specific NMDA receptor antagonists in vitro and in vivo We report that ambient glutamate levels are high (≈100 nm) in the neonatal cortex and decrease (to ≈50 nm) during the first weeks of life, coincident with increases in astrocytic glutamate uptake. Consistent with elevated ambient glutamate, putative parvalbumin-positive interneurons in the cortex (identified using G42:GAD1-eGFP reporter mice) exhibit a transient, tonic NMDA current at the end of the first postnatal week. GluN2C/GluN2D-containing NMDA receptors mediate the majority of this current and contribute to the resting membrane potential and intrinsic properties of developing putative parvalbumin interneurons. Pharmacological blockade of GluN2C/GluN2D-containing NMDA receptors in vivo during the period of tonic interneuron activation, but not later, leads to lasting decreases in interneuron morphological complexity and causes deficits in cortical inhibition later in life. These results demonstrate that dynamic ambient glutamate signaling contributes to cortical interneuron maturation via tonic activation of GluN2C/GluN2D-containing NMDA receptors.SIGNIFICANCE STATEMENT Inhibitory GABAergic interneurons make up 20% of cortical neurons and are critical to controlling cortical network activity. Dysfunction of cortical inhibition is associated with multiple neurological disorders, including epilepsy. Establishing inhibitory cortical networks requires in utero proliferation, differentiation, and migration of immature GABAergic interneurons, and subsequent postnatal morphological maturation and circuit integration. Here, we demonstrate that ambient glutamate provides tonic activation of immature, putative parvalbumin-positive GABAergic interneurons in the neonatal cortex via high-affinity NMDA receptors. When this activation is blocked, GABAergic interneuron maturation is disrupted, and cortical networks exhibit lasting abnormal hyperexcitability. We conclude that temporally precise activation of developing cortical interneurons by ambient glutamate is critically important for establishing normal cortical inhibition.

The awareness, visibility and support for young carers across Europe: a Delphi study.

BACKGROUND: Across Europe, young carers (YCs) and their need for support receive limited attention in the media, policy and empirical research, even though, similar to adult carers, they also provide care to ill family members. The Delphi study, a qualitative research methodology, which provides the focus for this article, had the overall aim of exploring existing successful strategies to support YCs. Compared to YCs, even less is known about adolescent young carers (AYCs), a group that is in a critical life transition phase. The study forms part of an EU Horizon 2020 funded research project on AYCs aged 15-17 years old. METHODS: A two-round Delphi study was conducted with 66 experts on YCs from 10 European countries. Topics included: (i) visibility and awareness-raising of YCs at local, regional, and national levels, (ii) current interventions to support YCs, and (iii) future strategies to support YCs. RESULTS: Experts reported a lack of visibility and awareness about YCs in general, and AYCs in particular. Although awareness is slowly increasing in most countries, with the UK ranked highest, experts acknowledged that it remains challenging to identify YCs in many countries. Furthermore, the level and type of support available for YCs differs, with most countries mainly offering support on a local level. Diverse views were expressed regarding future strategies to support YCs. Experts highlighted the importance of specific legislation to formalise the rights of YCs, and the issue of whether young people should be safeguarded from caregiving or if this should be considered part of regular family life. They also emphasised the relevance of available integrated support services for YCs, including schools, family, health and social care. CONCLUSIONS: In most European countries, there is a lack of awareness and visibility on YCs. Identification of YCs is a crucial first step and there is need for a common definition of YCs, together with greater opportunities for young adults to identify themselves as YCs.

Support Interventions for Family Members of Adults with Mental Illness: A Narrative Literature Review.

The aim of this review was to describe research related to support interventions for adult family members of people with mental illness and the significance that support may have. The results indicate the importance of flexible and individualized forms of support from both professionals and people with personal experience as a family member of someone with mental illness. In many cases, the intervention studies revealed that family members' burden decreased, their knowledge of the disease and treatment increased, and their ability to cope with the situation was improved. The results highlight the importance of support both from professionals and peers.

Nursing staff's experiences of intensive care unit diaries: a qualitative study.

BACKGROUND: Diaries as an intervention to aid psychological recovery among intensive care patients have been used for about 20 years, and findings tend to be positive. The provision of a diary directed at the patient may clarify the story of the intensive care unit (ICU) even for the family members and the family members of non-survivors. Members of nursing staff are the primary authors, but how they themselves experience the use of ICU diaries has been minimally explored. AIMS AND OBJECTIVES: This study aimed to explore how nursing staff experienced the use of ICU patient diaries. DESIGN: Qualitative design using focus group interviews. METHODS: A qualitative methodology was used. Six focus group interviews were conducted with 27 nursing staff recruited from one university and two county hospitals. The data were analysed via thematic content analysis. FINDINGS: One overarching theme, 'An effort to do good in words and actions', and four interconnected themes were derived from the analysis. By creating the diary, nursing staff had to deal with a variety of ethical and practical dilemmas, but feedback from patients, family members and ICU follow-up services reinforced the feeling of doing good. This overarching feeling of beneficence encouraged diary authoring and increased motivation and commitment to strive towards excellent patient care. To sustain the use of ICU diaries, collegiate and organizational support was deemed essential. CONCLUSIONS: Nursing staff strived to do good in words and actions for patients and their families when writing the diaries. Positive feedback from patients, family members and ICU follow-up services reinforced feelings of doing good, which served to enhance work satisfaction and a commitment to good-quality nursing care. Experiential-based education was recommended to help sustain ICU diary writing. RELEVANCE TO CLINICAL PRACTICE: Nursing staff requested mentoring and group discussions concerning the format, content and communication channels of the diary.

Family members' experiences with intensive care unit diaries when the patient does not survive.

OBJECTIVE: The aim of the study was to explore how family members experienced the use of a diary when a relative does not survive the stay in the intensive care unit (ICU). METHOD: A qualitative method with a hermeneutic approach was used. Nine participants who read/wrote eight diaries in total were interviewed. The collected data were analysed using a hermeneutic technique inspired by Geanellos. FINDINGS: The analysis revealed an overall theme 'the diary was experienced as a bridge connecting the past with the future', which was a metaphor referring to the temporal aspect where there was the period with the diary up until the patient's death and then the postbereavement period. The diary contributed to both a rational and emotional understanding of the death of the patient and disclosed glimmers of light that still existed before the illness deteriorated. Further, the diary bridged the space between family members themselves and between family and nursing staff. It helped to maintain a feeling of togetherness and engagement in the care of the patient which family members found comforting. CONCLUSION: Family members of nonsurvivors had a need to have the ICU time explained and expressed. The diary might work as a form of 'survival kit' to gain coherence and understanding; to meet their needs during the hospital stay; and, finally, to act as a bereavement support by processing the death of the patient.

Usage and Usability of a Web-based Program for Family Caregivers of Older People in Three European Countries: A Mixed-Methods Evaluation.

InformCare is a European Web platform that supports informal caregivers of older people by providing access to online information and professional and peer support. The aim of this study was to assess the usage and usability of a psychosocial Web-based program carried out in three European countries (Italy, Sweden, and Germany). A mixed-methods sequential explanatory design was adopted, comprising baseline and postintervention assessments, as well as combined thematic content analysis of results and focus group findings. A convenience sample of 118 caregivers was enrolled, of whom 94 used the services offered by the program at least once. The subsamples in the three countries used the platform in different ways, with a predominance of passive strategies (eg, seeking information and reading other people's comments) for Italian caregivers, and more active usage by Swedish and German caregivers. The usability assessment showed that the platform was perceived well by Italian and German caregivers, whereas technical problems affected the Swedish sample's experiences. Focus group data highlighted user satisfaction with the online support and reliability of the environment. Recommendations for practitioners are to ensure digital training for caregivers who have lower confidence in use of the Internet, to involve different healthcare professionals in the provision of professional support, and to adequately manage online community building.

An integrative review of information and communication technology based support interventions for carers of home dwelling older people.

BACKGROUND: A growing number of studies of informal carers of older people reveal positive results concerning support via Information and Communication Technologies (ICT). Systematic examination of factors that have a potential impact on carer outcomes are needed to inform future research. OBJECTIVE: To explore studies concerning ICT support of adult carers of older people and to identify study characteristics that have a potential impact on carer outcomes. METHODS: This integrative review includes 123 studies published since 2005. Fundamental questions for designing sensitive support interventions; 'who, what, and how' were applied to a synthesis of the results. RESULTS: Identified characteristics from the studies responding to the who question included variables of the carers, such as their relationship with the care recipient or their ethnicity. Characteristics related to the what question related to the types of interventions, and the how question concerned the different services or programs offered, the idiosyncratic needs of the carers, and the types of technologies used. CONCLUSION: Results are discussed according to micro, meso and macro levels of analysis. This extensive review can inform future studies and highlight the evidence in the area for decision makers, practitioners and/or NGOs working with innovative forms of support for carers of older people.

Glutamate Clearance Is Locally Modulated by Presynaptic Neuronal Activity in the Cerebral Cortex.

Excitatory amino acid transporters (EAATs) are abundantly expressed by astrocytes, rapidly remove glutamate from the extracellular environment, and restrict the temporal and spatial extent of glutamate signaling. Studies probing EAAT function suggest that their capacity to remove glutamate is large and does not saturate, even with substantial glutamate challenges. In contrast, we report that neuronal activity rapidly and reversibly modulates EAAT-dependent glutamate transport. To date, no physiological manipulation has shown changes in functional glutamate uptake in a nonpathological state. Using iGluSnFr-based glutamate imaging and electrophysiology in the adult mouse cortex, we show that glutamate uptake is slowed up to threefold following bursts of neuronal activity. The slowing of glutamate uptake depends on the frequency and duration of presynaptic neuronal activity but is independent of the amount of glutamate released. The modulation of glutamate uptake is brief, returning to normal within 50 ms after stimulation ceases. Interestingly, the slowing of glutamate uptake is specific to activated synapses, even within the domain of an individual astrocyte. Activity-induced slowing of glutamate uptake, and the increased persistence of glutamate in the extracellular space, is reflected by increased decay times of neuronal NR2A-mediated NMDA currents. These results show that astrocytic clearance of extracellular glutamate is slowed in a temporally and spatially specific manner following bursts of neuronal activity ≥30 Hz and that these changes affect the neuronal response to released glutamate. This suggests a previously unreported form of neuron-astrocyte interaction. SIGNIFICANCE STATEMENT: We report the first fast, physiological modulation of astrocyte glutamate clearance kinetics. We show that presynaptic activity in the cerebral cortex increases the persistence of glutamate in the extracellular space by slowing its clearance by astrocytes. Because of abundant EAAT expression, glutamate clearance from the extracellular space has been thought to have invariant kinetics. While multiple studies report experimental manipulations resulting in altered EAAT expression, our findings show that astrocytic glutamate uptake is dynamic on a fast time-scale. This shows rapid plasticity of glutamate clearance, which locally modulates synaptic signaling in the cortex. As astrocytic glutamate uptake is a fundamental and essential mechanism for neurotransmission, this work has implications for neurotransmission, extrasynaptic receptor activation, and synaptic plasticity.

When a parent dies - a systematic review of the effects of support programs for parentally bereaved children and their caregivers.

BACKGROUND: The death of a parent is a highly stressful life event for bereaved children. Several studies have shown an increased risk of mental ill-health and psychosocial problems among affected children. The aims of this study were to systematically review studies about effective support interventions for parentally bereaved children and to identify gaps in the research. METHODS: The review's inclusion criteria were comparative studies with samples of parentally bereaved children. The focus of these studies were assessments of the effects on children of a bereavement support intervention. The intervention was directed towards children 0-18 years; but it could also target the children's remaining parent/caregiver. The study included an outcome measure that dealt with effects of the intervention on children. The following electronic databases were searched up to and including November 2015: PubMed, PsycINFO, Cinahl, PILOTS, ProQuest Sociology (Sociological Abstracts and Social Services Abstracts). The included studies were analysed and summarized based on the following categories: type of intervention, reference and grade of evidence, study population, evaluation design, measure, outcome variable and findings as effect size within and between groups. RESULTS: One thousand, seven hundred and-six abstracts were examined. Following the selection process, 17 studies were included. The included studies consisted of 15 randomized controlled studies, while one study employed a quasi-experimental and one study a pre-post-test design. Thirteen studies provided strong evidence with regards to the quality of the studies due to the grade criteria; three studies provided fairly strong evidence and one study provided weaker evidence. The included studies were published between 1985 and 2015, with the majority published 2000 onwards. The studies were published within several disciplines such as psychology, social work, medicine and psychiatry, which illustrates that support for bereaved children is relevant for different professions. The interventions were based on various forms of support: group interventions for the children, family interventions, guidance for parents and camp activities for children. In fourteen studies, the interventions were directed at both children and their remaining parents. These studies revealed that when parents are supported, they can demonstrate an enhanced capacity to support their children. In three studies, the interventions were primarily directed at the bereaved children. The results showed positive between group effects both for children and caregivers in several areas, namely large effects for children's traumatic grief and parent's feelings of being supported; medium effects for parental warmth, positive parenting, parent's mental health, grief discussions in the family, and children's health. There were small effects on several outcomes, for example children's post-traumatic stress disorder (PTSD) symptoms, anxiety, depression, self-esteem and behaviour problems. There were studies that did not show effects on some measures, namely depression, present grief, and for the subgroup boys on anxiety, depression, internalizing and externalizing. CONCLUSIONS: The results indicate that relatively brief interventions can prevent children from developing more severe problems after the loss of a parent, such as traumatic grief and mental health problems. Studies have shown positive effects for both children's and remaining caregiver's health. Further research is required including how best to support younger bereaved children. There is also a need for more empirically rigorous effect studies in this area.

The experiences of working carers of older people regarding access to a web-based family care support network offered by a municipality.

Policy makers in Sweden and other European Member States pay increasing attention as to how best support working carers; carers juggling providing unpaid family care for older family members while performing paid work. Exploring perceived benefits and challenges with web-based information and communication technologies as a means of supporting working carers' in their caregiving role, this paper draws on findings from a qualitative study. The study aimed to describe working carers' experiences of having access to the web-based family care support network 'A good place' (AGP) provided by the municipality to support those caring for an older family member. Content analysis of interviews with nine working carers revealed three themes: A support hub, connections to peers, personnel and knowledge; Experiencing ICT support as relevant in changing life circumstances; and Upholding one's personal firewall. Findings indicate that the web-based family care support network AGP is an accessible, complementary means of support. Utilising support while balancing caregiving, work obligations and responsibilities was made easier with access to AGP; enabling working carers to access information, psychosocial support and learning opportunities. In particular, it provided channels for carers to share experiences with others, to be informed, and to gain insights into medical and care issues. This reinforced working carers' sense of competence, helping them meet caregiving demands and see positive aspects in their situation. Carers' low levels of digital skills and anxieties about using computer-based support were barriers to utilising web-based support and could lead to deprioritising of this support. However, to help carers overcome these barriers and to better match web-based support to working carers' preferences and situations, web-based support must be introduced in a timely manner and must more accurately meet each working carer's unique caregiving needs.

Astrocyte membrane properties are altered in a rat model of developmental cortical malformation but single-cell astrocytic glutamate uptake is robust.

Developmental cortical malformations (DCMs) are linked with severe epilepsy and are caused by both genetic and environmental insults. DCMs include several neurological diseases, such as focal cortical dysplasia, polymicrogyria, schizencephaly, and others. Human studies have implicated astrocyte reactivity and dysfunction in the pathophysiology of DCMs, but their specific role is unknown. As astrocytes powerfully regulate glutamate neurotransmission, and glutamate levels are known to be increased in human epileptic foci, understanding the role of astrocytes in the pathological sequelae of DCMs is extremely important. Additionally, recent studies examining astrocyte glutamate uptake in DCMs have reported conflicting results, adding confusion to the field. In this study we utilized the freeze lesion (FL) model of DCM, which is known to induce reactive astrocytosis and cause significant changes in astrocyte morphology, proliferation, and distribution. Using whole-cell patch clamp recording from astrocytes, we recorded both UV-uncaging and synaptically evoked glutamate transporter currents (TCs), widely accepted assays of functional glutamate transport by astrocytes. With this approach, we set out to test the hypothesis that astrocyte membrane properties and glutamate transport were disrupted in this model of DCM. Though we found that the developmental maturation of astrocyte membrane resistance was disrupted by FL, glutamate uptake by individual astrocytes was robust throughout FL development. Interestingly, using an immunolabeling approach, we observed spatial and developmental differences in excitatory amino acid transporter (EAAT) expression in FL cortex. Spatially specific differences in EAAT2 (GLT-1) and EAAT1 (GLAST) expression suggest that the relative contribution of each EAAT to astrocytic glutamate uptake may be altered in FL cortex. Lastly, we carefully analyzed the amplitudes and onset times of both synaptically- and UV uncaging-evoked TCs. We found that in the FL cortex, synaptically-evoked, but not UV uncaging-evoked TCs, were larger in amplitude. Additionally, we found that the amount of electrical stimulation required to evoke a synaptic TC was significantly reduced in the FL cortex. Both of these findings are consistent with increased excitatory input to the FL cortex, but not with changes in how individual astrocytes remove glutamate. Taken together, our results demonstrate that the maturation of astrocyte membrane resistance, local distribution of glutamate transporters, and glutamatergic input to the cortex are altered in the FL model, but that single-cell astrocytic glutamate uptake is robust.

Telephone talk: effects of two access methods on phone call success.

The slower and unnatural timing of speech inherent to speech-generating devices (SGDs) can be a barrier to successful aided telephone calls. The timing of message delivery when using an SGD may vary depending on the type of access method used. We measured the difference in the success rate of telephone calls made with an SGD either using switch scanning or direct selection with eye gaze. The scripted calls, asking for directions, were placed to 100 randomly selected businesses. Analysis showed a statistically significant difference in the success rate between the two conditions, with eye gaze access resulting in more successful calls. Findings from this study suggest that people who use SGDs for phone calls may improve the timing of message delivery by using eye gaze access compared to switch scanning.

Astrocytic glutamate uptake is slow and does not limit neuronal NMDA receptor activation in the neonatal neocortex.

Glutamate uptake by astrocytes controls the time course of glutamate in the extracellular space and affects neurotransmission, synaptogenesis, and circuit development. Astrocytic glutamate uptake has been shown to undergo post-natal maturation in the hippocampus, but has been largely unexplored in other brain regions. Notably, glutamate uptake has never been examined in the developing neocortex. In these studies, we investigated the development of astrocytic glutamate transport, intrinsic membrane properties, and control of neuronal NMDA receptor activation in the developing neocortex. Using astrocytic and neuronal electrophysiology, immunofluorescence, and Western blot analysis we show that: (1) glutamate uptake in the neonatal neocortex is slow relative to neonatal hippocampus; (2) astrocytes in the neonatal neocortex undergo a significant maturation of intrinsic membrane properties; (3) slow glutamate uptake is accompanied by lower expression of both GLT-1 and GLAST; (4) glutamate uptake is less dependent on GLT-1 in neonatal neocortex than in neonatal hippocampus; and (5) the slow glutamate uptake we report in the neonatal neocortex corresponds to minimal astrocytic control of neuronal NMDA receptor activation. Taken together, our results clearly show fundamental differences between astrocytic maturation in the developing neocortex and hippocampus, and corresponding changes in how astrocytes control glutamate signaling.