Overexpression of pendrin in intercalated cells produces chloride-sensitive hypertension.

Inherited and acquired disorders that enhance the activity of transporters mediating renal tubular Na(+) reabsorption are well established causes of hypertension. It is unclear, however, whether primary activation of an Na(+)-independent chloride transporter in the kidney can also play a pathogenic role in this disease. Here, mice overexpressing the chloride transporter pendrin in intercalated cells of the distal nephron (Tg(B1-hPDS) mice) displayed increased renal absorption of chloride. Compared with normal mice, these transgenic mice exhibited a delayed increase in urinary NaCl and ultimately, developed hypertension when exposed to a high-salt diet. Administering the same sodium intake as NaHCO3 instead of NaCl did not significantly alter BP, indicating that the hypertension in the transgenic mice was chloride-sensitive. Moreover, excessive chloride absorption by pendrin drove parallel absorption of sodium through the epithelial sodium channel ENaC and the sodium-driven chloride/bicarbonate exchanger (Ndcbe), despite an appropriate downregulation of these sodium transporters in response to the expanded vascular volume and hypertension. In summary, chloride transport in the distal nephron can play a primary role in driving NaCl transport in this part of the kidney, and a primary abnormality in renal chloride transport can provoke arterial hypertension. Thus, we conclude that the chloride/bicarbonate exchanger pendrin plays a major role in controlling net NaCl absorption, thereby influencing BP under conditions of high salt intake.

Spouse caregivers of people with advanced dementia in nursing homes: a longitudinal narrative study.

BACKGROUND: Dementia is a life limiting illness and is becoming a major cause of death in developed countries. Many people with dementia die in nursing homes or long-term residential care settings. Spouse caregivers of people with dementia living in nursing homes find themselves in a position which is difficult to understand and live with. AIM: To explore the caregiving experiences of spouse carers of people with advanced dementia living in nursing homes. DESIGN: Longitudinal narrative study using three sequential interviews and diary accounts. SETTING/PARTICIPANTS: Spouse caregivers of people with dementia nearing the end of life were recruited from two nursing homes in Northern England. RESULTS: Twenty-seven interviews were conducted and seven diaries collected from 10 spouse caregivers (7 women and 3 men). We demonstrate that for this group the experience of caregiving is one of struggle to live in 'two worlds', the world of the nursing home and the world of wider society, where, in both settings, their role is often ambiguous and their position liminal. We also identify that feelings of guilt associated with nursing home placement of a spouse with dementia endure far beyond the time of the move. CONCLUSIONS: Nursing home staff need to acknowledge spouse carers in their own right, inviting them to tell their stories. We recommend that communication skills be included in educational programmes for nursing home staff. Further research is needed to determine the shape and context of carer needs assessment and support, as recommended in health policy.

Effect of methanol fixation on single-cell RNA sequencing of the murine dentate gyrus.

Single-cell RNA sequencing (scRNA-seq) provides a powerful tool to evaluate the transcriptomic landscape and heterogeneity of thousands of cells in parallel. However, complex study designs or the unavailability of in-house instruments require the temporal disconnection between sample preparation and library construction, raising the need for efficient sample preservation methods which are compatible with scRNA-seq downstream analysis. Several studies evaluated the effect of methanol fixation as preservation method, yet none of them deeply assessed its effect on adult primary dissociated brain tissue. Here, we evaluated its effect on murine dentate gyrus (DG) single cell suspensions and on subsequent scRNA-seq downstream analysis by performing SOrting and Robot-assisted Transcriptome SEQuencing (SORT-seq), a partially robotized version of the CEL-seq2 protocol. Our results show that MeOH fixation preserves RNA integrity and has no apparent effects on cDNA library construction. They also suggest that fixation protects from sorting-induced cell stress and increases the proportion of high-quality cells. Despite evidence of mRNA leakage in fixed cells, their relative gene expression levels correlate well with those of fresh cells and fixation does not significantly affect the variance of the dataset. Moreover, it allows the identification of all major DG cell populations, including neural precursors, granule neurons and different glial cell types, with a tendency to preserve more neurons that are underrepresented in fresh samples. Overall, our data show that MeOH fixation is suitable for preserving primary neural cells for subsequent single-cell RNA profiling, helping to overcome challenges arising from complex workflows, improve experimental flexibility and facilitate scientific collaboration.

The meaning of cancer: implications for family finances and consequent impact on lifestyle, activities, roles and relationships.

OBJECTIVE: This study explores the impact that cancer-related financial hardship/worries can have on family life. METHODS: Forty patients (19 male and 21 female) and 17 carers participated in a qualitative study, which drew on certain elements of grounded theory methods. Participants were 18 years or older and were accessed through a regional cancer centre, an acute National Health Service trust, a support group and the Macmillan Benefits Helpline. Interviews were transcribed verbatim and analysed thematically with the aid of nvivo 7 (QSR International, Cambridge, MA, USA). RESULTS: Many participants said that prior to experiencing cancer, they had never thought about its effects on finances. The early part of the cancer journey was characterised by a need to be positive about the future, limited discussion about money within families and a lack of action in relation to finances. Many participants, especially those of working age, described cancer-related financial worries and difficulties that had impacted on family lifestyle, roles and relationships. Consequences included house repossession, bankruptcy, loss of independence and relationship breakdown. CONCLUSIONS: Health and social care professionals have a role in prompting people affected by cancer to take stock of their finances early in the cancer trajectory, in order to avert knock-on effects. An approach that combines hope with proactivity is needed. More work into the long-term effects of financial difficulties/worries and specific financial issues that affect people from Black and minority ethnic backgrounds is needed.

Carbonic anhydrases CA4 and CA14 both enhance AE3-mediated Cl--HCO3- exchange in hippocampal neurons.

Carbonic anhydrase (CA) activity in the brain extracellular space is attributable mainly to isoforms CA4 and CA14. In brain, these enzymes have been studied mostly in the context of buffering activity-dependent extracellular pH transients. Yet evidence from others has suggested that CA4 acts in a complex with anion exchangers (AEs) to facilitate Cl(-)-HCO(3)(-) exchange in cotransfected cells. To investigate whether CA4 or CA14 plays such a role in hippocampal neurons, we studied NH(4)(+)-induced alkalinization of the cytosol, which is mitigated by Cl(-) entry and HCO(3)(-) exit. The NH(4)(+)-induced alkalinization was enhanced when the extracellular CAs were inhibited by the poorly permeant CA blocker, benzolamide, or by inhibitory antibodies specific for either CA4 or CA14. The NH(4)(+)-induced alkalinization was also increased with inhibition of anion exchange by 4,4*-diisothiocyanostilbene-2,2*-disulfonic acid, or by eliminating Cl(-) from the medium. No effect of benzolamide was seen under these conditions, in which no Cl(-)-HCO(3)(-) exchange was possible. Quantitative PCR on RNA from the neuronal cultures indicated that AE3 was the predominant AE isoform. Single-cell PCR also showed that Slc4a3 (AE3) transcripts were abundant in isolated neurons. In hippocampal neurons dissociated from AE3-null mice, the NH(4)(+)-induced alkalinization was much larger than that seen in neurons from wild-type mice, suggesting little or no Cl(-)-HCO(3)(-) exchange in the absence of AE3. Benzolamide had no effect on the NH(4)(+)-induced alkalinization in the AE3 knock-out neurons. Our results indicate that CA4 and CA14 both play important roles in the regulation of intracellular pH in hippocampal neurons, by facilitating AE3-mediated Cl(-)-HCO(3)(-) exchange.

Evaluation of a British child bereavement service: the user's perspective.

OBJECTIVE: This article summarizes the findings from a 3-year independent evaluation of a regional Child Bereavement Service (CBS). The service was commissioned by a Primary Care Trust in Northern England, and funded by a British cancer charity, Macmillan Cancer Support. The need for a CBS was recognized by members of a Palliative Care Group who identified a gap in local services for bereaved children, who may be susceptible to short/long-term psychiatric/psychological disorders. The service was established to offer support for professionals working with bereaved children and their family. METHOD: Interventions provided by the service included pre/post bereavement support, individual work with the child and/or family, and group work. An evaluation (2004-2007), was conducted to inform service development utilizing semi-structured interviews with parents/carers of service users (n = 20), and semi-structured interviews with healthcare professionals (n = 8). Interviews were recorded, transcribed verbatim, and analyzed using grounded theory methods. RESULTS: Referrals were higher than expected. Sixty per year were anticipated; however, in the first year alone, there were 255 referrals. Health and social care professionals who attended training courses, provided by the CBS staff, expressed confidence in providing bereavement support themselves, or by making appropriate referrals to the CBS. Parents and carers welcomed a service specifically for their children. SIGNIFICANCE OF RESULTS: The CBS is a viable organization that supports bereaved children as expressed in this article.

Recommendations for Developing Support Tools With People Suffering From Chronic Obstructive Pulmonary Disease: Co-Design and Pilot Testing of a Mobile Health Prototype.

BACKGROUND: Gaps exist between developers, commissioners, and end users in terms of the perceived desirability of different features and functionalities of mobile apps. OBJECTIVE: The objective of this study was to co-design a prototype mobile app for people with chronic obstructive pulmonary disease (COPD). We present lessons learned and recommendations from working on a large project with various stakeholders to develop a mobile app for patients with COPD. METHODS: We adopted a user-centered, participatory approach to app development. Following a series of focus groups and interviews to capture requirements, we developed a prototype app designed to enable daily symptom recording (experience sampling). The prototype was tested in a usability study applying the think aloud protocol with people with COPD. It was then released via the Android app store, and experience sampling data and event data were captured to gather further usability data. RESULTS: A total of 5 people with COPD participated in the pilot study. Identified themes include familiarity with technology, appropriate levels for feeding back information, and usability issues such as manual dexterity. Moreover, 37 participants used the app over a 4-month period (median age 47 years). The symptoms most correlated to perceived well-being were tiredness (r=0.61; P<.001) and breathlessness (r=0.59; P<.001). CONCLUSIONS: Design implications for COPD apps include the need for clearly labeled features (rather than relying on colors or symbols that require experience using smartphones), providing weather information, and using the same terminology as health care professionals (rather than simply lay terms). Target users, researchers, and developers should be involved at every stage of app development, using an iterative approach to build a prototype app, which should then be tested in controlled settings as well as in the wild (ie, when deployed and used in real-world settings) over longer periods.

The experiences of family caregivers of people with advanced dementia living in nursing homes, with a specific focus on spouses: A narrative literature review.

Dementia affects individuals, families and their relationships. While there is increasing evidence about the experiences of family caregivers of people with dementia, relatively little is known of their experiences when their relatives are living in nursing homes with dementia. This narrative literature review aimed to synthesise current knowledge about family caregivers' experience of having relatives living in nursing homes with advanced dementia, particularly focussing on community-dwelling spouses. Using a systematic approach, textual narrative synthesis was undertaken. Four themes were identified: changing relationships, the need for companionship, adjusting to new roles and relationships and anticipating death/looking towards the future. Two additional themes were present only for spouses: changing identity - feeling married, being married; and alone but… The review demonstrates that some aspects of spouses' experiences are different from those of other family caregivers. Longitudinal studies are required to better understand spouses' motivations to continue caring in this context and to find ways of supporting them.

Chair massage for patients and carers: a pilot service in an outpatient setting of a cancer care hospital.

PURPOSE: To gather patient and carer evaluations of a 20 min chair massage treatment provided one afternoon a week in an outpatient waiting area. METHOD: Information gathered over a year included documented evaluation of chair massage, pre- and post-treatment well-being scores (visual analogue scale). RESULTS: Both patients (n=224) and carers (n=185) positively evaluated the treatment. Key benefits reported included: relaxation, comfort, time out/treat, distraction, and relief of anxiety. There were significant changes in self-reported well-being score (p=<0.001), but no significant changes between scores for males and females. The changes in well-being scores on occasions (n=3) did not match the positive feedback. CONCLUSIONS: The findings suggest that the service was appreciated by patients and carers. The project was continued for a further year with internal funding. Further research is warranted to ascertain the added and longer-term value of this intervention.

Lay educators in asthma self management: reflections on their training and experiences.

OBJECTIVE: To capture the experiences and feelings of lay educators in an asthma self-management programme to aid understanding of optimal methods of recruitment, training and retention, and to enhance their value within the programme. METHODS: A multi site randomised controlled equivalence trial of asthma educators and primary care practice based nurses during which the educators were asked to keep a diary of their experience. A qualitative thematic analysis of these diaries was undertaken. RESULTS: Eight lay educators supplied diaries. From these diaries emerged personal reasons for involvement in the programme, constructive comments on the training programme, a need for preparation for the realities of clinical practice and significant ongoing support and training. CONCLUSION: Lay educators are a potential resource for giving self-management education to patients with long-term conditions such as asthma. However, there are some considerations that need to be taken into account regarding contracts, retention and continual support. PRACTICE IMPLICATIONS: Lay educators need a flexible but comprehensive training programme, contracts, on site mentoring and support. They seem most contented when welcomed by health professionals and treated as part of the team.