Participatory asset mapping and photovoice interviews to scope cultural and community resources to reduce alcohol harm in Chitwan, Nepal.

AIMS: To scope the breadth of existing cultural and community assets and how alcohol drinkers and community health workers perceived them in relation to reducing alcohol-related harm. METHODS: The study was conducted in Chitwan, south-central Nepal, which has considerable alcohol problems. Participatory asset mapping was conducted using field notes, photography, and through engaging with communities to explore how community assets affect alcohol consumption. Semi-structured photovoice interviews were conducted with harmful/hazardous drinkers (AUDIT score 8 to 19) and community health workers. Purposive and snowball sampling were used to recruit participants. During interviews, participants used their photographs to reflect on how community assets influenced alcohol use. Thematic framework analysis was used to analyse the data. RESULTS: We recruited 12 harmful/hazardous drinkers (3 females) and 6 health workers (2 females). The mean AUDIT score of the former was 12.17 (SD ±2.86). Thematic analysis of the photovoice interviews produced three themes: 'influences and impact of families and communities'; 'culture and spirituality'; and 'nature and the environment'. The community mapping produced five assets that promoted alcohol consumption: (1) availability; (2) advertising; (3) negative attitudes towards users; (4) festivals/gatherings; and (5) illiteracy/poverty. Six assets that discouraged consumption were: (1) legislation restricting use; (2) community organisations; (3) cultural/spiritual sites; (4) healthcare facilities; (5) family and communities; and (6) women's community groups. Those from certain ethnic groups consumed more alcohol, experienced more family discord, or felt stigmatised due to their drinking. Assets 'festivals/gatherings' and 'negative attitudes toward users' and the theme 'family and communities' concerned with relationships and community activities were perceived to both promote and reduce alcohol use. CONCLUSIONS: This study provides new insight into a variety of cultural and community assets that promote and reduce alcohol use. The study identifies new possibilities to build on visual participatory and arts-based methods that have potential to be effectively implemented at scale.

Systematic review on the effects of the physical and social aspects of community pharmacy spaces on service users and staff.

AIM: This systematic review aimed to provide new insights into how pharmacy spaces, or the architecture of pharmacies, are experienced by pharmacy service users and staff. The review sought to identify environmental factors which may influence service users' and staff participation in community-based pharmacy health services. METHOD: Ten databases were searched for English language publications, using a combination of search terms relating to pharmacy service users and staff; pharmacy spaces; and health and social care outcomes. Data from the final selected studies were extracted, thematically analysed using a narrative approach and the quality of each study assessed using the Integrated quality Criteria for the Review of Multiple Study designs (ICROMS). RESULTS: 80 articles reporting 80 studies published between 1994 and 2020 were identified; they were from 28 countries, involving around 3234 community pharmacies, 13,615 pharmacy service users, 5056 pharmacists and 78 pharmacy health staff. Most studies (94%) met the ICROMS minimum score, and half did not meet the mandatory quality criteria. Four themes likely to influence service users' and staff experiences of pharmacy health services were identified: (1) privacy; (2) experience of the physical environment; (3) professional image; and (4) risk of error. CONCLUSION: To optimise the delivery and experience of pharmacy health services, these spaces should be made more engaging. Future applied research could focus on optimising inclusive pharmacy design features.

Mental health and caregiving experiences of family carers supporting people with psychosis.

AIMS: Family carers supporting an individual with psychosis often experience poorer mental health, however, little is known about specific risk factors among these carers. We investigated the associations between demographic, caregiving characteristics and mental health outcomes in family carers supporting an individual with psychosis and compared carers' outcomes with general population norms. METHODS: We analysed baseline data from the COPe-support randomised controlled trial of online psychoeducation and peer support for adult carers supporting an individual with psychosis between 2018 and 2020. We collected carers' demographic and health outcome data, including wellbeing using Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS as primary outcome), quality of life using EQ-5D-5L and caregiving experience assessed with Experience of Caregiving Inventory. We tested associations between carers' demographic and caregiving characteristics for each outcome in turn and meta-analysed carers' WEMWBS and EQ-5D-5L with Health Survey England (HSE) general population data from 2016 and 2017, respectively. RESULTS: The 407 carers of people with psychosis had a mean WEMWBS score of 42.2 (s.d. 9.21) and their overall weighted pooled WEMWBS score was 7.3 (95% confidence interval (CI) -8.6 to -6.0, p < 0.01) lower than the HSE general population sample, indicating carers have poorer mental wellbeing by more than double the minimum clinically important difference of 3 points on WEMWBS. Among all caring relationships, partners had poorer wellbeing compared to parents with lower WEMWBS score (-6.8, -16.9 to 3.3, p = 0.03). Single carers had significantly poorer wellbeing (-3.6, -5.6 to -1.5, p < 0.01) and a more negative caregiving experience than those who were cohabiting. Spending more than 35 h per week caregiving increased carers' negative experience significantly (p = 0.01). CONCLUSION: Carers of people with psychosis have poorer mental health than non-carers. Partners, lone carers and those spending more than 35 h per week on caring were found to be most at risk of poor mental health. Based on the results, we advocate that the details of carers for individuals with psychosis should be added to the existing carers or severe mental illness registers at all general practitioner surgeries and for their wellbeing screened routinely. Future large-scale prospective studies are needed to develop a predictive model to determine risk factors, hence to aid early identification of carers' support needs. Such understandings are also useful to inform tailored intervention development.

Therapeutic drug monitoring of antitubercular agents for disseminated Mycobacterium tuberculosis during intermittent haemodialysis and continuous venovenous haemofiltration.

WHAT IS KNOWN AND OBJECTIVE: There is a lack of data regarding therapeutic drug monitoring (TDM) of antitubercular agents in the setting of continuous venovenous haemofiltration (CVVH). We describe TDM results of numerous antitubercular agents in a critically ill patient during CVVH and haemodialysis. CASE SUMMARY: A 49-year-old man was initiated on treatment for disseminated Mycobacterium tuberculosis. During hospital admission, the patient developed critical illness and required renal replacement therapy. TDM results and pharmacokinetic calculations showed adequate serum concentrations of rifampin, ethambutol and amikacin during CVVH and of rifampin, pyrazinamide, ethambutol and levofloxacin during intermittent haemodialysis. WHAT IS NEW AND CONCLUSION: The presence of critical illness and renal replacement therapy can induce pharmacokinetic changes that may warrant vigilant TDM to ensure optimal therapy. To our knowledge, this is the first report to describe TDM for several antitubercular agents during CVVH in a critically patient with disseminated M. tuberculosis.

Gene therapy using plasmid DNA-encoded anti-HER2 antibody for cancers that overexpress HER2.

Plasmid DNA-encoded antibodies, or DNA-based monoclonal antibodies (dMAbs), are delivered by intramuscular injection and in vivo electroporation (EP) and are effective in virus neutralization, although they have not been evaluated for tumor gene therapy. Here we investigated whether a dMAb was appropriate for tumor gene therapy. We constructed the expression plasmids coding for the heavy or light chain of a parental murine antibody of Herceptin with the antibody genes codon- and RNA-optimized and fused to the Kozak-IgE leader sequence in pVax1. Transfection of the plasmids into human muscle RD cells resulted in functional expression of the antibody, and this exhibited the same in vitro antiproliferative activity as Herceptin. A single intramuscular injection and in vivo EP of the plasmids (100 µg per head) resulted in high and sustained antibody expression in the sera of normal mice and in effective inhibition of tumor growth in nude mice bearing HER2-positive human breast carcinoma BT474 xenografts. The antitumor efficacy of the anti-HER2 dMAb was similar to that of four doses of intravenously injected 10 mg kg-1 Herceptin. The results demonstrate that the dMAb is effective in the treatment of HER2-positive breast cancer, suggesting that this dMAb may be applicable for tumor gene therapy.

MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome.

The methyl-CpG-binding protein 2 (MeCP2) gene, MECP2, is an X-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT). However, the molecular mechanism of MECP2-mutation-caused RTT is less known. Here we find that MeCP2 could be SUMO-modified by the E3 ligase PIAS1 at Lys-412. MeCP2 phosphorylation (at Ser-421 and Thr-308) facilitates MeCP2 SUMOylation, and MeCP2 SUMOylation is induced by NMDA, IGF-1 and CRF in the rat brain. MeCP2 SUMOylation releases CREB from the repressor complex and enhances Bdnf mRNA expression. Several MECP2 mutations identified in RTT patients show decreased MeCP2 SUMOylation. Re-expression of wild-type MeCP2 or SUMO-modified MeCP2 in Mecp2-null neurons rescues the deficits of social interaction, fear memory and LTP observed in Mecp2 conditional knockout (cKO) mice. These results together reveal an important role of MeCP2 SUMOylation in social interaction, memory and synaptic plasticity, and that abnormal MeCP2 SUMOylation is implicated in RTT.

Cutaneous Mycobacterium massiliense infection associated with cupping therapy.

Nontuberculous mycobacteria (NTM) are ubiquitous organisms that are now seen as emerging human pathogens. NTM infections are very difficult to diagnose and treat, therefore a high index of clinical suspicion is needed for diagnosis. Cutaneous NTM infections have been primarily reported associated with previous invasive procedures. We report the case of a healthy 59-year-old woman who developed recurring abdominal skin lesions caused by Mycobacterium massiliense after she underwent noninvasive cupping therapy. We identified the pathogen using a PCR assay targeting the erm(41) gene of the bacterium. The patient was treated successfully by en bloc excision and long-term antibiotic treatment. This case shows that cutaneous infection with M. massiliense may occur in an immunocompetent person without an antecedent invasive procedure.

Corrosion and tribocorrosion of hafnium in simulated body fluids.

Hafnium is a passive metal with good biocompatibility and osteogenesis, however, little is known about its resistance to wear and corrosion in biological environments. The corrosion and tribocorrosion behavior of hafnium and commercially pure (CP) titanium in simulated body fluids were investigated using electrochemical techniques. Cyclic polarization scans and open circuit potential measurements were performed in 0.9% NaCl solution and 25% bovine calf serum solution to assess the effect of organic species on the corrosion behavior of the metal. A pin-on-plate configuration tribometer and a three electrode electrochemical cell were integrated to investigate the tribocorrosion performance of the studied materials. The results showed that hafnium has good corrosion resistance. The corrosion density currents measured in its passive state were lower than those measured in the case of CP titanium; however, it showed a higher tendency to suffer from localized corrosion, which was more acute when imperfections were present on the surface. The electrochemical breakdown of the oxide layer was retarded in the presence of proteins. Tribocorrosion tests showed that hafnium has the ability to quickly repassivate after the oxide layer was damaged; however, it showed higher volumetric loss than CP titanium in equivalent wear-corrosion conditions. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1157-1164, 2014.

The development of a family intervention competency assessment and reflection scale (FICARS) for psychosis.

Family intervention (FI) for psychosis has a robust evidence base. In recommending its use the revised NICE schizophrenia guideline states 'Healthcare professionals providing psychological interventions should have an appropriate level of competence'. Yet, no definitive instrument exists to outline what competences are required during and post FI training or help recruit staff with the appropriate knowledge and skill. This paper reports on the development of a Family Intervention competency assessment and reflection scale (FICARS). Using a systematic three-staged approach commonly used in health outcomes measurement development, a comprehensive literature review on UK-based FI training and commonly used assessment tools was undertaken. A FICARS draft was then constructed and revised in consultation with expert FI clinicians. Finally, a content validity study with FI trainers and students across three FI training programmes was undertaken to optimize FICARS aim to promote reflective assessment and professional development in FI skills and practice.

Implementing a structured psychosocial interventions group programme for people with bipolar disorder.

It has been reported that, at any time, over half of the people with bipolar disorder are receiving no active treatment. Despite the availability of effective medications and psychotherapies, research concludes that the care of bipolar disorder in everyday practice is often deficient. Evidence base reports the effectiveness of psychosocial interventions using many of the same ideas as the recovery approach; both attempt to place clients at the heart of service delivery. This paper reports on the development and implementation of three pilot group programmes for service users with bipolar disorder, in a community clinical setting in South East England. The group programme design and development was based upon the evidence-based psychosocial interventions advocated in national clinical guidelines and research literature. The programme incorporated the key effective psychosocial interventions and self-management mechanisms within its 12 sessions spanning over 3 months, followed by three booster sessions in 6 months' time. Twenty-three service users have to date completed the programme. Participant feedback will be discussed and reported to inform further development and research implications of such innovative evidence-based interventions for service users with bipolar disorder.

Differential recruitment of nuclear receptor coregulators in ligand-dependent transcriptional repression by estrogen receptor-α.

Estrogen receptors (ERs) are normally expressed in breast tissues and mediate hormonal functions during development and in female reproductive physiology. In the majority of breast cancers, ERs are involved in regulating tumor cell proliferation and serve as prognostic markers and therapeutic targets in the management of hormone-dependent tumors. At the molecular level, ERs function as ligand-dependent transcription factors and activate target-gene expression following hormone stimulation. Recent transcriptomic and whole-genome-binding studies suggest, however, that ligand-activated ERs can also repress the expression of a significant subset of target genes. To characterize the molecular mechanisms of transcriptional repression by ERs, we examined recruitment of nuclear receptor coregulators, histone modifications and RNA polymerase II docking at ER-binding sites and cis-regulatory regions adjacent to repressed target genes. Moreover, we utilized gene expression data from patient samples to determine potential roles of repressed target genes in breast cancer biology. Results from these studies indicate that nuclear receptor corepressor recruitment is a key feature of ligand-dependent transcriptional repression by Ers, and some repressed target genes are associated with disease progression and response to endocrine therapy. These findings provide preliminary insights into a novel aspect of the molecular mechanisms of ER functions and their potential roles in hormonal carcinogenesis and breast cancer biology.

HEART--the Hounslow Early Active Recovery Team: implementing an inclusive strength-based model of care for people with early psychosis.

In recent years in the UK, the National Health Service has made policy commitments to delivering mental health services based on recovery principles. In general though, the UK mental health service providers are in the early stages of implementing recovery principles and approaches in front-line services. This paper describes the work of the Hounslow Early Active Recovery Team (HEART), which has made substantial progress in placing recovery principles and approaches at the heart of the work of an early intervention for psychosis team working in an ethnically diverse area of West London. As evidence of the success of the HEART, in its first year and half, the team has achieved high levels of customer satisfaction with its work and a recent audit has revealed that 57% of respondents were in employment or education contrasting with the extremely high unemployment rates reported in several UK studies of people with serious mental health problems.

Endoscopic evaluation of significant gastrointestinal lesions in patients with iron deficiency with and without anaemia: a Korean Association for the Study of Intestinal Disease study.

BACKGROUND: Although endoscopy is recommended for patients with iron deficiency anaemia, there is, currently, no consensus on the role of endoscopy for iron-deficient patients without anaemia. The goal of this study was to determine the prevalence of serious gastrointestinal (GI) lesions, identified by endoscopy in patients with iron deficiency and anaemia compared with patients with iron deficiency without anaemia. METHODS: One thousand five hundred and eighteen patients with a ferritin value of or=300 mg/dL were retrospectively investigated using oesophagogastroduodenoscopy and colonoscopy between January 2005 and September 2006. The lesions identified were classified as clinically important according to standard predetermined criteria. RESULTS: Among the 1518 cases, 749 patients had anaemia and 769 had normal haemoglobin levels. Clinically important lesions were identified in 24.6% of the patients with anaemia and in 22.8% of the patients without anaemia (P > 0.05). The frequency of lower GI tract lesions (13.6 vs 11.4%, P > 0.05) and upper GI tract lesions (11.9 vs 12.5%, P > 0.05) was similar in the comparisons between the two groups. However, the frequency of malignant GI lesions was higher in the patients with anaemia (5.1 vs 0.7%, P < 0.01). In addition, the patients without anaemia were significantly more likely to have early-stage neoplasia (adenoma, early gastric cancer and Dukes' A and B colon cancer) than were the patients with anaemia (98.4 vs 52.5%, P < 0.01). CONCLUSION: The results of this study suggest that patients with iron deficiency should undergo endoscopic evaluation of the GI tract, irrespective of whether they have anaemia. The endoscopic evaluation of the GI tract in patients with iron deficiency without anaemia could provide an opportunity for the detection of early-stage neoplasia at a curable stage.

An evaluation of education and implementation of psychosocial interventions within one UK mental healthcare trust.

Psychosocial interventions (PSI), though recommended in the NICE guidelines for schizophrenia and bipolar affective disorder, are not routinely available to people with a serious mental illness in the UK. Education and training initiatives to equip mental health professionals with skills in PSI have grown over the last decade; yet the literature indicates serious problems in implementation of PSI in routine service provision. This paper examines on a local level the factors which support and limit the education and practice of PSI in one UK mental healthcare trust. It reports on a survey of trainees and their managers which aims to evaluate the impact of a PSI training programme and practice development strategy on staff, managers and service provision. The key findings are: a high rate of implementation of PSI by PSI-trained staff in the Trust; a strong association between PSI training and career progression for staff; and the support mechanisms which are most effective in the education and implementation of PSI. The paper concludes that certain measures and support mechanisms have facilitated the successful implementation of PSI with positive outcomes for staff and service provision. Further recommendations are made identifying measures which facilitate the implementation of PSI through an integrated education and practice development strategy owned by all stakeholders.

Developing services for the carers of young adults with early-onset psychosis - implementing evidence-based practice on psycho-educational family intervention.

This paper describes a series of practice and service development initiatives to incorporate the family-inclusive approach into the newly established Early Intervention in Psychosis Service in Berkshire, England. Following a local study on carers' experiences and needs from those who cared for a young adult with a first-episode psychosis (FEP), a series of flexible services for this group of carers has been developed incorporating the much-researched psycho-educational family interventions. The findings of our local phenomenological study on the carers for young adults with FEP clearly specified the unique needs of this group of carers and that well-established approaches in family work and carers support facilities may have to be adapted to meet such needs. This paper reports the service development process through which a series of specially designed carers' services were set up for carers caring for a young adult with FEP. These services were developed to address carers' needs for knowledge, skills and support to cope with their caring roles and situation, from the stressful beginning of a potentially long caring journey.

Tau overexpression in transgenic mice induces glycogen synthase kinase 3beta and beta-catenin phosphorylation.

The abnormal phosphorylations of tau, GSK3beta, and beta-catenin have been shown to perform a crucial function in the neuropathology of Alzheimer's disease (AD). The primary objective of the current study was to determine the manner in which overexpressed htau23 interacts and regulates the behavior and phosphorylation characteristics of tau, GSK3beta, and beta-catenin. In order to accomplish this, transgenic mice expressing neuron-specific enolase (NSE)-controlled human wild-type tau (NSE/htau23) were created. Transgenic mice evidenced the following: (i) tendency toward memory impairments at later stages, (ii) dramatic overexpression of the tau transgene, coupled with increased tau phosphorylation and paired helical filaments (PHFs), (iii) high levels of GSK3beta phosphorylation with advanced age, resulting in increases in the phosphorylations of tau and beta-catenin, (iv) an inhibitory effect of lithium on the phosphorylations of tau, GSK3beta, and beta-catenin, but not in the non-transgenic littermate group. Therefore, the overexpression of NSE/htau23 in the brains of transgenic mice induces abnormal phosphorylations of tau, GSK3beta, and beta-catenin, which are ultimately linked to neuronal degeneration in cases of AD. These transgenic mice are expected to prove useful for the development of new drugs for the treatment of AD.

Impact of hemoglobin on survival of cervical carcinoma patients treated with concurrent chemoradiotherapy is dependent on lymph node metastasis findings by magnetic resonance imaging.

The objective of this study was to confirm whether hemoglobin (Hb) levels during chemoradiotherapy are associated with survival in patients with locally advanced cervical carcinoma and to assess impact of the Hb level on survival according to lymph node (LN) metastasis. A retrospective review of 85 cervical carcinoma patients treated with concurrent chemoradiotherapy was conducted. The stage of disease ranged between FIGO stage IB and stage IVA. Disease-free and overall survivals were evaluated by univariate and multivariate analyses. After median follow-up of 35.7 months, 24 patients developed recurrence of disease and 14 patients died from their disease. Stage, LN metastasis, and squamous cell carcinoma antigen and Hb levels during chemoradiation were correlated significantly with survival (P < 0.05). Maintenance of Hb above 10.0 g/dL was associated with better survival (P < 0.05). However, no such benefits were observed in patients with LN metastasis by magnetic resonance imaging (MRI). Multivariate Cox regression hazard model showed that Hb levels during chemoradiation were an independent prognostic factor in patients without LN metastasis by MRI. Maintenance of Hb during chemoradiation is of benefit in cervical carcinoma patients without LN metastasis but not with LN metastasis by MRI.

Developing services for the carers of young adults with early-onset psychosis--listening to their experiences and needs.

The care-giving experience of carers of young adults with early onset psychosis is relatively unexplored. New carers are less likely to be engaged with local services for carers and families, than those more established in their caring role. Understanding the experience of these carers provides some valuable insight into the value of caring and in guiding service development. This paper reports on a study designed to explore carers' experiences of caring for a young adult diagnosed with a first psychotic episode and their needs in relation to the development of an early intervention for psychosis service. A phenomenological approach was used. Eleven carers were given a semi-structured interview in their own homes. All of the carers in the study had a son with early onset psychosis. The outcome revealed that all carers were providing a comprehensive range of practical, emotional and financial support for their son including initiating and sustaining engagement between them and local mental health services. Many carers were felt to be invisible and silent partners in care and felt under-valued by mental health services.

Implementing a self-management model of relapse prevention for psychosis into routine clinical practice.

This paper describes an implementation project to incorporate an evidence-based, structured model of relapse prevention into routine clinical practice at the Community Mental Health Team in Reading, Berkshire. This project has currently reached the end of the pilot stage, which this paper reports in details. It is proposed that clinicians will adopt Smith's Self-Management Training Manual for individuals with psychosis as a clinical tool for working with patients who have schizophrenic-form disorders or bipolar affective disorders with psychosis. Effects of the proposed change are considered from the viewpoint of the clients and families/carers, the clinicians and the service. The process of transition and its impact on members of the multidisciplinary team is examined. It includes an audit of Care Programme Approach (CPA) forms and a staff survey, which give background information on the needs for improvement and staff development initiatives. A pilot study incorporating the structured relapse prevention work into the local community mental health team is also underway. The method of evaluation and dissemination to the wider team and service settings across the organizational boundaries is reviewed with implications for practice drawn. This paper aims to describe the background and development of this ongoing development project whilst focusing on the current pilot stage. Ongoing work will be carried out in addressing and reporting the outcomes of the full project in future papers.