Basement membrane extract potentiates the endochondral ossification phenotype of bone marrow-derived mesenchymal stem cell-based cartilage organoids.

Endochondral ossification is a developmental process in the skeletal system and bone marrow of vertebrates. During endochondral ossification, primitive cartilaginous anlages derived from mesenchymal stem cells (MSCs) undergo vascular invasion and ossification. In vitro regeneration of endochondral ossification is beneficial for research on the skeletal system and bone marrow development as well as their clinical aspects. However, to achieve the regeneration of endochondral ossification, a stem cell-based artificial cartilage (cartilage organoid, Cart-Org) that possesses an endochondral ossification phenotype is required. Here, we modified a conventional 3D culture method to create stem cell-based Cart-Org by mixing it with a basement membrane extract (BME) and further characterized its chondrogenic and ossification properties. BME enlarged and matured the bone marrow MSC-based Cart-Orgs without any shape abnormalities. Histological analysis using Alcian blue staining showed that the production of cartilaginous extracellular matrices was enhanced in Cart-Org treated with BME. Transcriptome analysis using RNA sequencing revealed that BME altered the gene expression pattern of Cart-Org to a dominant chondrogenic state. BME triggered the activation of the SMAD pathway and inhibition of the NK-κB pathway, which resulted in the upregulation of SOX9, COL2A1, and ACAN in Cart-Org. BME also facilitated the upregulation of genes associated with hypertrophic chondrocytes (IHH, PTH1R, and COL10A1) and ossification (SP7, ALPL, and MMP13). Our findings indicate that BME promotes cartilaginous maturation and further ossification of bone marrow MSC-based Cart-Org, suggesting that Cart-Org treated with BME possesses the phenotype of endochondral ossification.

Accurate carbon storage estimation for the salt marsh ecosystem based on Bayesian maximum entropy approach - A case study for the Spartina alterniflora ecosystem.

The blue carbon ecosystem, including the salt marsh ecosystem, possesses a significant carbon sequestration potential. Therefore, accurately quantifying the carbon storage within such ecosystems is crucial for the adequate accounting of carbon sequestration. The present work chose a Spartina alterniflora ecosystem in the Xiaogan Island (China) as the study area (approximately 11 ha), and employed the Bayesian maximum entropy (BME) approach to assimilate both hard organic carbon (OC) data and soft OC data measured from 2 cm and 10 cm stratified samples. A 3-dimensional model was developed for space-time OC estimation purposes based on the sediment chronology results. The 10-fold BME cross validation results demonstrated a high estimation accuracy, with the R2, RMSE and MAE values equal to 0.8564, 0.1026 % and 0.0748 %, respectively. A noteworthy outcome was the BME-generated carbon storage density maps with 1 m spatial resolution. These maps revealed that the carbon storage density at the top 30 cm sediment depth in the stable zone (with elder stand age of S. alterniflora) was higher than that in the rapid expansion zone, i.e., 71.79 t/ha vs. 69.82 t/ha, respectively. Additionally, the study found that the averaged carbon burial rate and the total carbon storage at the top 30 cm sediment depth across the study area were 266 g C/m2/yr and 781.50 t, respectively. Lastly, the proposed BME-based framework of carbon storage estimation was found to be versatile and applicable to other blue carbon ecosystems. This approach can foster the development of a standardized carbon sink metrological methodology for diverse blue carbon ecosystems.

Human milk extracellular vesicles enhance muscle growth and physical performance of immature mice associating with Akt/mTOR/p70s6k signaling pathway.

Extracellular vesicles (EVs) play an important role in human and bovine milk composition. According to excellent published studies, it also exerts various functions in the gut, bone, or immune system. However, the effects of milk-derived EVs on skeletal muscle growth and performance have yet to be fully explored. Firstly, the current study examined the amino acids profile in human milk EVs (HME) and bovine milk EVs (BME) using targeted metabolomics. Secondly, HME and BME were injected in the quadriceps of mice for four weeks (1 time/3 days). Then, related muscle performance, muscle growth markers/pathways, and amino acids profile were detected or measured by grip strength analysis, rotarod performance testing, Jenner-Giemsa/H&E staining, Western blotting, and targeted metabolomics, respectively. Finally, HME and BME were co-cultured with C2C12 cells to detect the above-related indexes and further testify relative phenomena. Our findings mainly demonstrated that HME and BME significantly increase the diameter of C2C12 myotubes. HME treatment demonstrates higher exercise performance and muscle fiber densities than BME treatment. Besides, after KEGG and correlation analyses with biological function after HME and BME treatment, results showed L-Ornithine acts as a "notable marker" after HME treatment to affect mouse skeletal muscle growth or functions. Otherwise, L-Ornithine also significantly positively correlates with the activation of the AKT/mTOR pathway and myogenic regulatory factors (MRFs) and can also be observed in muscle and C2C12 cells after HME treatment. Overall, our study not only provides a novel result for the amino acid composition of HME and BME, but the current study also indicates the advantage of human milk on skeletal muscle growth and performance.

Alveolar bone remodelling and stability of mandibular incisors in adult patients after orthodontic treatment with premolar extractions: A prospective follow-up study.

OBJECTIVE: To evaluate alveolar bone remodelling and stability of mandibular incisors in adult orthodontic extraction patients. MATERIALS AND METHODS: Cone-beam computed tomography images of 25 adult patients undergoing extraction were collected before orthodontic treatment (T1), after orthodontic treatment (T2), and after at least 1 year of retention (T3). The labial and lingual alveolar bone heights (ABH), thickness (ABT), and tooth movement of the mandibular incisors were measured during the retraction (T2-T1) and retention (T3-T2) periods. According to the tooth movement during the retention period, the mandibular incisors were further divided into stable and unstable groups, and the correlation between L1-BMe and stability was evaluated. RESULTS: The labial and lingual ABHs significantly increased after orthodontic treatment and decreased during the retention period. The lingual ABH was 7.36 ± 2.27 mm at T2 and 5.37 ± 1.98 mm at T3, indicating a great bone remodelling capacity. The labial ABT exhibited a significant increase during orthodontic treatment and a slight decrease during the retention period, while the lingual ABT showed an opposite trend. During the retention period, the root apex moved labially into the alveolar bone housing. L1-BMe significantly increased during orthodontic treatment and decreased during the retention period. Compared to the stable group, lingual ABH and L1-BMe at T2 was significantly higher, and lingual ABT was smaller in the unstable group. CONCLUSION: Post-treatment lingual alveolar bone defects of the mandibular incisors could recover to some extent during the retention period. There was a negative correlation between post-treatment L1-BMe and mandibular incisor stability.

Adaptive Responses of a Peroxidase-like Polyoxometalate-Based Tri-Assembly to Bacterial Microenvironment (BME) Significantly Improved the Anti-Bacterial Effects.

The present study presents the tertiary assembly of a POM, peptide, and biogenic amine, which is a concept to construct new hybrid bio-inorganic materials for antibacterial applications and will help to promote the development of antivirus agents in the future. To achieve this, a Eu-containing polyoxometalate (EuW10) was first co-assembled with a biogenic amine of spermine (Spm), which improved both the luminescence and antibacterial effect of EuW10. Further introduction of a basic peptide from HPV E6, GL-22, induced more extensive enhancements, both of them being attributed to the cooperation and synergistic effects between the constituents, particularly the adaptive responses of assembly to the bacterial microenvironment (BME). Further intrinsic mechanism investigations revealed in detail that the encapsulation of EuW10 in Spm and further GL-22 enhanced the uptake abilities of EuW10 in bacteria, which further improved the ROS generation in BME via the abundant H2O2 involved there and significantly promoted the antibacterial effects.

Prediction of radiographic progression during a treat-to-target strategy by the sequential application of MRI-proven bone marrow oedema and power-Doppler grade ≥2 articular synovitis in rheumatoid arthritis: Retrospective observational study.

OBJECTIVES: To investigate the appropriate timing, useful findings and combination of magnetic resonance imaging (MRI) and ultrasound (US) for predicting the radiographic progression in early rheumatoid arthritis (RA). METHODS: Forty-four active RA patients, who examined by both of MRI and US in the symptomatic wrist and finger joints, were recruited in Nagasaki University Hospital from 2010 to 2017 and treated by the treat-to-target therapeutic strategy for 1 year. MRI was evaluated by RA MRI scoring and US by Outcomes Measures in Rheumatology Clinical Trial, respectively. Plain radiographs were assessed by the Genant-modified Sharp score for the symptomatic side in the same manner as MRI and US. Radiographic progression was defined as an annual increase ≥0.75 at 1 year. Factors associated with radiographic progression were analysed. Also, the optimal combination of MRI and US at each timepoint was considered. RESULTS: Logistic regression model revealed that MRI-proven bone marrow oedema at baseline and 6 months and joint counts of power-Doppler grade ≥2 articular synovitis at 3 or 6 months were significantly associated with radiographic progression at 1 year. CONCLUSION: This study may suggest the favourable timing and combination of MRI and US at each point to predict radiographic progression in patients with early-stage RA.

Multiple stakeholder perspectives of factors influencing differential outcomes for ethnic minority students on health and social care placements: a qualitative exploration.

BACKGROUND: Despite considerable efforts there continues to be a degree awarding gap within the United Kingdom (UK) between the proportion of White British students receiving higher classifications, compared to ethnic minority UK-domiciled students. Practice placement elements constitute approximately 50% of most health and social care programmes, yet surprisingly little research exists related to the factors which may contribute to ethnic minority student placement outcomes or experiences. This study bridges this evidence gap by exploring factors influencing differential placement outcomes of ethnic minority students from the perspectives of key stakeholders. METHODS: The study followed a descriptive qualitative research design and was multi-disciplinary, with participants drawn from across nursing, midwifery, social work and the allied health professions. Participants from four stakeholder categories (ethnic minority students, academic staff, placement educators and student union advisors) were invited to join separate focus groups. Focus groups were recorded and transcribed and analysed thematically. RESULTS: Ten separate focus groups [n = 66] yielded three primary themes: 1) recognition, which highlighted stakeholder perceptions of the issues [sub-themes: acknowledging concerns; cultural norms; challenging environments]; 2) the lived experience, which primarily captured ethnic minority student perspectives [sub-themes: problematising language and stereotyping, and being treated differently]; 3) surviving not thriving, which outlines the consequences of the lived experience [sub-themes: withdrawing mentally, feeling like an alien]. CONCLUSION: This study presents a rich exploration of the factors affecting differential outcomes of ethnic minority students on practice placements through the lens of four different stakeholder groups. To our knowledge this is the first study in which this comprehensive approach has been taken to enable multiple viewpoints to be accessed across a wide range of health and social care professions. The issues and challenges raised appear to be common to most if not all of these disciplines. This study highlights the urgent need to value and support our ethnic minority students to remove the barriers they face in their practice learning settings. This is a monumental challenge and requires both individuals and organisations to step up and take collective responsibility.

'Black African' identification and the COVID-19 pandemic in Britain: A site for sociological, ethical and policy debate.

This paper is a narrative review of the use of collective terminology in relation to race and health in Britain, with particular reference to the 'Black African' community. 'Black Africans' have been categorised in the 1991-2011 censuses with added free-text in 2021 in response to user demand. However, the UK government is increasingly reporting data for the 'Black' pan-ethnicity, especially in the even more generalised 'BAME' ('Black, Asian and Minority Ethnic') acronym in COVID-19 pandemic reports. The consequences of this practice are addressed. Firstly, with respect to ethical challenges, Black Africans find their conscription by government into the term BAME offensive and do not accept it as a self-descriptor. This labelling, which subsumes Black Africans' self-assigned ethnicity in the census, and consequent misrecognition may be interpreted as a micro-aggression (a term coined in the 1970s but used here to denote microinvalidation), as suggested in the current black activism of the 'Black Lives Matter movement'. Secondly, ONS has warned that concealed heterogeneity renders the pan-ethnicities unreliably crude, making them scientifically inaccurate. Analysts are recommended to present ethnic group data for the full census classification where possible for reasons of validity and respect for the patient as arbiter of their ethnic group.

Contrasting effects of transforming growth factor ß1 on programmed cell death of bovine mammary epithelial cell lines MAC-T and BME-UV1.

A previous study in the bovine mammary epithelial cell line BME-UV1 demonstrated that suppression of the phosphatidylinositol-4,5-biphosphate 3 kinase (PI3K)/AKT (somatotropic) signaling pathway was required for transforming growth factor ß1 (TGFß1)-induced programmed cell death (PCD). To investigate whether this is a universal mechanism for TGFß1 to induce PCD in bovine mammary epithelium, we compared TGFß1 modulation of PI3K/AKT and its role in PCD in 2 bovine mammary epithelial cell lines: MAC-T and BME-UV1. In MAC-T cells, TGFß1 promoted cell survival, and this paralleled a reduction in PI3K/AKT activity, rather than an increase. In BME-UV1 cells, TGFß1 induced PCD, and this was accompanied by a time-dependent effect on PI3K/AKT activity, including an initial significant increase in the phosphorylation of AKT at 3 h, followed by a reduction between 12 and 24 h, and then an increase at 48 h. Inhibition of AKT activity enhanced TGFß1-induced PCD in BME-UV1 cells but had no effect on MAC-T cells, suggesting that TGFß1 mediates PCD in BME-UV1 cells through suppression of AKT activity. Inhibition of TGFß receptor type I (TßRI) kinase activity completely abrogated TGFß1-induced PCD in BME-UV1 cells but had no effect on TGFß1-induced suppression of PCD in MAC-T cells, demonstrating that TGFß1-induced PCD in BME-UV1 cells is dependent on TßRI/SMAD signaling. These and previous observations suggest that the different effects of TGFß1 on PCD in these cell lines might involve noncanonical signaling pathways other than PI3K/AKT, and may reflect their different lineages. Future studies should address this finding, taking into consideration the effect that different culture conditions might have on cell phenotype.

Using Card Games to study cultural differences in men's social talk about prostate cancer.

AIM: To report the Card Games approach used to study men's talk about their risk for prostate cancer and as a method of data collection to analyse patterns of talk among distinct cultural groups. DESIGN: A constructivist grounded theory approach using focus groups to analyse men's social talk about prostate cancer. METHODS: Data were collected using three focus groups with African-Caribbean, Somali, and White British men. The focus groups were conducted in a location of the men's choice with a focus group facilitator and observer. Four Card Games were given to the men to encourage social talk. RESULTS: The African-Caribbean men had the most democratic talk with the use of agreement and disagreement and the Somali men were the most inclusive of others and used the most humour. The White British men were competitive in their talk and the least inclusive of each other's views. CONCLUSION: The Card Games revealed differences in the pattern of talk, which provided insight into how men may use social talk to develop their understanding of prostate cancer risk. This is useful for healthcare professionals as it provides a grounding for structuring discussions with men about prostate cancer, while understanding of how risk-related knowledge may be reconstructed in social talk and interactions. IMPACT: The methodology discussed in this paper addressed the use of focus group to analyse talk of men from culturally diverse groups. The use of Card Games allowed the talk between the men to take centre stage and this allowed differences in the social talk of the men to become apparent. The use of this methodology could have an impact on approaches to researching cultural understandings of cancer risk, which may provide evidence on effective delivery of sociocultural relevant health education relating to cancer screening.

The IDEMCare Study-Improving Dementia Care in Black African and Caribbean Groups: A feasibility cluster randomised controlled trial.

OBJECTIVE: We evaluated the feasibility and acceptability of a tailored evidence-based intervention, consisting of a leaflet and a letter, to encourage timely help-seeking for dementia in Black elders. METHODS: Participating GP surgeries were randomised to send either the intervention or a control leaflet about ageing well to Black patients aged ≥50 years old without known dementia. We interviewed patients 2 weeks later about the intervention's acceptability using closed and open-ended questions, and they completed a Theory-of-Planned-behaviour questionnaire about what they would do if they developed memory problems, which they also completed 4 months later. RESULTS: Five of 26 surgeries approached agreed to invite patients. Sixty-five patients responded, of whom 61 (93.8%) agreed to participate. At 2 weeks, we consented and interviewed 47/61 (77%), of whom 24 received the intervention, and at 4 months we followed up 43/47 (91.5%). At 2 weeks, 44/47 (93.6%) found either intervention acceptable to receive by post, including 23/24 of the intervention. Nineteen of 24 (79.2%) reported reading the intervention leaflet compared with 13/23 (56.5%) controls. The intervention leaflet made 16/24 (66.7%) think about visiting their doctor for memory problems and led 4 to help-seeking behaviour. We calculated that 191 patients and 24 surgeries are required for an efficacy trial. CONCLUSIONS: Given the intervention is acceptable, inexpensive, and unlikely to cause harm, we judge it appropriate to disseminate it without a full-scale trial. Recruitment attainment, retention, and projected sample size calculation indicated feasibility for a larger trial.

Inhibition of silkworm vacuolar-type ATPase activity by its inhibitor Bafilomycin A1 induces caspase-dependent apoptosis in an embryonic cell line of silkworm.

Vacuolar-type ATPase (V-ATPase) is a type of hydrogen ion transporter located in the vesicular membrane-like system, which mediates active transport and intracellular acidification in various compartments. In mammals, V-ATPase has been reported to play a key role in cell proliferation and apoptosis. The studies of V-ATPase in silkworm mainly focus on the acidification regulation of midgut and silk gland and immune resistance. However, there are few reports about the function of silkworm V-ATPase on cell proliferation, autophagy, and apoptosis. Thus, the function of V-ATPase in a cell line of Bombyx mori (BmE) was investigated by treating the cell line with bafilomycin A1, a specific inhibitor of V-ATPase. Cell counting kit 8 (CCK8) and flow cytometry analysis showed that bafilomycin A1 treatment decreased the cell proliferation activity, affected the cell cycle progression and induced cell apoptosis. LysoTracker Red staining showed that the target of bafilomycin A1 is lysosome. The expression of all autophagy-related genes ( BmATG5, BmATG6, and BmATG8) decreased, indicating that cell autophagy was inhibited. The analysis of the apoptosis pathway demonstrated that inhibiting the activity of V-ATPase of BmE cells could promote mitochondria to release cytochrome C, inhibit the expression of BmIAP, and activate the caspase cascade to induce apoptosis. All these findings systematically illustrate the effects of V-ATPase on the proliferation, autophagy, and apoptosis in BmE cells, and provide new ideas and a theoretical basis for further study on the function of V-ATPase in BmE.

Relative transcription of autophagy-related genes in Amblyomma sculptum and Rhipicephalus microplus ticks.

Ticks endure stressful off-host periods and perform as vectors of a diversity of infectious agents, thus engaging pathways that expectedly demand for autophagy. Little is known of ticks' autophagy, a conserved eukaryotic machinery assisting in homeostasis processes that also participates in tissue-dependent metabolic functions. Here, the autophagy-related ATG4 (autophagin-1), ATG6 (beclin-1) and ATG8 (LC3) mRNAs from the human diseases vector Amblyomma sculptum and the cattle-tick Rhipicephalus microplus were identified. Comparative qPCR quantifications evidenced different transcriptional status for the ATG genes in the salivary glands (SG), ovaries and intestines of actively feeding ticks. These ATGs had increased relative transcription under nutrient-deprivation, as determined by validation tests with R. microplus embryo-derivative cells BME26 and A. sculptum SG explants incubations in HBSS. Starvation lead to 4-31.8× and ~ 60-500× increments on the ATGs mRNA loads in BME26 and A. sculptum SG explants, respectively. PI3K inhibitor 3MA treatment also affected ATGs expression in BME26. Some ATGs were more transcribed in the SGs than in the ovaries of cattle-ticks. Amblyomma sculptum/R. microplus interspecific comparisons showed that ATG4 and ATG6 were 0.18× less expressed in A. sculptum SGs, but ~ 10-100× more expressed in their ovaries when compared to R. microplus organs. ATG4 and ATG8a transcript loads were ~ 120× and ~ 40× higher, respectively, in A. sculptum intestines when compared to cattle-ticks of similar weight category. ATGs expression in A. sculptum intestines increased with tick weight, indicating Atgs contribution to intracellular blood digestion. Possible roles of the autophagy machinery and their organ-specific expression profile on vector biology are discussed.

A Bayesian maximum entropy-based methodology for optimal spatiotemporal design of groundwater monitoring networks.

This paper presents a new methodology for analyzing the spatiotemporal variability of water table levels and redesigning a groundwater level monitoring network (GLMN) using the Bayesian Maximum Entropy (BME) technique and a multi-criteria decision-making approach based on ordered weighted averaging (OWA). The spatial sampling is determined using a hexagonal gridding pattern and a new method, which is proposed to assign a removal priority number to each pre-existing station. To design temporal sampling, a new approach is also applied to consider uncertainty caused by lack of information. In this approach, different time lag values are tested by regarding another source of information, which is simulation result of a numerical groundwater flow model. Furthermore, to incorporate the existing uncertainties in available monitoring data, the flexibility of the BME interpolation technique is taken into account in applying soft data and improving the accuracy of the calculations. To examine the methodology, it is applied to the Dehgolan plain in northwestern Iran. Based on the results, a configuration of 33 monitoring stations for a regular hexagonal grid of side length 3600 m is proposed, in which the time lag between samples is equal to 5 weeks. Since the variance estimation errors of the BME method are almost identical for redesigned and existing networks, the redesigned monitoring network is more cost-effective and efficient than the existing monitoring network with 52 stations and monthly sampling frequency.

The supervisory ward manager's role: progress on Compassion in Practice action area four.

In 2012, the Department of Health published Compassion in Practice, which included six areas for action. Action area four suggests that ward managers and leaders should be supervisory, and not included in ward staff numbers. The recommendation has recently been changed to promote black and minority ethnic (BME) leadership in the NHS. This article examines the literature on supervisory nurse leader roles between 2007 and 2017 to identify what, if any, progress has been made. Although supervisory status can improve care at ward level, and was endorsed by the Francis Report, it seems that few care providers in England have invested in this, possibly because it is voluntary, rather than a statutory requirement. The article argues that, rather than focusing on BME leadership, commissioners and providers should consider implementing the original action four to support the lessons learned in the Francis Report.

Equality in sexual health promotion: a systematic review of effective interventions for black and minority ethnic men who have sex with men.

BACKGROUND: Over the past decade, new diagnoses of HIV have increased eightfold among men who have sex with men (MSM) of other or of mixed ethnicity in the UK. Yet there is little intervention research on HIV among black and minority ethnic (BME) MSM. This article aimed to identify effective HIV and sexual health prevention strategies for BME MSM. METHODS: We searched three databases PubMed, Scopus and PsychInfo using a combination of search terms: MSM or men who have sex with men and women (MSMW); Black and Minority Ethnic; HIV or sexual health; and evaluation, intervention, program* or implementation. We identified a total of 19 studies to include in the review including those which used randomised control, pre/post-test and cross-sectional design; in addition, we included intervention development studies. RESULTS: A total of 12 studies reported statistically significant results in at least one of the behavioural outcomes assessed; one study reported significant increases in HIV knowledge and changes in safer sex practices. In 10 studies, reductions were reported in unprotected anal intercourse (UAI), number of sexual partners, or in both of these measures. Six out of the 13 studies reported reductions in UAI; while seven reported reductions in number of sexual partners. Seven were intervention development studies. CONCLUSIONS: Research into the mechanisms and underpinnings of future sexual health interventions is urgently needed in order to reduce HIV and other sexually transmitted infection (STI) among UK BME MSM. The design of interventions should be informed by the members of these groups for whom they are targeted to ensure the cultural and linguistic sensitivity of the tools and approaches generated.

Ethnicity and detention: are Black and minority ethnic (BME) groups disproportionately detained under the Mental Health Act 2007?

PURPOSE: There is substantial evidence to suggest that Black and minority ethnic (BME) patients are disproportionately detained under the Mental Health Act (MHA). We examined ethnic differences in patients assessed for detention and explored the effect of ethnicity after controlling for confounders. METHODS: A prospective study of all MHA assessments conducted in 1 year (April 2009-March 2010) within Birmingham and Solihull Mental Health Foundation Trust, UK. Proportion of assessments and detentions within denominator population of service users and regional populations were calculated. Multiple regression analysis was conducted to determine which variables were associated with the outcome of MHA assessment and the role of ethnicity. RESULTS: Of the 1115 assessments, 709 led to detentions (63.58 %). BME ethnic groups were statistically more likely to be assessed and detained under the MHA as compared to Whites, both in the service user and the ethnic population estimates in Birmingham, UK. MHA detention was predicted by having a serious mental illness, the presence of risk, older age and living alone. Ethnicity was not associated with detention under the MHA with age, diagnosis, risk and level of social support accounted for. CONCLUSION: The BME 'disproportionality' in detention rates seems to be due to higher rates of mental illness, greater risk and poorer levels of social support rather than ethnicity per se.

Community Engagement in a complex intervention to improve access to primary mental health care for hard-to-reach groups.

BACKGROUND: Despite the availability of effective evidence-based treatments for depression and anxiety, many 'harder-to-reach' social and patient groups experience difficulties accessing treatment. We developed a complex intervention, the AMP (Improving Access to Mental Health in Primary Care) programme, which combined community engagement (CE), tailored (individual and group) psychosocial interventions and primary care involvement. OBJECTIVES: To develop and evaluate a model for community engagement component of the complex intervention. This paper focuses on the development of relationships between stakeholders, their engagement with the issue of access to mental health and with the programme through the CE model. DESIGN: Our evaluation draws on process data, qualitative interviews and focus groups, brought together through framework analysis to evaluate the issues and challenges encountered. SETTING & PARTICIPANTS: A case study of the South Asian community project carried out in Longsight in Greater Manchester, United Kingdom. KEY FINDINGS: Complex problems require multiple local stakeholders to work in concert. Assets based approaches implicitly make demands on scarce time and resources. Community development approaches have many benefits, but perceptions of open-ended investment are a barrier. The time-limited nature of a CE intervention provides an impetus to 'do it now', allowing stakeholders to negotiate their investment over time and accommodating their wider commitments. Both tangible outcomes and recognition of process benefits were vital in maintaining involvement. CONCLUSIONS: CE interventions can play a key role in improving accessibility and acceptability by engaging patients, the public and practitioners in research and in the local service ecology.

Measures of gene expression in sputum cells can identify TH2-high and TH2-low subtypes of asthma.

BACKGROUND: The 3-gene signature of periostin, chloride channel accessory 1 (CLCA1), and Serpin ß2 (SERPINB2) in airway epithelial brushings is used to classify asthma into TH2-high and TH2-low endotypes. Little is known about the utility of gene profiling in sputum as a molecular phenotyping method. OBJECTIVE: We sought to determine whether gene profiling in sputum cells can identify T(H)2-high and T(H)2-low subtypes of asthma. METHODS: In induced sputum cell pellets from 37 asthmatic patients and 15 healthy control subjects, PCR was used to profile gene expression of the epithelial cell signature of IL-13 activation (periostin, CLCA1, and SERPINB2), TH2 genes (IL4, IL5, and IL13), and other genes associated with airway TH2 inflammation. RESULTS: Gene expression levels of CLCA1 and periostin, but not SerpinB2, were significantly higher than normal in sputum cells from asthmatic subjects. Expression levels of IL-4, IL-5, and IL-13 were also significantly increased in asthmatic patients and highly correlated within individual subjects. By combining the expression levels of IL-4, IL-5, and IL-13 in a single quantitative metric ("T(H)2 gene mean"), 26 (70%) of the 37 asthmatic patients had T(H)2-high asthma, which was characterized by more severe measures of asthma and increased blood and sputum eosinophilia. TH2 gene mean values tended to be stable when initial values were very high or very low but fluctuated above or below the T(H)2-high cutoff when initial values were intermediate. CONCLUSION: IL-4, IL-5, and IL-13 transcripts are easily detected in sputum cells from asthmatic patients, and their expression levels can be used to classify asthma into T(H)2-high and T(H)2-low endotypes.

Meeting the unmet support needs of BME men with prostate cancer.

Men with prostate cancer from black and minority ethnic (BME) communities have reported many unmet information and support needs. A literature review identified the many challenges health professionals face in addressing these unmet needs, and suggested that not enough is known about the psychosocial effects of a prostate cancer diagnosis on men from BME communities in the UK. Affected men may have little or no awareness or knowledge of prostate cancer, receive inadequate information and fear the disease. Nurses can address these issues through improving patients' knowledge and awareness of prostate cancer, providing high-quality information to patients and their families, alleviating fear and promoting survivorship among this minority group; they can also facilitate staff training. Health professionals should look beyond the physical effects and consider the psychosocial effects of such a diagnosis when assessing the needs of these men. Practitioners need to overcome the various challenges to meeting these needs to provide more effective care to men from BME groups.