The nature and correlates of paid and unpaid work among service users of London Community Mental Health Teams

Aims Little is known about how the rates and characteristics of mental health service users in unpaid work, training and study compare with those in paid employment. Methods: From staff report and patient records, 1353 mental health service users of seven Community Mental Health Teams in two London boroughs were categorised as in paid work, unpaid vocational activity or no vocational activity. Types of work were described using Standard Occupational Classifications. The characteristics of each group were reported and associations with vocational status were explored. Results: Of the sample, 5.5% were in paid work and 12.7% were in unpaid vocational activity, (including 5.3% in voluntary work and 8.1% in study or training). People in paid work were engaged in a broader range of occupations than those in voluntary work and most in paid work (58.5%) worked part-time. Younger age and high educational attainment characterised both groups. Having sustained previous employment was most strongly associated with being in paid work. Conclusions: Rates of vocational activity were very low. Results did not suggest a clear clinical distinction between those in paid and unpaid activity.The motivations for and functions of unpaid work need further research

Promising inhibition of diabetes-related enzymes and antioxidant properties of Ptilostemon casabonae leaves extract

Type 2 diabetes (T2D) is a progressive metabolic disorder of glucose metabolism. One of the therapeutic approaches for the treatment of T2D is reducing postprandial hyperglycaemia through inhibition of the digestive enzymes α-glucosidase and α-amylase. In this context, aimed at identifying natural products endowed with anti-T2D potential, we focused on Ptilostemon casabonae (L.) Greuter, a species belonging to Asteraceae family. Enzymatic inhibition, antioxidant activity, phenolic composition and cellular assays were performed. This study revealed that the P. casabonae hydroalcoholic extract exerts a potent inhibitory activity against α-glucosidase. This activity is supported by an antioxidant effect, preventing ROS formation in a stressed cellular system. HPLC-PDA-MS/MS analysis, revealed a complex polyphenolic fraction. Among the tested pure compounds, 1,5-dicaffeoylquinic acid, apigenin and rutin displayed good α-glucosidase inhibitory activity. Our study suggested new potential of P. casabonae encouraging us to further testing the possible therapeutic potential of this extract

Pathogenic and Prognostic Roles of Paraneoplastic Leukocytosis in Cervical Cancer: Can Genomic-Based Targeted Therapies Have a Role? A Literature Review and an Emblematic Case Report

Tumor-associated leukocytosis has been associated with poor prognosis in cervical cancer. Leukemoid reaction (i.e., white blood cell count > 40,000/µL) is defined paraneoplastic (PLR) when it occurs in the presence of a cytokine-secreting tumor (CST) without neoplastic bone marrow infiltration. Cervical cancers displaying PLR represent a peculiar entity characterized by a rapidly progressive behavior typically associated with chemo-radioresistance. The present paper aims to review the literature about the pathogenetic mechanisms of PLR and its prognostic role in cervical cancer. Moreover, it reports the emblematic case of a patient with an advanced cervical cancer associated with PLR that was chemotherapy resistant. The patient underwent a palliative cytoreductive surgery of high complexity, obtaining a temporary regression of PLR. The tumor sample stained positive for G-CSF and IL-6, thus indicating a CST. Notably, the tumor genomic analysis revealed a PI3CKA mutation. Therefore, at the instrumental evidence of a rapidly progressive disease relapse, which was accompanied by reappearance of PLR, we started a targeted treatment with a selective PIK3 inhibitor alpesilib combined with the JAK1-2 inhibitor ruxolitinib. We achieved a relief of symptoms and leukocytosis; however, severe side effects necessitated the treatment suspension. In conclusion, as therapeutic strategies for cancer with PLR are scarcely reported in literature, our study could contribute to expand our understanding of the topic and provide a basis for further research

Service user and carer experiences of seeking help for a first episode of psychosis: a UK qualitative study

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Long duration of untreated psychosis (DUP) is associated with poor outcomes and low quality of life at first contact with mental health services. However, long DUP is common. In order to inform initiatives to reduce DUP, we investigated service users' and carers' experiences of the onset of psychosis and help-seeking in two multicultural, inner London boroughs and the roles of participants' social networks in their pathways to care. Method In-depth interviews were conducted with service users and carers from an early intervention service in North London, purposively sampled to achieve diversity in sociodemographic characteristics and DUP and to include service users in contact with community organisations during illness onset. Interviews covered respondents' understanding of and reaction to the onset of psychosis, their help-seeking attempts and the reactions of social networks and health services. Thematic analysis of interview transcripts was conducted. Results Multiple barriers to prompt treatment included not attributing problems to psychosis, worries about the stigma of mental illness and service contact, not knowing where to get help and unhelpful service responses. Help was often not sought until crisis point, despite considerable prior distress. The person experiencing symptoms was often the last to recognise them as mental illness. In an urban UK setting, where involved, workers in non-health community organisations were frequently willing to assist help-seeking but often lacked skills, time or knowledge to do so. Conclusion Even modest periods of untreated psychosis cause distress and disruption to individuals and their families. Early intervention services should prioritise early detection. Initiatives aimed at reducing DUP may succeed not by promoting swift service response alone, but also by targeting delays in initial help-seeking. Our study suggests that strategies for doing this may include addressing the stigma associated with psychosis and community education regarding symptoms and services, targeting not only young people developing illness but also a range of people in their networks, including staff in educational and community organisations. Initiatives to enhance the effective involvement of staff in community organisations working with young people in promoting help-seeking merit research.Peer Reviewe

Mendelian breeding units <i>versus</i> standard sampling strategies: mitochondrial DNA variation in southwest Sardinia

We report a sampling strategy based on Mendelian Breeding Units (MBUs), representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region) in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits

Generation of quantum-certified random numbers using on-chip path-entangled single photons from an LED

Single-photon entanglement is a peculiar type of entanglement in which two or more degrees of freedom of a single photon are correlated quantum-mechanically. Here, we demonstrate a photonic integrated chip (PIC) able to generate and manipulate single-photon path-entangled states, using a commercial red LED as light source. A Bell test, in the Clauser, Horne, Shimony and Holt (CHSH) form, is performed to confirm the presence of entanglement, resulting in a maximum value of the CHSH correlation parameter equal to $2.605 \pm 0.004$. This allows us to use it as an integrated semi-device independent quantum random number generator able to produce certified random numbers. The certification scheme is based on a Bell's inequality violation and on a partial characterization of the experimental setup, without the need of introducing any further assumptions either on the input state or on the particular form of the measurement observables. In the end a min-entropy of $33\%$ is demonstrated.Comment: 22 pages, 8 figure

Interaction between dietary and lifestyle risk factors and N-Acetyltransferase polymorphisms in B-Cell lymphoma etiology

Background: Gene-environment interactions are suggested to play a role in lymphomagenesis. Methods: We tested the interaction between the NAT1/NAT2 phenotype, as inferred by the respective genotypes, and exposure to dietary and lifestyle risk factors, in 199 incident lymphoma cases and 188 population controls. We used unconditional logistic regression to calculate the odds ratio (OR) and its 95% confidence interval for lymphoma (all subtypes combined) and B cell lymphoma, associated to the rapid NAT1 phenotype and to the intermediate and slow NAT2 phenotype, and to the estimated dietary intake of heterocyclic amines and folate, current smoking, coffee, and use of permanent hair dyes, as well as the respective interaction terms. We adjusted the ORs by age, gender, and education, and we used the likelihood ratio test to test the interaction between the NAT1, NAT2 phenotype and the dietary and lifestyle variables. Results: We observed an increase in risk of lymphoma (all subtypes combined) and B-cell lymphoma in particular associated with the estimated above median dietary intake of heterocyclic amines (OR = 4.2, 95%CI 1.2 – 14.8) and folate (OR = 4.1, 95%CI 0.7 – 22.4) among subjects with the NAT1 rapid acetylator phenotype, but not independent on the NAT1 phenotype. The test for interaction was significant for heterocyclic amines, but not for folate (p for interaction = 0.026 and 0.076 respectively). Ever use of permanent hair dyes was associated with an elevated risk independent on the NAT1, NAT2 phenotypes; risk decreased to null among intermediate and slow NAT1 acetylators (p for interaction = 0.010). Conclusions: Our results suggest that NAT1, NAT2 polymorphisms interact with dietary and lifestyle exposures in modulating risk of lymphoma and particularly B-cell lymphoma

Evaluation of a community awareness programme to reduce delays in referrals to early intervention services and enhance early detection of psychosis.

BACKGROUND: Reducing treatment delay and coercive pathways to care are accepted aims for Early Intervention Services (EIS) for people experiencing first episode psychosis but how to achieve this is unclear. A one-year community awareness programme was implemented in a London EIS team, targeting staff in non-health service community organisations. The programme comprised psycho-educational workshops and EIS link workers, and offering direct referral routes to EIS. Its feasibility and its impact on duration of untreated psychosis and pathways to EIS were evaluated. METHODS: Evaluation comprised: pre and post questionnaires with workshop participants assessing knowledge and attitudes to psychosis and mental health services; and a comparison of new service users' "service DUP"(time from first psychotic symptom to first contact with EIS) and pathways to care in the intervention year and preceding year. Focus groups sought stakeholders' views regarding the benefits and limitations of the programme and what else might promote help-seeking. RESULTS: 41 workshops at 36 community organisations were attended by 367 staff. 19 follow up workshops were conducted and 16 services were allocated an EIS link worker. Participants' knowledge and attitudes to psychosis and attitudes to mental health services improved significantly following workshops. In the year of the intervention, only 6 of 110 new service users reached EIS directly via community organisations. For all new referrals accepted by EIS, in the intervention year compared to the previous year, there was no difference in mean or median service DUP. A clear impact on pathways to care could not be discerned. Stakeholders suggested that barriers to referral remained. These included: uncertainty about the signs of early psychosis, disengagement by young people when becoming unwell, and worries about stigma or coercive treatment from mental health services. More general, youth focused, mental health services were proposed. CONCLUSIONS: The community awareness programme did not reduce treatment delays for people experiencing first episode psychosis. Further research is needed regarding effective means to reduce duration of untreated psychosis. Although EIS services are guided to promote access through community engagement, this may not be an effective use of their limited resources. TRIAL REGISTRATION: Current Controlled Trial ISRCTN98260910 Registered 19th May 2010

Single-step green synthesis and characterization of gold-conjugated polyphenol nanoparticles with antioxidant and biological activities

Background: Gold nanoparticles (GNPs) are likely to provide an attractive platform for combining a variety of biophysicochemical properties into a unified nanodevice with great therapeutic potential. In this study we investigated the capabilities of three different natural polyphenols, epigallocatechin-3-gallate (EGCG), resveratrol (RSV), and fisetin (FS), to allow synergistic chemical reduction of gold salts to GNPs and stabilization in a single-step green process. Moreover, antioxidant properties of the nanosystems, as well as preliminary antiproliferative activity and apoptotic process investigation of model EGCG-GNPs on stable clones of neuroblastoma SH-SY5Y cells expressing CFP-DEVD-YFP reporter, were examined. Methods: The GNPs were characterized by physicochemical techniques, polyphenol content, and in vitro stability. The antioxidant activity of the GNPs was also determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) cation (ABTS) radical-scavenging assays. Stable clones of neuronal SH-SY5Y-CFP-DEVD-YFP were generated and characterized, and cell viability after treatment with EGCG-GNPs was assessed after 72 hours through a 3(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Activation of the apoptotic pathways was also investigated by Western blot analysis. Results: With a diameter in the size range of 10–25 nm, the obtained nanoparticles (NPs) were found to contain 2.71%, 3.23%, and 5.47% of EGCG, RSV, and FS, respectively. Nanoprototypes exhibited remarkable in vitro stability in various media, suggesting that NP surface coating with phytochemicals prevents aggregation in different simulated physiological conditions. The scavenging activities for DPPH and ABTS were highly correlated with EGCG, RSV, and FS content. Moreover, high correlation coefficients between the ABTS and DPPH values were found for the prepared nanosystems. EGCG-GNPs induce a dose-dependent reduction on SH-SY5Y-CFP-DEVD-YFP cell viability that is likely to involve the activation of the apoptotic pathways, similarly to free EGCG, as suggested by the processing of the CFP-DEVD-YFP reporter. Conclusion: These results prompted us to propose the ecofriendly synthesized EGCG-, RSV-, and FS-based nanogold conjugates as suitable carriers for bioactive polyphenols to be used for the treatment of disorders associated with oxidative stress, including neurodegenerative disorders, cardiovascular disease, and cancer.</br