Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Nrf2 Expression Is Regulated by Epigenetic Mechanisms in Prostate Cancer of TRAMP Mice

Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is a transcription factor which regulates the expression of many cytoprotective genes. In the present study, we found that the expression of Nrf2 was suppressed in prostate tumor of the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice. Similarly, the expression of Nrf2 and the induction of NQO1 were also substantially suppressed in tumorigenic TRAMP C1 cells but not in non-tumorigenic TRAMP C3 cells. Examination of the promoter region of the mouse Nrf2 gene identified a CpG island, which was methylated at specific CpG sites in prostate TRAMP tumor and in TRAMP C1 cells but not in normal prostate or TRAMP C3 cells, as shown by bisulfite genomic sequencing. Reporter assays indicated that methylation of these CpG sites dramatically inhibited the transcriptional activity of the Nrf2 promoter. Chromatin immunopreceipitation (ChIP) assays revealed increased binding of the methyl-CpG-binding protein 2 (MBD2) and trimethyl-histone H3 (Lys9) proteins to these CpG sites in the TRAMP C1 cells as compared to TRAMP C3 cells. In contrast, the binding of RNA Pol II and acetylated histone H3 to the Nrf2 promoter was decreased. Furthermore, treatment of TRAMP C1 cells with DNA methyltransferase (DNMT) inhibitor 5-aza-2′-deoxycytidine (5-aza) and histone deacetylase (HDAC) inhibitor trichostatin A (TSA) restored the expression of Nrf2 as well as the induction of NQO1 in TRAMP C1 cells. Taken together, these results indicate that the expression of Nrf2 is suppressed epigenetically by promoter methylation associated with MBD2 and histone modifications in the prostate tumor of TRAMP mice. Our present findings reveal a novel mechanism by which Nrf2 expression is suppressed in TRAMP prostate tumor, shed new light on the role of Nrf2 in carcinogenesis and provide potential new directions for the detection and prevention of prostate cancer

Treatment-seeking for febrile illness in north-east India: an epidemiological study in the malaria endemic zone

<p>Abstract</p> <p>Background</p> <p>This paper studies the determinants of utilization of health care services, especially for treatment of febrile illness in the malaria endemic area of north-east India.</p> <p>Methods</p> <p>An area served by two districts of Upper Assam representing people living in malaria endemic area was selected for household survey. A sample of 1,989 households, in which at least one member of household suffered from febrile illness during last three months and received treatment from health service providers, were selected randomly and interviewed by using the structured questionnaire. The individual characteristics of patients including social indicators, area of residence and distance of health service centers has been used to discriminate or group the patients with respect to their initial and final choice of service providers.</p> <p>Results</p> <p>Of 1,989 surveyed households, initial choice of treatment-seeking for febrile illness was self-medication (17.8%), traditional healer <it>(Vaidya)</it>(39.2%), government (29.3%) and private (13.7%) health services. Multinomial logistic regression (MLR) analysis exhibits the influence of occupation, area of residence and ethnicity on choice of health service providers. The traditional system of medicine was commonly used by the people living in remote areas compared with towns. As all the febrile cases finally received treatment either from government or private health service providers, the odds (Multivariate Rate Ratio) was almost three-times higher in favour of government services for lower households income people compared to private.</p> <p>Conclusion</p> <p>The study indicates the popular use of self-medication and traditional system especially in remote areas, which may be the main cause of delay in diagnosis of malaria. The malaria training given to the paramedical staff to assist the health care delivery needs to be intensified and expanded in north-east India. The people who are economically poor and living in remote areas mainly visit the government health service providers for seeking treatment. So, the improvement of quality health services in government health sector and provision of health education to people would increase the utilization of government health services and thereby improve the health quality of the people.</p

MED12 Alterations in Both Human Benign and Malignant Uterine Soft Tissue Tumors

The relationship between benign uterine leiomyomas and their malignant counterparts, i.e. leiomyosarcomas and smooth muscle tumors of uncertain malignant potential (STUMP), is still poorly understood. The idea that a leiomyosarcoma could derive from a leiomyoma is still controversial. Recently MED12 mutations have been reported in uterine leiomyomas. In this study we asked whether such mutations could also be involved in leiomyosarcomas and STUMP oncogenesis. For this purpose we examined 33 uterine mesenchymal tumors by sequencing the hot-spot mutation region of MED12. We determined that MED12 is altered in 66.6% of typical leiomyomas as previously reported but also in 11% of STUMP and 20% of leiomyosarcomas. The mutated allele is predominantly expressed in leiomyomas and STUMP. Interestingly all classical leiomyomas exhibit MED12 protein expression while 40% of atypical leiomyomas, 50% of STUMP and 80% of leiomyosarcomas (among them the two mutated ones) do not express MED12. All these tumors without protein expression exhibit complex genomic profiles. No mutations and no expression loss were identified in an additional series of 38 non-uterine leiomyosarcomas. MED12 mutations are not exclusive to leiomyomas but seem to be specific to uterine malignancies. A previous study has suggested that MED12 mutations in leiomyomas could lead to Wnt/β-catenin pathway activation however our immunohistochemistry results show that there is no association between MED12 status and β-catenin nuclear/cytoplasmic localization. Collectively, our results show that subgroups of benign and malignant tumors share a common genetics. We propose here that MED12 alterations could be implicated in the development of smooth muscle tumor and that its expression could be inhibited in malignant tumors

Quality of Neonatal Healthcare in Kilimanjaro Region, Northeast Tanzania: Learning from Mothers' Experiences.

With a decline of infant mortality rates, neonatal mortality rates are striking high in development countries particularly sub Saharan Africa. The toolkit for high quality neonatal services describes the principle of patient satisfaction, which we translate as mother's involvement in neonatal care and so better outcomes. The aim of the study was to assess mothers' experiences, perception and satisfaction of neonatal care in the hospitals of Kilimanjaro region of Tanzania. A cross sectional study using qualitative and quantitative approaches in 112 semi structured interviews from 14 health facilities. Open ended questions for detection of illness, care given to the baby and time spent by the health worker for care and treatment were studied. Probing of the responses was used to extract and describe findings by a mix of in-depth interview skills. Closed ended questions for the quantitative variables were used to quantify findings for statistical use. Narratives from open ended questions were coded by colours in excel sheet and themes were manually counted. 80 mothers were interviewed from 13 peripheral facilities and 32 mothers were interviewed at a zonal referral hospital of Kilimanjaro region. 59 mothers (73.8%) in the peripheral hospitals of the region noted neonatal problems and they assisted for attaining diagnosis after a showing a concern for a request for further investigations. 11 mothers (13.8%) were able to identify the baby's diagnosis directly without any assistance, followed by 7 mothers (8.7%) who were told by a relative, and 3 mothers (3.7%) who were told of the problem by the doctor that their babies needed medical attention. 24 times mothers in the peripheral hospitals reported bad language like "I don't have time to listen to you every day and every time." 77 mothers in the periphery (90.6%) were not satisfied with the amount of time spent by the doctors in seeing their babies. Mothers of the neonates play great roles in identifying the illness of the newborn. Mother's awareness of what might be needed during neonatal support strategies to improve neonatal care in both health facilities and the communities

Activation of Estrogen-Responsive Genes Does Not Require Their Nuclear Co-Localization

The spatial organization of the genome in the nucleus plays a role in the regulation of gene expression. Whether co-regulated genes are subject to coordinated repositioning to a shared nuclear space is a matter of considerable interest and debate. We investigated the nuclear organization of estrogen receptor alpha (ERα) target genes in human breast epithelial and cancer cell lines, before and after transcriptional activation induced with estradiol. We find that, contrary to another report, the ERα target genes TFF1 and GREB1 are distributed in the nucleoplasm with no particular relationship to each other. The nuclear separation between these genes, as well as between the ERα target genes PGR and CTSD, was unchanged by hormone addition and transcriptional activation with no evidence for co-localization between alleles. Similarly, while the volume occupied by the chromosomes increased, the relative nuclear position of the respective chromosome territories was unaffected by hormone addition. Our results demonstrate that estradiol-induced ERα target genes are not required to co-localize in the nucleus

Seeking treatment for symptomatic malaria in Papua New Guinea

Background: Malaria places a significant burden on the limited resources of many low income countries. Knowing more about why and where people seek treatment will enable policy makers to better allocate the limited resources. This study aims to better understand what influences treatment-seeking behaviour for malaria in one such low-income country context, Papua New Guinea (PNG). Methods: Two culturally, linguistically and demographically different regions in PNG were selected as study sites. A cross sectional household survey was undertaken in both sites resulting in the collection of data on 928 individuals who reported suffering from malaria in the previous four weeks. A probit model was then used to identify the factors determining whether or not people sought treatment for presumptive malaria. Multinomial logit models also assisted in identifying the factors that determined where people sought treatments. Results: Results in this study build upon findings from other studies. For example, while distance in PNG has previously been seen as the primary factor in influencing whether any sort of treatment will be sought, in this study cultural influences and whether it was the first, second or even third treatment for a particular episode of malaria were also important. In addition, although formal health care facilities were the most popular treatment sources, it was also found that traditional healers were a common choice. In turn, the reasons why participants chose a particular type of treatment differed according to the whether they were seeking an initial or subsequent treatments. Conclusions: Simply bringing health services closer to where people live may not always result in a greater use of formal health care facilities. Policy makers in PNG need to consider within-country variation in treatment-seeking behaviour, the important role of traditional healers and also ensure that the community fully understands the potential implications of not seeking treatment for illnesses such as malaria at a formal health care facility.Carol P Davy, Elisa Sicuri, Maria Ome, Ellie Lawrence-Wood, Peter Siba, Gordon Warvi, Ivo Mueller and Lesong Conte

Estrogen receptor transcription and transactivation: Basic aspects of estrogen action

Estrogen signaling has turned out to be much more complex and exciting than previously thought; the paradigm shift in our understanding of estrogen action came in 1996, when the presence of a new estrogen receptor (ER), ERβ, was reported. An intricate interplay between the classical ERα and the novel ERβ is of paramount importance for the final biological effect of estrogen in different target cells

Does transcranial direct current stimulation to prefrontal cortex affect mood and emotional memory retrieval in healthy individuals?

Studies using transcranial direct current stimulation (tDCS) of prefrontal cortex to improve symptoms of depression have had mixed results. We examined whether using tDCS to change the balance of activity between left and right dorsolateral prefrontal cortex (DLPFC) can alter mood and memory retrieval of emotional material in healthy volunteers. Participants memorised emotional images, then tDCS was applied bilaterally to DLPFC while they performed a stimulus-response compatibility task. Participants were then presented with a set of images for memory retrieval. Questionnaires to examine mood and motivational state were administered at the beginning and end of each session. Exploratory data analyses showed that the polarity of tDCS to DLPFC influenced performance on a stimulus-response compatibility task and this effect was dependent on participants' prior motivational state. However, tDCS polarity had no effect on the speed or accuracy of memory retrieval of emotional images and did not influence positive or negative affect. These findings suggest that the balance of activity between left and right DLPFC does not play a critical role in the mood state of healthy individuals. We suggest that the efficacy of prefrontal tDCS depends on the initial activation state of neurons and future work should take this into account. © 2014 Morgan et al