For the love of a barking lady: an exploration of mental illness in the light of Max Scheler's "Invisible person"

N/

Paracrine control of tissue regeneration and cell proliferation by Caspase-3.

Executioner caspases such as Caspase-3 and Caspase-7 have long been recognised as the key proteases involved in cell demolition during apoptosis. Caspase activation also modulates signal transduction inside cells, through activation or inactivation of kinases, phosphatases and other signalling molecules. Interestingly, a series of recent studies have demonstrated that caspase activation may also influence signal transduction and gene expression changes in neighbouring cells that themselves did not activate caspases. This review describes the physiological relevance of paracrine Caspase-3 signalling for developmental processes, tissue homeostasis and tissue regeneration, and discusses the role of soluble factors and microparticles in mediating these paracrine activities. While non-cell autonomous control of tissue regeneration by Caspase-3 may represent an important process for maintaining tissue homeostasis, it may limit the efficiency of current cancer therapy by promoting cell proliferation in those cancer cells resistant to radio- or chemotherapy. We discuss recent evidence in support of such a role for Caspase-3, and discuss its therapeutic implication

Breaking new ground: New Zealand Certificates of Steiner Education

The New Zealand Certificates of Steiner Education (CSE) are secondary qualifications at levels 1, 2 and 3, recognized by the New Zealand Qualifications Authority. They give access to tertiary education in New Zealand and beyond. The impulse for new qualifications grew from a wish to have important aspects of the taught Steiner curriculum recognized and valorized, that these aspects be credit bearing toward tertiary study, an option not offered by existing qualifications. The certificates were developed over an 18-month period and were implemented by the (then) four New Zealand Steiner schools with high school classes. The CSE are based on a suite of learning outcomes which give teachers a substantial degree of assessment autonomy, allowing them to tailor assessment modalities to the student or class being taught. Since 2012, the qualifications have been offered overseas and are now used as a pathway to university by Steiner schools in a growing number of countries. This article draws on the experiences of one of the developers of the qualification and two teachers in schools using the certificate in the UK, and outlines some of the challenges faced when breaking new ground in the advancement of Waldorf education internationally

Paediatric radiology from a psychosocial lens

Globally, hospitals and medical centres have a reputation of causing individual patients an increased level of anxiety, stress and pain owing to their foreign environments, intimidating examinations and rigorous treatments. Because of children’s cognitive and developmental levels of understanding and communication, they are more susceptible to increased levels of stress and trauma associated with medical examinations and hospitalisation. Certified Child Life Specialists (CCLSs) are professionals trained in child development and family systems expertise who work directly with children and families to meet their psychosocial and emotional needs in order to help them overcome some of life’s most challenging events, including hospitalisation, illness and trauma. This article aims to address the history of the child life profession and the significance of child life in a paediatric imaging unit, and to discuss the current and future status of psychosocial services in South Africa

Targeting the 19S proteasomal subunit, Rpt4, for the treatment of colon cancer.

Deregulation of the ubiquitin-proteasome pathway has been frequently observed in a number of malignancies. Using quantitative Western blotting of normal and matched tumour tissue, we here identified a significant increase in the 19S proteasome subunit Rpt4 in response to chemoradiation in locally advanced rectal cancer patients with unfavourable outcome. We therefore explored the potential of Rpt4 reduction as a therapeutic strategy in colorectal cancer (CRC). Utilizing siRNA to down regulate Rpt4 expression, we show that silencing of Rpt4 reduced proteasomal activity and induced endoplasmic reticulum stress. Gene silencing of Rpt4 also inhibited cell proliferation, reduced clonogenic survival and induced apoptosis in HCT-116 colon cancer cells. We next developed a cell penetrating peptide-based nanoparticle delivery system to achieve in vivo gene silencing of Rpt4. Administration of Rpt4 siRNA nanoparticles reduced tumour growth and improved survival in a HCT-116 colon cancer xenograft tumour model in vivo. Collectively, our data suggest that inhibition of Rpt4 represents a novel strategy for the treatment of CRC

Raleigh, Wake County : an action-oriented community diagnosis for people living with disabilities in Raleigh, NC

Universal Disability Advocates (UDA) is a grassroots, nonprofit organization in Raleigh, N.C. that advocates for people of all ages and abilities in the community. Through a partnership with the North Carolina Office on Disability and Health, UDA invited a team of six students from the UNC School of Public Health in Chapel Hill, NC to conduct an Action-Oriented Community Diagnosis (AOCD) of people living with disabilities in Raleigh. Two UDA members and two employees of the NC Office on Disability and Health agreed to serve as preceptors and mentors for the project and as liaisons between the students and the community. The team first entered the community in October 2003 and the AOCD process was completed following a community forum held in April 2004. The goal of an Action Oriented Community Diagnosis (AOCD) is to gather, analyze, and summarize the perspectives of community members and service providers in a community for the purpose of creating a complete vision of the community’s strengths, challenges, and existing resources on which to build. The AOCD process is designed to culminate in a Community Forum where all community stakeholders come together to create action steps to improve existing situations. The team in Raleigh began the AOCD process by examining secondary data and attending community meetings and events. The team then conducted 32 interviews and 2 focus groups with service providers, individuals with disabilities, and family members of people with disabilities in Raleigh, and identified recurrent themes raised by interviewees. Following a thorough review of all interview transcripts, the team identified the most frequently recurring issues and strengths (called domains) raised by interviewees. The AOCD team then worked with a planning group of community members and service providers to prioritize the recurrent domains. The most important and changeable issues identified by people with disabilities in Raleigh included: the accessibility and affordability of housing and Raleigh; issues of public transportation in Raleigh, the Raleigh built environment, specifically, the accessibility of sidewalks, parking lots and buildings; community awareness in Raleigh and communication with people with disabilities; the unemployment and underemployment of people with disabilities in Raleigh; and the challenges around obtaining services in Raleigh. Each of these domains was the topic of a small group discussion at the Raleigh Community Forum. The Raleigh Community Forum was held on Monday April 19th from 6:00 to 8:30 pm at the Hudson Memorial Presbyterian Church on Six Forks Road in Raleigh. Twenty-five community members and service providers attended the forum. After opening remarks, a brief overview of the methodology of the AOCD process and a detailed description of the prioritized issues for discussion, forum attendees divided into small groups. Small group discussions surrounding each domain led to the generation and prioritization of action steps for the future. Action steps resulting from the small group discussion on the accessibility and affordability of housing in Raleigh included: to attend and speak at at least one builders convention to raise awareness about the needs of people living with disabilities and access to affordable, accessible housing; to raise awareness among the general public through publicity and collaborations with existing organizations like Universal Disability Advocates, The Raleigh Mayor’s Committee, Center for Independent Living, and the Center for Universal Design at North Carolina State University; to include housing information on an existing disability advocacy website now in a design phase; and, to, in the long-term, build a visitable housing complex in accordance with the principles of universal design. Following a discussion on the Raleigh built environment, specifically, the accessibility of sidewalks, parking lots, and buildings, an action step was to form an email group that will arrive at action steps involving collaboration with other organizations. Resulting from a discussion on community awareness in Raleigh and communication issues with health care providers, action steps were to: attend existing community activities, such as health fairs, to increase awareness about this uses; to create a “tips for consumers” brochure focusing on how to advocate for ones’ own health needs; and to continue providing continuing education courses for health care professionals regarding communication with people with disabilities. Action steps resulting from the small group discussion on the unemployment and underemployment of people with disabilities in Raleigh were to: advocate at the state and federal levels by contacting legislators and the governor to ask: Where do people with disabilities fit into your action plans? And is there an action plan for employment for people with disabilities?; to educate the community through existing organizations, to register to vote, and to learn how to effectively advocate for equal employment; and, to educate the community about taking legal action through the Americans with Disabilities Act when necessary. As a discussion of issues of public transportation in Raleigh did not occur during the community forum, no action steps were created. In addition to bringing together Raleigh community members and service providers in communication about the future, the AOCD team involved in this project was particularly interested in the influence of the Americans with Disabilities Act on the presence and functions of community among adults living with disabilities in Raleigh, N.C. Through their research, AOCD team members identified dramatically different views on the existence of a Raleigh community of people with disabilities. This document, which complies information collected through interviews, secondary data sources, and observations of team members, is written with the understanding that the definition of “community of people living with disabilities” used by the team is meaningful and a truth to some, while not believed to exist nor advocated for by others. The definition of a cross-disability community is considered by some to be the critical foundation for continued efforts to secure rights for people living with disabilities. For others, defining people with disabilities as a community is perceived as furthering the historical segregation of this group from the rest of society. For still others, community is defined within the boundaries of one’s own disability and/or geographical or relational factors. This AOCD document is intended to serve as a resource to the people of Raleigh. The document is organized into six sections: an Introduction to the Project, Findings from Secondary Data, Results, Community Forum, Methodology, and Conclusions and Next Steps. The team presents this document in the hope that it will contribute to the existing body of knowledge supporting and advancing people living with disabilities in Raleigh, North Carolina. It has been the team’s privilege to learn from so many people working to make Raleigh a more inclusive community for people with disabilities, and the team hopes the action steps for change generated by the community during this project will compliment existing work or serve as a catalyst for new action.Master of Public Healt

Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn's Disease But Not Ulcerative Colitis.

Background & aimsPatients with Crohn's disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration.MethodsWe analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (>2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes.ResultsWithin 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P < .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC.ConclusionsPatients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC

Activin Signaling in Microsatellite Stable Colon Cancers Is Disrupted by a Combination of Genetic and Epigenetic Mechanisms

Activin receptor 2 (ACVR2) is commonly mutated in microsatellite unstable (MSI) colon cancers, leading to protein loss, signaling disruption, and larger tumors. Here, we examined activin signaling disruption in microsatellite stable (MSS) colon cancers.Fifty-one population-based MSS colon cancers were assessed for ACVR1, ACVR2 and pSMAD2 protein. Consensus mutation-prone portions of ACVR2 were sequenced in primary cancers and all exons in colon cancer cell lines. Loss of heterozygosity (LOH) was evaluated for ACVR2 and ACVR1, and ACVR2 promoter methylation by methylation-specific PCR and bisulfite sequencing and chromosomal instability (CIN) phenotype via fluorescent LOH analysis of 3 duplicate markers. ACVR2 promoter methylation and ACVR2 expression were assessed in colon cancer cell lines via qPCR and IP-Western blots. Re-expression of ACVR2 after demethylation with 5-aza-2'-deoxycytidine (5-Aza) was determined. An additional 26 MSS colon cancers were assessed for ACVR2 loss and its mechanism, and ACVR2 loss in all tested cancers correlated with clinicopathological criteria.Of 51 MSS colon tumors, 7 (14%) lost ACVR2, 2 (4%) ACVR1, and 5 (10%) pSMAD2 expression. No somatic ACVR2 mutations were detected. Loss of ACVR2 expression was associated with LOH at ACVR2 (p<0.001) and ACVR2 promoter hypermethylation (p<0.05). ACVR2 LOH, but not promoter hypermethylation, correlated with CIN status. In colon cancer cell lines with fully methylated ACVR2 promoter, loss of ACVR2 mRNA and protein expression was restored with 5-Aza treatment. Loss of ACVR2 was associated with an increase in primary colon cancer volume (p<0.05).Only a small percentage of MSS colon cancers lose expression of activin signaling members. ACVR2 loss occurs through LOH and ACVR2 promoter hypermethylation, revealing distinct mechanisms for ACVR2 inactivation in both MSI and MSS subtypes of colon cancer

Tobacco use and asking prices of used cars: prevalence, costs, and new opportunities for changing smoking behavior

Secondhand smoke (SHS) causes premature death and disease in children and adults, and the scientific evidence indicates that there is no risk-free level of exposure to SHS. Smoking tobacco in a car can pollute the microenvironment of the car with residual SHS, leaving telltale signs to potential buyers (e.g., odor, used ash tray). This study examined (a) the proportion of used cars sold in the private party market that may be polluted with tobacco smoke and (b) whether asking prices of smoker and nonsmoker cars differed for cars of otherwise equivalent value. A random sample of 1,642 private party sellers were interviewed by telephone, and content analyses of print advertisements were conducted. Findings indicate that 22% of used cars were advertised by smokers or had been smoked in during the previous year. Among nonsmokers, 94% did not allow smoking in their car during the past year. Only 33% of smokers had the same restrictions. The smoking status of the seller and tobacco use in the car were significantly (p < .01) associated with the asking price independent of a car's Kelley Blue Book value (KBB). Used nonsmoker cars were offered at a considerable premium above their KBB value (>11%) and above comparable smoker cars (7–9%). These findings suggest that community preferences are affecting the value of smoke-free cars. New directions for research, tobacco control policies, and health education are discussed to further reduce smoking behavior, to help consumers make informed purchasing decisions, and to protect nonsmokers from SHS exposure

Recruitment using mobile telephones in an Irish general population sexual health survey: challenges and practical solutions

BACKGROUND: Non-coverage of households without a landline telephone is a major concern of telephone survey researchers. Sampling mobile telephone users in national surveys is vital in order to gain access to the growing proportion of households that use mobile telephones extensively or exclusively. The complex logistics of conducting surveys with mobile telephones have been discussed in the literature. This paper outlines the actual challenges encountered during a recent national sexual health survey in Ireland, which utilized a mobile telephone sampling frame to recruit approximately half of the sample. METHOD: The 2010 Irish Contraception and Crisis Pregnancy Survey (ICCP-2010) is a nationally representative sample of adults aged 18-45 years living in Ireland (n = 3002; 1416 recruited by landline telephone and 1586 recruited by mobile telephone). The overall response rate for the survey was 69% (79% for the landline telephone strand; 61% for the mobile telephone strand). All interviews were conducted using computer-assisting telephone interviewing. RESULTS: During the 18-week fieldwork period, five main challenges relating to the use of mobile telephones were encountered: (1) explaining to respondents how random digit dialling works in relation to mobile telephones; (2) establishing the respondent\u27s eligibility; (3) calling the respondent with the Caller ID blocked or withheld; (4) calling the respondent when they are in any number of locations or situations; and (5) explaining to respondents the importance of refusal conversion calls for the response rate calculation. Details of how the survey protocols and procedures were monitored and adapted throughout the study to ensure a high response rate are outlined. CONCLUSION: It is undeniably more challenging to recruit respondents using mobile telephones as opposed to landline telephones. Respondents are generally not familiar with being contacted on their personal mobile telephone for the purposes of being recruited for a research study. The main challenge for survey methodologists and interviewers is to devise simple protocols to explain to respondents why they are being contacted on a mobile telephone. Recommendations for survey researchers interested in using this methodological approach in the future are discussed