Targeting IL-23 for the interception of obesity-associated colorectal cancer.

Inflammation and obesity are two major factors that promote Colorectal cancer (CRC). Our recent data suggests that interleukin (IL)-23, is significantly elevated in CRC tumors and correlates with patient obesity, tumor grade and survival. Thus, we hypothesize that obesity and CRC may be linked via inflammation and IL-23 may be a potential target for intervention in high-risk patients. TCGA dataset and patient sera were evaluated for IL-23A levels. IL-23A [IL-23 p19-/-] knockout (KO) mice were crossed to Apcmin/+ mice and progeny were fed low-fat or high-fat diets. At termination intestines were evaluated for tumorigenesis. Tumors, serum, and fecal contents were analyzed for protein biomarkers, cytokines, and microbiome profile respectively. IL-23A levels are elevated in the sera of patients with obesity and colon tumors. Genetic ablation of IL-23A significantly suppressed colonic tumor multiplicity (76-96 %) and incidence (72-95 %) in male and female mice. Similarly, small-intestinal tumor multiplicity and size were also significantly reduced in IL-23A KO mice. IL-23A knockdown in Apcmin/+ mice fed high-fat diet, also resulted in significant suppression of colonic (50-58 %) and SI (41-48 %) tumor multiplicity. Cytokine profiling showed reduction in several circulating pro-inflammatory cytokines including loss of IL-23A. Biomarker analysis suggested reduced tumor cell proliferation and immune modulation with an increase in tumor-infiltrating CD4+ and CD8+ T-lymphocytes in the IL-23A KO mice compared to controls. Fecal microbiome analysis revealed potentially beneficial changes in the bacterial population profile. In summary, our data indicates a tumor promoting role for IL-23 in CRC including diet-induced obesity. With several IL-23 targeted therapies in clinical trials, there is a great potential for targeting this cytokine for CRC prevention and therapy.

COMMENT: Bioethics in Unani medicine: Relevant quotes from Kamilussanah, a 10th century manuscript.

The World Health Organization (WHO) in its Alma Ata Declaration, 1978, focuses on the development, promotion and recognition of the traditional medical systems. India has taken steps in this direction by recognising Unani medicine with other traditional medical systems practised in India. Presently, Government is promoting integration of the recognised traditional medical systems with conventional medicine at the national level, as an interdisciplinary approach to providing better patient-centred care. Bioethics is a field of enquiry that examines ethical issues and dilemmas emerging from medical care and research involving humans. Although the term 'bioethics' was first mentioned in 1927 and later established as a distinct discipline in 1970s, the ethical principles in various contexts had been described centuries ago in the classical texts pertaining to traditional medical systems. Since ethics as a code of conduct was followed by ancient Unani physicians to safeguard the interests of humanity when providing healthcare, it was felt that a review of classical Unani manuscripts should be attempted to give an insight into codes of conduct described by various Unani physicians. In this paper, a 10th century book, "Kamilussanah" authored by Ali ibn Abbas al-Majoosi, also known as Majoosi (930-994 CE), is reviewed through the prism of ethics.

Research, biomedicine and Ayurveda: From evidence-based medicine to evidence-informed healthcare.

As the search for effective treatment for Covid-19 intensifies, traditional medicine systems are receiving increasing attention from researchers as well as the public. While scientific rigour is non-negotiable, there remain fundamental issues to be addressed when bringing evidence from traditional systems. Here we examine some of these issues pertaining to Ayurveda and the underlying philosophical underpinnings, and suggest potential ways to move forward. We find an ability to emerge from the cage of "biomedicalism" and its foundational reductionism essential for appropriate research in Ayurveda. We caution against pursuing research in Ayurveda by just mimicking modern medicine and highlight the need for appropriate use of modern science tools and methods to understand Ayurveda and explore its potential for healthcare. We emphasise the need and potential for transdisciplinary research in Ayurveda. A balance between evidence-based medicine and evidence-informed healthcare is required.

AYUSH, modern medicine and the Covid-19 pandemic.

The COVID-19 pandemic has posed several challenges to the Indian healthcare system. Here, we examine the situation in India considering the moral and ethical imperatives of decision making for public health. Currently, in the absence of proven therapies, empirical evidence is being used for treatment of Covid-19 disease. We find a dual standard of practice. Currently, only modern medicine therapies are used on an empirical basis, however, the same principle is not considered for the use of AYUSH systems. Appropriate use of evidence is required. In the ethics context and in the interest of the larger public good, we suggest the inclusion of simple and safe measures from AYUSH systems in the integrative protocols for prophylaxis and treatment of Covid-19. Keywords: AYUSH systems, Covid-19, pandemic, prophylaxis, evidence, empirical evidence, priority setting, public health decision making, global health emergencies,complementary medicine, integrative healthcare.

Results of a self-assessment tool to assess the operational characteristics of research ethics committees in low- and middle-income countries.

PURPOSE: Many research ethics committees (RECs) have been established in low- and middle-income countries (LMICs) in response to increased research in these countries. How well these RECs are functioning remains largely unknown. Our objective was to assess the usefulness of a self-assessment tool in obtaining benchmarking data on the extent to which RECs are in compliance with recognised international standards. METHODS: REC chairs from several LMICs (Egypt, South Africa and India) were asked to complete an online self-assessment tool for RECs with a maximum score of 200. Individual responses were collected anonymously. RESULTS: The aggregate mean score was 137.4±35.8 (∼70% of maximum score); mean scores were significantly associated with the presence of a budget (p<0.001), but not with duration of existence, frequency of meetings, or the presence of national guidelines. As a group, RECs achieved more than 80% of the maximum score for the following domains: submission processes and documents received, recording of meeting minutes, criteria for ethical review and criteria for informed consent. RECs achieved less than 80% of the maximum score for the following domains: institutional commitment, policies and procedures of the REC, membership composition and training, policies and procedures for protocol review, elements of a decision letter and criteria for continuing review. CONCLUSIONS: This study highlights areas where RECs from LMICs can improve to be in compliance with recommended international standards for RECs. The self-assessment tool provides valuable benchmarking data for RECs and can serve as a quality improvement method to help RECs enhance their operations.

Perspectives from South and East Asia on clinical and research ethics: a literature review.

A review was conducted of English-language peer-reviewed and gray literature on health and ethics written by authors from Bangladesh, China, India, and Pakistan. This was supplemented by the knowledge of co-authors who are involved in bioethics capacity building in these countries. Of the identified literature that focused on the application of Western principles, it largely discussed informed consent and revealed norms in clinical decision-making that include physician paternalism, family involvement in decision-making, and reluctance to provide information that might upset patients. It appears that Western ethical principles may be interpreted and applied in unexpected ways. The literature further indicates that, although there is some consistency with Western ideas, Islamic, Confucian, and Indian religious and philosophical traditions contain concepts not reflected in international guidance. Findings suggest scholars from these countries seek to enter into a bioethics dialogue with the potential to enrich and inform "international" frameworks.

Knowledge & attitudes of mental health professionals regarding psychiatric research.

BACKGROUND & OBJECTIVES: Mental health professionals have varied attitudes and views regarding informed consent and confidentiality protections in psychiatric research and clinical care. The present study was designed to understand the knowledge and views of mental health professionals (MHPs) regarding informed consent and confidentiality protection practices. METHODS: Mental health professionals (n=121) who were members of the Delhi Psychiatric Society, were invited to participate in this questionnaire-based study of their knowledge and attitudes regarding informed consent and confidentiality. Half of them expressed willingness to discuss participation and gave initial oral consent (n=62); of these, 31 gave written informed consent to participate and completed the questionnaires. The questionnaires included both forced choice (yes / no / do not know) and open-ended questions. Questionnaires content reflected prominent guidelines on informed consent and confidentiality protection. RESULTS: Attitudes of the majority of the participants towards informed consent and confidentiality were in line with ethical principles and guidelines. All expressed the opinion that confidentiality should generally be respected and that if confidentiality was breached, there could be mistrust of the professional by the patient/participant. The mean knowledge scores regarding informed consent and confidentiality were 8.55 ± 1.46 and 8.16 ± 1.29, respectively. INTERPRETATION & CONCLUSIONS: The participating mental health professionals appeared to have adequate knowledge of basic ethical guidelines concerning informed consent and confidentiality. Most respondents were aware of ethical issues in research. Given the small sample size and low response rate, the significance of the quantitative analysis must be regarded with modesty, and qualitative analysis of open-ended questions may be more valuable for development of future research. Increased efforts to involve mental health professionals in research on ethical concerns pertinent to their work must be made, and the actual practices of these professionals with regard to ethical guidelines need to be studied.

Knowledge and practice of clinical ethics among healthcare providers in a government hospital, Chennai.

The growing public concern about the ethical conduct of healthcare professionals highlights the need to incorporate clinical ethics in medical education. This study examined the knowledge and practice of clinical ethics among healthcare providers in a government hospital in Chennai. A sample of 51 treating physicians and 58 other non-physician service providers from the hospital answered a self-administered, semi-structured questionnaire on their knowledge of and adherence to ethical principles, and the problems they faced related to healthcare ethics. More than 30% did not give a definition of healthcare ethics, and 40% did not name a single ethical principle. 51% stated that they witnessed ethical problems in their settings and named patient dissatisfaction, gender bias by provider, and not maintaining confidentiality. The responses of healthcare providers to various ethical scenarios are reported.

Bioethics activities in India.

The Indian Council of Medical Research formulates, coordinates and promotes biomedical research in India. In 1980, they formulated the first national ethical guidelines. They offer a number of different training programmes, from 1 day to 6 months. The council is developing a core curriculum for teaching bioethics, which would be applied uniformly in medical schools throughout the country. Drug development and ethics is also important in India, particularly now that the local pharmaceutical industry is expanding and so many drugs trials are outsourced to the country. The council is also very active in encouraging the development of ethics review committees.

"Harnessing genomics to improve health in India" - an executive course to support genomics policy.

BACKGROUND: The benefits of scientific medicine have eluded millions in developing countries and the genomics revolution threatens to increase health inequities between North and South. India, as a developing yet also industrialized country, is uniquely positioned to pioneer science policy innovations to narrow the genomics divide. Recognizing this, the Indian Council of Medical Research and the University of Toronto Joint Centre for Bioethics conducted a Genomics Policy Executive Course in January 2003 in Kerala, India. The course provided a forum for stakeholders to discuss the relevance of genomics for health in India. This article presents the course findings and recommendations formulated by the participants for genomics policy in India. METHODS: The course goals were to familiarize participants with the implications of genomics for health in India; analyze and debate policy and ethical issues; and develop a multi-sectoral opinion leaders' network to share perspectives. To achieve these goals, the course brought together representatives of academic research centres, biotechnology companies, regulatory bodies, media, voluntary, and legal organizations to engage in discussion. Topics included scientific advances in genomics, followed by innovations in business models, public sector perspectives, ethics, legal issues and national innovation systems. RESULTS: Seven main recommendations emerged: increase funding for healthcare research with appropriate emphasis on genomics; leverage India's assets such as traditional knowledge and genomic diversity in consultation with knowledge-holders; prioritize strategic entry points for India; improve industry-academic interface with appropriate incentives to improve public health and the nation's wealth; develop independent, accountable, transparent regulatory systems to ensure that ethical, legal and social issues are addressed for a single entry, smart and effective system; engage the public and ensure broad-based input into policy setting; ensure equitable access of poor to genomics products and services; deliver knowledge, products and services for public health. A key outcome of the course was the internet-based opinion leaders' network - the Indian Genome Policy Forum - a multi-stakeholder forum to foster further discussion on policy. CONCLUSION: We expect that the process that has led to this network will serve as a model to establish similar Science and Technology policy networks on regional levels and eventually on a global level.