AMP-activated protein kinase promotes epithelial-mesenchymal transition in cancer cells through Twist1 upregulation.

The developmental programme of epithelial-mesenchymal transition (EMT), involving loss of epithelial and acquisition of mesenchymal properties, plays an important role in the invasion-metastasis cascade of cancer cells. In the present study, we show that activation of AMP-activated protein kinase (AMPK) using A769662 led to a concomitant induction of EMT in multiple cancer cell types, as observed by enhanced expression of mesenchymal markers, decrease in epithelial markers, and increase in migration and invasion. In contrast, inhibition or depletion of AMPK led to a reversal of EMT. Importantly, AMPK activity was found to be necessary for the induction of EMT by physiological cues such as hypoxia and TGFß treatment. Furthermore, AMPK activation increased the expression and nuclear localization of Twist1, an EMT transcription factor. Depletion of Twist1 impaired AMPK-induced EMT phenotypes, suggesting that AMPK might mediate its effects on EMT, at least in part, through Twist1 upregulation. Inhibition or depletion of AMPK also attenuated metastasis. Thus, our data underscore a central role for AMPK in the induction of EMT and in metastasis, suggesting that strategies targeting AMPK might provide novel approaches to curb cancer spread.

Ethical and definitional considerations in research on child sexual violence in India.

BACKGROUND: While critically important, child sexual violence (CSV) research poses numerous ethical and safety challenges. Recently, the studies dedicated to understanding and addressing CSV in India have been on the rise, but no published ethical guidelines to direct such research currently exist. To help inform ethical and safety recommendations for the design, conduct, and reporting of future CSV research in India and similar settings, we systematically reviewed the ethics and safety practices reported in recent Indian CSV literature. METHODS: A multi-tiered approach was used to understand current ethical practices and gaps: 1) systematic review of Indian CSV studies published over the past decade, 2) examination of existing guidelines on related topics to develop an ethical framework, 3) development of an ethics checklist based on the recommendations from the surveyed guidelines, and 4) application of the checklist to each of the reviewed studies. RESULT: Our search yielded 51 eligible studies. From each, data from 6 major thematic areas was extracted: informed consent, confidentiality, selection, training, and protection of study team members, validity of CSV measurement methods, measures to minimize participant harm, and participant compensation. Several gaps were noted: only two-thirds reported approval by ethics committees, obtaining informed consent, and assured participants of confidentiality. Only 25% (13/51) reported assessing ongoing CSV risk and providing necessary support services, none noted whether ongoing CSV was reported to authorities (required by Indian law), and none reported safeguards to protect staff from the effects of conducting CSV research. Further, 43% (22/51) limited surveillance of CSV to one form of abuse and/or used a "loaded term," increasing the potential for underreporting. CONCLUSIONS: Through enhancing understanding of current ethical practices and gaps in CSV research in India, this systematic review informs reporting protocols and future guidelines for CSV research in India and other similar settings.

Individualized Pain Treatment in Chronic Pancreatitis (INPAIN): An International, Multicenter, Investigator-initiated, Prospective, Cohort Study.

INTRODUCTION: Pain is the foremost complication of chronic pancreatitis (CP), affecting about 70% of patients. However, the pathophysiological understanding and management of CP-related pain is complex, likely as patients have diverse "pain phenotypes" responding differently to treatment. This study aims to develop a bedside test panel to identify distinct pain phenotypes, investigate the temporal evolution, and determine whether they can be used to predict treatment response. METHOD: The INPAIN study is an international, multi-center, observational, longitudinal cohort study comprised of 4 sub-studies. The studies will prospectively enroll 400 CP patients (50 without pain and 350 with pain) and 50 control subjects, conducting biannual observations for four years. The test panel is comprised of comprehensive subjective and objective assessment parameters. Statistical analysis strategies differ across the sub-studies. A model to predict treatment efficacy will be developed using various machine learning techniques, including an artificial intelligence approach, with internal cross-validation. Trajectories in pain parameters will be characterized by graphical analysis and mixed effect models. DISCUSSION: The INPAIN study aims to comprehensively understand pain in CP through a test panel developed for routine clinical use. This tool has the potential to personalize treatments, improve clinical practice, enhance patient care, improve quality of life, and minimize treatment side effects.

Fruit and vegetable purchasing patterns and preferences in South Delhi.

This study examines associations between consumer characteristics, beliefs, and preferences and fruit and vegetable (FV) purchasing and intake in South Delhi, India. Home interviews were conducted with 245 households, using a structured questionnaire to assess FV consumption and purchasing frequency, spending, place of purchase, mode of travel, knowledge and attitudes toward organics, and beliefs about barriers to FV consumption. In-depth interviews with 62 experts and key informants validated survey findings that street vendors and markets are currently the dominant source of FV in South Delhi and that affordability, not accessibility, is the main barrier to increasing FV intake.

Co-Creation of Breast Cancer Risk Communication Tools and an Assessment of Risk Factor Awareness: A Qualitative Study of Patients and the Public in India.

BACKGROUND: Low awareness of BC and its associated risk factors causes delays in diagnosis and impacts survival. It is critical to communicate BC risk to patients in a format that they are easily able to understand. Our study aim was to develop easy-to-follow transmedia prototypes to communicate BC risk and evaluate user preferences, alongside exploring awareness of BC and its risk factors. METHODS: Prototypes of transmedia tools for risk communication were developed with multidisciplinary input. A qualitative in-depth online interview study was undertaken using a pre-defined topic guide of BC patients (7), their relatives (6), the general public (6), and health professionals (6). Interviews were analyzed using a thematic approach. FINDINGS: Most participants preferred pictographic representations (frequency format) of lifetime risk and risk factors and storytelling using short animations and comic strips (infographics) for communicating genetic risk and testing: "In a short time, they explained it very well, and I liked it". Suggestions included minimizing technical terminology, decreasing the delivery speed, "two-way dialogue", and using local "language for different locations". There was low awareness of BC, with some understanding of age and hereditary risk factors but limited knowledge of reproductive factors. INTERPRETATION: Our findings support use of multiple context-specific multimedia tools in communicating cancer risk in an easy-to-understand way. The preference for storytelling using animations and infographics is a novel finding and should be more widely explored.

Developing a community-based breast cancer risk prediction tool for resource-poor settings.

BACKGROUND: With an estimation of every two women newly diagnosed with breast cancer, one dies. It is accounted that 1 in 28 women is likely to develop breast cancer during her lifetime. Developing a risk prediction tool by assessing the prevalence of known risk factors in the community will help public health intervention. METHODOLOGY: A cross-sectional study was conducted among 18-64-year-old women to gather the prevalence of known breast cancer risk factors, through a community survey (sample survey). In this multistage random number-based cluster sampling study, the results were compiled, collated, and analyzed in rates and proportions. Statistical conclusions were made using spreadsheets (Microsoft) and the values were converted into ordinal values using modified Likert scale and median was used to estimate central values. The estimated prevalence of these known risk factors was re-assorted for analysis and these re-assorted data were categorized into range of values across the communities. The internal validity of the survey questionnaire was measured using Cronbach's alpha (α). RESULTS: The analysis of 558 participants was performed for the known risk factors for breast cancer including participant's age, age at menarche, marriage, first childbirth, menopause, family history of breast cancer and benign breast disease, history of abortion, and body mass index. Based on the estimated prevalence of these risk factors, a community-based risk prediction tool was developed with Cronbach's α score of medium internal validity. CONCLUSIONS: The risk assessment tool has collated most of the risk factors of breast cancer that are capable of being measured at community level. The survey findings concluded that the community under survey was bearing moderate risk for breast cancer for women.

Quality assessment of cryopreserved biospecimens reveals presence of intact biomolecules.

Recapitulation of tumor features in isolated biomolecules is preeminently dependent on obtaining reliable quality biospecimen. Moreover, quality assessment of biobanked specimens at regular intervals is an essential intervention for carrying out effective translational and clinical research. In the current study, genomic DNA was extracted from 140 fresh frozen tissues of oral, breast and colorectal specimens cryopreserved over a period of 3 to 8 months (short term) and 3 to 4 years (long term). Quantification of genomic DNA by absorption and fluorescence spectroscopy confirmed high concentration while qualitative analysis by gel electrophoresis showed intact bands for 94% and 87% of short- and long-term cohorts, respectively. PC-LDA based classification of Raman spectra showed overlapping groups of both cohorts suggesting the quality of DNA being preserved irrespective of storage period. To the best of our knowledge this is the first Indian biobank study reporting quality analysis of biospecimens cryopreserved at different time periods.

Child sexual abuse in India: A systematic review.

OBJECTIVE: Child Sexual Abuse (CSA) is a pressing human right issue and public health concern. We conducted a systematic review of quantitative and qualitative studies published in the past decade on CSA in India to examine the distribution of the prevalence estimates for both genders, to improve understanding of the determinants and consequences of CSA and identify gaps in the current state of research. METHODS: For this systematic review, we searched electronic literature databases (PubMed, POPLINE, and PsycINFO) for articles published in English on Child Sexual Abuse in India between January 1, 2006 and January 1, 2016 using 55 search terms. Data were extracted from published articles only. FINDINGS: Fifty-one studies met inclusion criteria for the review. The review indicates that prevalence rates of CSA is high among both boys and girls in India. Due to heterogeneity of study designs and lack of standardised assessments, reported prevalence estimates varied greatly among both genders in different studies. There is a need to conduct representative studies using a validated instrument to obtain valid epidemiological estimates. Commercial sex workers, men who have sex with men, and women with psychiatric disorders were at higher risks for sexual abuse during childhood. In addition, the synthesis of qualitative data across studies included in the review suggests that exposure and perpetration of CSA is a multifaceted phenomenon grounded in the interplay between individual, family, community, and societal factors. The review indicates poor physical, behavioural, social, and mental health outcomes of CSA in India. We conclude with a research agenda calling for quantitative and qualitative studies to explore the determinants and perpetration of child sexual abuse in India from an ecological lens. This research agenda may be necessary to inform the development of a culturally tailored primary prevention and treatment strategy for CSA victims in India.

Determination of Quality Standards for Draksharishta, a Polyherbal Ayurvedic Formulation.

Draksharishta is an ayurvedic polyherbal formulation is prescribed for digestive impairment, respiratory disorders and weakness. Though the formula composition and therapeutic claims of draksharishta are part of the Ayurvedic Formulary of India, the scientific methods for its quality and safety evaluation are yet to be documented. The current work is an attempt to evaluate the quality parameters of draksharishta which has been checked vis a vis herbs used in the formulation by modern scientific control procedures like macroscopic and microscopic study, physico-chemical analysis, preliminary phytochemical analysis, thin layer chromatography and high performance thin layer chromatography to fix the quality standard of this formulation with reference to two marketed formulations i.e. M1 and M2, respectively. The quality control parameters were within the limit as per the Ayurvedic Pharmacopeia of India which signifies good quality and purity of the plant materials. Thin layer chromatography profiles showed the presence of gallic acid, catechin and resveratrol and further it was confirmed by HPTLC fingerprints. The results obtained can be used by pharmaceutical companies as quality control parameters in order to have a proper quality check during processing.

Validated high performance thin layer chromatography method for the quantification of bioactive marker compounds in Draksharishta, an ayurvedic polyherbal formulation

ABSTRACT Draksharishta is an ayurvedic polyherbal formulation with Draksha (Vitis vinifera L., Vitaceae) as chief ingredient prescribed for digestive impairment, respiratory disorders and weakness. These herbal medicines containing biologically active compounds play a significant role. Therefore it is necessary to carry out the chemical standardization of bioactive marker compounds present in the polyherbal ayurvedic formulation like Draksharishta. The aim of the present work was to develop and validate a HPTLC method for determination of gallic acid, catechin and resveratrol in commercially available marketed and in-house prepared formulations of Draksharishta. This is the first report of quantification of bioactive marker compound resveratrol using HPTLC in Draksharishta. The method employed silica gel precoated thin layer chromatography plates with F254 as the stationary phase. The respective mobile phases were used to develop the plates which separated bands according to the marker compound. Camag scanner V was used for densitometric scanning. Further, the method was validated according to International Conference of Harmonization (ICH) guidelines. The Rƒ values of the three marker compounds were measured. Correlation coefficients were calculated from the standard graph of linearity. Accuracy, precision and recovery were all within the required limits. The developed HPTLC methods for bioactive marker compounds present in in-house and marketed formulations were found to be simple, accurate, precise and robust.