Qualitative Explorations into Customer Based Brand Equity (CBBE) for Medical Tourism in India

The focus of our research is Customer Based Brand Equity (CBBE) in Indian medical tourism which has gained wider attention world-wide. To be able to operationalize CBBE (brand equity) for medical tourism scale development, we generated items for such a scale through content analysis. The research questions for this study were (a) What are the dimensions for a brand equity scale for medical tourism considering social, economic, and market influences? (b) How is culture along with an economic indicator such as infrastructure/superstructure relevant in the context of CBBE for medical tourism? and (c) To what extent does the content analysis of interviews based on questionnaires from literature reviews support the variable? The respondents were contacted from two large East Indian Hospitals with continuous visits by heterogeneous foreign patients. Content analysis was used to evaluate the responses using the framework for coding as given by Corbin and Strauss (2008). This paper explores the reasons as to why the patients from western countries and the Middle East prefer other destinations as compared to India for medical tourism. The medical tourism market is growing due to comparatively affluent middle class, better connectivity and wiser cost decisions by patients. The Indian medical tourism market has gained wider attention due to well trained and competent physicians, cost consideration, quality service, better international accessibility and popular use of English as the primary mode for spoken and written communication language. However, there is no general relevant Customer Based Brand Equity (CBBE) scale for medical tourism market till present day. We have identified six dimensions (three new) for a consolidated and unified CBBE scale for medical tourism. In the later part, we have done a content analysis of 90 patient interviews conducted in Eastern Indian hospitals. The interview questionnaire was developed from the literature review. Lastly, a content analysis is done using Nvivo software for logical validation of literature findings. The content findings and prior literature review enabled us to propose the dimensions of the CBBE scale for medical tourism. The new dimensions may be used for future CBBE research in medical tourism at the global level

High monocytic MDSC signature predicts multi-drug resistance and cancer relapse in non-Hodgkin lymphoma patients treated with R-CHOP

IntroductionNon-Hodgkin Lymphoma (NHL) is a heterogeneous lymphoproliferative malignancy with B cell origin. Combinatorial treatment of rituximab, cyclophsphamide, hydroxydaunorubicin, oncovin, prednisone (R-CHOP) is the standard treatment regimen for NHL, yielding a complete remission (CR) rate of 40-50%. Unfortunately, considerable patients undergo relapse after CR or initial treatment, resulting in poor clinical implications. Patient’s response to chemotherapy varies widely from static disease to cancer recurrence and later is primarily associated with the development of multi-drug resistance (MDR). The immunosuppressive cells within the tumor microenvironment (TME) have become a crucial target for improving the therapy efficacy. However, a better understanding of their involvement is needed for distinctive response of NHL patients after receiving chemotherapy to design more effective front-line treatment algorithms based on reliable predictive biomarkers.MethodsPeripheral blood from 61 CD20+ NHL patients before and after chemotherapy was utilized for immunophenotyping by flow-cytometry at different phases of treatment. In-vivo and in-vitro doxorubicin (Dox) resistance models were developed with murine Dalton’s lymphoma and Jurkat/Raji cell-lines respectively and impact of responsible immune cells on generation of drug resistance was studied by RT-PCR, flow-cytometry and colorimetric assays. Gene silencing, ChIP and western blot were performed to explore the involved signaling pathways.ResultsWe observed a strong positive correlation between elevated level of CD33+CD11b+CD14+CD15- monocytic MDSCs (M-MDSC) and MDR in NHL relapse cohorts. We executed the role of M-MDSCs in fostering drug resistance phenomenon in doxorubicin-resistant cancer cells in both in-vitro, in-vivo models. Moreover, in-vitro supplementation of MDSCs in murine and human lymphoma culture augments early expression of MDR phenotypes than culture without MDSCs, correlated well with in-vitro drug efflux and tumor progression. We found that MDSC secreted cytokines IL-6, IL-10, IL-1β are the dominant factors elevating MDR expression in cancer cells, neutralization of MDSC secreted IL-6, IL-10, IL-1β reversed the MDR trait. Moreover, we identified MDSC secreted IL-6/IL-10/IL-1β induced STAT1/STAT3/NF-κβ signaling axis as a targeted cascade to promote early drug resistance in cancer cells.ConclusionOur data suggests that screening patients for high titre of M-MDSCs might be considered as a new potential biomarker and treatment modality in overcoming chemo-resistance in NHL patients

Assessment of WRF-CO2 simulated vertical profiles of CO2 over Delhi region using aircraft and global model data

Abstract High-resolution regional model simulation of CO2 may be more beneficial to reduce the uncertainty in estimation of CO2 source and sink via inverse modeling. However, the study of atmospheric CO2 transport with regional models is rare over India. Here, weather research and forecasting chemistry model adjusted for CO2 (WRF-CO2) is used for simulating vertical profile of CO2 and its assessment is performed over Delhi, India (27.4–28.6° N and 77–96° E) by comparing aircraft observations (CONTRAIL) and a global model (ACTM) data. During August and September, the positive vertical gradient (~ 13.4 ppm) within ~ 2.5 km height is observed due to strong CO2 uptake by newly growing vegetation. A similar pattern (~ 4 ppm) is noticed in February due to photosynthesis by newly growing winter crops. The WRF-CO2 does not show such steep increasing slope (capture up to 5%) during August and September but same for February is estimated ~ 1.7 ppm. Generally, CO2 is quite well mixed between ~ 2.5 and ~ 8 km height above ground which is well simulated by the WRF-CO2 model. During stubble burning period of 2010, the highest gradient within 2.5 km height above ground was recorded in October (− 9.3 ppm), followed by November (− 7.6 ppm). The WRF-CO2 and ACTM models partially capture these gradients (October − 3.3 and − 2.7 ppm and November − 3.8 and − 4.3 ppm respectively). A study of the seasonal variability of CO2 indicates seasonal amplitudes decrease with increasing height (amplitude is ~ 21 ppm at the near ground and ~ 6 ppm at 6–8 km altitude bin). Correlation coefficients (CC) between the WRF-CO2 model and observation are noted to be greater than 0.59 for all the altitude bins. In contrast to simulated fossil CO2, the biospheric CO2 is in phase with observed seasonality, having about 80% at the lowest level and gradually declines with height due to mixing processes, reaching around 60% at the highest level. The model simulation reveals that meteorology plays a significant role of the horizontal and vertical gradient of CO2 over the region

Involvement of ROS in Chlorogenic Acid-Induced Apoptosis of Bcr-Abl+ CML Cells

Chlorogenic acid (Chl) has been reported to possess a wide range of biological and pharmacological properties including induction of apoptosis of Bcr-Abl+ chronic myeloid leukemia (CML) cell lines and clinical leukemia samples via inhibition of Bcr-Abl phosphorylation. Here we studied the mechanisms of action of Chl in greater detail. Chl treatment induced an early accumulation of intracellular reactive oxygen species (ROS) in Bcr-Abl+ cells leading to downregulation of Bcr-Abl phosphorylation and apoptosis. Chl treatment upregulated death receptor DR5 and induced loss of mitochondrial membrane potential accompanied by release of cytochrome c from the mitochondria to the cytosol. Pharmacological inhibition of caspase-8 partially inhibited apoptosis, whereas caspase-9 and pan-caspase inhibitor almost completely blocked the killing. Knocking down DR5 using siRNA completely attenuated Chlinduced caspase-8 cleavage but partially inhibited apoptosis. Antioxidant NAC attenuated Chl-induced oxidative stress-mediated inhibition of Bcr-Abl phosphorylation, DR5 upregulation, caspase activation and CML cell death. Our data suggested the involvement of parallel death pathways that converged in mitochondria. The role of ROS in Chl-induced death was confirmed with primary leukemia cells fromCML patients in vitro as well as in vivo in nude mice bearing K562 xenografts. Collectively, our results establish the role of ROS for Chl-mediated preferential killing of Bcr-Abl+ cells

Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance

Alcoholic extract of Piper betle (Piper betle L.) leaves was recently found to induce apoptosis of CML cells expressing wild type and mutated Bcr-Abl with imatinib resistance phenotype. Hydroxy-chavicol (HCH), a constituent of the alcoholic extract of Piper betle leaves, was evaluated for anti-CML activity. Here, we report that HCH and its analogues induce killing of primary cells in CML patients and leukemic cell lines expressing wild type and mutated Bcr-Abl, including the T315I mutation, with minimal toxicity to normal human peripheral blood mononuclear cells. HCH causes early but transient increase of mitochondria-derived reactive oxygen species. Reactive oxygen species-dependent persistent activation of JNK leads to an increase in endothelial nitric oxide synthase-mediated nitric oxide generation. This causes loss of mitochondrial membrane potential, release of cytochrome c from mitochondria, cleavage of caspase 9, 3 and poly-adenosine diphosphate-ribose polymerase leading to apoptosis. One HCH analogue was also effective in vivo in SCID mice against grafts expressing the T315I mutation, although to a lesser extent than grafts expressing wild type Bcr-Abl, without showing significant bodyweight loss. Our data describe the role of JNK-dependent endothelial nitric oxide synthase-mediated nitric oxide for anti-CML activity of HCH and this molecule merits further testing in pre-clinical and clinical settings