IIMA in HealthCare Management: Abstract of Publications (2000-2010)

The Indian Institute of Management, Ahmedabad (IIMA), was established in 1961 as an autonomous institution by the Government of India in collaboration with the Government of Gujarat and Indian industry. IIMA’s involvement in the health sector started with the establishment of the Public Systems Group in 1975. In the initial period, our research focused on the management of primary healthcare services and family planning. We expanded our research activities to include the management of secondary healthcare services in the 80s and to tertiary healthcare services in the 90s. Currently our research interests focus on the governance and management issues in the areas on Rural Health, Urban Health, Public Health and Hospital Management. In June 2004, IIMA Board approved the setting up of a Centre for Management Health Services (CMHS) in recognition of IIMA’s contributions to the health sector in the past and the felt need to strengthen the management of health sector in the context of socio-economic developments of our country. The overall objectives of CMHS are to address the managerial challenges in the delivery of health services to respond to the needs of different segments of our population efficiently and effectively, build institutions of excellence in the health sector, and influence health policies and wider environments. All our research projects are externally funded and we have developed research collaborations with 15-20 international universities in USA, UK, Europe, and Asia. CMHS has also established strong linkages with the Ministry of Health and Family Welfare at the national and state government levels, particularly in the states of Gujarat, Maharashtra, Rajasthan, Madhya Pradesh, Chattisgarh, Orissa, and Bihar. This working paper is a compilation of the abstracts of all our publications in the last 10 years, which include 40 referred journal articles, 54 Working Papers, 19 Chapters in Books and 18 Case Studies.

The Role of the District Public Health Nurses: A Study from Gujarat

The role of District Public Health Nurses (DPHN) and District Public Health Nurse Officers (DPHNOs) as supervisors of the Public Health nursing and midwifery staff in a district was investigated. Thirteen DPHNs and DPHNOs from six districts selected from six geographic zones of Gujarat were observed for one week using the time motion method. Their activities and time spent were noted and the DPHNs/DPHNOs and their supervisors were interviewed. The role of the DPHNs has reduced over the years because they have not been assigned new roles with change in programmes and policies. Most of the DPHNs have training for clinical work in hospitals. Their 10 month training to qualify for PHN is inadequate to develop knowledge and skills in public health. There is a gap between their training and posting due to delays in government procedures of promotion. The DPHN/DPHNOs spend majority of their time in the office (49%) where they have a limited role. Their supervisory role for nurses and midwives has lost its importance. They spend about 1/3rd of their time in field supervision mostly visiting centres accessible by public transport as they do not have an allotted government vehicle. As they do not submit any field report, there is no follow-up action from their visit. Nevertheless they seem to have an important role in solving problems of field workers as they are mediators between the district and peripheral facilities. To conclude the DPHNs are under utilized which affects the quality of maternal and child health services in the district.

3D Modeling of Epithelial Tumors-The Synergy between Materials Engineering, 3D Bioprinting, High-Content Imaging, and Nanotechnology

The current statistics on cancer show that 90% of all human cancers originate from epithelial cells. Breast and prostate cancer are examples of common tumors of epithelial origin that would benefit from improved drug treatment strategies. About 90% of preclinically approved drugs fail in clinical trials, partially due to the use of too simplified in vitro models and a lack of mimicking the tumor microenvironment in drug efficacy testing. This review focuses on the origin and mechanism of epithelial cancers, followed by experimental models designed to recapitulate the epithelial cancer structure and microenvironment, such as 2D and 3D cell culture models and animal models. A specific focus is put on novel technologies for cell culture of spheroids, organoids, and 3D-printed tissue-like models utilizing biomaterials of natural or synthetic origins. Further emphasis is laid on high-content imaging technologies that are used in the field to visualize in vitro models and their morphology. The associated technological advancements and challenges are also discussed. Finally, the review gives an insight into the potential of exploiting nanotechnological approaches in epithelial cancer research both as tools in tumor modeling and how they can be utilized for the development of nanotherapeutics

Genome-Wide Screen for Mycobacterium tuberculosis Genes That Regulate Host Immunity

In spite of its highly immunogenic properties, Mycobacterium tuberculosis (Mtb) establishes persistent infection in otherwise healthy individuals, making it one of the most widespread and deadly human pathogens. Mtb's prolonged survival may reflect production of microbial factors that prevent even more vigorous immunity (quantitative effect) or that divert the immune response to a non-sterilizing mode (qualitative effect). Disruption of Mtb genes has produced a list of several dozen candidate immunomodulatory factors. Here we used robotic fluorescence microscopy to screen 10,100 loss-of-function transposon mutants of Mtb for their impact on the expression of promoter-reporter constructs for 12 host immune response genes in a mouse macrophage cell line. The screen identified 364 candidate immunoregulatory genes. To illustrate the utility of the candidate list, we confirmed the impact of 35 Mtb mutant strains on expression of endogenous immune response genes in primary macrophages. Detailed analysis focused on a strain of Mtb in which a transposon disrupts Rv0431, a gene encoding a conserved protein of unknown function. This mutant elicited much more macrophage TNFα, IL-12p40 and IL-6 in vitro than wild type Mtb, and was attenuated in the mouse. The mutant list provides a platform for exploring the immunobiology of tuberculosis, for example, by combining immunoregulatory mutations in a candidate vaccine strain

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Chitosan–Cellulose Multifunctional Hydrogel Beads: Design, Characterization and Evaluation of Cytocompatibility with Breast Adenocarcinoma and Osteoblast Cells

Cytocompatible polysaccharide-based functional scaffolds are potential extracellular matrix candidates for soft and hard tissue engineering. This paper describes a facile approach to design cytocompatible, non-toxic, and multifunctional chitosan-cellulose based hydrogel beads utilising polysaccharide dissolution in sodium hydroxide-urea-water solvent system and coagulation under three different acidic conditions, namely 2 M acetic acid, 2 M hydrochloric acid, and 2 M sulfuric acid. The effect of coagulating medium on the final chemical composition of the hydrogel beads is investigated by spectroscopic techniques (ATR–FTIR, Raman, NMR), and elemental analysis. The beads coagulated in 2 M acetic acid displayed an unchanged chitosan composition with free amino groups, while the beads coagulated in 2 M hydrochloric and sulfuric acid showed protonation of amino groups and ionic interaction with the counterions. The ultrastructural morphological study of lyophilized beads showed that increased chitosan content enhanced the porosity of the hydrogel beads. Furthermore, cytocompatibility evaluation of the hydrogel beads with human breast adenocarcinoma cells (soft tissue) showed that the beads coagulated in 2 M acetic acid are the most suitable for this type of cells in comparison to other coagulating systems. The acetic acid fabricated hydrogel beads also support osteoblast growth and adhesion over 192 h. Thus, in future, these hydrogel beads can be tested in the in vitro studies related to breast cancer and for bone regeneration

Supramolecular design of cellulose-based hydrogel beads

The degree of polymerization (DP) of cellulose fibres is an important factor to consider during dissolution in water-based solvent system and to design further advanced biomaterials. The lower is the DP, the higher cellulose concentration solutions can be prepared. Therefore, the DP of the cellulose fibres needs to be controlled. This was achieved by chemical pretreatment of the pulp in which the pKa of the chosen acid and the solvent used had a direct impact on the DP of the treated pulp. Stronger acids resulted in lower DP values of pulp in comparison to weaker acids. Higher ethanol concentration in the treatment solvent mixture lead to the enhanced recovery of the final pretreated pulp. The pretreated pulp was used to design pristine cellulose beads in 7 % NaOH-12 % Urea-81 % water based solvent system. The cellulose beads were further functionalized into zwitterionic cellulose beads by performing (2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl (TEMPO) mediated oxidation reaction followed by hydrazide coupling. The sodium chlorite (NaClO2)/sodium hypochlorite (NaClO)/TEMPO oxidation system resulted in the generation of carboxylic and carbonyl moieties in the beads. A coupling reaction between the carbonyl and carboxymethyl trimethylammonium chloride hydrazide (Girard’s reagent T) resulted in the introduction of cationic moieties in the beads. The molar ratio of the reagents had a crucial role in tailoring carboxylic and carbonyl content generation in the beads. The ultrastructural study of beads showed that zwitterionic beads had larger pores than the pristine cellulose beads. Anionic cellulose hydrogel beads were designed by blending sodium cellulose ethylsulfonate (CES) an anionic cellulose derivative, with the pretreated cellulose in the 7 % NaOH -12 % Urea - 81 % water based solvent system. The rheology of the blends was studied and the hydrogel beads were coagulated in 2 M sulfuric acid bath. The effect of increasing CES polymer concentration on the hydrogel beads shape, water holding capacity, stability and ultrastructural morphology was studied. The incorporation of CES up to 50 % concentration resulted in stable hydrogel beads with enhanced porosity and water holding capacity. Functional chitosan-based cellulose hydrogel beads were designed by blending cellulose with chitosan in the sodium hydroxide-urea-water solvent system and consecutive coagulating in 2 M acetic, hydrochloric and sulfuric acid systems. The concentration of chitosan and type of coagulating acid played a decisive role in selecting the hydrogel beads for testing in tissue engineering applications. The hydrogel beads with 70 % chitosan- 30 % cellulose coagulated in acetic acid showed the highest cytocompatibility with breast adenocarcinoma (soft tissue) and osteoblast (hard tissue) cells. The chitosan based hydrogel beads have the potential to be tested further for applications in the field of tissue engineering

CONTROLLED DEPOLYMERISATION OF CELLULOSE TO A GIVEN DEGREE OF POLYMERISATION

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A Study of Referral System for EmOC in Gujarat

An effective referral system is an essential prerequisite for a well functioning Emergency Obstetric Care (EmOC) service. It is the link between the home of the mother and a well equipped facility. The study attempts to explore the crucial link of referral system between the primary and higher level facilities. [W.P. No. 2009-06-02]effective, Emergency Obstetric Care, facility

IIMA in HealthCare Management: Abstract of Publications (2000-2010)

This working paper is a compilation of the abstracts of all our publications in the last 10 years, which include 40 referred journal articles, 54 Working Papers, 19 Chapters in Books and 18 Case Studies.[W.P. No. 2010-04-04]Journal Articles, Working Papers, Chapters in Books, Case Studies