Dentition Status and its effect on the Oral Health Related Quality of Life in a Rural Elderly Population: A Cross Sectional Study

Background: This study was conducted to find out the effect of dentition status on the oral health related quality of life of rural elderly people residing in an Indian population.Methods: A total of 368 elderly subjects from eight villages were included in the study. OHRQoL was measured by using a validated Hindi version of Geriatric Oral Health AsBackground: This study was conducted to find out the effect of dentition status on the oral health related quality of life (OHRQoL) of rural elderly people in an Indian population. The main objectives included the assessment of age wise differences among the elderly segment, particularly the effect of coronal and root caries, missing teeth and filled teeth.Methods: A total of 368 (192 (52.17%) males and 176 (47.83%) females) elderly subjects from eight villages were included in the study. Oral Health Related Quality of life was measured by using a validated Hindi version of Geriatric Oral Health Assessment Index (GOHAI). Clinical assessment of the subjects was done regarding carious, missing, and filled teeth, and carious roots.Results: The mean GOHAI score was found to be 18.14 ± 5.71. The mean number of decayed crown was 1.34 ± 1.63, mean number of missing teeth was 12.74 ± 11.14, mean DMFT score was 14.08 ± 10.13, and mean number of teeth with root caries was 0.55 ± 1.17. Average number of carious roots was found to be maximum among 70-79 years age group followed by 60-69 years age group. Age wise differences were found to be statistically significant for mean number of decayed crown, missing teeth, root caries and mean DMFT.Conclusion: The results revealed that having more teeth present and less decayed teeth were found to be associated with better oral health related quality of life. The elderly are a special part of our society and need the utmost attention since they are most susceptible to oral diseases which impact their daily activities. Hence more light needs to be thrown on such issues to improve the overall health including the oral component.sessment Index (GOHAI). Clinical assessment of the subjects was done regarding carious, missing, filled teeth and carious roots.Results: The mean GOHAI score was found to be 18.14 ± 5.71. The mean decayed teeth were found to be 1.34 and mean DMFT was 14.08. Age wise differences were found to be statistically significant for mean number of decayed crown, missing teeth, root caries and mean DMFT.Conclusion: The results revealed the having more teeth present and less decayed teeth were found to be associated with better oral health related quality of life

Targeting PI3K Pathway in Pancreatic Ductal Adenocarcinoma: Rationale and Progress

Pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest solid tumors that remain treatment-refractory and show a dismal prognosis. More than 90% of PDAC tumors harbor mutations in the K-Ras that exert a strong pro-tumorigenic effect by activating several downstream effector pathways, including phosphatidylinositol-3-kinase (PI3K)-Akt. The role of frequently activated PI3K/Akt pathway in promoting PDAC aggressiveness is well established. Therapeutic approaches targeting PI3K and downstream signaling components in different cellular compartments, including tumor, stromal and immune cells, have directly impacted the tumor burden in this cancer type. Our previous work has demonstrated that targeting the PI3K/Akt/mTOR pathway reduced tumor growth and improved survival in the genetic mouse model of PDAC. Here, we discuss the significance of targeting PI3K signaling and the biological impact of PI3K inhibition in modulating the tumor–stromal immune crosstalk within the microenvironment of pancreatic cancer. Furthermore, this review updates on the current challenges involving the therapeutic implications of targeting this pathway in PDAC

Materiality Analyses: Evolution and Importance

Firms deal with a range of issues that they report in Corporate Social Responsibility (CSR) reports. However, not all issues are relatively important to correctively reflect environmental, social and economic impacts and influence stakeholder’s decisions. In addition, there is variability in reporting practices. At this point, corporate materiality analyses come to the rescue for the firms and aid them in prioritizing and reporting the most important issues. Materiality analyses have gained increased popularity and adoption by firms globally. GRI (Global Reporting Initiative) rates materiality as the most important criteria while publishing CSR reports. The current study\u27s objective was to understand how materiality analyses have evolved. With the evolution, are there any trends that could be observed? For the study, 14 firms were chosen belonging to different sectors. The firms used were Firms of Endearment. Fortune 100 and two of the big four consulting firms. The study was carried by using two-order scheme for coding data by using Gioia methodology into different categories in NVIVO (software for qualitative research). Categories were created, and frequency of the each of the categories were computed. Percentage values were calculated using the frequency of each of the categories. There were positive and contradicting trends that were observed in the evolution of materiality analyses for current research. The findings from the current research give a new perspective to look at materiality and pave the way for more investigation in this area

Emerging Role of CREB in Epithelial to Mesenchymal Plasticity of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid malignancy with a high rate of metastasis and therapeutic resistance as its major hallmarks. Although a defining mutational event in pancreatic cancer initiation is the presence of oncogenic KRAS, more advanced PDAC lesions accumulate additional genomic alterations, including loss of tumor suppressor gene TP53. Co-occurrence of mutant KRAS and TP53 in PDAC promotes hyperactivation of cancer cell signaling pathways driving epithelial to mesenchymal plasticity (EMP). The cellular process of EMP influences the biological behavior of cancer cells by increasing their migratory and invasive properties, thus promoting metastasis. Our previous work has demonstrated that oncogenic KRAS-mediated activation of cyclic AMP response element-binding protein 1 (CREB) is one of the critical drivers of PDAC aggressiveness. The therapeutic approach of targeting this key transcription factor attenuates tumor burden in genetically engineered mouse models (GEMMs) of this disease. Herein, we discuss the significant role of CREB in perpetuating disease aggressiveness and therapeutic resistance through the EMP process. Furthermore, this review updates the therapeutic implications of targeting CREB, highlighting the challenges and emerging approaches in PDAC

Targeting PI3K Pathway in Pancreatic Ductal Adenocarcinoma: Rationale and Progress

Pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest solid tumors that remain treatment-refractory and show a dismal prognosis. More than 90% of PDAC tumors harbor mutations in the K-Ras that exert a strong pro-tumorigenic effect by activating several downstream effector pathways, including phosphatidylinositol-3-kinase (PI3K)-Akt. The role of frequently activated PI3K/Akt pathway in promoting PDAC aggressiveness is well established. Therapeutic approaches targeting PI3K and downstream signaling components in different cellular compartments, including tumor, stromal and immune cells, have directly impacted the tumor burden in this cancer type. Our previous work has demonstrated that targeting the PI3K/Akt/mTOR pathway reduced tumor growth and improved survival in the genetic mouse model of PDAC. Here, we discuss the significance of targeting PI3K signaling and the biological impact of PI3K inhibition in modulating the tumor–stromal immune crosstalk within the microenvironment of pancreatic cancer. Furthermore, this review updates on the current challenges involving the therapeutic implications of targeting this pathway in PDAC

Psychogenic hiccup in children and adolescents: A case series

Hiccups can be due to organic diseases or psychogenic causes. Psychogenic hiccup in children is an understudied area. We report a series of four cases presenting with psychogenic hiccups to the Psychiatry Outpatient Clinic of a tertiary care hospital in North India. The cases were aged 11 to 13 years; three of them were males and one female. Three of the patients belonged to a rural background and all of them were from Hindu nuclear families. The duration of hiccups for which treatment was sought ranged from three to fourteen months. The most common gains seen in two of the patients were, lesser scolding from the parents and getting eatables of their choice. The patients were managed by counseling and psychoeducation about the problem and cutting down the secondary gain. Techniques of suggestion and double bind were tried. Two of the patients had improved on the day detailed assessments were done, and all of the patients had improved on follow up. Psychogenic hiccups in children and in the adolescent age group can be effectively managed by using non-pharmacological methods and appropriate education of the parents

Abstract C020: Neutrophil-mediated stromal-tumor IL-6/STAT-3 signaling underlies the association between neutrophil-to-lymphocyte ratio dynamics and chemotherapy response in localized pancreatic cancer: A hybrid clinical-preclinical study

Abstract Background: Partial/complete pathologic response following neoadjuvant chemotherapy (NAC) in pancreatic cancer (PDAC) patients undergoing pancreatectomy is associated with improved survival. We sought to determine whether neutrophil-to-lymphocyte ratio (NLR) dynamics predict pathologic response following chemotherapy in PDAC, and if manipulating NLR impacts chemosensitivity in preclinical models and uncovers potential mechanistic underpinnings underlying these effects. Methods: Pathologic response in PDAC patients (n=94) undergoing NAC and pancreatectomy (7/2015-12/2019) was dichotomized as partial/complete or poor/absent (case-cohort design). Bootstrap-validated multivariable models assessed associations between pre-chemotherapy NLR (%neutrophils÷%lymphocytes) or NLR dynamics during chemotherapy (ΔNLR=pre-surgery—pre-chemotherapy NLR) and pathologic response, disease-free survival (DFS), and overall survival (OS). To preclinically model effects of NLR attenuation on chemosensitivity, C57BL/6 mice (n=8-10/arm) were orthotopically injected with KrasG12D/+;Trp53fl/+;PdxCre(KPC) cells and randomized to vehicle, NLR-attenuating anti-Ly6G, gemcitabine/paclitaxel, or gemcitabine/paclitaxel+anti-Ly6G treatments. Results: In 94 PDAC patients undergoing NAC (median:4 months), pre-chemotherapy NLR (P<0.001) and ΔNLR attenuation during NAC (P=0.002) were independently associated with partial/complete pathologic response. An NLR score=pre-chemotherapy NLR+ΔNLR correlated with DFS (P=0.006) and OS (P=0.002). Upon preclinical modeling, combining NLR-attenuating anti-Ly6G treatment with gemcitabine/paclitaxel—compared with gemcitabine/paclitaxel or anti-Ly6G alone—not only significantly reduced tumor burden and metastatic outgrowth, but also augmented tumor-infiltrating CD107a+-degranulating CD8+ T-cells (P<0.01) while dampening inflammatory cancer-associated fibroblast (CAF) polarization (P=0.006) and chemoresistant IL-6/STAT-3 signaling in vivo. Neutrophil-derived IL-1β emerged as a novel mediator of stromal inflammation, inducing inflammatory CAF polarization and CAF-tumor cell IL-6/STAT-3 signaling in ex vivo co-cultures. Conclusions: Therapeutic strategies to mitigate neutrophil-CAF-tumor cell IL-1β/IL-6/STAT-3 signaling during NAC may improve pathologic responses and/or survival in PDAC. Citation Format: Iago De Castro Silva, Anna Bianchi, Nilesh Deshpande, Prateek Sharma, Siddharth Mehra, Peter Hosein, Deukwoo Kwon, Nipun Merchant, Jashodeep Datta. Neutrophil-mediated stromal-tumor IL-6/STAT-3 signaling underlies the association between neutrophil-to-lymphocyte ratio dynamics and chemotherapy response in localized pancreatic cancer: A hybrid clinical-preclinical study [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C020