Background & Objectives: Hepatitis B is the most important infectious occupational disease for the health care workers. Dental surgeons are frequently in contact with blood and saliva and hence are at high risk for Hepatitis B Virus (HBV) exposure. HBV infection is a major public health problem in India, as there are 45 million estimated carriers. Immunization against HBV reduces the risk of transmission of HBV to dental personnel and from dental personnel to patients. The present study was aimed to evaluate the serum levels of anti-HBs in vaccinated dental health care workers. Methods: In this study, estimation of serum levels of Anti- HBs in 40 dental students vaccinated against HBV was done. Data was obtained regarding vaccination data, age, sex, weight, height and smoking history. Anti-HBs level was evaluated two years after the 1st dose of vaccination. Low responders were given booster vaccination and post booster anti HBs assay was done. Results: The study included 110 hepatitis B vaccinated dental students. Out of 110 students only 40 students had documented history of complete vaccination and volunteered to be a part of the study. Among these 40 students, three students (7.5%) had less than 100 IU/L anti–HBs level and 37 students (92.5%) had more than 100 IU/L anti–HBs level. Anti- HBS level above 100 IU/L is identified to be protective. Following booster vaccination, low responders showed anti -HBs titre more than 100 IU/L. Conclusion: In this study majority dental students had desirable immune response to the HBV vaccine. Male gender and positive smoking history could have attributed to low anti-HBs titre in subjects who had inadequate levels in our study. Hence, all Health Care Workers, in particular dental surgeons with contributory factors like smoking habit, male gender should undergo periodic assessment of anti-HBs titre.

The endoplasmic reticulum (ER) is a dynamic organelle that responds to demand in secretory proteins by undergoing expansion. The mechanisms that control the homeostasis of ER size and function involve the activation of the unfolded protein response (UPR). The UPR plays a role in various effector functions of immune cells. Mast cells (MCs) are highly granular tissue-resident cells and key drivers of allergic inflammation. Their diverse secretory functions in response to activation through the high-affinity receptor for IgE (FcεRI) suggest a role for the UPR in their function. Using human cord blood-derived MCs, we found that FcεRI triggering elevated the expression level and induced activation of the UPR transducers IRE1α and PERK, accompanied by expansion of the ER. In mouse bone marrow-derived MCs and peritoneal MCs, the ER underwent a more moderate expansion, and the UPR was not induced following MC activation. The deletion of IRE1α in mouse MCs did not affect proliferation, survival, degranulation, or cytokine stimulation following FcεRI triggering, but it did diminish the surface expression of TLR4 and the consequent response to LPS. A similar phenotype was observed in human MCs using an IRE1α inhibitor. Our data indicate that the ER of MCs, primarily of humans, undergoes a rapid remodeling in response to activation that promotes responses to TLR4. We suggest that IRE1α inhibition can be a strategy for inhibiting the hyperactivation of MCs by LPS over the course of allergic responses.

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Multiple myeloma (MM) causes approximately 20% of deaths from blood cancers. Notwithstanding significant therapeutic progress, such as with proteasome inhibitors (PIs), MM remains incurable due to the development of resistance. mTORC1 is a key metabolic regulator, which frequently becomes dysregulated in cancer. While mTORC1 inhibitors reduce MM viability and synergize with other therapies in vitro, clinically, mTORC1 inhibitors are not effective for MM. Here we show that the inactivation of mTORC1 is an intrinsic response of MM to PI treatment. Genetically enforced hyperactivation of mTORC1 in MM was sufficient to compromise tumorigenicity in mice. In vitro, mTORC1-hyperactivated MM cells gained sensitivity to PIs and hypoxia. This was accompanied by increased mitochondrial stress and activation of the eIF2α kinase HRI, which initiates the integrated stress response. Deletion of HRI elevated the toxicity of PIs in wt and mTORC1-activated MM. Finally, we identified the drug PMA as a robust inducer of mTORC1 activity, which synergized with PIs in inducing MM cell death. These results help explain the clinical inefficacy of mTORC1 inhibitors in MM. Our data implicate mTORC1 induction and/or HRI inhibition as pharmacological strategies to enhance MM therapy by PIs.