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Otitis media (OM) is a very common pediatric disease and nontypeable Haemophilus influenzae (NTHI) is the predominant causative agent. We've developed a chimeric immunogen, chimV4, that simultaneously targets two NTHI adhesins, OMP P5 and the type IV pilus. Transcutaneous immunization (TCI) via bandaid with chimV4 plus the adjuvant dmLT provides significant protection against experimental NTHI-induced OM in chinchilla models. Herein, we now examined the durability and boostability of the induced immune response. Bandaid immunization with chimV4+dmLT followed by two sequential middle ear challenges with NTHI resulted in rapid bacterial clearance and significantly accelerated disease resolution. Moreover, TCI with chimV4+dmLT significantly increased mature B-cell phenotypes and antibody-secreting cells within nasal-associated lymphoid tissues, a response that was further augmented upon TCI two months later. Thus, bandaid immunization induced durable and boostable immunity. The simplicity and non-invasive nature of TCI with chimV4+dmLT supports its utility as a highly effective additional immunization strategy for NTHI-induced OM. BACKGROUND Vaccine hesitancy is a complex behaviour which involves various degrees of indecision about specific vaccines or vaccination uptake. Access to antenatal care had been associated with positive vaccine behavior. OBJECTIVE To determine the prevalence of vaccine hesitancy towards childhood immunisation amongst urban pregnant mothers and the associated socio-demographic factors. METHODS A cross-sectional study was conducted among 1081 women who received antenatal care at a teaching hospital in Kuala Lumpur. Vaccine hesitancy was assessed using the Parent Attitudes about Childhood Vaccines (PACV) Survey in both English and validated Malay versions. The sociodemographic data of the mothers and their partners, source of vaccine information and reasons for hesitancy were analysed. RESULTS Eighty-six (8.0%) pregnant mothers were vaccine hesitant. Ethnicity, religion, number of children, educational level and employment status were significantly associated with vaccine hesitancy. Multivariable analysis showed that a low level of education was the most significant risk factor (p less then 0.001), followed by religion (p = 0.03). Health professionals was the main source of information about vaccine. The non-vaccine hesitant women were more likely to seek information from health professionals, and health books and magazine. Fear of adverse side effects of vaccines was the predominant concern for all participants (58%) whilst fear of vaccination pain, preference for alternative medicine and lack of trust in the pharmaceutical industry were significant reasons given by the vaccine hesitant group. Partners' ethnicity, a low educational level and a low income were significantly associated with vaccine hesitancy amongst pregnant mothers. CONCLUSION Prevalence of vaccine hesitancy amongst urban Malaysian pregnant women was relatively low. Muslim mothers are less likely to be vaccine hesitant. Educational level of mothers and their partners are the common determinant of vaccine hesitancy amongst antenatal mothers. Stereotactic radiosurgery/radiotherapy (SRS/SRT) is a hypofractionated treatment where accurate dose calculation is of prime importance. The accuracy of the dose calculation depends on the treatment planning algorithm. This study is a retrospective dosimetric comparison of iPlanⓇ Monte Carlo (MC) and Pencil Beam (PB) algorithms in SRS/SRT plans of cranial arteriovenous malformations (AVMs). PB plans of 60 AVM patients who were already treated using 6 MV photons from a linear accelerator were selected and divided into 2 groups. Group-I consists of 30 patients who have undergone embolization procedure with high density OnyxⓇ prior to radiosurgery whereas Group-II had 30 patients who did not have embolization. These plans were recalculated with MC algorithm while keeping parameters like beam orientation, multileaf collimator (MLC) positions, MLC margin, prescription dose, and monitor units constant. Several treatment coverage parameters, isodose volumes, plan quality metrics, dose to organs at risk, and integralof lateral charged particle equilibrium and lateral broadening of small photon beams by PB algorithm. MC algorithms are generally considered not essential for dose calculations for target volumes located in the brain. This study demonstrates PB algorithm may not be sufficiently accurate to predict dose distributions for small fields where there is loss of LCPE. The lateral broadening due to the loss of LCPE as predicted by the MC algorithm could be the main reason for significant differences in the parameters compared. Hence, an accurate MC algorithm if available may prove valuable for intracranial SRS treatment planning of such benign lesions where the long life expectancy of patients makes accurate dosimetry critical. Fibroblast growth factor-23 (FGF23) is a hormone indispensable for maintaining phosphate homeostasis. In response to phosphate intake, FGF23 is secreted from osteocytes/osteoblasts and acts on the kidney to increase urinary phosphate excretion. However, the mechanism by which these cells sense phosphate intake remains elusive. https://www.selleckchem.com/products/pepstatin-a.html Calciprotein particles are nanoparticles of calcium-phosphate precipitates bound to serum protein fetuin-A and are generated spontaneously in solution containing calcium, phosphate, and fetuin-A to be dispersed as colloids. In cultured osteoblastic cells, increase in either calcium or phosphate concentration in the medium induced FGF23 expression, which was dependent on calciprotein particle formation. When transition of calcium-phosphate precipitates from the amorphous phase to the crystalline phase was blocked by bisphosphonate, the calciprotein particle size was reduced and FGF23 expression was augmented, suggesting that small calciprotein particles containing amorphous calcium-phosphate precipitates function as a more potent FGF23 inducer than larger calciprotein particles containing crystalline calcium-phosphate precipitates. In mice, bolus phosphate administration by oral gavage transiently increased circulating calciprotein particle levels followed by a modest increase in FGF23 expression and serum FGF23 levels. However, continuous dietary phosphate load induced robust and persistent increase in circulating calciprotein particles and FGF23 levels. We confirmed by in vivo imaging that calciprotein particles injected intravenously extravasated into the bone marrow and were deposited on the inner surface of the bone, indicating that these particles have direct access to osteoblasts. Thus, we propose that osteoblasts induce FGF23 expression and secretion when they sense an increase in extracellular calciprotein particles following phosphate ingestion.
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