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Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease without meaningful therapeutic options beyond the first salvage therapy. Targeting PDAC metabolism through amino acid restriction has emerged as a promising new strategy, with asparaginases, enzymes that deplete plasma glutamine and asparagine, reaching clinical trials. In this study, we investigated the anti-PDAC activity of the asparaginase formulation Pegcrisantaspase (PegC) alone and in combination with standard-of-care chemotherapeutics. Methods Using mouse and human PDAC cell lines, we assessed the impact of PegC on cell proliferation, cell death, and cell cycle progression. We further characterized the in vitro effect of PegC on protein synthesis as well as the generation of reactive oxygen species and levels of glutathione, a major cellular antioxidant. Additional cell line studies examined the effect of the combination of PegC with standard-of-care chemotherapeutics. In vivo, the tolerability and efficacy of PegC, as well as the impact on plasma amino acid levels, was assessed using the C57BL/6-derived KPC syngeneic mouse model. Results Here we report that PegC demonstrated potent anti-proliferative activity in a panel of human and murine PDAC cell lines. This decrease in proliferation was accompanied by inhibited protein synthesis and decreased levels of glutathione. In vivo, PegC was tolerable and effectively reduced plasma levels of glutamine and asparagine, leading to a statistically significant inhibition of tumor growth in a syngeneic mouse model of PDAC. There was no observable in vitro or in vivo benefit to combining PegC with standard-of-care chemotherapeutics, including oxaliplatin, irinotecan, 5-fluorouracil, paclitaxel, and gemcitabine. Notably, PegC treatment increased tumor expression of asparagine and serine biosynthetic enzymes. Conclusions Taken together, our results demonstrate the potential therapeutic use of PegC in PDAC and highlight the importance of identifying candidates for combination regimens that could improve cytotoxicity and/or reduce the induction of resistance pathways.

Introduction: Endotracheal intubation is a strong adrenergic stimulus leading to unpredictable increase in heart rate, systolic and diastolic blood pressure which can be detrimental. Various drugs like dexmedetomidine and fentanyl are used for the attenuation of these responses. Aim: To compare the effects of Dexmedetomidine (1 μg/kg) and Fentanyl (2 μg/kg) on haemodynamic response to endotracheal intubation and on anaesthetic requirements. Materials and Methods: This study included 100 patients, undergoing elective surgeries under general anaesthesia. Patients were randomised into Group D (Inj. Dexmedetomidine 1 μ μg/kg iv in 100 mL normal saline) and Group F (Inj. Fentanyl 2 μ μg/kg iv in 100 mL normal saline). Vital monitoring (HR, SBP, DBP, MAP, SpO2) was done. Continuous variables were analysed with unpaired t-test and Mann Whitney U test. Categorical variables were analysed with the Chi-square test. Results: The age range of the study participants were 20-60 years. It was found that magnitude of increase in heart rate at intubation and 1 min after intubation was statistically higher in Group F as compared to Group D. SBP and DBP during intubation and at 1 min after intubation were also significantly higher in group F as compared to Group D. Conclusion: Dexmedetomidine is more effective in attenuating the sympathetic response of laryngoscopy and intubation as compared to Fentanyl.

Superficial angiomyxoma (SA) is one of the superficially located myxoid soft tissue tumor. Because of the rarity of this tumor, there is paucity of fine needle aspiration cytology (FNAC) findings. Here, we present a case of SA in a 14-year-old girl who presented with a left leg swelling. The cytology of the lesion along with the histopathologic correlation is presented.

Human satellites (HSats) are pericentric, tandemly repeating satellite DNA sequences in the human genome. While silent in normal cells, a subset of HSat2 noncoding RNA is expressed and accumulates in the nucleus of cancer cells. We developed a FISH-based approach for identification of the distribution of three subfamilies of HSat2 (A1, A2, B) sequences on individual human chromosomes. Further, using the HSat subfamily annotations in the T2T completed centromere satellite (CenSat) sequence, we isolated, defined and mapped differentially expressed sequence variants of nuclear-restricted HSat2 and HSat3 RNA from cancer cell lines and heat-shocked cells. We identified chromosome-specific and subfamily-specific expression of HSat2 and HSat3 and established a computational pipeline for differential expression analysis of tandemly repeated satellite sequences. Results suggest the differential expression of chromosome-specific HSat2 arrays in the human genome may underlie their accumulation in cancer cells and that specific HSat3 loci are upregulated upon heat shock.

Accidental exposure to ionizing radiation may lead to delayed effects of acute radiation exposure (DEARE) in many organ systems. Activated protein C (APC) is a known mitigator of the acute radiation syndrome. To examine the role of APC in DEARE, we used a transgenic mouse model with 2- to 3-fold increased plasma levels of APC (high in APC, APCHi). Male and female APCHi mice and wild-type littermates were exposed to 9.5 Gy γ-rays with their hind-legs (bone marrow) shielded from radiation to allow long-term survival. At 3 and 6 months after irradiation, cardiac function was measured with ultrasonography. At 3 months, radiation increased cardiac dimensions in APCHi males, while decreases were seen in wild-type females. At this early time point, APCHi mice of both sexes were more susceptible to radiation-induced changes in systolic function compared to wild-types. At 6 months, a decrease in systolic function was mainly seen in male mice of both genotypes. At 6 months, specimens of heart, small intestine and dorsal skin were collected for tissue analysis. Female APCHi mice showed the most severe radiation-induced deposition of cardiac collagens but were protected against a radiation-induced loss of microvascular density. Both male and female APCHi mice were protected against a radiation induced upregulation of toll-like receptor 4 in the heart, but this did not translate into a clear protection against immune cell infiltration. In the small intestine, the APCHi genotype had no effect on an increase in the number of myeloperoxidase positive cells (seen mostly in females) or an increase in the expression of T-cell marker CD2 (males). Lastly, both male and female APCHi mice were protected against radiation-induced epidermal thickening and increase in 3-nitrotyrosine positive keratinocytes. In conclusion, prolonged high levels of APC in a transgenic mouse model had little effects on indicators of DEARE in the heart, small intestine and skin, with some differential effects in male compared to female mice.

Background. Oral health is dependent on the knowledge and awareness of the individuals. Teachers as individuals influence the children in every aspect including oral health maintenance. The objective of this study was to assess the oral health knowledge, attitude, practices, and oral health status among school teachers in Chitwan District, Nepal. Materials and Methods. A cross-sectional study was conducted on 550 school teachers of private and government schools in Chitwan District, to assess the knowledge, attitude, practices, and oral health status. Descriptive analysis was done and data were analyzed using chi-square. A five-point Likert Scale was applied to compute knowledge, attitude, and practices of the school teachers. Results. Most of the school teachers had good knowledge about periodontal diseases in comparison to dental caries. Private school (20.7% : 57) teachers had higher good oral health knowledge as compared to government school teachers (9.8% : 27). An almost equal percentage of private and government teachers (73.5% : 202 and 74.2% : 204, respectively) were found with fair knowledge about oral health. Males had a higher percentage for good oral health knowledge as compared to females. Conclusion. There is an incredible need to improve oral health knowledge and attitude among school teachers concerning different problems of the oral cavity and the avoidance of dental diseases. These enhancements can be applied through regular training of teachers by oral health seminars, materials, and other such types of methods.