Heat shock proteins may be a missing link between febrile infection and cancer tumor rejection via autoantigen molecular mimicry

Numerous epidemiological studies suggest febrile infections could confer long-term immunity to certain types of cancers, though the precise mechanisms for this phenomenon remain unclear. Systemic heat-shock responses to fever may be key to understanding the overlapping outcomes of immune responses to infection and cancer. To investigate this hypothesis, we performed epitope discovery between heat-shock proteins (HSP) and cancer-associated antigens (CAA) and annotated the results with experimentally validated epitopes in the Immune Epitope Database (IEDB) (Vita et al., 2019). Further, epitopes were matched with their homologs in human pathogens. Results identified 94 epitopes shared between HSPs and CAAs, with experimental evidence of presentation at MHC molecules and with high homology to several epitopes of human pathogens. The identified epitopes can be used as candidates for designing cancer vaccines. They may also be used to identify autoreactive antibodies or TCR specificities that, as antibody drugs and cell therapies, would reproduce the effect of febrile infection in conferring cancer immunity. Our results support the hypothesis that the loss of self-tolerance to HSPs during febrile infection confers tumor immunity through molecular mimicry.Comment: 16 pages, 3 figures, one tabl

Program directors’ perceptions of importance of pediatric procedural skills and resident preparedness

Background The Royal College of Physicians and Surgeons of Canada (RCPSC) objectives for training in pediatrics include 26 procedural skills, 11 of which are included in the final in-training evaluation report (FITER). The importance of each procedure for practice and the preparedness of pediatric residency graduates to perform these procedures are not known. Methods A questionnaire was distributed to all pediatric residency program directors and members of the RCPSC Specialty Committee in Pediatrics (N = 21) in October 2010, requesting them to rate the perceived importance and preparedness of graduating pediatric residents in all procedural skills on a 5 point Likert scale, as well as the presence of a curriculum and documentation for each procedure. Mean importance and preparedness were calculated for each procedure. Results Response rate was 16/21 (76 %). Perceived preparedness was significantly lower than importance for the majority of procedures (p 3) but a low mean preparedness rating (<3). Presence of a curriculum and documentation for procedures varied across centers, and their presence was correlated with both perceived importance and preparedness (p < 0.0001). Conclusions Many procedures in which pediatric residents are required to be competent by the RCPSC are felt to be important. Residents are not felt to be adequately prepared in several of the required procedures by the time of graduation. Procedures with high ratings of importance but low preparedness ratings should be targeted for curricular interventions

Salivary Composition of Oral Squamous Cell Carcinoma Patients

OBJECTIVES: The purpose of the study was to determine the salivary composition of Oral squamous cell carcinoma patients. METHODOLOGY: A retrospective study was conducted over 6 months on data of 60 Oral squamous cell carcinoma patients obtained from the patient records of the Institute of Radiotherapy and Nuclear Medicine, Peshawar. Salivary pH, Sodium, Potassium, and total proteins of Oral squamous cell carcinoma patients were recorded. RESULTS: Sodium, Potassium, and total protein concentration in saliva of oral squamous cell carcinoma patients were 23.5 mM/L, 96.7mM/L, and 234.6 mM/L, respectively. These values were significantly higher than normal salivary concentration. CONCLUSION: It was concluded that the saliva of oral squamous cell carcinoma patients contains higher concentrations of Sodium, Potassium, and total proteins

Comparison of Different Types of Water Melon for Their Important Nutrients

In the present study three different types (Green, light green and light green banded) of water melon was collected from local market of Peshawar and were analyzed for certain physical parameters (TSS, RI, pH, EC, and acidity) proximate composition and sugars content. The data indicated that TSS (6.90), acidity (10.08) and pH (5.79) were higher in light green banded while EC (472.33) was higher in Green type. RI (1.34) was found same in all types. Proximate showed higher values of moisture (91.93%) and crude fat (43.00 x 10 -3 %) in light green banded while ash (9.60 x 10-3 %) and crude protein (1.75 %) were higher in green. The sugar content of green was highest among all others.    It could be concluded from the data that various types of water melon along with apparent difference are also different according to their composition. So for any nutritional formulations the nutritional composition of each type should considered

In vitro Transdermal Permeation of Fenoterol Hydrobromide

The aim of this study was to determine if transdermal penetration of fenoterol, a β-agonist drug, could be enhanced and controlled by formulation modification and formulation of transdermal patches. Pre-formulation studies were performed to determine the feasibility of a transdermal dosage form of fenoterol. Penetration of fenoterol was determined using the hairless guinea pig skin with unjacketed Franz diffusion cell. Transdermal patches were formulated using drug in-adhesive technique. Several enhancers were investigated for fenoterol skin penetration. Transcutol–oleic acid co-solvent gives the highest drug flux among all tested liquid formulations. Pretreatment of the skin with oleic acid 2 h before patch application significantly increases drug diffusion. Cis-oleic acid gives best results compared to oleic acid. Azone derivative (1-dodecyl-2-pyrrolidinone) gives the highest drug diffusion amongst all tested enhancers. Results of this study show the feasibility of using fenoterol formulated in transdermal delivery system in the treatment of chronic asthma to improve patient compliance, bioavailability and reduce the inter-subject variability

Enhanced Bioavailability of Fenoterol Transdermal Systems in Rabbits

The pharmacokinetic and bioavailability of fenoterol, a B2 adrenergic agonist were studied to determine the feasibility of enhanced transdermal delivery. Fenoterol has been widely used to treat asthmatic patients. Two fenoterol formulations were studied; the first was a liquid formulation of fenoterol in Transcutol: Oleic acid in a ratio 1:1(F1), while the second was a matrix system of fenoterol in Duro-tak® 87-2074 adhesive with 10% 1-dodecyl-2-pyrrolidinone as an enhancer (F2). For comparison, control matrix with fenoterol without any enhancer (F3) was also tested. The tested formulations were applied to the shaved back skin of rabbits using HILL TOP CHAMBER® in case of liquid formula. Blood samples were collected via auricle central vein for 24 hours and the plasma concentrations of fenoterol were determined by LC-MS/MS method. Pharmacokinetic parameters were calculated using the WinNonlin computer program. The results showed a maximum concentration of fenoterol in plasma of 514.8 ng/ml after application of the liquid formula while its AUC0-∞ amounted to be 485972(ng*min/ml) with a dose of 3mg/kg. The transdermal matrix prepared with 10% 1-dodecyl-2-pyrollidinone had a Cmax of 219 ng/ml and AUC0-∞ was 124636 (ng*min/ml) which is significantly higher than that obtained after application of the control patch without any enhancer. Therefore, the transdermal systems will offer an efficient drug delivery system for the treatment of bronchial asthma

On-site cellulase production by Trichoderma reesei 3EMS35 mutant and same vessel saccharification and fermentation of acid treated wheat straw for ethanol production

Bioethanol production from lignocellulosic raw materials involves process steps like pretreatment, enzymatic hydrolysis, fermentation and distillation. In this study, wheat straw was explored as feedstock for on-site cellulase production by T. reesei 3EMS35 mutant, and as a substrate for second generation bioethanol production from baker yeast. Scanning electron microscopy (SEM) and X-ray diffractography (XRD) of untreated wheat straw (UWS) and acid treated wheat straw (TWS) were done to understand the structural organization and changes in the cellulase accessibility and reactivity. The effect of delignification and structural modification for on-site cellulase enzyme production was comparably studied. The efficiency of crude cellulase enzyme for digestion of UWS and TWS and then production of ethanol from TWS was studied using same-vessel saccharification and fermentation (SVSF) technique, both in shaking flasks as well as in fermenters. Two different methods of operation were tested, i.e. the UWS Enz method, where UWS was used for on-site enzyme production, and TWS Enz method where TWS was applied as substrate for cellullase production. Results obtained showed structural modifications in cellulose of TWS due to delignification, removal of wax and change of crystallinity. UWS was better substrate than TWS for cellulase production due to the fact that lignin did not hinder the enzyme production by fungus but acted as a booster. On-site cellulase enzyme produced by T. reesei 3EMS35 mutant hydrolyzed most of cellulose (91 %) in TWS within first 24 hrs. Shake flasks experiments showed that ethanol titers and yields with UWS Enz were 2.9 times higher compared to those obtained with TWS Enz method respectively. Comparatively, titer of ethanol in shake flask experiments was 10 % higher than this obtained in 3 L fermenter with UWS Enz. Outcomes from this investigation clearly demonstrated the potential of on-site cellulase enzyme production and SVSF for ethanol production from wheat straw

Compact beam-switchable antenna for mm-wave 5G handheld devices

An electronically beam-steerable antenna (BSA) is envisioned. The presented BSA is a possible solution to overthrow the limitations inherent to phased antenna arrays. The design consists of a gap coupling inset feed rectangular patch (driven element) and 3 x 1 passive parasitic patches deployed on both sides of the driven patch. Prototype having 20 x 20 mm dimensions is printed on Rogers(R) RT/duroid(R)5870. Four switches are used to load the reactive impedance on parasitic patches, which in turn, change the phases of surface current on parasitic elements and the driven element. Based on the different ON and OFF configuration of switches in parasitic array elements, the main beam is steered along with different directions. The simulated results show that the design can operate between 26.8 and 30.3 GHz a wide impedance bandwidth |S-11|< -10 dB (12.5%) with a peak gain of 8.9 dBi and wide 3-dB scanning angle that is, -37 degrees to 156 degrees in the azimuth plane. The exhibited performance of BSA with favourable characteristics, such as wideband, adequate gain, wide-angle beam switching, and low profile renders the BSA a good candidate for 5G millimetre wave handheld devices. Moreover, to corroborate the performance, the design is fabricated, and experimental measurements were performed. Congruence is observed between the experimentally measured and computationally simulated results. The simulated results of spherical coverage analysis of BSA with the integration of smartphone form factor are also presented

BINARY SOFT PRE-SEPARATION AXIOMS IN BINARY SOFT TOPOLOGICAL SPACES

In this article, we introduce binary soft pre-separation axioms in binary soft Topological space along with several properties of binary soft pre τ△i , i = 0; 1; 2, binary soft pre-regular, binary soft pre τ△3 , binary soft pre-normal and binary soft τ△4 axioms using binary soft points. We also mention some binary soft invariance properties namely binary soft topological property and binary soft hereditary property. We hope that these results will be useful for the future study on binary soft topology to carry out general background for the practical applications and to solve the thorny problems containing doubts in different grounds