Performance characteristics and commissioning of MOSFET as an in-vivo dosimeter for high energy photon external beam radiation therapy

AimIn vivo dosimetry is an essential tool of quality assurance programmes in radiotherapy. In fact, the assessment of the final uncertainty between the prescribed dose and the dose actually delivered to the patient is an effective way of checking the entire dosimetric procedure. Metal oxide semiconductor field effect transistors (MOSFETs) have recently been proposed for use in radiation therapy. The purpose of this work is to study the performance characteristics and to carry out the commissioning of MOSFET as an in-vivo dosimeter for high-energy photon external beam radiation therapy.Material and MethodsCharacterization and commissioning of low sensitivity TN502RD and high sensitivity TN1002RD MOSFETs for entrance and exit dosimetry respectively for application in in-vivo dosimetry in radiotherapy was carried out. The MOSFETs were characterized in terms of reproducibility, short-term constancy, long-term constancy, linearity, angular dependence, energy dependence, source to skin distance (SSD) dependence and field size dependence.ResultsThe reproducibility of standard sensitivity MOSFET is about 1.4% (1 SD) and 1.98% (1 SD) for high sensitivity detectors. The linearity of both MOSFETs was excellent (R2 = 0.996). The response of MOSFETs varies linearly for square fields from 3 × 3 cm2 to 30 × 30 cm2. For beam incidence ranging from ±45° the MOSFET response varies within ±3%. Commissioning of both MOSFETs was carried out in terms of entrance dose calibration factor, exit dose calibration factor, SSD correction factor, field size correction factor, wedge correction factor and shielding tray correction factor. The average calibration factor for low and high sensitivity MOSFET detectors is 0.9065 cGy/mV and 0.3412 cGy/mV respectively. The average SSD correction factors are quite small and vary between 0.968 and 1.027 for both types of detectors for the range of clinical SSDs from 80 cm to 120 cm. The field size correction factor varies from 1.00 to 1.02 for both types of detectors. The wedge and the shielding tray correction factors for both the detectors also show quite small variation. MOSFET characteristics are suitable for in vivo dosimetry of entrance and exit dose measurement relevant to 6 MV treatment.ConclusionIt can be concluded that MOSFET dosimetry's low energy dependence, high sensitivity and immediate readout make it a good replacement for TLD in radiation therapy dosimetry

A randomized, controlled, double-blind trial of air vs carbon dioxide insufflation during ERCP

Visualization during gastrointestinal endoscopy requires distention of the bowel lumen. Carbon dioxide (CO2) insufflation decreases post-procedure abdominal discomfort and distension after colonoscopy, but there have been few published studies on its use in endoscopic retrograde cholangiopancreatography (ERCP)

Discovery and Development of Toll-Like Receptor 4 (TLR4) Antagonists: A New Paradigm for Treating Sepsis and Other Diseases

Abstract. Sepsis remains the most common cause of death in intensive care units in the USA, with a current estimate of at least 750,000 cases per year, and 215,000 deaths annually. Despite extensive research still we do not quite understand the cellular and molecular mechanisms that are involved in triggering and propagation of septic injury. Endotoxin (lipopolysaccharide from Gram-negative bacteria, or LPS) has been implicated as a major cause of this syndrome. Inflammatory shock as a consequence of LPS release remains a serious clinical concern. In humans, inflammatory responses to LPS result in the release of cytokines and other cell mediators from monocytes and macrophages, which can cause fever, shock, organ failure and death. A number of different approaches have been investigated to try to treat and/or prevent the septic shock associated with infections caused by Gram-negative bacteria, including blockage of one or more of the cytokines induced by LPS. Recently several novel amphipathic compounds have been developed as direct LPS antagonists at the LPS receptor, TLR4. This review article will outline the current knowledge on the TLR4-LPS synthesis and discuss the signaling, in vitro pre-clinical and in vivo clinical evaluation of TLR4 antagonists and their potential use in sepsis and a variety of diseases such as atherosclerosis as well as hepatic and renal malfunction. KEY WORDS: drug discovery; LPS; sepsis; toll-like receptor antagonists

MicroRNA-155 Deficiency Attenuates Liver Steatosis and Fibrosis without Reducing Inflammation in a Mouse Model of Steatohepatitis

BACKGROUND & AIM: MicroRNAs (miRs) regulate hepatic steatosis, inflammation and fibrosis. Fibrosis is the consequence of chronic tissue damage and inflammation. We hypothesized that deficiency of miR-155, a master regulator of inflammation, attenuates steatohepatitis and fibrosis. METHODS: Wild type (WT) and miR-155-deficient (KO) mice were fed methionine-choline-deficient (MCD) or -supplemented (MCS) control diet for 5 weeks. Liver injury, inflammation, steatosis and fibrosis were assessed. RESULTS: MCD diet resulted in steatohepatitis and increased miR-155 expression in total liver, hepatocytes and Kupffer cells. Steatosis and expression of genes involved in fatty acid metabolism were attenuated in miR-155 KO mice after MCD feeding. In contrast, miR-155 deficiency failed to attenuate inflammatory cell infiltration, nuclear factor kappa beta (NF-kappaB) activation and enhanced the expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFalpha) and monocyte chemoattractant protein-1 (MCP1) in MCD diet-fed mice. We found a significant attenuation of apoptosis (cleaved caspase-3) and reduction in collagen and alpha smooth muscle actin (alphaSMA) levels in miR-155 KO mice compared to WTs on MCD diet. In addition, we found attenuation of platelet derived growth factor (PDGF), a pro-fibrotic cytokine; SMAD family member 3 (Smad3), a protein involved in transforming growth factor-beta (TGFbeta) signal transduction and vimentin, a mesenchymal marker and indirect indicator of epithelial-to-mesenchymal transition (EMT) in miR-155 KO mice. Nuclear binding of CCAAT enhancer binding protein beta (C/EBPbeta) a miR-155 target involved in EMT was significantly increased in miR-155 KO compared to WT mice. CONCLUSIONS: Our novel data demonstrate that miR-155 deficiency can reduce steatosis and fibrosis without decreasing inflammation in steatohepatitis

Adjuvant Effect of Killed Propionibacterium acnes on Mouse Peritoneal B-1 Lymphocytes and Their Early Phagocyte Differentiation

B-1 lymphocytes are the predominant cells in mouse peritoneal cavity. They express macrophage and lymphocyte markers and are divided into B-1a, B-1b and B-1c subtypes. The role of B-1 cells is not completely clear, but they are responsible for natural IgM production and seem to play a regulatory role. An enriched B-1b cell population can be obtained from non-adherent peritoneal cell cultures, and we have previously demonstrated that these cells undergo differentiation to acquire a mononuclear phagocyte phenotype upon attachment to the substrate in vitro. Nevertheless, the B-1 cell response to antigens or adjuvants has been poorly investigated. Because killed Propionibacterium acnes exhibits immunomodulatory effects on both macrophages and B-2 lymphocytes, we analyzed whether a killed bacterial suspension or its soluble polysaccharide (PS) could modulate the absolute number of peritoneal B-1 cells in BALB/c mice, the activation status of these cells and their ability to differentiate into phagocytes in vitro. In vivo, P. acnes treatment elevated the absolute number of all B-1 subsets, whereas PS only increased B-1c. Moreover, the bacterium increased the number of B-1b cells that were positive for MHC II, TLR2, TLR4, TLR9, IL-4, IL-5 and IL-12, in addition to up-regulating TLR9, CD80 and CD86 expression. PS increased B-1b cell expression of TLR4, TLR9, CD40 and CD86, as well as IL-10 and IL-12 synthesis. Both of the treatments decreased the absolute number of B-1b cells in vitro, suggesting their early differentiation into B-1 cell-derived phagocytes (B-1CDP). We also observed a higher phagocytic activity from the phagocytes that were derived from B-1b cells after P. acnes and PS treatment. The adjuvant effect that P. acnes has on B-1 cells, mainly the B-1b subtype, reinforces the importance of B-1 cells in the innate and adaptive immune responses

Gut microbiota and diabetes: from pathogenesis to therapeutic perspective

More than several hundreds of millions of people will be diabetic and obese over the next decades in front of which the actual therapeutic approaches aim at treating the consequences rather than causes of the impaired metabolism. This strategy is not efficient and new paradigms should be found. The wide analysis of the genome cannot predict or explain more than 10–20% of the disease, whereas changes in feeding and social behavior have certainly a major impact. However, the molecular mechanisms linking environmental factors and genetic susceptibility were so far not envisioned until the recent discovery of a hidden source of genomic diversity, i.e., the metagenome. More than 3 million genes from several hundreds of species constitute our intestinal microbiome. First key experiments have demonstrated that this biome can by itself transfer metabolic disease. The mechanisms are unknown but could be involved in the modulation of energy harvesting capacity by the host as well as the low-grade inflammation and the corresponding immune response on adipose tissue plasticity, hepatic steatosis, insulin resistance and even the secondary cardiovascular events. Secreted bacterial factors reach the circulating blood, and even full bacteria from intestinal microbiota can reach tissues where inflammation is triggered. The last 5 years have demonstrated that intestinal microbiota, at its molecular level, is a causal factor early in the development of the diseases. Nonetheless, much more need to be uncovered in order to identify first, new predictive biomarkers so that preventive strategies based on pre- and probiotics, and second, new therapeutic strategies against the cause rather than the consequence of hyperglycemia and body weight gain

Predictors of textbook outcome following oesophagogastric cancer surgery

Textbook outcome (TO) is a composite measure representing an ideal perioperative course, which has been utilized to assess the quality of care in oesophagogastric cancer (OGC) surgery. We aim to determine TO rates among OGC patients in a UK tertiary center, investigate predictors of TO attainment, and evaluate the relationship between TO and survival. A retrospective analysis of a prospectively collected departmental database between 2006 and 2021 was conducted. Patients that underwent radical OGC surgery with curative intent were included. TO attainment required margin-negative resection, adequate lymphadenectomy, uncomplicated postoperative course, and no hospital readmission. Predictors of TO were investigated using multivariable logistic regression. The association between TO and survival was evaluated using Kaplan–Meier analysis and Cox regression modeling. In sum, 667 esophageal cancer and 312 gastric cancer patients were included. TO was achieved in 35.1% of esophagectomy patients and 51.3% of gastrectomy patients. Several factors were independently associated with a low likelihood of TO attainment: T3 stage (odds ratio (OR): 0.41, 95% confidence interval (CI) [0.22–0.79], p = 0.008) and T4 stage (OR:0.26, 95% CI [0.08–0.72], p = 0.013) in the esophagectomy cohort and high BMI (OR:0.93, 95% CI [0.88–0.98], p = 0.011) in the gastrectomy cohort. TO attainment was associated with greater overall survival and recurrence-free survival in esophagectomy and gastrectomy cohorts. TO is a relevant quality metric that can be utilized to compare surgical performance between centers and investigate patients at risk of TO failure. Enhancement of preoperative care measures can improve TO rates and, subsequently, long-term survival

Impact of Number and Placement of High-dose Vertices on Equivalent Uniform Dose and Peak-to-valley Ratio for Lattice Radiotherapy

Aims: This study evaluated the influence of high dose (HD) vertex numbers and its placement on equivalent uniform dose (EUD) and peak-to-valley dose ratio (PVDR) in lattice radiotherapy (LRT). Settings and Design: One hundred and eighty-eight RapidArc (RA) plans were created for a cohort of 15 patients. Materials and Methods: RA plans were created with zero to eight HD vertices to analyze their relationship with EUD. Eight lattices were systematically and optimally placed (by avoiding proximity to organs at risks [OARs]) to study the impact of vertex placement. Variations in PVDR were assessed using PVDR1 (mean dose to HD vertices by the difference of mean doses to planning target volume [PTV] and HD vertices) and PVDR2 (D10/D90 of PTV in composite plans) across 38 RA plans with HD vertex doses of 9 Gy, 12 Gy, 15 Gy, and 18 Gy. PVDR3 (product of PVDR1 and PVDR2) was evaluated for its variation with peak dose. Statistical Analysis Used: Hypothesis testing between vertex placements was performed using a two-tailed Student’s t-test. Results: EUD values ranged from 32.88 Gy to 40.63 Gy. In addition, statistical analysis revealed significant associations (P = 0.0074) between the placement patterns of HD vertices, both in systematic and optimized arrangements. The PVDR and D10/D90 product values were 1.6, 1.8, 2.1, and 2.3 for peak doses of 9 Gy, 12 Gy, 15 Gy, and 18 Gy, respectively. Conclusions: The addition of one HD vertex increased EUD, emphasizing the impact of individual vertex increments on outcomes. Systematic and optimized vertex placements enhance EUD, with optimized placement yielding better doses to PTV and OARs. PVDR3 offers superior dose reporting for LRT compared to PVDR1 and PVDR2