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

Experimental analysis of process parameters in drilling nimonic C263 alloy under nano fluid mixed MQL environment

Nimonic C263 is a super alloy and it is difficult to cut. As this alloy possess high proportion of chromium, cobalt, and molybdenum, which fortify the material by solution hardening, which inhibits the dislocation movement, resulting in higher plastic deformation. In this research, an attempt has been made to model, analysis and investigate the machining characteristics such as thrust force, temperature at drill cutting edge, flank wear and surface finish during drilling of this alloy using silver nano fluid mixed Minimum Quantity Lubrication (MQL) environment. Residual stress at various combinations of process parameters was also observed and discussed. RSM based empirical models of the process parameters and optimization of multi response was developed. Thrust force, Temperature at drill cutting edge, surface roughness and tool wear affected by feed rate (percentage of contribution-60%), spindle speed (percentage of contribution-88.63%), spindle speed (percentage of contribution-71.42%) and feed rate (percentage of contribution-67.76%) respectively followed by other parameters

Barriers to antiretroviral treatment access for injecting drug users living with HIV in Chennai, South India

This is an accepted manuscript of an article published in AIDS Care by Taylor & Francis in 2014.India's National AIDS Control Organization provides free antiretroviral treatment (ART) to people living with HIV (PLHIV), including members of marginalized groups such as injecting drug users (IDUs). To help inform development of interventions to enhance ART access, we explored barriers to free ART access at government ART centers for IDUs living with HIV in Chennai by conducting three focus groups (n = 19 IDUs) and four key informant interviews. Data were explored using framework analysis to identify categories and derive themes. We found interrelated barriers at the family and social, health-care system, and individual levels. Family and social level barriers included lack of family support and fear of societal discrimination, as well as unmet basic needs, including food and shelter. Health-care system barriers included actual or perceived unfriendly hospital environment and procedures such as requiring proof of address and identity from PLHIV, including homeless IDUs; provider perception that IDUs will not adhere to ART, resulting in ART not being initiated; actual or perceived inadequate counseling services and lack of confidentiality; and lack of effective linkages between ART centers, needle/syringe programs, and drug dependence treatment centers. Individual-level barriers included active drug use, lack of self-efficacy in ART adherence, low motivation to initiate ART stemming from a fatalistic attitude, and inadequate knowledge about ART. These findings indicate that to facilitate IDUs gaining access to ART, systemic changes are needed, including steps to make the environment and procedures at government ART centers more IDU-friendly and steps to decrease HIV- and drug use-related stigma and discrimination faced by IDUs from the general public and health-care providers. Housing support for homeless IDUs and linkage of IDUs with drug dependence treatment are also essential.This study was partly supported by the International Treatment Preparedness Coalition (ITPC) and the Yale AIDS International Training and Research Program (5 D43 TW001028), funded by the Fogarty International Center of the US National Institutes of Health. Dr. Newman was supported in part by grants from the Canadian Institutes of Health Research (THA-118570; MOP-102512) and the Canada Research Chairs program

Synthesis and optical properties of red and deep-red emissive polymeric and copolymeric BODIPY dyes

Deep-red emissive polymeric BODIPY dyes (polymers A and B), poly(2,6-BODIPY-ethynylene)s, were prepared by palladium-catalyzed Sonogashira polymerization of 2,6-diiodo-functionalized BODIPY monomers with 2,6-diethynyl-functionalized BODIPY monomers. Poly(2,6-BODIPY-ethynylene)s emit in the deep-red region with emission spectral maxima at around 680 nm and exhibit significant red shifts (up to 163 and 172 nm) of both absorption and emission maxima compared with their initial BODIPY dyes due to significant extension of π-conjugation. Red emissive copolymeric BODIPY dyes (polymers C, D, and E) were also prepared by palladium-catalyzed Sonogashira polymerization of a diethynyl-functionalized BODIPY monomer with 9,9-bis(6′-(hexylthio)hexyl)-2,7-diiodo-9H-fluorene, 1,4-diiodo-2,5-didecyloxybenzene, and 2,5-diiodo-3-decylthiophene, respectively. Incorporation of different band gap monomer units into poly(2,6-BODIPY-ethynylene)s resulted in copolymers with a range of emission wavelengths from 641 to 664 nm. The fluorescence lifetimes of these polymers (polymers A−D) are from 2.8 to 3.8 ns except the copolymer with thiophene moieties (polymer E), which displays a much shorter lifetime of 0.23 ns with low fluorescence quantum yield due to efficient intersystem crossing induced by the heavy atom effect of sulfur