How accurate is a CT-based dose calculation on a pencil beam TPS for a patient with a metallic prosthesis?

The accuracy of a CT-based dose calculation on a treatment planning system (TPS) for a radiotherapy patient with a metallic prosthesis has not previously been reported. In this study, the accuracy of the CT-based inhomogeneity correction on a pencil beam TPS (Helax TMS) was determined in a phantom containing a metallic prosthesis. A steel prosthesis phantom and a titanium prosthesis phantom were investigated. The phantoms were CT-scanned and dose plans produced on the TPS, using the CT images to provide density information for the inhomogeneity corrections. Verification measurements were performed on a linear accelerator for 6 and 15 MV x-rays. Measured dose profiles at three different depths were compared to the calculations of the TPS. For the titanium prosthesis and for 6 MV x-rays, the TPS overestimated the beam attenuation by approximately 20% at 15 and 20 cm depths in the phantom. This is due to a limitation in the density allocation of this TPS: any Hounsfield number (HN) above a certain threshold is allocated the density of steel. For the steel prosthesis, the TPS performed the correct mapping of HN to mass density. The dose calculation was within 6% for 6 MV x-rays at 15 and 20 cm depths. However. the accuracy of dose calculation varied with beam energy and depth, with large errors in the region close to the prosthesis. The TPS overestimated the dose by 11% for 6 MV and 15% for 15 MV x-rays at 11 cm depth. 2.5 cm beyond the steel prosthesis. These results highlight the limitations in the density allocation of this TPS and demonstrate shortcomings in the pencil beam dose calculation.     

How is post-mortem microbiology appraised by pathologists? Results from a practice survey conducted by ESGFOR

Post-mortem microbiology (PMM) is an important tool in forensic pathology, assisting to determine the cause and manner of death. However, there is a lack of standardisation of PMM sampling. In order to get a better insight into the methods used, the available technical options and developmental needs, ESCMID Study Group for Forensic and Postmortem Microbiology (ESGFOR) members designed a survey aimed at pathologists regarding common practices of PMM in clinical and forensic autopsies. Multiple choice questions were developed based on Cumulative Techniques and Procedures in Clinical Microbiology (Cumitech). The questionnaire was sent to pathologists mainly across Europe and Turkey using SurveyMonkey. The survey had 147 respondents. Although all pathologists were aware of the existence of PMM, 39% (19/49) of the participants were not using it. The three main indications for PMM were: (i) clinical suspicion of an infection not confirmed antemortem (83%), (ii) infectious signs at autopsy (83%) and (iii) as part of a standard protocol for foetal/perinatal or paediatric death (67%). Almost 80% of the participants using PMM stated taking 1–10 samples per case. Of the requested examinations, a general bacteriological culture (96%) and a specific polymerase chain reaction (PCR) assay for a particular infectious agent (34%) were most popular. The most frequent samples were: heart blood (66%), peripheral femoral blood (49%), spleen (64%) and lung (56%). Eighty-nine percent of the participants considered PMM a useful resource when investigating the cause of death. Although there are some common uses, this survey indicates that there is a need for improvement towards standardising sampling procedures in PMM.     

SALSA—A dance on a slippery floor with changing partners

It is becoming increasingly clear that the connections between our immune system and the microbiota colonizing us have a tremendous impact on human health. A number of innate molecular defence mechanisms cooperate to selectively target unwanted microorganisms at the mucosal surfaces. Amongst others these include the complement system, IgA and the SALSA molecule. The salivary scavenger and agglutinin (SALSA), also known as deleted in malignant brain tumors 1 (DMBT1), salivary agglutinin (SAG) or gp340 is a multifunctional molecule with important functions in innate immunity, inflammation and epithelial homeostasis. The SALSA protein is expressed at most mucosal surfaces, where it is one of the most abundant proteins. In the fetal meconium and infant intestine it may constitute even up to 10% of the total protein amount. SALSA is found either directly associated with the epithelial surface or secreted into the lining fluids. In the fluid-phase SALSA interacts with a number of bacterial and viral organisms, as well as with endogenous ligands, including IgA, lactoferrin, surfactant proteins and complement components. While complement has been shown to impact the mucosal environment, this remains an area of limited research. The multiple interactions of the SALSA molecule provide a scaffold, where this potent defence system may engage in cooperative microbial clearance together with corresponding mucosal host ligands.With its high abundance, and multiple effects on both host and microbes, the SALSA molecule is a key player in maintaining the immunological balance at the mucosal surfaces. This is further supported by observations linking the expression of different SALSA isoforms to the development of chronic inflammatory conditions, such as Crohn’s disease and ulcerative colitis. This review describes the latest advances in understanding functions of SALSA and its different isoforms. Recently recognized functions are related to complement activation and regulation, endothelial development and epithelial homeostasis. In addition, we suggest mechanisms how SALSA regulates inflammation at the mucosal surfaces.     

TLR2 - promiscuous or specific? A critical re-evaluation of a receptor expressing apparent broad specificity

Of all pattern recognition receptors (PRR) in innate immunity, Toll-like receptor 2 (TLR2) recognizes the structurally broadest range of different bacterial compounds known as pathogen-associated molecular patterns (PAMPs). TLR2 agonists identified so far are lipopolysaccharides (LPSs) from different bacterial strains, lipoproteins, (synthetic) lipopeptides, lipoarabinomannans, lipomannans, glycosylphosphatidylinositol, lipoteichoic acids (LTA), various proteins including lipoproteins and glycoproteins, zymosan, and peptidoglycan (PG). Because these molecules are structurally diverse, it seems unlikely that TLR2 has the capability to react with all agonists to the same degree. The aim of this review is to identify and describe well-defined structure-function relationships for TLR2. Because of its biomedical importance and because its genetics and biochemistry are presently most completely known among all Gram-positive bacteria, we have chosen Staphylococcus aureus as a focus. Our data together with those reported by other groups reveal that only lipoproteins/lipopeptides are sensed at physiologically concentrations by TLR2 at picomolar levels. This finding implies that the activity of all other putative bacterial compounds so far reported as TLR2 agonists was most likely due to contaminating highly active natural lipoproteins and/or lipopeptides.     

How is an Electronic Screening and Brief Intervention Tool on Alcohol Use Received in a Student Population? A Qualitative and Quantitative Evaluation

Background

A previous study among Antwerp college and university students showed that more male (10.2%–11.1%) than female (1.8%–6.2%) students are at risk for problematic alcohol use. The current literature shows promising results in terms of feasibility and effectiveness for the use of brief electronic interventions to address this health problem in college and university students. We evaluated this type of intervention and cite existing literature on the topic.

Objective

To develop a website, www.eentjeteveel.be, to motivate college and university students with problematic alcohol use to reduce alcohol consumption and increase their willingness to seek help.

Method

The website contained a questionnaire (Alcohol Use Disorders Identification Test [AUDIT]) for students to test their alcohol use. According to their answers, the students immediately received personalized feedback (personal AUDIT score and additional information on risks associated with alcohol use) and a suggestion for further action. Afterward, students could send an email to a student counselor for questions, guidance, or advice. To obtain in-depth qualitative information on the opinions and experiences of students, we held 5 focus group discussions. The topics were publicity, experiences, impressions, and effects of the website. We analyzed the quantitative results of the online test in SPSS 15.0.

Results

More than 3500 students visited www.eentjeteveel.be; over half were men (55.0%). A total of 34 students participated in the focus group discussions. The mixture of quantitative and qualitative methods to evaluate the intervention allowed a thorough analysis and provided complementary results. The intervention was well received by the student population. However, some minor aspects should be reconsidered, such as website publicity and providing students with options that were added after intermediate evaluation. The intervention increased the motivation of students to think about their alcohol use but could not stimulate them to change their behavior. The website attracted relatively more male than female students and more students in the high-risk group than in the low-risk group. The high-risk group was more inclined to seek advice or guidance (23/400, 6%; χ² _{2 = 32.4,} P < .001) than the low-risk group (34/1714, 2%; χ² _{2 = 32.4,} P < .001).

Conclusions

We gained unique insight into students’ experiences, opinions, and perceptions with regard to the intervention. The results show that the intervention was positively received in the population, and the willingness to seek help was increased. However, real behavior change needs further research. The results of this study can assist health providers and researchers in better understanding college and university students’ perceptions of eHealth initiatives.     

What is a good medical decision? A research agenda guided by perspectives from multiple stakeholders

Informed and shared decision making are critical aspects of patient-centered care, which has contributed to an emphasis on decision support interventions to promote good medical decision making. However, researchers and healthcare providers have not reached a consensus on what defines a good decision, nor how to evaluate it. This position paper, informed by conference sessions featuring diverse stakeholders held at the 2015 Society of Behavioral Medicine and Society for Medical Decision Making annual meetings, describes key concepts that influence the decision making process itself and that may change what it means to make a good decision: interpersonal factors, structural constraints, affective influences, and values clarification methods. This paper also proposes specific research questions within each of these priority areas, with the goal of moving medical decision making research to a more comprehensive definition of a good medical decision, and enhancing the ability to measure and improve the decision making process.     

Vaginal polyps and hormones—is there a link?: A case series

Fibroepithelial stromal polyps (FSP) of the vault after hysterectomy are an uncommon, though well recognised finding. Both tibolone and tamoxifen have been reported to cause polyps in the endometrium but their connection with the same pathology in the vagina has never been described. Here, we report a case of a patient presenting with a symptomatic FSP 30 years after her hysterectomy while on treatment with both tamoxifen and tibolone. This prompted us to see if there was an association between these hormone-modulating agents with vaginal polyp formation. We reviewed all the cases notes of patients having FSP surgically removed in Hull over a 4 years period. Thirty-four women were identified. Some kind of hormonal influence, natural or otherwise, was found in 22 out of the 34 women. Endogenous or exogenous gonadal hormones or hormones modulators thus appear to influence the formation of vaginal polyps, but in this cohort a precise contribution of specific drugs could not be established.     

How much mutant protein is needed to cause a protein aggregate myopathy in vivo? Lessons from an exceptional desminopathy

Myofibrillar myopathies are caused by mutations in desmin, B‐crystallin, myotilin, ZASP, and filamin genes. Since the vast majority of myofibrillar myopathy causing mutations are heterozygous single amino acid substitutions or small in‐frame deletions, the pathogenic role of mutant versus wild‐type protein cannot be assessed in human skeletal muscle by standard immunodetection techniques. We report on an exceptional desminopathy due to a heterozygous c.735G>C mutation. Immunoblotting detected full‐length 53desmin and a truncated 50variant in skeletal muscle from three affected patients of two different families. RT‐PCR identified three desmin mRNA species encoding for wild‐type and two mutant proteins, p.Glu245Asp and p.Asp214_Glu245del. Since previous functional studies on the p.Glu245Asp mutant showed biological properties identical to wild‐type desmin, the truncated p.Asp214_Glu245del desmin is the disease‐causing mutant. Semiquantitative RT‐PCR established a fraction of the truncated desmin mRNA species in a range from 24% to 37%. Initial quantification of corresponding desmin proteins in the muscle biopsy of the index patient of one family indicated a fraction of only 10% of the truncated species. However, serial analyses of different sections from each muscle biopsy revealed a high intra‐ and interindividual variability of the truncated desmin protein level within a range from 5% to 43%. Desmin assembly studies in vitro have established clear‐cut pathogenic ratios of mutant versus wild‐type proteins. However, our findings point out a far more complex situation in human skeletal muscle. The heterogeneously distributed mutation load within and between individual specimens, which reflects local differences in the expression and/or turnover of the mutant protein in different areas containing multiple myonuclear domains, renders it impossible to define an exact pathogenic threshold of a specific mutant in vivo. © 2008 Wiley‐Liss, Inc.     

Effect of cyclosporin—A on histamine release from tracheal strips of sensitized guinea pigs

Inflammation Research -