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Tumor progression largely depends on the presence of alternatively polarized (M2) tumor-associated macrophages (TAMs), whereas the classical M1-polarized macrophages can promote anti-tumorigenic immune responses. Thus, selective inhibition of M2-TAMs is a desirable anti-cancer approach in highly resistant tumor entities such as hepatocellular carcinoma (HCC) or breast cancer. We here examined whether a peptide that selectively binds to and is internalized by in vitro-differentiated murine M2 macrophages as compared to M1 macrophages, termed M2pep, could be used to selectively target TAMs in HCC and breast carcinoma. We confirmed selectivity of M2pep for in vitro M2 polarized macrophages. Upon incubation of suspended mixed 4T1 tumor cells with M2pep, high amounts of the TAMs were found to be associated with M2pep, whereas in mixed tumor cell suspensions from two HCC mouse models, M2pep showed only low-degree binding to TAMs. M2pep also showed low-degree targeting of liver macrophages. This indicates that the TAMs in different tumor entities show different targeting of M2pep and that M2pep is a very promising approach to develop selective M2-TAM-targeting in tumor entities containing M2-TAMs with significant amounts of the so far elusive M2pep receptor(s).
Background: Despite the numerous associations of vitamin D with health and disease, vitamin D deficiency is still common from a global perspective. While basic research, clinical and preventive activities grow constantly in vitamin D research, there is no in-depth analysis of the related global scientific productivity available so far.
Methods: Density equalizing mapping procedures (DEMP) were combined with socioeconomic benchmarks using the NewQIS platform.
Results: A total of 25,992 vitamin D-related research articles were identified between 1900 to 2014 with a significant increase (r2 = .6541) from 1900 to 2014. Authors located in Northern America – especially in the USA – distributed the majority of global vitamin D research, followed by their Western European counterparts. DEMP-analysis illustrates that Africa and South America exhibit only minor scientific productivity. Among high-income group countries, Scandinavian nations such as Denmark or Finland (2147.9 and 1607.7 vitamin D articles per GDP in 1000 billion USD) were highly active with regard to socioeconomic figures.
Conclusion: Networks dedicated to vitamin D research are present around the world. Overall, the Northern American and Western European nations occupy prominent positions. However, South American, African and Asian countries apart from Japan only play a minor role in the global research production related to vitamin D. Since vitamin D deficiency is currently increasing in the Americas, Europe and parts of the Middle East, research in these regions may need to be encouraged.
AKTIVA-MCI is a program for patients with mild cognitive impairment (MCI) that aims to enhance participation in cognitively stimulating leisure activities. Participation in cognitively stimulating activities seems to be a potential strategy for people with MCI delaying cognitive decline for a while. In total, 35 MCI patients were enrolled in the pilot study of whom 29 completed the whole program (16 female, 71.1±7.5 years; Mini Mental Status Examination score: 28±2.2). Daily activity protocols were used to measure the frequency of participation in cognitively stimulating activities during the program (12 sessions). Additional standardized psychometric tests and questionnaires were used to assess cognition, mood, and subjective memory decline. Analyses of the daily activity protocols showed that during the intervention participants increased the frequency of several cognitively stimulating leisure activities. Comparison of pre-post data indicates no changes in cognitive status, mood, and subjective memory decline. These findings indicate that the program is suitable for patients with MCI.
Motion analysis in the field of dentistry : a kinematic comparison of dentists and orthodontists
(2016)
Objectives: To conduct a kinematic comparison of occupational posture in orthodontists and dentists in their workplace.
Design: Observational study.
Setting: Dentist surgeries and departments of orthodontics at university medical centres in Germany.
Participants: A representative sample of 21 (10 female, 11 male) dentists (group G1) and 21 (13 female, 8 male) orthodontists (G2) with one male dropout in G2.
Outcome measures: The CUELA (computer-assisted acquisition and long-term analysis of musculoskeletal loads) system was used to analyse occupational posture. Parallel to the recording through the CUELA system, a software-supported analysis of the activities performed (I: treatment; II: office; III: other activities) was carried out. In line with ergonomic standards the measured body angles are categorised into neutral, moderate and awkward postures. Activities between the aforementioned groups are compared using the stratified van Elteren U test and the Wilcoxon–Mann–Whitney U test. All p values are subject to the Bonferroni–Holm correction. The level of significance is set at 5%.
Results: The percentage of time spent on activities in categories I–II–III was as follows: dentists 41%–23%–36% and orthodontists 28%–37%–35%. The posture analysis of both groups showed, for all percentiles (P5–95), angle values primarily in the neutral or moderate range. However, depending on the activity performed, between 5% and 25% of working hours were spent in unfavourable postures, especially in the head-and-neck area. Orthodontists have a greater tendency than dentists to perform treatment activities with the head and torso in unfavourable positions. The statistically significant differences between the two groups with regard to the duration and the relevance of the activities performed confirm this assumption for all three categories (p<0.01, p<0.05).
Conclusions: Generally, both groups perform treatment activities in postures that are in the neutral or medium range; however, dentists had slightly more unfavourable postures during treatment for a greater share of their work day.
Endometriosis and its global research architecture : an in-depth density-equalizing mapping analysis
(2016)
Background: Endometriosis is one of the most common gynecological diseases. It is still a chameleon in many aspects and urges intense research activities in the fields of diagnosis, therapy and prevention. Despite the need to foster research in this area, no in-depth analysis of the global architecture of endometriosis research exists yet.
Methods: We here used the NewQIS platform to conduct a density equalizing mapping study, using the Web of Science as database with endometriosis related entries between 1900 and 2009. Density equalizing maps of global endometriosis research encompassing country-specific publication activities, and semi-qualitative indices such as country specific citations, citation rates, h-Indices were created.
Results: In total, 11,056 entries related to endometriosis were found. The USA was leading the field with 3705 publications followed by the United Kingdom (952) and Japan (846). Concerning overall citations and country-specific h-Indices, the USA again was the leading nation with 74,592 citations and a modified h-Index of 103, followed by the UK with 15,175 citations (h-Index 57). Regarding the citation rate, Sweden and Belgium were at top positions with rates of 22.46 and 22.26, respectively. Concerning collaborative studies, there was a steep increase in numbers present; analysis of the chronological evolution indicated a strong increase in international collaborations in the past 10 years.
Conclusions: This study is the first analysis that illustrates the global endometriosis research architecture. It shows that endometriosis research is constantly gaining importance but also underlines the need for further efforts and investments to foster research and ultimately improve endometriosis management on a global scale.
In patients with glioblastoma, antiangiogenic therapy with bevacizumab (BEV) has been shown to improve progression-free survival (PFS), but not overall survival (OS). Especially in patients with an unusual infiltrative phenotype as seen in multifocal glioblastoma, the use of BEV therapy is still more controversial. Therefore, we prepared a retrospective case series with 16 patients suffering from a multifocal glioblastoma treated with BEV. We compared these patients to a matched control cohort of 16 patients suffering from glioblastoma with a single lesion treated with BEV. The objective of this study was to evaluate whether the course of disease differs in glioblastoma patients with a multifocal disease pattern compared to those with a single lesion only. Patients were treated with BEV monotherapy or BEV in combination with irinotecan or lomustine (CCNU). Response rates and PFS were similar in both groups. There was a trend for an unfavorable OS in the patient group with multifocal glioblastoma, which was expected due to the generally worse prognosis of multifocal glioblastoma. We investigated whether BEV therapy affects the invasive growth pattern as measured by the appearance of new lesions on magnetic resonance imaging (MRI). Under BEV therapy, there was a trend for a lower frequency of new lesions both in multifocal and solitary glioblastoma. Based on these results, BEV therapy at relapse appears to be justified to no lesser extent in multifocal glioblastoma than in solitary glioblastoma.
Background: Lectures remain an important teaching method to present and structure knowledge to many students concurrently. Adequate measures are necessary to maintain the quality of the lectures. The aim of this study was to determine the impact on the lecture quality using written structured feedback and to compare the ratings of surgical lectures between students and surgical peers.
Methods: Prospective analysis of two consecutive surgical lecture series for undergraduate students at Goethe-University Medical School was performed before and after evaluation of the lecturers via independent written feedback from trained undergraduate students and surgeons. The 22-item feedback instrument covered three areas of performance: content, visualization, and delivery. Additional suggestions for improvement were provided from
both students and surgical peers who anonymously attended the lectures. The lecturers, experienced surgeons, as well as the student and peer raters were blinded in terms of the aim and content of the study. Their response to the feedback was collected using a web-based 13-item questionnaire. The Kendall’s-W coefficient was computed to calculate inter-rater reliability (IRR). Differences between ratings before and after feedback were analyzed using Student’s t-test for dependent samples. The Kolmogorov-Smirnov-test was used for independent samples.
Results: A total of 22 lectures from a possible 32 given by 13 lecturers were included and analyzed by at least three surgeons and two students. There were significant improvements in overall score as well as in the details of 9 of the 13 items were found. The average inter-rater reliability was 0.71. There were no differences in the ratings as a function of the rater’s level of expertise (peers vs. students). We found that 13/23 lecturers (56.5%) answered the questionnaire, and 92% strongly agreed that the written feedback was useful. 76.9% of the lecturers revised their lecture based on the written feedback requiring on average 112.5 min (range from 20 to 300 min).
Conclusions: Overall, this study indicates that structured written feedback provided by trained peers and students that is subsequently discussed by the lecturers concerned is a highly effective and efficient method to improve aspects of lecturing. We anticipate that structured written feedback by trained students that is discussed by the lecturers concerned will improve lecturing.
Keywords: Lecture, Feedback, Surgery, Peer-feedback, Evaluation, Undergraduate training
Gendermetrics.NET : a novel software for analyzing the gender representation in scientific authoring
(2016)
Background: Imbalances in female career promotion are believed to be strong in the field of academic science. A primary parameter to analyze gender inequalities is the gender authoring in scientific publications. Since the presently available data on gender distribution is largely limited to underpowered studies, we here develop a new approach to analyze authors’ genders in large bibliometric databases.
Results: A SQL-Server based multiuser software suite was developed that serves as an integrative tool for analyzing bibliometric data with a special emphasis on gender and topographical analysis. The presented system allows seamless integration, inspection, modification, evaluation and visualization of bibliometric data. By providing an adaptive and almost fully automatic integration and analysis process, the inter-individual variability of analysis is kept at a low level. Depending on the scientific question, the system enables the user to perform a scientometric analysis including its visualization within a short period of time.
Conclusion: In summary, a new software suite for analyzing gender representations in scientific articles was established. The system is suitable for the comparative analysis of scientific structures on the level of continents, countries, cities, city regions, institutions, research fields and journals.
Background: Environmental tobacco smoke (ETS) is associated with human morbidity and mortality, particularly chronic obstructive pulmonary disease (COPD and lung cancer. Although direct DNA-damage is a leading pathomechanism in active smokers, passive smoking is enough to induce bronchial asthma, especially in children. Particulate matter (PM) demonstrably plays an important role in this ETS-associated human morbidity, constituting a surrogate parameter for ETS exposure.
Methods: Using an Automatic Environmental Tobacco Smoke Emitter (AETSE) and an in-house developed, non-standard smoking regime, we tried to imitate the smoking process of human smokers to demonstrate the significance of passive smoking. Mean concentration (Cmean) and area under the curve (AUC) of particulate matter (PM2.5) emitted by 3R4F reference cigarettes and the popular filter-tipped and non-filter brand cigarettes “Roth-Händle” were measured and compared. The cigarettes were not conditioned prior to smoking. The measurements were tested for Gaussian distribution and significant differences.
Results: Cmean PM2.5 of the 3R4F reference cigarette: 3911 µg/m3; of the filter-tipped Roth-Händle: 3831 µg/m3; and of the non-filter Roth-Händle: 2053 µg/m3. AUC PM2.5 of the 3R4F reference cigarette: 1,647,006 µg/m3·s; of the filter-tipped Roth-Händle: 1,608,000 µg/m3·s; and of the non-filter Roth-Händle: 858,891 µg/m3·s.
Conclusion: The filter-tipped cigarettes (the 3R4F reference cigarette and filter-tipped Roth-Händle) emitted significantly more PM2.5 than the non-filter Roth-Händle. Considering the harmful potential of PM, our findings note that the filter-tipped cigarettes are not a less harmful alternative for passive smokers. Tobacco taxation should be reconsidered and non-smoking legislation enforced.
In their post-traumatic course, trauma patients suffering from multiple injuries have a high risk for immune dysregulation, which may contribute to post-injury complications and late mortality. Monocytes as specific effector cells of the innate immunity play a crucial role in inflammation. Using their Pattern Recognition Receptors (PRRs), notably Toll-Like Receptors (TLR), the monocytes recognize pathogens and/or pathogen-associated molecular patterns (PAMPs) and organize their clearance. TLR2 is the major receptor for particles of gram-positive bacteria, and initiates their phagocytosis. Here, we investigated the phagocytizing capability of monocytes in a long-term porcine severe trauma model (polytrauma, PT) with regard to their TLR2 expression. Polytrauma consisted of femur fracture, unilateral lung contusion, liver laceration, hemorrhagic shock with subsequent resuscitation and surgical fracture fixation. After induction of PT, peripheral blood was withdrawn before (-1 h) and directly after trauma (0 h), as well as 3.5 h, 5.5 h, 24 h and 72 h later. CD14+ monocytes were identified and the expression levels of H(S)LA-DR and TLR2 were investigated by flow cytometry. Additionally, the phagocytizing activity of monocytes by applying S. aureus particles labelled with pHrodo fluorescent reagent was also assessed by flow cytometry. Furthermore, blood samples from 10 healthy pigs were exposed to a TLR2-neutralizing antibody and subsequently to S. aureus particles. Using flow cytometry, phagocytizing activity was determined. P below 0.05 was considered significant. The number of CD14+ monocytes of all circulating leukocytes remained constant during the observational time period, while the percentage of CD14+H(S)LA-DR+ monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of TLR2+ expressing cells out of all monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of phagocytizing monocytes decreased immediately and remained lower during the first 3.5 h after trauma, but increased after 24 h. Antagonizing TLR2 significantly decreased the phagocytizing activity of monocytes. Both, decreased percentage of activated as well as TLR2 expressing monocytes persisted as long as the reduced phagocytosis was observed. Moreover, neutralizing TLR2 led to a reduced capability of phagocytosis as well. Therefore, we assume that reduced TLR2 expression may be responsible for the decreased phagocytizing capacity of circulating monocytes in the early post-traumatic phase.