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Phenomenon : Faculty career success in academic medicine is complex. Dynamic interactions among faculty and between faculty and their socio-cultural working environments contribute to the mystique of academic advancement. There are few empirical studies that analyze the social practice of faculty career advancement in academic medicine, especially those that focus on relations between individual and environmental contexts. This study aimed to investigate various faculty members' experiences around career advancement in a medical school. Through the analytical lens of Bourdieu's theory of practice, we focused on the relationship among individuals, positions, and environmental contexts. Approach : Following a general process of interpretive grounded theory, we collected faculty members' perceptions and experiences related to their career development and advancement via in-depth semi structured-interviews of 23 faculty at a medical school in the United States. We analyzed the interview transcripts using thematic and constant-comparison analyses, informed by Bourdieu's theory of practice emphasizing the concepts of habitus, field, doxa, illusio, and capital. Findings : While there was a general perception of collaborative success in the school, access to resources seemed to be unequally distributed and linked to faculty positions. Career opportunities, such as leadership and promotion, were mostly granted by leaders based on interpersonal relationships (social capital). Clinical faculty's limited access to professional development activities (cultural capital), including research, limited their likelihood for promotion (symbolic capital) at the school. An institutional emphasis on clinical productivity reinforced clinical faculty's constraints on academic scholarship, which led to perceived inequities by clinical faculty. Participants also perceived subtle gender bias and an unequal distribution of power among the specialties, which contradicted a culture of collaboration and support in the school. Insights : Complex power structures influence faculty career success. Unequal access and differential power among faculty positions resulted in disparities in career advancement. Greater transparency, equity, and inclusivity are obvious suggestions for change to allow all faculty to benefit from essential resources and career building opportunities. Furthermore, building high-quality relationships between leaders and faculty and mutual respect between specialties are essential to sustaining an organizational culture conducive to career success for all faculty. Faculty will benefit from a greater awareness of the structural and normative aspects of a medical school that are less obvious and more difficult to change. This is the value of applying Bourdieu's theory of practice to the socio-cultural dynamics of the medical school.

The chloropropanols, monochloropropane-1,2-diol (3-MCPD) and 1,3-dichloro-2-propanol (1,3-DCP) are potential contaminants that may be found in food contact materials (FCM) from paper and paperboard that have been treated with certain wet-strength resins. They can migrate from the paper matrix to aqueous food and beverages and, due to their potentially carcinogenic properties, are of increasing interest in quality assurance or official controls of paper-based FCM. We hereby describe an improved method for the analysis of 3-MCPD and 1,3-DCP in water extracts of FCM making use of 1-chloro-3-methoxy-2-propanol (CMP) as a novel internal standard. The LOD and LOQ were determined to be 0.4 µg/L and 1.2 µg/L for both analytes, making the method appropriate for the quantification of 3-MCPD and 1,3-DCP below the current legal limits. The method was applied to an extensive market survey of food contact articles made from paper and paperboard including 674 samples. The survey revealed that a high percentage of the products available on the market (e.g., up to 55% of the analysed drinking straws) exceed the BfR limits with values of up to 327 µg/L 3-MCPD and 20 µg/L 1,3-DCP detected in the cold water extract. Remarkable differences were observed concerning the release of 3-MCPD and 1,3-DCP from different kinds of paper-based FCM products, with drinking straws, cupcake cases, bagasse bowls and kitchen rolls showing particularly high rates (>10%) of non-conformity with the legal limits. A number of samples with especially high concentrations were additionally analysed by hot water extraction, which surprisingly yielded considerably lower results for the release of 3-MCPD and 1,3-DCP than cold water extraction. The results indicate that cold water extraction is the most sensitive method to detect the migration and control the risk of exposure to 3-MCPD and 1,3-DCP.

Upon intravenous administration of nanoparticles (NP) into the bloodstream, proteins bind rapidly on their surface resulting in a formation of a so-called 'Protein Corona'. These proteins are strongly attached to the NP surface and provide a new biological identity which is crucial for the reaction at the nano-biointerface. The structure and composition of the protein corona is greatly determined by the physico-chemical properties of the NP and the characteristics of the biological environment. The overall objective of this study was to characterize the role of NP size/surface curvature and PEGylation on the formation of the protein corona. Therefore, we prepared NP in a size of 100 and 200 nm using the biodegradable polymers poly(DL-lactide-co-glycolide) (PLGA) and poly(DL-lactide-co-glycolide)-co-polyethylene glycol diblock (PLGA-PEG) and subsequently incubated them with fetal bovine serum (FBS) to induce the formation of a protein corona. After removal of unbound protein, we employed different analytical approaches to study the corona in detail. Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) was performed to gain a first impression about amount and composition of the corona proteins. Identification was carried out after tryptic in-solution digestion and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). In addition, we successfully established the Bradford protein assay as a suitable colorimetric method to quantify total adsorbed protein amount after alkaline hydrolysis of PLGA based NP. Our results revealed that protein adsorption on PLGA- and PLGA-PEG-NP didn't depend on NP size within the range of 100 and 200 nm. PEGylation led to a significant reduced amount of bound proteins. The depletion of proteins which are involved in immune response was remarkable and indicated a prolonged circulation time in body., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: When nanoparticles (NPs) are applied into a biological fluid, such as blood, proteins bind rapidly to their surface forming a so-called "protein corona". These proteins are strongly attached to the NP surface and confers them a new biological identity that is crucial for the biological response in terms of body biodistribution, cellular uptake, and toxicity. The corona is dynamic in nature and it is well known that the composition varies in dependence of the physicochemical properties of the NPs. In the present study we investigated the protein corona that forms around poly(lactide- co -glycolide) (PLGA) NPs at different serum concentrations using two substantially different serum types, namely fetal bovine serum (FBS) and human serum. The corona was characterized by means of sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE), Bradford protein assay, zeta potential measurements, and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Additionally, the time-dependent cell interaction of PLGA NPs in the absence or presence of a preformed protein corona was assessed by in vitro incubation experiments with the human liver cancer cell line HepG2. Results: Our data revealed that the physiological environment critically affects the protein adsorption on PLGA NPs with significant impact on the NP-cell interaction. Under comparable conditions the protein amount forming the protein corona depends on the serum type used and the serum concentration. On PLGA NPs incubated with either FBS or human serum a clear difference in qualitative corona protein composition was identified by SDS-PAGE and LC-MS/MS in combination with bioinformatic protein classification. In the case of human serum a considerable change in corona composition was observed leading to a concentration-dependent desorption of abundant proteins in conjunction with an adsorption of high-affinity proteins with lower abundance. Cell incubation experiments revealed that the respective corona composition showed significant influence on the resulting nanoparticle-cell interaction. Conclusion: Controlling protein corona formation is still a challenging task and our data highlight the need for a rational future experimental design in order to enable a prediction of the corona formation on nanoparticle surfaces and, therefore, the resulting biodistribution in the body.

Food allergies are a growing worldwide concern and the contamination of products with food allergens represents a significant health risk to allergic consumers. With the introduction of reference doses, quantitative methods are needed for the monitoring of allergen levels, and the potential of LC-MS/MS is of hugely growing interest. In this study, we demonstrate that relevant food matrices (bakery products and chocolates) and thermal food processing substantially influence the quantification of 18 marker peptides from various nut and peanut allergens via targeted proteomics. In addition, we characterize the individual release kinetics of marker peptides and provide examples for metastable marker peptide candidates. Matrix recovery rates overall ranged between 15 and 250% with the observed variation being linked to the individual peptide structure as well as to specific matrix interferences. In contrast, thermal processing considerably influences the detectability of allergens on the protein level as different marker peptides from the identical parent allergen are similarly affected, leading to a loss in signal of up to 83% in extreme cases after a 45-min simulated baking. Provided data are finally used for evaluation of different calibrators as well as the overall potential and challenges of LC-MS for the absolute quantification of food allergens. SIGNIFICANCE: With the scientific discussion moving towards a risk-based management of food allergens, including the establishment of threshold doses, robust methods for the absolute quantification of allergens in food samples are urgently needed. Because the currently used antibody- and DNA-based technologies show severe limitations in terms of specificity and reproducibility, LC-MS has emerged as a promising alternative. Its application to absolute quantification, however, first requires an understanding of the various impacts that affect quantification results, including different food matrices, sample preparation, and thermal processing of foodstuffs. Knowledge of these factors, which are assessed as part of a comprehensive survey in this study, is also an important prerequisite to evaluate means of calibration for an LC-MS-based quantification of food allergens., (Copyright © 2018. Published by Elsevier B.V.)

Scope: Allergy to hazelnut seeds ranks among the most prevalent food allergies in Europe. The aim of this study was to elucidate the gastrointestinal digestion of hazelnut allergens on molecular level., Methods and Results: Hazelnut flour was digested in vitro following the Infogest consensus model. For six allergenic proteins, the time-dependent course of digestion was monitored by SDS-PAGE and HPLC-MS/MS, and degradation products were characterized by a bottom-up proteomics approach. Depending on the molecular structure, a specific biochemical fate was observed for each allergen, and degradation kinetics were traced back to the peptide level. 1183 peptides were characterized, including 130 peptides that carry known IgE-binding epitopes and may represent sensitizers for hazelnut allergy. The kinetics of peptide formation and degradation were determined by label-free quantification and follow a complex multi-stage mechanism., Conclusion: We present a comprehensive survey on the gastrointestinal digestion of a relevant allergenic food on level of the peptidome, including the first systematic characterization and quantification of degradation products. This provides information on the differential resistance of plant food allergens and their structural elements undergoing digestion and forms the basis for a deeper understanding of the molecular principles responsible for sensitization to food allergy., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The hazelnut allergen Cor a 14 belongs to the 2S albumins, a family of heterodimeric seed storage proteins exhibiting a high degree of structural diversity. Given its relevance as an allergen and the potential to elicit severe reactions, elucidation of the sequence heterogeneity of naturally occurring Cor a 14 is essential for the development of reliable diagnostics and risk evaluation. We therefore performed a comprehensive survey on the proteoforms of Cor a 14 and determined their quantitative distribution in three different hazelnut cultivars by a combinatory HPLC-HRMS approach including bottom-up and intact mass analysis. Compared with the Cor a 14 prototype sequence, we identified three sequence polymorphisms, two of the small and one of the large subunit, and elucidated their specific pairing on the protein level. Furthermore, we located a pronounced microheterogeneity on the protein termini and, for the first time, provide data on varying proteoform patterns between different cultivars of an allergenic seed. Together, these data present the basis for a more detailed investigation on the allergenicity of Cor a 14 in different cultivars and constitute, to be best of our knowledge, the largest set of proteoforms so far reported for a 2S albumin.

Food allergies have become a global challenge to food safety in industrialized countries in recent years. With governmental monitoring and legislation moving towards the establishment of threshold allergen doses, there is a need for sensitive and quantitative analytical methods for the determination of allergenic food contaminants. Targeted proteomics employing liquid chromatography-mass spectrometry (LC-MS) has emerged as a promising technique that offers increased specificity and reproducibility compared to antibody and DNA-based technologies. As the detection of trace levels of allergenic food contaminants also demands excellent sensitivity, we aimed to significantly increase the analytical performance of LC-MS by utilizing multiple reaction monitoring cubed (MRM 3 ) technology. Following a bottom-up proteomics approach, including a straightforward sample preparation process, 38 MRM 3 experiments specific to 18 proteotypic peptides were developed and optimized. This permitted the highly specific identification of peanut, almond, cashew, hazelnut, pistachio, and walnut. The analytical performance of the method was assessed for three relevant food matrices with different chemical compositions. Limits of detection were around 1 μg/g or below in fortified matrix samples, not accounting for the effects of food processing. Compared to an MRM-based approach, the MRM 3 -based method showed an increase in sensitivity of up to 30-fold. Regression analysis demonstrated high linearity of the MRM 3 signal in spiked matrix samples together with robust intersample reproducibility, confirming that the method is highly applicable for quantitative purposes. To the best of our knowledge, we describe here the most sensitive LC-MS multi-method for food allergen detection thus far. In addition, this is the first study that systematically compares MRM 3 with MRM for the analysis of complex foods. Graphical abstract Allergen detection by MRM 3 .

Crustacean shellfish allergy ranks among the most frequent and severe food allergies for adults, demanding rugged and sensitive analytical routine methods. The objective of this study was therefore to develop a mass spectrometric approach for the detection of contamination with shrimp and lobster, two economically important types of crustaceans, in complex food matrices. Following a biomarker approach, we identified proteotypic peptides and developed a multiple reaction monitoring (MRM) method allowing for the identification and differentiation of shrimp and lobster in the food matrix at concentrations down to 0.1%. To further enhance sensitivity, we employed the MRM-cubed (MRM(3)) mode, which allowed us to detect crustaceans down to concentrations of 25 μg/g (crustacean/food, 0.0025%). We hereby present the first mass spectrometric method for the detection of shrimp and lobster in food matrices.

Food allergies have emerged as a global problem over the last few decades; therefore, reliable and sensitive analytical methods to ensure food safety for allergic consumers are required. The application of mass spectrometry is of growing interest in this field and several procedures based on low resolution tandem mass spectrometry using single tryptic peptides as analytical targets have recently been described. However, a comprehensive survey of marker peptides for the development of multi-methods is still missing, as is a consensus guide to marker identification. In this study, we therefore report a consistent approach to the development of liquid chromatography-mass spectrometry (LC-MS) multi-screening methods for the detection of allergens in food matrices. Proteotypic peptides were identified by a shotgun proteomics approach and verified through a thorough investigation of specificity and sensitivity. On the basis of this procedure, we identified 44 suitable tryptic marker peptides from six allergenic nut species and developed the first analytical LC-MS method for the detection of trace nut contaminations in processed foods using high resolution mass spectrometry (HRMS). The analysis of spiked matrix samples gave limits of detection (LODs) below 10 μg/g for several nuts; these LODs are comparable with routinely used methods such as ELISA and PCR. Notably, the HRMS approach can be used in an untargeted fashion to identify multiple allergens also retrospectively. In conclusion, we present here the so far largest consensus set of analytical markers from nut allergens and to the best of our knowledge the first multi-allergen method based on LC-HRMS.

Internationalizing higher education is considered to be a major goal for universities in Germany and many medical students aspire to include international experiences into their academic training. However, the exact meaning of "internationalizing" medical education is still poorly defined, just as is the possible pedagogic impact and effects. Against this background, this article presents the special track curriculum on global health (in German: Schwerpunktcurriculum Global Health, short: SPC) at Justus Liebig University Giessen, which was established in 2011 as a comprehensive teaching program to integrate international perspectives and activities systematically into the clinical years of the medical curriculum. The report of the structure, content, didactic principles and participants' evaluations of the SPC is embedded into a larger discussion of the pedagogic value of a broad and interdisciplinary perspective on "global health" in medical education, that explicitly includes attention for health inequities, social determinants of health and the cultural dimensions of medicine and health abroad and "at home" (e.g. in relation to migration). We conclude that if properly defined, the emerging field of "global health" represents a didactically meaningful approach for adding value to medical education through internationalizing the curriculum, especially in regard to themes that despite of their uncontested value are often rather weak within medical education. The concrete curricular structures, however, have always to be developed locally. The "SPC" at Giessen University Medical School is only one possible way of addressing these globally relevant issues in one particular local academic setting.

Purpose: To understand medical students' learning experiences in clerkships: learning expectations (what they expect to learn), learning process (how they learn), and learning outcomes (what they learn)., Method: Using a longitudinal qualitative research design, the authors followed the experiences of 12 participants across their clerkship year (2011-2012) at the Southern Illinois University School of Medicine. Interview data from each participant were collected at three points (preclerkship, midclerkship, and postclerkship) and analyzed using a grounded theory approach. Additionally, the authors observed participants through a full clerkship day to augment the interviews., Results: Before clerkships, students expected to have more hands-on experiences and become more knowledgeable by translating textbook knowledge to real patients and practicing diagnostic thinking. During clerkships, students experienced ambiguity and subjectivity of attending physicians' expectations and evaluation criteria. They perceived that impression management was important to ensure that they received learning opportunities and good evaluations. After clerkships, students perceived that their confidence increased in navigating the health care environments and interacting with patients, attendings, and residents. However, they felt that there were limited opportunities to practice diagnostic thinking. Students could not clearly discern the decision-making processes used by attending physicians. Although they saw many patients, they perceived that their learning was at the surface level., Conclusions: Students' experiential learning in clerkships occurred through impression management as a function of dynamic social and reciprocal relationships between students and attendings or residents. Students reported that they did not learn comprehensive clinical reasoning skills to the degree they expected in clerkships.

Recognising global health as a rapidly emerging policy field, the German federal government recently released a national concept note for global health politics (July 10, 2013). As the German government could have a significant impact on health globally by making a coherent, evidence-informed, and long-term commitment in this field, we offer an initial appraisal of the strengths, weaknesses, and opportunities for development recognised in this document. We conclude that the national concept is an important first step towards the implementation of a coherent global health policy. However, important gaps were identified in the areas of intellectual property rights and access to medicines. In addition, global health determinants such as trade, economic crises, and liberalisation as well as European Union issues such as the health of migrants, refugees, and asylum seekers are not adequately addressed. Furthermore, little information is provided about the establishment of instruments to ensure an effective inter-ministerial cooperation. Finally, because implementation aspects for the national concept are critical for the success of this initiative, we call upon the newly elected 2013 German government to formulate a global health strategy, which includes a concrete plan of action, a time scale, and measurable goals.