Lars Kayser

Effects of human anti-IL-1α autoantibodies on receptor binding and biological activities of IL-1

Immunoglobulin G (IgG) antibodies to interleukin 1 alpha (IL-1 alpha) are frequently found in the sera of healthy human individuals. The effects of these autoantibodies on receptor binding and biological activities of human IL-1 were tested. Using the murine T-lymphocyte line NOB-1, human thyrocytes and human foreskin fibroblasts, the antibodies competitively inhibited the biological activity of human recombinant IL-1 alpha (rIL-1 alpha). The degree of inhibition correlated with 125I-rIL-1 alpha binding to IgG in different immunoglobulin preparations and in individual sera. These antibodies also neutralized the IL-1 activity of isolated membrane fragments and lysates of human blood monocytes activated by lipopolysaccharide. In contrast, the supernatant IL-1 activity was not affected. Stronger inhibition of biological activity and cell binding of 125I-rIL-1 alpha was obtained with NOB-1 cells than with human thyrocytes. The antibodies failed to interfere with the biological activity of rIL-1 beta. It is concluded that IgG autoantibodies of IL-1 alpha in the sera of healthy humans selectively inhibit the biological activity of the soluble and membrane-associated forms of IL-1 alpha in vitro, and that the degree of biological inhibition afforded by these antibodies depends upon the target cell.

Learning to be a doctor while learning anatomy

This article presents results from a longitudinal study following a cohort of medical students. Semistructured interviews are conducted every year, in which the students tell about their experiences learning medicine, their daily life, and their social activities in relation to university. The aim of the study is to analyze how medical students develop their professional competencies, values, and attitudes. This article focuses on the medical students professional development in relation to the process of studying and learning anatomy. We analyze interviews conducted while the students are in their third and fifth semester. Anatomy plays a significant role in the medical students educational process, on both a cognitive and emotional level. It seems that students in learning the subject matter adapt to fundamental values in the medical profession and are thus transformed into real medical students, sharing a unique experience. The implications for curricular development and professionalism are discussed, and this article argues that the issue of professionalism must be addressed in the educational process in the preclinical years and in relation to the basic sciences. Anat Sci Ed 2008.

Enhancing the Effectiveness of Consumer-Focused Health Information Technology Systems Through eHealth Literacy: A Framework for Understanding Users' Needs

Background eHealth systems and applications are increasingly focused on supporting consumers to directly engage with and use health care services. Involving end users in the design of these systems is critical to ensure a generation of usable and effective eHealth products and systems. Often the end users engaged for these participatory design processes are not actual representatives of the general population, and developers may have limited understanding about how well they might represent the full range of intended users of the eHealth products. As a consequence, resulting information technology (IT) designs may not accommodate the needs, skills, cognitive capacities, and/or contexts of use of the intended broader population of health consumers. This may result in challenges for consumers who use the health IT systems, and could lead to limitations in adoption if the diversity of user attributes has not been adequately considered by health IT designers. Objective The objective of this paper is to propose how users’ needs and competences can be taken into account when designing new information and communications technology solutions in health care by expanding the user-task-context matrix model with the domains of a new concept of eHealth literacy. Methods This approach expands an existing method for supporting health IT system development, which advocates use of a three-dimensional user-task-context matrix to comprehensively identify the users of health IT systems, and what their needs and requirements are under differing contexts of use. The extension of this model involved including knowledge about users’ competences within the seven domains of eHealth literacy, which had been identified based on systematic engagement with computer scientists, academics, health professionals, and patients recruited from various patient organizations and primary care. A concept map was constructed based on a structured brainstorm procedure, card sorting, and computational analysis. Results The new eHealth literacy concept (based on 7 domains) was incorporated as a key factor in expanding the user-task-context matrix to describe and qualify user requirements and understanding related to eHealth literacy. This resulted in an expanded framework and a five-step process, which can support health IT designers in understanding and more accurately addressing end-users’ needs, capabilities, and contexts to improve effectiveness and broader applicability of consumer-focused health IT systems. It is anticipated that the framework will also be useful for policy makers involved in the planning, procuring, and funding of eHealth infrastructure, applications, and services. Conclusions Developing effective eHealth products requires complete understanding of the end-users’ needs from multiple perspectives. In this paper, we have proposed and detailed a framework for modeling users’ needs for designing eHealth systems that merges prior work in development of a user-task-context matrix with the emerging area of eHealth literacy. This framework is intended to be used to guide design of eHealth technologies and to make requirements explicitly related to eHealth literacy, enabling a generation of well-targeted, fit-for-purpose, equitable, and effective products and systems.

Human thyroid epithelial cells cultured in monolayers. I. Decreased thyroglobulin and cAMP response to TSH in 12-week-old secondary and tertiary cultures

An in vitro system of secondary and tertiary cultures of human thyroid epithelial cells (TFECs) in monolayer is described. The function of the cells was evaluated by the second messenger cAMP and the end product thyroglobulin (Tg). The Tg production from the cells was measured in the supernatant by a newly developed enzyme-linked immunosorbent assay. The TFECs in secondary monolayer cultures had preserved the ability to produce Tg and cAMP despite lack of polarization. Furthermore, a preserved ability of TSH-stimulated production of Tg and cAMP in 12-week-old secondary and tertiary cultures was found. However, the Tg and cAMP levels decreased gradually with the age of the cultures. In the secondary culture the TSH-stimulated Tg production decreased from 253 ng/micrograms DNA (205-263) after 3 weeks to 18 ng/micrograms DNA (6-81), P < 0.001, n = 6 after 12 weeks and TSH-stimulated cAMP production from 660 pmol/micrograms DNA (500-840) to 60 (40-200), P < 0.001, n = 6. The decreased responsiveness of long-term cultures results in preference of short-term secondary cultures, which provide a more suitable experimental model for in vitro investigation of human thyroid cell functions.

Interleukin-1 receptors on human thyroid cells and on the rat thyroid cell line FRTL-5

Cellular binding of interleukin-1 (IL-1) was tested on monolayers of human thyrocytes in secondary culture, on long-term cultures of human thyrocytes, and on the rat thyroid cell line FRTL-5. The human thyrocytes in secondary culture showed specific binding of human 125I-rIL-1 alpha. Scatchard plots of data obtained at 4 degrees C indicated the presence of a single population of receptors with a Kd of 30 to 170 pM and 2,000 to 6,000 receptors per cell. Incubation at room temperature resulted in internalization of the receptor-ligand complex. Parallel experiments were performed with the IL-1 receptor-positive murine T-cell lines EL-4 and NOB-1. The IL-1 receptors on these cells had Kd values one fifth to one tenth those on human thyroid cells in secondary culture. Both rIL-1 alpha and rIL-1 beta inhibited 125I-rIL-1 alpha binding to human thyrocytes and the murine T cells. In contrast to the cells in secondary culture, there was no specific binding of 125I-rIL-1 alpha to long-term cultivated human thyroid cells or to the FRTL-5 cells. We concluded that recently described differences in the response to IL-1 of different thyroid cell culture systems are most likely caused by differences in expression of IL-1 receptors.

Transforming students into digital academics: a challenge at both the individual and the institutional level

BackgroundLittle is known of students’ Information and Communication Technology (ICT) readiness in a learning context. Information about students’ capabilities and resources is an important prerequisite for designing meaningful teaching and learning activities that engage and motivate students. To learn about health science students’ usage of digital equipment, familiarity with software, online behavior and communication with the university, we have conducted a survey focusing on these areas.MethodsA digital questionnaire was sent to 9134 health science students, of whom 1165 responded (12.8%).ResultsAlmost all students owned a laptop (98.3%) and a smartphone (86.5%) and used these for internet access. The students were most familiar with typical office programs like word processing and spread sheets. Students used social media in their private lives but to a lesser extent in relation to their studies; they also experienced that their teachers made limited use of these media. The most commonly used tool for working with fellow students was email (80%) and for communication, SMS (47.6%). An age difference was found in relation to the way students communicated with each other. The mean age of chat users was 23.8 (Standard deviation 3.7) years, SMS users, 25 (Standard deviation 4.2) years and email users, 27.9 (Standard deviation 6.5) years. Over half of the students (53.4%) found that the degree of ICT incorporated in the teaching and learning activities was insufficient to provide them with the skills necessary in their future profession.ConclusionsAlthough a large percentage of the students had access to the internet, reported familiarity with basic software and used online services in their private lives, they were unfamiliar with the software and services they were expected to use in their studies. The students experienced that teachers did not use internet resources, which apparently influenced their perception of the importance of, and thereby their usage of, these services. The way the younger students communicate differs from the way communication takes place at the university, and it is recommended that the institutions should look into how they can meet the students in ways they are familiar with.

The acquisition and retention of ECG interpretation skills after a standardized web-based ECG tutorial-a randomised study

BackgroundElectrocardiogram (ECG) interpretation is of great importance for patient management. However, medical students frequently lack proficiency in ECG interpretation and rate their ECG training as inadequate.Our aim was to examine the effect of a standalone web-based ECG tutorial and to assess the retention of skills using multiple follow-up intervals.Methods203 medical students were included in the study. All participants completed a pre-test, an ECG tutorial, and a post-test. The participants were also randomised to complete a retention-test after short (2–4 weeks), medium (10–12 weeks), or long (18–20 weeks) follow-up.Intragroup comparisons of test scores were done using paired-samples t-test. Intergroup comparisons of test scores were performed using independent-samples t-test and ANOVA, whereas demographic data were compared using ANOVA and Chi-squared test.ResultsThe overall mean test score improved significantly from 52.7 (SD 16.8) in the pre-test to 68.4 (SD 12.3) in the post-test (p < 0.001). Junior and senior students demonstrated significantly different baseline scores (45.5 vs. 57.8 points; p < 0.001), but showed comparable score gains (16.5 and 15.1 points, respectively; p = 0.48).All three follow-up groups experienced a decrease in test score between post-test and retention-test: from 67.4 (SD 12.3) to 60.2 (SD 8.3) in the short follow-up group, from 71.4 (SD 12.0) to 60.8 (SD 8.9) in the medium follow-up group, and from 66.1 (SD 12.1) to 58.6 (SD 8.6) in the long follow-up group (p < 0.001 for all). However, there were no significant differences in mean retention-test score between the groups (p = 0.33). Both junior and senior students showed a decline in test score at follow-up (from 62.0 (SD 10.6) to 56.2 (SD 9.8) and from 72.9 (SD 11.4) to 62.5 (SD 6.6), respectively). When comparing the pre-test to retention-test delta scores, junior students had learned significantly more than senior students (junior students improved 10.7 points and senior students improved 4.7 points, p = 0.003).ConclusionA standalone web-based ECG tutorial can be an effective means of teaching ECG interpretation skills to medical students. The newly acquired skills are, however, rapidly lost when the intervention is not repeated.

The effect of constructing versus solving virtual patient cases on transfer of learning : a randomized trial

The purpose of this study was to explore the effect of actively constructing virtual patient (VP) cases compared with solving VP cases on knowledge gains, skills transfer and time spent on cases. Forty-five fourth-year medical students were randomized to constructing (VP-construction, n = 23) or solving (VP-solving, n = 22) four cardiopulmonary VP cases. Whereas the VP-solving group solved the cases, the VP-construction group only received the final diagnosis and had to complete the history, physical findings, and lab results. After a week, participants completed a transfer test involving two standardized patients representing cardiopulmonary cases. Performances on the transfer test were video-recorded and assessed by two blinded raters using the Reporter, Interpreter, Manager, Educator (RIME) framework. Thirty-nine participants completed the transfer test. The VP-construction group spent significantly more time on the VP cases compared with the VP-solving group, p = 0.002. There were no significant differences in RIME scores between the VP-construction group and VP-solving group, p = 0.54.In conclusion, engaging novice students in active VP case construction may be more time consuming than solving VP cases, without resulting in superior skills transfer.

Responses and relationship dynamics of men and their spouses during active surveillance for prostate cancer: health literacy as an inquiry framework

BackgroundEarly stage prostate cancer patients may be allocated to active surveillance, where the condition is observed over time with no intervention. Living with a cancer diagnosis may impose stress on both the men and their spouses.In this study we explore whether the scores of and verbal responses to a Health Literacy Questionnaire can be used to identify individuals in need of information and support and to reveal differences in perception and understanding in health related situations within couples.MethodsWe used the nine-domain Health Literacy Questionnaire (HLQ) as a framework to explore health literacy in eight couples where the men were on active surveillance for prostate cancer progression. Scores were calculated for each domain for both individuals. For each couple differences in scores were also calculated and related to the informants’ self-reported experiences and reflections in relation to participating in an active surveillance program. Also an inductive analysis was performed to identify themes in the responses and these themes were compared to those of HLQ.ResultsThe men tended to score higher than their spouses. There was no consistent relation between scores and the reported experiences and reflections.However, some interesting patterns emerged, e.g. in two of the three couples with the largest within couple differences in HLQ scores, responses revealed discrepancies in how the men and their spouses perceived their situation.Also, three themes emerged which related to six of the HLQ domains, i.e. involvement of spouses and other people around the men; support from and interaction with healthcare professionals; and use of the Internet for information retrieval.ConclusionsUsing the HLQ as an interview framework provided insight into the differences within couples and provided new perspectives on their experiences, including their contact with health professionals and the patient-spouse interaction when dealing with prostate cancer. The HLQ used as a dialogue tool may be an adjunct to assist healthcare providers to understand the need for support and information of men with prostate cancer on active surveillance and the dynamics within couples.

Optimization of an Acridine Orange-bisbenzimide procedure for the detection of apoptosis-associated fluorescence colour changes in etoposide-treated cell cultures.

This study was initiated in order to investigate the possibility of improving fluorescence microscopy as a method for evaluating apoptosis in cells by combining two fluorescent dyes with different staining characteristics. Cells were vitally stained with bisbenzimide (1.3 uM) and Acridine Orange (6.6 uM) and observed using the following filter configuration: excitation 380 nm, beamsplitter 395 nm and longpass filter 397 nm. Control cells exhibited clear blue fluorescent nuclei and red fluorescing lysosomes. In cells treated with etoposide to induce apoptosis, two distinct occurrences were observed: a change in the spectrum of emitted light from bisbenzimide bound to the nuclear region and an increase in lysosomal Acridine Orange fluorescence. The two occurrences together permit a more unbiased detection of apoptosis than most assays. Only one filter set is required for evaluation and the resulting images can be easily evaluated visually or processed further by image analysis.