Cathepsin S as a biomarker of low-grade inflammation, insulin resistance, and cardiometabolic disease risk

Cathepsin S is a protease important in major histocompatibility complex (MHC) class II antigen presentation and also in degrading the extracellular matrix. Studies, most of them experimental, have shown that cathepsin S is involved in different pathological conditions such as obesity, inflammation, atherosclerosis, diabetes, and cancer.    The overall hypothesis of this report is that high levels of circulating cathepsin S, is a biomarker that reflects pathology induced by inflammation and obesity. The overall aim of this report was to investigate possible associations between circulating cathepsin S, inflammation, glucometabolic disturbance, and its associated diseases in the community. As cathepsin S appears to be a novel risk marker for several pathological conditions, we also wanted to examine the effect of dietary intervention on circulating cathepsin S concentrations.    This thesis is based on data from three community-based cohorts, the Uppsala longitudinal study of adult men (ULSAM), the prospective investigation of the vasculature in Uppsala seniors (PIVUS), and a post-hoc study from the randomized controlled NORDIET trial.    In the first study, we identified a cross-sectional positive association between serum cathepsin S and two markers of cytokine-mediated inflammation, CRP and IL-6. These associations were similar in non-obese individuals. In longitudinal analyses, higher cathepsin S at baseline was associated with higher CRP and IL-6 levels after six years of follow-up. In the second study, we identified a cross-sectional association between increased serum levels of cathepsin S and reduced insulin sensitivity. These associations were similar in non-obese individuals. No significant association was observed between cathepsin S and insulin secretion. In longitudinal analysis, higher cathepsin S levels were associated with an increased risk of developing diabetes during the six-year follow-up. In the third study, we found that higher serum levels of cathepsin S were associated with increased mortality risk. Moreover, in the ULSAM cohort, serum cathepsin S was independently associated with cause-specific mortality from cardiovascular disease and cancer. In the fourth study, we identified that adherence to an ad libitum healthy Nordic diet for 6 weeks slightly decreased the levels of plasma cathepsin S in normal or marginally overweight individuals, relative to the control group. Changes in circulating cathepsin S concentrations were correlated with changes in body weight, LDL-C, and total cholesterol.    Conclusion: This thesis shows that circulating cathepsin S is a biomarker that independently reflects inflammation, insulin resistance, the risk of developing diabetes, and mortality risk. Furthermore, a Nordic diet moderately reduced cathepsin S levels in normal-weight and overweight men and women. This effect may be partially mediated by diet-induced weight loss and possibly by reduced LDL-C concentrations. 

Target language use : An empirical study of the target language use in the Swedish 4-6 grade classroom

A consistent use of the target language during English lessons is beneficial for pupils’ linguistic development, but also challenging for both teachers and pupils. The main purpose for pupils to learn English is to be able to use it in communication, which requires that they develop the ability to comprehend input, produce output and use language strategies. Several researchers claim that a consistent use of the target language is necessary in order to develop these abilities. Therefore, the aim of this study is to examine the target language use during English lessons in Swedish grades 4-6, and what pupils’ opinions regarding target language use are. The methods used to collect data consisted of a pupil questionnaire with 42 respondents and an observation of two teachers’ English lessons during a week’s time. The results from the observations show that the teachers use plenty of target language during lessons, but the first language as well to explain things that pupils might experience difficult to understand otherwise. The results from the questionnaire mainly show that the pupils seem to enjoy English and like to both speak and hear the target language during lessons. The main input comes from listening to a CD with dialogues and exercises in the textbook and the workbook, and from the teacher speaking. The results also show that a majority of the pupils use the target language in their spare time. A conclusion that can be drawn from this study is that the TL should be used to a large extent in order to support pupils’ linguistic development. However, teachers may sometimes need to use L1 in order to facilitate understanding of the things that many pupils find difficult, for example grammar. Suggestions for further research in this area include similar studies conducted on a larger scale.

Student's second-language grade may depend on classroom listening position

The purpose of this experiment was to explore whether listening positions (close or distant location from the sound source) in the classroom, and classroom reverberation, influence students' score on a test for second-language (L2) listening comprehension (i.e., comprehension of English in Swedish speaking participants). The listening comprehension test administered was part of a standardized national test of English used in the Swedish school system. A total of 125 high school pupils, 15 years old, participated. Listening position was manipulated within subjects, classroom reverberation between subjects. The results showed that L2 listening comprehension decreased as distance from the sound source increased. The effect of reverberation was qualified by the participants' baseline L2 proficiency. A shorter reverberation was beneficial to participants with high L2 proficiency, while the opposite pattern was found among the participants with low L2 proficiency. The results indicate that listening comprehension scores-and hence students' grade in English-may depend on students' classroom listening position.