Ghrelin is related to lower brain reward activation during touch

The gut hormone ghrelin drives food motivation and increases food intake, but it is also involved in the anticipation of and response to rewards other than food. This pre-registered study investigated how naturally varying ghrelin concentrations affect the processing of touch as a social reward in humans. Sixty-seven volunteers received slow caressing touch (so-called CT-targeted touch) as a social reward and control touch on their shins during 3T functional imaging on two test days. On one occasion, participants were fasted, and on another, they received a meal. On each occasion, plasma ghrelin was measured at three time points. All touch was rated as more pleasant after the meal, but there was no association between ghrelin concentrations and pleasantness. CT-targeted touch was rated as the most pleasant and activated somatosensory and reward networks (whole brain). A region-of-interest in the right medial orbitofrontal cortex (mOFC) showed lower activation during all touches, the higher the ghrelin concentrations were. During CT-targeted touch, a larger satiety response (ghrelin decrease after the meal) was associated with higher mOFC activation, and this mOFC activation was associated with higher experienced pleasantness. Overall, higher ghrelin concentrations appear to be related to a lower reward value for touch. Ghrelin may reduce the value of social stimuli, such as touch, to promote food search and intake in a state of low energy. This suggests that the role of ghrelin goes beyond assigning value to food reward.publishedVersio

Preproglucagon neurons in the hindbrain have IL-6 Receptor α (IL-6Rα) and show Ca 2+ influx in response to IL-6

Neuronal circuits in the hypothalamus and hindbrain are of importance for control of food intake, energy expenditure, and fat mass. We have recently shown that treatment with exendin-4 (Ex-4), an analog of the proglucagon-derived molecule glucagon-like peptide 1 (GLP-1), markedly increases mRNA expression of the cytokine interleukin-6 (IL-6) in the hypothalamus and hindbrain and that this increase partly mediates the suppression of food intake and body weight by Ex-4. Endogenous GLP-1 in the central nervous system (CNS) is produced by preproglucagon (PPG) neurons of the nucleus of the solitary tract (NTS) in the hindbrain. These neurons project to various parts of the brain, including the hypothalamus. Outside the brain, IL-6 stimulates GLP-1 secretion from the gut and pancreas. In this study, we aim to investigate whether IL-6 can affect GLP-1-producing PPG neurons in the nucleus of the solitary tract (NTS) in mouse hindbrain via the ligand binding part of the IL-6 receptor, IL-6 receptor-α (IL-6Rα). Using immunohistochemistry, we found that IL-6Rα was localized on PPG neurons of the NTS. Recordings of these neurons in GCaMP3/GLP-1 reporter mice showed that IL-6 enhances cytosolic Ca2+ concentration in neurons capable of expressing PPG. We also show that the Ca2+ increase originates from the extracellular space. Furthermore, we found that IL-6Rα was localized on cells in the caudal hindbrain expressing immunoreactive NeuN (a neuronal marker) or CNP:ase (an oligodendrocyte marker). In summary, IL-6Rα is present on PPG neurons in the NTS, and IL-6 can stimulate these cells by increasing influx of Ca2+ to the cytosol from the extracellular space

From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling

Body fat regulating neuropeptides: relation to interleukines and gut microbiota

Previous studies have shown that mice lacking interleukin-6 (IL-6), an important cytokine in the immune system, develop obesity, and that central, but not peripheral, administration of IL-6 induces energy expenditure. These findings suggest that IL-6 suppresses fat mass through the central nervous system. The mechanism behind this, however, is not understood. The aim of this thesis was to investigate possible neurobiological mechanisms, by which IL-6, during health, could exert its fat suppressing effect. Using immunohistochemistry, we aimed to map the distribution of the IL-6 receptor α (IL-6Rα) in human and mouse hypothalamus. In IL-6 knockout mice, we measured the gene expression of key hypothalamic neuropeptides known to regulate energy homeostasis. In mice, IL-6Rα was present mainly on neurons, and was widely distributed throughout the hypothalamus. IL-6Rα was found in a large number of neurons in the fat suppressing arcuate nucleus (ARC) and paraventricular nucleus (PVN), as well as in the fat promoting lateral hypothalamic area (LHA). We also found the IL-6Rα to be co-localized with several energy balance regulating neuropeptides in these hypothalamic sites, for instance with orexin and melanin concentrating hormone (MCH) in the LHA. In humans, IL-6Rα was only found in MCH neurons, but virtually all MCH neurons contained IL-6Rα. Depletion of IL-6 reduced the expression of the fat suppressing neuropeptides corticotrophin-releasing hormone (CRH) and oxytocin, as well as of arginine-vasopressin (AVP). In addition, we found IL-6Rα on neurons that produce these neuropeptides. This indicates that IL-6 could directly act on these neurons to increase the expression of CRH, oxytocin and AVP. Depletion of IL-6 induced the expression of the fat suppressing cytokine IL-1. In addition, IL-6 expression was reduced in mice with IL-1 receptor 1 knockout. This indicates that, in the hypothalamus, IL-1 receptor 1 signaling increase IL-6 expression, while IL-6 decreases IL-1 expression. Based on our findings in this thesis we speculate that IL-6 could act on several hypothalamic neurons and sites involved in energy homeostasis to increase energy expenditure and eventually weight loss in mice, while a similar effect could by exerted via the pro-obesity neuropeptide MCH in humans. Previous studies show that gut microbiota contributes to obesity, in part by facilitating nutritional uptake, but probably also through other mechanisms. We aimed to investigate possible effects of gut microbiota on central energy balance regulation. We measured the gene expression of several important energy balance regulating neuropeptides in the hypothalamus and brainstem of germ free mice. The fat suppressing neuropeptides glucagon-like peptide-1(GLP-1) and brain-derived neurotrophic factor (BDNF) was downregulated in the presence of gut microbiota, which could explain the elevated fat mass. In addition, we found that mice with gut microbiota were less sensitive to leptin, providing another mechanism by which gut microbiota could increase fat mass. In conclution, our findings are in line the assumption that components of the immune system and the commensal gut microbiota can affect fat mass in part via energy balance-regulating circuits in the brain

Könade upplevelser av arbetsmiljö : En studie av stress och ambiguitet bland tandläkarstudenter i Sverige

This thesis explores how dental students experience their education. We aim to generate ways to understand which elements relate to the students’ experience based on current theories and models regarding the quality of working life and gender (and) power relations.   Methods Twelve interviews with Umeå dental students in their clinical semesters were analysed with a Grounded Theory (GT) as well as a content analysis approach. A web-survey was sent to all clinical dental students in Sweden (P ≈ 805) with a response rate of 40% (p = 322). The quantitative methods included structural equation modelling and cluster analysis. Results The GT analysis resulted in the core category “Experiencing ambiguity,” that captured the student’s role-ambiguity. Central categories focused on perceived stress and performance assessment in relation to ambiguous inner and outer demands. The content analysis resulted in three categories: “Notions of inequalities,” “Gendering,” and “The student position.” These categories present the ways groups of students are constructed in relation to the student/dentist norm and social gender relations, and how women and men of foreign descent risk subordination and stereotyping. The SEM-model contained psychosocial work environment, tolerance for ambiguity, perceived stress, and student satisfaction. Work environment influenced both perceived stress and satisfaction, and stood for almost all of the explained variance in perceived stress for women, indicating that women are constructed as co-responsible for the work environment. About half of the variance for the men was explained by tolerance for ambiguity, indicating that the feeling of uncertainty may lead to stress in men who include “being in control” in their gender identity. The cluster analysis resulted in a six-cluster solution ranging from “The fresh and positive” to “The worn critiques.” Psychosocial work environment again appeared to be the main factor. Gender also appears to be a factor as the gender distribution in the best as well as the two worst clusters differs from the population. Conclusion Work environment stands out among the factors that relate to the students wellbeing and satisfaction, but the student group is heterogeneous and the ways students perceive their work environment relate to different processes and experiences. We suggest that the ways gender and ethnicity appear to be constructed in relation to the sociocultural gender power relations and the (traditional) medical hierarchy could be of importance for how the students’ experience their psychosocial work environment

Nedskrivningar -för en rättvisande bild eller eget intresse?

Den pågående övergången till mer internationella redovisningsregler och rekommendationer diskuteras just nu flitigt i Sverige. Samtidigt som den internationella harmoniseringen ska stärkas och jämförbarheten öka, finns oro för att en mängd nya valmöjligheter ger ett allt för stort spelrum för uppskattningar och bedömningar av företagsledningen. Via EU:s fjärde bolagsdirektiv har begreppet ”rättvisande bild” kommit in i den svenska årsredovisningslagen och i Sverige har Redovisningsrådet förbundit sig att verka för att IASB:s standarder kommer till uttryck i de svenska rekommendationerna. Exempel på detta är RR17, om nedskrivningar, som införts i Sverige från och med år 2002. RR17 ger ett visst handlingsutrymme när det gäller vilken metod som ska tillämpas vid nedskrivning av anläggningstillgångar. De metoder som tillåts ger dessutom utrymme för subjektiva bedömningar. Genom att utgå från teorier som handlar om att människor är rationella och strävar efter att maximera sin egen nytta är syftet med denna studie att undersöka om nedskrivningar görs av företagsledningar för att uppnå en rättvisande bild, om nedskrivningar görs i eget intresse eller på grund av institutionella faktorer. Genom att statistiskt analysera ett material som samlats in via granskning av de svenska börsföretagens årsredovisningar, testas hypoteser som är ställda utifrån Positive Accounting Theory och Institutionell teori. Studien visar att det finns starka samband mellan nedskrivningarnas storlek och företagens räntabilitet på totalt kapital samt mellan nedskrivningarnas storlek och huruvida företagen gjort VD-byte eller inte. Dessutom konstateras att någonting händer år 2004 som skulle kunna härledas till den stundande övergången till IAS/IFRS

Self-Efficacy, Psychological Flexibility, and Basic Needs Satisfaction Make a Difference : Recently Graduated Psychologists at Increased or Decreased Risk for Future Health Issues

The transition from university to working life appears a critical period impacting human service workers' long-term health. More research is needed on how psychological factors affect the risk. We aimed to investigate how subgroups, based on self-efficacy, psychological flexibility, and basic psychological needs satisfaction ratings, differed on self-rated health, wellbeing, and intention to leave. A postal survey was sent to 1,077 recently graduated psychologists in Sweden (≤3 years from graduation), response rate 57.5%, and final sample 532 (75% women and 23% men). A hierarchical cluster analysis resulted in a satisfactory eight-cluster solution. We identified two at-risk subgroups, displaying the lowest scores on health and wellbeing, and one potential low-risk subgroup with the highest ratings on said variables. The "Low risk?" group rated high on all three psychological constructs, a positive transition to working life, a work environment where resources balanced relatively high emotional demands, good health, and wellbeing. Almost the complete opposite ratings characterized the potential risk groups. "Quitting?" scored significantly higher than "Getting sick?" on self-efficacy and psychological flexibility as well as actively seeking new employment and reporting daily thoughts on leaving the profession. We suggest that a combination of low self-efficacy and psychological flexibility could increase the risk of individuals staying despite suboptimal working conditions. With combined higher self-efficacy and psychological flexibility, individuals in similar circumstances appear more inclined to quit. We conclude that the ways recently graduated psychologists rate their self-efficacy, psychological flexibility, and basic needs satisfaction appear to be reflected in their self-rated health and wellbeing.dnr_14027

Prototype stories of life with Chemical Intolerance : when the environment becomes a threat to health and well-being

We aimed to explore how individuals living with Chemical Intolerance (CI) describe the onset and progression of CI, and how they live and cope with CI. The participants were recruited via Swedish websites hosted by CI support groups. A postal survey, including a Life history calender, was sent to potential participants. Eleven respondents fitted the consensus-based criteria for CI while not reporting comorbidity. A narrative analysis of their written replies resulted in five prototypical stories based on similarities in the onset and course of CI. All five stories contain descriptions of alienation from society and insufficient social support. Differences in participants’ perceptions of the symptom onset – with regard to suddenness, the point in life and the perceived cause of symptoms – partly corresponded to etiological theories of CI related to stress or inflammation. Further differences between the prototype stories mainly concern the possible effects on health and well-being related to social support and coping. Given these differences, we recommend that medical professionals and others apply a holistic, context-sensitive approach before discouraging or promoting a specific coping strategy in relation to CI

Implementing test enhanced learning : Swedish teacher students’ perception of quizzing

Given previous findings on test enhanced learning, the present study examined the implementation of this practice in terms of quizzing, during the progress of a course. After completing the university course, 88 Swedish teacher students were asked to answer an adapted Retrieval Practice and Test Anxiety Survey. The results showed that students perceived quizzing to improve learning, and reduce test anxiety. Nonetheless, based on students’ misconceptions regarding why quizzing actually enhances learning, it is suggested that implications of test enhanced learning was not fully conveyed. It is for educational purpose imperative to not forget this application