Inflammation as a transdiagnostic factor in the development of psychopathology and somatic symptoms

This dissertation focuses on the role of inflammation in the development of psychopathology andsomatic symptoms. Our question was whether different types of stressors lead to the development of psychiatric or somatic symptoms via an activated immune system. We have focused on herpes infections, childhood trauma and sleep as stressors that might be related to both inflammation and psychiatric and somatic symptoms.We studied associations in a large group of adolescents from the TRAILS cohort. We performed a clinical study to study whether inhibiting virus activity has an effect on inflammation in the brain. In a small group of 10 participants, we focused on the link between sleep, inflammation and somatic symptoms, by following them for 63 days with diary measurements. We found no evidence for our hypothesis that stressors lead to psychiatric or somatic symptoms via inflammation. Herpes simplex type 1 infection was associated with decreased cognitive functioning. CRP level was associated with specific somatic symptoms. We found that stressful childhood life events were associated with higher CRP levels and with psychiatric symptoms. We found that virus inhibitors improved neuroinflammation, but not symptoms. And we found that there were large individual differences in the relationship between sleep, inflammation, and somatic symptoms.Our findings could suggest that stressors are a common cause of inflammation and psychiatric or somatic symptoms, but that inflammation does not explain the association between stressors and psychiatric or somatic symptoms

Antiviral treatment in schizophrenia:a randomized pilot PET study on the effects of valaciclovir on neuroinflammation

BACKGROUND: Patients with schizophrenia experience cognitive impairment, which could be related to neuroinflammation in the hippocampus. The cause for such hippocampal inflammation is still unknown, but it has been suggested that herpes virus infection is involved. This study therefore aimed to determine whether add-on treatment of schizophrenic patients with the anti- viral drug valaciclovir would reduce hippocampal neuroinflammation and consequently improve cognitive symptoms.METHODS: We performed a double-blind monocenter study in 24 male and female patients with schizophrenia, experiencing active psychotic symptoms. Patients were orally treated with the anti-viral drug valaciclovir for seven consecutive days (8 g/day). Neuroinflammation was measured with Positron Emission Tomography using the translocator protein ligand [ 11C]-PK11195, pre-treatment and at seven days post-treatment, as were psychotic symptoms and cognition. RESULTS: Valaciclovir treatment resulted in reduced TSPO binding (39%) in the hippocampus, as well as in the brainstem, frontal lobe, temporal lobe, parahippocampal gyrus, amygdala, parietal lobe, occipital lobe, insula and cingulate gyri, nucleus accumbens and thalamus (31-40%) when using binding potential (BPND) as an outcome. With total distribution volume (VT) as outcome we found essentially the same results, but associations only approached statistical significance ( p = 0.050 for hippocampus). Placebo treatment did not affect neuroinflammation. No effects of valaciclovir on psychotic symptoms or cognitive functioning were found. CONCLUSION: We found a decreased TSPO binding following antiviral treatment, which could suggest a viral underpinning of neuroinflammation in psychotic patients. Whether this reduced neuroinflammation by treatment with valaciclovir has clinical implications and is specific for schizophrenia warrants further research.</p

Exploring immune status in peripheral blood and tumor tissue in association with survival in patients with multi-organ metastatic colorectal cancer

Colorectal cancer (CRC) raises considerable clinical challenges, including a high mortality rate once the tumor spreads to distant sites. At this advanced stage, more accurate prediction of prognosis and treatment outcome is urgently needed. The role of cancer immunity in metastatic CRC (mCRC) is poorly understood. Here, we explore cellular immune cell status in patients with multi-organ mCRC. We analyzed T cell infiltration in primary tumor sections, surveyed the lymphocytic landscape of liver metastases, and assessed circulating mononuclear immune cells. Besides asking whether immune cells are associated with survival at this stage of the disease, we investigated correlations between the different tissue types; as this could indicate a dominant immune phenotype. Taken together, our analyses corroborate previous observations that higher levels of CD8+ T lymphocytes link to better survival outcomes. Our findings therefore extend evidence from earlier stages of CRC to indicate an important role for cancer immunity in disease control even after metastatic spreading to multiple organs. This finding may help to improve predicting outcome of patients with mCRC and suggests a future role for immunotherapeutic strategies.</p

Technology and Society in Equilibrium:

This sector portrait of the design engineering sciences describes the common denominator of the various design disciplines in the Netherlands. In a future sector plan, the above investment areas will be further explored and purposefully developed. The implementation of technological innovations aligned to societal issues encompasses a design challenge. This increasingly demands science-based design methodologies. The broad Dutch design landscape can fulfil the role of connector well in this regard. In order to optimally strengthen this bridging function, three areas for further investment have been identified: Research More research and research funding are needed to meet the design challenges posed by Dutch societal missions, as well as for the further development of Key Enabling Methodologies (KEMs) as the basis for effective design. Educational Capacity Expanded teaching capacity and further development of design-driven didactics are needed to meet the growing demand for designers, This demand stems from the emerging need for design approaches in new research programmes within Horizon Europe and the Dutch Research Council (NWO). Access to Technology Continuous access to the rapidly evolving technological disciplines must be guaranteed for professionals who can both understand the technology and meet the investigative design challenge

Reproducibility and day time bias correction of optoelectronic leg volumetry: a prospective cohort study

Background Leg edema is a common manifestation of various underlying pathologies. Reliable measurement tools are required to quantify edema and monitor therapeutic interventions. Aim of the present work was to investigate the reproducibility of optoelectronic leg volumetry over 3 weeks' time period and to eliminate daytime related within-individual variability. Methods Optoelectronic leg volumetry was performed in 63 hairdressers (mean age 45 ± 16 years, 85.7% female) in standing position twice within a minute for each leg and repeated after 3 weeks. Both lower leg (legBD) and whole limb (limbBF) volumetry were analysed. Reproducibility was expressed as analytical and within-individual coefficients of variance (CVA, CVW), and as intra-class correlation coefficients (ICC). Results A total of 492 leg volume measurements were analysed. Both legBD and limbBF volumetry were highly reproducible with CVA of 0.5% and 0.7%, respectively. Within-individual reproducibility of legBD and limbBF volumetry over a three weeks' period was high (CVW 1.3% for both; ICC 0.99 for both). At both visits, the second measurement revealed a significantly higher volume compared to the first measurement with a mean increase of 7.3 ml ± 14.1 (0.33% ± 0.58%) for legBD and 30.1 ml ± 48.5 ml (0.52% ± 0.79%) for limbBF volume. A significant linear correlation between absolute and relative leg volume differences and the difference of exact day time of measurement between the two study visits was found (P < .001). A therefore determined time-correction formula permitted further improvement of CVW. Conclusions Leg volume changes can be reliably assessed by optoelectronic leg volumetry at a single time point and over a 3 weeks' time period. However, volumetry results are biased by orthostatic and daytime-related volume changes. The bias for day-time related volume changes can be minimized by a time-correction formula

Technologie en Maatschappij in Balans:

Dit sectorbeeld van de ontwerpende ingenieurswetenschappen beschrijft de grote gemeenschappelijke deler van de verschillende ontwerpdisciplines in Nederland. In aanloop naar het schrijven van dit sectorbeeld hebben we gezamenlijk bepaald waar onze sterkte ligt, en waar we concreet kunnen bijdragen aan het oplossen van maatschappelijke knelpunten. Implementatie van technologische innovaties in aansluiting op maatschappelijke uitdagingen omvat een ontwerpopgave. Dit vereist in toenemende mate wetenschappelijk onderbouwde ontwerpmethodieken. Het brede Nederlandse ontwerplandschap kan hierbij de rol van verbinder goed vervullen. Teneinde deze brugfunctie optimaal te versterken worden drie gebieden voor verdere investeringen gezien: Onderzoek Er is meer onderzoek en onderzoeksfinanciering nodig voor het volbrengen van ontwerpuitdagingen die in de Nederlandse maatschappelijke missies worden gesteld, evenals voor de verdere ontwikkeling van Key Enabling Methodologies als basis voor effectief ontwerp. Onderwijscapaciteit Er is een ruimere onderwijscapaciteit en verdere ontwikkeling van ontwerp gestuurde didactiek nodig om te kunnen voldoen aan de groeiende vraag naar ontwerpers, een vraag die voortkomt uit de opkomende behoefte aan ontwerpaanpakken in nieuwe onderzoeksprogramma’s binnen Horizon Europe en NWO. Toegang tot technologie Er moet voortdurend toegang gegarandeerd zijn tot de zich snel ontwikkelende technologische disciplines voor professionals die zowel de technologie doorgronden als de onderzoekende ontwerpuitdaging aankunnen. Dit sectorbeeld van de ontwerpende ingenieurswetenschappen beschrijft de grote gemeenschappelijke deler van de verschillende ontwerpdisciplines in Nederland. In een toekomstig sectorplan zullen bovenstaande inversteringsgebieden verder en doelgericht worden uitgewerkt