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For adipose stromal/stem cell (ASCs)-based immunomodulatory therapies, it is important to study how donor characteristics, such as obesity and type 2 diabetes (T2D), influence ASCs efficacy. Here, ASCs were obtained from 2 groups, donors with T2D and obesity (dASCs) or nondiabetic donors with normal-weight (ndASCs), and then cultured with anti-CD3/CD28-stimulated allogeneic CD4 T cells. ASCs were studied for the expression of the immunomodulators CD54, CD274, and indoleamine 2, 3 dioxygenase 1 (IDO) in inflammatory conditions. CD4 T cells cultured alone or in cocultures were assessed to evaluate proliferation, activation marker surface expression, apoptosis, the regulatory T cells (Tregs; CD4⁺ CD25high FOXP3⁺) frequency, and intracellular cytokine expression using flow cytometry. Modulation of T-cell subset cytokines was explored via ELISA. In inflammatory conditions, the expression of CD54, CD274, and IDO was significantly upregulated in ASCs, with no significant differences between ndASCs and dASCs. dASCs retained the potential to significantly suppress CD4 T-cell proliferation, with a slightly weaker inhibitory effect than ndASCs, which was associated with significantly reduced abilities to decrease IL-2 production and increase IL-8 levels in cocultures. Such attenuated potentials were significantly correlated with increasing body mass index. dASCs and ndASCs comparably reduced CD4 T-cell viability, HLA-DR expression, and interferon-gamma production and conversely increased CD69 expression, the Tregs percentage, and IL-17A production. Considerable amounts of the immunomodulators prostaglandin E2 (PGE2) and IL-6 were detected in the conditioned medium of cocultures. These findings suggest that ASCs obtained from donors with T2D and obesity are receptive to the inflammatory environment and able to modulate CD4 T cells accordingly.

Objectives: To assess whether mammographic breast density in women diagnosed with breast cancer correlates with the total number of incidental magnetic resonance imaging (MRI)-detected lesions and the likelihood of the lesions being malignant. Methods: Patients diagnosed with breast cancer meeting the EUSOBI and EUSOMA criteria for preoperative breast MRI routinely undergo mammography and ultrasound before MRI at our institution. Incidental suspicious breast lesions detected in MRI are biopsied. We included patients diagnosed with invasive breast cancers between 2014 and 2019 who underwent preoperative breast MRI. One reader retrospectively determined breast density categories according to the 5th edition of the BI-RADS lexicon. Results: Of 946 patients with 973 malignant primary breast tumors, 166 (17.5%) had a total of 175 (18.0%) incidental MRI-detected lesions (82 (46.9%) malignant and 93 (53.1%) benign). High breast density according to BI-RADS was associated with higher incidence of all incidental enhancing lesions in preoperative breast MRIs: 2.66 (95% confidence interval: 1.03–6.86) higher for BI-RADS density category B, 2.68 (1.04–6.92) for category C, and 3.67 (1.36–9.93) for category D compared to category A (p < 0.05). However, high breast density did not predict higher incidence of malignant incidental lesions (p = 0.741). Incidental MRI-detected lesions in the contralateral breast were more likely benign (p < 0.001): 18 (27.3%)/48 (72.7%) vs. 64 (58.7%)/45 (41.3%) malignant/benign incidental lesions in contralateral vs. ipsilateral breasts. Conclusion: Women diagnosed with breast cancer who have dense breasts have more incidental MRI-detected lesions, but higher breast density does not translate to increased likelihood of malignant incidental lesions. Clinical relevance statement: Dense breasts should not be considered as an indication for preoperative breast MRI in women diagnosed with breast cancer. Key points: • The role of preoperati

Insulinomas are rare pancreatic neuroendocrine tumours. Most patients can be cured with surgery, but patients with a metastatic disease show impaired survival. The aim of this study was to evaluate somatostatin receptor (SSTR) 1‐5 expression in insulinomas and to correlate the expression profile with clinicopathological variables and with patient outcome. This retrospective study involved 52 insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with monoclonal SSTR1‐5 antibodies. All the 52 tumours (49 non-metastatic, 3 metastatic) expressed at least one SSTR subtype. SSTR2 was expressed most frequently (71%), followed by SSTR3 (33%), SSTR1 (27%), SSTR5 (6%) and SSTR4 (0%). SSTR3 expression was associated with a larger tumour size (median diameter 19 mm vs. 13 mm, p = 0.043), and SSTR3 and SSTR5 expression were associated with impaired overall survival [HR 3.532 (95% CI 1.106‐11,277), p = 0.033, and HR 6.805 (95% CI 1.364‐33.955), p = 0.019 respectively]. Most insulinomas express SSTR2, which may be utilized in diagnostic imaging, and in planning individualized treatment strategies for insulinoma patients. Further studies are needed to clarify the association between SSTR profile and overall survival.

Background: Preeclampsia causes significant maternal and perinatal morbidity. Genetic factors seem to affect the onset of the disease. We aimed to investigate whether the polygenic risk score for blood pressure (BP; BP-PRS) is associated with preeclampsia, its subtypes, and BP values during pregnancy. Methods: The analyses were performed in the FINNPEC study (Finnish Genetics of Pre-Eclampsia Consortium) cohort of 1514 preeclamptic and 983 control women. In a case-control setting, the data were divided into percentiles to compare women with high BP-PRS (HBP-PRS; >95th percentile) or low BP-PRS (≤5th percentile) to others. Furthermore, to evaluate the effect of BP-PRS on BP, we studied 3 cohorts: women with preeclampsia, hypertensive controls, and normotensive controls. Results: BP values were higher in women with HBP-PRS throughout the pregnancy. Preeclampsia was more common in women with HBP-PRS compared with others (71.8% and 60.1%, respectively; P=0.009), and women with low BP-PRS presented with preeclampsia less frequently than others (44.8% and 61.5%, respectively; P<0.001). HBP-PRS was associated with an increased risk for preeclampsia (odds ratio, 1.7 [95% CI, 1.1–2.5]). Furthermore, women with HBP-PRS presented with recurrent preeclampsia and preeclampsia with severe features more often. Conclusions: Our results suggest that HBP-PRS is associated with an increased risk of preeclampsia, recurrent preeclampsia, and preeclampsia with severe features. Furthermore, women with HBP-PRS present higher BP values during pregnancy. The results strengthen the evidence pointing toward the role of genetic variants associated with BP regulation in the etiology of preeclampsia, especially its more severe forms.

The concept of mimesis can be utilized in educational theorizations of democratic citizenship and in fleshing out learning paths related to citizenship. It offers the possibility to examine citizenship from the viewpoint of an informal way of learning that is, at times, unconscious, and even accidental, and which can lead to unwanted outcomes. Such characteristics of learning are inescapable for human beings and, thus, hold crucial importance for education for democratic citizenship. Drawing on the theory of mimesis, the chapter argues for the importance of acknowledging the mimetic power of emotions. It employs particularly Theodor W. Adorno and Max Horkheimer’s account of mimesis in which mimesis is both a possibility and a threat. However, according to them, the modern individual has a strong tendency toward unfavourable mimesis due to an unbalanced human-nature relationship. The overall purpose is to examine how the notion of mimesis can contribute to education for democracy.

This dissertation presents a philosophical inquiry into the concept of intelligence by reconstructing John Dewey’s theory of intelligence and investigating its educational implications. It presents three critiques of educational practices and theories that, from a Deweyan point of view, are built on misconceptions or oversimplifications of intelligence. While his theory of intelligence is primarily expressed in implicit terms, it offers a nuanced analysis of the sociality and contextuality of intelligence, questioning some of its traditional or mainstream conceptions. The reconstructed theory presented in this dissertation implies that rather than holding onto the idea of individual intelligence, education (and those who are being educated) might benefit from focusing on the social practices and contexts that enable intelligence. The contextuality of intelligence suggests that conceiving intelligence as something that can be universalized, abstracted, and then redistributed is problematic. Dewey’s theory also suggests that people are rich with experience-based contextualized intelligence. To make the most of this, education needs to provide people with a robust theory of knowledge and an aspiration to be informed about the world in multiple and diverse ways. Learning the habit and processes of different kinds of inquiries could benefit societies by contributing to creative and intelligent democratic problem-solving in the inevitably unknown contexts of the future., Tiivistelmä Tämä väitöskirja on filosofinen tutkimus älyn käsitteestä: se esittää rekonstruktion John Deweyn älyn teoriasta ja tarkastelee, mitä siitä voidaan johtaa kasvatuksen näkökulmasta. Se tarjoaa kolme kritiikkiä kasvatuksen käytännöistä ja teorioista, jotka Deweyn älyn teorian näkökulmasta rakentuvat väärinkäsityksille tai liialliselle yksinkertaistamiselle. Deweyn tuotannossa läsnä oleva älyn teoria näyttäytyy ensisijaisesti epäsuorasti hänen käsitellessään muita aiheita. Siitä huolimatta hänen teoriansa analysoi vivahteikkaasti älyn sosiaalisuutta ja kontekstuaalisuutta, samalla kyseenalaistaen joitakin siihen perinteisesti liitettyjä tai yleisesti hyväksyttyjä mielikuvia. Tässä väitöskirjassa esitetty älyn teorian rekonstruktio esittää, että kasvatus (ja kasvatettavat) saattaisivat hyötyä siitä, että huomioimme yksilöllisen älykkyyden sijaan paremmin ne sosiaaliset käytännöt, jotka mahdollistavat älykkään toiminnan. Älyn kontekstuaalisuus puolestaan muistuttaa, että sen käsittäminen jonain, minkä voi yleistää, abstrahoida ja tarjoilla eteenpäin, on ongelmallista. Deweyn teoria esittää myös, että ihmisillä on huomattava määrä kokemukseen pohjaavaa kontekstuaalista älykkyyttä. Jotta tämä äly saadaan hyödynnettyä, tulee kasvatuksen tarjota kasvatettaville vankka ymmärrys siitä, mitä tieto on sekä halu olla perillä maailmasta erilaisin ja monimuotoisin tavoin. Yhteiskunnille on hyödyllistä, jos kasvatettavat tottuvat erilaisiin maailman tutkimisen tapoihin ja prosesseihin, sillä nämä edesauttavat luovaa, älykästä ja demokraattista ongelmanratkaisua tulevaisuuden konteksteissa, jotka ovat vääjäämättömän tuntemattomia.

Objective: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. Design: Retrospective cohort study. Methods: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980–2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel–Haenszel method. Overall survival was analysed with Kaplan–Meier and Cox regression analyses Results: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02–4.22)), intestinal obstruction (18.65 (2.09–166.86)), and possibly breast (4.46 (1.29–15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). Conclusions: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.