Uppsala University Research Articles

Difference in functional constituents of myocardial passive compliance renders BalbC/J mice sensitive to pulmonary edema compared to C57BL6/J mice

Study objective: We have found different survival rates in response to a 4-day angiotensin II (AngII) and high salt diet - treatment in two mouse strains, BalbC/J and C57BL6/J. The mortality is increased in BalbC/J mice alongside increased lung weight but the reason is unknown. Hypothesis: We hypothesize the increased mortality is due to differences in myocardial compliance. Methodology: Male mice were treated with AngII by osmotic mini-pump infusion and fed a high salt-diet (3%) for 4 days. At the end of the treatment the lungs were weighed. Left ventricle (LV) passive compliance was assessed by Langendorff, and collagen and non-collagen functional fractions using demembranated trabecular strips. A commercial assay was used to determine total collagen of the myocardium. All procedures were approved by the local ethics committee. Comparisons were carried out using unpaired t-test. All intervals reflect standard error of the mean. Data: Lung weights of animals before treatment were similar in BalbC/J (148 ± 8.8 mg (n=5)) and C57BL6/J (155 ± 12 mg (n=5)) mice (p>0.05). After treatment they were higher in BalbC/J (255 ± 24 mg (n=7)) than C57BL6/J (166 ± 5.1 mg (n=6)) (p<0.01). LV passive strain was higher in BalbC/J (62.4 ± 11.9 mN/mm2 (n=9)) than C57BL6/J (28.2 ± 2.3 mN/mm2 (n=7)) (p<0.05), at 36 μl LV inflation past 5 mmHg end-diastolic pressure. In demembranated trabeculae, passive stiffness was higher in BalbC/J (38.7 ± 5.5 mN/mm2 (n=6)) than C57BL6/J (22.5 ± 2.0 mN/mm2 (n=6)) (p<0.05) at baseline, as measured by passive tension at 15 % stretch from sarcomere length 2.0 μm. This was derived from the non-collagen fraction which was higher in BalbC (23.4 ± 2.8 mN/mm2 (n=6)) than C57BL6/J (12.4 ± 1.3 mN/mm2 (n=6)) (p<0.01), unlike the collagen fraction that was the same (BalbC/J 15.3 ± 3.8 mN/mm2 (n=6), C57BL6/J 10.1 ± 1.5 mN/mm2 (n=6) (p>0.05)). There was no difference in myocardial collagen content (BalbC/J 0.20 ± 0.01 μg/μl (n=7), C57BL6/J 0.18 ± 0.01 μg/μl (n=9) (p>0.05)). Summary of results: Gross organ evaluation by Langendorff indicates higher myocardial stiffness in BalbC/J than C57BL6/. This renders the heart susceptible to backward failure. This is supported by findings in demembranated tissue bundles. The origin of this appears to lie in the non-collagen fraction of passive stiffness, as indicated by functional and biochemical assays. Conclusion: An acute lung weight increase indicates pulmonary edema. The most common reason for this is backwards failure of the LV. Our investigations into myocardial function suggest that BalbC/J mice has a propensity for this due to lower compliance secondary to increased non-collagen fraction, compared to C57BL6/J. This is likely caused by titin-derived stiffness. Therapies to modulate titin-derived stiffness may be useful to avoid backward failure. These findings also represent important knowledge for the research community modeling human heart disease on the backbone of two common mouse strains. The study was funded with grants from the Swedish Society of Medical Research and Åke Wiberg Foundation to HI, Swedish Heart-Lung Foundation to MH, and from Uppsala University Hospital to HI and MH. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

In Memoriam: Mats Morell

In Memoriam: Mats Morell

ZNAČAJ ISTRAŽIVANJA ISTORIJSKOG PROCESA REVALORIZIRANJA NACIONALNOG IDENTITETA MUSLIMANA U SOCIJALISTIČKOJ JUGOSLAVIJI (1956–1971) / THE IMPORTANCE OF RESEARCHING THE HISTORICAL PROCESS OF REVALUATING THE MUSLIMS' NATIONAL IDENTITY IN SOCIALIST YUGOSLAVIA

After defending her doctoral dissertation at Uppsala University in 2016, Dr. Iva Lučić edited the book In the Name of the Nation, translated from German into Bosnian by professor Sulejman Bosto. The book presents a comprehensive historical research of the genesis of the Muslim nation recognition in socialist Yugoslavia during the period 1956–1971. Based on the study of archival material in the institutions of the Yugoslav Federation and the Socialist Republic of Bosnia and Herzegovina, as well as an insight into the reference literature, Dr. Iva Lučić scientifically elaborates one of the crucial historical questions for the development of Bosnia and Herzegovina’s statehood. It is about the recognition of the Muslim’s national subjectivity, which during the several decades course led to a positive historical outcome at the Central Committee of the League of Communists of Bosnia and Herzegovina’s 17th Session and at the implementation of the Yugoslav population census of 1971. In the book’s final part, Dr. Iva Lučić does a comprehensive historical and sociological-political synthesis of the wholeness of her research. The scientific findings released by Dr. Iva Lučić represent a contribution to the study and establishment of contemporary political history of Bosnia and Herzegovina in the 20th century.

Signet Ring Cell Colorectal and Appendiceal Cancer: A Small Signet Ring Cell Component Is Also Associated with Poor Outcome.

Colorectal signet ring cell (SRC) carcinoma with ≥50% SRCs (SRC ≥ 50) has a poor prognosis, but the prognostic role of SRCs < 50% (SRC < 50) is unclear. The aim of this study was to provide a clinicopathological characterization of SRC colorectal and appendiceal tumours and analyse the importance of the SRC component size. All patients in the Swedish Colorectal Cancer Registry diagnosed with colorectal or appendiceal cancer in 2009-2020 at Uppsala University Hospital, Sweden, were included. The SRCs were verified, and the components estimated by a gastrointestinal pathologist. Of the 2229 colorectal cancers, 51 (2.3%) had SRCs, with a median component size of 30% (interquartile range of 12.5-40) and 10 (0.45%) had SRC ≥ 50. The SRC tumours were primarily localized in the right colon (59%) and appendix (16%). No patients with SRCs had stage I disease, and 26 (51%) had stage IV, of whom, 18 (69%) had peritoneal metastases. The SRC tumours were often high grade with perineural and vascular invasion. The 5-year overall survival (OS) rate for patients with SRC ≥ 50 were 20% (95% confidence interval (CI) 6-70), for SRC < 50, 39% (95% CI 24-61); and for non-SRCs, 55% (95% CI 55-60). Among the patients with SRC < 50 and <50% extracellular mucin, the 5-year OS was 34% (95% CI 19-61), while those with ≥50% extracellular mucin had an OS of 50% (95% CI 25-99). The 5-year recurrence-free survival rates were 51% (95% CI 13-83) for patients with SRC tumours, as compared to 83% (95% CI 77-89) and 81% (95% CI 79-84) for mucinous and non-mucinous adenocarcinoma, respectively. The presence of SRCs was strongly associated with aggressive clinicopathological features, peritoneal metastases, and poor prognosis, also when they make up <50% of a tumour.

Notes on Contributors

Previous article FreeNotes on ContributorsPDFPDF PLUSFull Text Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinked InRedditEmailQR Code SectionsMoreAshley Shaw received his PhD from University College London and is currently a Leverhulme Early Career Fellow at the University of Leeds. His primary research interests are in the philosophy of mind and action, in particular, the nature of desire, rational agency, and reasons for action. He is working on a book on desire alongside a project on the nature of need. [email protected]Nils-Hennes Stear is a Humboldt Fellow at the University of Hamburg and incoming associate lecturer in philosophy at Uppsala University. His research focuses include aesthetics, ethics, feminist philosophy, and their intersections. He is writing a book on the relationship between ethical and aesthetic value in artworks. [email protected]Teemu Toppinen is a tenure-track professor at the unit of philosophy, history, and literary studies at the University of Tampere and a visiting researcher at the University of Helsinki. His research interests often revolve around expressivism but include all sorts of issues related to normativity. [email protected]Vilma Venesmaa is a PhD student in practical philosophy at the University of Helsinki. Her doctoral thesis focuses on the issue of explaining our knowledge of normative supervenience. [email protected]Robin Zheng is a lecturer in philosophy at the University of Glasgow. Her research spans moral psychology, political philosophy, and the philosophies of race and gender. It addresses questions of responsibility, solidarity, and injustice, among other things. [email protected] Previous article DetailsFiguresReferencesCited by Ethics Volume 133, Number 3April 2023 Article DOIhttps://doi.org/10.1086/723252 Views: 83Total views on this site © 2023 The University of Chicago. All rights reserved.PDF download Crossref reports no articles citing this article.

Chilean feminist collective LASTESIS: Performative and viral agency

The purpose of this article is to explore and reflect on the concept of performative agency and feminism applying Haraway’s Cyborg analytical model to the creative work of Chilean artistic collective LASTESIS as a case study. Based on a review of the literature, the article examines the concept of performative feminist agency and how this agency functioned in artistic and political action in more than fifty countries around the world. The data includes class lectures from the course digital media, participation and agency at Uppsala University, previous research about the performance Un violador en tu camino (A Rapist in Your Path) by the Chilean feminist collective LASTESIS, other studies into performative agency, and LASTESIS zoom conferences. The collected data leads to the analysis of the following four themes: feminism, language, participation and agency. These topics are important for comprehending how performative agency can empower individuals to speak out against injustices. Methods of inquiry included phenomenological reflection on data elicited by feminism, agency and language. These findings have important implications for the broader domain of participation and agency. The theoretical lens provided an overall orientation, using the speech act theory and the sociotechnical theory, transformative perspectives that shaped the questions asked, providing a call for action. Haraway’s Cyborg analytical model helped to guide as to what issues are important to examine. The study did not find any other case as ‘complete’ as A Rapist in Your Path, meaning the theory behind the production and how it went viral around the world; but a comparative study case was not the focus. This study attempts to contribute to the knowledge exploring the influence of participation, language and feminism on performative agency.

Correction to: Mortality and Cardiovascular Outcomes in Patients Presenting With Non-ST Elevation Myocardial Infarction Despite No Standard Modifiable Risk Factors: Results From the SWEDEHEART Registry.

HomeJournal of the American Heart AssociationVol. 12, No. 7Correction to: Mortality and Cardiovascular Outcomes in Patients Presenting With Non‐ST Elevation Myocardial Infarction Despite No Standard Modifiable Risk Factors: Results From the SWEDEHEART Registry Open AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessCorrectionPDF/EPUBCorrection to: Mortality and Cardiovascular Outcomes in Patients Presenting With Non‐ST Elevation Myocardial Infarction Despite No Standard Modifiable Risk Factors: Results From the SWEDEHEART Registry Originally published28 Mar 2023https://doi.org/10.1161/JAHA.121.027668Journal of the American Heart Association. 2023;12:e027668This article corrects the followingMortality and Cardiovascular Outcomes in Patients Presenting With Non–ST Elevation Myocardial Infarction Despite No Standard Modifiable Risk Factors: Results From the SWEDEHEART RegistryOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: March 28, 2023: Ahead of Print In the article by Gemma A. Figtree et al, “Mortality and Cardiovascular Outcomes in Patients Presenting With Non‐ST Elevation Myocardial Infarction Despite No Standard Modifiable Risk Factors: Results From the SWEDEHEART Registry,” which published on July 25, 2022, and appeared in the August 2, 2022, issue of the Journal (J Am Heart Assoc. 2022;11:e024818. DOI: 10.1161/JAHA.121.024818), a correction was needed.The affiliation for Dr Hagström was incorrect in the published version of the article. On page 12, under the Affiliations heading, Dr Hagström's affiliation has been updated as follows:Department of Medical Sciences, Uppsala University, Uppsala, Sweden (N.H., J.S., E.H.)The authors regret the error.The online version of the article has been updated and is available here: https://www.ahajournals.org/doi/10.1161/JAHA.121.024818. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesMortality and Cardiovascular Outcomes in Patients Presenting With Non–ST Elevation Myocardial Infarction Despite No Standard Modifiable Risk Factors: Results From the SWEDEHEART RegistryGemma A. Figtree, et al. Journal of the American Heart Association. 2022;11 April 4, 2023Vol 12, Issue 7Article InformationMetrics Copyright © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.121.027668PMID: 36974762 Originally publishedMarch 28, 2023 PDF download

Ex vivo assessment of chemotherapy sensitivity of colorectal cancer peritoneal metastases.

Patients with peritoneal metastasis from colorectal cancer (PMCRC) may have a chance of cure when treated with cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC)1–5. Choice of chemotherapy for HIPEC has been based on knowledge of its systemic effects, pharmacokinetics, technical feasibility, hyperthermic efficacy enhancement, and tolerance6–8. Selection of cancer drugs for treatment based on phenotypical assessment of patient cancer cell drug sensitivity ex vivo is one approach to personalized cancer treatment. One technique for this is the fluorometric microculture cytotoxicity assay (FMCA) that has been used in drug development and for the development of personalized cancer medicine9–16. This study investigated whether ex vivo assessment of drug sensitivity by the FMCA provides predictive information in terms of peritoneal recurrence-free survival (PRFS) and overall survival (OS) in patients treated with CRS and HIPEC for isolated PMCRC. The patient cohort for this study was from a prospectively maintained institutional database at the Uppsala University Hospital, a tertiary care unit for PMCRC in Uppsala, Sweden. Patients with PMCRC treated with CRS and HIPEC have been registered since 2003. Ex vivo drug sensitivity testing using the FMCA started in April 2007. Thus, consecutive patients treated with CRS and HIPEC for PMCRC from April 2007 to October 2018 were considered for providing data for this report. Patients underwent HIPEC with either single-drug oxaliplatin, mitomycin C, or irinotecan, or a combination of oxaliplatin and irinotecan. HIPEC was performed in an open manner according to the coliseum method. Single-drug oxaliplatin was dosed at 350–460 mg/m2, and oxaliplatin and irinotecan combined at 360 mg/m2 for both drugs. These treatments lasted for 30 min. Mitomycin C was dosed at 35 mg/m2 divided into three injections with 50 per cent given at time 0, 25 per cent at 30 min, and 25 per cent at 60 min from the start of HIPEC for a total of 90 min. Follow-up data on PRFS and OS were collected for the final analysis. The Uppsala University ethical committee approved the study (Dnr 2007/237 for tumour sampling and ex vivo assessment of drug activity, and Dnr 2013/203 for clinical data collection).

Antithrombotic agent usage before ictus in aneurysmal subarachnoid hemorrhage: relation to hemorrhage severity, clinical course, and outcome

BackgroundThe number of patients with aneurysmal subarachnoid hemorrhage (aSAH) who are on antithrombotic agents before ictus is rising. However, their effect on early brain injury and disease development remains unclear. The primary aim of this study was to determine if antithrombotic agents (antiplatelets and anticoagulants) were associated with a worse initial hemorrhage severity, rebleeding rate, clinical course, and functional recovery after aSAH.MethodsIn this observational study, those 888 patients with aSAH, treated at the neurosurgical department, Uppsala University Hospital, between 2008 and 2018 were included. Demographic, clinical, radiological (Fisher and Hijdra score), and outcome (Extended Glasgow Outcome Scale one year post-ictus) variables were assessed.ResultsOut of 888 aSAH patients, 14% were treated with antithrombotic agents before ictus. Seventy-five percent of these were on single therapy of antiplatelets, 23% on single therapy of anticoagulants, and 3% on a combination of antithrombotic agents. Those with antithrombotic agents pre-ictus were significantly older and exhibited more co-morbidities and a worse coagulation status according to lab tests. Antithrombotic agents, both as one group and as subtypes (antiplatelets and anticoagulants), were not associated with hemorrhage severity (Hijdra score/Fisher) nor rebleeding rate. The clinical course did not differ in terms of delayed ischemic neurological deficits or last-tier treatment with thiopental and decompressive craniectomy. These patients experienced a higher mortality and lower rate of favorable outcome in univariate analyses, but this did not hold true in multiple logistic regression analyses after adjustment for age and co-morbidities.ConclusionsAfter adjustment for age and co-morbidities, antithrombotic agents before aSAH ictus were not associated with worse hemorrhage severity, rebleeding rate, clinical course, or long-term functional recovery.

Letter's to the editor.

Journal Article Accepted manuscript Letter’s to the editor Get access Thierry Soussi Thierry Soussi Dept of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Clinical Genetics, Uppsala University Hospital, SE-751 85 Uppsala, SwedenHematopoietic and Leukemic Development team, UMRS_938, Sorbonne Université, Centre de Recherche Saint-Antoine 75012 Paris, Paris France Corresponding author: thierry.soussi@sorbonne-universite.fr https://orcid.org/0000-0001-8184-3293 Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, ddad037, https://doi.org/10.1093/hmg/ddad037 Published: 10 March 2023 Article history Received: 08 January 2023 Revision received: 26 February 2023 Published: 10 March 2023

The impact on postoperative outcomes of intraoperative fluid management strategies during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

BackgroundThe impact of intraoperative fluid management during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on postoperative outcomes has been poorly investigated. This study aimed to retrospectively evaluate the impact of intraoperative fluid management strategy on postoperative outcomes and survival. Methods509 patients undergoing CRS and HIPEC at Uppsala University Hospital/Sweden 2004–2017 were categorized into two groups according to the intraoperative fluid management strategy: pre-goal directed therapy (pre-GDT) and goal directed therapy (GDT), where a hemodynamic monitor (CardioQ or FloTrac/Vigileo) was used to optimize fluid management. Impact on morbidity, postoperative hemorrhage, length-of-stay and survival was analyzed. ResultsThe pre-GDT group received higher fluid volume compared to the GDT group (mean 19.9 vs. 16.2 ml/kg/h, p < 0.001). Overall postoperative morbidity Grade III-V was higher in the GDT group (30% vs. 22%, p = 0.03). Multivariable adjusted odds ratio (OR) for Grade III-V morbidity was 1.80 (95%CI 1.10–3.10, p = 0.02) in the GDT group. Numerically, more cases of postoperative hemorrhage were found in the GDT group (9% vs. 5%, p = 0.09), but no correlation was observed in the multivariable analysis 1.37 (95%CI 0.64–2.95, p = 0.40). An oxaliplatin regimen was a significant risk factor for postoperative hemorrhage (p = 0.03). Mean length of stay was shorter in the GDT group (17 vs. 26 days, p < 0.0001). Survival did not differ between the groups. ConclusionWhile GDT increased the risk for postoperative morbidity, it was associated with shortened hospital stay. Intraoperative fluid management during CRS and HIPEC did not affect the postoperative risk for hemorrhage, while the use of an oxaliplatin regimen did.

O.16.3 - Pharmacists' experiences of using a QPL to improve patient activation during dispensing of medicines: Presenter(s): Karin Svensberg, Uppsala University, Sweden

O.16.3 - Pharmacists' experiences of using a QPL to improve patient activation during dispensing of medicines: Presenter(s): Karin Svensberg, Uppsala University, Sweden

O.26.2 - Shared decision-making in goal-setting: from clinical dietitians’ and patients’ perspectives: Presenter(s): Lina Aladili, Uppsala University, Sweden

O.26.2 - Shared decision-making in goal-setting: from clinical dietitians’ and patients’ perspectives: Presenter(s): Lina Aladili, Uppsala University, Sweden

Economic Consequences of Surgery for Adhesive Small Bowel Obstruction: A Population-Based Study.

Most patients develop adhesions after abdominal surgery, some will be hospitalized with small bowel obstruction (SBO), and some also require surgery. The operations and follow-up are expensive, but recent data of costs are scarce. The aim of this study was to describe the direct costs of SBO-surgery and follow-up, in a population-based setting. The association between cost of SBO and peri- and postoperative data was also studied. In a retrospective cohort study, all patients (n = 402) operated for adhesive SBO in Gävleborg and Uppsala counties (2007-2012) were studied. The median follow-up was 8 years. Costs were calculated according to the pricelist of Uppsala University Hospital, Uppsala, Sweden. Overall total costs were €16.267 million, corresponding to a mean total cost per patient of €40,467 during the studied period. Diffuse adhesions and postoperative complications were associated with increased costs for SBO in a multivariable analysis (P < 0.001). Most costs, about €14 million (85%), arouse in conjunction with the SBO-index surgery period. In-hospital stay was the dominating cost, accounting for 70% of the total costs. Surgery for SBO generates substantial economic burden for healthcare systems. Measures that reduce the incidence of SBO, the frequency of postoperative complication, or the length of stay have the potential to reduce this economic burden. The cost estimates from this study may be valuable for future cost-benefit analyses in intervention studies.

The relationship between self-control and symptoms of anxiety and depression in patients with eating disorders: a cross-sectional study including exploratory longitudinal data

BackgroundPersonality style can partly be described as the way an individual controls and regulates emotions and can be divided into over- and undercontrol. Studies have indicated that personality style may impact the onset, clinical presentation, and recovery from an eating disorder (ED). Furthermore, symptoms of anxiety and depression are common in patients with EDs. However, the association between self-control levels and anxiety/depression symptoms in patients with EDs remains unknown. The main aim of this study was to assess how levels of self-control relate to anxiety/depression symptoms in patients with EDs, with a secondary, exploratory aim to assess the stability of self-control during treatment.MethodsPatients were recruited from the outpatient ED clinic at the Uppsala University Hospital, between October 2014 and December 2019. In total, 227 patients (age: 25.4, SD: 7.1) were included at the start of their treatment, with 14 participants also completing post-treatment measurements. Self-control was assessed with the Ego Undercontrol scale (EUC-13), anxiety/depression symptoms with the Hopkins Symptoms Checklist (HSCL-25), and ED diagnosis and symptoms with the Eating Disorder Examination Interview (EDE-I) and Questionnaire (EDE-Q), respectively.ResultsA quadratic regression (n = 227) showed that levels of self-control accounted for about four percent of the variance in degree of global anxiety/depressive symptoms. Anxiety/depression symptoms were better explained by ED symptoms (R2 = 0.24). Visualizations in boxplots revealed a tendency for extreme values of both over- and undercontrol to be associated with higher levels of depression, whereas symptoms of anxiety increased with increasing undercontrol. In the exploratory analyses (n = 14) levels of self-control remained more stable than symptoms of anxiety and depression, which decreased significantly during ED treatment.ConclusionsOur results indicated that anxiety/depression symptoms, in patients with EDs, were not strongly correlated with levels of self-control, but rather with ED symptoms. However, extreme values of both over- and undercontrol showed a tendency to be associated with higher levels of depression symptoms, whereas anxiety symptoms increased with increasing levels of undercontrol. Future studies could benefit from considering both over- and undercontrol as potentially dysfunctional.

Study protocol: The cross-sectional Uppsala weight gain in pregnancy study (VIGA study).

More than two in five Swedish women are overweight or obese when becoming pregnant. Maternal overweight or obesity and excessive pregnancy weight gain are associated with several adverse pregnancy outcomes. The underlying mechanisms that link maternal adiposity, diet, exercise, pregnancy weight gain with pregnancy outcome are incompletely understood. We describe the design for a cross-sectional study of pregnant women at Uppsala University Hospital, Sweden. All participants delivered by elective cesarean section before the onset of labor. At inclusion, participants answered two questionnaires concerning their dietary and exercise habits. Fasting maternal blood samples (buffy coat, plasma, serum) were collected. During the cesarean section, biopsies of maternal subcutaneous and visceral adipose tissues were obtained. Placental tissue was collected after delivery. All biological samples were processed as soon as possible, frozen on dry ice, and stored at -70 °C. Pregnancy outcomes and supplementary maternal characteristics were collected from medical records. In total, 143 women were included in the study. Of these women, 33.6% were primiparous, 46.2% had a pre-pregnancy body mass index (BMI) over 25 kg/m2, and 11.2% of the offspring were born large for gestational age (LGA). Complete collection, that is both questionnaires and all types of biological samples, was obtained from 81.1% of the participants. This study is expected to provide a resource for exploration of the associations between maternal weight, diet, exercise, pregnancy weight gain, and pregnancy outcome. Results from this study will be published in peer-reviewed, international scientific journals. This study was approved by the Regional Ethics Review Board in Uppsala (approval no 2014/353) and with an amendment by the Swedish Ethical Review Authority (approval no 2020-05844).

Risk factors for incident open-angle glaucoma in clinical practice in Sweden: A population-based case-control study.

To study predictors of open-angle glaucoma (OAG) in newly diagnosed patients detected in clinical practice in a defined population and to estimate the frequency of normal-tension glaucoma (NTG). Predictors of OAG were analysed in a case-control study, nested in a cohort of 481 people, 55-84 years of age, in two rural districts in Sweden, examined at the Eye Department in Tierp from 1988 to 2003. To make the sample complete, 63 residents first examined at the Uppsala University Hospital (UUH), 60 of whom were identified with the help of registers, were invited to attend the study. In this way, the cohort included 544 individuals. Automated perimetry was used to find cases of OAG. In people first examined in Tierp, incident OAG was found in 99 subjects. Of these cases, six were diagnosed with NTG. Increased intraocular pressure (IOP), higher age, male sex, a positive family history, pseudoexfoliation (PEX), and haemorrhages of the optic disc were associated with OAG. In a logistic regression model including PEX, every increase in IOP by 5 mmHg increased the risk for OAG four-fold (odds ratio 4.04; 95% confidence interval 2.91-5.62). The effect of PEX was essentially mediated by increased pressure. The inclusion of the 63 subjects first examined at the UUH had no impact on the results. In this study on patients aged 55-84-years old in clinical practice in Sweden, increased IOP was strongly associated with incident OAG, while NTG was a rare finding.

Antibiotic use during coronavirus disease 2019 intensive care unit shape multidrug resistance bacteriuria: A Swedish longitudinal prospective study.

High frequency of antimicrobial prescription and the nature of prolonged illness in COVID-19 increases risk for complicated bacteriuria and antibiotic resistance. We investigated risk factors for bacteriuria in the ICU and the correlation between antibiotic treatment and persistent bacteria. We conducted a prospective longitudinal study with urine from indwelling catheters of 101 ICU patients from Uppsala University Hospital, Sweden. Samples were screened and isolates confirmed with MALDI-TOF and whole genome sequencing. Isolates were analyzed for AMR using broth microdilution. Clinical data were assessed for correlation with bacteriuria. Length of stay linearly correlated with bacteriuria (R2 = 0.99, p ≤ 0.0001). 90% of patients received antibiotics, primarily the beta-lactams (76%) cefotaxime, piperacillin-tazobactam, and meropenem. We found high prevalence of Enterococcus (42%) being associated with increased cefotaxime prescription. Antibiotic-susceptible E. coli were found to cause bacteriuria despite concurrent antibiotic treatment when found in co-culture with Enterococcus. Longer stays in ICUs increase the risk for bacteriuria in a predictable manner. Likely, high use of cefotaxime drives Enterococcus prevalence, which in turn permit co-colonizing Gram-negative bacteria. Our results suggest biofilms in urinary catheters as a reservoir of pathogenic bacteria with the potential to develop and disseminate AMR.

History of Ceremonial Conferments in Turku

&#x0D; &#x0D; &#x0D; The history of ceremonial conferments organised by European universities goes back to the Middle Ages, as bachelors were conferred as masters in Paris and Bologna already in the 13th century. From the European universities, the tradition of conferring academic degrees spread to Sweden, where the ceremony was first organised at the Uppsala University in 1600 and at the Royal Academy of Turku in 1643. At that time, Finland and Turku were part of the Swedish kingdom and the Royal Academy of Turku, founded in 1640, was the first university in Finland. This university was situated in Turku until the great fire of 1827, after which the university was moved to Helsinki, the new capital of Finland. Ceremonial conferments have been an important celebration for the community, as not only does the ceremony confer scholars as part of the academic community, but it also builds internal hierarchy and symbolism. &#x0D; &#x0D; &#x0D;

An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers.

Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression. Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations. By combining the prognostic information of anti-tumoural CD8+ lymphocytes and tumour supportive CD68+CD163+ macrophages in colorectal cancer we generated a signature of immune activation (SIA). The prognostic impact of SIA was independent of conventional parameters and comparable with the state-of-art immune score. The SIA was also associated with patient survival in oesophageal adenocarcinoma, bladder cancer, lung adenocarcinoma and melanoma, but not in endometrial, ovarian and squamous cell lung carcinoma. We identified CD68+CD163+ macrophages as the major producers of complement C1q, which could serve as a surrogate marker of this macrophage subset. Consequently, the RNA-based version of SIA (ratio of CD8A to C1QA) was predictive for survival in independent RNAseq data sets from these six cancer types. Finally, the CD8A/C1QA mRNA ratio was also predictive for the response to checkpoint inhibitor therapy. Our findings extend current concepts to procure prognostic information from the tumour immune microenvironment and provide an immune activation signature with high clinical potential in common human cancer types. Swedish Cancer Society, Lions Cancer Foundation, Selanders Foundation, P.O. Zetterling Foundation, U-CAN supported by SRA CancerUU, Uppsala University and Region Uppsala.