Upsala journal of medical sciences最新文献

{"title":"Toward a granular molecular-anatomic map of the blood vasculature - single-cell RNA sequencing makes the leap.","authors":"Christer Betsholtz","doi":"10.48101/ujms.v127.9051","DOIUrl":"https://doi.org/10.48101/ujms.v127.9051","url":null,"abstract":"<p><p>Single-cell RNA sequencing (scRNAseq) marks the birth of a new era in physiology and medicine. Within foreseeable future, we will know exactly what genes are expressed - and at what levels - in all the different cell types and subtypes that make up our bodies. We will also learn how a particular cell state, whether it occurs during development, tissue repair, or disease, reflects precise changes in gene expression. While profoundly impacting all areas of life science, scRNAseq may lead to a particular leap in vascular biology research. Blood vessels pervade and fulfill essential functions in all organs, but the functions differ. Innumerable organ-specific vascular adaptations and specializations are required. These, in turn, are dictated by differential gene expression by the two principal cellular building blocks of blood vessels: endothelial cells and mural cells. An <i>organotypic</i> vasculature is essential for functions as diverse as thinking, gas exchange, urine excretion, and xenobiotic detoxification in the brain, lung, kidney, and liver, respectively. In addition to the organotypicity, vascular cells also differ along the vascular arterio-venous axis, referred to as <i>zonation</i>, differences that are essential for the regulation of blood pressure and flow. Moreover, gene expression-based molecular changes dictate states of <i>cellular activity</i>, necessary for angiogenesis, vascular permeability, and immune cell trafficking, i.e. functions necessary for development, inflammation, and repair. These different levels of cellular heterogeneity create a nearly infinite phenotypic diversity among vascular cells. In this review, I summarize and exemplify what scRNAseq has brought to the picture in just a few years and point out where it will take us.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40446746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ulcerative colitis progression: a retrospective analysis of disease burden using electronic medical records.","authors":"David Dahlgren,&nbsp;Lars Agréus,&nbsp;Jan Stålhammar,&nbsp;Per M Hellström","doi":"10.48101/ujms.v127.8833","DOIUrl":"https://doi.org/10.48101/ujms.v127.8833","url":null,"abstract":"Background Ulcerative colitis (UC) is a debilitating inflammatory bowel disease. Present knowledge regarding UC disease progression over time is limited. Objective To assess UC progression to severe disease along with disease burden and associated factors. Methods Electronic medical records linked with Swedish national health registries (2005–2015) were used to identify disease progression of UC. Odds of all-cause and disease-related hospitalization within 1 year were compared between patients with disease progression and those without. Annual indirect costs were calculated based on sick leave, and factors related to UC progression were examined. Results Of the 1,361 patients with moderate UC, 24% progressed to severe disease during a median of 5.2 years. Severe UC had significantly higher odds for all-cause (OR [odds ratio] 1.47, 95% CI [confidence interval]: 1.12–1.94, P < 0.01) and UC-related hospitalization (OR 2.47, 95% CI: 1.76–3.47, P < 0.0001) compared to moderate disease. Average sick leave was higher in patients who progressed compared to those who did not (64.4 vs 38.6 days, P < 0.001), with higher indirect costs of 151,800 SEK (16,415 €) compared with 92,839 SEK (10,039 €) (P < 0.001), respectively. UC progression was related to young age (OR 1.62, 95% CI: 1.17–2.25, P < 0.01), long disease duration (OR 1.09, 95% CI: 1.03–1.15, P < 0.001), and use of corticosteroids (OR 2.49, 95% CI: 1.67–3.72, P < 0.001). Conclusion Disease progression from moderate to severe UC is associated with more frequent and longer hospitalizations and sick leave. Patients at young age with long disease duration and more frequent glucocorticosteroid medication are associated with progression to severe UC.","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2022-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40446747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular tools to monitor health and disease - and lucky coincidences.","authors":"Ulf Landegren","doi":"10.48101/ujms.v127.8987","DOIUrl":"https://doi.org/10.48101/ujms.v127.8987","url":null,"abstract":"<p><p>Improved methods for molecular analyses are obviously central for medical research. I will describe herein our work developing tools to reveal molecular states in health and disease. I will recount how I got started in this endeavor, and how our early work characterizing genetic variation led onto high-throughput protein measurements and to techniques for imaging the distribution of proteins and their activity states in tissues. I will also describe a more recent technique to measure even exceedingly rare genetic variants in order to monitor recurrence of disease for tumor patients.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40456245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-based diagnosis of systemic amyloidosis: Experience of the informal diagnostic center at Uppsala University Hospital.","authors":"Justina Damjanovic Vesterlund,&nbsp;Elisabet Ihse,&nbsp;Ulrika Thelander,&nbsp;Alice Zancanaro,&nbsp;Gunilla T Westermark,&nbsp;Per Westermark","doi":"10.48101/ujms.v127.8913","DOIUrl":"https://doi.org/10.48101/ujms.v127.8913","url":null,"abstract":"Diagnosis of systemic amyloidosis is a clinical challenge and usually relies on a tissue biopsy. We have developed diagnostic methods based on the presence of amyloid deposits in abdominal subcutaneous fat tissue. This tissue is also used to determine the biochemical type of amyloidosis, performed by western blot and immunohistochemical analyses with the aid of in-house developed rabbit antisera and mouse monoclonal antibodies. Mass spectrometric methods are under development for selected cases. The diagnostic outcome for 2018-2020 was studied. During this period, we obtained 1,562 biopsies, of which 1,397 were unfixed subcutaneous fat tissue with varying degrees of suspicion of systemic amyloidosis. Of these, 440 contained amyloid deposits. The biochemical nature of the amyloid was determined by western blot analysis in 319 specimens and by immunohistochemistry in further 51 cases.","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2022-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40456246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are off-target effects of imatinib the key to improving beta-cell function in diabetes?","authors":"Nils Welsh","doi":"10.48101/ujms.v127.8841","DOIUrl":"https://doi.org/10.48101/ujms.v127.8841","url":null,"abstract":"<p><p>The small tyrosine kinase (TK) inhibitor imatinib mesylate (Gleevec, STI571) protects against both type 1 and type 2 diabetes, but as it inhibits many TKs and other proteins, it is not clear by which mechanisms it acts. This present review will focus on the possibility that imatinib acts, at least in part, by improving beta-cell function and survival via off-target effects on beta-cell signaling/metabolic flow events. Particular attention will be given to the possibility that imatinib and other TK inhibitors function as inhibitors of mitochondrial respiration. A better understanding of how imatinib counteracts diabetes will possibly help to clarify the pathogenic role of beta-cell signaling events and mitochondrial function, and hopefully leading to improved treatment of the disease.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2022-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40391896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of COVID-19 on patients treated with autologous hematopoietic stem cell transplantation: A retrospective cohort study.","authors":"Thomas Silfverberg,&nbsp;Björn Wahlin,&nbsp;Kristina Carlson,&nbsp;Honar Cherif","doi":"10.48101/ujms.v127.8611","DOIUrl":"https://doi.org/10.48101/ujms.v127.8611","url":null,"abstract":"<p><strong>Objective: </strong>To describe how coronavirus disease 2019 (COVID-19) affects patients with hematological malignancies treated with autologous hematopoietic stem cell transplantation (ASCT).</p><p><strong>Methods: </strong>This retrospective observational cohort study includes all patients with hematological malignancies treated with ASCT in Sweden from 1 January 2020 to 31 December 2020. Patients who subsequently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) until 31 March 2021 were analyzed for morbidity, mortality, need for supportive care, and risk factors related to COVID-19.</p><p><strong>Results: </strong>This study identified 442 patients who underwent ASCT in Sweden in 2020, among whom 20 (4.5%) subsequently tested positive for COVID-19. The overall mortality was 15%, and the COVID-19-related mortality was 10% among the patients who contracted COVID-19. Six (35%) patients were hospitalized, of which four (24%) needed supplementary oxygen and two (12%) needed intensive care. The absolute risk of COVID-19-related mortality was 0.45%.</p><p><strong>Conclusions: </strong>ASCT patients have a higher risk of severe outcome of COVID-19 compared to the normal population. However, the risks of death, inpatient care, oxygen therapy, and intensive care seem lower in this study compared to previous studies, possibly due to fewer mildly ill patients in other studies. The risk of contracting SARS-CoV-2 appears to be comparable to that in the general population. This study suggests that the COVID-19 pandemic is not a strong argument for refraining from ASCT in the case of hematological malignancy.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9447418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40367648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of post-COVID-19 and the impact of persistent symptoms in non-hospitalized patients 12 months after COVID-19, with a focus on work ability.","authors":"Marta A Kisiel,&nbsp;Helena Janols,&nbsp;Tobias Nordqvist,&nbsp;Jonas Bergquist,&nbsp;Simone Hagfeldt,&nbsp;Andrei Malinovschi,&nbsp;Magnus Svartengren","doi":"10.48101/ujms.v127.8794","DOIUrl":"https://doi.org/10.48101/ujms.v127.8794","url":null,"abstract":"<p><strong>Background: </strong>Better knowledge of long-term symptoms following coronavirus disease 2019 (COVID-19), the so-called post-COVID-19, in non-hospitalized patients is needed. The aim of this study was to study persisent symptoms up to 12 months after COVID-19 in non-hospitalized patients and their impact on work ability. We also investigated predictors of persistent symptoms.</p><p><strong>Methods: </strong>This study encompassed non-hospitalized adult subjects with a COVID-19 infection confirmed via positive nasopharyngeal swab polymerase chain reaction test during the first wave of the pandemic in Uppsala, Sweden. In total, 566 subjects were sent a survey via e-mail or post with an invitation to participate in the survey 12 months post-diagnosis. The majority of subjects were healthcare workers, as this group was prioritized for testing.</p><p><strong>Results: </strong>A total of 366 subjects responded, with 47% reporting persistent symptoms 12 months after their COVID-19 diagnosis. The most commonly reported symptoms at this time were impaired sense of smell and/or taste and fatigue. Among the predictors of persistent symptoms were being born abroad, lower physical fitness compared with peers before COVID-19, body mass index >25 kg/m², cooccurrence of hypertension and chronic pain, and having more than seven of the general COVID-19 symptoms at the onset. Respondents with symptoms after 12 months self-reported negatively about their general health and work ability.</p><p><strong>Conclusions: </strong>This study indicated that many people who had mild COVID-19 might have a variety of long-term symptoms. It highlights the importance of considering work ability after mild COVID-19.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2022-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9383047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40645606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive behavioral treatment for disordered gaming and problem gambling in adolescents: a pilot feasibility study.","authors":"Frida André,&nbsp;Isak Einarsson,&nbsp;Elisabeth Dahlström,&nbsp;Katalin Niklasson,&nbsp;Anders Håkansson,&nbsp;Emma Claesdotter-Knutsson","doi":"10.48101/ujms.v127.8693","DOIUrl":"https://doi.org/10.48101/ujms.v127.8693","url":null,"abstract":"<p><strong>Background: </strong>Disordered gaming and problem gambling (DG/PG) are associated with a range of functional impairments as well as psychiatric comorbidity. With the proliferation of digital gaming apps aimed at children and adolescents, which involve in-game purchases, there is increasing evidence that DG/PG are on the rise in this age range. The behavior can be detected in youth presenting at school-based health clinics and community psychiatric clinics. Cognitive behavioral therapy (CBT) is one of several recommended treatments for adults, but little evidence is available for the efficacy of this approach in adolescents with DG/PG.</p><p><strong>Aim: </strong>To evaluate the acceptability and feasibility of a CBT-based intervention developed for adolescents with DG/PG, which can be delivered in routine psychiatric care facilities.</p><p><strong>Methods: </strong>Adolescents who were patients at a child and adolescent psychiatry service were screened for DG/PG. Those aged 12-17 years with pronounced symptoms were invited to participate in a 7-week CBT program called Relapse Prevention. Nine adolescents agreed to participate and five consented to repeated assessments of outcome (pre-, post-treatment, and 6-month follow-up). In addition to acceptability and satisfaction with treatment, symptoms of DG were assessed with standardized interview and self-report measures.</p><p><strong>Results: </strong>There were no dropouts from the treatment. Participants who completed treatment and all outcome assessments reported satisfaction with the treatment. The participants showed fewer symptoms of DG after treatment, and the proportion who met criteria for computer game addiction decreased from 56 to 0%. There was no reduction in the number of participants who met criteria for PG.</p><p><strong>Conclusion: </strong>This study provides preliminary evidence for the acceptability and feasibility of a CBT-based intervention for DG/PG in adolescents. Preliminary data suggest that the treatment may be effective for DG but not PG. Further studies are needed to evaluate the efficacy of this approach for both conditions.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2022-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9383045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40645605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Misinterpretations of P-values and statistical tests persists among researchers and professionals working with statistics and epidemiology.","authors":"Per Lytsy,&nbsp;Mikael Hartman,&nbsp;Ronnie Pingel","doi":"10.48101/ujms.v127.8760","DOIUrl":"https://doi.org/10.48101/ujms.v127.8760","url":null,"abstract":"<p><strong>Background: </strong>The aim was to investigate inferences of statistically significant test results among persons with more or less statistical education and research experience.</p><p><strong>Methods: </strong>A total of 75 doctoral students and 64 statisticians/epidemiologist responded to a web questionnaire about inferences of statistically significant findings. Participants were asked about their education and research experience, and also whether a 'statistically significant' test result (<i>P</i> = 0.024, α-level 0.05) could be inferred as proof or probability statements about the truth or falsehood of the null hypothesis (H₀) and the alternative hypothesis (H₁).</p><p><strong>Results: </strong>Almost all participants reported having a university degree, and among statisticians/epidemiologist, most reported having a university degree in statistics and were working professionally with statistics. Overall, 9.4% of statisticians/epidemiologist and 24.0% of doctoral students responded that the statistically significant finding proved that H₀ is not true, and 73.4% of statisticians/epidemiologists and 53.3% of doctoral students responded that the statistically significant finding indicated that H₀ is improbable. Corresponding numbers about inferences about the alternative hypothesis (H₁) were 12.0% and 6.2% about proving H₁ being true and 62.7 and 62.5% for the conclusion that H₁ is probable. Correct inferences to both questions, which is that a statistically significant finding cannot be inferred as either proof or a measure of a hypothesis' probability, were given by 10.7% of doctoral students and 12.5% of statisticians/epidemiologists.</p><p><strong>Conclusions: </strong>Misinterpretation of <i>P</i>-values and statistically significant test results persists also among persons who have substantial statistical education and who work professionally with statistics.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2022-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9383044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40645607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of musculoskeletal pain in patients with idiopathic pulmonary fibrosis: a review.","authors":"Svetlana Kašiković Lečić,&nbsp;Jovan Javorac,&nbsp;Dejan Živanović,&nbsp;Aleksandra Lovrenski,&nbsp;Dragana Tegeltija,&nbsp;Jelena Zvekić Svorcan,&nbsp;Jadranka Maksimović","doi":"10.48101/ujms.v127.8739","DOIUrl":"https://doi.org/10.48101/ujms.v127.8739","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic, and fatal interstitial lung disease (ILD) of unknown etiology that primarily affects the elderly. Patients with IPF suffer from a heavy symptom burden and usually have a poor quality of life. Dyspnea and dry cough are predominant symptoms of IPF. Although pain is not considered one of the main symptoms of IPF, it can occur for a variety of reasons, such as hypoxia, coughing, muscle and nerve damage, deconditioning, and steroid use. The prevalence of pain in IPF patients varies greatly, ranging from around 30 to 80%, with the prevalence being estimated mostly among patients in the end-of-life period. It manifests itself in the form of muscle pain, joint discomfort, or back and chest pain. Approaches to the treatment of chronic musculoskeletal pain in patients with IPF include pharmacological and non-pharmacological measures that are also important to optimize the treatment of other symptoms (dyspnea and cough) and the optimal treatment of comorbidities. Given the scarcity of data on this symptom in the literature, this article summarizes what is currently known about the etiology and treatment of musculoskeletal pain in IPF.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2022-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40659164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}