Upsala journal of medical sciences最新文献

{"title":"A light at the end of the tunnel - from mutation identification to a potential treatment for Alzheimer's disease.","authors":"Lars Lannfelt","doi":"10.48101/ujms.v128.10316","DOIUrl":"https://doi.org/10.48101/ujms.v128.10316","url":null,"abstract":"<p><p>Recent advances have driven the development of immunotherapies that act by either promoting or suppressing a patient's immune system to treat inflammation, autoimmune disease, cardiovascular disease, infectious diseases, and several cancers. In addition, research conducted over the past 25 years has identified therapeutic targets and indicated that immunotherapy could be used to treat Alzheimer's disease (AD). Despite a number of setbacks, this approach has now led to the development of the first disease-modifying treatments for this devastating disease. A key neuropathological feature of AD is the accumulation of a ~40-amino acid peptide known as amyloid β (Aβ) in the brain and cerebrovasculature. Our detection of an Aβ precursor protein mutation that caused early-onset AD in a Swedish family by enhancing Aβ protofibril formation sharpened the focus on soluble Aβ aggregates (oligomers and protofibrils) as viable therapeutic targets. Initial studies developed and tested a mouse monoclonal antibody (mAb158) with specific conformation-dependent binding to these soluble Aβ aggregates. Treatment with mAb158 selectively reduced Aβ protofibrils in the brain and cerebrospinal fluid of a transgenic mouse model of AD. A humanized version of mAb158 (lecanemab) subsequently entered clinical trials. Based on promising Phase 2 data showing plaque clearance and reduced cognitive decline, a Phase 3 trial found that lecanemab slowed decline on the primary cognitive endpoint by 27% over 18 months and also produced positive effects on secondary clinical endpoints and key biomarkers. In July 2023, the FDA granted lecanemab a full approval, and this therapeutic antibody will be marketed as Leqembi®. This represents a significant advance for patients with AD, although many challenges remain. In particular, it is now more important than ever to identify individuals who are vulnerable to AD, so that treatment can be initiated at an early stage in the disease process.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138809772","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":"Vitamin D status in longstanding type 1 diabetes and controls. Association with upper extremity impairments.","authors":"Hans J Arnqvist, Per Leanderson, Anna Spångeus","doi":"10.48101/ujms.v128.9888","DOIUrl":"10.48101/ujms.v128.9888","url":null,"abstract":"<p><strong>Background: </strong>Patients with type 1 diabetes have a high prevalence of upper extremity impairments (UEIs), such as frozen shoulder, carpal tunnel syndrome, and trigger finger. The UEIs are strongly associated with activity limitations and impaired quality of life. The etiology of the UEI is not clear. Vitamin D deficiency has been considered to play a role in the pathogenesis of type 1 diabetes and in the development of macro- and microvascular complications in diabetes.</p><p><strong>Aim: </strong>To characterize vitamin D status in a large population of patients with type 1 diabetes, if vitamin D deficiency is associated with metabolic factors and possible association with UEI.</p><p><strong>Material and methods: </strong>Patients who diagnosed before 35 years of age, whose diabetes duration >20 years, and who are not older than 65 years were invited to participate in this cross-sectional case-control, multicenter study. Controls matched for age and sex were obtained from the national population registry. Fasting blood samples were collected and stored at -80°C until analyzed regarding 25-hydroxy-vitamin D (25(OH)D3) by a liquid chromatographic-mass spectrometric method (LC-MS/MS).</p><p><strong>Results: </strong>Vitamin D levels varied with season as expected in the northern hemisphere. The association between 25(OH)D3 and clinical variables was analyzed in a univariate general linear model, which indicated no difference in 25(OH)D3 in men with and without diabetes but higher values in women with diabetes. About 30% of both patients and controls had vitamin D deficiency (≤50 nmol/L). Analyzed by binary logistic regression UEIs was not associated with 25(OH)D3 levels. In both patients and controls, 25(OH)D3 was correlated to apolipoprotein A1 (<i>r</i> = 0.153; 0.220, <i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>In patients with type 1 diabetes and a duration of 20 years or more, vitamin D level is not lower than in nondiabetic controls and is not associated with UEIs.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10710851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138809802","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":"Distribution of cup-disc ratio in a Swedish population.","authors":"Edvin Svedberg,&nbsp;Curt Ekström","doi":"10.48101/ujms.v128.9805","DOIUrl":"10.48101/ujms.v128.9805","url":null,"abstract":"<p><strong>Background: </strong>Increased cup-disc ratio (CDR) is a hallmark of open-angle glaucoma (OAG), an age-related neurodegenerative disease of significant importance for public health. There are few studies on the distribution of CDR in the Nordic populations.</p><p><strong>Methods: </strong>The distribution of CDR was studied in 749 subjects aged 65-74 years in a population survey in the rural district of Tierp, Sweden, from 1984 to 86. The optic discs were assessed with binocular ophthalmoscopy at a slit lamp. Drawings of the discs were made in the protocol and used for the calculation of vertical CDRs. Odds ratios, adjusted for age and sex, according to Mantel-Haenszel (OR_MH), were determined to estimate predictors of increased CDR, defined as a ratio in the upper quartile. For these analyses, the eye with the most advanced OAG or the highest pressure was chosen. Automated perimetry was used to identify OAG.</p><p><strong>Results: </strong>The distribution of vertical CDR was fairly close to that of other European-derived populations. The mean CDR was 0.45 in both eyes, with no difference between women and men. An increased ratio was associated with the age ≥70 years, a positive family history of OAG and intraocular pressure ≥20 mmHg. OAG increased the risk 8-fold (OR_MH 8.06; 95% CI 4.12-15.8).</p><p><strong>Conclusions: </strong>In this study, the distribution of CDR was fairly close to that of other European-derived populations. As expected, OAG increased the risk of having a CDR in the upper quartile. The CDR increased with age.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427253","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":"Persistent SARS-CoV-2 infection in patients with B-cell deficiency: a case series of successful antiviral treatment of four patients.","authors":"Lisa Faxén,&nbsp;Marie Edvinsson","doi":"10.48101/ujms.v128.9807","DOIUrl":"10.48101/ujms.v128.9807","url":null,"abstract":"<p><p>Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunocompromised patients remains a major medical challenge. Diagnosing the syndrome is difficult as symptoms may mimic other diseases and treatment guidelines are lacking. We describe a case series of four patients with persistent SARS-CoV-2 infection that all had an underlying B-cell deficiency due to rituximab treatment (in one case in combination with epcoritamab). In all four patients, it was initially difficult to recognize the persistent disease, leading to a duration of illness between 45 and 242 days. Two patients were only positive for SARS-CoV-2 by polymerase chain reaction (PCR) in the nasopharynx at the beginning of the disease but were later repeatedly negative. However, when bronchoalveolar lavage was performed, a positive SARS-CoV-2 PCR was revealed from the lower airways in both patients. The difficulties establishing diagnosis contributed to these two patients' long disease course. The longest disease duration was in the patient treated with rituximab and epcoritamab, who also responded poorly to single standard antiviral treatment. This patient ultimately cleared the infection after administering a combination treatment with remdesivir and nirmatrelvir/ritonavir. After a confirmed diagnosis, the other three patients cleared the infection when they were finally treated with antivirals. Increasing clinicians' awareness of this condition is important as it might be treatable once diagnosed. Further studies are warranted to define the condition and treatment strategy with greater precision.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10578053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238906","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":"Associations of spleen volume with markers of blood count and lipid profile in a large population-based study.","authors":"Muhammad Naeem,&nbsp;Till Ittermann,&nbsp;Marcello Ricardo Paulista Markus,&nbsp;Mohammed Farah Mahmoud Mousa,&nbsp;Laura von Heder,&nbsp;Robin Bülow,&nbsp;Marcus Dörr,&nbsp;Matthias Nauck,&nbsp;Ali Agdassi,&nbsp;Florian H Heidel,&nbsp;Henry Völzke","doi":"10.48101/ujms.v128.9785","DOIUrl":"10.48101/ujms.v128.9785","url":null,"abstract":"<p><strong>Background: </strong>The aim of our study was to investigate associations of spleen volume with blood count markers and lipid profile in the general population.</p><p><strong>Materials & methods: </strong>Cross-sectional data from 1,106 individuals aged 30-90 years from the population-based Study of Health in Pomerania (SHIP-START-2) were analyzed. Blood count markers included red blood cell (RBC) counts, hemoglobin, platelet count, and white blood cell (WBC) counts. Lipid profile included total-cholesterol, high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) as well as triglycerides. Linear regression models adjusted for age, sex, body height, and weight were used to associate standardized spleen volume with blood counts and lipid profile markers.</p><p><strong>Results: </strong>Spleen volume was positively associated with RBC (<i>β</i> = 0.05; 95% confidence interval [CI] = 0.03 to 0.08) and hemoglobin (β = 0.05; 95% CI = 0.01 to 0.09) but inversely with platelet count (β = -16.3; 95% CI = -20.5 to -12.1) and WBC (β = -0.25; 95% CI = -0.37 to -0.14). Furthermore, spleen volume showed inverse associations with total cholesterol (β = -0.17; 95% CI = -0.24 to -0.09), HDL-C (β = -0.08; 95% CI = -0.10 to -0.05), and LDL-C (β = -0.12; 95% CI = -0.17 to -0.06). There was no significant association of spleen volume with triglycerides.</p><p><strong>Conclusion: </strong>Our study showed that the spleen volume is associated with markers of the blood count and lipid profile in the general population.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41180054","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":"Stand-alone virtual reality exposure therapy as a treatment for social anxiety symptoms: a systematic review and meta-analysis.","authors":"Christian Rejbrand,&nbsp;Brynjar Fure,&nbsp;Karin Sonnby","doi":"10.48101/ujms.v128.9289","DOIUrl":"10.48101/ujms.v128.9289","url":null,"abstract":"<p><strong>Introduction: </strong>Social anxiety is common and can have far-reaching implications for affected individuals, both on social life and working performance. Usage of virtual reality exposure therapy (VRET) has gained traction. The aim of the present systematic review was to evaluate the effect of stand-alone VRET on social anxiety symptoms.</p><p><strong>Method: </strong>We searched systematically in <i>PubMed</i>, <i>Embase</i>, <i>PSYCinfo</i>, and <i>ERIC</i> in May 2022 for studies with participants with social anxiety symptoms receiving stand-alone VRET. Two reviewers independently selected relevant studies in a two-step procedure, and the risk of bias was assessed.</p><p><strong>Results: </strong>Of 158 hits, 7 studies were selected for full-text reading, 6 were chosen for evaluation, and 5 were included in meta-analyses. VRET resulted in a significantly lower anxiety score in treated individuals with a standard mean difference of -0.82, 95% confidence interval -1.52 to -0.13, compared to controls.</p><p><strong>Conclusion: </strong>Stand-alone VRET may reduce social anxiety symptoms. However, despite promising results, there is still uncertainty as the effect estimate is based on few studies with few participants each and a high risk of bias.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41150387","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":"The Aura-Gain laryngeal mask for airway management in neonatal inguinal hernia surgery. A feasibility study.","authors":"Ali-Reza Modiri, Robert Frithiof, Tomas Luther, Peter Frykholm","doi":"10.48101/ujms.v128.9234","DOIUrl":"10.48101/ujms.v128.9234","url":null,"abstract":"","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10084493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9673802","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":"Increased levels of a subset of angiogenesis-related plasma proteins in essential thrombocythemia.","authors":"Sofia Vikman,&nbsp;Anders Larsson,&nbsp;Måns Thulin,&nbsp;Torbjörn Karlsson","doi":"10.48101/ujms.v128.9194","DOIUrl":"https://doi.org/10.48101/ujms.v128.9194","url":null,"abstract":"<p><strong>Background: </strong>Increased local angiogenesis is important for the growth and dissemination of cancer. The myeloproliferative neoplasm essential thrombocythemia (ET) is known to involve increased bone marrow angiogenesis. Blood levels of several angiogenesis-related proteins are increased in different types of cancer. The aim of this study was to investigate whether a subset of such proteins was elevated in treatment-naïve ET patients.</p><p><strong>Methods: </strong>Blood plasma from 41 ET patients and 43 healthy aged-matched controls was analyzed for eight different angiogenesis-related proteins.</p><p><strong>Results: </strong>The ET cohort displayed a more homogenous expression pattern of these proteins compared with controls. Five of the eight proteins were significantly increased in ET patients.</p><p><strong>Conclusion: </strong>Increased plasma levels of matrix metallopeptidase 9 (MMP9) and endostatin have not previously been reported in ET. In our patients, MMP9 levels correlated positively with Janus kinase 2 (JAK2) V617F allele burden and leukocyte count.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10084492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9303875","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":"Assessing stress using repeated saliva concentration of steroid hormones in dementia care dyads: results from a controlled pilot care music intervention.","authors":"Azita Emami,&nbsp;Töres Theorell,&nbsp;Hyejin Kim,&nbsp;Lars Berglund,&nbsp;Helena Hallinder,&nbsp;Gabriella Engström","doi":"10.48101/ujms.v128.9340","DOIUrl":"https://doi.org/10.48101/ujms.v128.9340","url":null,"abstract":"<p><strong>Background: </strong>Stress-related biomarkers have the potential to provide objective measures of whether interventions directed at people with dementia (PWD) and their family caregivers (FCG) are successful. The use of such biomarkers has been limited by logistical barriers to sample collection.</p><p><strong>Objective: </strong>Explore saliva concentration of steroid hormones in dementia care dyads during a music intervention.</p><p><strong>Methods: </strong>Consecutive PWD attending a memory evaluation center and their FCG were allocated to either an intervention-with-music or a non-intervention control group. All were living at home. Stress biomarkers, salivary cortisol and dehydroepiandrosterone sulfate (DHEA-S) samples were collected by the PWD and their FCG, in the morning and evening, 5 days a week, for 8 consecutive weeks. Biomarker concentrations of the intervention and the control groups were compared at week 8, in an intention-to-treat approach with adjustment for baseline value.</p><p><strong>Results: </strong>Twenty-four PWD in the intervention group and 10 in the control group, and their FCG were included in the analyses. The mean number of morning saliva collections was similar in the intervention and the control groups, ranging from 4.3 to 4.9 per participant weekly during the first 7 weeks, declining to 3.3 during week 8. Median log morning cortisol (pg/mL) among caregivers was lower in the intervention group than in the control group (8.09 vs. 8.57, <i>P</i> = 0.0133).</p><p><strong>Conclusion: </strong>This study demonstrates that music intervention was associated with lower morning saliva cortisol concentrations for FCGs.</p>","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"128 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10231046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9573276","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":"Study protocol: The cross-sectional Uppsala weight gain in pregnancy study (VIGA study).","authors":"Theodora Kunovac Kallak,&nbsp;Alice Zancanaro,&nbsp;Katja Junus,&nbsp;Anna-Karin Wikström,&nbsp;Inger Sundström Poromaa,&nbsp;Susanne Lager","doi":"10.48101/ujms.v128.8832","DOIUrl":"https://doi.org/10.48101/ujms.v128.8832","url":null,"abstract":"Background 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. Methods 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. Results 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. Conclusions 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).","PeriodicalId":23458,"journal":{"name":"Upsala journal of medical sciences","volume":"127 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9310076","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}