Upsala journal of medical sciences最新文献

Background: This study aimed to describe eating patterns among individuals with overweight and obesity and to investigate associations between eating patterns and anthropometric measures, including body mass index (BMI) and waist circumference, and blood pressure.

Methods: This study enrolled a cohort of adults with overweight or obesity (n = 176) participating in a clinical trial focused on weight reduction. Self-reported eating patterns were assessed as part of the trial's baseline survey. Trained study nurses conducted measurements of anthropometric indicators and blood pressure. To examine associations, statistical analyses included the application of the Mann-Whitney U-test, Fisher's exact test, the chi-squared test, and linear regression models as appropriate.

Results: The median age of the participants was 55 years (interquartile range [IQR] 12), 79% were female, and the median BMI was 33 kg/m² (IQR 5). The predominant eating pattern identified was characterized by five meals per day, including breakfast, two prepared meals, and two snacks. Among older participants (≥ 55 years), 51% reported eating two prepared meals per day as compared to 75% among the younger (P <> 0.05). A higher percentage of older participants reported consuming more than one snack per day (82% vs. 68%, P = 0.04). Additionally, older participants were more likely to rate their eating habits as 'good' compared to their younger counterparts (64% vs. 52%, P = 0.03). Women reported a higher number of eating occasions than men (> 3/day: 93% vs. 78%, P = 0.01) and a higher frequency of snacks (> 1 snack/day: 79% vs. 61%, P = 0.03). No significant associations between the number of eating occasions or number of snacks and BMI, waist circumference, or blood pressure (systolic and/or diastolic) were found in regression models when age and sex were considered.

Conclusions: Varying eating patterns were observed among adults with overweight and obesity according to age and sex. No association between eating patterns and anthropometric measures or blood pressure independent of age and sex was found.

Background: Acute respiratory distress syndrome (ARDS), which is often observed in severe cases of coronavirus disease 2019 (COVID-19), is known to be a major contributor to higher mortality rates. This study assesses how hematological parameters, inflammatory biomarkers, cytokines, and the -1,082 A/G polymorphism are associated with ARDS severity in COVID-19 patients.

Methods: Following exclusions, a 6-month prospective case-control study included 82 healthy controls (HCs) and 158 COVID-19 patients with varying severities of ARDS (mild: 73, moderate: 53, and severe: 32). Blood samples were collected at admission, and laboratory biomarkers were assessed using various methods. Statistical analyses included one-way analysis of variance with Tukey's test for group comparisons, Pearson correlation, and receiver operating characteristic curve for analyzing independent associations with COVID-19 severity. Multiple linear regression and chi-square tests were used to evaluate quantitative outcomes and categorical associations, respectively.

Results: Severe ARDS patients exhibited higher C-reactive protein (CRP) levels compared to HCs. Compared to HCs, patients with moderate and severe ARDS had higher neutrophil to lymphocyte ratio (NLR), neutrophil counts, tumor necrosis factor-alpha, and interleukin-10 (IL-10), as well as lower lymphocyte counts and reduced partial pressure of oxygen/fraction of inspired oxygen (PaO₂/FiO₂) ratio. IL-10, body mass index, CRP, and NLR were associated with reduced PaO₂/FiO₂ ratio. IL-10 and CRP had the highest area under curve values toward ARDS severity. COVID-19 patients possessing the -1,082 A/G single nucleotide IL-10 GG and GA genotypes and the G allele presented with less severe ARDS.

Conclusion: Hematological indices (neutrophil count and NLR), CRP, and serum IL-10 hold promise in monitoring ARDS severity in COVID-19 patients. In addition, COVID-19 patients with GG and AG genotypes and the G allele of the IL-10 gene's-1,082 A/G polymorphism experience less severe ARDS. This highlights the potential protective role of IL-10 genetic variation in modulating the severity of inflammatory responses during severe acute respiratory syndrome-coronavirus-2 infection and may serve as a useful genetic marker for risk stratification in clinical settings.

Introduction and aim: The risk of asthma and its phenotypes may be modified by gene-environmental interactions. The previous studies on the interactions between genetic variations in the toll like 4 (TLR4), the main receptor for bacterial endotoxin, and asthma were contradictory as they were underpowered and did not consider different asthma phenotypes. The main aim of this study was to identify interactions between two single nucleotide polymorphisms (SNPs) within the TLR4 gene, Asp299Gly and Thr399Ile, and residential area (urban or rural) in females and males with asthma and different asthma phenotypes.

Method: This study was performed on 38,332 asthmatics and 322,852 non-asthma (both British Caucasians) subjects from the UK Biobank database. Asthma was also divided into phenotypes, such as asthma with/without allergy and early/late onset asthma. The residential area was based on the population area density and classified as urban or rural living. Multivariate regression models adjusted for age, body mass index, and smoking status were used to analyze interactions between the SNPs, residential area in asthma, and asthma phenotypes. The association between asthma and residential area or the SNPs was also determined.

Result: There were no significant associations between the SNPs and asthma risk (for Asp299Gly: OR (95% CI): 1.00 (0.97-1.02), for Thr399Ile: 0.99 (0.96-1.02) or between the SNPs and asthma phenotypes in either sex or combined cohorts. The effects of the SNPs were not modified by residential area population density in either sex with asthma or across asthma phenotypes. Asthma and its phenotypes were not associated with the SNPs or residential area.

Conclusions: Our study found no statistically significant association between TLR4 polymorphisms and asthma, regardless of sex or residential area. Further studies are needed to clarify the functional impact of TLR4 variation in asthma pathophysiology.

Background and aims: The associations between physical fitness markers and liver volume in the general population are unclear. We investigated the associations of peak oxygen uptake (VO_2peak)and handgrip strength with liver volume in a general population sample.

Methods and results: Data were taken from 1,531 German adults (51.3% women), aged 20 to 88 years, from two cohorts of the population-based Study of Health in Pomerania (SHIP-START-2 and SHIP-TREND-0). We analysed cross-sectional associations of VO_2peak and handgrip strength with liver volume derived from magnetic resonance imaging (MRI) by using multivariable linear regression models. These models were adjusted for age, sex, body fat mass, pre-existing type 2 diabetes, daily alcohol consumption, smoking status, and use of hypoglycaemic or antihypertensive medications. We observed significant associations of lower VO_2peak and handgrip strength with a smaller liver volume in the whole population, as well as in both men and women. In the whole population, a 1 L/min lower VO_2peak was associated with a 0.15 cm³ (95% confidence interval [CI]: 0.11 to 0.19; P < 0.0001) smaller liver volume for both sexes together. Similarly, a 1 kg lower handgrip strength was associated with a 7.05 cm³ (95% CI: 4.87 to 9.23; P < 0.001) smaller liver volume in the whole population.

Conclusion: Our results derived from a large community-based sample showed that lower values of VO_2peak and handgrip strength were associated with a smaller liver volume. These results might explain the possible negative effects of sedentary lifestyle on liver volume - the sedentary liver.

Background: Transcatheter aortic valve implantation (TAVI) has shown similar or improved clinical outcomes compared with surgical aortic valve replacement (SAVR) in patients with symptomatic severe aortic stenosis at low risk for surgical mortality. This cost-utility analysis compared TAVI with SAPIEN 3 versus SAVR in symptomatic severe aortic stenosis patients at low risk of surgical mortality from the perspective of the Swedish healthcare system.

Methods: A published, two-stage, Markov-based cost-utility model that captured clinical outcomes from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated according to Recommended Therapies (SWEDEHEART) registry (2018-2020) was adapted from the perspective of the Swedish healthcare system using local general population mortality, utility and costs data. The model had a lifetime horizon. Model outputs included changes in direct healthcare costs and health-related quality of life from using TAVI as compared with SAVR.

Results: TAVI with SAPIEN 3 resulted in lifetime costs per patient of 484,142 SEK Swedish krona (SEK) and lifetime quality-adjusted life years (QALYs) per patient of 7.16, whilst SAVR resulted in lifetime costs and QALYs per patient of 457,625 SEK and 6.81 QALYs, respectively. Compared with SAVR, TAVI offered an incremental improvement of +0.35 QALY per patient at an increased cost of +26,517 SEK per patient over a lifetime horizon, resulting in an incremental cost-effectiveness ratio of 76,532 SEK per QALY gained.

Conclusion: TAVI with SAPIEN 3 is a cost-effective option versus SAVR for patients with symptomatic severe aortic stenosis at low risk for surgical mortality treated in the Swedish healthcare setting. These findings may inform policy decisions in Sweden for the management of this patient group.

[This corrects the article DOI: 10.48101/ujms.v129.10741.].

Objectives: To examine a hypothetical dysfunction of the brain water channels in bipolar disorder by analyzing aquaporin-4 (AQP4) exposing extracellular vesicles (EVs) in cerebrospinal fluid (CSF) from individuals with bipolar disorder types 1 and 2, and healthy controls.

Methods: We analyzed exposure of AQP4 EVs to three different epitopes - the N- and C-terminals, and the epitope containing amino acids 273-291 - in CSF by flow cytometry in 24 individuals with bipolar disorder (type 1, n = 20; type 2, n = 4) and in 14 healthy controls.

Results: We observed significantly higher levels of EVs expressing AQP4 in the CSF from individuals with bipolar disorder compared with healthy controls. Specifically, the mean ± SD concentration of AQP4 + EVs per μl CSF for the N-terminal epitope was 346 ± 22 in patients with bipolar disorder type 1, 386 ± 78 in those with bipolar disorder type 2, compared with 39 ± 6.9 in the healthy control group (P < 0.0001). For AQP4+ EVs targeting the C-terminal epitope, the corresponding values were 350 ± 22 for bipolar disorder type 1, 374 ± 46 for bipolar disorder type 2, and 36 ± 6.3 for healthy controls. Similarly, EVs expressing AQP4+ epitopes containing amino acids 273-291 showed concentrations of 344 ± 17 in bipolar disorder type 1, 398 ± 63 in bipolar disorder type 2, and 38 ± 6.4 in the control group (P < 0.0001).

Conclusion: Our findings revealed significantly more EVs expressing the three AQP4 epitopes in patients with bipolar disorder compared with healthy controls. This suggests a dysregulated expression of AQP4, implicating a potential disruption in brain water homeostasis as a contributing pathogenic mechanism in bipolar disorder.

Background: In recent years, transcatheter aortic valve implantation (TAVI) has rapidly emerged as a key treatment option for aortic stenosis. TAVI has been performed at Uppsala University Hospital since 2009. Data on TAVI procedures have been collected in a nation-wide all-comer registry, the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY). However, only limited analysis has been conducted on trends in short- and long-term outcomes of TAVI patients in Sweden.

Methods: This registry-based cohort study aims to evaluate outcome trends and long-term prognosis in patients who underwent TAVI in a Swedish single center between 2009 and 2023. Survival outcomes were studied using the Kaplan-Meier method. Cox Proportional Hazards models were used to adjust for differences in patient characteristics over time.

Results: In total, 1,741 TAVI procedures were performed between 2009 and 2023. Immediate procedural mortality and 1-year mortality averaged at 0.9 and 8.1%, respectively. Both procedural and long-term mortality showed a decreasing trend over time. Similar results were observed when controlling for comorbidities and age.

Conclusions: Short-term outcomes and long-term prognosis have been constantly improving for patients undergoing TAVI within this study. Similar mortality and complication trends have been observed in other registry studies. These trends may be attributed to improvements in the quality of care, and the increased use of TAVI in lower risk patients.

This paper summarizes the efforts to develop novel biomarkers for diagnosis and screening of the three main gynecological cancers, cervical, endometrial, and ovarian cancer, with an emphasis on research performed during the last 20 years in Uppsala. A cervical cancer screening program has existed in Sweden since 1966 using cytology as the primary test. Over the last two decades, research has provided the scientific base for a transition to self-sampling to improve convenience of the woman and achieve higher population coverage, and use of human papillomavirus as the primary test. Also, efficient prophylactic vaccines and more efficient treatment strategies of women with cervical dysplasia have been introduced. Together, these medical tools have the potential to eradicate cervical cancer by 2120, as envisaged by WHO. By contrast, efficient biomarkers for endometrial and ovarian cancer are still lacking. Through the use of high-throughput proteomics, we have identified novel plasma protein biomarkers to be used in the diagnosis of women with adnexal ovarian mass upon transvaginal ultrasound, and possibly also for early detection in population screening. Similarly, novel biomarkers for the diagnosis of endometrial cancer are being evaluated. To establish a population-based screening program requires careful cost-benefit analyses. One alternative would be to broaden the focus of the current cervical cancer screening program to include also the novel biomarkers for ovarian and endometrial cancer, and thereby achieve screening for all three gynecological cancers. A program that screens for all three diseases could increase motivation to participate and thereby population coverage.

Background: Oncolytic viruses are promising tools for immune stimulatory gene therapy of cancer, but their clinical effect on solid tumors have so far been limited. Transduction of the target tumor cells is limited by both extracellular matrix that blocks viral spread within the solid tumor tissue and electrostatic forces that inhibit virus from binding its entry receptor on the cell surface. The enzymes hyaluronidase and collagenase and the polycations diethylaminoethyl (DEAE)-dextran, branched Polyethylenimine (PEI) and protamine sulfate have previously shown potential to improve gene transfer in different forms of viral gene therapy, since they may help the virus to overcome these barriers. In this study, we compared the transduction-enhancing potential of these substances when used as vehicles for adenoviral transduction in solid tumor tissue.

Methods: Subcutaneous tumors of pancreatic ductal adenocarcinoma were established in mice and treated with a mix of adenoviral vector Adf35(GFP-Luc) and either one of the selected vehicles. Transduction efficacy was determined by quantification of the viral transgene expression level using live imaging.

Results: Addition of hyaluronidase tripled the transgene expression of Adf35(GFP-Luc) when compared to virus alone. No such positive effect was seen for the other tested vehicles.

Conclusions: Out of the tested candidates, hyaluronidase showed the best potential to facilitate viral spread in tumor tissue and transduction of tumor cells. Therefore, hyaluronidase may be used as vehicle to improve clinical efficacy of oncolytic virotherapies.