| 76701. |
- Kalinen, Sofia, et al.
(författare)
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Differences in Gut Microbiota Profiles and Microbiota Steroid Hormone Biosynthesis in Men with and Without Prostate Cancer.
- 2024
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Ingår i: European urology open science. - 2666-1683. ; 62, s. 140-150
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Tidskriftsartikel (refereegranskat)abstract
- Although prostate cancer (PCa) is the most common cancer in men in Western countries, there is significant variability in geographical incidence. This might result from genetic factors, discrepancies in screening policies, or differences in lifestyle. Gut microbiota has recently been associated with cancer progression, but its role in PCa is unclear.Characterization of the gut microbiota and its functions associated with PCa.In a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of PCa were assessed utilizing 16S rRNA sequencing.Sequences were assigned to operational taxonomic units, differential abundance analysis, and α- and β-diversities, and predictive functional analyses were performed. Plasma steroid hormone levels corresponding to the predicted microbiota steroid hormone biosynthesis profiles were investigated.Of 364 patients, 181 were analyzed, 60% of whom were diagnosed with PCa. Microbiota composition and diversity were significantly different in PCa, partially affected by Prevotella 9, the most abundant genus of the cohort, and significantly higher in PCa patients. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinol metabolism in the PCa-associated microbiome. Plasma testosterone was associated negatively with the predicted microbial 5-α-reductase level.Gut microbiota of the PCa patients differed significantly compared with benign individuals. Microbial 5-α-reductase, copper absorption, and retinol metabolism are potential mechanisms of action. These findings support the observed association of lifestyle, geography, and PCa incidence.In this report, we found that several microbes and potential functions of the gut microbiota are altered in prostate cancer compared with benign cases. These findings suggest that gut microbiota could be the link between environmental factors and prostate cancer.
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| 76702. |
- Kalinowska, M., et al.
(författare)
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Deletion of Fmr1 in parvalbumin-expressing neurons results in dysregulated translation and selective behavioral deficits associated with fragile X syndrome
- 2022
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Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Fragile X syndrome (FXS), the most common genetic cause of autism spectrum disorder and intellectual disability, is caused by the lack of fragile X mental retardation protein (FMRP) expression. FMRP is an mRNA binding protein with functions in mRNA transport, localization, and translational control. In Fmr1 knockout mice, dysregulated translation has been linked to pathophysiology, including abnormal synaptic function and dendritic morphology, and autistic-like behavioral phenotypes. The role of FMRP in morphology and function of excitatory neurons has been well studied in mice lacking Fmr1, but the impact of Fmr1 deletion on inhibitory neurons remains less characterized. Moreover, the contribution of FMRP in different cell types to FXS pathophysiology is not well defined. We sought to characterize whether FMRP loss in parvalbumin or somatostatin-expressing neurons results in FXS-like deficits in mice. Methods We used Cre-lox recombinase technology to generate two lines of conditional knockout mice lacking FMRP in either parvalbumin or somatostatin-expressing cells and carried out a battery of behavioral tests to assess motor function, anxiety, repetitive, stereotypic, social behaviors, and learning and memory. In addition, we used fluorescent non-canonical amino acid tagging along with immunostaining to determine whether de novo protein synthesis is dysregulated in parvalbumin or somatostatin-expressing neurons. Results De novo protein synthesis was elevated in hippocampal parvalbumin and somatostatin-expressing inhibitory neurons in Fmr1 knockout mice. Cell type-specific deletion of Fmr1 in parvalbumin-expressing neurons resulted in anxiety-like behavior, impaired social behavior, and dysregulated de novo protein synthesis. In contrast, deletion of Fmr1 in somatostatin-expressing neurons did not result in behavioral abnormalities and did not significantly impact de novo protein synthesis. This is the first report of how loss of FMRP in two specific subtypes of inhibitory neurons is associated with distinct FXS-like abnormalities. Limitations The mouse models we generated are limited by whole body knockout of FMRP in parvalbumin or somatostatin-expressing cells and further studies are needed to establish a causal relationship between cellular deficits and FXS-like behaviors. Conclusions Our findings indicate a cell type-specific role for FMRP in parvalbumin-expressing neurons in regulating distinct behavioral features associated with FXS.
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| 76703. |
- Kalinowski, A., et al.
(författare)
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Evaluation of C4 gene copy number in Pediatric Acute Neuropsychiatric Syndrome
- 2023
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Ingår i: Developmental Neuroscience. - 0378-5866. ; 45:6, s. 315-324
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Tidskriftsartikel (refereegranskat)abstract
- Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is an abrupt-onset neuropsychiatric disorder. PANS patients have an increased prevalence of co-morbid autoimmune illness, most commonly arthritis. In addition, an estimated one-third of PANS patients present with low serum C4 protein, suggesting decreased production or increased consumption of C4 protein. To test the possibility that copy number (CN) variation contributes to risk of PANS illness, we compared mean total C4A and total C4B CN in ethnically-matched subjects from PANS DNA samples and controls (192 cases and 182 controls). Longitudinal data from the Stanford PANS cohort (n = 121) was used to assess whether the time to Juvenile Idiopathic Arthritis (JIA) or Autoimmune Disease (AI) onset was a function of total C4A or C4B. Lastly, we performed several hypothesis-generating analyses to explore the correlation between individual C4 gene variants, sex, specific genotypes and age of PANS onset. Although the mean total C4A or C4B CN did not differ in PANS compared to controls, PANS patients with low C4B CN were at increased risk for subsequent JIA diagnosis (Hazard Ratio = 2 7, p-value = 0 004). We also observed a possible increase in risk for AI in PANS patients and a possible correlation between lower C4B and PANS age of onset. An association between rheumatoid arthritis and low C4B CN has been reported previously. However, patients with PANS develop different types of JIA: enthesitis-related arthritis, spondyloarthritis and psoriatic arthritis. This suggests that C4B plays a role that spans these arthritis types.
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| 76704. |
- Kalinowski, Birgitta E., 1900, et al.
(författare)
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Microbial leaching of uranium and other trace elements from shale mine tailings at Ranstad
- 2004
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Ingår i: Geoderma. - : Elsevier BV. - 0016-7061. ; 122:2-4, s. 177-194
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Tidskriftsartikel (refereegranskat)abstract
- High levels of heavy metals have been found in the surroundings of the closed uranium (U) mine in Ranstad in southern Sweden. These findings cannot be explained entirely by abiotic processes. It was not until recently that biology was taken into account in the discussion about mobilization of metals at this site. It is well known that bacteria produce short-chain organic acids and element-specific ligands (siderophores) that are able to change pH and enhance chelation, which results in increased mobilization of many trace elements. Other (nonessential) elements, such as thallium (Tl), lanthanides, and actinides, may also be mobilized as a result of such bacterial action. This paper describes the mobilization of U and other elements from U ores by bacteria. Three common siderophore-producing bacterial species, Pseudomonas fluorescens, Shewanella putrefaciens and Pseudomonas stutzeri, were incubated in a chemically defined medium supplemented with tailings material with a content of 0.0013% U by weight, which had been exposed to natural weathering for 30 years. Nonleached U ore (0.61% U by weight) from the same area was incubated with P. fluorescens and S. putrefaciens for comparison. P. fluorescens grown with ore caused a change in pH in the growth medium from 4.7 to 9.3, which was significantly higher than for the other two species, for which pH was about 5.2. P. fluorescens was the only species that thrived and mobilized measurable amounts of U from the two ores, leaching out 0.001–0.005% of the total amount of U from both. The release of U is attributed to the production of pyoverdine chelators, since U could not be detected either in sterile controls or in the experiments with the other two bacteria. P. fluorescens also doubled the chromium (Cr) concentration in solution as compared with the sterile controls, whereas P. stutzeri and S. putrefaciens caused a five to sixfold increase in Cr concentration. Thallium, cobalt (Co), zinc (Zn), manganese (Mn), and vanadium (V) concentrations initially resembled those in the sterile controls, but from day 2 of the experiment, a decrease was observed. The difference in leaching behavior between the bacteria used in this study is likely to have been due to the production of different chelators rather than being an effect of pH, since many metals have low solubility at neutral to alkaline pH. This study using laboratory incubations shows that mobilization of U from ore can occur aerobically at neutral to alkaline conditions, which may be an important process behind the high content of heavy metals in the surroundings of the closed U mine at Ranstad.
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| 76705. |
- Kalinowski, Birgitta E., et al.
(författare)
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Microbial mobilization of uranium from shale mine waste
- 2006
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Ingår i: Geomicrobiology Journal. - : Informa UK Limited. - 0149-0451 .- 1521-0529. ; 23:3-4, s. 157-164
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Tidskriftsartikel (refereegranskat)abstract
- The alum shale in the Billingen area in southern Sweden was mined in Ranstad for 5 years during the 1960s. The crushed tailings (processed and unprocessed) were left behind when the Ranstad mine was closed that has caused leaching of metals to the surroundings. The siderophore producing bacterium Pseudomonas fluorescens (sp, SE Sweden) was grown in batch cultures for 5 to 8 days with naturally weathered (unprocessed) uranium ore (0.0029% U by weight), kolm (0.52% U by weight) and acid-leached ore (0.0099% U by weight) in chemically defined media (unbuffered and buffered). Pseudomonas fluorescens grown with ore and unbuffered medium changed the pH from 4.7 to 9.3 and leached out 0.016 to 0.9% (normalized to surface area) of the total amount of U from the different ores. Incubation of the acid-leached ore with bacteria in buffered medium leached out 0.04% of the total U. Uranium was leached out selectively at all conditions, but this could be a pH effect, as pH increased at the same time as the U concentrations did. The observed release of Fe was most likely attributed to the production of microbial siderophores (Fe3+ specific chelators) since Fe3+ has a low solubility at pH > 4. As siderophores contain a number of chelating groups they may still function as complexators even in partly degraded form also for other metals than Fe. Thus, the production of microbial chelators could contribute to the elevated metal concentrations in the drainage water from the closed Ranstad mine, as abiotic processes cannot fully explain these high metal concentrations. In the extension: ligand promoted leaching of toxic elements could also be the key to bioremediation as there is a need for nontoxic cleanup methods for metal contaminated sites.
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| 76706. |
- Kalischer Wellander, B., et al.
(författare)
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High correlation between the different measures suggests that mortality is relatively correctly reported in Sweden : God samstämmighet mellan olika svenska mått på avlidna i covid-19
- 2021
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Ingår i: Läkartidningen. - 0023-7205. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- Infection fatality ratio (IFR) in covid-19 is highly debated in international and Swedish press. In Sweden, three different estimates have been used to estimate mortality, based on statistics either from the Swedish National Board of Health and Welfare, and the Public Health Agency of Sweden, whereas excess mortality calculated by EuroMOMO. Mortality is based on death certificates, which can be accurate or erroneous, but previous analyses have suggested that over- and underdiagnosis usually even out. EuroMOMO on the other hand reports all-cause mortality compared to an estimated baseline. In view of high correlation between the different measures, we suggest that mortality is relatively correctly reported in Sweden. We discuss IFR internationally and in Sweden, and suggest that IFR in the Western world is approximately 0.5-1%. However, these numbers will change over time depending on immunity induced by vaccination efforts, but also the potential spread of new virus variants.
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| 76707. |
- Kaliyugarasan, Satheshkumar, et al.
(författare)
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Multi-Center CNN-Based Spine Segmentation from T2W MRI Using Small Amounts of Data
- 2023
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Ingår i: Proceedings - International Symposium on Biomedical Imaging. - 1945-7928 .- 1945-8452. - 9781665473583
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Konferensbidrag (refereegranskat)abstract
- Segmentation of the spinal tissues on MRI is the basis for quantitative analyses, but time-consuming if done manually. In this work, we construct a pipeline for automatic vertebrae segmentation from T2w MRI scans, assessing performance and generalizability by external validation. Our study used 15 scans from one site (Haukeland University Hospital, HUH) and 10 scans from another (Sahlgrenska University Hospital, SUH). MRI experts manually delineated the vertebral bodies Th12-L5 on all the HUH data and a subset of six scans from SUH. We trained multiple convolutional neural networks, assessing the performance in an experimental design tailored to small-data contexts and also on external data. Our best model achieved a mean Dice score of 0.899. This is comparable to results in the literature, but our system required much less training data.
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| 76708. |
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Kalk & Hantverk för byggnadsvård och nybyggnad : Dokumentation av konferens på Läckö slott 26-27 augusti 1999
- 2000
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Kalk har använts i Norden alltsedan det medeltida kyrkobyggandet. Den fortsatta utvecklingen har varit likartad i hela Norden men regionala variationer förekommer. Byggnader murades fram till 1950-talet i huvudsak av tegel och kalkbruk.Efter 1950-talet blev kalk undanträngt av cementsom har visat sig dåligt anpassat till äldre murverk. Brottet i traditionen har lett till en kris i byggnadsvården och kulturvården.Idag är intresset åter väckt både för kalk och murat nybyggande. Boken redovisar dagens läge (1999) inför 2000-talet.
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| 76709. |
- Kallak, Theodora Kunovac, 1985-, et al.
(författare)
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Higher than expected estradiol levels in aromatase inhibitor-treated, postmenopausal breast cancer patients
- 2012
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Ingår i: Climacteric. - London, United Kingdom : Informa Healthcare. - 1369-7137 .- 1473-0804. ; 15:5, s. 473-480
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Vaginal estradiol is considered contraindicated in aromatase inhibitor (AI)-treated patients because of the risk of elevated estrogen levels. This leaves limited treatment options for patients experiencing gynecological symptoms. However, in clinical practice, no precise estimation has been performed of circulating estrogens and aromatase index in postmenopausal breast cancer patients on long-lasting AI or tamoxifen treatment.Methods: Steroid hormones were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) and extraction radioimmunoassay (RIA). Postmenopausal AI-treated patients (n =33) were compared with tamoxifen-treated patients (n =34) and controls without vaginal treatment (n =56), with vaginal estradiol (n =25), or with estriol (n =11) treatment.Results: By use of LC-MS/MS, median (range) estradiol plasma concentrations were 16.7 (2.4-162.6), 31.0 (13.4-77.1), 27.2 (7.8-115.8) and 33.3 (20.3-340.1) pmol/l in AI-treated breast cancer patients, tamoxifen-treated breast cancer patients, postmenopausal controls and postmenopausal controls on vaginal estradiol, respectively. The AI-treated group and subgroups had significantly lower estradiol and estrone concentrations than all other groups (p <0.05). There was extensive interindividual variation in estradiol concentration within the AI-treated group, measured using both LC-MS/MS (2.3-182.0 pmol/l) and extraction RIA (2.4-162.6 pmol/l). The AI-treated group had lower aromatase index compared to all other groups (p <0.05-0.001).Conclusion: Circulating estrogen levels may have been underestimated in previous longitudinal studies of AI-treated breast cancer patients. Additional studies are required to further evaluate the role of circulating estrogens in breast cancer patients suffering from gynecological symptoms.
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| 76710. |
- Kalland, Kristine, et al.
(författare)
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Similar outcome of femoral neck fractures treated with Pinloc or Hansson Pins: 1-year data from a multicenter randomized clinical study on 439 patients
- 2019
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 90:6, s. 542-546
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - There are few reports on the efficiency of the Hansson Pinloc System (Pinloc) for fixation of femoral neck fractures. We compare Pinloc with the commonly used Hansson Pin System in a randomized clinical trial. The primary outcome measure is non-union or avascular necrosis within 2 years. We now report fracture failures and reoperations within the first year. Patients and methods - Between May 2014 and February 2017, 439 patients were included in the study. They were above 50 years of age and treated for a femoral neck fracture at 9 orthopedic departments in Sweden. They were randomized to either Pinloc or Hansson pins. The fractures were grouped as (a) non-displaced regardless of age, (b) displaced in patients < 70 years, or (c) >= 70 years old, but deemed unfit to undergo arthroplasty. Follow-up with radiographs and outpatient visits were at 3 and 12 months. Failure was defined as early displacement/non-union, symptomatic segmental collapse, or deep infection. Results - 1-year mortality was 11%. Of the 325 undisplaced fractures, 12% (21/169) Pinloc and 13% (20/156) Hansson pin patients had a failure during the first year. The reoperation frequencies were 10% (16/169) and 8% (13/156) respectively. For the 75 patients 50-69 years old with displaced fractures, 11/39 failures occurred in the Pinloc group and 11/36 in the Hansson group, and 8/39 versus 9/36 patients were reoperated. Among those 39 patients >= 70 years old, 7/21 failures occurred in the Pinloc group and 4/18 in the Hansson group. Reoperation frequencies were 4/21 for Pinloc and 3/18 for the Hansson pin patients. No statistically significant differences were found in any of the outcomes between the Pinloc and Hansson groups. Interpretation - We found no advantages with Pinloc regarding failure or reoperation frequencies in this 1-year follow-up.
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