| 31. |
- Moraes Holst, Luiza, et al.
(författare)
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Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 23:24
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Tidskriftsartikel (refereegranskat)abstract
- Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography-mass spectrometry and distinguished patients with CC (n = 6), UC (n = 6), IBS (n = 6) and healthy subjects (n = 6). Caco-2 monolayers and human apical-out colonoids underwent stimulation with fecal supernatants from different patient groups and healthy subjects. Their addition did not impair monolayer integrity, as measured by transepithelial electrical resistance; however, fecal supernatants from different patient groups and healthy subjects altered the gene expression of Caco-2 monolayers, as well as colonoid cultures. In conclusion, the stimulation of Caco-2 cells and colonoids with fecal supernatants derived from CC, UC and IBS patients altered gene expression profiles, potentially reflecting the luminal microenvironment of the fecal sample donor. This experimental approach allows for investigating the crosstalk at the gut barrier and the effects of the gut microenvironment in the pathogenesis of intestinal diseases.
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| 32. |
- Nilsson, Johanna, et al.
(författare)
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Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1.
- 2013
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Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 74:6, s. 914-919
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Tidskriftsartikel (refereegranskat)abstract
- Glycogen storage diseases are important causes of myopathy and cardiomyopathy. We describe ten patients from eight families with childhood or juvenile onset of myopathy, eight of whom also had rapidly progressive cardiomyopathy requiring heart transplant in four. The patients were homozygous or compound heterozygous for missense or truncating mutations in the ubiquitin ligase RBCK1 and had extensive polyglucosan accumulation in skeletal muscle and in the heart in cases of cardiomyopathy. We conclude that RBCK1 deficiency is a frequent cause of polyglucosan storage myopathy associated with progressive muscle weakness and cardiomyopathy. ANN NEUROL 2013. © 2013 American Neurological Association.
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| 33. |
- Shahim, Pashtun, 1984, et al.
(författare)
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Cerebrospinal Fluid Stanniocalcin-1 as a Biomarker for Alzheimer’s Disease and Other Neurodegenerative Disorders
- 2017
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 19:1, s. 154-160
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 Springer Science+Business Media New YorkStanniocalcin-1 (STC-1) is a nerve cell-enriched protein involved in intracellular calcium homeostasis regulation. Changes in calcium regulation are hypothesized to play a role in the pathophysiology of Alzheimer’s disease (AD). The expression of STC-1 increases in response to ischemic stroke, but whether it is altered in neurodegenerative disorder, particularly Alzheimer’s disease (AD), has not been investigated before. We measured STC-1 in cerebrospinal fluid (CSF) samples from a total of 163 individuals including AD, prodromal AD (pAD), mixed AD, stable mild cognitive impairment (sMCI), and diagnoses of other dementia than AD, as well as cognitively normal controls (CNC) enrolled at academic centers in France and Sweden. STC-1 concentration was reliably measureable in all CSF samples and was significantly increased in the initial exploratory cohort of neurochemically enriched AD patients versus AD biomarker-negative controls. In the second cohort, STC-1 was increased in AD versus pAD, and other dementia disorders, but the difference was not statistically significant. In the third cohort, there was no significant difference in STC-1 concentration between AD and CNC; however, STC-1 concentration was significantly decreased in patients with other dementia disorders compared with AD and CNC. Taken together, CSF STC-1 showed an increasing trend in AD, but the findings were not consistent across the three study cohorts. In contrast, CSF STC-1 concentrations were reduced in patients with dementia diagnoses other than AD, as compared with both AD patients and CNC. The findings from these studies suggest CSF STC-1 as a potential biomarker in differential diagnosis of dementias.
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| 34. |
- Ahmadpour, Doryaneh, 1973, et al.
(författare)
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Inventory study of an early pandemic COVID- 19 cohort in South-Eastern Sweden, focusing on neurological manifestations
- 2023
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 18:1 January
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Tidskriftsartikel (refereegranskat)abstract
- Background Neurological manifestations in patients with COVID-19 have been reported previously as outcomes of the infection. The purpose of current study was to investigate the occurrence of neurological signs and symptoms in COVID-19 patients, in the county ofÖstergötland in southeastern Sweden. Methods This is a retrospective, observational cohort study. Data were collected between March 2020 and June 2020. Information was extracted from medical records by a trained research assistant and physician and all data were validated by a senior neurologist. Results Seventy-four percent of patients developed at least one neurological symptom during the acute phase of the infection. Headache (43%) was the most common neurological symptom, followed by anosmia and/or ageusia (33%), confusion (28%), hallucinations (17%), dizziness (16%), sleep disorders in terms of insomnia and OSAS (Obstructive Sleep Apnea) (9%), myopathy and neuropathy (8%) and numbness and tingling (5%). Patients treated in the ICU had a higher male presentation (73%). Several risk factors in terms of co-morbidities, were identified. Hypertension (54.5%), depression and anxiety (51%), sleep disorders in terms of insomnia and OSAS (30%), cardiovascular morbidity (28%), autoimmune diseases (25%), chronic lung diseases (24%) and diabetes mellitus type 2 (23%) founded as possible risk factors. Conclusion Neurological symptoms were found in the vast majority (74%) of the patients. Accordingly, attention to neurological, mental and sleep disturbances is warranted with involvement of neurological expertise, in order to avoid further complications and long-term neurological effect of COVID-19. Furthermore, risk factors for more severe COVID-19, in terms of possible co-morbidities that identified in this study should get appropriate attention to optimizing treatment strategies in COVID-19 patients.
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| 35. |
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| 36. |
- Brun, Arne, et al.
(författare)
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The Birth and Early Evolution of the Frontotemporal Dementia (FTD) Concept.
- 2011
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Ingår i: Journal of Molecular Neuroscience : MN. - : Springer Science and Business Media LLC. - 1559-1166 .- 0895-8696. ; 45, s. 324-329
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Tidskriftsartikel (refereegranskat)abstract
- An historical overview of the development of the concept of frontotemporal dementia is presented, regarding the last 30 years, using as a backbone the conferences held on this theme, with a start in 1986 in Lund, Sweden. Since then, a dramatic increase in research activities and publications has rapidly expanded our knowledge in this field, a step necessary for the ultimate goal to find an effective treatment of this devastating disorder.
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| 37. |
- Ranebo, Mats, 1970-
(författare)
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Rotator Cuff Tears : Short- and long-term aspects on treatment outcome
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rotator cuff tear is a common disorder and there is a lack of knowledge of appropriate treatment and consequences of different treatment modalities. The overall aim of this thesis was to examine short- and long-term results of rotator cuff tear treatment.In Paper I we did a retrospective 21 to 25-year follow-up of a consecutive series of patients with partial and full-thickness rotator cuff tears, treated with acromioplasty without cuff repair. The cuff status had been documented in a specific perioperative protocol in all patients at the index operation. We did x-ray, ultrasonography and clinical scores with Constant score and Western Ontario Rotator Cuff index (WORC) at follow-up. We identified 111 patients with either a partial or a full-thickness tear, but at follow-up 21 were deceased and 11 were too ill from medical conditions unrelated to their shoulder. Out of the remaining 78 eligible patients, 69 were examined (follow-up rate 88 %) and they had a mean age at the index operation of 49 years (range 19-69 years). Forty-five had a partial tear and 24 a full-thickness tear at the index operation. At follow-up, 74% of patients with full-thickness tear had cuff tear arthropathy grade 2 or more according to the arthropathy classification of Hamada (grade 1 to 5) and 87% had developed tear progression (i.e. a larger tear). Corresponding numbers in those with a partial tear was 7 % arthropathy and 42 % tear progression, and the differences between the full-thickness group and the partial tear group was significant for both outcome measures (P<0.001 for both analyses). In those with arthropathy, the mean Constant score was 47 (standard deviation [SD], 23), the mean age and gender-adjusted Constant score 62 (SD, 27) and the mean WORC 58 % (SD, 26). Patients with a partial tear at follow-up had mean Constant score and WORC within the normal range. In multivariable analysis with logistic regression, having a full-thickness tear at the index operation was a risk factor for arthropathy (odds ratio [OR] 37.8; 95% confidence interval [CI], 8.2-175.0) and for tear progression (OR 6.09; 95% CI, 1.41-26.29).In Paper II we examined the contralateral shoulder in the same patients as in paper I and with the same methodology. Sixty-one patients were examined and 38 had had a partial tear at the index operation 21-25 years ago and 23 a full-thickness tear. The overall rate of contralateral full-thickness tears was 50.8 %, which is higher than the 16-35 % rate found in previous studies of newly diagnosed cuff patients. The rate of contralateral full-thickness tear ranged from 13.6 % in patients with a partial tear in the index shoulder at follow-up, to 90 % in patients with a full-thickness tear and arthropathy in the index shoulder. There was a significant correlation regarding conditions between shoulders in the same patient, with a Spearman coefficient of 0.72 for the number of ten-dons with a full-thickness tear, 0.31 for Hamada grade of arthropathy and 0.65 for Constant score. The number of tendons with a full-thickness tear in the index shoulder at follow-up was a risk factor for a contralateral full-thickness tear (OR 3.28; 95% CI, 1.67-6.44) in a multi-variable logistic regression model. We also found that cuff tear arthropathy was significantly more common in patients who had undergone an acromioplasty (P<0.001), a finding which is not confirmatory but may generate a hypothesis.Paper III addressed 17 to 20-year results after operation with a synthetic interposition graft for irreparable cuff tears. We used X-ray, ultrasonography and clinical scores at follow-up. We identified a consecutive series of 13 patients, one of whom was deceased at follow-up. Ten of the remaining 12 participated in a complete follow-up and 2 did only x-ray examination. Nine out of 12 (75 %; 95% CI, 43-95 %) had cuff tear arthropathy Hamada grade 2 or more in the index shoulder at follow-up. The mean Constant score was 46 (SD, 26) and the mean WORC 59 % (SD, 20). Seven out of 12 had contralateral cuff tear arthropathy, and the difference in frequency of arthropathy between shoulders was not statistically significant (P=0.667).In Paper IV we tested whether early repair of small cuff tears, involving mainly supraspinatus, would give a superior clinical result com-pared to physiotherapy without repair in a prospective randomised trial with 12 months follow-up. We used Constant score as the primary out-come, and WORC, EQ-VAS and Numerical Rating Scale for pain (NRS) as secondary outcomes. We also aimed at assessing the rate of tear progression in unrepaired shoulders and the healing rate in repaired shoulders by Magnetic Resonance Imaging (MRI) performed at 12 months. With a high grade of follow-up (100 % for 12 months Constant score and 95 % for 12 months MRI), the repair group had a 12 months median Constant score of 83 (Quartile range [QR], 25) and the conservative group 78 (QR, 22). This between-group difference in medians of 4.5 (95% CI,-5 to 9; P=0.68) was not statistically significant and we did not detect any significant differences in the secondary outcomes at 12 months. The retear rate was 6.5 % in repaired patients and 29 % of unrepaired patients had a tear enlargement >5 mm.The results in this thesis indicate that patients with small, traumatic, full-thickness tears of mainly supraspinatus have no clinical benefit of early surgical repair compared to physiotherapy alone, but in the long-term, patients with full-thickness tears have an increased risk of tear progression, cuff tear arthropathy and low clinical scores. These results are especially important in the treatment decision of repair or not in younger patients. Having a full-thickness tear is also a risk factor for having a contralateral cuff tear, a phenomenon that underlines the importance of endogenous factors in the development of rotator cuff tears. If a cuff tear is not repairable to bone, the addition of a synthetic inter-position graft does not seem to prevent cuff tear arthropathy.
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| 38. |
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| 39. |
- Carstam, Louise, et al.
(författare)
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WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas.
- 2021
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: While molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with isocitrate dehydrogenase (IDH) mutation has recently been questioned. We studied the prognostic role of WHO grade in molecularly defined subgroups and evaluated earlier used prognostic factors in the current molecular setting.Material and Methods: A total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. IDH mutations, codeletion of chromosomal arms 1p/19q, and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions were analyzed.Results: There was no survival benefit for patients with WHO grade 2 over grade 3 IDH-mut dLGG after exclusion of tumors with known CDKN2A/B homozygous deletion (n=157) (log-rank p=0.97). This was true also after stratification for oncological postoperative treatment and when astrocytomas and oligodendrogliomas were analyzed separately. In IDH-mut astrocytomas, residual tumor volume after surgery was an independent prognostic factor for survival (HR 1.02; 95% CI 1.01-1.03; p=0.003), but not in oligodendrogliomas (HR 1.02; 95% CI 1.00-1.03; p=0.15). Preoperative tumor size was an independent predictor in both astrocytomas (HR 1.03; 95% CI 1.00-1.05; p=0.02) and oligodendrogliomas (HR 1.05; 95% CI 1.01-1.09; p=0.01). Age was not a significant prognostic factor in multivariable analyses (astrocytomas p=0.64, oligodendrogliomas p=0.08).Conclusion: Our findings suggest that WHO grade is not a robust prognostic factor in molecularly well-defined dLGG. Preoperative tumor size remained a prognostic factor in both IDH-mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in IDH-mut astrocytomas only. The age cutoffs for determining high risk in patients with IDH-mut dLGG from the pre-molecular era are not supported by our results.
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| 40. |
- Friberg, Hans, et al.
(författare)
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Internationell och nationell konsensus om bästa vård efter hävt hjärtstopp. Många patienter blir helt återställda.
- 2010
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 107:8, s. 2-514
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Forskningsöversikt (refereegranskat)abstract
- An international consensus report on postresuscitation care after cardiac arrest has recently been published. Its content and main messages are in line with the recommendations from The Swedish Resuscitation Council, which include: diagnosing and treating the underlying disease, offering good general intensive care, considering hypothermia treatment, standardising prognostication and follow-up.
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