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- Osterlund, P., et al.
(author)
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Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study
- 2022
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In: ESMO Open. - : Elsevier. - 2059-7029. ; 7:3
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Journal article (peer-reviewed)abstract
- Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce.Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity.Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/ infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11).Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.
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| 7. |
- Ekblad, M., et al.
(author)
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Influence of operational conditions and wastewater properties on the removal of organic micropollutants through ozonation
- 2021
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In: Journal of Environmental Management. - : Elsevier BV. - 0301-4797. ; 286
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Journal article (peer-reviewed)abstract
- The objective of this study was to evaluate the influence of operational conditions and wastewater properties on the removal of pharmaceuticals, contrast media and antibiotics through ozonation, in order to facilitate the optimization of treatment and its implementation on a full scale. Pilot-scale ozone oxidation trials were performed on treated wastewater, before and after post-precipitation, over a seven-month period, including summer and winter months. Hydraulic retention times as short as 7 min were found to be sufficient for organic micropollutant removal. A short hydraulic retention time reduces both investment costs and land use. Neither the choice of ozone dispersion method, a static mixer or a Venturi injector, nor the wastewater temperature had any significant effect on the removal efficiency of organic micropollutants, however, higher removal was achieved after on-site post-precipitation with aluminum chloride.
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| 8. |
- Ekblad, M., et al.
(author)
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Is dissolved COD a suitable design parameter for ozone oxidation of organic micropollutants in wastewater?
- 2019
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In: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 658, s. 449-456
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Journal article (peer-reviewed)abstract
- Ozone oxidation of organic micropollutants in biologically treated wastewater was investigated in pilot-scale after a high- and a low loaded activated sludge process. Higher ozone doses were required to remove organic micropollutants in the effluent wastewater from the high loaded activated sludge process. Further comparison of the micropollutant removal was based on normalized ozone doses, expressed as g O3/g DOC and g O3/g soluble COD (sCOD). A clear difference was noted for the two effluents when the micropollutant removal was normalized by DOC. This difference disappeared almost completely when the removal was linked to ozone doses normalized by sCOD. The dose-response curves for the organic micropollutants were practically linear in the removal range up to 95%. A linear prediction model was developed and compared with literature values to test the transferability of the obtained results. Results from this comparison indicated that the slope of the dose-response functions could be used to predict the removal efficiency of organic micropollutants at a third plant with an average uncertainty of 10%. The modeled ozone requirements were then set in relation to the COD concentrations in the discharged water from approximately 90 Swedish activated sludge treatment plants with and without nitrogen removal. This comparison highlighted the need for a well-functioning biological treatment for an effective ozone oxidation of organic micropollutants. The results in this study suggest that soluble COD should be further explored for design and modeling of ozone oxidation of organic micropollutants in biologically treated wastewater.
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| 9. |
- El-taliawy, H., et al.
(author)
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Ozonation efficiency in removing organic micro pollutants from wastewater with respect to hydraulic loading rates and different wastewaters
- 2017
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In: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947. ; 325, s. 310-321
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Journal article (peer-reviewed)abstract
- Organic micro pollutants can be removed from water by ozonation. In this article we studied the performance of ozonation under real life conditions and compared results of the same ozonation pilot plant installed at different wastewater treatment plants (WWTPs) thus operating with different waters. The comparability of the removal and reaction rate constants from one waste water treatment plant were low in respect to reaction rate, removal as well as to response to the specific ozone dose. Neither pH-value nor residual nitrite concentrations were the driving force considering these differences. Further tests with different loadings were conducted at the same WWTP under different weather conditions. For the different hydraulic loading of the biological plant, the ozonation was running with rather similar removal rates concerning the same specific (TOC normalized) ozone dose. The compounds that were removed quantitatively under dry weather were still removed well with three times dry weather flow. Using a dataset from one WWTP to optimize operation in another one is thus questionable.
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| 10. |
- Krustrup, P., et al.
(author)
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Effects of recreational football on women's fitness and health: adaptations and mechanisms
- 2018
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In: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 118:1, s. 11-32
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Journal article (peer-reviewed)abstract
- The review describes the fitness and health effects of recreational football in women aged 18-65 years. The review documents that 2×1 h of recreational football training for 12-16 weeks causes marked improvements in maximal oxygen uptake (5-15%) and myocardial function in women. Moreover, mean arterial blood pressure was shown to decrease by 2-5 mmHg in normotensive women and 6-8 mmHg in hypertensive women. This review also show that short-term (<4 months) and medium-term (4-16 months) recreational football training has major beneficial impact on metabolic health profile in women, with fat losses of 1-3 kg and improvements in blood lipid profile. Lastly, 2×1 h per week of recreational football training for women elevates lower extremity bone mineralisation by 1-5% and whole-body bone mineralization by 1-2% within 4-12-month interventions. These training adaptations are related to the high heart rates, high number of fast runs, and multiple changes of direction and speed occurring during recreational football training for untrained women. In conclusion, regular small-sided football training for women is an intense and versatile type of training that combines elements of high-intensity interval training (HIIT), endurance training and strength training, thereby providing optimal stimuli for cardiovascular, metabolic and musculoskeletal fitness. Recreational football, therefore, seems to be an effective tool for prevention and treatment of lifestyle diseases in young and middle-aged women, including hypertension, type 2 diabetes and osteopenia. Future research should elucidate effects of football training for elderly women, and as treatment and rehabilitation of breast cancer patients and other women patient groups.
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| 11. |
- Larsson, L. E., et al.
(author)
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Association of Sarcopenia and Its Defining Components with the Degree of Cognitive Impairment in a Memory Clinic Population
- 2023
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In: Journal of Alzheimer's Disease. - : IOS Press BV. - 1387-2877 .- 1875-8908. ; 96:2, s. 777-788
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Journal article (peer-reviewed)abstract
- Background: Sarcopenia and cognitive impairment are two leading causes of disabilities. Objective: The objective was to examine the prevalence of sarcopenia and investigate the association between sarcopenia diagnostic components (muscle strength, muscle mass, and physical performance) and cognitive impairment in memory clinic patients. Methods: 368 patients were included (age 59.0±7.25 years, women: 58.7%), displaying three clinical phenotypes of cognitive impairments, i.e., subjective cognitive impairment (SCI, 57%), mild cognitive impairment (MCI, 26%), and Alzheimer's disease (AD, 17%). Sarcopenia was defined according to diagnostic algorithm recommended by the European Working Group on Sarcopenia in Older People. Components of sarcopenia were grip strength, bioelectrical impedance analysis, and gait speed. They were further aggregated into a score (0-3 points) by counting the numbers of limited components. Multi-nominal logistic regression was applied. Results: Probable sarcopenia (i.e., reduced grip strength) was observed in 9.6% of the patients, and 3.5% were diagnosed with sarcopenia. Patients with faster gait speed showed less likelihood of MCI (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.06-0.90) and AD (OR: 0.12, 95% CI: 0.03-0.60). One or more limited sarcopenia components was associated with worse cognitive function. After adjusting for potential confounders, the association remained significant only for AD (OR 4.29, 95% CI 1.45-11.92). Conclusion: The results indicate a connection between the sarcopenia components and cognitive impairments. Limitations in the sarcopenia measures, especially slow walking speed, were related to poorer cognitive outcomes. More investigationsare required to further verify the causal relationship between sarcopenia and cognitive outcomes.
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| 12. |
- Loren, N., et al.
(author)
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Fluorescence recovery after photobleaching in material and life sciences: putting theory into practice
- 2015
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In: Quarterly Reviews of Biophysics. - : Cambridge University Press (CUP). - 0033-5835 .- 1469-8994. ; 48:3, s. 323-387
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Journal article (peer-reviewed)abstract
- Fluorescence recovery after photobleaching (FRAP) is a versatile tool for determining diffusion and interaction/binding properties in biological and material sciences. An understanding of the mechanisms controlling the diffusion requires a deep understanding of structure-interaction-diffusion relationships. In cell biology, for instance, this applies to the movement of proteins and lipids in the plasma membrane, cytoplasm and nucleus. In industrial applications related to pharmaceutics, foods, textiles, hygiene products and cosmetics, the diffusion of solutes and solvent molecules contributes strongly to the properties and functionality of the final product. All these systems are heterogeneous, and accurate quantification of the mass transport processes at the local level is therefore essential to the understanding of the properties of soft (bio)materials. FRAP is a commonly used fluorescence microscopy-based technique to determine local molecular transport at the micrometer scale. A brief high-intensity laser pulse is locally applied to the sample, causing substantial photobleaching of the fluorescent molecules within the illuminated area. This causes a local concentration gradient of fluorescent molecules, leading to diffusional influx of intact fluorophores from the local surroundings into the bleached area. Quantitative information on the molecular transport can be extracted from the time evolution of the fluorescence recovery in the bleached area using a suitable model. A multitude of FRAP models has been developed over the years, each based on specific assumptions. This makes it challenging for the non-specialist to decide which model is best suited for a particular application. Furthermore, there are many subtleties in performing accurate FRAP experiments. For these reasons, this review aims to provide an extensive tutorial covering the essential theoretical and practical aspects so as to enable accurate quantitative FRAP experiments for molecular transport measurements in soft (bio)materials.
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| 14. |
- Sen, Partha, et al.
(author)
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Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain
- 2013
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In: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 34:6, s. 801-811
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Journal article (peer-reviewed)abstract
- Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.
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| 15. |
- Sindi, S., et al.
(author)
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Multimodal Preventive Trial for Alzheimer’s Disease : MIND-ADmini Pilot Trial Study Design and Progress
- 2022
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In: The Journal of Prevention of Alzheimer's Disease. - : Serdi-Editions. - 2274-5807 .- 2426-0266. ; 9:1, s. 30-39
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Journal article (peer-reviewed)abstract
- Background: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer’s disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. Objectives: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. Methods: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/ care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. Results: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. Conclusions: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions).
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| 16. |
- Bloniecki, V, et al.
(author)
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Digital Screening for Cognitive Impairment - A Proof of Concept Study
- 2021
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In: The journal of prevention of Alzheimer's disease. - : SERDI. - 2426-0266 .- 2274-5807. ; 8:2, s. 127-134
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Journal article (peer-reviewed)abstract
- Background: Due to an ageing demographic and rapid increase of cognitive impairment and dementia, combined with potential disease-modifying drugs and other interventions in the pipeline, there is a need for the development of accurate, accessible and efficient cognitive screening instruments, focused on early-stage detection of neurodegenerative disorders. Objective: In this proof of concept report, we examine the validity of a newly developed digital cognitive test, the Geras Solutions Cognitive Test (GCST) and compare its accuracy against the Montreal Cognitive Assessment (MoCA). Methods: 106 patients, referred to the memory clinic, Karolinska University Hospital, due to memory complaints were included. All patients were assessed for presence of neurodegenerative disorder in accordance with standard investigative procedures. 66% were diagnosed with subjective cognitive impairment (SCI), 25% with mild cognitive impairment (MCI) and 9% fulfilled criteria for dementia. All patients were administered both MoCA and GSCT. Descriptive statistics and specificity, sensitivity and ROC curves were established for both test. Results: Mean score differed significantly between all diagnostic subgroups for both GSCT and MoCA (p<0.05). GSCT total test time differed significantly between all diagnostic subgroups (p<0.05). Overall, MoCA showed a sensitivity of 0.88 and specificity of 0.54 at a cut-off of <=26 while GSCT displayed 0.91 and 0.55 in sensitivity and specificity respectively at a cut-off of <=45. Conclusion: This report suggests that GSCT is a viable cognitive screening instrument for both MCI and dementia.
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| 17. |
- Fleenor, Courtney J., et al.
(author)
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Zinc Finger Protein 521 Regulates Early Hematopoiesis through Cell-Extrinsic Mechanisms in the Bone Marrow Microenvironment
- 2018
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In: Molecular and Cellular Biology. - : AMER SOC MICROBIOLOGY. - 0270-7306 .- 1098-5549. ; 38:17
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Journal article (peer-reviewed)abstract
- Zinc finger protein 521 (ZFP521), a DNA-binding protein containing 30 Kruppel-like zinc fingers, has been implicated in the differentiation of multiple cell types, including hematopoietic stem and progenitor cells (HSPC) and B lymphocytes. Here, we report a novel role for ZFP521 in regulating the earliest stages of hematopoiesis and lymphoid cell development via a cell-extrinsic mechanism. Mice with inactivated Zfp521 genes (Zfp521(-/-)) possess reduced frequencies and numbers of hematopoietic stem and progenitor cells, common lymphoid progenitors, and B and T cell precursors. Notably, ZFP521 deficiency changes bone marrow microenvironment cytokine levels and gene expression within resident HSPC, consistent with a skewing of hematopoiesis away from lymphopoiesis. These results advance our understanding of ZFP521s role in normal hematopoiesis, justifying further research to assess its potential as a target for cancer therapies.
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| 20. |
- Hagman, M, et al.
(author)
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Football and team handball training postpone cellular aging in women
- 2021
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 11733-
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Journal article (peer-reviewed)abstract
- Several hallmarks of aging have been identified and examined separately in previous exercise studies. For the first time, this study investigates the effect of lifelong regular exercise in humans on two of the central aging hallmarks combined. This cross-sectional study involved 129 healthy, non-smoking women, including young elite football players (YF, n = 29), young untrained controls (YC, n = 30), elderly team handball players (EH, n = 35) and elderly untrained controls (EC, n = 35). From a resting blood sample, mononuclear cells (MNCs) were isolated and sorted into monocytes and lymphocytes. Telomere length, mitochondrial (mtDNA) copy number and key regulators of mitochondrial biogenesis and function (PGC-1α and PGC-1β expression) were measured using quantitative polymerase chain reaction (qPCR). Overall, young women showed significantly longer telomeres and higher PGC-1α and PGC-1β expression, but lower mtDNA copy number compared to elderly subjects. A multivariate analysis showed that YF had 22–24% longer telomeres in lymphocytes and MNCs compared to YC. In addition, YF showed 19–20% higher mtDNA copy number in lymphocytes and MNCs compared to YC. The two young groups did not differ in PGC-1α and PGC-1β expression. EH showed 14% lower mtDNA copy number in lymphocytes compared to EC, but 3.4-fold higher lymphocyte PGC-1α expression compared to EC. In MNCs, EH also showed 1.4–1.6-fold higher PGC-1α and PGC-1β expression. The two elderly groups did not differ in telomere length. Elite football training and lifelong team handball training are associated with anti-aging mechanisms in leukocytes in women, including maintenance of telomere length and superior mitochondrial characteristics.
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| 22. |
- Iregren, A, et al.
(author)
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Effects on the nervous system in different groups of workers exposed to aluminium
- 2001
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In: Occupational and Environmental Medicine. ; 58, s. 453-60
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Journal article (peer-reviewed)abstract
- OBJECTIVE - To investigate possible neurotoxic effects in groups of aluminium pot room and foundry workers, aluminium welders, and a small group of workers exposed to aluminium in the production of flake powder.METHODS - Exposure to aluminium was evaluated with aluminium concentrations in blood and urine as well as a questionnaire. The groups exposed to aluminium were compared with a group of mild steel welders. Neurotoxic effects were studied with mood and symptom questionnaires and several psychological and neurophysiological tests.RESULTS - The pot room and foundry workers showed very low aluminium uptake as their aluminium concentrations in blood and urine were close to normal, and no effects on the nervous system were detected. The group of workers exposed to flake powder had high concentrations of aluminium in blood and urine, even higher than those of the aluminium welders. However, aluminium could not be shown to affect the functioning of the nervous system in flake powder producers. Although significant effects could not be shown in the present analysis of the data on welders, the performance of the welders exposed to high concentrations of aluminium was affected according to the analyses in the original paper from this group.CONCLUSIONS - For the pot room and foundry workers no effects related to the exposure to aluminium could be found. For the group of flake powder producers exposed for a short term no effects on the nervous systems were evident despite high levels of exposure. Due to the high concentrations of aluminium in the biological samples of this group, measures to reduce the exposure to aluminium are recommended, as effects on the central nervous system might develop after protracted exposures. However, this assumption needs to be verified in further studies.
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