| 1. |
|
|
| 2. |
- Dolinska, Monika, et al.
(författare)
-
Characterization of Bone Marrow Niche in Chronic Myeloid Leukemia Patients Identifies CXCL14 as a New Therapeutic Option
- 2023
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
-
Tidskriftsartikel (refereegranskat)abstract
- Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long-term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
|
|
| 3. |
|
|
| 4. |
- Edouard, T., et al.
(författare)
-
Management of growth failure and other endocrine aspects in patients with Noonan syndrome across Europe: A sub-analysis of a European clinical practice survey
- 2022
-
Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212. ; 65:1
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To date, there is a lack of international guidelines regarding the management of the endocrine features of individuals with Noonan syndrome (NS). The aim was to develop a clinical practice survey to gather information on current treatment and management of these patients across Europe. Materials and methods: A group of 10 experts from three clinical specialities involved in the management of NS patients (clinical geneticists, paediatric endocrinologists, and paediatric cardiologists) developed a 60-question clinical practice survey. The questionnaire was implemented in Survey Monkey and sent to physicians from these three specialities via European/national societies. Contingency tables and the Chi-Squared test for independence were used to examine differences between specialities and countries. Results: In total, responses of 364 specialists (paediatric endocrinologists, 40%; geneticists, 30%; paediatric cardiologists, 30%) from 20 European countries were analysed. While endocrinologists mostly referred to national growth charts for the general population, geneticists mostly referred to NS-specific growth charts. Approximately half of the endocrinologists perform growth hormone (GH) stimulation tests in short patients with low IGF1 levels. Two thirds of endocrinologists begin GH treatment for short patients in early childhood (4–6.9 years), and over half of them selected a threshold of −2 standard deviation score (SDS) according to national growth charts. The main concerns about GH treatment appear to be presence of hypertrophic cardiomyopathy (HCM) (59%), increased risk of malignancy (46%), and limited efficacy (31%). When asked if they consider HCM as a contraindication for GH treatment, one third of respondents skipped this question, and among those who replied, two thirds selected ‘cannot answer’, suggesting a high level of uncertainty. A total of 21 adverse cardiac responses to GH treatment were reported. Although most respondents had not encountered any malignancy during GH treatment, six malignancies were reported. Finally, about half of the endocrinologists expected a typical final height gain of 1–1.5 SDS with GH treatment. Conclusion: This survey describes for the first time the current clinical practice of endocrine aspects of NS across Europe and helps us to identify gaps in the management but also in the knowledge of this genetic disorder. © 2021 The Authors
|
|
| 5. |
- Eklöf, Johan S., 1978-, et al.
(författare)
-
Effects of seasonal spawning closures on pike (Esox lucius L.) and perch (Perca fluviatilis L.) catches and coastal food webs in the western Baltic Sea
- 2023
-
Ingår i: Fisheries Research. - : Elsevier BV. - 0165-7836 .- 1872-6763. ; 263
-
Tidskriftsartikel (refereegranskat)abstract
- Marine protected areas have become one of the main tools in the battle to curb marine biodiversity loss and habitat degradation. Yet, implementation of permanent fishery closures has often generated resource user conflicts that ultimately undermine conservation goals. Here we assessed the influence of an alternative and often more accepted measure – seasonal fish spawning closures – on large predatory fish and coastal food webs in the western Baltic Sea (Sweden). In spring 2017, we conducted a multivariable field survey in 11 seasonal closures and 11 paired references areas open to fishing. In each area, pike was sampled through angling, and perch and mesopredators through gillnet surveys. To assess trophic cascades, we measured zooplankton abundance and loss of tethered gammarids from predation. Catches per unit effort of northern pike (Esox lucius) – the main target species in recreational fisheries – were ca. 2.5 times higher per unit effort in closures than reference areas; an effect that may be caused by higher abundance and/or higher catchability of pike in the absence of fishing. Catch and weight per unit effort of the more common predator European perch (Perca fluviatilus), and the mesopredators roach (Rutilus rutilus) and three-spined stickleback (Gasterosteus aculeatus) in survey nets were, however, unaffected by closures. Moreover, a previously hypothesized trophic cascade from perch to zooplankton via three-spined stickleback was supported by the analyses, but appeared independent of closures. Yet, predation risk for tethered gammarid amphipods (a prey of stickleback and an important grazer on macroalgae) was three times higher in fished areas than in closures; a cascading closure effect that may potentially be caused by small predatory fish being less active in protected areas to avoid pike predation. Overall, our results suggest that spawning closures impact pike abundance and/or behavior and could help limit the effects of fishing, but that more research is needed to disentangle i) what mechanism(s) that underlie the protection effect on pike catches, ii) the apparently weaker closure impacts on other fish species, as well as iii) the potential for cascading effects on lower trophic levels. Therefore, new seasonal spawning closures should be implemented in addition to (and not instead of) much-needed permanent closures, which have well-known effects on the wider ecosystem.
|
|
| 6. |
- Garcia-Minaur, S., et al.
(författare)
-
European Medical Education Initiative on Noonan syndrome: A clinical practice survey assessing the diagnosis and clinical management of individuals with Noonan syndrome across Europe
- 2022
-
Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212. ; 65:1
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Noonan syndrome (NS) is a rare genetic disorder caused by mutations in genes encoding components of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway. Patients with NS exhibit certain characteristic features, including cardiac defects, short stature, distinctive facial appearance, skeletal abnormalities, cognitive deficits, and predisposition to certain cancers. Here, a clinical practice survey was developed to learn more about differences in the diagnosis and management of this disease across Europe. The aim was to identify gaps in the knowledge and management of this rare disorder. Materials and methods: The European Medical Education Initiative on NS, which comprised a group of 10 experts, developed a 60-question clinical practice survey to gather information from European physicians on the diagnosis and clinical management of patients with diseases in the NS phenotypic spectrum. Physicians from three specialities (clinical genetics, paediatric endocrinology, paediatric cardiology) were invited to complete the survey by several national and European societies. Differences in answers provided by respondents between specialities and countries were analysed using contingency tables and the Chi-Squared test for independence. The Friedman's test was used for related samples. Results: Data were analysed from 364 respondents from 20 European countries. Most respondents came from France (21%), Spain (18%), Germany (16%), Italy (15%), United Kingdom (8%) and the Czech Republic (6%). Respondents were distributed evenly across three specialities: clinical genetics (30%), paediatric endocrinology (40%) and paediatric cardiology (30%). Care practices were generally aligned across the countries participating in the survey. Delayed diagnosis did not emerge as a critical issue, but certain unmet needs were identified, including transition of young patients to adult medical services and awareness of family support groups. Conclusion: Data collected from this survey provide a comprehensive summary of the diagnosis and clinical management practices for patients with NS across different European countries.
|
|
| 7. |
- Horner, Nolan S, et al.
(författare)
-
Timing of hip hemiarthroplasty and the influence on prosthetic joint infection.
- 2020
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:3
-
Tidskriftsartikel (refereegranskat)abstract
- Previous research suggested that patients have increased risk of infection with increased time from presentation with a femoral neck fracture to treatment with a hip hemiarthroplasty (HHA). The purpose of this study was to determine if rates of prosthetic joint infections within 3 months of surgery was affected by the time from patient presentation with a femoral neck fracture to the time of treatment with HHA.Acute hip fractures treated with HHA between 2005 and 2017 at three centres in Norway were enrolled in the study. Multi-trauma patients were excluded. Univariable analysis was performed to determine any significant effect of pre-operative waiting time on infection rate. Two pre-planned analyses dichotomizing pre-operative waiting time cut-offs were performed.There were 2300 patients with an average age of 82 (range, 48-100) years included of which 3.4% experienced a prosthetic joint infection within 3 months. The primary analysis found no significant difference in infection rate depending on time to surgery (OR = 1.06 (95% CI 0.94-1.20, p = 0.33)). The secondary analyses showed no significant differences in infection rates when comparing pre-operative waiting time of <24 hours vs ≥24 hours (OR = 0.92 (95% CI 0.58-1.46, p = 0.73)) and <48 hours vs ≥48 hours (OR = 1.39 (95% CI 0.81-2.38, p = 0.23)).Based off of a large retrospective Norwegian database of hip fractures there did not appear to be a significant difference in infection rate based on pre-operative wait time to surgery.
|
|
| 8. |
- Niemi, Niklas, et al.
(författare)
-
Influence of reed beds (Phragmites australis) and submerged vegetation on pike (Esox lucius)
- 2023
-
Ingår i: Fisheries Research. - : Elsevier BV. - 0165-7836 .- 1872-6763. ; 261
-
Tidskriftsartikel (refereegranskat)abstract
- Eutrophication and reduced grazing have led to an expansion of the common reed (Phragmites australis) in archipelago areas in the Baltic Sea, while at the same time the composition of submerged vegetation has changed. Although reed is important as nursery habitat for many fish species, extensive emergent vegetation may reduce biodiversity and abundance of predatory fish. Pike (Esox lucius) is a predatory fish whose larvae and young-of-the-year find both food and shelter in reed but use different micro-habitats during different life-stages. Here we investigate the influence of reed and submerged vegetation on abundance and body size of adult pike during the spawning season. We predicted that coastal bays with extensive but heterogeneous reed beds with higher cover of submerged vegetation would have more and larger pike than bays with smaller, homogenous reed belts or with less submerged vegetation. To test these predictions, we estimated abundance and size-structure of adult pike from catches in angling fishing among 22 bays in the Stockholm archipelago at the Swedish Baltic Sea coast. Our analyses show that catches of adult pike were positively associated with both extensive reed beds and cover of rooted submerged vegetation. However, pike size was not correlated with any vegetation variable, but instead increased with wave exposure and bay area. Our study suggests that reed beds and submerged vegetation are important for adult pike during the spawning season, and even the most extensive reed beds had no evident negative effect on pike populations. We could not see any clear relationship between emergent reed habitat and cover of submerged vegetation among the studied bays, and conclude that to maintain pike population during the spawning season it is important that coastal bays have sufficient amounts of both reed beds and rooted submerged vegetation.
|
|
| 9. |
- Paul, Elisabeth, et al.
(författare)
-
Towards a multilevel model of major depression: genes, immuno-metabolic function, and cortico-striatal signaling
- 2023
-
Ingår i: Translational Psychiatry. - : SPRINGERNATURE. - 2158-3188. ; 13:1
-
Forskningsöversikt (refereegranskat)abstract
- Biological assay and imaging techniques have made visible a great deal of the machinery of mental illness. Over fifty years of investigation of mood disorders using these technologies has identified several biological regularities in these disorders. Here we present a narrative connecting genetic, cytokine, neurotransmitter, and neural-systems-level findings in major depressive disorder (MDD). Specifically, we connect recent genome-wide findings in MDD to metabolic and immunological disturbance in this disorder and then detail links between immunological abnormalities and dopaminergic signaling within cortico-striatal circuitry. Following this, we discuss implications of reduced dopaminergic tone for cortico-striatal signal conduction in MDD. Finally, we specify some of the flaws in the current model and propose ways forward for advancing multilevel formulations of MDD most efficiently.
|
|
| 10. |
- Wasenius, Niko S, et al.
(författare)
-
Low-cost exercise interventions improve long-term cardiometabolic health independently of a family history of type 2 diabetes : a randomized parallel group trial
- 2020
-
Ingår i: BMJ open diabetes research & care. - : BMJ. - 2052-4897. ; 8:2
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: To investigate the effect of an exercise prescription and a 1-year supervised exercise intervention, and the modifying effect of the family history of type 2 diabetes (FH), on long-term cardiometabolic health.RESEARCH DESIGN AND METHODS: For this prospective randomized trial, we recruited non-diabetic participants with poor fitness (n=1072, 30-70 years). Participants were randomly assigned with stratification for FH either in the exercise prescription group (PG, n=144) or the supervised exercise group (EG, n=146) group and compared with a matched control group from the same population study (CON, n=782). The PG and EG received exercise prescriptions. In addition, the EG attended supervised exercise sessions two times a week for 60 min for 12 months. Cardiometabolic risk factors were measured at baseline, 1 year, 5 years, and 6 years. The CON group received no intervention and was measured at baseline and 6 years.RESULTS: The EG reduced their body weight, waist circumference, diastolic blood pressure, and low-density lipoprotein-cholesterol (LDL-C) but not physical fitness (p=0.074) or insulin or glucose regulation (p>0.1) compared with the PG at 1 year and 5 years (p≤0.011). The observed differences were attenuated at 6 years; however, participants in the both intervention groups significantly improved their blood pressure, high-density lipoprotein-cholesterol, and insulin sensitivity compared with the population controls (p≤0.003). FH modified LDL-C and waist circumference responses to exercise at 1 year and 5 years.CONCLUSIONS: Low-cost physical activity programs have long-term beneficial effects on cardiometabolic health regardless of the FH of diabetes. Given the feasibility and low cost of these programs, they should be advocated to promote cardiometabolic health.TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT02131701.
|
|
