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Distinct inflammatory profiles in young-onset versus late-onset Alzheimer's disease
No full textINTRODUCTION: Neuroinflammation, a key player in Alzheimer's disease (AD) pathogenesis, may be differentially involved in young-onset (YOAD) compared to late-onset (LOAD) AD. METHODS: Using proximity extension assay technology, we examined 737 inflammatory markers in the CSF of 26 healthy controls (63.9 +/- 8.7; 12 female), 57 patients with YOAD (60.8 +/- 4.9 y/o; 40 female), and 33 with LOAD (76.6 +/- 4.5 y/o; 18 female). We also assessed biomarkers of AD pathology (A beta 42, p-tau181, t-tau) and neurodegeneration (neurofilament light-chain [NfL]). RESULTS: Compared to controls, SCRN1 and MMP10 were increased in LOAD and YOAD, but 16 markers showed YOAD-specific increases. Forty-six markers were significantly associated with NfL. P-tau181 and t-tau mediated the association between inflammatory markers and NfL in YOAD. In LOAD we could not identify a direct or indirect relationship between neuroinflammation and neurodegeneration. DISCUSSION: Using a proteomics approach, we observed an exacerbation of neuroinflammatory changes and a differential contribution of neuroinflammation to AD pathology and neurodegeneration in YOAD compared to LOAD
Prospective evaluation of surgical treatment of liver metastasizing pancreatic cancer - ScanPan study protocol
No full textIntroduction Patients with pancreatic ductal adenocarcinoma (PDAC) have a dismal prognosis. The majority of patients are diagnosed at an advanced stage, and for these patients, the only possible treatment is palliative chemotherapy. There are increasing data from retrospective studies indicating that a subgroup of patients with liver-limited metastases may benefit from surgical treatment of liver metastases. However, there is a need for prospective trials. Objective The aim of this study is to prospectively investigate the safety and feasibility of surgically treating patients who are resectable, including those with borderline venous resectable, histopathologically confirmed PDAC, and histopathologically or radiologically confirmed liver metastases. Methods Five Swedish and one Finnish hepatopancreaticobiliary (HPB) centre will participate. Eligible patients will be identified at regional multidisciplinary conferences (MDTs). Before inclusion, they will undergo computed tomography (CT), magnetic resonance imaging (MRI, ) and (positron emission tomography computed tomography)PET-CT to rule out extrahepatic metastases. To be included, patients will have to have four or fewer liver metastases, which must be no larger than 5 cm for patients planning for resection and no larger than 2 cm for patients planning for ablation. The metastases may be either synchronous or metachronous. Patients will undergo four months of chemotherapy before surgical treatment (either resection or ablation), and postoperatively, they will undergo two months of chemotherapy. For those with synchronous metastases, resection of the pancreatic tumour will be performed. Follow-up will be performed over two years postoperatively with regular CT scans and assessments of quality of life. Conclusions In conclusion, this trial will provide increased knowledge concerning whether surgical treatment of liver metastases from pancreatic cancer can result in improved survival. Clinical Trial Number Clinical.Trials.gov (NCT05271110), registered February 26th 202
Robustness of dynamical coupling between wintertime European weather extremes and the large-scale circulation
No full textAtmospheric circulation plays a key role in driving extreme weather events. A coupling measure, termed the co-recurrence ratio (α), has been introduced to study the link between surface extremes and large-scale circulation patterns. Stemming from dynamical systems theory, the co-recurrence ratio quantifies joint recurrences of multiple atmospheric variables. Here, we evaluate the robustness of the performance of the co-recurrence ratio to the choice of geographical domains, the variables used to characterize the large-scale circulation, and the thresholds used to define extremes. We adopt a bivariate focus, diagnosing the coupling between large-scale circulation patterns and European winter extremes in temperature, wind, and precipitation. We find that the choice of domain significantly affects the interpretation of the spatial patterns and how strongly the hazard variables are coupled to the circulation variables. For some of the extremes, there are also notable differences in the coupling depending on whether the atmospheric circulation is diagnosed at the surface, by sea-level pressure, or in the mid-troposphere, by 500 hPa geopotential height. Finally, changing the threshold values used to define the extremes does not affect the robustness of our coupling results for the extreme event types that we consider. We conclude that the co-recurrence ratio provides valuable insights into the atmospheric drivers of surface extremes, but our findings also highlight the importance of choosing key parameters in the analysis with care
Ethics support personnel’s perceptions of patient and parent participation in clinical ethics support services in pediatric oncology
No full textBackground There is an ongoing discourse about patient and parent participation (PPP) in Clinical Ethics Support Services (CESS), and this paper focuses specifically on case-based CESS. Participation in CESS is increasing slowly in many contexts due to practical and moral complexity. To gain deeper understanding of PPP in CESS, we need to delve into stakeholders’ perspectives and the landscape in which they operate. The aim of the study was to explore perceptions regarding feasibility and moral appropriateness of PPP in CESS in pediatric oncology. Methods Nordic healthcare personnel (n = 26) working as ethics support personnel in pediatric oncology (and/or pediatrics in general) participated in focus group interviews (n = 6). Data was analyzed with qualitative inductive content analysis. Results Despite engagement in CESS, most ethics support personnel had no former experience of PPP in CESS. The ethics support personnel expressed potential benefits with PPP in CESS, but these were overshadowed by fear of causing participant harm. The potential benefits and harms included to deepen understanding and trust, to catalyze confrontation and to create dilemmas of decision-making participation. Reported strategies to mitigate potential negative consequences and reduce risk of causing harm were at organizational, relational and individual levels. Conclusions Despite seeing positive reasons for PPP in CESS, the ethics support personnel were mainly concerned about the potential participant harm and wanted to protect the child and the parent. This could be interpreted as a form of disguised paternalism. The perceived appropriateness of PPP in CESS in pediatric oncology seems to depend on the situation. Furthermore, in cases where it can be considered, there is no universal way of doing it. An important enabler may be to customize PPP in CESS on a case-by-case basis and to apply the identified strategies to reduce potential risk of causing harm. This study contributes to increased knowledge about PPP in CESS from the perspectives of ethics support personnel in pediatric oncology and informs us about what is needed to carefully foster PPP in CESS, both practically and morally
Role of B vitamins in modulating homocysteine and metabolic pathways linked to brain atrophy : Metabolomics insights from the VITACOG trial
No full textINTRODUCTION Elevated total homocysteine (tHcy) is a major predictor of brain atrophy, cognitive decline, and Alzheimer's disease (AD) progression. The VITACOG trial, a randomized, placebo-controlled study in mild cognitive impairment (MCI), previously showed that B vitamin supplementation lowered tHcy, slowing brain atrophy and cognitive decline; however, the underlying mechanisms remained unclear. METHODS We used untargeted, multi-platform metabolomics, with nuclear magnetic resonance and liquid chromatography-mass spectrometry to analyze serum samples from 89 B vitamin–treated and 84 placebo-treated MCI participants over a 2 year follow-up period. RESULTS Multivariate modeling distinguished treated from placebo groups with 91.2 ± 1.8% accuracy. B vitamin supplementation induced significant metabolic reprogramming, lowering quinolinic acid, α-ketoglutarate, α-ketobutyrate, glucose, and glutamate. DISCUSSION These findings reveal that B vitamins influence metabolic pathways beyond tHcy reduction, particularly the tricarboxylic acid cycle and glutamine–glutamate cycling, critical for brain energy homeostasis and neurotransmission. This metabolic signature supports B vitamin supplementation as a strategy for slowing MCI progression. Highlights Nuclear magnetic resonance and multi-platform liquid chromatography tandem mass spectrometry metabolomics were performed on serum samples from 89 B vitamin–treated and 84 placebo participants in the VITACOG trial. Multi-platform metabolomics revealed B vitamin–driven metabolic reprogramming, achieving 91% classification accuracy. B vitamin supplementation modulates key neuroprotective metabolic pathways. Regulation of energy metabolism and neurotransmission by B vitamins contributes to brain health in elderly individuals. B vitamins demonstrate potential as an adjunct therapy in mild cognitive impairment, potentially mitigating progression to Alzheimer's disease
The healthcare system in Sweden
No full textThe Swedish population is characterized by high life expectancy and low avoidable mortality rates. This review outlines the Swedish healthcare system, which offers universal access to all residents and has a long tradition of reforms for social equity. Responsibility for healthcare is shared between the state, the regions, and the municipalities. The Ministry of Health and Social Affairs provides the overall healthcare framework; additionally, several governmental agencies are directly involved in healthcare and public health initiatives. The 21 regions organize, finance, and provide most primary, secondary, and tertiary care, as well as health information channels. Resources for primary care are less plentiful than in many other countries. The 290 municipalities deliver care to elderly people and those with functional impairment. The Swedish healthcare system is primarily tax-funded, with 86% of total healthcare expenditures from public expenses and < 1% from voluntary health insurance. The gross domestic product (GDP) share of healthcare expenditures, 10.5% in 2022, is above the EU average. The level of unmet needs in the population is low, due to universal coverage and caps on user charges except for dental care. Sweden's healthcare system performs well on care quality and patient satisfaction, but suffers from workforce shortage and care fragmentation. Limitations in care coordination can be attributed to a siloed digital infrastructure and care governance, a low number of hospital beds per capita, and a compensation system that often does not incentivize coordination. Despite these challenges, life expectancy is high and avoidable mortality rates are low in Sweden
Ethical entanglements : human remains, museums and ethics in a European perspective
No full textThe ethical treatment of human remains after excavation is a core debate in archaeology. This project explores the treatment of human remains in some European museums with an aim to support open discussion of complex ethical issues among research and heritage professionals involved in the care of human remains
Advanced stage classical Hodgkin lymphoma patients with a positive interim-PET (PET-2) Deauville score 5 after 2 ABVD cycles : a pooled analysis of three multicenter trials
No full textPET after 2 ABVD cycles (PET-2) is widely adopted to select patients with classical Hodgkin lymphoma (cHL), who might benefit from intensifying or de-escalating therapy. Prolonged progression-free survival (PFS) has been reported in PET-2 positive patients switched to escalated BEACOPP (eBEACOPP) or BEACOPP-14. Nevertheless, the subgroup of patients with a PET-2 scored 5 according to Deauville score (PET-2 DS5) are known to poorly benefit from treatment intensification. To elucidate PET-2 DS5 outcome along with possible predictive factors of response to intensification, a pooled analysis from three multicenter trials, GITIL/FIL HD0607, RATHL, and SWOG S0816, was conducted. PFS and overall survival (OS) were assessed after 41-month median follow-up, the prognostic value of clinical, laboratory, and PET parameters at diagnosis was evaluated. Among 2231 patients, 136 (6%) PET-2 DS5 patients were identified. Their 3-year PFS was 32% (95% CI, 25-42), while the 3-year OS was 82% (95% CI, 75-89). In multivariate analysis low lymphocyte (< 600/mm3) counts were adversely associated with PFS, whereas age ≥ 45 years and leukocytes cells count <15 x 103/μL were barely associated with short OS. The study confirms on a suitable cohort of PET-2 DS5 patients, that this high-risk cHL subgroup has an inadequate response to treatment intensification. Nevertheless, PET-2 DS5 patients may still have good outcome after subsequent salvage treatments with > 80% survival at 3 years, thus excluding a real disease refractoriness. Few distinct parameters may have specific prediction for PFS or OS
Hallmark features of conventional BCS superconductivity in 2H-TaS2
No full textLayered transition metal dichalcogenides (TMDs) are model systems to investigate the interplay between superconductivity and the charge density wave (CDW) order. Here, we use muon spin rotation and relaxation (μ+SR) to probe the superconducting ground state of polycrystalline 2H-TaS2, which hosts a CDW transition at 76 K and superconductivity below 1 K. The μ+SR measurements, conducted down to 0.27 K, are consistent with a nodeless, BCS-like single-gap s-wave state. Fits to the temperature dependence of the depolarization rate and Knight shift measurements support spin-singlet pairing. Crucially, no evidence of time-reversal symmetry breaking (TRSB) is observed, distinguishing 2H-TaS2 from polymorphs like 4Hb-TaS2, where TRSB and unconventional superconductivity have been reported. These findings establish 2H-TaS2 as a canonical BCS superconductor and provide a reference point for understanding the diverse electronic ground states that emerge in structurally distinct TMD polymorphs