Search Results (390)

Acute myocardial hypoxia/ischemia is associated with abnormal accumulation of myocardial lipids, including dihydroceramides. Here, we characterized how dihydroceramides are remodeled in response to hypoxia and assessed how dihydroceramide remodeling correlates to human cardiac pathophysiology. Hypoxia resulted in a marked accumulation of very-long-chain (VLC)-dihydroceramides in cultured HL-1 cardiomyocytes. In humans, we identified a correlation between the abundance of VLC-dihydroceramides in myocardial biopsies and arrhythmias and heart failure and showed that cardiac expression of CERS2, coding for an enzyme that promotes synthesis of VLC-dihydroceramides, was associated with signaling pathways linked to cardiac arrhythmia and cardiomyopathy. In cultured HL-1 cardiomyocytes, we showed that CerS2 knockdown reduced accumulation of VLC dihydroceramides and altered the expression of mediators regulating Ca²⁺ cycling and electrical conduction. In conclusion, our findings indicate that increased abundance of VLC-dihydroceramides, promoted by increased activity of CerS2 in response to hypoxia, could play a role in cardiac arrhythmias and heart failure. Full article

Background/Objectives: Worldwide, men experience a higher incidence of pancreatic cancer (PC) than women. Methods: To increase understanding of the underlying reasons for this sex-related difference, we analysed general and sex-related risk factors for PC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (women/men No. = 293,682/136,728; 717/577 PC-cases). Results: Cox proportional hazards models showed a 1.31-fold higher risk of developing PC for men compared to women (HR, 95% CI 1.15–1.49) after adjustment for age, smoking history, BMI, diabetes, and alcohol consumption. Associations of PC with established risk factors did not differ between men and women, with the exception of a greater risk of PC among women with greater attained body height, meat consumption and cigarettes smoked (1.12 (1.05–1.19) per 5 cm, 1.18 (1.02–1.36) per 100 g/d, 1.42 (1.27–1.59) per 10/d; respectively). Among child-bearing women, long cumulative duration of breastfeeding was inversely associated with risk of PC (HR 0.74, 95% CI 0.61–0.89) for >5.7 months of breastfeeding (median) relative to ≤5.7 months and among HRT users, cumulative duration of HRT use was inversely associated with PC risk (HR 0.71, 95% CI 0.53–0.95, >2.4 versus ≤2.4 years). Further reproductive and hormonal factors, such as age at menarche, number of full-term pregnancies, age at menopause, or use of oral contraceptives, were not significantly associated with PC risk. Conclusions: Pooled analyses of large cohort studies are needed to confirm these results, and detailed data on the type and intensity of HRT are required to better evaluate its effect. Full article

This randomized, double-blind, placebo-controlled, three-arm clinical trial evaluated the effects of a proprietary bioactive fucoidan-rich extract derived from Saccharina latissima (SLE-F) on gut microbial composition and function in healthy adults. The objective of the study was to assess the potential of SLE-F to beneficially modulate the gut microbiome, with this paper specifically reporting on microbial diversity, taxonomic shifts, and functional pathway outcomes. Ninety-one participants received either a low dose (125 mg), high dose (500 mg), or placebo twice daily for four weeks. The primary endpoint was the microbiome composition assessed via 16S rRNA sequencing (V3–V4 region), with secondary outcomes including surveys, adverse event monitoring, and clinical evaluations. High-dose supplementation resulted in dose-dependent improvements in the microbial diversity; increased abundance of beneficial taxa, including Bifidobacterium, Faecalibacterium, and Lachnospiraceae; and reductions in inflammation-associated taxa, such as Enterobacteriaceae and Pseudomonadota. A functional pathway analysis showed enhancement in short-chain fatty acid biosynthesis and carbohydrate metabolism. The low-dose group showed modest benefits, primarily increasing Bifidobacterium, with limited functional changes. In vitro colonic simulations further demonstrated a dose-dependent increase in short-chain fatty acids and postbiotic metabolite production following SLE-F exposure. SLE-F was well tolerated, with only mild, nonspecific adverse events reported. These findings support the potential of SLE-F as a safe and effective microbiome-modulating agent, warranting further study of the long-term use and synergy with dietary interventions. Full article

Methotrexate (MTX), the most common first-line treatment in rheumatoid arthritis, is often insufficient, with no model capable of predicting response. The RA classification criteria, including autoantibodies and inflammation, were applied to 257 patients with newly diagnosed inflammatory arthritis in the cohort study, estimating MTX response. A total of 172 patients received MTX as the first anti-rheumatic drug and response was recorded at 1 year follow-up. A multivariable logistic regression used variables distinct between MTX-responders and non-responders to build the predictive model of response. Overall, 53.5% of MTX treated patients responded. Non-responders were frequently autoantibody positive, and responders were older, had lower RA classification scores, frequent corticosteroid use, and high insulin levels at baseline. Inflammation parameters were comparable between the groups. In the multiple regression analysis, the RA classification score and age at the first visit were strong predictors of MTX response (AUC 0.697, p < 0.0001). Including blood levels of insulin and IFNg improved AUC to 0.782 (p < 0.0001), offering early discrimination between responders and non-responders with high accuracy. Cellular experiments showed that insulin could be used to estimate MTX response by demonstrating that insulin changed the transcription of MTX target genes in the folate metabolism after exposing CD4+ cells ex vivo, which could facilitate MTX response in immune cells. Full article

Tetrodotoxin (TTX), earlier known as a tropical paralytic neurotoxin from pufferfish poisoning, has increasingly been occurring in edible marine species, including filter-feeding bivalves, from relatively cold marine waters of some European countries. The defined conditions that promote the production of TTX, its origin or the processes of its accumulation in seafood are still not clarified. Recent studies in temperate waters show, however, that the accumulation of quantifiable levels of TTX in bivalves appears to be influenced by seawater temperature (>15 °C), which indicates a seasonal occurrence at these latitudes. Uncertainties still remain regarding how seawater temperature interacts with other climate and environmental factors or organisms in the marine ecosystem to result in detectable levels of TTX in shellfish. Knowledge of the occurrence and distribution of TTX in the marine environment where the edible bivalves grow is important for maintaining seafood safety, as the toxin is heat-stable and remains potent even after cooking. Therefore, in this study, 264 bivalve samples collected in 2019 and 2021 from 17 sites along the Swedish west coast were analyzed with LC-MS/MS to search for TTX. The study explores the hypothesis of TTX presence in Swedish marine waters, outlines the sample screening strategy and objectives, and reports no evidence of TTX presence in Swedish bivalve shellfish (≥7.8 µg/kg) based on the analyzed samples and the time periods in which the studied samples were collected. Full article

Background: Associations between high physical activity (PA) levels and incident atrial fibrillation (AF) is found in some earlier studies. We aim to study the association between levels of PA and AF in two cohorts. Methods: We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM) study, initiated in 1970, included men aged 50 years, with 2202 included in the study. Examinations were reiterated three times, with follow-up after in median 33 years, with 3.8–6.0% on the highest PA level. We also used data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; with women 50%); mean age 70 years, baseline 2001–2004, median follow-up 15 years, with 961 included in the study, with 4.8% on the highest PA level. Cox regression analysis with hazard ratios (HRs) was used to study association between PA levels and incident AF, adjusted for CV risk factors: systolic blood pressure, LDL- and HDL-cholesterol, BMI, diabetes, and smoking. Results: Totally, in ULSAM 504 men during 59,958 person-years at risk, and in PIVUS 204 individuals during a follow-up of 11,293 person-years experienced an AF. Neither in ULSAM, PIVUS, nor in the meta-analysis of both cohorts, individuals with the highest PA level showed an increased AF risk, compared to individuals with lowest level of PA. Conclusions: The benefits of PA in community dwelling individuals for its benefits to mental, metabolic, and cardiovascular health should guide public recommendations, rather than a possible risk of AF. Lay Summary: We studied the risk of incident atrial fibrillation at various levels of physical activity in two cohorts and found no statistically significant increased risk after adjusting for cardiovascular risk factors (systolic blood pressure, LDL- and HDL-cholesterol, BMI, diabetes, and smoking). Full article

The pathogenesis of psoriasis is complex and many specific immunopathogenic mechanisms still remain unclear. Our goal was to identify novel pathways involved in the pathogenesis of psoriasis by analyzing differentially expressed genes, and to conduct pathway and cluster analysis by comparing lesional and non-lesional skin with healthy controls. Accordingly, 2 mm punch biopsies were taken from lesional elbow skin and non-affected adjacent skin of 23 patients with plaque-type psoriasis and from the elbow skin of 25 healthy controls. Differentially expressed genes were analyzed through RNA sequencing, and gene set enrichment analysis was used to analyze biological pathways. Our results showed downregulation of the pathway clusters “Mitophagy” and “Respiratory Electron Transport” when comparing both lesional and non-lesional skin to control skin. The pathway “Signaling by ROBO receptors” was downregulated in all three comparisons. Conversely, pathways relating to SUMOylation were upregulated when comparing lesional skin to both non-lesional and control skin, and those relating to the synthesis of PIPs at the early endosome membrane were found to be upregulated in lesional skin compared to control skin. The dysregulation of pathways relating to mitophagy (involved in the removal of damaged mitochondria), complex I biogenesis (a component of the mitochondrial respiratory chain), signaling by ROBO receptors (important for cell migration), and the synthesis of PIPs at the early endosome membrane (with a pivotal role in endocytic pathways and autophagy) suggests their potential role in psoriasis. Further research into the mechanisms of these dysregulated pathways, along with confirmation of protein expression levels, is necessary to validate their roles in psoriasis pathogenesis. Full article

Background: Tooth loss results in hard- and soft-tissue volume loss over time. We compared the handling of three different soft tissue substitutes (STS) to the subepithelial connective tissue graft (SCTG) for soft tissue volume augmentation in a pig ex vivo model. Methods: Five dentists simultaneously shaped, placed and sutured randomized four graft types in single-tooth soft tissue defects created in pig mandibles. The STS, produced from slightly crosslinked collagen fibres (VCMX), were either 3 mm or 6 mm thick blocks or a newly developed pre-customized saddle-shape. Each graft type was handled 20 times. The time required for shaping, placement, and suturing was recorded. Dentists reported outcomes on the grafts’ handling were evaluated with a visual-analogue-scale (VAS). Statistical analysis included calculating means and medians and testing significance. Results: The mean time of 0.72 min for shaping the pre-customized saddle-shape STS was significantly lower than 1.31 min for SCTG, 1.73 min for 3 mm STS and 2.17 min for 6 mm STS. Placement/suturing time was similar for all grafts. The dentists mainly preferred the saddle-shape STS and the SCTG. Conclusions: The saddle-shape STS required less time for graft-shaping and, therefore, reduced the overall treatment time, suggesting a more efficient and less invasive workflow for soft tissue augmentation. Full article

Ecosystem-based adaptation (EbA) has been widely recognized as the key strategy for supporting farmers in adapting to climate change. The success of EbA requires a cohesive alignment from the national level to community implementation. However, harmonized efforts from central governments to local farmers remain underexplored in the literature on climate change and adaptation, especially in the context of mountainous areas of Vietnam. This study applied multiple qualitative research methods, including 12 key informant interviews, six focus group discussions, and 18 in-depth interviews to explore the varying perspectives of EbA between government officials and farmers, and how these perspectives influence their involvement in governmental initiatives. Using matrix coding visualization in NVIVO, this study revealed notable differences in perceptions of EbA between government officials and farmers, which in turn impact EbA practices at the commune level. This study also found factors affecting EbA practices, including knowledge, economic priorities, institutional support, labor shortages, limited market access, and funding inadequacies. The policy implications drawn from this study are necessary for bridging top-down policy with local realities, to ensure the sustainability and effectiveness of EbA. Furthermore, this paper contributes to the EbA literature by highlighting the need for context-specific adaptation strategies to enhance the effectiveness and inclusivity of EbA practices in vulnerable communities. Full article

Fluidized bed-chemical vapor deposition (FB-CVD) technology stands as a cross-cutting achievement of fluidized bed technology in chemical engineering and chemical vapor deposition (CVD) in materials science, finding applications in particle coating, granulation, and material preparation. As compared to conventional CVD technology, FB-CVD distinguishes itself through enhanced heat/mass transfer efficiency, achieving a uniform coating layer while maintaining low production costs. Given the related research on FB-CVD micro-nano particle coating, the mechanism of particle fluidization and chemical vapor deposition, and the difficulty of micro-nano particle agglomeration were summarized. The process intensification of micro-nano particle fluidization assisted by particle design and external force field, such as vibration field, magnetic field, and sound field, and micro-nano particle chemical vapor deposition coating were summarized. In particular, applications of FB-CVD micro-nano particle coating are introduced. Finally, the opportunities and challenges faced by FB-CVD micro-nano particle coating technology are discussed, and the development prospect of this technology is prospected. This review is beneficial for the researchers of the fluidization field, and also the particle coating technology. Full article

Pinus species are extensively abundant in Europe and, as pioneer trees, prominently influence local ecology. However, pine forests in Lithuania, Montenegro, and Ukraine have been significantly damaged by pine bark beetles (Tomicus sp.), which are closely associated with ophiostomatoid and other pathogenic fungi. This study aimed to identify the diversity of ophiostomatoid and other fungi associated with Tomicus sp. in these three countries. Fungi were isolated from beetles and identified. High-throughput sequencing of ITS2 rDNA yielded 285,828 reads, of which 91,141 high-quality reads were retained, representing 561 fungal operational taxonomic units (OTUs). The most important groups of fungi included ophiostomatoids, yeasts, and plant pathogens. While the fungal communities associated with Tomicus spp. were influenced more by environmental factors than by beetle species, the presence of known pathogens such as Ophiostoma spp. indicates that Tomicus spp. could play a significant role in dispersing harmful fungi. Although the virulence of these fungi may vary, their association with potentially pathogenic species suggests that Tomicus spp. may contribute to forest health decline, especially if environmental conditions or host susceptibility change. Full article

Background: Children in pediatric oncology report unmet needs related to communication and information about the illness, care involvement, and psychosocial support. Supporting the whole family involves challenges, with a risk that children’s voices are not heard above those of the adults. Article 12 of the UNCRC has been a catalyst in supporting children’s voices and their right to participate in processes that affect them. The aim of this study was to explore how children with cancer and their siblings experienced participation in a family-centered psychosocial support intervention, the Family Talk Intervention (FTI). Methods: Interviews were held with 35 children (ill and siblings) from 26 families in pediatric oncology after having completed the FTI. A combined deductive and inductive qualitative content analysis was undertaken, guided by the Lundy model of child participation. Results: Children’s experiences of being able to express their views, being listened to, and being involved during FTI were mainly positive. This was related to their participation in individual meetings where they could raise their concerns and views, undertake small activities while talking, and have their voices and needs mediated to relevant adults, such as parents and professionals. Conclusions: The findings of this study showed that the FTI for families in pediatric oncology created opportunities to promote child participation. These findings indicate that, by offering children an individual space where they can express themselves freely and supporting them in various ways to do so, the children’s voices and involvement are strengthened. Full article

Background/Objectives: Early pediatric cochlear implantation positively impacts early language outcomes. The Teenager and Young Adults Cochlear Implant (TAYACI) study investigates the long-term outcomes of early implantation and factors influencing variability among cochlear implant (CI) users. This article outlines participants’ background, early language outcomes, and multidisciplinary study protocol. Methods and Materials: Individuals aged 12–22 received CIs before 30 months of age, followed-up at the same hearing implant center, and adhered to a standard school curriculum were invited to participate. Out of 109 eligible CI users, 50 participated; 46 agreed to undergo clinical assessments, while four completed questionnaires only. Results: The mean age at the first CI was 15.63 months (SD = 6.0). All but one communicated with spoken language(s). Participants attended mainstream schools and had highly educated parents. Over half (56%) had received Auditory Verbal Therapy in early childhood. Earlier implantation correlated with better language understanding one year post-CI. Conclusions: Earlier implantation was associated with better early language outcomes, with parental education level and early family-centered intervention likely contributing. Future sub-studies will investigate multidisciplinary long-term effects of pediatric cochlear implantation in adolescents. Full article

To understand how telework is perceived among occupational groups with different work tasks within the same company, this qualitative study aimed to explore how managers and employees experience telework in relation to well-being, individual performance, and the work environment. This qualitative study used a phenomenographic approach. Fourteen online interviews, comprising seven managers and seven employees from the same industrial company, were conducted between February 2022 and September 2023. The data were analyzed inductively to capture variations in telework perceptions. The findings showed that telework is not universally beneficial or challenging; its effectiveness depends on contextual factors such as team setting, job role, type of work, and organizational culture. Telework benefits both employees and managers engaged in individual tasks (e.g., reading, drafting contracts, and preparing reports) or global collaborations, including improved well-being, work–life balance, and overall performance. However, starting with an office-based period that facilitated team cohesion, faster learning, and a deeper understanding of the organizational culture. Face-to-face onsite work could be time-consuming and, therefore, stressful for some, but it is time-saving for others. Onsite employees and managers faced increased workloads when colleagues teleworked, as employees tended to rely more on colleagues physically present in the office. This research highlights the need for tailored strategies to enhance the advantages of telework while reducing its challenges. It contributes to existing research by providing nuanced insights into the relationship between telework and occupational groups within an industrial setting and offering practical guidance for telework in this field. Full article