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Exploring the Impact of Environmental Chemical Pollutants in Alzheimer's Disease: Insights from SH-SY5Y Cell Line Studies and Literature Review on Blood-Brain Barrier Involvement
No full textTo restrict transportation to and from the brain, the blood-brain barrier works as a border between the blood system and the brain. It is an important hinder for xenobiotics to reach the brain were molecules’ characteristics, such as lipophilicity can determine the cross over. Alzheimer's disease is a progressive neurodegenerative disease which is connected to old age and gene mutations. However, the cause for the disease has also been linked to environmental risk factors. Environmental pollutants are present in many different matrixes in the environment and can cause adverse health effects to living organisms. In recent years, environmental pollution has been connected to the development of diseases like Alzheimer's disease. The aim of this project was to combine in vitro studies with existing literature to assess the potential effects of environmental pollutants exposure on neuronal cells and their relevance to Alzheimer's disease. For the literature review, Web of Science was used where searches were limited by the occurrence of “chemical name” and “Blood-Brain- Barrier" in the abstract. A typical flow diagram was then used to narrow down the hits to relevant articles, which were then included. The literature review included 17-β-estradiol, Estrone, Erytromycine, Clarithromycin, Sulfamethoxazole, Paracetamol, Ibuprofen, Salbutamol, Oxazepam, Nicotine, α-Hexachlorocyclohexane, Lindane, Perfluorooctanoic acid and Perfluorooctane sulfonic acid. Findings from the literature review included different types of Alzheimer's markers, like tau protein aggregation, Blood-Brain Barrier transporter proteins like, breast cancer resistant protein and P glycoprotein and tight junction protein, such as Claudin-5 and Occludin. Other Blood-Barin barrier related markers, indicating inflammatory responses, permeability and dysfunction were also found. Negative effects which could be linked to Alzheimer's disease by chemicals tested was 17-β-estradiol which reduced breast cancer resistant protein transport. Positive effects relating to Alzheimer's disease was seen for Sulfamethoxazole and Salbutamol which inhibited tau aggregation. In the in vitro experiment, SH-SY5Y cells were exposed to chemicals (17-β-estradiol, Estrone, Erytromycine, Azithromycin, Dinclofenac, Paracetamol, Ibuprofen, Oxadiazon, Triallat, Imidacloprid, Thiacloprid, Thiamethoxam, Clothianidin, Acetamiprid, Mepanipyrim, Cyprodinil, 2,6-ditert-butyl-4-methylphenol and 4methoxycinnamate de 2-ethylhexyle) for 24 h in 1, 10, and 50 µM concentrations, with three replicas for each chemical. The cell viability was tested by the AlamarBlue assay. Based on the in vitro study, a significant effect (P-value=0.039) was seen for the chemical 4methoxycinnamate de 2-ethylhexyle where a metabolic activation increase was seen for the largest concentration (50 µM). Due to the lack of studies focusing on pollutants’ effect on Alzheimer's disease related markers, a large knowledge gap is yet to be filled.
Temporal Synchrony Across Trophic Levels : Linking Vegetation Green-Up, Caterpillar Phenology and Breeding Timing in Ficedula Flycatchers
No full textClimate change brings with it many changes throughout natural ecosystems. One of the manyimpacts it has is changes to trophic interactions, especially between closely interactingspecies. One such interaction is the Collared flycatcher (Ficedula albicollis) which attemptsto match the hatching of their young to the peak abundance of their preferred prey, leaf eatingcaterpillars. The caterpillars in turn attempt to synchronize their egg hatching to the bud burstof their host trees. However, since each trophic level may respond differently toenvironmental cues such as temperature, climate change may cause phenological mismatch. Being phenologically mismatched can have a negative effect on fitness and understandinghow the trophic levels of deciduous trees, leaf eating caterpillars and flycatchers interact isimportant to understand the effects of climate change. In this study, this will be investigatedby using remotely sensed data on tree phenology and data on temperature to model caterpillaroccurrence. This model will in turn be used to investigate how the flycatcher breedingperiods are matched/mismatched to the caterpillar occurrences and the effect of mismatch onoffspring fitness. Our results show that caterpillar phenology is more strongly influenced bytemperature than by vegetation green-up. We also find that flycatchers whose breeding ismismatched with the peaks in caterpillar abundance experience negative fitness consequencescompared to flycatchers breeding more in synchrony with the caterpillar phenology.Furthermore, rising temperatures caused by climate change is found to increase thephenological mismatch, hinting at potential risks for the flycatchers in the future. Finally, wedemonstrate that remotely sensed tree phenology is a useful tool in predicting the occurrenceof caterpillars, providing possibilities for studying current and historical trophic interactions.Our findings highlight the importance of phenological mismatch in this study system andsuggest potential adaptive responses in flycatchers that warrant further investigation
The impact of policy design on public opposition to restrictive climate policies
No full textWith the growing emergency of global warming and biodiversity loss, and difficulties to reduce the impact of consumption, some researchers and government authorities have raised the idea of using rationing to reduce individuals' climate impact. Yet public opinion research on such policies and whether policy design affects public attitudes remain scant. Surveying over 3000 Swedish citizens, we provide the first experimental test of people's attitudes towards the rationing of transportation fuels and red meat in two identical, but separate, conjoint experiments. Our results reveal that the vast majority of our sample have conditional preferences, meaning their support for rationing is contingent on its specific design. In contrast, 23 % of the sample remain strongly opposed to all fuel and meat rationing proposals, irrespective of their design. Opposition to rationing decreases if people are allowed to consume more, if the allocation takes people's needs into account, if people are allowed to consume similar amounts over time and if the price for consumption does not rise unchecked. We uncover clear heterogeneities in design preferences depending on respondent characteristics, particularly for perceived fairness and effectiveness of rationing and current consumption behavior. Our findings add to the growing evidence indicating that the design of climate policies matters for people, but they also uncover the limits of policy design when climate policies have clear material implications
Empowering women through radio : Evidence from Occupied Japan
No full textI study the impact of women's radio programs that the US-led occupying force aired nationwide in Occupied Japan (1945-1952) to dismantle the prewar patriarchal norms. From the perspective of the economics of identity, the radio messages can be viewed as attempts to alter gendered identity norms, and thus to shift women's political, economic and family outcomes. Using local variation in radio signal strength driven by soil conditions as an instrumental variable, I show that greater exposure to women's radio programs increased women's electoral turnout, and the vote share for female candidates, highlighting women's votes matter. I find no effects on women's labor market outcomes, but exposure to women's radio programs accelerated the postwar fertility transition. Overall, disseminating pro-gender-equality messages can have significant implications for both women's lives and society at large, potentially paving the way for rapid economic growth that would follow
Development of quantitative geophysical proxy indicators for urban underground space use : An analysis of Stockholm and its city plan
No full textIn the absence or unavailability of geometric information about underground structures, conventional quantitative indicators of Urban Underground Space (UUS) usage become challenging to obtain. Socio-economic proxy indicators, that are reportedly well correlated with these conventional indicators, are inherently unstable measures given their susceptibility to non-linear human decision-making processes. To address this limitation, we evaluated the potential of geophysical proxy indicators, specifically the magnetic 3D analytic signal (AS), as a basis for UUS assessment. We also assessed the suitability of the magnetic susceptibility model as a framework for three-dimensional subsurface planning. Stockholm's airborne magnetic data acquired in 1995 were processed to generate an AS map that delineated its metro system (tunnelbana) and similar subsurface structures. Observed signatures, correlated with the overlain metro layout, were independently validated on an electrical current density map derived from co-acquired tensor very low-frequency electromagnetic data. Because AS emphasizes the sharp edges of magnetic contrasts, it provides a direct geophysical marker of anthropogenic underground structures and, consequently, an effective proxy indicator for UUS utilization. We introduce two new indicators: analytic signal density (ASD, expressed in nT/m per hectare, interpreted as "the amount of underground structure from a certain depth range that fits a surface area of 1 ha"), and analytic signal per capita (ASPC, expressed in nT/m per 100 person, interpreted as "the amount of underground structure from a certain depth range per capita". Both demonstrate strong correlations, comparable with those of conventional indicators, with population density (r = 0.88 and r = -0.69, respectively). The 3D magnetic susceptibility inversion model further predicted known infrastructure with a vertical accuracy of similar to 20 m, which can be improved with better data quality. Our results indicate that central Stockholm exhibited significantly higher UUS usage in 1995 (> 1.2 nT/m per hectare and < 2.0 nT/m per 100 person) than other Stockholm areas in the same year. The model for 2023, based on population density, estimated a 20-60 % increase in UUS use in central Stockholm since 1995. This trend underscores the need to integrate UUS in planning and development in both the central districts and the development focus areas of Stockholm city plan, where substantial UUS use was also evident. We conclude that, pending the establishment and adoption of standards for UUS use, Stockholm municipality needs a rethink of its population-driven (coined as "first-full first-developed") underground development strategy, identified through the comparative analysis of the geophysical proxy UUS use indicators of 1995 and model estimates for 2023. Given the rapid and extensive coverage afforded by airborne magnetic surveys, ASD and ASPC provide a novel, scalable, and tangible proxy for estimating and comparing UUS use across cities, particularly in data-limited or data-denied environments
A systematic analysis of the impact of data variation on AI-based histopathological grading of prostate cancer
No full textThe histopathological evaluation of biopsies by human experts is a gold standard in clinical disease diagnosis. While recent artificial intelligence-based (AI) approaches have reached human expert-level performance, they often display shortcomings caused by variations in sample preparation, limiting clinical applicability. This study investigates the impact of data variation on AI-based histopathological grading and explores algorithmic approaches that confer prediction robustness. To evaluate the impact of data variation in histopathology, we collected a multicentric, retrospective, observational prostate cancer (PCa) trial consisting of six cohorts in 3 countries with 25,591 patients, 83,864 images. This includes a high-variance dataset of 8,157 patients and 28,236 images with variations in section thickness, staining protocol, and scanner. This unique training dataset enabled the development of an AI-based PCa grading framework by training on patient outcome, not subjective grading. It was made robust through several algorithmic adaptations, including domain adversarial training and credibility-guided color adaptation. We named the final grading framework PCAI. We compare PCAI to a BASE model and human experts on three external test cohorts, comprising 2,255 patients and 9,437 images. Variations in sample processing, particularly section thickness and staining time, significantly reduced the performance of AI-based PCa grading by up to 8.6 percentage points in the event-ordered concordance index (EOC-Index) thus highlighting serious risks for AI-based histopathological grading. Algorithmic improvements for model robustness, credibility, and training on high-variance data as well as outcome-based severity prediction give rise to robust models with grading performance surpassing experienced pathologists. We demonstrate how our algorithmic enhancements for greater robustness lead to significantly better performance, surpassing expert grading on EOC-Index and 5-year AUROC by up to 21.2 percentage points
Percutaneous and surgical management of aortic stenosis in the SWEDEHEART registry (2013-2023) : a nationwide observational study.
No full textBACKGROUND: Management of severe aortic stenosis (AS) has evolved over the past decade, driven by the widespread adoption of transcatheter aortic valve implantation (TAVI). This study aims to assess trends in procedural volumes, patient characteristics, and outcomes for patients undergoing TAVI or surgical aortic valve replacement (SAVR) in Sweden. METHODS: This was a descriptive, non-comparative, nationwide cohort study using the SWEDEHEART registry. We included 21,383 patients who underwent TAVI or SAVR between 2013 and 2023 (11,366 TAVI and 10,017 SAVR). Trends in patient characteristics, preoperative risk, complications and mortality were examined. FINDINGS: TAVI procedures increased from 307 (26.1%, n = 307/1174) in 2013 to 1851 (71.2%, n = 1851/2601) in 2023, while SAVR volumes declined from ∼1000 annually before 2018 to roughly 750 procedures annually. Median age of TAVI patients were 81 (IQR 77, 85) years and 71 (IQR 65, 76) years for SAVR patients. The median EuroSCORE II for TAVI decreased from 5.6 (IQR 3.3, 10.2) to 2.7 (IQR 1.7, 4.6) (p = 0.002), and STS-PROM from 3.3 (IQR 1.9, 4.1) to 1.6 (IQR 1.1, 2.8) (p = 0.0021). Among SAVR patients, EuroSCORE II decreased from 1.5 (IQR 1.0, 2.3) to 1.3 (IQR 0.9, 2.1) (p = 0.022) and STS-PROM from 1.8 (IQR 1.2, 3.0) to 1.6 (IQR 1.1, 2.6) (p = 0.0082). Any in-hospital complications declined significantly for TAVI (29.2%, n = 210/719 to 13.2%, n = 244/1851), while SAVR complication rates increased slightly (18.4%, n = 354/1921 to 18.7%, n = 140/750). In-hospital mortality for TAVI declined from 3.6% (n = 26/719) to 1.0% (n = 18/1851), and 1-year mortality from 11.1% to 6.9% (p = 0.019). SAVR in-hospital all-cause death decreased from 1.6% to 0.4% (n = 3/750) and 5.0% to 2.2% for 1-year mortality (p = 0.013). INTERPRETATION: TAVI has become the predominant treatment strategy for AS in Sweden expanding access within the treated cohort. Despite this, current 2023 SAVR results demonstrate similar in-hospital complication rates compared to TAVI (18.7% vs 13.2%), but lower in-hospital (0.4% vs 1.0%) and 1-year mortality rates (2.2% vs 6.9%). FUNDING: This study was supported by ALF and national research funding bodies
Radiation doses in ventriculoperitoneal shunt catheter imaging - Comparing traditional plain radiography with computed tomography and photon counting computed tomography.
No full textINTRODUCTION: Hydrocephalus is a common condition with enlarged ventricles in the brain. It is often surgically treated with a ventriculoperitoneal shunt system. These patients require regular radiological controls, which exposes them to a cumulative dose of ionizing radiation. The aim with this study was to identify CT protocols that provide diagnostically adequate image quality with equal or lower radiation dose, compared with traditional plain radiography. METHODS: Four anthropomorphic phantoms representing pediatric patients of ages 1, 5 and 10, and an adult, were imaged with a series of CT protocols on three different scanners (including one photon counting) to determine a protocol that would offer the lowest radiation dose with adequate image quality. The image quality was visually assessed and graded by two radiologists. For comparison, a retrospective study was conducted on patients who had undergone a shunt series with plain radiography from April 2021 to December 2023. RESULTS: The mean effective dose for all the 137 patients imaged with plain radiography was 2.35 mSv, ranging from 0.14 to 3.73 mSv. The mean effective dose increased with age. For all four phantoms, the study identified at least one CT protocol that provided a lower effective dose than the mean dose from plain radiography in the respective age group, as well as one minimal dose protocol per patient group. As expected, CT examinations had significantly shorter time durations (approximately 10 s vs 14.9 min for adults). CONCLUSION: This study showed that various low-dose CT protocols, with or without photon counting technology, can be used for imaging ventriculoperitoneal shunt catheters, with comparable or lower effective dose compared with plain radiography. IMPLICATIONS FOR PRACTICE: A transition from plain radiography to CT offers several benefits, such as decreased discomfort for the patient, shorter examination time, richer imaging data, and decreased radiation dose
Temporal meal patterns in relation to diet quality and body mass index : findings from a cross-sectional analysis
No full textPurpose Although recent studies suggest associations between temporal meal patterns, diet quality, and health outcomes such as obesity and cardiometabolic risk, the evidence remains inconclusive, highlighting the need for further investigation. This study aimed to evaluate meal patterns, including meal frequency, breakfast skipping and timing of energy intake (late or early), and their associations with diet quality and body mass index. Methods The study was completed as a secondary analysis of two cross-sectional, national dietary surveys, Riksmaten Adults 2010-11 (n = 1796) and Riksmaten Adolescents 2016-17(n = 2967). Meal patterns were reported for 3-4 days using two different web-based methods. Among adolescents, weight was measured using standardised methods, whereas adults provided self-reported weight. Diet quality was evaluated with the Swedish Healthy Eating Index 2025. Results Meal patterns differed according to weight status, where adults with obesity or adolescents with overweight or obesity reported a lower meal frequency and more often skipped breakfast. A low eating frequency, breakfast skipping, and a late energy distribution were negatively associated with diet quality. A high meal frequency (OR 0.44 CI 0.28-0.68) and a late energy distribution (OR 0.70 CI 0.57-0.85) were associated with a decreased risk for overweight or obesity in adolescents. Conclusion Our study suggests that there may be a benefit in having a higher eating frequency and consuming breakfast, with regard to diet quality and weight
Dissecting the details : A case-based anatomical walkthrough of the antegrade posterior interosseous artery flap for elbow reconstruction
No full textThe pedicled posterior interosseous artery flap is a reliable and effective option for reconstructing soft tissue defects in the upper extremity. Commonly described in a retrograde fashion for distal defects, its antegrade counterpart is less frequently reported, particularly in relation to elbow reconstructions. Additionally, there are few and less detailed descriptions on how to safely and correctly identify the posterior interosseous nerve (PIN) in the harvest. The current case describes the use of the pedicled antegrade posterior interosseous artery flap to resurface a complex elbow wound with exposed triceps tendon, exposed ulnar nerve and an open elbow joint. We present a detailed step-by-step harvest with the additional anatomical description of the topography of the PIN branches relative to the PIA pedicle. (c) 2025 The Author(s). Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/