Although the basis of Alzheimer's disease (AD) etiology remains unknown, oxidative stress (OS) has been recognized as a prodromal factor associated to its progression. OS refers to an imbalance ...between oxidant and antioxidant systems, which usually consist in an overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) which overwhelms the intrinsic antioxidant defenses. Due to this increased production of ROS and RNS, several biological functions such as glucose metabolism or synaptic activity are impaired. In AD, growing evidence links the ROS-mediated damages with molecular targets including mitochondrial dynamics and function, protein quality control system, and autophagic pathways, affecting the proteostasis balance. In this scenario, OS should be considered as not only a major feature in the pathophysiology of AD but also a potential target to combat the progression of the disease. In this review, we will discuss the role of OS in mitochondrial dysfunction, protein quality control systems, and autophagy associated to AD and suggest innovative therapeutic strategies based on a better understanding of the role of OS and proteostasis.
Background
18F‐FDG PET‐CT is a potentially useful technique to help manage invasive fungal infection (IFI), but information on this topic is scarce.
Objectives
To describe our experience using ...18F‐FDG PET‐CT for IFI management.
Patients/Methods
Retrospective cohort of IFI episodes in a university hospital from 2018 to 2023 with a18F‐FDG PET‐CT performed during the episode. We analysed its impact on IFI management compared to conventional imaging.
Results
Thirty‐five patients diagnosed with 36 episodes of IFI (52.8% moulds, 44.4% yeasts and 2.8% Pneumocystis) underwent 55 18F‐FDG PET‐CT. 74.3% were immunocompromised, including 45.7% solid organ transplant recipients. Indications for 18F‐FDG PET‐CT were diagnostic (10.9%), staging (47.3%) and follow‐up (41.8%). Altogether 18F‐FDG PET‐CT added value to IFI management in 50.9% episodes. In 26 patients who had both staging 18F‐FDG PET‐CT and conventional imaging, sites of IFI dissemination were detected in 53.8% and 19.2%, respectively. Staging 18F‐FDG PET‐CT unveiled occult sites in 34.6%, uncovering unknown dissemination in 19.2%. In the evaluation of endocarditis in patients with fungemia, it contributed in at least 38.5%.
Follow‐up 18F‐FDG PET‐CTs had an added value in 47.8% episodes. They were allowed to de‐escalate antifungal therapy in 26.1%. There were discordant findings between 18F‐FDG PET‐CT and CT follow‐up in 40% cases.
Conclusions
Overall, 18F‐FDG PET‐CT added value to IFI management in more than 50% of the episodes. It increased the diagnosis of occult sites, unveiled disseminated disease missed out by conventional imaging, and contributed to diagnose or rule out endocarditis in fungemia. Follow‐up 18F‐FDG PET‐CT helped adjust the treatment duration and deserves further study.
Background: Chemical methods allowing a single soil extraction followed by multi‐elemental simultaneous measurement by ICP‐OES are increasingly used to predict plant uptake; however, calibration ...results against crop response are scarce and contradictory.
Aims: Our aims were to evaluate the efficacy of five extractants to predict nutrient uptake by a greenhouse wheat crop, as well as the influence of soil properties on nutrient concentrations in soil extracts and wheat plants.
Methods: Unlike other calibration studies, we monitored the pre‐seeding to post‐harvesting changes in soil available Ca, K, Mg, Cu, Fe, Mn, Zn, and Al. We extracted 14 acidic soils (C content: 47–114 g kg−1) with two traditional (AA: ammonium acetate; DTPA: diethylenetriamine‐pentaacetic acid) and three multi‐element extractants (AB‐DTPA: ammonium bicarbonate‐DTPA; Mehlich‐3; AA‐DTPA: ammonium acetate‐DTPA).
Results: Relationships between bioavailable and chemically extractable elements were strong for K (R2 = 0.776 to R2 = 0.882; p < 0.001) and Zn (R2 = 0.663 to R2 = 0.721; p < 0.001), especially for AB‐DTPA and AA‐DTPA. Multiple regressions including also soil properties can predict wheat‐Ca (Feoxihydroxides, clay and CaAB‐DTPA; R2 = 0.656; p < 0.001) and wheat‐Cu Aloxihydroxides and either CuAB‐DTPA (R2 = 0.515; p < 0.01) or CuAA‐DTPA (R2 = 0.472; p < 0.01). Pre‐seeding to post‐harvesting changes in KAA‐DTPA and KAB‐DTPA were strongly related with K uptake by wheat (R2 = 0.927 and R2 = 0.949, respectively; p < 0.001); similarly, for wheat‐Zn the best relationships were with ZnMehlich‐3 and ZnAA‐DTPA (R2 = 0.654 and R2 = 0.757, respectively; p < 0.001).
Conclusion: Consequently, chemical extractants alone can adequately predict K and Zn bio‐availability, and combined with some soil properties can predict wheat uptake of Ca and Cu, but not that of other nutrients.
Ubiquinol can protect endothelial cells from multiple mechanisms that cause endothelial damage and vascular dysfunction, thus contributing to dementia. A total of 69 participants diagnosed with mild ...cognitive impairment (MCI) received either 200 mg/day ubiquinol (Ub) or placebo for 1 year. Cognitive assessment of patients was performed at baseline and after 1 year of follow-up. Patients' cerebral vasoreactivity was examined using transcranial Doppler sonography, and levels of Ub and lipopolysaccharide (LPS) in plasma samples were quantified. Cell viability and necrotic cell death were determined using the microvascular endothelial cell line bEnd3. Coenzyme Q10 (CoQ) levels increased in patients supplemented for 1 year with ubiquinol versus baseline and the placebo group, although higher levels were observed in male patients. The higher cCoQ concentration in male patients improved cerebral vasoreactivity CRV and reduced inflammation, although the effect of Ub supplementation on neurological improvement was negligible in this study. Furthermore, plasma from Ub-supplemented patients improved the viability of endothelial cells, although only in T2DM and hypertensive patients. This suggests that ubiquinol supplementation could be recommended to reach a concentration of 5 μg/mL in plasma in MCI patients as a complement to conventional treatment.
During the last two decades, over 100 proteomics studies have identified a variety of potential biomarkers in CSF of Alzheimer's (AD) patients. Although several reviews have proposed specific ...biomarkers, to date, the statistical relevance of these proteins has not been investigated and no peptidomic analyses have been generated on the basis of specific up- or down- regulation. Herein, we perform an analysis of all unbiased explorative proteomics studies of CSF biomarkers in AD to critically evaluate whether proteins and peptides identified in each study are consistent in distribution; direction change; and significance, which would strengthen their potential use in studies of AD pathology and progression.
We generated a database containing all CSF proteins whose levels are known to be significantly altered in human AD from 47 independent, validated, proteomics studies. Using this database, which contains 2022 AD and 2562 control human samples, we examined whether each protein is consistently present on the basis of reliable statistical studies; and if so, whether it is over- or under-represented in AD. Additionally, we performed a direct analysis of available mass spectrometric data of these proteins to generate an AD CSF peptide database with 3221 peptides for further analysis.
Of the 162 proteins that were identified in 2 or more studies, we investigated their enrichment or depletion in AD CSF. This allowed us to identify 23 proteins which were increased and 50 proteins which were decreased in AD, some of which have never been revealed as consistent AD biomarkers (i.e. SPRC or MUC18). Regarding the analysis of the tryptic peptide database, we identified 87 peptides corresponding to 13 proteins as the most highly consistently altered peptides in AD. Analysis of tryptic peptide fingerprinting revealed specific peptides encoded by CH3L1, VGF, SCG2, PCSK1N, FBLN3 and APOC2 with the highest probability of detection in AD.
Our study reveals a panel of 27 proteins and 21 peptides highly altered in AD with consistent statistical significance; this panel constitutes a potent tool for the classification and diagnosis of AD.
A collision tumour (CT) is a neoplastic lesion comprised of two or more distinct cell populations that maintain distinct borders. Mostly, these are incidental findings in skin biopsies, whose ...pathologic mechanism and prevalence remain unknown, with few references among literature. Here, we present a retrospective study of CT, diagnosed by a dermatopathologist in our hospital between 2019-2022. Lesions have been defined individually and organized into three categories: benign-benign (BB), benign-malignant (BM) and malignant-malignant (MM). A total of 108 CT were diagnosed (1,4% of the biopsies from the dermatopathologist during this period), from which BM was the most frequent collision (48,5%). Globally, basal cell carcinoma (BCC) was the main malignant lesion and melanocytic nevus (MN) the main benign lesion. We have used the software Stata 14.2 in order to analyse results, and we have detected a statistically significant difference between age and collision type.
Abstract Background 18 F‐FDG PET‐CT is a potentially useful technique to help manage invasive fungal infection (IFI), but information on this topic is scarce. Objectives To describe our experience ...using 18 F‐FDG PET‐CT for IFI management. Patients/Methods Retrospective cohort of IFI episodes in a university hospital from 2018 to 2023 with a 18 F‐FDG PET‐CT performed during the episode. We analysed its impact on IFI management compared to conventional imaging. Results Thirty‐five patients diagnosed with 36 episodes of IFI (52.8% moulds, 44.4% yeasts and 2.8% Pneumocystis) underwent 55 18 F‐FDG PET‐CT. 74.3% were immunocompromised, including 45.7% solid organ transplant recipients. Indications for 18 F‐FDG PET‐CT were diagnostic (10.9%), staging (47.3%) and follow‐up (41.8%). Altogether 18 F‐FDG PET‐CT added value to IFI management in 50.9% episodes. In 26 patients who had both staging 18 F‐FDG PET‐CT and conventional imaging, sites of IFI dissemination were detected in 53.8% and 19.2%, respectively. Staging 18 F‐FDG PET‐CT unveiled occult sites in 34.6%, uncovering unknown dissemination in 19.2%. In the evaluation of endocarditis in patients with fungemia, it contributed in at least 38.5%. Follow‐up 18 F‐FDG PET‐CTs had an added value in 47.8% episodes. They were allowed to de‐escalate antifungal therapy in 26.1%. There were discordant findings between 18 F‐FDG PET‐CT and CT follow‐up in 40% cases. Conclusions Overall, 18 F‐FDG PET‐CT added value to IFI management in more than 50% of the episodes. It increased the diagnosis of occult sites, unveiled disseminated disease missed out by conventional imaging, and contributed to diagnose or rule out endocarditis in fungemia. Follow‐up 18 F‐FDG PET‐CT helped adjust the treatment duration and deserves further study.
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