Chitosan-coated manganese ferrite nanoparticles enhanced Rhodotorula toruloides carotenoid production.

The present study aims to analyze the interaction between Rhodotorula toruloides and magnetic nanoparticles and evaluate their effect on carotenoid production. The manganese ferrite nanoparticles were synthesized without chitosan (MnFe2O4) and chitosan coating (MnFe2O4-CS) by the co-precipitation method assisted by hydrothermal treatment. XRD (X-ray diffraction), Magnetometry, Dynamic Light Scattering (DLS) and FTIR (Fourier-Transform Infrared Spectroscopy), are used to characterize the magnetic nanoparticles. The crystallite size of MnFe2O4 was 16 nm for MnFe2O4 and 20 nm for MnFe2O4-CS. The magnetic saturation of MnFe2O4-CS was lower (39.6 ± 0.6 emu/g) than the same MnFe2O4 nanoparticles (42.7 ± 0.3 emu/g), which was attributed to the chitosan fraction presence. The MnFe2O4-CS FTIR spectra revealed the presence of the characteristic chitosan bands. DLS demonstrated that the average hydrodynamic diameters were 344 nm for MnFe2O4 and 167 nm for MnFe2O4-CS. A kinetic study of cell immobilization performed with their precipitation with a magnet demonstrated that interaction between magnetic nanoparticles and R. toruloides was characterized by an equilibrium time of 2 h. The adsorption isotherm models (Langmuir and Freundlich) were fitted to the experimental values. The trypan blue assay was used for cell viability assessment. The carotenoid production increased to 256.2 ± 6.1 µg/g dry mass at 2.0 mg/mL MnFe2O4-CS. The use of MnFe2O4-CS to stimulate carotenoid yeast production and the magnetic separation of biomass are promising nanobiotechnological alternatives. Magnetic cell immobilization is a perspective technique for obtaining cell metabolites.

COVID-19 and Cognitive Decline in Older Adults with High-Cardiovascular Risk: A Post Hoc Analysis.

Cognitive decline has been reported as a short-term sequela in patients hospitalized for coronavirus disease-19 (COVID-19). Whether COVID-19 is associated with late cognitive impairment in older free-living individuals with high cardiovascular risk, a group at greater risk of cognitive decline, is unknown. We determined this association of COVID-19 through a longitudinal evaluation of post-COVID-19 cognitive performance and impairment as post hoc analysis in 5,179 older adults (48% female) with mean (SD) age 68.5 (5.0) years, body mass index 31.7 (3.7) kg/m2, harboring ≥ 3 criteria for metabolic syndrome (e.g., hypertension, hyperlipidemia, hyperglycemia etc.) enrolled in PREDIMED-Plus trial. Pre- and post-COVID-19 cognitive performance was ascertained from scheduled assessments conducted using a battery of neuropsychological tests, including 5 domains: Global Cognitive Function, General Cognitive Function, Execution Function, Verbal Fluency and Attention domains, which were standardized for the cohort. Cognitive impairment was defined as the bottom 10 percentile of the sample. Multivariable linear and logistic regression models assessed the association of COVID-19 with cognitive decline and impairment, respectively. After a mean 50-week follow-up, no significant associations were observed between COVID-19 status and post-COVID-19 scores of all tapped neuropsychological domains, except Global Cognitive Function (GCF). When fully adjusted, COVID-19 was marginally associated with higher (better) post-pandemic GCF score (ßadj (95% CI): 0.06 (0.00, 0.13) p=.05). However, the odds for post-COVID-19 cognitive impairment in GCF domain were not associated with the disease (ORadj (95% CI): 0.90 (0.53, 1.51) p=.68). In the PREDIMED-Plus cohort, COVID-19 status and cognitive impairment determined 50 weeks post-infection showed no association in older adults at high cardiovascular risk. This suggests that cognitive changes observed shortly after COVID-19 revert over time. However, cautious interpretation is warranted as these data were obtained within the framework of a clinical trial encouraging a healthy lifestyle.

Comparative effects of viable Lactobacillus rhamnosus GG and its heat-inactivated paraprobiotic in the prevention of high-fat high-fructose diet-induced non-alcoholic fatty liver disease in rats.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver alterations worldwide, being gut microbiota dysbiosis one of the contributing factors to its development. The aim of this research is to compare the potential effects of a viable probiotic (Lactobacillus rhamnosus GG) with those exerted by its heat-inactivated paraprobiotic counterpart in a dietary rodent model of NAFLD. The probiotic administration effectively prevented the hepatic lipid accumulation induced by a high-fat high-fructose diet feeding, as demonstrated by chemical (lower TG content) and histological (lower steatosis grade and lobular inflammation) analyses. This effect was mainly mediated by the downregulation of lipid uptake (FATP2 protein expression) and upregulating liver TG release to bloodstream (MTTP activity) in rats receiving the probiotic. By contrast, the effect of the paraprobiotic preventing diet-induced liver lipid accumulation was milder, and mainly derived from the downregulation of hepatic de novo lipogenesis (SREBP-1c protein expression and FAS activity) and TG assembly (DGAT2 and AQP9 protein expression). The obtained results demonstrate that under these experimental conditions, the effects induced by the administration of viable L. rhamnosus GG preventing liver lipid accumulation in rats fed a diet rich in saturated fat and fructose differ from those induced by its heat-inactivated paraprobiotic counterpart.

Time-of-Day Adrenal Modulation of Corticosterone Synthesis is Affected by Sex and Diet but Not by Proanthocyanidins in Rat.

SCOPE: The aim of this study is to investigate the effect of time-of-day on serum hormones and gene expression in adrenal glands, studying the impact of sex, obesogenic diet, and timing of proanthocyanidins administration, with a focus on glucocorticoids synthesis by this gland. METHODS AND RESULTS: Female and male rats, assigned to a standard chow or a cafeteria diet-fed group, receive a daily oral dose of a grape seed proanthocyanidin extract (GSPE), or a vehicle (when light is turned on, or when light is turned off). Corticosterone, estradiol, and testosterone serum levels, and the expression analysis of clock genes and genes related to corticosterone synthesis pathway, are assessed. Serum hormone levels exhibited a marked time-of-day effect also see in the expression of scavenger receptor class B member 1 (Scarb1) and cyp11b genes. The correlation between these two genes and period circadian regulator 2 (Per2) is also extended to other clock genes, although to a lesser extent: cryptochrome (Cry) and nuclear receptor subfamily 1 group D member 1 (Rev-erba). CONCLUSION: The strong correlations found suggest an important role of local Per2 (but also of Cry and Rev-erbA) in regulating the expression of the enzymes involved in the corticosterone synthesis pathway. The expression of clock genes in adrenals is influenced by sex and diet but not by GSPE.

Association between overall quality of macronutrients and incidence of overweight and obesity in the SUN (Seguimiento Universidad de Navarra) cohort.

INTRODUCTION: no previous large prospective studies have assessed the global quality of macronutrients in association with the risk of overweight/obesity. OBJECTIVE: to prospectively assess the association of an overall macronutrient quality index (MQI) with weight change and the incidence of overweight/obesity in the Seguimiento Universidad de Navarra (SUN) cohort. METHODS: the diet of 9,344 Spanish university graduates (mean age: 36.5 [SD, 11.1]) was assessed through a validated 136-item food frequency questionnaire. The MQI was calculated as the sum of the Carbohydrate Quality Index, the Fat Quality Index, and the Healthy Plate Protein Quality Index. Participants were classified into groups according to MQI. Incident overweight/obesity was defined if follow-up questionnaires indicated BMI was ≥ 25 kg/m2. Multiple linear regression models and Cox proportional hazard models were used to assess the average yearly weight change and the risk of overweight/obesity over follow-up time. RESULTS: 2,465 cases of incident overweight/obesity were identified (median follow-up: 10.7 years). Increasing MQI was significantly associated with lower annual weight gain (g): ß coefficient: -99.0, (95 % CI: -173.6 to -24.5) in the Q4 vs Q1, p for trend = 0.007. In the fully adjusted model the incidences of overweight/obesity in Q4 and Q1 were 21.7 % (431 cases) and 29.3 % (954 cases), respectively. The adjusted HR was 0.87 (95 % CI, 0.77-0.98, p for trend = 0.036). When we used repeated analyses updating the MQI after 10 years of follow-up, results remained similar. CONCLUSIONS: a significant inverse association between a multidimensional MQI and the risk of overweight/obesity was found in this Mediterranean cohort of adults.

Vitamin D and the Risk of Developing Hypertension in the SUN Project: A Prospective Cohort Study.

Vitamin D deficiency has been associated with a higher risk of multiple diseases, including cardiovascular disorders. The purpose of this study was to examine the potential association between predicted levels of serum 25(OH)D and the risk of new-onset hypertension in a large Mediterranean cohort. A validated 136-item food frequency questionnaire was used as the dietary assessment tool. 25(OH)D serum levels were predicted using a previously validated equation. We performed Cox regression models to analyze the association between predicted serum 25(OH)D and the risk of hypertension, according to quartiles of forecasted vitamin D at baseline, after adjusting for multiple potential confounders. Over a median follow-up of 12.3 years, 2338 new cases of hypertension were identified. The analyses revealed a significant inverse association between predicted serum levels of 25(OH)D at baseline and the risk of hypertension. Individuals in the highest quartile showed a 30% relatively lower risk of hypertension compared to the lowest quartile (hazard ratio (HR): 0.70; 95% confidence interval (CI): 0.60-0.80, p-trend < 0.001). The outcomes remained significant after performing sensitivity analyses. The findings suggested that higher levels of forecasted vitamin D are inversely and independently associated with the risk of incident hypertension, implying that vitamin D may offer protective benefits against the disease.

Screen exposure, mental health and emotional well-being in the adolescent population: is it time for governments to take action?

During the last decade, a multitude of epidemiological studies with different designs have been published assessing the association between the use of digital media and psychological well-being, including the incidence of mental disorders and suicidal behaviours. Particularly, available research has very often focused on smartphone use in teenagers, with highly addictive potential, coining the term 'problematic smartphone use' and developing specific scales to measure the addictive or problematic use of smartphones. Available studies, despite some methodological limitations and gaps in knowledge, suggest that higher screen time is associated with impaired psychological well-being, lower self-esteem, higher levels of body dissatisfaction, higher incidence of eating disorders, poorer sleeping outcomes and higher odds of depressive symptoms in adolescents. Moreover, a significant association has also been found between screen time and higher suicide risk. Finally, problematic pornography has been shown to be highly prevalent and it is a strong cause of concern to many public health departments and national governments because it might be eventually associated with aggressive sexual behaviours.

Lipidome changes due to improved dietary fat quality inform cardiometabolic risk reduction and precision nutrition.

Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabolite concentrations. In the EPIC-Potsdam cohort, a difference in the MLS, reflecting better dietary fat quality, was associated with a significant reduction in the incidence of cardiovascular disease (-32%; 95% confidence interval (95% CI): -21% to -42%) and type 2 diabetes (-26%; 95% CI: -15% to -35%). We built a closely correlated simplified score, reduced MLS (rMLS), and observed that beneficial rMLS changes, suggesting improved dietary fat quality over 10 years, were associated with lower diabetes risk (odds ratio per standard deviation of 0.76; 95% CI: 0.59 to 0.98) in the Nurses' Health Study. Furthermore, in the PREDIMED trial, an olive oil-rich Mediterranean diet intervention primarily reduced diabetes incidence among participants with unfavorable preintervention rMLS levels, suggestive of disturbed lipid metabolism before intervention. Our findings indicate that the effects of dietary fat quality on the lipidome can contribute to a more precise understanding and possible prediction of the health outcomes of specific dietary fat modifications.

Mediterranean Diet and Cardiometabolic Biomarkers in Children and Adolescents: A Systematic Review and Meta-Analysis.

Importance: No prior systematic review and meta-analysis has specifically verified the association of Mediterranean diet (MedDiet)-based interventions with biomarkers of cardiometabolic health in children and adolescents. Objective: To review and analyze the randomized clinical trials (RCTs) that assessed the effects of MedDiet-based interventions on biomarkers of cardiometabolic health among children and adolescents. Data Sources: Four electronic databases were searched (PubMed, Cochrane Library, Web of Science, and Scopus) from database inception to April 25, 2024. Study Selection: Only RCTs investigating the effect of interventions promoting the MedDiet on cardiometabolic biomarkers (ie, systolic blood pressure [SBP], diastolic blood pressure [DBP], triglycerides [TGs], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], glucose, insulin, and homeostatic model assessment for insulin resistance [HOMA-IR]) among children and adolescents (aged ≤18 years) were included. Data Extraction and Synthesis: A systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data were extracted from the studies by 2 independent reviewers. Results across studies were summarized using random-effects meta-analysis. Main Outcome and Measures: The effect size of each trial was computed by unstandardized mean differences (MDs) of changes in biomarker levels (ie, SBP, DBP, TGs, TC, HDL-C, LDL-C, glucose, insulin, HOMA-IR) between the intervention and the control groups. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Results: Nine RCTs were included (mean study duration, 17 weeks; range, 8-40 weeks). These studies involved 577 participants (mean age, 11 years [range, 3-18 years]; 344 girls [59.6%]). Compared with the control group, the MedDiet-based interventions showed a significant association with reductions in SBP (mean difference, -4.75 mm Hg; 95% CI, -8.97 to -0.52 mm Hg), TGs (mean difference, -16.42 mg/dL; 95% CI, -27.57 to -5.27 mg/dL), TC (mean difference, -9.06 mg/dL; 95% CI, -15.65 to -2.48 mg/dL), and LDL-C (mean difference, -10.48 mg/dL; 95% CI, -17.77 to -3.19 mg/dL) and increases in HDL-C (mean difference, 2.24 mg/dL; 95% CI, 0.34-4.14 mg/dL). No significant associations were observed with the other biomarkers studied (ie, DBP, glucose, insulin, and HOMA-IR). Conclusions and Relevance: These findings suggest that MedDiet-based interventions may be useful tools to optimize cardiometabolic health among children and adolescents.

Early versus Delayed Vitrectomy for Open Globe Injuries: A Systematic Review and Meta-Analysis.

Background: Open globe injuries (OGIs) are a leading cause of monocular blindness worldwide and require prompt intervention to prevent proliferative vitreoretinopathy (PVR) and endophthalmitis when serious intraocular damage occurs. The management of OGIs involves initial wound closure within 24 hours, followed by vitrectomy as a secondary surgery. However, there is a lack of consensus regarding the optimal timing of vitrectomy for maximizing visual outcomes. This meta-analysis aimed to investigate whether early or delayed vitrectomy leads to better outcomes in patients with OGIs. Methods: This review was conducted based on PRISMA guidelines. The Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched (October 23, 2023). Clinical studies that used vitrectomy to manage OGIs as early (within 7 days) or delayed (8-14 days) interventions were included. Randomized controlled trials (RCTs) and non-RCTs were appraised using the Cochrane risk of bias and JBI tools, respectively. Results: Eleven studies met the inclusion criteria and were included in the quantitative analyses. There were 235 patients with OGIs who received early intervention and 211 patients who received delayed intervention. The retina was reattached in 91% and 76% of the patients after early and delayed intervention, respectively. Traumatic PVR was present in 9% and 41% of the patients in the early and delayed groups, respectively. The odds of retinal reattachment after vitrectomy were greater in the early group (OR = 3.42, p = 0.010, 95% CI=1.34-8.72), and the odds of visual acuity ≥ 5/200 were 2.4 times greater in the early group. The incidence of PVR was significantly greater in the delayed surgery group (OR = 0.16, p < 0.0001; 95% CI=0.06-0.39), which also required more than one vitrectomy surgery. Conclusion: Early vitrectomy results in better postoperative visual acuity, a greater proportion of retinal reattachment, and a decreased incidence of PVR.

Spermidine Synthase Localization in Retinal Layers: Early Age Changes.

Polyamine (PA) spermidine (SPD) plays a crucial role in aging. Since SPD accumulates in glial cells, particularly in Müller retinal cells (MCs), the expression of the SPD-synthesizing enzyme spermidine synthase (SpdS) in Müller glia and age-dependent SpdS activity are not known. We used immunocytochemistry, Western blot (WB), and image analysis on rat retinae at postnatal days 3, 21, and 120. The anti-glutamine synthetase (GS) antibody was used to identify glial cells. In the neonatal retina (postnatal day 3 (P3)), SpdS was expressed in almost all progenitor cells in the neuroblast. However, by day 21 (P21), the SpdS label was pronouncedly expressed in multiple neurons, while GS labels were observed only in radial Müller glial cells. During early cell adulthood, at postnatal day 120 (P120), SpdS was observed solely in ganglion cells and a few other neurons. Western blot and semi-quantitative analyses of SpdS labeling showed a dramatic decrease in SpdS at P21 and P120 compared to P3. In conclusion, the redistribution of SpdS with aging indicates that SPD is first synthesized in all progenitor cells and then later in neurons, but not in glia. However, MCs take up and accumulate SPD, regardless of the age-associated decrease in SPD synthesis in neurons.

Adenosine-assisted embolization of cerebral arteriovenous malformations: a systematic review and meta-analysis.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are complex lesions that can cause hemorrhagic stroke and significant neurological disability. Adenosine induces cardiac standstill and hypotension, which are thought to be useful during cerebral AVM embolization. Herein, we conducted a systematic review and meta-analysis of the technique's safety. METHODS: Following PRISMA guidelines, four databases were queried for studies describing the use of adenosine-assisted embolization of cerebral AVMs. Adenosine-related intraoperative complications, permanent neurological outcomes, morbidity, and mortality assessed the technique's safety. Single proportion analysis under a random-effects model was performed. Heterogeneity was assessed using I² statistics, and publication bias was evaluated through funnel plot analysis and Egger's regression test. RESULTS: Ten studies were included, involving 79 patients (55.7% male) with 79 AVMs (54.4% unruptured and 70.9% Spetzler-Martin grade III-V) who underwent 123 embolizations (80.4% and 5.9% under transarterial and transvenous approaches, respectively) with n-butyl cyanoacrylate (80.4%), ethylene vinyl alcohol (14.4%), or both (5.2%). The incidence of transient adenosine-related intraoperative complications was 0% (95% CI 0% to 3%, I2=24%). Besides, the incidence of adenosine-related morbidity, mortality, and permanent outcomes was 0% (95% CI 0% to 3%, I2=0%). During follow-up, good functional outcomes were reported for 64 patients (81%). CONCLUSIONS: Adenosine's effects on blood flow control can facilitate embolization and mitigate the risk of AVM rupture and embolic agent migration. Although current evidence stems from observational studies, the results of this meta-analysis suggest a safe drug profile due to minimal associated morbidity and mortality. Further research from larger randomized and controlled studies is warranted to attain a higher level of evidence. PROSPERO REGISTRY NUMBER: CRD42023494116.

Precision Atomistic Structures of Actinium-/Radium-/Barium-Doped Lanthanide Nanoconstructs for Radiotherapeutic Applications.

Lanthanide vanadate (LnVO4) nanoconstructs have generated considerable interest in radiotherapeutic applications as a medium for nanoscale-targeted drug delivery. For cancer treatment, LnVO4 nanoconstructs have shown promise in encapsulating and retaining radionuclides that emit alpha-particles. In this work, we examined the structure formation of LnVO4 nanoconstructs doped with actinium (Ac) and radium (Ra), both experimentally and using large-scale atomistic molecular dynamics simulations. LnVO4 nanoconstructs were synthesized via a precipitation method in aqueous media. The reaction conditions and elemental compositions were varied to control the structure, fluorescence properties, and size distribution of the LnVO4 nanoconstructs. LnVO4 nanoconstructs were characterized by X-ray diffraction, Raman spectroscopy, and fluorescence spectroscopy. Molecular dynamics simulations were performed to obtain a fundamental understanding of the structure-property relationship between radionuclides and LnVO4 nanoconstructs at the atomic length scale. Molecular dynamics simulations with well-established force field (FF) parameters show that Ra atoms tend to distribute across the nanoconstructs' surface in a broader coordination shell, while the Ac atoms are arranged inside a smaller coordination shell within the nanocluster. The Ba atoms prefer to self-assemble around the surface. These theoretical/simulation predictions of the atomistic structures and an understanding of the relationship between radionuclides and LnVO4 nanoconstructs at the atomic scale are important because they provide design principles for the future development of nanoconstructs for targeted radionuclide delivery.

Effect of internal limiting membrane surgical techniques on the idiopathic and refractory management of macular holes: a systematic review and meta-analysis.

Macular holes (MHs), including atraumatic idiopathic and refractory MHs, affect central vision acuity due to full-thickness defects in the retinal tissue. The existing controversy regarding the pathophysiology and management of MHs has significantly improved with the implementation of internal limiting membrane (ILM) surgical techniques and improved MH closure rates. Thus, to determine the effect of ILM techniques on large idiopathic and refractory MH management, the present study systematically reviewed 5910 original research articles extracted from online literature databases, including PubMed, Cochrane, Google Scholar, and Embase, following the PRISMA guidelines. The primary outcome measures were MH closure rate and postoperative visual acuity. A total of 23 randomized controlled trials (RCTs) with adequate patient information and information on the effect of ILM peeling, inverted ILM flaps, autologous retinal transplantation (ART), and ILM insertion techniques on large idiopathic and refractory MH patients were retrieved and analyzed using RevMan software (version 5.3) provided by the Cochrane Collaboration. Statistical risk of bias analysis was also conducted on the selected sources using RoB2, which showed a low risk of bias in the included studies. A meta-analysis indicated that the inverted ILM flap technique had a significantly greater MH closure rate for primary MH than the other treatment methods (OR = 3. 22, 95% CI 1.34-7.43; p = 0.01). Furthermore, the findings showed that the inverted ILM flap group had significantly better postoperative visual acuity than did the other treatment options for patients with idiopathic MH (WMD = - 0.13; 95% CI = 0.22-0.09; p = 0.0002). The ILM peeling technique had the second highest statistical significance for MH closure rates in patients with idiopathic MH (OR = 2. 72, 95% CI: 1.26-6.32; p = 0.016). In refractory MHs, autologous retinal transplant (ART) and multilayer ILM plug (MIP) techniques improve the closure rate and visual function; human amniotic membrane grafting (hAMG) provides a high degree of anatomical outcomes but disappointing visual results. This study demonstrated the reliability and effectiveness of ILM techniques in improving the functional and anatomical outcomes of large idiopathic and refractory MH surgery. These findings will help clinicians choose the appropriate treatment technique for patients with idiopathic and refractory MH.

Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention.

BACKGROUND: The Mediterranean diet (MedDiet) has demonstrated efficacy in preventing age-related cognitive decline and modulating plasma concentrations of endocannabinoids (eCBs) and N-acylethanolamines (NAEs, or eCB-like compounds), which are lipid mediators involved in multiple neurological disorders and metabolic processes. Hypothesizing that eCBs and NAEs will be biomarkers of a MedDiet intervention and will be related to the cognitive response, we investigated this relationship according to sex and apolipoprotein E (APOE) genotype, which may affect eCBs and cognitive performance. METHODS: This was a prospective cohort study of 102 participants (53.9% women, 18.8% APOE-ɛ4 carriers, aged 65.6 ± 4.5 years) from the PREDIMED-Plus-Cognition substudy, who were recruited at the Hospital del Mar Research Institute (Barcelona). All of them presented metabolic syndrome plus overweight/obesity (inclusion criteria of the PREDIMED-Plus) and normal cognitive performance at baseline (inclusion criteria of this substudy). A comprehensive battery of neuropsychological tests was administered at baseline and after 1 and 3 years. Plasma concentrations of eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and N-docosahexaenoylethanolamine (DHEA), were also monitored. Baseline cognition, cognitive changes, and the association between eCBs/NAEs and cognition were evaluated according to gender (crude models), sex (adjusted models), and APOE genotype. RESULTS: At baseline, men had better executive function and global cognition than women (the effect size of gender differences was - 0.49, p = 0.015; and - 0.42, p = 0.036); however, these differences became nonsignificant in models of sex differences. After 3 years of MedDiet intervention, participants exhibited modest improvements in memory and global cognition. However, greater memory changes were observed in men than in women (Cohen's d of 0.40 vs. 0.25; p = 0.017). In men and APOE-ε4 carriers, 2-AG concentrations were inversely associated with baseline cognition and cognitive changes, while in women, cognitive changes were positively linked to changes in DHEA and the DHEA/AEA ratio. In men, changes in the OEA/AEA and OEA/PEA ratios were positively associated with cognitive changes. CONCLUSIONS: The MedDiet improved participants' cognitive performance but the effect size was small and negatively influenced by female sex. Changes in 2-AG, DHEA, the OEA/AEA, the OEA/PEA and the DHEA/AEA ratios were associated with cognitive changes in a sex- and APOE-dependent fashion. These results support the modulation of the endocannabinoid system as a potential therapeutic approach to prevent cognitive decline in at-risk populations. TRIAL REGISTRATION: ISRCTN89898870.

Computational Insights into Dion-Jacobson Type Oxide Ion Conductors.

Dion-Jacobson type materials have recently emerged as a new structural family of oxide ion conductors, materials important for applications in a variety of electrochemical devices. While some attempts to improve their ionic conductivity have been reported, a detailed understanding of the underlying oxide ion diffusion mechanisms in these materials is still missing. To explore the structure-property relationships leading to the favorable properties, we carried out ab initio molecular dynamics simulations of oxide ion diffusion in CsBi2Ti2NbO10-δ. Our computational study reveals significant out-of-plane dynamics, indicating that the dominant pathway for oxide ion migration is via jumps into and out of the (ab) crystallographic plane. This suggests that further improvement of oxide ion conductivity relative to CsBi2Ti2NbO10-δ could be achieved by enhancing the rotational flexibility of the coordination polyhedra located in the inner perovskite layer, thereby facilitating faster out-of-plane motions.

Development of 225Ac-doped biocompatible nanoparticles for targeted alpha therapy.

Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([225Ac]Ac3+). Encapsulation of [225Ac]Ac3+ within PLGA nanoparticles (Zave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [225Ac]Ac3+. Chelation of [225Ac]Ac3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([225Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [225Ac]AcBLPhen significantly increased the delivery of [225Ac]Ac3+ to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [225Ac]Ac3+ in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles.

Férulas de Gunning. Una alternativa de tratamiento que sigue presente. Reporte de 02 casos / Gunning's splints. An alternative treatment that is still present. A report of 02 cases

Las fracturas condilares continúan siendo un desafío para los cirujanos maxilofaciales, debido a los múltiples tipos de fracturas que pueden ocurrir y los tratamientos disponibles. El tratamiento de este tipo de fractura podría dificultarse si el paciente presenta edentulismo. Así, entre las opciones de tratamiento, el uso de una férula o la prótesis dental preexistente como medio de fijación se muestra como una opción viable. Se presentan 02 casos clínicos de pacientes masculinos de 36 y 83 años de edad que presentan un maxilar edéntulo y fracturande cóndilo mandibular de lado derecho; para su tratamiento se utilizó una férula de Gunning superior con fijación intermaxilar mediante el uso de tornillos de fijación intermaxilar y elásticos intermaxilares durante 4 semanas. Después de 3 meses de evolución, ambos pacientes presentaron una adecuada apertura bucal, sin desviaciones o limitación a la apertura bucal. Las férulas de Gunning, a pesar que actualmente son poco usadas, continúan siendo una opción apropiada para los casos de fractura del cóndilo mandibular en pacientes edéntulos.

Condylar fractures continue to be a challenge for maxillofacial surgeons, due to the multiple types of fractures that can occur and the treatments available. Treatment of this type of fracture could be difficult if the patient has edentulism. Thus, among the treatment options, the use of a splint or the pre-existing dental prosthesis as a means of fixation appears to be a viable option. Two clinical cases are presented of male patients aged 36 and 83 years who present an edentulous maxilla and fracture of the mandibular condyle on the right side; For treatment, an upper Gunning splint with intermaxillary fixation was used through the use of intermaxillary fixation screws and intermaxillary elastics for 4 weeks. After 3 months of evolution, both patients presented adequate mouth opening, without deviations or limitations to mouth opening. Gunning splints, although they are currently rarely used, continue to be an appropriate option for cases of fracture of the mandibular condyle in edentulous patients.

Arabidopsis AGO1 N-terminal extension acts as an essential hub for PRMT5 interaction and post-translational modifications.

Plant ARGONAUTE (AGO) proteins play pivotal roles regulating gene expression through small RNA (sRNA) -guided mechanisms. Among the 10 AGO proteins in Arabidopsis thaliana, AGO1 stands out as the main effector of post-transcriptional gene silencing. Intriguingly, a specific region of AGO1, its N-terminal extension (NTE), has garnered attention in recent studies due to its involvement in diverse regulatory functions, including subcellular localization, sRNA loading and interactions with regulatory factors. In the field of post-translational modifications (PTMs), little is known about arginine methylation in Arabidopsis AGOs. In this study, we show that NTE of AGO1 (NTEAGO1) undergoes symmetric arginine dimethylation at specific residues. Moreover, NTEAGO1 interacts with the methyltransferase PRMT5, which catalyzes its methylation. Notably, we observed that the lack of symmetric dimethylarginine has no discernible impact on AGO1's subcellular localization or miRNA loading capabilities. However, the absence of PRMT5 significantly alters the loading of a subgroup of sRNAs into AGO1 and reshapes the NTEAGO1 interactome. Importantly, our research shows that symmetric arginine dimethylation of NTEs is a common process among Arabidopsis AGOs, with AGO1, AGO2, AGO3 and AGO5 undergoing this PTM. Overall, this work deepens our understanding of PTMs in the intricate landscape of RNA-associated gene regulation.

Correlating activities and defects in (photo)electrocatalysts using in-situ multi-modal microscopic imaging.

Photo(electro)catalysts use sunlight to drive chemical reactions such as water splitting. A major factor limiting photocatalyst development is physicochemical heterogeneity which leads to spatially dependent reactivity. To link structure and function in such systems, simultaneous probing of the electrochemical environment at microscopic length scales and a broad range of timescales (ns to s) is required. Here, we address this challenge by developing and applying in-situ (optical) microscopies to map and correlate local electrochemical activity, with hole lifetimes, oxygen vacancy concentrations and photoelectrode crystal structure. Using this multi-modal approach, we study prototypical hematite (α-Fe2O3) photoelectrodes. We demonstrate that regions of α-Fe2O3, adjacent to microstructural cracks have a better photoelectrochemical response and reduced back electron recombination due to an optimal oxygen vacancy concentration, with the film thickness and extended light exposure also influencing local activity. Our work highlights the importance of microscopic mapping to understand activity, in even seemingly homogeneous photoelectrodes.