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The aim of our cross-sectional and longitudinal study is to assess the relationship between daytime and night-time sleep duration and health-related quality of life (HRQoL) in adults with metabolic syndrome after a 1-year healthy lifestyle intervention. Analysis of the data from 2119 Spanish adults aged 55-75 years from the PREDIMED-Plus study was performed. Sleep duration was assessed using a wrist-worn accelerometer. HRQoL was measured using the SF-36 questionnaire. Linear regression models adjusted for socioeconomic and lifestyle factors and morbidity were developed. In cross-sectional analyses, participants with extreme night-time sleep duration categories showed lower physical component summary scores in Models 1 and 2 [ß-coefficient (95% confidence interval) <6 h vs. 7-9 h: -2, 3 (-3.8 to -0.8); p = 0.002. >9 h vs. 7-9 h: -1.1 (-2.0 to -0.3); p = 0.01]. Participants who sleep less than 7 h a night and take a nap are associated with higher mental component summary scores [ß-coefficient (95% confidence interval) 6.3 (1.3 to 11.3); p = 0.01]. No differences between night-time sleep categories and 12-month changes in HRQoL were observed. In conclusion, in cross-sectional analyses, extremes in nocturnal sleep duration are related to lower physical component summary scores and napping is associated with higher mental component summary scores in older adults who sleep less than 7 h a night.
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Síndrome Metabólico , Calidad de Vida , Sueño , Humanos , Anciano , Persona de Mediana Edad , Masculino , Femenino , Estudios Longitudinales , Sueño/fisiología , Síndrome Metabólico/psicología , Síndrome Metabólico/epidemiología , Estudios Transversales , España/epidemiología , Factores de Tiempo , Encuestas y Cuestionarios , Acelerometría , Estilo de Vida Saludable , Duración del SueñoRESUMEN
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.
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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.
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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.
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Hepatocellular carcinoma (HCC) presents high mortality rates worldwide, with limited evidence on prognostic factors at diagnosis. This study evaluates the utility of common scores incorporating albumin as predictors of mortality at HCC diagnosis using Machine Learning techniques. They are also compared to other scores and variables commonly used. A retrospective cohort study was conducted with 191 patients from Virgen de la Luz Hospital of Cuenca and University Hospital of Guadalajara. Demographic, analytical, and tumor-specific variables were included. Various Machine Learning algorithms were implemented, with eXtreme Gradient Boosting (XGB) as the reference method. In the predictive model developed, the Barcelona Clinic Liver Cancer score was the best predictor of mortality, closely followed by the Platelet-Albumin-Bilirubin and Albumin-Bilirubin scores. Albumin levels alone also showed high relevance. Other scores, such as C-Reactive Protein/albumin and Child-Pugh performed less effectively. XGB proved to be the most accurate method across the metrics analyzed, outperforming other ML algorithms. In conclusion, the Barcelona Clinic Liver Cancer, Platelet-Albumin-Bilirubin and Albumin-Bilirubin scores are highly reliable for assessing survival at HCC diagnosis. The XGB-developed model proved to be the most reliable for this purpose compared to the other proposed methods.
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Enolase is a 47 kDa enzyme that functions within the glycolysis and gluconeogenesis pathways involved in the reversible conversion of D-2-phosphoglycerate (2PGA) to phosphoenolpyruvate (PEP). However, in the context of host-pathogen interactions, enolase from different species of parasites, fungi and bacteria have been shown to contribute to adhesion processes by binding to proteins of the host extracellular matrix (ECM), such as fibronectin (FN) or laminin (LM). In addition, enolase is a plasminogen (PLG)-binding protein and induces its activation to plasmin, the main protease of the host fibrinolytic system. These secondary 'moonlighting' functions of enolase are suggested to facilitate pathogen migration through host tissues. This study aims to uncover the moonlighting role of enolase from the parasite Fasciola hepatica, shedding light on its relevance to host-parasite interactions in fasciolosis, a global zoonotic disease of increasing concern. A purified recombinant form of F. hepatica enolase (rFhENO), functioning as an active homodimeric glycolytic enzyme of ~94 kDa, was successfully obtained, fulfilling its canonical role. Immunoblotting studies on adult worm extracts showed that the enzyme is present in the tegument and the excretory/secretory products of the parasite, which supports its key role at the host-parasite interface. Confocal immunolocalisation studies of the protein in newly excysted juveniles and adult worms also localised its expression within the parasite tegument. Finally, we showed by ELISA that rFhENO can act as a parasitic adhesin by binding host LM, but not FN. rFhENO also binds PLG and enhances its conversion to plasmin in the presence of the tissue-type and urokinase-type PLG activators (t-PA and u-PA). This moonlighting adhesion-like function of the glycolytic protein enolase could contribute to the mechanisms by which F. hepatica efficiently invades and migrates within its host and encourages further research efforts that are designed to impediment this function by vaccination or drug design.
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BACKGROUND: Meat consumption could increase the risk of type 2 diabetes. However, evidence is largely based on studies of European and North American populations, with heterogeneous analysis strategies and a greater focus on red meat than on poultry. We aimed to investigate the associations of unprocessed red meat, processed meat, and poultry consumption with type 2 diabetes using data from worldwide cohorts and harmonised analytical approaches. METHODS: This individual-participant federated meta-analysis involved data from 31 cohorts participating in the InterConnect project. Cohorts were from the region of the Americas (n=12) and the Eastern Mediterranean (n=2), European (n=9), South-East Asia (n=1), and Western Pacific (n=7) regions. Access to individual-participant data was provided by each cohort; participants were eligible for inclusion if they were aged 18 years or older and had available data on dietary consumption and incident type 2 diabetes and were excluded if they had a diagnosis of any type of diabetes at baseline or missing data. Cohort-specific hazard ratios (HRs) and 95% CIs were estimated for each meat type, adjusted for potential confounders (including BMI), and pooled using a random-effects meta-analysis, with meta-regression to investigate potential sources of heterogeneity. FINDINGS: Among 1â966â444 adults eligible for participation, 107â271 incident cases of type 2 diabetes were identified during a median follow-up of 10 (IQR 7-15) years. Median meat consumption across cohorts was 0-110 g/day for unprocessed red meat, 0-49 g/day for processed meat, and 0-72 g/day for poultry. Greater consumption of each of the three types of meat was associated with increased incidence of type 2 diabetes, with HRs of 1·10 (95% CI 1·06-1·15) per 100 g/day of unprocessed red meat (I2=61%), 1·15 (1·11-1·20) per 50 g/day of processed meat (I2=59%), and 1·08 (1·02-1·14) per 100 g/day of poultry (I2=68%). Positive associations between meat consumption and type 2 diabetes were observed in North America and in the European and Western Pacific regions; the CIs were wide in other regions. We found no evidence that the heterogeneity was explained by age, sex, or BMI. The findings for poultry consumption were weaker under alternative modelling assumptions. Replacing processed meat with unprocessed red meat or poultry was associated with a lower incidence of type 2 diabetes. INTERPRETATION: The consumption of meat, particularly processed meat and unprocessed red meat, is a risk factor for developing type 2 diabetes across populations. These findings highlight the importance of reducing meat consumption for public health and should inform dietary guidelines. FUNDING: The EU, the Medical Research Council, and the National Institute of Health Research Cambridge Biomedical Research Centre.
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Diabetes Mellitus Tipo 2 , Carne , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Humanos , Incidencia , Carne/efectos adversos , Adulto , Masculino , Femenino , Estudios de Cohortes , Persona de Mediana Edad , Factores de Riesgo , Dieta/efectos adversos , Animales , Aves de CorralRESUMEN
BACKGROUND & AIMS: The double burden of malnutrition compels us to reconsider macronutrients from a diet quality perspective. The Macronutrient Quality Index (MQI) has been designed to reflect overall macronutrient quality and is based on three sub-indexes: the carbohydrate quality index (CQI), the healthy plate protein quality index (HPPQI) and the fat quality index (FQI). Nutritional adequacy is an essential aspect of diet quality that should be captured by reliable dietary indexes. METHODS: We analyzed the association between the Macronutrient Quality Index (MQI) and micronutrient adequacy. Participants were children aged 4 and 5 years, recruited in the SENDO cohort. Baseline information was collected through a self-administered online questionnaire, which included information on sociodemographic, dietary, and lifestyle variables. Dietary information was obtained using a 147-item validated semi-quantitative food frequency questionnaire. Participants were categorized into tertiles based on their MQI score. We evaluated the intake of 20 micronutrients and assessed the probability of micronutrient adequacy using the Estimated Average Requirement cut-off point. RESULTS: Children in the highest tertile of MQI had 0.33-fold lower odds (95%CI 0.17-0.66) of having ≥3 inadequate micronutrient intakes than their peers in the lowest tertile, after adjusting for potential confounders. The adjusted proportions of children with inadequate intake of ≥3 micronutrients were 18%, 14% and 11% in the first, second, and third tertiles of MQI respectively. The MQI appears to be capable of capturing nutrient adequacy in children, although our results suggest that a modified MQI, with eggs and dairy products weighted positively, might be more adequate for the pediatric population.
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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.
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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.
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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.
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Biomarcadores , Dieta Mediterránea , Humanos , Niño , Adolescente , Biomarcadores/sangre , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/sangre , Femenino , Masculino , Factores de Riesgo Cardiometabólico , Ensayos Clínicos Controlados Aleatorios como Asunto , Presión Sanguínea/fisiologíaRESUMEN
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.
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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.
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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.
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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.
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Hipertensión , Deficiencia de Vitamina D , Vitamina D , Humanos , Vitamina D/sangre , Vitamina D/análogos & derivados , Hipertensión/epidemiología , Hipertensión/etiología , Hipertensión/sangre , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Factores de Riesgo , Adulto , Modelos de Riesgos Proporcionales , IncidenciaRESUMEN
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.
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Células Ependimogliales , Retina , Espermidina Sintasa , Animales , Ratas , Espermidina Sintasa/metabolismo , Espermidina Sintasa/genética , Retina/metabolismo , Células Ependimogliales/metabolismo , Envejecimiento/metabolismo , Espermidina/metabolismo , Neuroglía/metabolismo , Animales Recién NacidosRESUMEN
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.
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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.
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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.