A Photodynamic and Photochemotherapeutic Platinum-Iridium Charge-Transfer Conjugate for Anticancer Therapy.

The novel hetero-dinuclear complex trans,trans,trans-[PtIV(py)2(N3)2(OH)(µ-OOCCH2CH2CONHCH2-bpyMe)IrIII(ppy)2]Cl (Pt-Ir), exhibits charge transfer between the acceptor photochemotherapeutic Pt(IV) (Pt-OH) and donor photodynamic Ir(III) (Ir-NH2) fragments. It is stable in the dark, but undergoes photodecomposition more rapidly than the Pt(IV) parent complex (Pt-OH) to generate Pt(II) species, an azidyl radical and 1O2. The Ir(III)* excited state, formed after irradiation, can oxidise NADH to NAD⋅ radicals and NAD+. Pt-Ir is highly photocytotoxic towards cancer cells with a high photocytotoxicity index upon irradiation with blue light (465 nm, 4.8 mW/cm2), even with short light-exposure times (10-60 min). In contrast, the mononuclear Pt-OH and Ir-NH2 subunits and their simple mixture are much less potent. Cellular Pt accumulation was higher for Pt-Ir compared to Pt-OH. Irradiation of Pt-Ir in cancer cells damages nuclei and releases chromosomes. Synchrotron-XRF revealed ca. 4× higher levels of intracellular platinum compared to iridium in Pt-Ir treated cells under dark conditions. Luminescent Pt-Ir distributes over the whole cell and generates ROS and 1O2 within 1 h of irradiation. Iridium localises strongly in small compartments, suggestive of complex cleavage and excretion via recycling vesicles (e.g. lysosomes). The combination of PDT and PACT motifs in one molecule, provides Pt-Ir with a novel strategy for multimodal phototherapy.

Management, risk factors and treatment outcomes of rhegmatogenous retinal detachment associated with giant retinal tears: scoping review.

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a serious condition that occurs when the retina detaches from its underlying retinal pigment epithelium. RRDs associated with giant retinal tears (GRTs) are caused by retinal tears at least 90° or one-quarter of the circumferential extent. This scoping review systematically identifies and summarizes clinical studies evaluating surgical techniques for the management of GRT-related RRDs, discusses functional and visual outcomes and the risk factors affecting treatment outcomes. METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, Google Scholar, and Springer Link databases were searched for relevant papers (from January 2001 to March 2023). Studies that were published in the English language and reported the risk factors, management, and treatment outcomes of GRT-related RRDs were included in the review. The outcome measures included anatomic success rates, changes in BCVA (logMAR) from baseline to the final follow-up, and adverse events. RESULTS: A total of 11,982 articles were identified. After the title and abstract review, 71 studies were deemed eligible for full-text review. Thirty-six studies that met the eligibility criteria were included in the final review. Four surgical techniques were identified: pars plana vitrectomy (PPV), combined PPV and scleral buckling, scleral buckling alone, and pneumatic retinopexy. Various types of tamponades, including gas, silicone oil, and air, have been used. PPV was the most commonly used surgical technique in 33.1-100% of patients. Among the 20 studies that used PPV alone, 17 were associated with preoperative PVR. In addition, scleral buckling alone or in combination with PPV was reported as a treatment option in 10 studies, with 2-100% of patients experiencing scleral buckling alone and 13.6-100% experiencing combined PPV and complementary scleral buckling. Primary anatomic success (PAS) was achieved with retinal reattachment via a single operation with no residual tamponade, whereas final anatomic success (FAS) was achieved via more than one operation with no residual tamponade. Reported single surgery anatomic success (SSAS) rates range from 65.51 to 100%. The preoperative best-corrected visual acuity (BCVA) ranged from 0.067 to 2.47 logMAR, whereas the postoperative BCVA ranged from 0.08 to 2.3 logMAR. An improvement in visual acuity was observed in 29 studies. Cataracts (3.9-28.3%) were the most common postoperative complication, followed by high IOP (0.01-51.2%) and PVR (0.8-31.57%). CONCLUSION: PPV is the most common surgical technique, and currently microincision vitrectomy surgery (MIVS) systems are commonly employed. Silicone oil is the most frequently used tamponade in RRD repair. Risk factors for GRT-related RRD include age, sex, lens status, high myopia status, proliferative vitreoretinopathy (PVR), presenting visual acuity, the extent of the GRT and retinal detachment, and macular involvement. Future research areas include guidelines to reduce variability in the reporting of surgical methodology, choice of tamponades, and reporting of functional and visual outcomes to inform the best therapeutic interventions in GRT-related RRD.

Novel surgical approaches for treating myopic traction maculopathy: a meta-analysis.

BACKGROUND: Myopic traction maculopathy (MTM) is a complication of pathological myopia and encompasses various pathological conditions caused by tractional changes in the eye. These changes include retinoschisis, foveal retinal detachment, and lamellar or full-thickness macular holes (FTMHs). This meta-analysis evaluated the safety and efficacy of novel surgical for treating MTM. METHODS: To compare the outcomes of different surgical approaches for MTM, multiple databases, including Web of Science, PubMed, Scopus, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, and the Meta-Register of Controlled Trials, were comprehensively searched. The meta-analysis was performed using RevMan 5.1. RESULTS: Nine comparative studies involving 350 eyes were included in this meta-analysis. There were significant differences between fovea-sparing internal limiting membrane peeling (FSIP) and standard internal limiting membrane peeling (ILMP). Preoperative best-corrected visual acuity BCVA (standard mean difference (SMD): -0.10, 95% CI: -0.32 to 0.12) and central foveal thickness CFT (SMD: 0.05, 95% CI: -0.22 to 0.33) were not significantly different (p = 0.39 and p = 0.71, respectively). However, the postoperative BCVA improved significantly (SMD = - 0.47, 95% CI: - 0.80, - 0.14, p = 0.006) in the FSIP group compared to the standard ILMP group. Postoperative CFT did not differ significantly between the two groups (p = 0.62). The FSIP group had a greater anatomical success rate than the other groups, although the difference was not statistically significant (p = 0.26). The incidence of postoperative macular hole formation was significantly lower (OR = 0.19, 95% CI = 0.07-0.54; p = 0.05) in the FSIP group than in the standard ILMP group. The unique characteristics of highly myopic eyes, such as increased axial length and structural changes, may have contributed to the greater incidence of FTMH in the ILMP group. CONCLUSION: Based on the findings of this meta-analysis, FSIP is the initial surgical approach for early-stage MTM and has shown promising outcomes. However, to establish the safest and most efficient surgical technique for treating different MTM stages, further comparative studies, specifically those focusing on ILMP and FSIP, are necessary. TRIAL REGISTRATION: Retrospectively registered.

Viscosities and Densities of Binary and Ternary Mixtures of Aliphatic and Polyaromatic Hydrocarbons: Pyrene +1-Methylnaphthalene + Dodecane at T = (293.15 to 343.15) K. Experiment and Modeling.

This work presents new experimental viscosity and density data for aromatic and polyaromatic compounds in binary and ternary pyrene, 1-methylnaphthalene, and dodecane mixtures. The lack of experimental viscosity data for these mixtures requires the development of a new database, which is vital for understanding the behavior of mixtures in more complex systems, such as asphaltenes and fuels. The mixtures proposed in this work have been measured over a temperature range of (293.15 to 343.15) K at atmospheric pressure. Several mixture compositions have been studied at these conditions: 1.0, 2.5, 5.0, 7.5, 10.0, 12.5, and 15.0% pyrene mass fraction. The concentration of pyrene correlates with an increase in the viscosity and density values. At the lowest temperature in binary mixtures, the corresponding values reach 4.4217 mPa·s for viscosity and 1.0447 × 103 kg·m-3 for density, respectively. In ternary mixtures, the introduction of dodecane leads to the lowest maximum values of 3.5555 mPa·s for viscosity and 1.0112 × 103 kg·m-3 for density at the same temperature. The experimental data have been employed for the specific modification of viscosity models. These modifications could facilitate the prediction of the viscosity of mixtures that are more complex than those presented in this work. Various viscosity models have been employed, such as Linear, Ratcliff and Khan, modified UNIFAC-Visco, and Krieger-Dougherty. The settings in the models used reliably reproduce the experiment reliably. However, the Ratcliff model agrees excellently with the experiment, having a low standard deviation (2.0%) compared to other models. Furthermore, a model based on the equation of state of Guo is proposed to predict the viscosity values by modifying the specific parameters and adjusting them to the mixtures proposed in this work. The results from this study are compared to previous work, where pyrene, toluene, and heptane mixtures were analyzed. In this case, we find that the decrease of aggregation grade in the present systems is predicted by the model fixed in this work.

Associations of Alcohol Consumption With Left Atrial Morphology and Function in a Population at High Cardiovascular Risk.

BACKGROUND: Excessive alcohol consumption has been associated with increased risk of atrial fibrillation, although the underlying mechanisms remain unclear. An enlarged left atrium and impaired left atrial function may lead to atrial fibrillation. The association of alcohol consumption with structural and functional left atrial measures, however, has received limited attention. METHODS AND RESULTS: We studied 503 participants from the PREDIMED-Plus (Prevención con Dieta Mediterránea) trial, a randomized trial testing intensive weight loss intervention with an energy-reduced Mediterranean diet and physical activity promotion in preventing cardiovascular disease in adults with metabolic syndrome. Participants underwent transthoracic echocardiography at baseline, year 3, and year 5 of the study. Outcomes of interest included volume index and reservoir, conduit, and contractile strains of the left atrium. Alcohol consumption was calculated through food frequency questionnaires and presented as drinks consumed per day. Multiple linear regression and mixed models estimated the association of alcohol consumption with left atrial measurements at baseline and through follow-up. Cross-sectionally, higher alcohol consumption (per 1 drink/day increases) was associated with larger left atrial volume (0.65 mL/m2 [95% CI, 0.18-1.11]) and lower left atrial reservoir and contractile strain (-0.44% [95% CI, -0.87 to -0.01]; and -0.44% [95% CI, -0.75 to -0.14]). Baseline alcohol consumption was not associated with changes in left atrial measurements, but increases in alcohol consumption (per 1 drink/day increase) during follow-up were associated with left atrial enlargement (0.71 mL/m2 [95% CI, 0.17-1.26]). CONCLUSIONS: In a population at high cardiovascular risk, increased alcohol consumption was associated with left atrial enlargement and worsening atrial function. REGISTRATION: URL: http://www.controlled-trials.com; Unique identifier: ISRCTN89898870.

Daily time spent on screens and psychological well-being: Cross-sectional association within the SUN cohort.

BACKGROUND: The impact of various lifestyles on psychological well-being (PWB) remains under-studied. We aimed to explore the cross-sectional association between daily screen use (television, tablet and mobile phone) and PWB within the SUN cohort. METHODS: PWB was assessed using the 29-item Ryff scale (ranging from 29 to 174), and participants with scores >75th percentile were considered as having optimal PWB. Participants were categorized based on their self-reported weekly screen usage hours. Postestimation logistic regression models assessing the prevalence likelihood of not achieving optimal PWB were adjusted for sociodemographic, psychological, personality and lifestyles factors. Isotemporal substitution models explored the potential impact on PWB resulting from replacing 1 h/day of screen time with 1 h/day of exercise. RESULTS: The study included 3051 participants (55.8% women, mean age 57.3 ± 11.1 years, mean Ryff's score: 139.1 ± 17.4 points). Daily screen use for ≥2 h was associated with a higher prevalence likelihood of not achieving an optimal PWB (Prevalence Ratio [PR]:1.09; 95% CI:1.01-1.18). Among PWB dimensions, screen use ≥2 h/day was linked to an increased likelihood of not achieving optimal scores in environmental mastery (PR:1.11; 95% CI:1.02-1.20), life purpose (PR:1.10; 95% CI:1.02-1.18), and personal growth (PR:1.09; 95% CI:1.01-1.18). Replacing 1 h of daily screens time with 1 h of exercise may lead to potential improvements in environmental mastery (Odds Ratio [OR]:0.87; 95% CI:0.76-0.99), purpose in life (OR:0.86; 95% CI: 0.76-0.98), personal growth (OR:0.84; 95% CI:0.73-0.96) and positive interpersonal relationships (OR:0.86; 95% CI:0.75-0.99). CONCLUSIONS: These findings highlight the importance of reducing screen use activities and increasing physical exercise for achieving optimal PWB.

Plasma metabolites of a healthy lifestyle in relation to mortality and longevity: Four prospective US cohort studies.

BACKGROUND: A healthy lifestyle is associated with a lower premature mortality risk and with longer life expectancy. However, the metabolic pathways of a healthy lifestyle and how they relate to mortality and longevity are unclear. We aimed to identify and replicate a healthy lifestyle metabolomic signature and examine how it is related to total and cause-specific mortality risk and longevity. METHODS: In four large cohorts with 13,056 individuals and 28-year follow-up, we assessed five healthy lifestyle factors, used liquid chromatography mass spectrometry to profile plasma metabolites, and ascertained deaths with death certificates. The unique healthy lifestyle metabolomic signature was identified using an elastic regression. Multivariable Cox regressions were used to assess associations of the signature with mortality and longevity. FINDINGS: The identified healthy lifestyle metabolomic signature was reflective of lipid metabolism pathways. Shorter and more saturated triacylglycerol and diacylglycerol metabolite sets were inversely associated with the healthy lifestyle score, whereas cholesteryl ester and phosphatidylcholine plasmalogen sets were positively associated. Participants with a higher healthy lifestyle metabolomic signature had a 17% lower risk of all-cause mortality, 19% for cardiovascular disease mortality, and 17% for cancer mortality and were 25% more likely to reach longevity. The healthy lifestyle metabolomic signature explained 38% of the association between the self-reported healthy lifestyle score and total mortality risk and 49% of the association with longevity. CONCLUSIONS: This study identifies a metabolomic signature that measures adherence to a healthy lifestyle and shows prediction of total and cause-specific mortality and longevity. FUNDING: This work was funded by the NIH, CIHR, AHA, Novo Nordisk Foundation, and SciLifeLab.

Effect of the Mediterranean diet in cardiovascular prevention.

The Mediterranean diet is the best evidence-based model for cardiovascular prevention. In addition to 2 major randomized secondary prevention trials (Lyon Heart and CORDIOPREV) and 1 primary prevention trial (PREDIMED) that have demonstrated these benefits, there is an unprecedented body of high-quality prospective epidemiological evidence supporting these beneficial effects. The key elements of this traditional pattern are the abundant use of extra-virgin olive oil and high consumption of foods of natural plant-based origin (fruits, vegetables, nuts, and legumes) and fish, along with a reduction in processed meats, red meats, and ultraprocessed products. Moderate consumption of wine, preferably red wine, with meals is an essential element of this traditional pattern. Although removing wine consumption from the Mediterranean diet has been associated with a reduction in its preventive efficacy, doubts have recently arisen about the possible adverse effect of even low or moderate intake of any alcoholic beverages. A new large Spanish trial, UNATI, which will begin in June 2024, will randomize 10 000 drinkers aged 50 to 75 years to abstention or moderate consumption. UNATI aims to answer these doubts with the best possible evidence.

Gene editing: a near future for the treatment of genetic kidney diseases.

The study by Chen et al. is the first to apply the revolutionary genetic engineering tool, base editing, in a rat model for the treatment of primary hyperoxaluria type 1, a disease that originates in the liver but in which the kidney is the main organ affected. This commentary contextualizes and describes the gene-editing technology applied by the authors, provides an interpretation and opinion of their results, and indicates possible future applications.

Plasma metabolite profile of legume consumption and future risk of type 2 diabetes and cardiovascular disease.

BACKGROUND: Legume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume consumption, and subsequently investigate its potential association with the incidence of T2D and CVD. METHODS: The current cross-sectional and longitudinal analysis was conducted in 1833 PREDIMED study participants (mean age 67 years, 57.6% women) with available baseline metabolomic data. A subset of these participants with 1-year follow-up metabolomics data (n = 1522) was used for internal validation. Plasma metabolites were assessed through liquid chromatography-tandem mass spectrometry. Cross-sectional associations between 382 different known metabolites and legume consumption were performed using elastic net regression. Associations between the identified metabolite profile and incident T2D and CVD were estimated using multivariable Cox regression models. RESULTS: Specific metabolic signatures of legume consumption were identified, these included amino acids, cortisol, and various classes of lipid metabolites including diacylglycerols, triacylglycerols, plasmalogens, sphingomyelins and other metabolites. Among these identified metabolites, 22 were negatively and 18 were positively associated with legume consumption. After adjustment for recognized risk factors and legume consumption, the identified legume metabolite profile was inversely associated with T2D incidence (hazard ratio (HR) per 1 SD: 0.75, 95% CI 0.61-0.94; p = 0.017), but not with CVD incidence risk (1.01, 95% CI 0.86-1.19; p = 0.817) over the follow-up period. CONCLUSIONS: This study identified a set of 40 metabolites associated with legume consumption and with a reduced risk of T2D development in a Mediterranean population at high risk of cardiovascular disease. TRIAL REGISTRATION: ISRCTN35739639.

Pluronic F127 "nanoarmor" for stabilization of Cowpea mosaic virus immunotherapy.

Our lab demonstrated that intratumoral Cowpea mosaic virus (CPMV) is a potent antitumor immunotherapy when used as in situ vaccine. As we pave the way for human clinical translation, formulation chemistry needs to be optimized for long-term storage of the drug candidate. In this work, CPMV was nanoengineered with Pluronic F127 to realize liquid and gel formulations which mitigate structural changes and RNA release during long-term storage. We evaluated the CPMV-F127 formulations for their stability and biological activity through a combination of in vitro assays and efficacy in vivo using a B16F10 murine melanoma model. Results demonstrate that both F127 liquid and gel formulations preserve CPMV structure and function following extended periods of thermal incubation at 4°C, 25°C, and 37°C. Heat-incubated CPMV without formulation resulted in structural changes and inferior in vivo efficacy. In stark contrast, in vivo efficacy was preserved when CPMV was formulated and protected with the F127 "nanoarmor."

Plasma metabolite predictors of metabolic syndrome incidence and reversion.

BACKGROUND: Metabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion. METHODS: The study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was defined by not having MetS at baseline but meeting the MetS criteria at a follow-up visit. MetS reversion was defined by MetS at baseline but not meeting MetS criteria at a follow-up visit. Plasma metabolome was profiled by LC-MS. Multivariable-adjusted Cox regression models and elastic net regularized regressions were used to assess the association of 385 annotated metabolites with MetS incidence and MetS reversion after adjusting for potential risk factors. RESULTS: Of the 603 participants without baseline MetS, 298 developed MetS over the median 4.8-year follow-up. Of the 865 participants with baseline MetS, 285 experienced MetS reversion. A total of 103 and 88 individual metabolites were associated with MetS incidence and MetS reversion, respectively, after adjusting for confounders and false discovery rate correction. A metabolomic signature comprised of 77 metabolites was robustly associated with MetS incidence (HR: 1.56 (95 % CI: 1.33-1.83)), and a metabolomic signature of 83 metabolites associated with MetS reversion (HR: 1.44 (95 % CI: 1.25-1.67)), both p < 0.001. The MetS incidence and reversion signatures included several lipids (mainly glycerolipids and glycerophospholipids) and branched-chain amino acids. CONCLUSION: We identified unique metabolomic signatures, primarily comprised of lipids (including glycolipids and glycerophospholipids) and branched-chain amino acids robustly associated with MetS incidence; and several amino acids and glycerophospholipids associated with MetS reversion. These signatures provide novel insights on potential distinct mechanisms underlying the conditions leading to the incidence or reversion of MetS.

Should we remove wine from the Mediterranean diet?: a narrative review.

Moderate alcohol intake (or, more specifically, red wine) represents one of the postulated beneficial components of the traditional Mediterranean diet. Many well-conducted nonrandomized studies have reported that light-to-moderate alcohol intake is not only associated with reduced risk of cardiovascular disease, but also of all-cause mortality. Nonetheless, alcohol is an addictive substance imposing huge threats for public health. Alcohol consumption is associated with increased risks of cancer, neurological harms, injuries, and other adverse outcomes. Both the Global Burden of Disease (2016) and Mendelian randomization studies recently supported that the healthiest level of alcohol intake should be 0. Therefore, despite findings of conventional observational epidemiologic studies supporting a potential beneficial role of wine in the context of a healthy Mediterranean dietary pattern, a strong controversy remains on this issue. Age, sex, and drinking patterns are likely to be strong effect modifiers. In this context, a new 4-y noninferiority pragmatic trial in Spain (University of Navarra Alumni Trialist Initiative or "UNATI"), publicly funded by the European Research Council, will randomly assign >10,000 current drinkers (males, 50-70 y; females, 55-75 y) to repeatedly receive advice on either abstention or moderation in alcohol consumption. The recruitment will begin in mid-2024. The primary endpoint is a composite of the main clinical outcomes potentially related to alcohol intake including all-cause mortality. Clinical trial registry number: PREDIMED, ISRCTN35739639, www.predimed.es; SUN, clinicaltrials.gov identifier: NCT02669602, https://medpreventiva.es/i2CmeL.

Non-Newtonian Dynamics in Water-in-Salt Electrolytes.

Water-in-salt electrolytes have attracted considerable interest in the past decade for advanced lithium-ion batteries, possessing important advantages over the non-aqueous electrolytes currently in use. A battery with a LiTFSI-water electrolyte was demonstrated in which an operating window of 3 V is made possible by a solid-electrolyte interface. Viscosity is an important property for such electrolytes, because high viscosity is normally associated with low ionic conductivity. Here, we investigate shear and longitudinal viscosities using shear stress and compressional longitudinal stress measurements as functions of frequency and concentration. We find that both viscosities are frequency-dependent and exhibit almost identical frequency and concentration dependences in the high-concentration region. A comparison to quasielastic neutron scattering experiments suggests that both are governed by structural relaxation of the TFSI- network. Thus, LiFTSI-water electrolytes appear to be an unusual case of a non-Newtonian fluid, where shear and longitudinal viscosities are determined by the same relaxation mechanism.

Surgical management, use and efficacy of adjuvant dyes in idiopathic epiretinal membranes: a systemic review with network meta-analysis.

BACKGROUND: The epiretinal membrane (ERM) is a nonvascular fibrocellular tissue formed by cellular metaplasia and proliferation at the vitreoretinal surface and is generally treated by pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peeling. This network meta-analysis aimed to compare the efficacy of all available ERM removal interventions and assessed the use and efficacy of surgical dyes in managing idiopathic ERMs. METHODS: MEDLINE, EMBASE, Cochrane CENTRAL, and the US National Library of Medicine were searched (June 28, 2023). Clinical studies that included patients with ERMs were included. Randomized controlled trials (RCTs) were also appraised using Cochrane risk of bias (ROB). RESULTS: Ten RCTs and ten non-RCTs were included in this study. A pairwise meta-analysis between ERM removal and combined ERM and ILM removal showed no significant difference in visual outcome (change in BCVA) 1 year postintervention (MD = - 0.0034, SE = 0.16, p = 0.832). Similarly, there was no significant difference in the central macular thickness postoperatively between the two groups (MD = - 4.95, SE = 11.11, p = 0.656) (Q = 4.85, df = 3, p = 0.182, I2 = 41.21%). The difference in ERM recurrence between the groups was also not statistically significant (OR = 4.64, p = 0.062, I2 = 0). In a network meta-analysis, there was no significant difference in visual outcomes between ERM removal only and other treatment modalities: combined ILM and ERM removal (MD = 0.039, p = 0.837) or watchful waiting (MD = 0.020, p = 0.550). In a network meta-analysis, there was no significant difference in the visual outcomes between ERM removal alone and dye-stained combined ERM and ILM peeling (MD = 0.122, p = 0.742 for brilliant blue G; BBG and MD = 0.00, p = 1.00 for membrane blue-dual; MBD). The probability of being a better surgical dye for better visual outcomes was 0.539 for the MBD group and 0.396 for the BBG group. The recurrence of ERM was not significantly different when the ILM was stained with any of the dyes. No study was judged on ROB assessment as having low ROB in all seven domains. CONCLUSION: The two types of surgical modalities provided comparable efficacy, with no significant differences between the outcomes. Among the dye-assisted ILM peeling methods, the membrane blue-dual dye was the most effective in providing better structural and functional outcomes.

Association between COVID-19 and outstanding academic performance at a Spanish university.

BACKGROUND: SARS-CoV-2 is the causative agent of COVID-19 identified in December 2019, an acute infectious respiratory disease that can cause persistent neurological and musculoskeletal symptoms such as headache, fatigue, myalgias difficulty concentrating, among others including acute cerebrovascular disease with a prevalence of 1-35%. The aim of this study is to evaluate the impact of COVID-19 in undergraduate students on their academic performance as an indicator of their intellectual ability and performance in a university that maintained 100% face-to-face teaching during the 2020-2021 academic year. METHODS: A total of 7,039 undergraduate students were analyzed in a prospective cohort study at the University of Navarra. A questionnaire including sociodemographic and behavioral questions was sent. PCRs were performed throughout the academic year for the diagnosis of SARS-CoV-2 infection and students' academic results were provided by the academic center, adjusted descriptive and multivariate models were performed to assess the association. RESULTS: A total of 658 (9.3%) participants were diagnosed with COVID-19, almost 4.0% of them achieved outstanding academic results, while uninfected students did so in 7.3%. SARS-CoV-2 infection was associated with a significant decrease in having outstanding academic results (OR = 0.57; 95% CI: 0.38-0.86). CONCLUSION: Having COVID-19 disease, decreased academic performance in undergraduate students. Therefore, it is necessary to prevent infection even in the youngest sections of the population.

Validation of a good manufacturing practice procedure for the production of [11 C]AZD4747, a CNS penetrant KRASG12c inhibitor.

AZD4747 is a KRASG12C inhibitor recently shown to cross the non-human primate blood-brain barrier efficiently. In the current study, a GMP-compliant production of [11 C]AZD4747 was developed to enable PET studies in human subjects. The validated procedure afforded [11 C]AZD4747 as an injectable solution in good radioactivity yield (1656 ± 532 MBq), excellent radiochemical purity (100%), and a molar activity of 77 ± 13 GBq/µmol at the end of the synthesis, which took 46 ± 1 min from the end of the bombardment. Quality control on the final product was performed satisfactorily and met all acceptance criteria.

Association of alcohol consumption with circulating biomarkers of atrial fibrillation-related pathways in a population at high cardiometabolic risk.

Background: The effect of alcohol consumption on cardiovascular health, including atrial fibrillation risk, remains controversial. Evaluating the association of alcohol consumption with circulating atrial fibrillation-related biomarkers may help better understand the relevant mechanistic underpinnings. Methods: We studied 523 participants from 3 sites for the PREDIMED-Plus study, a weight-loss randomized intervention trial in metabolically unhealthy adults. N-terminal pro-B-type natriuretic protein (NTproBNP), high sensitivity troponin-T (hsTnT), high-sensitivity C-reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and procollagen type 1 carboxy-terminal propeptide (PICP) were measured in fasting serum samples at baseline and years 3 and 5 of follow-up. We calculated alcohol consumption in drinks/day (1 drink = 14 grams alcohol) with validated food frequency questionnaires at each visit. Using multiple linear regression and mixed models we estimated the association of alcohol consumption with log-transformed biomarkers at baseline and longitudinally adjusting for potential confounders. Results: Among 523 participants (mean age: 65 years, 40% female), mean alcohol consumption was 1 drink/day. Cross-sectionally, alcohol consumption was not associated with cardiac biomarker concentrations. Longitudinally, compared to non-consumers, heavy drinkers (≥4 drinks/day) had smaller increases in hsTnT (ß: -0.11, 95%CI: -0.20, -0.01)and PICP (ß: -0.15, 95%CI: -0.30, 0.01) over the 5-year follow-up. In contrast, those who increased alcohol consumption over the 5-year period experienced greater increases in hsCRP (ß: 0.42, 95%CI: 0.11, 0.73) compared to those whose drinking behavior stayed the same. Conclusion: Alcohol consumption was associated with complex changes in circulating biomarkers, including comparatively lower fibrotic and myocardial damage, but higher levels of overall inflammation over time. These results underscore the need for further research to better understand the effects of alcohol on cardiovascular health.

Choroidal Perfusion Changes After Vitrectomy for Myopic Traction Maculopathy.

BACKGROUND: The choroidal vasculature supplies the outer retina and is altered in many retinal diseases, including myopic traction maculopathy (MTM). Choroid health is typically assessed by measuring the choroidal thickness; however, this method has substantial limitations. The choroidal vascularity index (CVI) was recently introduced to provide quantitative information on the vascular flow in the choroid. This index has been evaluated in a wide range of diseases but has not been extensively used to characterize MTM. AIM: This study aimed to investigate the CVI across different stages of MTM and the influence of macular surgery on choroidal perfusion markers in different surgically resolved MTM stages. METHODS: Eighteen healthy myopic eyes in the control group and forty-six MTM eyes in the surgical group were evaluated using enhanced optical coherence tomography (OCT) imaging. Binarized OCT images were processed to obtain the luminal choroidal area (LCA) and stromal choroidal area (SCA), which were used to calculate CVI in the form of a percentage ratio. CVI data were collected at baseline, one and four months postoperatively, and at the final clinical visit. MTM eyes were divided into four stages based on disease severity. The choriocapillaris flow area (CFA) and central subfield thickness (CSFT) were measured along side the CVI. RESULTS: No significant differences were observed between the two groups at baseline, except for visual acuity (p < 0.0001). Surgery significantly improved vision at all postoperative time points (p < 0.0001). At baseline, there were no significant differences in CVI, CFA, or CSFT scores between the control and surgical groups. However, all three measurements were lower at the final visit in the surgical group (p ≤0.0001). No significant differences were found in any of the parameters among the four stages of MTM (p > 0.05). Ultimately, correlation and multivariate linear regression analyses did not reveal any significant association between CVI and visual acuity. CONCLUSIONS: This study did not find significant preoperative differences in CVI between healthy myopic eyes and eyes with MTM. However, the postoperative CVI and CFA values were significantly lower than those of the control eyes. Thus, CVI may not be a good biomarker for surgical outcomes, as the correlation between CVI and visual acuity was not statistically significant.The CVI and CFA decreased after surgery, providing evidence of choroidal changes after surgical management.

Theoretical and experimental study of the 6S-8S two-photon absorption cross-section in cesium atoms.

The probability of a two-photon absorption (TPA) process is quantified by means of the TPA cross-section. In this work the TPA cross-section for the 6S1/2 → 8S1/2 transition in cesium (Cs) atoms is obtained from a theoretical and experimental approach. It is calculated using second order perturbation theory including hyperfine structure and Doppler broadening for a thermal atomic vapor. The theoretical values for the TPA cross-sections of the two allowed hyperfine transitions are σ~3,3=3.10×10-24 cm4/W and σ~4,4=3.65×10-24 cm4/W. An experiment is set up to measure these cross-sections based on the quadratic dependence between the TPA transition rate and the intensity of the laser light. Values of σ~3,3=(3.6±1.1)×10-24 cm4/W and σ~4,4=(4.6±1.1)×10-24 cm4/W are obtained from the measurements. The results show an agreement between theory and experiment. To the best of our knowledge, this is the first time that these cross-sections are reported.