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In this article we address two related issues on the learning of probabilistic sequences of events. First, which features make the sequence of events generated by a stochastic chain more difficult to predict. Second, how to model the procedures employed by different learners to identify the structure of sequences of events. Playing the role of a goalkeeper in a video game, participants were told to predict step by step the successive directions-left, center or right-to which the penalty kicker would send the ball. The sequence of kicks was driven by a stochastic chain with memory of variable length. Results showed that at least three features play a role in the first issue: (1) the shape of the context tree summarizing the dependencies between present and past directions; (2) the entropy of the stochastic chain used to generate the sequences of events; (3) the existence or not of a deterministic periodic sequence underlying the sequences of events. Moreover, evidence suggests that best learners rely less on their own past choices to identify the structure of the sequences of events.

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It has been assumed that exercise intensity variation throughout a cycling time trial (TT) occurs in alignment of various metabolic changes to prevent premature task failure. However, this assumption is based on target metabolite responses, which limits our understanding of the complex interconnection of metabolic responses during exercise. The current study characterized the metabolomic profile, an untargeted metabolic analysis, after specific phases of a cycling 4-km TT. Eleven male cyclists performed three separated TTs in a crossover counterbalanced design, which were interrupted at the end of the fast-start (FS, 600 ± 205 m), even-pace (EP, 3600 ± 190 m), or end-spurt (ES, 4000 m) phases. Blood samples were taken before any exercise and 5 min after exercise cessation, and the metabolomic profile characterization was performed using Nuclear Magnetic Resonance metabolomics. Power output (PO) was also continually recorded. There were higher PO values during the FS and ES compared to the EP (all p < 0.05), which were accompanied by distinct metabolomic profiles. FS showed high metabolite expression in TCA cycle and its related pathways (e.g., glutamate, citric acid, and valine metabolism); whereas, the EP elicited changes associated with antioxidant effects and oxygen delivery adjustment. Finally, ES was related to pathways involved in NAD turnover and serotonin metabolism. These findings suggest that the specific phases of a cycling TT are accompanied by distinct metabolomic profiles, providing novel insights regarding the relevance of specific metabolic pathways on the process of exercise intensity regulation.

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Heptagon-containing distorted nanographenes are used as stoppers for the capping of a [2]rotaxane through a Michael-type addition reaction to vinyl sulfone groups. These curved aromatics are bulky enough to prevent the disassembly of the rotaxane but also give emissive and nonlinear (two-photon absorption and emission) optical properties to the structure.

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In recent years, much of the emphasis for transformation of introductory STEM courses has focused on "active learning", and while this approach has been shown to produce more equitable outcomes for students, the construct of "active learning" is somewhat ill-defined and is often used as a "catch-all" that can encompass a wide range of pedagogical techniques. Here we present an alternative approach for how to think about the transformation of STEM courses that focuses instead on what students should know and what they can do with that knowledge. This approach, known as three-dimensional learning (3DL), emerged from the National Academy's "A Framework for K-12 Science Education", which describes a vision for science education that centers the role of constructing productive causal accounts for phenomena. Over the past 10 years, we have collected data from introductory biology, chemistry, and physics courses to assess the impact of such a transformation on higher education courses. Here we report on an analysis of video data of class sessions that allows us to characterize these sessions as active, 3D, neither, or both 3D and active. We find that 3D classes are likely to also involve student engagement (i.e. be active), but the reverse is not necessarily true. That is, focusing on transformations involving 3DL also tends to increase student engagement, whereas focusing solely on student engagement might result in courses where students are engaged in activities that do not involve meaningful engagement with core ideas of the discipline.

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BACKGROUND: Preterm birth and low birthweight (LBW) might be associated with reduced physical fitness, although evidence remains inconclusive. OBJECTIVE: To examine the influence of preterm birth and LBW on physical fitness, as well as to assess whether variables such as gestational age, birthweight, or age at assessment moderate these effects. METHODS: PubMed, Scopus, and PsycINFO were systematically searched from inception to 7 December 2023 for case-control and cohort studies analyzing the association between preterm birth or LBW (or gestational age or birthweight as continuous variables) with at least one physical fitness-related outcome (i.e., cardiorespiratory fitness (CRF), muscle strength, flexibility, speed, agility). Random-effects meta-analysis and meta-regression models were used to estimate the pooled effect size, as well as to examine potential associations between the magnitude of the effect and gestational age, birthweight, or age at assessment. RESULTS: Fifty-two studies (n = 920,603 participants, average age ranging from 4.7 to 34.4 years) were included. Preterm birth was associated with reduced CRF (standardized mean difference (SMD) = -0.38, 95% confidence interval (CI) = -0.51 to -0.25) and muscle strength (SMD = -0.44, 95% CI = -0.79 to -0.08). LBW was associated with reduced CRF (SMD = -0.40, 95% CI = -0.64 to -0.17), muscle strength (SMD = -0.18, 95% CI = -0.24 to -0.13), flexibility (SMD = -0.11, 95% CI = -0.22 to -0.01), and agility (SMD = -0.99, 95% CI = -1.91 to -0.07). Meta-regression analyses showed that a lower gestational age or birthweight were associated with larger reductions in physical fitness, whereas no consistent association was found for the age at assessment. CONCLUSION: Both preterm birth and LBW seem associated with reduced physical fitness regardless of age, with larger reductions overall observed in individuals with lower gestational age or birthweight. These findings might support the implementation of preventive strategies (e.g., fitness monitoring and physical exercise interventions) in these populations through the life course. PROSPERO registration: CRD42021231845.

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Click chemistry has reached its maturity as the weapon of choice for the irreversible ligation of molecular fragments, with over 20 years of research resulting in the development or improvement of highly efficient kinetically controlled conjugation reactions. Nevertheless, traditional click reactions can be disadvantageous not only in terms of efficiency (side products, slow kinetics, air/water tolerance, etc.), but also because they completely avoid the possibility to reversibly produce and control bound/unbound states. Recently, non-covalent click chemistry has appeared as a more efficient alternative, in particular by using host-guest self-assembled systems of high thermodynamic stability and kinetic lability. This review discusses the implementation of molecular switches in the development of such non-covalent ligation processes, resulting in what we have termed stimuli-responsive click chemistry, in which the bound/unbound constitutional states of the system can be favored by external stimulation, in particular using host-guest complexes. As we exemplify with handpicked selected examples, these supramolecular systems are well suited for the development of human-controlled molecular conjugation, by coupling thermodynamically regulated processes with appropriate temporally resolved extrinsic control mechanisms, thus mimicking nature and advancing our efforts to develop a more function-oriented chemical synthesis.

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INTRODUCTION: Pregnancy may contribute to an excess risk of thrombotic or cardiovascular events. COVID-19 increases the risk of these events, although the risk is relatively limited among outpatients. We sought to determine whether outpatient pregnant women with COVID-19 are at a high risk for cardiovascular or thrombotic events. MATERIALS & METHODS: We analyzed pregnant outpatients with COVID-19 from the multicenter CORONA-VTE-Network registry. The main study outcomes were a composite of adjudicated venous or arterial thrombotic events, and a composite of adjudicated cardiovascular events. Events were assessed 90 days after the COVID-19 diagnosis and reported for non-pregnant women ≤45 years, and for men ≤45 years, as points of reference. RESULTS: Among 6585 outpatients, 169 were pregnant at diagnosis. By 90-day follow-up, two pregnant women during the third trimester had lower extremity venous thrombosis, one deep and one superficial vein thrombosis. The cumulative incidence of thrombotic events was 1.20 % (95 % confidence interval [CI]: 0.0 to 2.84 %). Respective rates were 0.47 % (95 % CI: 0.14 % to 0.79 %) among non-pregnant women, and 0.49 % (95 % CI: 0.06 % to 0.91 %) among men ≤45 years. No non-thrombotic cardiovascular events occurred in pregnant women. The rates of cardiovascular events were 0.53 % (95 % CI: 0.18 to 0.87) among non-pregnant women, and 0.68 % (95 % CI: 0.18 to 1.18) in men aged ≤45 years. CONCLUSIONS: Thrombotic and cardiovascular events are rare among outpatients with COVID-19. Although a higher event rate among outpatient pregnant women cannot be excluded, the absolute event rates are low and do not warrant population-wide cardiovascular interventions to optimize outcomes.

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BACKGROUND: Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear. OBJECTIVE: To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism. DESIGN: Secondary analysis of a randomized, double-blind, placebo-controlled trial. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: 83 older (age ≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and persistently low AM testosterone (< 10.4 nmol/L) associated with frailty. INTERVENTIONS: LT (weight management and exercise training) plus either testosterone (LT+TRT) or placebo (LT+Pbo) for six months. OUTCOME MEASURES: Primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure, and metabolic syndrome score. RESULTS: HbA1c decreased similarly in LT+TRT and LT+Pbo groups (-0.5% vs. -0.6%, respectively; p= 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in LT+Pbo group vs. 0.2 ± 1.1 mg/dL in LT+TRT group, p= 0.01) and adiponectin levels (-408 ± 489 ng/mL in TRT+LT group vs 1832 ± 468 ng/mL in LT+Pbo group, p= 0.02). CONCLUSION: In older men with obesity and hypogonadism, adding TRT for six months to LT does not result in further improved cardiometabolic profiles, and could potentially blunt some of the metabolic benefits induced by LT.

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The release of extracellular vesicles (EVs) has been implicated as an alternative transport mechanism for the passage of macromolecules through the fungal cell wall, a phenomenon widely reported in yeasts but poorly explored in mycelial cells. In the present work, we have purified and characterized the EVs released by mycelia of the emerging, opportunistic, widespread and multidrug-resistant filamentous fungus Scedosporium apiospermum. Transmission electron microscopy images and light scattering measurements revealed the fungal EVs, which were observed individually or grouped with heterogeneous morphology, size and electron density. The mean diameter of the EVs, evaluated by the light scattering technique, was 179.7 nm. Overall, the structural stability of S. apiospermum EVs was preserved during incubation under various storage conditions. The lipid, carbohydrate and protein contents were quantified, and the EVs' protein profile was evidenced by SDS-PAGE, revealing proteins with molecular masses ranging from 20 to 118 kDa. Through immunoblotting, ELISA and immunocytochemistry assays, antigenic molecules were evidenced in EVs using a polyclonal serum (called anti-secreted molecules) from a rabbit inoculated with conditioned cell-free supernatant obtained from S. apiospermum mycelial cells. By Western blotting, several antigenic proteins were identified. The ELISA assay confirmed that the anti-secreted molecules exhibited a positive reaction up to a serum dilution of 1:3200. Despite transporting immunogenic molecules, S. apiospermum EVs slightly induced an in vitro cytotoxicity effect after 48 h of contact with either macrophages or lung epithelial cells. Interestingly, the pretreatment of both mammalian cells with purified EVs significantly increased the association index with S. apiospermum conidia. Furthermore, EVs were highly toxic to Galleria mellonella, leading to larval death in a typically dose- and time-dependent manner. Collectively, the results represent the first report of detecting EVs in the S. apiospermum filamentous form, highlighting a possible implication in fungal pathogenesis.

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Intermittent fasting (IF) has been suggested to reduce body fat percentage and improve non-communicable chronic diseases. However, little is known about resistance training (RT) and the subjective perception of hunger under fasted conditions. This study aimed to examine the effects of overnight fasting (12 h or 16 h fasting) on the maximum voluntary isometric contraction (MVIC) and countermovement jump (CMJ) performance in resistance-trained young male adults. In RT sessions, the maximum number of repetitions (MNR) and the total volume load (TVL) were evaluated in the back squat and leg press 45°. The volunteers performed all tests and the RT session in 3 different conditions: fed state, 12 and 16 hours of IF. The subjective perception of hunger was applied through an adapted visual analogue scale (adVAS). The results showed that strength and power variables did not change significantly: MVIC (p = 0.960), CMJ (p = 0.986), MNR back squat (p = 0.856), MNR leg press 45° (p = 0.998), TVL (p = 0.954). However, hunger was significantly greater after the 16-hour fasting (p = 0.001) compared to 12 hours of fasting and the fed state. Also, the desire to eat was greater after 16 hours (p = 0.001) compared to 12 hours of fasting and the fed state. This study indicates that IF for 12 or 16 hours does not significantly impair strength and power, but the longer the fasting duration, the greater are the hunger and desire to eat.

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Background: Non-germinomatous germ cell tumors (NGGCT) accounts for one third of intracranial GCT. While the germinoma group have an excellent overall survival, the standard of practice for children with NGGCT is still under evaluation. Aims: Describe the results of the of the Brazilian consortium protocol. Methods: Since 2013, 15 patients with a diagnosis of NGGCT by histopathology and/or serum/cerebrospinal fluid (CSF) tumor markers, ßHCG >200mlU/ml and/or positive alpha-fetoprotein were treated with neoadjuvant chemotherapy with carboplatin, cyclophosphamide and etoposide followed by ventricular radiotherapy (RTV) of 18Gy with boost (32Gy) to the primary site. Metastatic patients underwent craniospinal irradiation (CSI) and "slow responders" to the four initial cycles of CT, to autologous stem cell transplantation (ASCT) followed by CSI. Results: Mean age, 13.1 years. Thirteen males. Primary sites: pineal (n=12), suprasellar (n=2) and bifocal (n=1). Four patients were metastatic at diagnosis. Eight patients had CSF and/or serum alpha-fetoprotein levels > 1,000ng/ml. Tumor responses after chemotherapy demonstrated complete in six cases and partial in seven, with "second-look" surgery being performed in five cases, and two patients presenting viable lesions being referred to ASCT. The main toxicity observed was hematological grades 3/4. Two patients with metastatic disease, one with Down Syndrome and AFP > 1,000ng/ml and the other with choriocarcinoma and pulmonary metastases, developed progressive disease resulting in death, as well as two other patients without evidence of disease, due to endocrinological disorders. Event-free and overall survival at 2 and 5 years were 80% and 72.7%, respectively, with a mean follow-up of 48 months (range, 7-107). Conclusions: Despite the small number of patients, in our series, treatment with six cycles of chemotherapy and RTV with focal boost for localized disease (n=11) and ACST for identified slow responders (n=2) seem to be effective strategies contributing to the overall effort to improve outcomes of this group of patients.

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Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S. pyogenes. More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were shared across species. Assessing potential cross-protection from leading S. pyogenes vaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention.

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BACKGROUND: Guide catheter extensions (GCEs) increase support and facilitate equipment delivery, but aggressive instrumentation may be associated with a higher risk of complications. AIM: Our aim was to assess the impact of GCEs on procedural success and complications in patients submitted to chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We analyzed data from the multicenter LATAM CTO Registry. Procedural success was defined as <30% residual stenosis and TIMI 3 distal flow. Major adverse cardiac and cerebrovascular events (MACCE) was defined as the composite of all-cause death, myocardial infarction, target vessel revascularization, and stroke. Propensity score matching (PSM) was used to compare outcomes with and without GCE use. RESULTS: From August 2010 to August 2021, 3049 patients were included. GCEs were used in 438 patients (14.5%). In unadjusted analysis, patients in the GCE group were older and had more comorbidities. The median J-CTO score and its components were higher in the GCE group. After PSM, procedural success was higher with GCE use (87.7% vs. 80.5%, p = 0.007). The incidence of coronary perforation (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.78-2.71, p = 0.230), bleeding (OR: 1.99, 95% CI: 0.41-2.41, p = 0.986), in-hospital death (OR: 1.39, 95% CI: 0.54-3.62, p = 0.495) and MACCE (OR: 1.07, 95% CI: 0.52-2.19, p = 0.850) were similar in both groups. CONCLUSION: In a contemporary, multicenter cohort of patients undergoing CTO PCI, GCEs were used in older patients, with more comorbidities and complex anatomy. After PSM, GCE use was associated with higher procedural success, and similar incidence of adverse outcomes.

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Type 2 diabetes mellitus (DM) continues to escalate, necessitating innovative therapeutic approaches that target distinct pathways and address DM complications. Flavonoids have been shown to possess several pharmacological activities that are important for DM. This study aimed to evaluate the in vivo effects of the flavonoid melanoxetin using Goto-Kakizaki rats. Over a period of 14 days, melanoxetin was administered subcutaneously to investigate its antioxidant, anti-inflammatory, and antidiabetic properties. The results show that melanoxetin reduced insulin resistance in adipose tissue by targeting protein tyrosine phosphatase 1B. Additionally, melanoxetin counteracted oxidative stress by reducing nitrotyrosine levels and modulating superoxide dismutase 1 and hemeoxygenase in adipose tissue and decreasing methylglyoxal-derived hydroimidazolone (MG-H1), a key advanced glycation end product (AGE) implicated in DM-related complications. Moreover, the glyoxalase 1 expression decreased in both the liver and the heart, correlating with reduced AGE levels, particularly MG-H1 in the heart. Melanoxetin also demonstrated anti-inflammatory effects by reducing serum prostaglandin E2 levels, and increasing the antioxidant status of the aorta wall through enhanced acetylcholine-dependent relaxation in the presence of ascorbic acid. These findings provide valuable insights into melanoxetin's therapeutic potential in targeting multiple pathways involved in type 2 DM, particularly in mitigating oxidative stress and glycation.

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Doxorubicin is one of the most important antitumor drugs used in oncology; however, its cardiotoxic effect limits the therapeutic use and raises concerns regarding patient prognosis. Leucine is a branched-chain amino acid used in dietary supplementation and has been studied to attenuate the toxic effects of doxorubicin in animals, which increases oxidative stress. Oxidative stress in different organs can be estimated using several methods, including catalase expression analysis. This study aimed to analyze the effect of leucine on catalase levels in rat hearts after doxorubicin administration. Adult male Wistar rats were separated into two groups: Standard diet (SD) and 5% Leucine-Enriched Diet (LED). The animals had free access to diet from D0 to D28. At D14, the groups were subdivided in animals injected with Doxorubicin and animals injected with vehicle, until D28, and the groups were SD, SD + Dox, LED and LED + Dox. At D28, the animals were submitted do Transthoracic Echocardiography and euthanized. Despite Dox groups had impaired body weight gain, raw heart weight was not different between the groups. No substantial alterations were observed in macroscopic evaluation of the heart. Although, Doxorubicin treatment increased total interstitial collagen in the heart, which in addition to Type I collagen, is lower in LED groups. Western blot analysis showed that catalase expression in the heart of LED groups was lower than that in SD groups. In conclusion, leucine supplementation reduced both the precocious Dox-induced cardiac remodeling and catalase levels in the heart.

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We report the synthesis of a new set of amphiphilic saddle-shaped heptagon-containing polycyclic aromatic hydrocarbons (PAHs) functionalized with tetraethylene glycol chains and their self-assembly into large two-dimensional (2D) polymers. An in-depth analysis of the self-assembly mechanism at the air/water interface has been carried out, and the proposed arrangement models are in good agreement with the molecular dynamics simulations. Quite remarkably, the number and disposition of the tetraethylene glycol chains significantly influence the disposition of the PAHs at the interface and conditionate their packing under pressure. For the three compounds studied, we observed three different behaviors in which the aromatic core is parallel, perpendicular, and tilted with respect to the water surface. We also show that these curved PAHs are able to self-assemble in solution into remarkably large sheets of up to 150 µm2. These results show the relationship, within a family of curved nanographenes, between the monomer configuration and their self-assembly capacity in air/water interfaces and organic-water mixtures.

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Reactive oxygen species (ROS) are closely related to oxidative stress, aging, and the onset of human diseases. To mitigate ROS-induced damages, extensive research has focused on examining the antioxidative attributes of various synthetic/natural substances. Coordination compounds serving as synthetic antioxidants have emerged as a promising approach to attenuate ROS toxicity. Herein, we investigated the antioxidant potential of a series of Fe(III) (1), Mn(III)Mn(II) (2) and Cu(II) (3) coordination compounds synthesized with the ligand N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)[(3-chloro)(2-hydroxy)]-propylamine in Saccharomyces cerevisiae exposed to oxidative stress. We also assessed the antioxidant potential of these complexes in the alternative model of study, Galleria mellonella. DPPH analysis indicated that these complexes presented moderate antioxidant activity. However, treating Saccharomyces cerevisiae with 1, 2 and 3 increased the tolerance against oxidative stress and extended yeast lifespan. The treatment of yeast cells with these complexes decreased lipid peroxidation and catalase activity in stressed cells, whilst no change in SOD activity was observed. Moreover, these complexes induced the Hsp104 expression. In G. mellonella, complex administration extended larval survival under H2O2 stress and did not affect the insect's life cycle. Our results suggest that the antioxidant potential exhibited by these complexes could be further explored to mitigate various oxidative stress-related disorders.

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BACKGROUND: Metabolically healthy obesity is hypothesized to be a benign condition but whether this is the case for dementia remains debated. We examined the role of age at assessment of metabolic-obesity phenotypes in associations with incident dementia. METHODS: Obesity (body mass index ≥ 30 kg/m2) and poor metabolic health (≥ 2 of elevated serum triglycerides, low HDL-C, elevated blood pressure, and elevated serum fasting glucose) were used to define four metabolic-obesity phenotypes (metabolically healthy (MHNO) and unhealthy non-obesity (MUNO), metabolically healthy (MHO) and unhealthy obesity (MUO)) at < 60, 60 to < 70, and ≥ 70 years using 6 waves of data from the Whitehall II study and their associations with incident dementia was examined using Cox regression. RESULTS: Analyses with exposures measured < 60, 60 to < 70, and ≥ 70 years involved 410 (5.8%), 379 (5.6%), and 262 (7.4%) incident dementia cases over a median follow-up of 20.8, 10.3, and 4.2 years respectively. In analyses of individual components, obesity before 60 years (HR 1.41, 95% CI: [1.08, 1.85]) but not at older ages was associated with dementia; unhealthy metabolic status when present < 60 years (HR 1.33, 95% CI: [1.08, 1.62]) and 60 to < 70 years (HR 1.32, 95% CI: [1.07, 1.62]) was associated with dementia. Compared to the metabolically healthy non-obesity group, the risk of dementia was higher in those with metabolically healthy obesity before 60 years (1.69; 95% CI: [1.16, 2.45]); this was not the case when metabolic-obesity phenotype was present at 60 to < 70 years or ≥ 70 years. Analyses at older ages were on smaller numbers due to death and drop-out but inverse probability weighting to account for missing data yielded similar results. CONCLUSIONS: Individuals with metabolically healthy obesity before age 60 had a higher risk of incident dementia over a 27-year follow-up; the excess risk dissipates when metabolic health and obesity are measured after 70 years.

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Reactive oxygen species(ROS) generation with subsequent DNA damage is one of the principle mechanisms of action assigned to copper-based anticancer complexes. The efficacy of this type of chemotherapeutic may be reduced in the low oxygen environment of tumours. In this study the cytotoxicity of three complexes, [Cu(dips)(phen)] (1), [Cu(ph)(phen)]·2H2O (2) and [Cu(ph)(bpy)]·H2O (3) (disp: 3,5-diisopropylsalicylate, phen: 1,10- phenanthroline, ph: phthalate, bpy: 2,2'-bipyridyl) were assessed for anticancer activity in the breast-cancer derived MCF-7 line under normoxic, hypoxic and anoxic conditions. In an immortalised keratinocyte HaCaT cell line, the cytotoxicity of complexes 2 and 3 was significantly reduced under both normoxic and hypoxic conditions, whilst the cytotoxicity of complex 1 was increased under hypoxic conditions. The ability of the complexes to generate ROS in the MCF-7 cell line was evaluated as was their ability to act as superoxide dismutase(SOD) and catalase mimics using a yeast cell assay. ROS generation was significant for complexes 2 and 3, less so for complex 1 though all three complexes had SOD mimetic ability. Given the ternary nature of the complexes, solution speciation studies were undertaken but were only successful for complex 3, due to solubility issues with the other two complexes. The concentration distribution of various species, formed in aqueous solution, was evaluated as a function of pH and confirmed that complex 3 is the dominant species at physiological pH in the mM concentration range. However, as its concentration diminishes, it experiences a progressive dissociation, leading to the formation of binary complexes of bpy alongside unbound phthalate.

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