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The first monograph on the works of Patricia Urquiola, whose eclectic approach to product design and architecture has established her as one of the key figures in contemporary design. A superstar in the world of design, Patricia Urquiola's portfolio of architectural projects and product designs is as diverse as it is intensely personal-from a house for Patrizia Moroso, to the interiors of boutique hotels, to industrial design, and with products that include chairs, watches, and cutlery. Since the opening of her own design practice in Milan in 2001, Urquiola has taken on an ever-expanding number of projects, and has worked with all the great international design houses, including Moroso, De Padova, B&B Italia, Bisazza, Alessi, Driade, and Flos, to name a few. Urquiola's distinctive works straddle the boundary between architecture and design, the product of a rigorous, interdisciplinary education.

Functional status is considered the main determinant of healthy aging. Impairment in skeletal muscle and the cardiovascular system, two interrelated systems, results in compromised functional status in aging. Increased oxidative stress and inflammation in older subjects constitute the background for skeletal muscle and cardiovascular system alterations. Aged skeletal muscle mass and strength impairment is related to anabolic resistance, mitochondrial dysfunction, increased oxidative stress and inflammation as well as a reduced antioxidant response and myokine profile. Arterial stiffness and endothelial function stand out as the main cardiovascular alterations related to aging, where increased systemic and vascular oxidative stress and inflammation play a key role. Physical activity and exercise training arise as modifiable determinants of functional outcomes in older persons. Exercise enhances antioxidant response, decreases age-related oxidative stress and pro-inflammatory signals, and promotes the activation of anabolic and mitochondrial biogenesis pathways in skeletal muscle. Additionally, exercise improves endothelial function and arterial stiffness by reducing inflammatory and oxidative damage signaling in vascular tissue together with an increase in antioxidant enzymes and nitric oxide availability, globally promoting functional performance and healthy aging. This review focuses on the role of oxidative stress and inflammation in aged musculoskeletal and vascular systems and how physical activity/exercise influences functional status in the elderly.

Uraemic toxins increase in serum parallel to a decline in the glomerular filtration rate and the development of sarcopenia in patients with chronic kidney disease (CKD). This study analyses the role of uraemic toxins in sarcopenia at different stages of CKD, evaluating changes in the muscular regeneration process. Cultured C 2 C 12 cells were incubated with a combination of indoxyl sulphate and p-cresol at high doses (100 µg/mL) or low doses (25 µg/mL and 10 µg/mL) resembling late or early CKD stages, respectively. Cell proliferation (analysed by scratch assays and flow cytometry) was inhibited only by high doses of uraemic toxins, which inactivated the cdc2-cyclin B complex, inhibiting mitosis and inducing apoptosis (analysed by annexin V staining). By contrast, low doses of uraemic toxins did not affect proliferation, but reduced myogenic differentiation, primed with 2% horse serum, by inhibiting myogenin expression and promoting fibro-adipogenic differentiation. Finally, to assess the in vivo relevance of these results, studies were performed in gastrocnemii from uraemic rats, which showed higher collagen expression and lower myosin heavy chain expression than those from healthy rats. In conclusion, uraemic toxins impair the skeletal muscular regeneration process, even at low concentrations, suggesting that sarcopenia can progress from the early stages of CKD.

Background Hyperphosphatemia has been related to the development of sarcopenia in aging mice. We describe the intracellular mechanisms involved in the impairment of the myogenic differentiation promoted by hyperphosphatemia and analyse these mechanisms in the muscle from older mice. Methods C2C12 cells were grown in 2% horse serum in order to promote myogenic differentiation, in the presence or absence of 10 mM beta‐glycerophosphate (BGP) for 7 days. Troponin T, paired box 7 (Pax‐7), myogenic factor 5 (Myf5), myogenic differentiation 1 (MyoD), myogenin (MyoG), myocyte enhancer factor 2 (MEF2C), P300/CBP‐associated factor (PCAF), histone deacetylase 1 (HDAC1), fibronectin, vimentin, and collagen I were analysed at 48, 72, and 168 h, by western blotting or by immunofluorescence staining visualized by confocal microscopy. Studies in mice were performed in 5‐ and 24‐month‐old C57BL6 mice. Three months before sacrifice, 21‐month‐old mice were fed with a standard diet or a low phosphate diet, containing 0.6% or 0.2% phosphate, respectively. Serum phosphate concentration was assessed by a colorimetric method and forelimb strength by a grip test. Fibrosis was observed in the tibialis anterior muscle by Sirius Red staining. In gastrocnemius muscle, MyoG, MEF2C, and fibronectin expressions were analysed by western blotting. Results Cells differentiated in the presence of BGP showed near five times less expression of troponin T and kept higher levels of Pax‐7 than control cells indicating a reduced myogenic differentiation. BGP reduced Myf5 about 50% and diminished MyoD transcriptional activity by increasing the expression of HDAC1 and reducing the expression of PCAF. Consequently, BGP reduced to 50% the expression of MyoG and MEF2C. A significant increase in the expression of fibrosis markers as collagen I, vimentin, and fibronectin was found in cells treated with BGP. In mice, serum phosphate (17.24 ± 0.77 mg/dL young; 23.23 ± 0.81 mg/dL old; 19.09 ± 0.75 mg/dL old with low phosphate diet) correlates negatively (r = −0.515, P = 0.001) with the muscular strength (3.13 ± 0.07 gf/g young; 1.70 ± 0.12 gf/g old; 2.10 ± 0.09 gf/g old with low phosphate diet) and with the expression of MyoG (r = −0.535, P = 0.007) and positively with the expression of fibronectin (r = 0.503, P = 0.001) in gastrocnemius muscle. The tibialis anterior muscle from old mice showed muscular fibrosis. Older mice fed with a low phosphate diet showed improved muscular parameters relative to control mice of similar age. Conclusions Hyperphosphatemia impairs myogenic differentiation, by inhibiting the transcriptional activity of MyoD, and enhances the expression of fibrotic genes in cultured myoblasts. Experiments carried out in older mice demonstrate a close relationship between age‐related hyperphosphatemia and the decrease in the expression of myogenic factors and the increase in factors related to muscle fibrosis.

Background Sarcopenia is defined by the progressive and generalized loss of muscle mass and function associated with aging. We have previously proposed that aging‐related hyperphosphataemia is linked with the appearance of sarcopenia signs. Because there are not effective treatments to prevent sarcopenia, except for resistance exercise, we propose here to analyse whether the dietary restriction of phosphate could be a useful strategy to improve muscle function and structure in an animal model of aging. Methods Five‐month‐old (young), 24‐month‐old (old) and 28‐month‐old (geriatric) male C57BL6 mice were used. Old and geriatric mice were divided into two groups, one fed with a standard diet (0.6% phosphate) and the other fed with a low‐phosphate (low‐P) diet (0.2% phosphate) for 3 or 7 months, respectively. A phosphate binder, Velphoro®, was also supplemented in a group of old mice, mixed with a standard milled diet for 3 months. Muscle mass was measured by the weight of gastrocnemius and tibial muscles, and quality by nuclear magnetic resonance imaging (NMRI) and histological staining assays. Muscle strength was measured by grip test and contractile properties of the tibialis muscle by electrical stimulation of the common peroneal nerve. Gait parameters were analysed during the spontaneous locomotion of the mice with footprinting. Orientation and motor coordination were evaluated using a static rod test. Results Old mice fed with low‐P diet showed reduced serum phosphate concentration (16.46 ± 0.77 mg/dL young; 21.24 ± 0.95 mg/dL old; 17.46 ± 0.82 mg/dL low‐P diet). Old mice fed with low‐P diet displayed 44% more mass in gastrocnemius muscles with respect to old mice (P = 0.004). NMRI revealed a significant reduction in T2 relaxation time (P = 0.014) and increased magnetization transfer (P = 0.045) and mean diffusivity (P = 0.045) in low‐P diet‐treated mice compared with their coetaneous. The hypophosphataemic diet increased the fibre size and reduced the fibrotic area by 52% in gastrocnemius muscle with respect to old mice (P = 0.002). Twitch force and tetanic force were significantly increased in old mice fed with the hypophosphataemic diet (P = 0.004 and P = 0.014, respectively). Physical performance was also improved, increasing gait speed by 30% (P = 0.032) and reducing transition time in the static rod by 55% (P = 0.012). Similar results were found when diet was supplemented with Velphoro®. Conclusions The dietary restriction of phosphate in old mice improves muscle quantity and quality, muscle strength and physical performance. Similar results were found using the phosphate binder Velphoro®, supporting the role of phosphate in the impairment of muscle structure and function that occurs during aging.

Aging impairs vascular function, but the mechanisms involved are unknown. The aim of this study was to analyze whether aging-related hyperphosphatemia is implied in this effect by elucidating the role of oxidative stress. C57BL6 mice that were aged 5 months (young) and 24 months (old), receiving a standard (0.6%) or low-phosphate (0.2%) diet, were used. Isolated mesenteric arteries from old mice showed diminished endothelium-dependent vascular relaxation by the down-regulation of NOS3 expression, increased inflammation and increased fibrosis in isolated aortas, compared to those isolated from young mice. In parallel, increased Nox4 expression and reduced Nrf2, Sod2-Mn and Gpx1 were found in the aortas from old mice, resulting in oxidant/antioxidant imbalance. The low-phosphate diet improved vascular function and oxidant/antioxidant balance in old mice. Mechanisms were analyzed in endothelial (EC) and vascular smooth muscle cells (SMCs) treated with the phosphate donor ß-glycerophosphate (BGP). In EC, BGP increased Nox4 expression and ROS production, which reduced NOS3 expression via NFκB. BGP also increased inflammation in EC. In SMC, BGP increased Collagen I and fibronectin expression by priming ROS production and NFκB activity. In conclusion, hyperphosphatemia reduced endothelium-dependent vascular relaxation and increased inflammation and vascular fibrosis through an impairment of oxidant/antioxidant balance in old mice. A low-phosphate diet achieved improvements in the vascular function in old mice.

ABSTRACT Aims Approximately 10% of patients with myocardial infarction present with non‐obstructive coronary arteries (MINOCA), whose characteristics differ from those with obstructive coronary lesions (MICAD). Inflammation plays a key role in myocardial infarction. This study aims to develop a biomarker‐based index for accurate differentiation between MINOCA and MICAD. Methods A prospective, observational cohort study including 111 patients admitted for myocardial infarction: 46 with MINOCA and 65 with MICAD. Blood samples were collected within the first 24 h to measure high‐sensitivity C‐reactive protein, interleukin‐6, asymmetric dimethylarginine, and peak high‐sensitivity troponin T. The association of these biomarkers with MICAD risk was analyzed using logistic regression. Scoring systems were developed using optimization algorithms to predict the diagnosis before coronary angiography, applied to both individual biomarkers and a combined index. Results Patients had a mean age of 67 years (SD 13.3), with a male predominance (68.5%). Higher levels of IL‐6 and high‐sensitivity troponin T were significantly associated with increased MICAD risk (OR: 1.58; 95% CI: 1.01–2.46, and OR: 2.27; 95% CI: 1.61–3.26, respectively). As score increases, interleukin‐6 and high‐sensitivity troponin T increase the likelihood of MICAD classification, while higher asymmetric dimethylarginine levels reduce it. Each one‐point increase in the combined index multiplies MICAD risk by six (OR:6.16, 95%CI: 2.72–13.95; p < 0.001). While individual indexes improved the diagnostic performance of biomarkers, the combined index demonstrated superior accuracy (AUC: 0.918). Conclusions A biomarker‐based scoring system was developed, achieving superior discriminatory capacity for differentiating MINOCA from MICAD compared to the individual analysis of biomarkers in absolute values or independent indexes. Summary What is known about the topic? ◦ Patients with MINOCA have distinct characteristics compared to those with MICAD, with inflammation and endothelial dysfunction potentially serving as key differentiators. ◦ High‐sensitivity troponin, commonly used in clinical practice for diagnosing myocardial infarction, is valuable but does not allow for precise differentiation between MINOCA and MICAD when used alone. ◦ The integration of inflammatory and endothelial dysfunction biomarkers with troponin in a scoring system could potentially provide a more accurate method for distinguishing between these two types of infarction. What's new? ◦ This study is the first to develop a scoring system using circulating biomarkers to more accurately differenciate between MINOCA and MICAD. ◦ We focused on four key biomarkers: IL‐6, hs‐CRP, ADMA and hs‐troponin T. By combining troponin T, which is widely used in MI diagnosis, with inflammatory and endothelial dysfunction biomarkers, our approach captures the complex underlying processes involved in myocardial infarction. ◦ Our study found that combining these biomarkers into a single index demonstrated outstanding diagnostic discrimination, significantly improving the identification of MI type compared to using individual biomarkers alone. ◦ This innovative scoring system has the potential to optimize MI patient management and guide treatment strategies more accurately. Comparison of diagnostic performance in detecting obstructive coronary artery disease in patients with myocardial infarction: the biomarker‐based index demonstrates outstanding discrimination compared to individual biomarker levels (ln BM) and individual índices (4BM). AUC values for models based on log‐transformed biomarkers (ln BM), individual indices, and the combined four‐biomarker index (4BM) are shown. Abbreviations: AUC = area under the curve; MICAD = Myocardial Infarction with Obstructive Coronary Artery Disease; MINOCA = Myocardial Infarction with Non‐Obstructive Coronary Arteries; MI = myocardial infarction; IL‐6 = Interleukin‐6, hs‐CRP = high‐sensitivity C‐reactive protein, ADMA = Asymmetric Dimethylarginine, hs‐troponin T = High‐sensitivity troponin T.

Obesity can lead children and adolescents to an increased cardiovascular disease (CVD) risk. A diet supplemented with Plantago psyllium has been shown to be effective in reducing LDL-C and IL-6 in adolescents. However, there are no studies that have explored small-dense LDL (sdLDL) or HDL subclasses. The aim of this study was to evaluate the impact of a fiber dietary intervention on LDL and HDL subclasses in adolescents with obesity. In this parallel, double blind, randomized clinical trial, the participants were assigned to Plantago psyllium or placebo (10g/day for 7 weeks). We randomized 113 participants, and evaluated and analyzed 100 adolescents (50 in each group), 15 to 19 years with a body mass index of 29–34. We measured biochemical markers LDL and HDL subclasses using the Lipoprint system (Quantimetrix) and IL-6 by ELISA. Post-treatment there was a decrease in sdLDL between the groups 2.0 (0–5.0) vs 1 (0–3.0) mg/dl (p = 0.004), IL-6 median 3.32 (1.24–5.96) vs 1.76 (0.54–3.28) pg/ml, p <0.0001. There were no differences in HDL subclasses and no adverse effects were reported in either group.Conclusions: Small dense LDL and IL-6 reduced in adolescents with obesity when consuming Plantago psyllium. This may be an early good strategy for the reduction of cardiovascular disease risk in this vulnerable population.Trial registration: ISRCTN # 14180431. Date assigned 24/08/2020 What is Known:• Supplementing the diet with Plantago psyllium lowers LDL-C levels.What is New:• First evidence that soluble fiber supplementation like Plantago psyllium decreases small dense LDL particles in association with lowered IL-6, reducing the risk of cardiovascular disease in obese adolescents.