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Background: The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort., Methods: Participants ( n = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology., Results: COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted β = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women ( β = 1.38 points, 95% CI 0.44-2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, p = 0.008)., Conclusions: COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality.

Background: It has been proposed that physical activity (PA) could prevent cognitive decline., Objective: To evaluate the association between changes in PA and changes in cognitive function in a cohort of adults with metabolic syndrome., Methods: Longitudinal observational study including 5,500 adults (mean age 65 years, SD = 5; women = 49.3% ) with metabolic syndrome. Participants underwent physical activity measurements and cognitive evaluation at baseline and at two-years of follow-up. PA was quantified using the Minnesota questionnaire-shortened version. Cognitive function was evaluated using a battery of tests: Mini-Mental Test Examination, Clock Drawing Test, Trail Making Test A and B, Verbal Fluency Test, and Digit Span. The primary outcome was two-year change in cognition, measured through the Global Composite Score (GCS) of all neuropsychological tests. Multivariable-adjusted linear regression models were fitted with baseline PA and their changes as the main exposures and changes in cognitive function as the outcome., Results: No significant association was found between PA levels (or their changes) in the GCS of cognitive function. A greater increase in PA levels was associated with a more favorable two-year change in the Trail Making Test A (Q4 versus Q1: b = - 2.24s, 95% CI -4.36 to -0.12s; p-trend = 0.020). No significant association was found for other neuropsychological test., Conclusion: Our results do not support an association between increases in PA and the evolution of the global cognitive function at two-year in an intervention trial which included PA promotion in one of its two randomized arms, but they suggested a possible beneficial effect of PA on attentional function in older adults.

The production and consumption of ultra-processed foods (UPF) has increased considerably during the last years worldwide. Collective evidence shows the association between UPF consumption and adverse health outcomes, including inflammatory gastro-intestinal disorders and obesity. The gut microbiota has been suggested as potential mediator of the effects of UPF consumption on metabolism and health. However, few studies have been conducted in order to elucidate these aspects. Therefore, the aim of the present study was to assess the cross-sectional associations between UPF consumption and gut microbiota in a population of senior subjects ( n = 645) within the frame of the PREDIMED-Plus trial. Eligible participants were men and women (aged 55-75 years), without documented history of cardiovascular disease at enrollment, with overweight/obesity (body mass index ≤ 27 and <40 kg/m 2 ) and metabolic syndrome. Using the information of food frequency questionnaires, the consumption of UPF, expressed as a percentage of total dietary energy intake in kcal/day, was calculated considering those food items classified in group 4 of NOVA system. Population was categorized according to tertiles of UPF consumption. Taxonomic fecal microbiota information, along with blood biochemical parameters, anthropometric measurements and clinical data were obtained. Bioinformatics analysis was performed to study the association between fecal microbiota composition and UPF consumption. We observed that subjects allocated in the highest tertile of UPF consumption (21.4 ± 5.0 % kcal/day) presented lower adherence to MedDiet ( p < 0.001) and higher total energy intake ( p < 0.001). The taxonomic analysis of the fecal microbiota revealed a significant (Benjamini-Hochberg adjusted p < 0.2) positive association between specific taxa and tertiles (T) of UPF consumption: Alloprevotella ( p = 0.041 vs. T2; p = 0.065 vs. T3), Negativibacillus ( p = 0.096 vs. T3), Prevotella ( p = 0.116 vs. T3), and Sutterella ( p = 0.116 vs. T2). UPF consumption was positively associated with lower adherence to MedDiet and higher total energy intake in senior subjects with overweight obesity and metabolic syndrome. In addition, positive association with specific fecal microbiota taxa related to inflammatory gastro-intestinal diseases and low consumption of fruits and vegetables, was observed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Atzeni, Martínez, Babio, Konstanti, Tinahones, Vioque, Corella, Fitó, Vidal, Moreno-Indias, Pertusa-Martinez, Álvarez-Sala, Castañer, Goday, Damas-Fuentes, Belzer, Martínez-Gonzalez, Hu and Salas-Salvadó.)

Background: Diets high in acid load may contribute to kidney function impairment. This study aimed to investigate the association between dietary acid load and 1-year changes in glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (UACR)., Methods: Older adults with overweight/obesity and metabolic syndrome (mean age 65 ± 5 years, 48% women) from the PREDIMED-Plus study who had available data on eGFR ( n = 5,874) or UACR ( n = 3,639) at baseline and after 1 year of follow-up were included in this prospective analysis. Dietary acid load was estimated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) at baseline from a food frequency questionnaire. Linear and logistic regression models were fitted to evaluate the associations between baseline tertiles of dietary acid load and kidney function outcomes. One year-changes in eGFR and UACR were set as the primary outcomes. We secondarily assessed ≥ 10% eGFR decline or ≥10% UACR increase., Results: After multiple adjustments, individuals in the highest tertile of PRAL or NEAP showed higher one-year changes in eGFR (PRAL, β: -0.64 ml/min/1.73 m 2 ; 95% CI: -1.21 to -0.08 and NEAP, β: -0.56 ml/min/1.73 m 2 ; 95% CI: -1.13 to 0.01) compared to those in the lowest category. No associations with changes in UACR were found. Participants with higher levels of PRAL and NEAP had significantly higher odds of developing ≥10% eGFR decline (PRAL, OR: 1.28; 95% CI: 1.07-1.54 and NEAP, OR: 1.24; 95% CI: 1.03-1.50) and ≥10 % UACR increase (PRAL, OR: 1.23; 95% CI: 1.04-1.46) compared to individuals with lower dietary acid load., Conclusions: Higher PRAL and NEAP were associated with worse kidney function after 1 year of follow-up as measured by eGFR and UACR markers in an older Spanish population with overweight/obesity and metabolic syndrome., Competing Interests: Author JS-S reported receiving research support from the Instituto de Salud Carlos III (ISCIII), Ministerio de Educación y Ciencia, Departament de Salut Pública de la Generalitat de Catalunya, the European Commission, the California Walnut Commission, Patrimonio Comunal Olivarero, La Morella Nuts, and Borges S.A; receiving consulting fees or travel expenses from California Walnut Commission, Eroski Foundation, Instituto Danone, Abbott Laboratories and Mundifarma, receiving non-financial support from Hojiblanca, Patrimonio Comunal Olivarero, and Almond Board of California; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation and the Eroski Foundation; and grants and personal fees from Instituto Danone. Author ER reported receiving grants, personal fees, and non-financial support from the California Walnut Commission during the conduct of the study and grants, personal fees, non-financial support from Alexion; personal fees from Amarin; and non-financial support from the International Nut Council outside the submitted work. Author RE reported receiving grants from Instituto de Salud Carlos III and olive oil for the trial from Fundacion Patrimonio Comunal Olivarero/during the conduct of the study and personal fees from Brewers of Europe, Fundación Cerveza y Salud, Interprofesional del Aceite de Oliva, Instituto Cervantes, Pernaud Richar, Fundación Dieta Mediterránea, Wine and Culinary International Forum; non-financial support from Sociedad Española de Nutrición and Fundación Bosch y Gimpera; and grants from Uriach Laboratories outside the submitted work. Author XP reported receiving grants from ISCIII during the conduct of the study; receiving consulting fees from Sanofi Aventis, Amgen, and Abbott laboratories; receiving lecture personal fees from Esteve, Lacer and Rubio laboratories. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Valle-Hita, Becerra-Tomás, Díaz-López, Vázquez-Ruiz, Megías, Corella, Goday, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Martín-Sánchez, Pintó, Gaforio, Matía-Martín, Vidal, Amengual-Galbarte, Daimiel, Ros, García-Arellano, Barragán, Fitó, Peña-Orihuela, Asencio-Aznar, Gómez-Gracia, Martinez-Urbistondo, Morey, Casas, Garrido-Garrido, Tojal-Sierra, Damas-Fuentes, Goñi, Ortega-Azorín, Castañer, Garcia-Rios, Gisbert-Sellés, Sayón-Orea, Schröder, Salas-Salvadó and Babio.)

Backgrounds: Vitamin D and testosterone deficiency have been widely related to obesity. However, only a few studies have investigated the effect of vitamin D on testosterone in the context of obesity, in which controversial results have been raised., Objectives: The purpose of this study was to determine the relationship between serum 25-hydroxyvitamin D (25(OH)D) and testosterone levels in young men with different grade of obesity., Design and Methods: This cross-sectional study included 269 healthy young men with obesity (body mass index (BMI) ≥ 30 kg/m 2 ). Participants were divided into two groups based on their serum 25(OH)D levels (134 subjects with vitamin D sufficiency and 135 participants with vitamin D deficiency, according to the 50 th percentile of 25(OH)D). Serum 25(OH)D and sex hormones have been measured. The relationships between 25(OH)D, sex hormones, and obesity grades were investigated with linear and binary logistic regression analyses, as well as mediation analysis., Results: Compared to the 25(OH)D sufficiency group, total and free testosterone levels were found to be decreased, whereas serum androstenedione levels were increased in the 25(OH)D deficiency group ( p <0.05). Using multivariable lineal regression analyses, 25(OH)D was correlated with the majority of sex hormones ( p <0.05). When mediation with BMI was performed, the direct effect between 25(OH)D and sex hormones disappeared, and only the indirect effect via BMI remained (demonstrating the importance of BMI). Furthermore, after controlling for age and smoking status, we discovered that total testosterone and SHBG were both significantly associated with 25(OH)D ( p <0.05) in subjects with obesity type III. Using a mediation analysis, we discovered that BMI had a partial effect on the association between 25(OH)D and total testosterone levels in morbidly obese participants, indicating that a direct association between 25(OH)D and total testosterone levels, and that BMI partially mediated this association., Conclusions: Serum 25(OH)D is associated with total testosterone levels in only those subjects with morbid obesity, suggesting a specific benefit in severe cases of obesity. Additional research is needed to elucidate possible common mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Damas-Fuentes, Boughanem, Molina-Vega, Tinahones, Fernández-García and Macías-González.)

In the last decades, obesity has reached epidemic proportions worldwide. Obesity is a chronic disease associated with a wide range of comorbidities, including insulin resistance and type 2 diabetes mellitus (T2D), which results in significant burden of disease and major consequences on health care systems. Of note, intricate interactions, including different signaling pathways, are necessary for the establishment and progression of these two closely related conditions. Altered cell-to-cell communication among the different players implicated in this equation leads to the perpetuation of a vicious circle associated with an increased risk for the development of obesity-related complications, such as T2D, which in turn contributes to the development of cardiovascular disease. In this regard, the dialogue between the adipocyte and pancreatic beta cells has been extensively studied, although some connections are yet to be fully elucidated. In this review, we explore the potential pathological mechanisms linking adipocyte dysfunction and pancreatic beta cell impairment/insulin resistance. In addition, we evaluate the role of emerging actors, such as the gut microbiome, in this complex crosstalk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martínez-Montoro, Damas-Fuentes, Fernández-García and Tinahones.)

Genomic sequencing of tumor tissues provides information on actionable gene aberrations that have diagnostic and therapeutic significance and may guide clinical management through the use of targeted therapies. The indications for these techniques and their possible limitations for application in daily practice should be established as a priority. In the present study, a group of patients with few suitable therapeutic options who were eligible for a next-generation sequencing (NGS) analysis were analyzed, and the molecular targets identified and their therapeutic impact are described. A series of 26 patients treated at the Virgen Macarena Hospital for whom an NGS study was requested between January 2017 and December 2019 were reviewed. Actionable molecular alterations were identified in 20 of the cases, and 4 patients received NGS-guided treatment. NGS techniques represent a novel opportunity for guiding treatment in cancer patients. Patients with few therapeutic alternatives, either due to diagnosis, atypical evolution or resistance to standard therapy, may be suitable candidates., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Hernández-Pacheco Acosta et al.)

Competing Interests: The authors declare no conflict of interest.

Type A insulin resistance (IR) syndrome is a very uncommon genetic disorder affecting the insulin receptor (INSR) gene, characterized by severe IR without the presence of obesity. Patients with this condition will eventually develop diabetes, presenting a variable response to insulin-sensitizers, such as metformin and thiazolidinediones, and high doses of insulin. We report for the first time the results of the use of combination therapy with a glucagon-like peptide-1 receptor agonist and a sodium-glucose cotransporter 2 inhibitor for the treatment of diabetes in the context of type A IR syndrome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martínez-Montoro, Pinzón-Martín, Damas-Fuentes, Fernández-Valero and Tinahones.)

Heart failure (HF) has been a hot topic in diabetology in the last few years, mainly due to the central role of sodium-glucose cotransporter 2 inhibitors (iSGLT2) in the prevention and treatment of cardiovascular disease and heart failure. It is well known that HF is a common complication in diabetes. However, most of the knowledge about it and the evidence of cardiovascular safety trials with antidiabetic drugs refer to type 2 diabetes (T2D). The epidemiology, etiology, and pathophysiology of HF in type 1 diabetes (T1D) is still not well studied, though there are emerging data about it since life expectancy for T1D has increased in the last decades and there are more elderly patients with T1D. The association of T1D and HF confers a worse prognosis than in T2D, thus it is important to investigate the characteristics, risk factors, and pathophysiology of this disease in order to effectively design prevention strategies and therapeutic tools.

Despite bariatric surgery being the most effective treatment for obesity, some individuals do not respond adequately, especially in the long term. Identifying the predictors of correct weight maintenance in the medium (from 1 to 3 years after surgery) and long term (from 3 years and above) is of vital importance to reduce failure after bariatric surgery; therefore, we summarize the evidence about certain factors, among which we highlight surgical technique, psychological factors, physical activity, adherence to diet, gastrointestinal hormones or neurological factors related to appetite control. We conducted a search in PubMed focused on the last five years (2015-2021). Main findings are as follows: despite Roux-en-Y gastric bypass being more effective in the long term, sleeve gastrectomy shows a more beneficial effectiveness-complications balance; pre-surgical psychological and behavioral evaluation along with post-surgical treatment improve long-term surgical outcomes; physical activity programs after bariatric surgery, in addition to continuous and comprehensive care interventions regarding diet habits, improve weight loss maintenance, but it is necessary to improve adherence; the impact of bariatric surgery on the gut-brain axis seems to influence weight maintenance. In conclusion, although interesting findings exist, the evidence is contradictory in some places, and long-term clinical trials are necessary to draw more robust conclusions.

Male hypogonadism associated with obesity is a very prevalent condition and is increasing in parallel with the epidemic prevalence of obesity. Low testosterone levels promote higher fat mass with reduced lean mass. Male hypogonadism is related to an increase in associated cardiometabolic complications, such as hypertension, type 2 diabetes mellitus, the metabolic syndrome, and cardiovascular disease. Its influence as a comorbidity of obesity is becoming more evident and should be evaluated and treated in at-risk patients. Mechanisms involved in this relationship include body composition changes, the presence of adipokines, insulin resistance, and other factors, some of which are still unknown. Weight loss and treatment to replace testosterone levels improve the metabolic profile and quality of life in patients with obesity and hypogonadism; these beneficial effects depend on treatment modality and duration of therapy. The use of testosterone replacement therapy may be indicated, as it has not been shown to increase cardiovascular risk, and retrospective studies suggest a reduction in events in men with metabolic syndrome and type 2 diabetes., Competing Interests: None