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Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss.
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Sordera , Pérdida Auditiva , Animales , Cóclea , Estudio de Asociación del Genoma Completo , Pérdida Auditiva/genética , Humanos , Ratones , Estría VascularRESUMEN
OBJECTIVE: To review the evidence on the association between maternal exposure to ultra-processed food (UPF) categories, UPF diet items, and overall diet quality, as assessed by recognized dietary indices, and neurodevelopmental outcomes in offspring. METHODS: PubMed, MEDLINE, EMBASE, Scopus, Ovid, and Scholar databases were searched for original articles on female gestational exposure to UPF categories, individual elements of the UPF diet, or indices of diet quality, in relation to outcomes regarding their offspring's neurocognitive development, according to neuropsychometric and behavioral scales, anthropometric/psychomotor indices, and symptoms/diagnosis of neurodevelopmental disorders (NDDs). RESULTS: Fourteen articles were selected and underwent the quantitative analysis. Six of these examined diet quality, and eight exposure to UPF categories or specific UPF foods. The maternal population was adult (18+). Child cognitive development was negatively impacted by a diet featuring many processed foods, saturated fats, and sugars. Conversely, a Med-diet led to better neurodevelopment, particularly verbal intelligence and executive functions, in middle childhood. DISCUSSION: A maternal diet with many UPFs, saturated fats, and total sugars (especially those added or hidden in packaged carbonated beverages) can adversely affect a child's cognitive development. Knowledge needs to be further extended and managed from a prevention perspective in light of the well-known negative effects of UPFs on human health in all age groups.
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Ingestión de Energía , Alimentos Procesados , Adulto , Humanos , Niño , Femenino , Embarazo , Comida Rápida , Manipulación de Alimentos , Dieta , AzúcaresRESUMEN
BACKGROUND: Med-Index is a one-health front-of-pack (FOP) label, based on Mediterranean diet (MedDiet) principles, developed to summarize information about the nutritional properties and related-health benefits of any food as well as its sustainable production processes, and the associated food company's social responsibility parameters in a new "Planeterranean" perspective. Thus, Med-Index can be adopted in and by any European region and authority as well as worldwide; this is achieved by consumption and cooking of locally available and sourced foods that respect MedDiet principles, both in terms of healthy nutrition and sustainable production. The huge body of scientific evidence about the health benefits of the MedDiet model and principles requires a comprehensive framework to encompass the scientific reliability and robustness of this tool. A systematic review was carried out to examine the association between human health and adherence to MedDiet patterns upon which the "Med-Index" tool was subsequently developed. METHODS: MEDLINE and PubMed databases were searched for eligible publications from 1990 to April 2023. Systematic literature reviews, with or without meta-analysis, of clinical trials and observational studies were screened by two independent investigators for eligibility, data extraction, and quality assessment. English language and the time interval 1990-2023 were applied. A registry code CRD42023464807 was generated on PROSPERO and approved for this search protocol. The corrected covered area (CCA), calculated to quantify the degree of overlap between reviews, gave a slight overlap (CCA = 4%). RESULTS: A total of 84 systematic reviews out of 6681 screened records were selected. Eligible reviews included studies with predominantly observational designs (61/84, 72.6%%), of which 26/61 referenced studies of mixed observational and RCT designs, while 23/84 (27.4%) were RCT-only systematic reviews. Seventy-nine different entries were identified for health outcomes, clustered into 10 macro-categories, each reporting a statistically significant association with exposure to the MedDiet. Adherence to MedDiet was found to strongly benefit age-related chronic diseases (21.5%), neurological disorders (19%), and obesity-related metabolic features (12.65), followed by CVDs (11.4%), cancer (10.1%), diabetes (7.5%), liver health (6.3%), inflammation (5%), mortality (5%), and renal health (1.2%). The quality of the studies was moderate to high. CONCLUSION: In the context of a "Planeterranean" framework and perspective that can be adopted in any European region and worldwide, MedDiet represents a healthy and sustainable lifestyle model, able to prevent several diseases and reduce premature mortality. In addition, the availability of a FOP, such as Med-Index, might foster more conscious food choices among consumers, paying attention both to human and planetary health.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Dieta Mediterránea , Salud Única , Humanos , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: Growing awareness of the biological and clinical value of nutrition in frailty settings calls for further efforts to investigate dietary gaps to act sooner to achieve focused management of aging populations. We cross-sectionally examined the eating habits of an older Mediterranean population to profile dietary features most associated with physical frailty. METHODS: Clinical and physical examination, routine biomarkers, medical history, and anthropometry were analyzed in 1502 older adults (65 +). CHS criteria were applied to classify physical frailty, and a validated Food Frequency Questionnaire to assess diet. The population was subdivided by physical frailty status (frail or non-frail). Raw and adjusted logistic regression models were applied to three clusters of dietary variables (food groups, macronutrients, and micronutrients), previously selected by a LASSO approach to better predict diet-related frailty determinants. RESULTS: A lower consumption of wine (OR 0.998, 95% CI 0.997-0.999) and coffee (OR 0.994, 95% CI 0.989-0.999), as well as a cluster of macro and micronutrients led by PUFAs (OR 0.939, 95% CI 0.896-0.991), zinc (OR 0.977, 95% CI 0.952-0.998), and coumarins (OR 0.631, 95% CI 0.431-0.971), was predictive of non-frailty, but higher legumes intake (OR 1.005, 95%CI 1.000-1.009) of physical frailty, regardless of age, gender, and education level. CONCLUSIONS: Higher consumption of coffee and wine, as well as PUFAs, zinc, and coumarins, as opposed to legumes, may work well in protecting against a physical frailty profile of aging in a Mediterranean setting. Longitudinal investigations are needed to better understand the causal potential of diet as a modifiable contributor to frailty during aging.
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Anciano Frágil , Fragilidad , Humanos , Anciano , Café , Dieta , Fragilidad/epidemiología , Fenotipo , Examen FísicoRESUMEN
BACKGROUND AND AIMS: Non-alcoholic hepatic steatosis affects 25% of adults worldwide and its prevalence increases with age. There is currently no definitive treatment for NAFLD but international guidelines recommend a lifestyle-based approach, including a healthy diet. The aim of this study was to investigate the interactions between eating habits and the risk of steatosis and/or hepatic fibrosis, using a machine learning approach, in a non-institutionalized elderly population. METHODS AND RESULTS: We recruited 1929 subjects, mean age 74 years, from the population-based Salus in Apulia Study. Dietary habits and the risk of steatosis and hepatic fibrosis were evaluated with a validated food frequency questionnaire, the Fatty Liver Index (FLI) and the FIB-4 score, respectively. Two dietary patterns associated with the risk of steatosis and hepatic fibrosis have been identified. They are both similar to a "western" diet, defined by a greater consumption of refined foods, with a rich content of sugars and saturated fats, and alcoholic and non-alcoholic calorie drinks. CONCLUSION: This study further supports the concept of diet as a factor that significantly influences the development of the most widespread liver diseases. However, longitudinal studies are needed to better understand the causal effect of the consumption of particular foods on fat accumulation in the liver.
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BACKGROUND: the possible relationship between dietary habits and the incidence of late-onset depression (LOD), defined as first depression onset at later age, is unclear. OBJECTIVE: to investigate the relationship between consumption of different food groups and incident LOD. DESIGN: longitudinal population-based study with a 12-year follow-up. SETTING: Castellana Grotte, Bari, Italy. SUBJECTS: five hundred and forty-six older subjects from the Salus in Apulia Study. METHODS: baseline data were recorded in 2003-06, and diagnostic data were recorded in 2013-18 at follow-up. Dietary intake was assessed with a food frequency questionnaire. Depressive disorders were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders. Subjects who already suffered from depression or other psychiatric disorders at baseline were excluded from the analysis. The association between LOD and single dietary determinants was examined by Cox regression analysis and then applying the hazard ratio (HR). RESULTS: subjects with incident LOD (n = 34) had lower global cognition and total cholesterol levels and a higher body mass index (BMI) at baseline. Only processed meat significantly increased the risk of incident LOD of about 10% by 5 g/day intake (HR adjusted for age, sex, education, multimorbidity and BMI: 1.13, 95% confidence intervals: 1.04-1.22). A similar relationship was found for single foods in the processed meat food group such as sausages, salami and mortadella and baked ham, but not for raw ham. CONCLUSIONS: in midlife, a higher intake of processed meat was not only associated with an increased risk of cardiovascular- and metabolic-related chronic diseases in older age but also with an increased risk of developing LOD.
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Depresión , Carne , Depresión/diagnóstico , Depresión/epidemiología , Depresión/etiología , Dieta/efectos adversos , Conducta Alimentaria , Estudios de Seguimiento , Humanos , Carne/efectos adversos , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVES: Consistency among population-based studies investigating the relationship between diet and cognition in older inhabitants in the Mediterranean area is poor. The present study investigated whether diet changes over 12 years were associated with cognitive function in older people in Southern-Italy. METHODS: From the 'Salus in Apulia Study', that includes the MICOL and GreatAGE Studies, 584 participants were selected, firstly enrolled in MICOL3 (M3) and later in the GreatAGE Study (MICOL4, M4). Foods and micronutrients intake were recorded in both studies, and global cognitive function in M4, assessed with the Mini Mental State Examination. RESULTS: Plant-based foods, particularly coffee and vegetables, as well as vitamin A sources, were inversely associated to age-related cognitive impairment. Alcohol consumption showed a detrimental role on cognition, while red meat appeared to be beneficial in the present study, although its role is traditionally considered harmful for cognitive function. DISCUSSION: Our study confirmed that a traditional Mediterranean dietary pattern based on agricultural products and low alcohol consumption may help to prevent/delay age-related cognitive impairment.
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Disfunción Cognitiva , Dieta Mediterránea , Anciano , Cognición , Dieta , Dieta Vegetariana , Ingestión de Alimentos , HumanosRESUMEN
Dietary behaviour is a core element in diabetes self-management. There are no remarkable differences between nutritional guidelines for people with type 2 diabetes and healthy eating recommendations for the general public. This study aimed to evaluate dietary differences between subjects with and without diabetes and to describe any emerging dietary patterns characterizing diabetic subjects. In this cross-sectional study conducted on older adults from Southern Italy, eating habits in the "Diabetic" and "Not Diabetic" groups were assessed with FFQ, and dietary patterns were derived using an unsupervised learning algorithm: principal component analysis. Diabetic subjects (n = 187) were more likely to be male, slightly older, and with a slightly lower level of education than subjects without diabetes. The diet of diabetic subjects reflected a high-frequency intake of dairy products, eggs, vegetables and greens, fresh fruit and nuts, and olive oil. On the other hand, the consumption of sweets and sugary foods was reduced compared to non-diabetics (23.74 ± 35.81 vs. 16.52 ± 22.87; 11.08 ± 21.85 vs. 7.22 ± 15.96). The subjects without diabetes had a higher consumption of red meat, processed meat, ready-to-eat dishes, alcoholic drinks, and lower vegetable consumption. The present study demonstrated that, in areas around the Mediterranean Sea, older subjects with diabetes had a healthier diet than their non-diabetic counterparts.
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Diabetes Mellitus Tipo 2 , Anciano , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Conducta Alimentaria , Femenino , Humanos , Italia/epidemiología , Masculino , Aprendizaje Automático no SupervisadoRESUMEN
INTRODUCTION: In subjects with nonalcoholic fatty liver disease (NAFLD), advanced fibrosis (AF) carries the highest risk of adverse liver-related events. To reduce the number of unnecessary biopsies, several noninvasive tools (NITs) for the risk stratification of fibrosis have been developed. We conducted this meta-analysis to assess the performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis scores (NFS), the 2 most common NITs, for the appropriate selection of subjects with AF for biopsy. METHODS: Four databases were searched until December 2020 (CRD42021224766). Original articles reporting data on the performance of FIB-4 and NFS, interpreted according to standard cutoffs in subjects with biopsy-proven NAFLD, were included. Separate data extractions were performed according to the lower cutoff, the higher cutoff, and the dual threshold approach. The numbers of subjects classified as true-negative, true-positive, false-negative, and false-positive were extracted. Summary operating points were estimated using a random-effects model. RESULTS: Eighteen studies evaluating 12,604 subjects were included. Participants were adult outpatients with biopsy-proven NAFLD or nonalcoholic steatohepatitis. Overall, a weak-to-moderate performance was found for both scores. The head-to-head comparison showed FIB-4 to be associated with a higher performance in ruling in and NFS in ruling out AF in the single threshold approach, whereas, with the dual threshold approach, a lower prevalence of indeterminate findings was found for FIB-4. DISCUSSION: This meta-analysis suggested that currently available NITs have a limited performance in identifying AF among subjects with NAFLD. Further studies are needed to optimize existing thresholds or develop new NITs.
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Cirrosis Hepática/diagnóstico , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Biopsia , Humanos , Cirrosis Hepática/patología , Enfermedad del Hígado Graso no Alcohólico/patología , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Preventive nutritional management of frailty, a multidimensional intermediate status in the ageing process, may reduce the risk of adverse health-related outcomes. We investigated the ability of a measure combining physical frailty with nutritional imbalance, defined as nutritional frailty, to predict all-cause mortality over a period of up to 8 years. METHODS: We analysed data on 1,943 older adults from the population-based 'Salus in Apulia Study'. Physical frailty was operationalized using Cardiovascular Health Study criteria and cognitive frailty by combining physical frailty with cognitive impairment. A novel five-item construct was built to assess the extent of nutritional imbalance identified with a machine learning algorithm. Cox models and Kaplan-Meier survival probability analyses of physical frailty, nutritional imbalance (two or more of the following: low body mass index, low skeletal muscle index, ≥2.3 g/day sodium intake, <3.35 g/day potassium intake and <9.9 g/day iron intake), cognitive frailty and the novel nutritional frailty phenotype (physical frailty plus nutritional imbalance) were applied to assess all-cause mortality risk, adjusted for age, sex, education and multimorbidity. RESULTS: The overall prevalence of nutritional frailty was 4.52% (95% confidence interval, CI:3.55-5.44), being more frequent in males. Subjects with nutritional frailty were at higher risk for all-cause mortality [hazard ratio (HR):2.31; 95%CI:1.41-3.79] than those with physical frailty (HR:1.45,95% CI:1.0-2.02), nutritional imbalance (HR:1.39; 95%CI:1.05-1.83) and cognitive frailty (HR:1.06; 95%CI:0.56-2.01). CONCLUSIONS: Efforts to identify, manage and prevent frailty should include the nutritional domain. The nutritional frailty phenotype may highlight major nutritional determinants that could drive survival and health trajectories in older adults.
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Fragilidad , Mortalidad , Estado Nutricional , Anciano , Humanos , Masculino , Multimorbilidad , PrevalenciaRESUMEN
BACKGROUND AND PURPOSE: In older age, physical and cognitive declines have been shown to occur simultaneously or consequent to one another, and several operational definitions have been proposed to consider the co-presence of the two declines; for example, "Motoric cognitive risk syndrome" (MCR) has been proposed as a definition for the coexistence of slow gait plus subjective cognitive complaints. Given the increasing interest in MCR and its potential role as both biomarker and therapeutic target, we aimed to estimate its prevalence in a large cohort of non-demented older subjects, and to examine the associations between physical status, global cognitive dysfunction, and impairment in various cognitive domains in MCR. METHODS: A population-based sample of 1041 older people in Southern Italy (mean age 75.15 years) was enrolled. We defined MCR using slowness and a single question for subjective cognitive complaints. We also administered a comprehensive neuropsychological test battery, together with tests assessing physical function. RESULTS: The prevalence of MCR was 9.9% (95% confidence interval 8.2-11.9). MCR was associated with decreased processing speed and executive function after adjusting for all relevant confounders. However, we found no significant association of MCR with decreased global cognition and immediate/delayed free recall of verbal memory. MCR was also associated with increased exhaustion, low muscle strength, and low physical activity, and increased levels of C-reactive protein and interleukin-6. CONCLUSIONS: The present findings on MCR prevalence and associated cognitive and physical domains and inflammatory biomarkers may help to uncover altered pathways and therapeutic targets for intervention during the long preclinical phase of neurodegenerative dementia.
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Disfunción Cognitiva , Marcha , Anciano , Cognición , Disfunción Cognitiva/epidemiología , Humanos , Pruebas Neuropsicológicas , Factores de RiesgoRESUMEN
INTRODUCTION: Non-verbal figural fluency is related to executive functions and specifically to the ability to create as many unique designs as possible, while minimizing their repetitions. An Italian version of figural fluency is the Modified Five-Point Test (MFPT), which is highly employed in the clinical practice of neuropsychologists. To date, reference data of Italian population are limited to a sample aged between 16 and 60 years old. Thus, the current study aims to provide normative data of the MFPT in the context of a population-based setting, conducted in Southern Italy. MATERIAL AND METHODS: We collected N = 340 Italian healthy subjects, aged over 65 years old (range: 65-91), pooled across subgroups for age, sex, and education. Multiple regression analyses were performed to estimate the effect of age, education, and sex on the participant's performance. Equivalent scores and cut-off scores were also defined for the number of unique designs (UDs) and the number of strategies (CSs). RESULTS: Multiple regression analyses revealed that UDs increase with decreasing age and increasing educational level. CSs are influenced by higher educational levels but neither by age nor sex. A significant inverse correlation between the UDs and percentage of errors occurred, suggesting that a higher number of UDs are associated with a fewer number of errors and higher CSs employed. CONCLUSION: The MFPT provides a measure of cognitive functioning in terms of the ability to initiate and realize designs, affording useful hints for clinical settings. The MFPT may represent a handy and useful tool with a specific focus in the differentiation of healthy versus pathological aging.
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Envejecimiento , Cognición , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Escolaridad , Humanos , Italia , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valores de Referencia , Adulto JovenRESUMEN
Self-report questionnaires are a valuable method of physical activity measurement in public health research; however, accuracy is often lacking. Resolving the differences between self-reported and objectively measured physical activity is an important surveillance challenge currently facing population health experts. The present work aims at providing the relationship between activity energy expenditure estimated from wrist-worn accelerometers and intensity of self-reported physical activity (InCHIANTI structured interview questionnaire) in a sub-cohort of a population-based study on aging in Southern Italy. Linear regression was used to test the association between measured and reported physical activity. We found that activity energy expenditure predicted clinical average levels of PA assessed through InCHIANTI classification.
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Metabolismo Energético , Ejercicio Físico , Anciano , Humanos , Italia , Autoinforme , MuñecaRESUMEN
The well-established anti-inflammatory and antioxidant properties of red fruits leave room for a biological pathway of improved muscle health promoted by berries in the diet. Our objective was to systematically review the number of trials conducted on human and animal species around the relationship between a berry diet and muscle health outcomes. Two independent examiners conducted a search for studies that utilized keywords associated with muscle health outcomes and a berry-based diet in both human and animal trials, in accordance with the PRISMA statement guidelines. The literature was searched through six electronic databases until December 2023. Screening of 152 retrieved articles resulted in a final selection of 16 reports investigating the effect of exposure to a berry-based diet and skeletal muscle health outcomes. The study protocol was registered on PROSPERO (CRD42023479682). Among the selected studies, nine involved humans and seven animal models (rats and mice). Overall, most of the studies reported positive effects on performance or muscle health. Specifically, five studies investigated the possible effects of blackcurrant on active human subjects or athletes; three studies focused on blueberry and presented results on running performance (human sample) and muscle health (rat models). The rest of the studies involved raspberries (two studies, rat models), aronia (one study, rat models), elderberry (one study, rat models), and a mixed compound (one study, rat models). In conclusion, there is some early evidence that a berry-rich diet may increase performance or muscle health, but more research is needed to fully understand the underlying biological trajectories, and thus, no firm conclusions can yet be drawn.
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The conceptual change of frailty, from a physical to a biopsychosocial phenotype, expanded the field of frailty, including social and behavioral domains with critical interaction between different frailty models. Environmental exposures - including physical exercise, psychosocial factors and diet - may play a role in the frailty pathophysiology. Complex underlying mechanisms involve the progressive interactions of genetics with epigenetics and of multimorbidity with environmental factors. Here we review the literature on possible mechanisms explaining the association between epigenetic hallmarks (i.e., global DNA methylation, DNA methylation age acceleration and microRNAs) and frailty, considered as biomarkers of aging. Frailty could be considered the result of environmental epigenetic factors on biological aging, caused by conflicting DNA methylation age and chronological age.
The present narrative review describes the available evidence about epigenetic biological markers of frailty considered aging biomarkers, among others. Aging biomarkers can help in identifying frail and older individuals affected by multiple diseases to further increase the power of composite biomarker panels in the diagnostic and prognostic process. Among combined biomarkers, epigenetic regulators with different methylation patterns and small molecules such as microRNAs are included. Given that frailty involves multiple biological systems, it is possible to define it according to a novel model, including emotional and social domains and the influence of environmental factors, named the biopsychosocial phenotype. Different epigenetic biomarkers of frailty, from the first generation to the more specific and recent second-generation epigenetic aging biomarkers, may account for factors linked to different cellular types, such as heterogeneity, and a reverse causation process that requires integration with gene expression. A better understanding of the relationships among frailty, multimorbidity and overall mortality will help us to identify the best therapeutic targets.
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Fragilidad , MicroARNs , Humanos , Fragilidad/genética , Epigénesis Genética , Envejecimiento/genética , Metilación de ADN , MicroARNs/genéticaRESUMEN
Polyphenols are secondary metabolites found in plants, foods, and drinks, occurring in small quantities and showcasing antioxidant and anti-inflammatory qualities. The primary polyphenols consist of flavonoids, phenolic acids, stilbenes, and lignans. However, there is currently no comprehensive quantitative analysis of epidemiological data on overall death rates. This systematic review with meta-analysis aims to identify the exposure-response relationship between dietary polyphenol intake and all-cause mortality. The literature was reviewed from its earliest study to May 2024, utilizing six distinct electronic databases. No specific criteria were used to choose participants based on the recruiting environment, their general health condition, country, or ethnicity. The inclusion criteria for studies were as follows: a longitudinal design, exposure to dietary polyphenols, all-cause mortality as the outcome, and hazard risk (HR) as the impact measure. The Newcastle-Ottawa Scale was used to evaluate the methodological rigor of the study. The hazard risks (HRs) and 95% confidence intervals (CIs) were estimated by pooling data using common effects models. A protocol has been registered on PROSPERO with the identification number CRD42024545524. The meta-analysis comprised seven cohort studies that involved 178,657 adult people aged 18 years and older. These studies examined the relationship between total dietary polyphenol consumption and the risk of all-cause death. The recruitment settings exclusively used community-based approaches, with a preference for Europe (71%) in terms of geographic distribution. The study's quality was assessed to be moderate to high. The meta-analysis showed consistent evidence that increased dietary exposure to polyphenols reduces the risk of all-cause mortality by 7% (HR 0.93, 95% CI 0.91-0.95, I2: 48%). Pooled data from the available evidence consistently show that individuals exposed to an antioxidant diet rich in polyphenol sources may be at lower risk of all-cause mortality.
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BACKGROUND: The rising diffusion of vascular resections during complex pancreatectomy for malignancy, for both oncological and technical matters, brought with it the use of vascular shunts, either temporary or definitive, to prevent bowel congestion and liver ischemia. This study aimed to systematically review the literature on the technical feasibility of vascular shunts during advanced pancreatic surgery, analyzing intraoperative and postoperative outcomes. METHODS: A systematic literature search was performed on PubMed, Scopus, Web of Science, and the Cochrane Library Central, according to PRISMA guidelines. Studies published before 2006 were excluded, considering the lack of a standardized definition of locally advanced pancreatic cancer. The main outcomes evaluated were the overall complication rate and shunt patency. RESULTS: Among 789 papers retrieved from the database search, only five fulfilled the inclusion criteria and were included in the review, amounting to a total of 145 patients undergoing a shunt creation at the time of pancreatectomy. Pancreatic adenocarcinoma (PDAC) was found to be the most common diagnosis and pancreaticoduodenectomy was the main surgical procedure, accounting for 88% and 83% of the overall cohort, respectively. The distal splenorenal shunt was the most performed. Overall, 44 out of 145 patients (30%) experienced postoperative complications; the long-term patency of definitive shunts was 83% (110 out of 120 patients). CONCLUSIONS: An increasing number of patients with borderline resectable or locally advanced PDAC are becoming amenable to resection and shunt creation may facilitate vascular resection with clear margins, becoming a valid tool of modern pancreatic surgery.
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INTRODUCTION: In the last decade, the efforts conducted for discovering Alzheimer's Disease (AD) treatments targeting the best-known pathogenic factors [amyloid-ß (Aß), tau protein, and neuroinflammation] were mostly unsuccessful. Given that a systemic failure of Aß clearance was supposed to primarily contribute to AD development and progression, disease-modifying therapies with anti-Aß monoclonal antibodies (e.g. solanezumab, bapineuzumab, gantenerumab, aducanumab, lecanemab and donanemab) are ongoing in randomized clinical trials (RCTs) with contrasting results. AREAS COVERED: The present Drug Discovery Case History analyzes the failures of RCTs of solanezumab on AD. Furthermore, the authors review the pharmacokinetics, pharmacodynamics, and tolerability effect of solanezumab from preclinical studies with its analogous m266 in mice. Finally, they describe the RCTs with cognitive, cerebrospinal fluid and neuroimaging findings in mild-to-moderate AD (EXPEDITION studies) and in secondary prevention studies (A4 and DIAN-TU). EXPERT OPINION: Solanezumab was one of the first anti-Aß monoclonal antibodies to be tested in preclinical and clinical AD showing to reduce brain Aß level by acting on soluble monomeric form of Aß peptide without significant results on deposits. Unfortunately, this compound showed to accelerate cognitive decline in both asymptomatic and symptomatic trial participants, and this failure of solanezumab further questioned the Aß cascade hypothesis of AD.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Anticuerpos Monoclonales Humanizados , Ensayos Clínicos Controlados Aleatorios como Asunto , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/fisiopatología , Humanos , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Animales , Péptidos beta-Amiloides/metabolismo , Ratones , Insuficiencia del Tratamiento , Progresión de la EnfermedadRESUMEN
INTRODUCTION: Chronic liver disease is often combined with a morbidity burden that strongly affects the functional domain. In liver cirrhosis (LC), qualitative and quantitative muscle wasting, known as sarcopenia, poses an added clinical burden, together with comorbidities and a poor quality of life. METHODS: We conducted a systematic review and meta-analysis of the prevalence of sarcopenia in LC. The literature was screened through 6 electronic databases from the study's inception to January 2023. No exclusion criteria were applied to language, operative tools for diagnosing sarcopenia, population age, general health status, country, and study setting (cohort or cross-sectional). Two independent researchers applied the inclusion criteria in parallel to evaluate the eligibility of the 44 retrieved articles; only 36 met the eligibility requirements. RESULTS: The total sample (N = 8,821) was slightly dominated by men (N = 4,941). The cross-sectional design predominated over the longitudinal, and the hospital setting was prevalent. The pooled prevalence of sarcopenia across the selected studies was 33% (95% confidence interval [CI] 0.32-0.34), with high heterogeneity ( I2 = 96%). A further meta-analysis using the Child-Pugh (CP) score to stage LC was conducted on 24 entries, and the results showed that for the LC populations classified with the CP-A, CP-B, and CP-C staging, respectively, the overall mean prevalence was 33% (95% CI 0.31-0.35), 36% (95% CI 0.34-0.39) and 46% (95% CI 0.43-0.50). The risk of bias was moderate. In LC, 1 in 3 patients suffers sarcopenia. DISCUSSION: Poor management of muscle mass loss plays a role in the prognosis of death and quality of life of patients with LC. Clinicians in the field are recommended, when screening for sarcopenia, to pay close attention by carefully assessing body composition as part of the monitoring scheme.