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1.
Int J Mol Sci ; 22(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34769191

RESUMO

The balance between anti-tumor and tumor-promoting immune cells, such as CD4+ Th1 and regulatory T cells (Tregs), respectively, is assumed to dictate the progression of hepatocellular carcinoma (HCC). The transforming growth factor beta (TGFß) markedly shapes the HCC microenvironment, regulating the activation state of multiple leukocyte subsets and driving the differentiation of cancer associated fibroblasts (CAFs). The fibrotic (desmoplastic) reaction in HCC tissue strongly depends on CAFs activity. In this study, we attempted to assess the role of TGFß on transendothelial migration of Th1-oriented and Treg-oriented CD4+ T cells via a direct or indirect, CAF-mediated mechanisms, respectively. We found that the blockage of TGFß receptor I-dependent signaling in Tregs resulted in impaired transendothelial migration (TEM) of these cells. Interestingly, the secretome of TGFß-treated CAFs inhibited the TEM of Tregs but not Th1 cells, in comparison to the secretome of untreated CAFs. In addition, we found a significant inverse correlation between alpha-SMA and FoxP3 (marker of Tregs) mRNA expression in a microarray analysis involving 78 HCCs, thus suggesting that TGFß-activated stromal cells may counteract the trafficking of Tregs into the tumor. The apparent dual behavior of TGFß as both pro- and anti-tumorigenic cytokines may add a further level of complexity to the mechanisms that regulate the interactions among cancerous, stromal, and immune cells within HCC, as well as other solid tumors, and contribute to better manipulation of the TGFß signaling as a therapeutic target in HCC patients.

2.
Front Nutr ; 8: 762383, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778347

RESUMO

Little study has yet been made of the effect of different beverages on oral health outcomes in the aging population. The purpose of this systematic review is to evaluate the association between different beverages, including alcohol intake, coffee, milk, tea, and sugary drinks, and a cluster of oral health outcomes, including periodontal disease, oral dysbiosis, and tooth loss in older adults. The literature was screened from the inception up to May 2021 using six different electronic databases. Two independent researchers assessed the eligibility of 1308 retrieved articles regarding inclusion criteria; only 12 fitted the eligibility requirements, representing 16 beverage entries. A minimum age of 60 was the inclusion criterion. No exclusion criteria were applied to outcomes assessment tools, recruiting facilities (hospital or community), general health status, country, and study type (longitudinal or cross-sectional). The consumption of alcoholic beverages was expressed as alcohol intake in all eligible studies, thereby replacing alcoholic beverages in the analysis. The quality of evidence was judged as moderate for alcohol and low or very low for beverages. In regard to oral health in the elderly, the review identified information on alcohol (56.25%), followed by coffee (18.75%), milk (12.50%), tea (6.25%), and sugary drinks (6.25%). Alcohol, sugary drinks, and coffee were found to be related to tooth loss. Periodontal disease was inversely related to coffee and milk, but fostered by alcohol consumption. In one article, tea but not coffee seemed to improve oral microbiota. In summary, alcohol seems to be a driver for tooth loss and periodontal disease in the aging population. However, more research is needed to gain a more solid knowledge in this research area. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO, Identifier: CRD42021256386.

3.
Biomedicines ; 9(11)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34829846

RESUMO

Age is a major contributor to the liver fibrosis rate and its adverse health-related outcomes, including mortality, but older populations are still under-explored. We investigated multimorbidity and inflammatory biomarkers in relation to the increasing liver fibrosis risk to delineate 8-year all-cause mortality trajectories in 1929 older adults from the population-based Salus in Apulia Study. Liver fibrosis risk was assumed using the fibrosis-4 (FIB-4) score, assigned to three liver fibrosis risk groups (low, intermediate, high). In the secondary analyses, the APRI score was also calculated to allow for comparisons. Male subjects (prevalence difference: -13.49, 95% confidence interval (CI): -18.96 to -8.03), a higher multimorbidity burden (effect size, ES: -0.14, 95% CI: -0.26 to -0.02), a higher prevalence of physical frailty (ES: 6.77, 95% CI: 0.07 to 13.47), and a more pronounced inflammatory pattern as indicated by tumor growth factor-α circulating levels (ES: -0.12, 95% CI: -0.23 to -0.01) were significantly more common in the highest-risk FIB-4 score group. Liver function characterized by lipid profile and platelet levels worsened with increasing FIB-4 risk score. The 8-year risk of death was nearly double in subjects in the highest-risk FIB-4 score group, even after controlling for possible confounders. Furthermore, a steeper mortality curve was clearly observed for FIB-4 scores as compared with the APRI scoring system with respect to liver fibrosis risk. In conclusion, using a scoring tool based on simple routine biomarkers to detect liver fibrosis risk may enhance biological knowledge of age-related outcomes of chronic liver disease and be helpful in the clinical setting to identify subjects at risk for adverse health-related outcomes, including mortality.

4.
J Colloid Interface Sci ; 608(Pt 1): 239-254, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34626971

RESUMO

HYPOTHESIS: Solid lipid nanoparticles (SLNs), co-encapsulating superparamagnetic iron oxide nanoparticles and sorafenib, have been exploited for magnetic-guided drug delivery to the liver. Two different magnetic configurations, both comprising two small magnets, were under-skin implanted to investigate the effect of the magnetic field topology on the magnetic SLNP accumulation in liver tissues. A preliminary simulation analysis was performed to predict the magnetic field topography for each tested configuration. EXPERIMENTS: SLNs were prepared using a hot homogenization approach and characterized using complementary techniques. Their in vitro biological behavior was assessed in HepG-2 liver cancer cells; wild-type mice were used for the in vivo study. The magnet configuration that resulted in a higher magnetic targeting efficiency was investigated by evaluating the iron content in homogenated murine liver tissues. FINDINGS: SLNs, characterized by an average size smaller than 200 nm, retained their superparamagnetic behavior and relevant molecular resonance imaging properties as negative contrast agents. The evaluation of iron accumulation in the liver tissues was consistent with the magnetic induction profile of each magnet configuration, concurring with the results predicted by simulation analysis and obtained by measurements in living mice.

5.
Front Oncol ; 11: 730093, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671555

RESUMO

Frizzled (FZD) proteins are primary receptors for Wnt signaling that activates the mitogen-activated protein kinase (MAPK) pathways. Dysfunction of Wnt signals with consequently abnormal activation of MAPK3 pathways was found in colorectal cancer (CRC) and gastric cancer (GC). Upregulation of FZD10 protein, localized in the exosomes isolated from plasma of CRC and GC patients, was associated with a poor prognosis. Herein, the expression levels of circulating FZD10 were found to be strongly correlated to their expression levels in the corresponding tissues in CRC and GC patients. Bioinformatic prediction revealed a link between FZD10 and Ki-67 through MAPK3. In both CRC and GC tissues, pERK1/2 levels were significantly increased at more advanced disease stages, and pERK1/2 and Ki-67 were correlated. Silencing of FZD10 in CRC and GC cells resulted in a significant reduction of pERK1/2 and Ki-67 expression, while subsequent treatment with exogenous exosomes partially restored their expression levels. The strong correlation between the expression of Ki-67 in tissues and of FZD10 in exosomes suggests that the exosome-delivered FZD10 may be a promising novel prognostic and diagnostic biomarker for CRC and GC.

6.
J Clin Med ; 10(20)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34682759

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is most commonly considered as a complication of cirrhosis. However, an increasing number of HCC in subjects with non-alcoholic fatty liver disease (NAFLD) without cirrhosis is being reported. We conducted a meta-analysis to assess the prevalence of the absence of cirrhosis in NAFLD-associated HCC. METHODS: Four databases were searched until March 2021 (CRD42021242969). The original articles included were those reporting data on the presence or absence of cirrhosis among at least 50 subjects with NAFLD-associated HCC. The number of subjects with absent cirrhosis in each study was extracted. For statistical pooling of data, a random-effects model was used. Subgroup analyses according to the continent, target condition and reference standard for the diagnosis of cirrhosis were conducted. RESULTS: Thirty studies were included, evaluating 13,371 subjects with NAFLD-associated HCC. The overall prevalence of cases without cirrhosis was 37% (95%CI 28 to 46). A higher prevalence was reported in Asia versus Europe, North America and South America (45, 36, 37 and 22%, respectively) as well as in studies adopting histology only as the reference standard for the diagnosis of cirrhosis versus histology and other modalities (e.g., radiology, endoscopy, biochemistry or overt clinical findings) (53 and 27%, respectively). No difference was found between studies including subjects with non-alcoholic steatohepatitis (NASH) only, versus NAFLD with or without NASH (p = 0.385). One in three subjects with NAFLD-associated HCC presented without cirrhosis. This should be reflected in future guidelines and surveillance programs adapted to allow for the early detection of these cancers too.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34574477

RESUMO

Due to the COVID-19 pandemic, in December 2020, the Italian government established a second home confinement during the Christmas holidays. These restrictions offered the opportunity to utilize a well-defined model for observing the consequences of lifestyle changes of healthy individuals. This study aimed at estimating in healthy subjects from Southern Italy the physical activity (PA), the presence and the severity of gastrointestinal (GI) symptoms, and the association between the possible worsening of GI health status and the PA levels. An adapted version of the International PA Questionnaire-short form (IPAQ-SF) and the Gastrointestinal Symptom Rating Scale (GSRS) were proposed through Google's online survey platform in three different periods via WhatsAppTM to 499 healthy subjects (62% females) from Apulia (25%), Calabria (37%), and Campania (38%). Our results showed statistically significant changes during the home confinement: reduced energy expenditure (EE) among overweight subjects (-239.82, 95%CI -405.74; -73.89) or those who had high GSRS total score (-1079.54, 95%CI -2027.43; -131.66). An increase in GSRS total score was observed in overweight subjects, reaching statistical significance in those from Campania. Our study supports the importance of PA to reduce health risks, including those related to the possible onset of GI tract diseases.


Assuntos
COVID-19 , Exercício Físico , Feminino , Trato Gastrointestinal , Nível de Saúde , Humanos , Itália/epidemiologia , Masculino , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
8.
Geroscience ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34378088

RESUMO

The liver contribution to the biological network underlying physical frailty in aging is underestimated. How best to measure this contribution magnitude and impact on health risk trajectories in frail individuals is not yet entirely clear. We analyzed the association of a novel liver frailty phenotype with the risk of death in older participants of the Salus in Apulia Study cohort. Clinical and physical examination, routine biomarkers, medical history, and anthropometry were analyzed in 1929 older adults (65 +). Physical frailty was classified by Cardiovascular Health Study criteria, and liver fibrosis risk by fibrosis-4 (FIB-4). The liver frailty phenotype was defined as physical frailty plus high-risk liver fibrosis (score > 2.67). Physical frailty, high-risk liver fibrosis, and liver frailty subjects were compared to subjects without these conditions (non-frail). Proportional Cox regression tested the adjusted association between liver frailty and all-cause mortality for each category. The liver frailty prevalence was relatively low (3.8%), but higher in men (58.1%). Compared to non-frail older subjects, liver frailty subjects were significantly older (effect size (ES) - 1.11, 95% confidence interval (CI) - 1.35 to - 0.87), with a lower education (ES 0.48, 95%CI 0.24 to 0.71) and higher multimorbidity (ES 15.81, 95%CI 4.20 to 27.41). Cox multivariate analyses showed a two-fold increased risk of overall mortality (hazard ratio 2.09, 95%CI 1.16-3.74) even after the adjustment for age, sex, education, and alcohol consumption. The liver frailty phenotype runs twice the risk of overall mortality compared with the non-frail population. This clinical tool, validated in a Southern Italian population, is based on simple sets of measures that can conveniently be assessed also in the primary care setting.

9.
J Intern Med ; 290(5): 1071-1082, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34437740

RESUMO

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.

10.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073989

RESUMO

(1) Background: The transforming growth factor (TGF)-ß plays a dual role in liver carcinogenesis. At early stages, it inhibits cell growth and induces apoptosis. However, TGF-ß expression is high in advanced stages of hepatocellular carcinoma (HCC) and cells become resistant to TGF-ß induced suppressor effects, responding to this cytokine undergoing epithelial-mesenchymal transition (EMT), which contributes to cell migration and invasion. Metabolic reprogramming has been established as a key hallmark of cancer. However, to consider metabolism as a therapeutic target in HCC, it is necessary to obtain a better understanding of how reprogramming occurs, which are the factors that regulate it, and how to identify the situation in a patient. Accordingly, in this work we aimed to analyze whether a process of full EMT induced by TGF-ß in HCC cells induces metabolic reprogramming. (2) Methods: In vitro analysis in HCC cell lines, metabolomics and transcriptomics. (3) Results: Our findings indicate a differential metabolic switch in response to TGF-ß when the HCC cells undergo a full EMT, which would favor lipolysis, increased transport and utilization of free fatty acids (FFA), decreased aerobic glycolysis and an increase in mitochondrial oxidative metabolism. (4) Conclusions: EMT induced by TGF-ß in HCC cells reprograms lipid metabolism to facilitate the utilization of FFA and the entry of acetyl-CoA into the TCA cycle, to sustain the elevated requirements of energy linked to this process.


Assuntos
Carcinoma Hepatocelular/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Metaboloma/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica , Células Hep G2 , Humanos , Metaboloma/genética , Metabolômica , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transcriptoma/genética
12.
Am J Gastroenterol ; 116(9): 1833-1841, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34160377

RESUMO

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.


Assuntos
Cirrose Hepática/diagnóstico , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Biópsia , Humanos , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Índice de Gravidade de Doença
13.
Front Aging Neurosci ; 13: 629017, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025388

RESUMO

Objectives: Central auditory processing disorder (CAPD) commonly occurs in older age. However, few studies of a possible link between age-related CAPD and diet in an older population have been conducted. The objective of the present study was to investigate the relationship between eating habits and age-related CAPD in a population >65 years, using cross-sectional and retrospective data obtained in the same population-based study about 12 years ago. Methods: We selected 734 participants (403 men) from a large population-based study. For age-related CAPD assessment, we used the Synthetic Sentence Identification with Ipsilateral Competitive Message test. Dietary habits were assessed by a Food Frequency Questionnaire. Associations between age-related CAPD and food groups/macro-and micronutrients were explored using adjusted logistic regression models. Results: Age-related CAPD subjects consumed more dairy (111 vs. 98 g/d), olives and vegetable oil (63 vs. 52 g/d) and spirits (2 vs.1 g/d), and less fruits (536 vs. 651 g/d) in the cross-sectional analysis. Age-related CAPD subjects had a lower intake of potassium, vitamin C, and a higher fat intake. Further analyses identified dietary fiber as being inversely related to age-related CAPD. Discussion: The present study provided evidence that the dietary hypotheses proposed for explaining the development of cognitive disorders in older age might also hold for age-related CAPD. Further data from other large and prospective population-based studies are needed for confirming these findings.

14.
Acta Neurol Belg ; 121(5): 1295-1303, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33954931

RESUMO

COVID-19 (Coronavirus disease-19) may present with neurological signs, but whether people already affected by neurological conditions are at a higher risk of contracting COVID-19 is still not known. We, therefore, aimed to investigate the association of previously diagnosed neurological conditions with COVID-19. 502,536 community-dwelling UK Biobank participants (54.4% male, mean age 56.6 ± 10.3 years) were included. Among these, 57,463 participants had a diagnosis of neurological conditions (11.43%) and a total of 1326 COVID-19-positive cases were identified (0.26%). Neurological conditions were identified through medical history and linkage to data on hospital admissions (ICD-10 code G00-G99). COVID-19 presence was diagnosed using the data provided by Public Health England. The association of previous diagnosis of neurological conditions with COVID-19 was evaluated through logistic regressions, adjusted for potential confounders, reported as odds ratios (ORs) with their 95% confidence intervals (CIs). Nerve, nerve root and plexus disorders (G50-G59) were the most common conditions identified. The presence of COVID-19 was almost doubled in neurological conditions compared to the general population (0.45 vs. 0.24%, p < 0.0001). Previously diagnosed neurological conditions were associated with 60% higher odds of COVID-19 positive in the multivariable-adjusted model (OR = 1.6, 95% CI 1.4-1.8). Other degenerative diseases of the nervous system, extrapyramidal and movement disorders, polyneuropathies and other disorders of the peripheral nervous system, cerebral palsy and other paralytic syndromes were significantly associated with a higher odds of COVID-19. The presence of neurological conditions was associated with a significantly higher likelihood of COVID-19 compared to the general population.


Assuntos
COVID-19/epidemiologia , Doenças do Sistema Nervoso , Adulto , Idoso , Bancos de Espécimes Biológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reino Unido/epidemiologia
15.
J Clin Med ; 10(8)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920792

RESUMO

Screening for non-alcoholic fatty liver disease (NAFLD) is key step for primary management of fatty liver in the clinical setting. Excess weight subjects carry a greater metabolic risk even before exhibiting pathological patterns, including diabetes. We characterized the cross-sectional relationship between routine circulating biomarkers and NAFLD in a large sample of diabetes-free subjects with overweight or obesity, to elucidate any independent relationship. A population sample of 1232 consecutive subjects with a body mass index of at least 25 kg/m2, not receiving any drug or supplemental therapy, was studied. Clinical data and routine biochemistry were analyzed. NAFLD was defined using the validated fatty liver index (FLI), classifying subjects with a score ≥ 60% as at high risk. Due to extreme skewing of variables of interest, resampling matching for age and sex was performed. Our study population was characterized by a majority of females (69.90%) and a prevalence of NAFLD in males (88.90%). As a first step, propensity score matching was explicitly performed to balance the two groups according to the FLI cut-off. Based on the resulting statistical trajectories, corroborated even after data matching, we built two logistic regression models on the matched population (N = 732) to verify any independent association. We found that each unit increase of FT3 implicated a 50% increased risk of NAFLD (OR 1.506, 95%CI 1.064 to 2.131). When including glycated haemoglobin (HbA1c) in the model, free-triiodothyronine (FT3) lost significance (OR 1.557, 95%CI 0.784 to 3.089) while each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold (OR 2.32, 95%CI 1.193 to 4.512). Glucose metabolism dominates a key pathway along the hazard trajectories of NAFLD, turned out to be key biomarker in monitoring the risk of fatty liver in diabetes-free overweight subjects. Each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold, in our study.

16.
J Clin Med ; 10(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33925992

RESUMO

BACKGROUND: Fatty liver index (FLI) is a non-invasive tool used to stratify the risk of non-alcoholic fatty liver disease (NAFLD) in population studies; whether it can be used to exclude or diagnose this disorder is unclear. We conducted a meta-analysis to assess the prevalence of NAFLD in each FLI class and the performance of FLI in detecting NAFLD. METHODS: Four databases were searched until January 2021 (CRD42021231367). Original articles included were those reporting the performance of FLI and adopting ultrasound, computed tomography, or magnetic resonance as a reference standard. The numbers of subjects with NAFLD in FLI classes <30, 30-60, and ≥60, and the numbers of subjects classified as true/false positive/negative when adopting 30 and 60 as cut-offs were extracted. A random-effects model was used for pooling data. RESULTS: Ten studies were included, evaluating 27,221 subjects without secondary causes of fatty liver disease. The prevalence of NAFLD in the three FLI classes was 14%, 42%, and 67%. Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for positive results, likelihood ratio for negative results, and diagnostic odds ratio were 81%, 65%, 53%, 84%, 2.3, 0.3, and 7.8 for the lower cut-off and 44%, 90%, 67%, 76%, 4.3, 0.6, and 7.3 for the higher cut-off, respectively. A similar performance was generally found in studies adopting ultrasound versus other imaging modalities. CONCLUSIONS: FLI showed an adequate performance in stratifying the risk of NAFLD. However, it showed only weak evidence of a discriminatory performance in excluding or diagnosing this disorder.

17.
Eur J Neurol ; 28(8): 2565-2573, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33899997

RESUMO

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.


Assuntos
Disfunção Cognitiva , Marcha , Idoso , Cognição , Disfunção Cognitiva/epidemiologia , Humanos , Testes Neuropsicológicos , Fatores de Risco
18.
Cell Death Dis ; 12(4): 316, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767160

RESUMO

The prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling, and previous reports indicate that Wnt3a can activate p38 MAPK. Besides, p38 was shown to feed into the canonical Wnt/ß-catenin pathway. Here we show that patient-derived locally advanced CRC stem cells (CRC-SCs) are characterized by increased expression of p38α and are "addicted" to its kinase activity. Of note, we found that stage III CRC patients with high p38α levels display reduced disease-free and progression-free survival. Extensive molecular analysis in patient-derived CRC-SC tumorspheres and APCMin/+ mice intestinal organoids revealed that p38α acts as a ß-catenin chromatin-associated kinase required for the regulation of a signaling platform involved in tumor proliferation, metastatic dissemination, and chemoresistance in these CRC model systems. In particular, the p38α kinase inhibitor ralimetinib, which has already entered clinical trials, promoted sensitization of patient-derived CRC-SCs to chemotherapeutic agents commonly used for CRC treatment and showed a synthetic lethality effect when used in combination with the MEK1 inhibitor trametinib. Taken together, these results suggest that p38α may be targeted in CSCs to devise new personalized CRC treatment strategies.


Assuntos
Cromatina/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Células-Tronco Neoplásicas/metabolismo , Organoides/metabolismo , Processamento de Proteína Pós-Traducional/genética , beta Catenina/metabolismo , Neoplasias Colorretais/genética , Humanos , Prognóstico
19.
JAMA Otolaryngol Head Neck Surg ; 147(6): 561-571, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33570584

RESUMO

Importance: The association between age-related hearing loss (ARHL) and physical or cognitive frailty has been poorly explored. These associations could define new perspectives for delaying frailty-related processes in older age. Objective: To examine whether peripheral ARHL and age-related central auditory processing disorder (CAPD) are independently associated with physical or cognitive frailty. Design, Setting, and Participants: This cross-sectional study analyzed registry data from December 31, 2014, on 1929 older (≥65 years) participants of the Salus in Apulia Study (Southern Italy) who underwent audiologic, physical, and neuropsychological assessment. Data analysis was performed from December 12, 2019, to January 4, 2020. Main Outcomes and Measures: Prevalence of peripheral ARHL in older individuals with physical and/or cognitive frailty and those without frailty assessed using the Fried criteria (physical) and the Mini-Mental State Examination (cognitive). Multivariable logistic regression models were used to assess associations of audiologic variables with frailty phenotype. Results: Data from 1929 participants (mean [SD] age, 73.6 [6.3] years; 974 male [50.5%]) were eligible for the analyses. The prevalence of peripheral ARHL was higher in the physical frailty group (96 [26.6%]) than in the nonfrail group (329 [21.0%]) (difference, 5.61 percentage points; 95% CI, 0.63-10.59 percentage points) and in the cognitive frailty group (40 [38.8%]) than in the nonfrail group (385 [21.1%]) (difference, 17.75 percentage points; 95% CI, 8.2-27.3 percentage points). Age-related CAPD was more prevalent in the physical frailty group (62 [17.2%]) than in the nonfrail group (219 [14.0%]) (difference, 3.21 percentage points; 95% CI, -1.04 to 7.46 percentage points) and in the cognitive frailty group (28 [27.2%]) than in the nonfrail group (253 [13.9%]) (difference, 13.33 percentage points; 95% CI, 4.10-22.21 percentage points). In the multivariable models, age-related CAPD was associated with cognitive frailty in the fully adjusted model (odds ratio [OR], 1.889; 95% CI, 1.094-3.311). There was also an inverse association between the unitary increase in Synthetic Sentence Identification With the Ipsilateral Competitive Message scores, indicating a lower likelihood of this disorder, and cognitive frailty (OR, 0.989; 95% CI, 0.988-0.999). Peripheral ARHL was associated with cognitive frailty only in the partially adjusted model (OR, 1.725; 95% CI, 1.008-2.937). Conclusions and Relevance: In this cross-sectional study of 1929 participants, age-related CAPD was independently associated with cognitive frailty. Whether the management of ARHL may help prevent the development of different frailty phenotypes or improve their clinical consequences should be addressed in longitudinal studies and, eventually, well-designed randomized clinical trials.


Assuntos
Disfunção Cognitiva/epidemiologia , Idoso Fragilizado , Perda Auditiva/epidemiologia , Fatores Etários , Idoso , Estudos Transversais , Feminino , Perda Auditiva Central/epidemiologia , Humanos , Itália/epidemiologia , Masculino , Fenótipo , Prevalência
20.
J Cachexia Sarcopenia Muscle ; 12(2): 274-297, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33590975

RESUMO

Aging is often associated with a decline in physical function that eventually leads to loss of autonomy in activities of daily living (ADL). Walking is a very common ADL, important for main determinants of quality of life in older age, and it requires the integration of many physiological systems. Gait speed has been described as the 'sixth vital sign' because it is a core indicator of health and function in aging and disease. We reviewed original studies up to June 2020 that assessed frailty in both longitudinal and cross-sectional observational studies, paying particular attention to how gait is measured in older population and how the gait parameter adopted may influence the estimated frailty models and the health-related outcomes of the various studies (i.e. clinical, cognitive, physical, and nutritional outcomes). Eighty-five studies met the search strategy and were included in the present systematic review. According to the frailty tools, more than 60% of the studies used the physical phenotype model proposed by Fried and colleagues, while one-third referred to multi-domain indexes or models and only 5% referred to other single-domain frailty models (social or cognitive). The great heterogeneity observed in gait measurements and protocols limited the possibility to directly compare the results of the studies and it could represent an important issue causing variability in the different outcome measures in both clinical-and population-based settings. Gait appeared to be an indicator of health and function also in frail older adults, and different gait parameters appeared to predict adverse health-related outcomes in clinical, cognitive, and physical domains and, to a lesser extent, in nutritional domain. Gait has the potential to elucidate the common basic mechanisms of cognitive and motor decline. Advances in technology may extend the validity of gait in different clinical settings also in frail older adults, and technology-based assessment should be encouraged. Combining various gait parameters may enhance frailty prediction and classification of different frailty phenotypes.


Assuntos
Fragilidade , Marcha , Atividades Cotidianas , Idoso , Estudos Transversais , Fragilidade/diagnóstico , Avaliação Geriátrica , Humanos , Qualidade de Vida
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