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OBJECTIVE: Women with type 2 diabetes experience higher cardiovascular and mortality risk than men possibly because of a sub-optimal cardio-protective treatment. We evaluated whether an intensive multifactorial therapy (MT) produces similar protective effect on development of adverse outcomes in women and men. RESEARCH DESIGN AND METHODS: Nephropathy in Diabetes type 2 study is an open-label cluster randomized trial comparing the effect of Usual Care (UC) or MT of main cardiovascular risk factors (blood pressure < 130/80 mmHg, HbA1c < 7%, LDL < 100 mg/dL, and total cholesterol < 175 mg/dL) on cardiovascular and mortality risk in patients with type 2 diabetes. In this post-hoc analysis, we stratified patients by sex to compare the occurrence of MACEs (primary endpoint) and all-cause death (secondary endpoint) between women (104 MT and 105 UC) and men (103 MT and 83 UC). RESULTS: Achievement of therapeutic goals was similar by sex, with 44% and 47% of women and men in MT achieving at least 3 targets vs. 16% and 20% of women and men in UC. During a median follow-up of 13.0 years, we recorded 262 MACE (48.5% in women) and 189 deaths (53.6% in women). Compared to the UC group, the risk of MACE in the MT group was reduced by 52% in women and by 44% in men (P = 0.11). Conversely, the reduction in mortality risk by MT was greater in women (44% versus 12%, P = 0.019). CONCLUSIONS: MT similarly reduces the risk of MACEs in either sex. This therapeutic approach is associated with a survival advantage in women as compared with men and it may represent an important rationale to motivate physicians in overcoming their therapeutic inertia often encountered in female patients as well as to encourage patients of both sexes at improving their adherence to multidrug therapy.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Feminino , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Pessoa de Meia-Idade , Fatores Sexuais , Idoso , Medição de Risco , Resultado do Tratamento , Fatores de Tempo , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/terapia , Nefropatias Diabéticas/diagnóstico , Biomarcadores/sangue , Disparidades nos Níveis de Saúde , Hipoglicemiantes/uso terapêutico , Hemoglobinas Glicadas/metabolismo , Causas de Morte , Pressão SanguíneaRESUMO
Insulin signaling is vital for regulating cellular metabolism, growth, and survival pathways, particularly in tissues such as adipose, skeletal muscle, liver, and brain. Its role in the heart, however, is less well-explored. The heart, requiring significant ATP to fuel its contractile machinery, relies on insulin signaling to manage myocardial substrate supply and directly affect cardiac muscle metabolism. This review investigates the insulin-heart axis, focusing on insulin's multifaceted influence on cardiac function, from metabolic regulation to the development of physiological cardiac hypertrophy. A central theme of this review is the pathophysiology of insulin resistance and its profound implications for cardiac health. We discuss the intricate molecular mechanisms by which insulin signaling modulates glucose and fatty acid metabolism in cardiomyocytes, emphasizing its pivotal role in maintaining cardiac energy homeostasis. Insulin resistance disrupts these processes, leading to significant cardiac metabolic disturbances, autonomic dysfunction, subcellular signaling abnormalities, and activation of the renin-angiotensin-aldosterone system. These factors collectively contribute to the progression of diabetic cardiomyopathy and other cardiovascular diseases. Insulin resistance is linked to hypertrophy, fibrosis, diastolic dysfunction, and systolic heart failure, exacerbating the risk of coronary artery disease and heart failure. Understanding the insulin-heart axis is crucial for developing therapeutic strategies to mitigate the cardiovascular complications associated with insulin resistance and diabetes.
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Resistência à Insulina , Insulina , Transdução de Sinais , Humanos , Animais , Insulina/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Coração/fisiologia , Coração/fisiopatologia , Sistema Renina-Angiotensina/fisiologiaRESUMO
Diabetes mellitus, which comprises a group of metabolic disorders affecting carbohydrate metabolism, is characterized by improper glucose utilization and excessive production, leading to hyperglycemia. The global prevalence of diabetes is rising, with projections indicating it will affect 783.2 million people by 2045. Insulin treatment is crucial, especially for type 1 diabetes, due to the lack of ß-cell function. Intensive insulin therapy, involving multiple daily injections or continuous subcutaneous insulin infusion, has proven effective in reducing microvascular complications but poses a higher risk of severe hypoglycemia. Recent advancements in insulin formulations and delivery methods, such as ultra-rapid-acting analogs and inhaled insulin, offer potential benefits in terms of reducing hypoglycemia and improving glycemic control. However, the traditional subcutaneous injection method has drawbacks, including patient compliance issues and associated complications. Nanomedicine presents innovative solutions to these challenges, offering promising avenues for overcoming current drug limitations, enhancing cellular uptake, and improving pharmacokinetics and pharmacodynamics. Various nanocarriers, including liposomes, chitosan, and PLGA, provide protection against enzymatic degradation, improving drug stability and controlled release. These nanocarriers offer unique advantages, ranging from enhanced bioavailability and sustained release to specific targeting capabilities. While oral insulin delivery is being explored for better patient adherence and cost-effectiveness, other nanomedicine-based methods also show promise in improving delivery efficiency and patient outcomes. Safety concerns, including potential toxicity and immunogenicity issues, must be addressed, with the FDA providing guidance for the safe development of nanotechnology-based products. Future directions in nanomedicine will focus on creating next-generation nanocarriers with precise targeting, real-time monitoring, and stimuli-responsive features to optimize diabetes treatment outcomes and patient safety. This review delves into the current state of nanomedicine for insulin delivery, examining various types of nanocarriers and their mechanisms of action, and discussing the challenges and future directions in developing safe and effective nanomedicine-based therapies for diabetes management.
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Pseudowords offer a unique opportunity to investigate how humans deal with new (verbal) information. Within this framework, previous studies have shown that, at the implicit level, humans exploit systematic associations in the form-meaning interface to process new information by relying on (sub-lexical) contents already mapped in semantic memory. However, whether speakers exploit such processes in explicit decisions about the meanings elicited by unfamiliar terms remains an open, important question. Here, we tested this by leveraging computational models that are able to induce semantic representations for out-of-vocabulary stimuli. Across two experiments, we demonstrate that participants' guesses about pseudoword meanings in a 2AFC task consistently align with the model's predictions. This indicates that humans' ability to extract meaningful knowledge from complex statistical patterns can affect explicit decisions.
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When mentally exploring maps representing large-scale environments (e.g., countries or continents), humans are assumed to mainly rely on spatial information derived from direct perceptual experience (e.g., prior visual experience with the geographical map itself). In the present study, we rather tested whether also temporal and linguistic information could account for the way humans explore and ultimately represent this type of maps. We quantified temporal distance as the minimum time needed to travel by train across Italian cities, while linguistic distance was retrieved from natural language through cognitively plausible AI models based on non-spatial associative learning mechanisms (i.e., distributional semantic models). In a first experiment, we show that temporal and linguistic distances capture with high-confidence real geographical distances. Next, in a second behavioral experiment, we show that linguistic information can account for human performance over and above real spatial information (which plays the major role in explaining participants' performance) in a task in which participants have to judge the distance between cities (while temporal information was found to be not relevant). These findings indicate that, when exploring maps representing large-scale environments, humans do take advantage of both perceptual and linguistic information, suggesting in turn that the formation of cognitive maps possibly relies on a strict interplay between spatial and non-spatial learning principles.
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Julgamento , Percepção Espacial , Humanos , Feminino , Adulto , Masculino , Percepção Espacial/fisiologia , Adulto Jovem , Julgamento/fisiologia , Itália , Linguística , Percepção do Tempo/fisiologiaRESUMO
The formation of false memories is one of the most widely studied topics in cognitive psychology. The Deese-Roediger-McDermott (DRM) paradigm is a powerful tool for investigating false memories and revealing the cognitive mechanisms subserving their formation. In this task, participants first memorize a list of words (encoding phase) and next have to indicate whether words presented in a new list were part of the initially memorized one (recognition phase). By employing DRM lists optimized to investigate semantic effects, previous studies highlighted a crucial role of semantic processes in false memory generation, showing that new words semantically related to the studied ones tend to be more erroneously recognized (compared to new words less semantically related). Despite the strengths of the DRM task, this paradigm faces a major limitation in list construction due to its reliance on human-based association norms, posing both practical and theoretical concerns. To address these issues, we developed the False Memory Generator (FMG), an automated and data-driven tool for generating DRM lists, which exploits similarity relationships between items populating a vector space. Here, we present FMG and demonstrate the validity of the lists generated in successfully replicating well-known semantic effects on false memory production. FMG potentially has broad applications by allowing for testing false memory production in domains that go well beyond the current possibilities, as it can be in principle applied to any vector space encoding properties related to word referents (e.g., lexical, orthographic, phonological, sensory, affective, etc.) or other type of stimuli (e.g., images, sounds, etc.).
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Semântica , Software , Humanos , Feminino , Masculino , Adulto Jovem , Adulto , Repressão Psicológica , Reconhecimento Psicológico/fisiologia , Memória/fisiologia , Rememoração Mental/fisiologiaRESUMO
BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.45
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COVID-19 , Mortalidade Hospitalar , Cirrose Hepática , SARS-CoV-2 , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , COVID-19/patologia , Itália/epidemiologia , Cirrose Hepática/mortalidade , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Idoso de 80 Anos ou mais , Hospitalização/estatística & dados numéricos , AdultoRESUMO
Long-COVID19 has been recently associated with long-sick leave and unemployment. The autonomic nervous system functioning may be also affected by SARS-CoV-2, leading to a chronic autonomic syndrome. This latter remains widely unrecognized in clinical practice. In the present study, we assessed the occurrence of Long-COVID19 Autonomic Syndrome in a group of active workers as well as the relationships between their autonomic dysfunction and work ability. This prospective observational study was conducted during the 2nd wave of the pandemic in Italy. Forty-five patients (53.6 ± 8.4 years; 32 M) hospitalized for COVID19, were consecutively enrolled at the time of their hospital discharge (T0) and followed-up for 6 months. Autonomic symptoms and work ability were assessed by COMPASS31 and Work Ability Index questionnaires at T0, one (T1), three and six (T6) months after hospital discharge and compared to those retrospectively collected for a period preceding SARS-CoV-2 infection. Clinical examination and standing test were also performed at T1 and T6. One in three working-age people developed a new autonomic syndrome that was still evident 6 months after the acute infection resolution. This was associated with a significant reduction in the work ability. Recognition of Long-COVID19 Autonomic Syndrome may promote early intervention to facilitate return to work and prevent unemployment.
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COVID-19 , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , COVID-19/complicações , COVID-19/fisiopatologia , COVID-19/epidemiologia , COVID-19/virologia , Estudos Prospectivos , Itália/epidemiologia , Adulto , SARS-CoV-2/isolamento & purificação , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/epidemiologia , Síndrome de COVID-19 Pós-Aguda , Retorno ao Trabalho , Sistema Nervoso Autônomo/fisiopatologia , Inquéritos e QuestionáriosRESUMO
The human body is perhaps the most ubiquitous and salient visual stimulus that we encounter in our daily lives. Given the prevalence of images of human bodies in natural scene statistics, it is no surprise that our mental representations of the body are thought to strongly originate from visual experience. Yet, little is still known about high-level cognitive representations of the body. Here, we retrieved a body map from natural language, taking this as a window into high-level cognitive processes. We first extracted a matrix of distances between body parts from natural language data and employed this matrix to extrapolate a body map. To test the effectiveness of this high-level body map, we then conducted a series of experiments in which participants were asked to classify the distance between pairs of body parts, presented either as words or images. We found that the high-level body map was systematically activated when participants were making these distance judgments. Crucially, the linguistic map explained participants' performance over and above the visual body map, indicating that the former cannot be simply conceived as a by-product of perceptual experience. These findings, therefore, establish the existence of a behaviorally relevant, high-level representation of the human body.
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Hypercholesterolemia plays a crucial role in the formation of lipid plaques, particularly with elevated low-density lipoprotein (LDL-C) levels, which are linked to increased risks of cardiovascular disease, cerebrovascular disease, and peripheral arterial disease. Controlling blood cholesterol values, specifically reducing LDL-C, is widely recognized as a key modifiable risk factor for decreasing the morbidity and mortality associated with cardiovascular diseases. Historically, statins, by inhibiting the enzyme ß-hydroxy ß-methylglutaryl-coenzyme A (HMG)-CoA reductase, have been among the most effective drugs. However, newer non-statin agents have since been introduced into hypercholesterolemia therapy, providing a viable alternative with a favorable cost-benefit ratio. This paper aims to delve into the latest therapies, shedding light on their mechanisms of action and therapeutic benefits.
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The mental time line (MTL) is a spatial continuum on which earlier events are generally associated with the left space and later events with the right space. Accordingly, past- and future-related words receive faster responses with, respectively, the left and the right hand. Yet, it is currently unclear whether the MTL is activated by the whole word or whether it can be triggered by more subtle sublexical cues, such as verb-endings, and whether the activation of this spatial continuum is an automatic phenomenon. The aim of this study is to test whether verb-endings do bring conceptual information that is in turn capable to activate the MTL and whether this activation holds also when the temporal information is not explicitly processed. We designed three experiments. In Experiment 1, consisting of a temporal categorization task, and in Experiment 2, consisting of a lexical decision task, we tested Italian tensed verbs (trov-avo "I found," trov-erò "I will find") and pseudo-verbs (trop-avo, trop-erò). Results of Experiment 1 showed that both tensed verbs and pseudo-verbs were spatially coded on the MTL. Results from Experiment 2 showed that the MTL is activated by the verb-endings also when temporal information was task-irrelevant (i.e., lexical decision task). Experiment 3 further clarified that the spatial-temporal congruency effect does not emerge during the evaluation of an inhomogeneous set of stimuli (i.e., when adding to the stimuli time-unrelated fillers). Overall, the present findings indicate that sublexical strings carry specific semantic information that comes into play in the generation of spatial-temporal associations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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There is a fervent debate about the processes underpinning false memories formation. Seminal theories have suggested that semantic memory would be involved in false memories production, while episodic memory would counter their formation. Yet, direct evidence corroborating such view is still lacking. Here, we tested this possibility by asking participants to perform the Deese-Roediger-McDermott (DRM) task, a typical false memory paradigm, in which they had to study lists of words and subsequently to recognize and distinguish them from new words (i.e., the false memory items). The same participants were also required to perform a semantic task and an episodic-source memory task. Our results showed that a higher number of false memories in the DRM task occurred for those participants with better semantic memory abilities, while a lower number of false memories occurred for participants with better episodic abilities. These findings support a key role of semantic processes in false memory formation and, more generally, help clarify the specific contribution of different memory systems to false recognitions.
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Memória Episódica , Rememoração Mental , Humanos , Semântica , CogniçãoRESUMO
BACKGROUND AND AIMS: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. METHODS: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. RESULTS: 197 patients were included in the study (median age 83.0 [82.0-87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0-25.0] days. From the multivariable Cox regression analysis, after the application of Sidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan-Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). CONCLUSIONS: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.
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Although mouse-tracking has been taken as a real-time window on different aspects of human decision-making processes, whether purely semantic information affects response conflict at the level of motor output as measured through mouse movements is still unknown. Here, across two experiments, we investigated the effects of semantic knowledge by predicting participants' performance in a standard keyboard task and in a mouse-tracking task through distributional semantics, a usage-based modeling approach to meaning. In Experiment 1, participants were shown word pairs and were required to perform a two-alternative forced choice task selecting either the more abstract or the more concrete word, using standard keyboard presses. In Experiment 2, participants performed the same task, yet this time response selection was achieved by moving the computer mouse. Results showed that the involvement of semantic components in the task at hand is observable using both standard reaction times (Experiment 1) as well as using indexes extracted from mouse trajectories (Experiment 2). In particular, mouse trajectories reflected the response conflict and its temporal evolution, with a larger deviation for increasing word semantic relatedness. These findings support the validity of mouse-tracking as a method to detect deep and implicit decision-making features. Additionally, by demonstrating that a usage-based model of meaning can account for the different degrees of cognitive conflict associated with task achievement, these findings testify the impact of the human semantic memory on decision-making processes.
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Conhecimento , Semântica , Humanos , Memória , Movimento , Tempo de ReaçãoRESUMO
Long-COVID syndrome is characterized by fatigue, orthostatic intolerance, tachycardia, pain, memory difficulties, and brain fog, which may be associated with autonomic nervous system abnormalities. We aimed to evaluate the short and long-term course of COVID-19 autonomic symptoms and quality of life (QoL) after SARS-CoV-2 infection through a one-year follow-up combined with validated questionnaires. Additionally, we aimed to identify patients with worsening autonomic symptoms at 6 and 12 months by dividing the patient cohort into two sub-groups: the Post-COVID healed Control sub-group (total score<16.4) and the Long-COVID autonomic syndrome sub-group (total score>16.4). This prospective cohort studied 112 SARS-CoV-2 positive patients discharged from Humanitas Research Hospital between January and March 2021. Autonomic symptoms and QoL were assessed using the composite autonomic symptom scale 31 (COMPASS-31) and Short Form Health Survey (SF-36) questionnaires at various time points: before SARS-CoV-2 infection (PRE), at hospital discharge (T0), and at 1 (T1), 3 (T3), 6 (T6), and 12 (T12) months of follow-up. COMPASS-31 total score, Orthostatic Intolerance and Gastrointestinal function indices, QoL, physical functioning, pain, and fatigue scores worsened at T0 compared to PRE but progressively improved at T1 and T3, reflecting the acute phase of COVID-19. Unexpectedly, these indices worsened at T6 and T12 compared to T3. Subgroup analysis revealed that 47% of patients experienced worsening autonomic symptoms at T6 and T12, indicating Long-COVID autonomic syndrome. Early rehabilitative and pharmacological therapy is recommended for patients at the T1 and T3 stages after SARS-CoV-2 infection to minimize the risk of developing long-term autonomic syndrome.
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COVID-19 , Intolerância Ortostática , Humanos , Síndrome de COVID-19 Pós-Aguda , COVID-19/complicações , Estudos Prospectivos , Qualidade de Vida , SARS-CoV-2 , Fadiga/etiologia , DorRESUMO
Cervical cancer ranks as the fourth most prevalent cancer among women globally, with approximately 600,000 new cases being diagnosed each year. The principal driver of cervical cancer is the human papillomavirus (HPV), where viral oncoproteins E6 and E7 undertake the role of driving its carcinogenic potential. Despite extensive investigative efforts, numerous facets concerning HPV infection, replication, and pathogenesis remain shrouded in uncertainty. The virus operates through a variety of epigenetic mechanisms, and the epigenetic signature of HPV-related tumors is a major bottleneck in our understanding of the disease. Recent investigations have unveiled the capacity of viral oncoproteins to influence epigenetic changes within HPV-related tumors, and conversely, these tumors exert an influence on the surrounding epigenetic landscape. Given the escalating occurrence of HPV-triggered tumors and the deficiency of efficacious treatments, substantial challenges emerge. A promising avenue to address this challenge lies in epigenetic modulators. This review aggregates and dissects potential epigenetic modulators capable of combatting HPV-associated infections and diseases. By delving into these modulators, novel avenues for therapeutic interventions against HPV-linked cancers have come to the fore.
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BACKGROUND: Sepsis still represents a major public health issue worldwide, and the immune system plays a main role during infections; therefore, its activity is mandatory to resolve this clinical condition. In this report, we aimed to retrospectively verify in a real-life setting the possible usefulness of pentameric IgM plus antibiotics in recovering patients with sepsis after major abdominal surgery. MATERIALS/METHODS: We reviewed, from January 2013 until December 2019, all adult patients admitted to the ICU for sepsis or septic shock (2) after major abdominal surgery. Among these patients, were identified those that, according to legal indication and licenses in Italy, were treated with pentameric IgM plus antibiotics (Group A) or with antibiotics alone (Group B). The following parameters were evaluated: blood gas analysis, lactate, CRP, procalcitonin, endotoxin activity, liver and renal function, coagulation and blood cell count at different time points (every 48 h for at least 7 days). Differences between groups were analyzed using Fisher's exact test or a chi-square test for categorical variables. A Mann-Whitney U test or Kruskal-Wallis test were instead been performed to compare continuous variables. Univariate and multivariate analysis were also performed. RESULTS: Over a period of 30 months, 24 patients were enrolled in Group A and 20 patients in Group B. In those subjects, no statistical differences were found in terms of bacterial or fungal infection isolates, when detected in a blood culture test, or according to inflammatory index, a score, lactate levels and mortality rate. A 48 h response was statistically more frequent in Group B than in Group A, while no differences were found in other clinical and laboratory evaluations. CONCLUSIONS: Based on our results, the use of pentameric IgM does not seem to give any clinical advantages in preventing sepsis after major abdominal surgery.
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Type 2 diabetes mellitus (T2DM) is one of the most widespread diseases in Western countries, and its incidence is constantly increasing. Epidemiological studies have shown that in the next 20 years. The number of subjects affected by T2DM will double. In recent years, owing to the development and improvement in methods for studying the genome, several authors have evaluated the association between monogenic or polygenic genetic alterations and the development of metabolic diseases and complications. In addition, sedentary lifestyle and socio-economic and pandemic factors have a great impact on the habits of the population and have significantly contributed to the increase in the incidence of metabolic disorders, obesity, T2DM, metabolic syndrome, and liver steatosis. Moreover, patients with type 2 diabetes appear to respond to antihyperglycemic drugs. Only a minority of patients could be considered true non-responders. Thus, it appears clear that the main aim of precision medicine in T2DM is to identify patients who can benefit most from a specific drug class more than from the others. Precision medicine is a discipline that evaluates the applicability of genetic, lifestyle, and environmental factors to disease development. In particular, it evaluated whether these factors could affect the development of diseases and their complications, response to diet, lifestyle, and use of drugs. Thus, the objective is to find prevention models aimed at reducing the incidence of pathology and mortality and therapeutic personalized approaches, to obtain a greater probability of response and efficacy. This review aims to evaluate the applicability of precision medicine for T2DM, a healthcare burden in many countries.
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BACKGROUND AND AIMS: Cardiovascular disease (CVD) is the leading cause of early mortality in orthotopic liver transplantation (OLT) patients. The fatty liver index (FLI) is strongly associated with carotid and coronary atherosclerosis, as well as cardiovascular mortality, surpassing traditional risk factors. Given the lack of data on FLI as a predictor of cardiovascular events in OLT recipients, we conducted a retrospective study to examine this topic. METHODS AND RESULTS: We performed a multicenter retrospective analysis of adult OLT recipients who had regular follow-up visits every three to six months (or more frequently if necessary) from January 1995 to December 2020. The minimum follow-up period was two years post-intervention. Anamnestic, clinical, anthropometric and laboratory data were collected, and FLI was calculated for all patients. CLINICAL TRIAL: gov registration ID NCT05895669. A total of 110 eligible patients (median age 57 years [IQR: 50-62], 72.7% male) were followed for a median duration of 92.3 months (IQR: 45.7-172.4) post-liver transplantation. During this period, 16 patients (14.5%) experienced at least one adverse cardiovascular event (including fatal and non-fatal myocardial infarction and stroke). Receiver Operating Characteristic (ROC) analysis identified a cut-off value of 66.0725 for predicting cardiovascular events after OLT, with 86.7% sensitivity and 63.7% specificity (68% vs. 31%; p = 0.001). Kaplan-Meier analysis showed that patients with FLI > 66 had significantly reduced cardiovascular event-free survival than those with FLI ≤ 66 (log-rank: 0.0008). Furthermore, multivariable Cox regression analysis demonstrated that FLI > 66 and pre-OLT smoking were independently associated with increased cardiovascular risk. CONCLUSIONS: Our findings suggest that FLI > 66 and pre-OLT smoking predict cardiovascular risk in adult OLT recipients.
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Language processing is influenced by sensorimotor experiences. Here, we review behavioral evidence for embodied and grounded influences in language processing across six linguistic levels of granularity. We examine (a) sub-word features, discussing grounded influences on iconicity (systematic associations between word form and meaning); (b) words, discussing boundary conditions and generalizations for the simulation of color, sensory modality, and spatial position; (c) sentences, discussing boundary conditions and applications of action direction simulation; (d) texts, discussing how the teaching of simulation can improve comprehension in beginning readers; (e) conversations, discussing how multi-modal cues improve turn taking and alignment; and (f) text corpora, discussing how distributional semantic models can reveal how grounded and embodied knowledge is encoded in texts. These approaches are converging on a convincing account of the psychology of language, but at the same time, there are important criticisms of the embodied approach and of specific experimental paradigms. The surest way forward requires the adoption of a wide array of scientific methods. By providing complimentary evidence, a combination of multiple methods on various levels of granularity can help us gain a more complete understanding of the role of embodiment and grounding in language processing.