Insulin-like Growth Factor Binding Proteins and Cellular Senescence Are Involved in the Progression of Non-Alcoholic Fatty Liver Disease and Fibrosis in a Mouse Model.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. It progresses from simple steatosis to non-alcoholic steatohepatitis (NASH). Fibrosis is often present during NAFLD progression; however, factors determining which subjects develop NASH or fibrosis are unclear. Insulin-like growth factor binding proteins (IGFBPs) are a family of secreted proteins involved in senescence and scarring, mainly synthetized in the liver. Here, we aimed to study the association of IGFBPs and their induced senescence with the progression of NAFLD and liver fibrosis. Materials and Methods: A total of 16-week-old male C57BL/6 mice weighing 23 ± 3 g were fed either methionine/choline-deficient (MCD) or control diet for 2, 8, or 12 weeks. Blood and liver samples were collected, and a histological assessment of NAFLD and fibrosis was performed. Fat contents were measured. Cellular senescence was evaluated in the liver. IGFBP levels were assessed in the liver and serum. Data were expressed as mean ± SD and analyzed by a one-way ANOVA followed by Tukey's test. Lineal regression models were applied for NAFLD and fibrosis progression. p < 0.05 was considered significant. Results: IGFBP-1 and -2 were increased in serum during NAFLD. IGFBP-7 was significantly increased in the serum in NASH compared with the controls. Senescence increased in NAFLD. Serum and liver IGFBP-7 as well as SA-ß-gal activity increased as fibrosis progressed. Both IGFBP-7 and cellular senescence were significantly higher during NAFLD and fibrosis in MCD-fed mice. Conclusions: IGFBP-1, -2, and -7, through their consequent senescence, have a role in the progression of NAFLD and its associated fibrosis, being a plausible determinant in the progression from steatosis to NASH.

Auditory and visual P300 event-related potentials to detect minimal hepatic encephalopathy.

INTRODUCTION: the diagnosis of minimal hepatic encephalopathy (MHE) requires psychometric tests, although new methods are needed since their sensitivity, specificity, and accuracy are low. The P300 event-related potential (ERP) is obtained by auditory and visual stimuli, although only the auditory P300 has been used to detect MHE. This study aimed to compare the diagnostic features of auditory and visual P300 to detect MHE. MATERIALS AND METHODS: sixty patients with liver cirrhosis and thirty-five healthy controls completed the Psychometric Hepatic Encephalopathy Score (PHES), the critical flicker frequency (CFF), and auditory and visual P300 tests. MHE was diagnosed if PHES and CFF scores were abnormal. RESULTS: fifty-three cirrhotic patients (aged 54.5 ± 8.6 years) completed all tests. Abnormal scores were obtained for PHES (49.1 %) and CFF (67.9 %). The proportion of MHE was 21.4 %. The area under the receiver operating (ROC) curves (AUROC) for auditory P300 was better than for visual P300 for distinguishing MHE from controls (AUROC: 0.792 vs 0.725; p < 0.005 for both; accuracy: 73.8 % vs 70.2 %; sensitivity: 72.2 % for both; specificity: 74.2 vs 69.7, respectively). Among cirrhotic patients, only auditory P300 was useful to detect MHE (AUROC: 0.723; p < 0.05; 77.4 % accuracy; 61.1 % sensitivity, and 81.8 % specificity). CONCLUSIONS: auditory P300 sensitivity, specificity, and accuracy were similar to those of CFF. Our results showed that only auditory P300 is useful to differentiate patients with MHE, although both modalities, auditory and visual, differentiated patients with cirrhosis from controls. Thus, we consider that visual P300 is not suitable for detecting MHE.

Impact of COVID-19 Pandemic Lockdown on Migraine Patients in Latin America.

The coronavirus (COVID-19) pandemic, confinement, fear, lifestyle changes, and worldwide health care impacted almost all diseases. Reports from countries outside Latin America revealed differences in migraine patients. In this study, we describe and compare the immediate changes in migraine symptoms associated with COVID-19 quarantine in patients from Argentina, Mexico, and Peru. An online survey was conducted from May to July 2020. The survey was answered by 243 migraine patients, with questions related to sociodemographic data, quarantine conditions, changes in working conditions, physical activity, coffee intake, healthcare access, acute migraine medication use, symptoms of anxiety, depression, and fear of COVID-19. The results show that 48.6% of migraine patients experienced worsened symptoms, 15.6% improved, and 35.8% remained unchanged. Worsening migraine symptoms were associated with staying at home during the lockdown. Intake of analgesics was associated with an increase in migraine symptoms of 18 times relative to those who did not increase their intake. Migraine symptoms improved when the number of sleep hours was increased, and we observed an improvement when patients decreased analgesic intake. The uncertainty about the end of the pandemic, the news, and social media are three items that contributed to the worsening of migraine symptoms in patients in the three investigated countries. Confinement during the first pandemic wave in Latin America harmed migraine patients who stayed home during the lockdown.

Effect of 3D-MOT training on the execution of manual dexterity skills in a population of older adults with mild cognitive impairment and mild dementia.

Computerized cognitive training tools are an alternative to preventive treatments related to cognitive impairment and aging. In this study, the transfer of 3D multiple object tracking (3D-MOT) training on manual dexterity concerning fine and gross motor skills in 38 elderly participants, half of them with mild cognitive impairment (MCI) and the other half with mild dementia (MD) was explored. A total of 36 sessions of the 3D-MOT training program were administered to the subjects. The Montreal Cognitive Assessment (MoCA) test was used to assess the baseline cognitive status of the participants. Two batteries of manual motor skills (GPT and MMDT) were applied before and after the 3D-MOT training program. The results showed an interaction effect of training and improvement in manual dexterity tests, from the first training session until the fifteenth session, and after this range of sessions, the interaction effect was lost. However, the training effect continued to the end of the thirty-six-session program. The experimental results show the effect of cognitive training on the improvement of motor skills in older adults. This type of intervention could have a broad impact on the aging population in terms of their attention, executive functions, and therefore, their quality of life.

Auditory and visual P300 event-related potentials to detect minimal hepatic encephalopathy

Introduction: the diagnosis of minimal hepatic encephalopathy (MHE) requires psychometric tests, although new methods are needed since their sensitivity, specificity, and accuracy are low. The P300 event-related potential (ERP) is obtained by auditory and visual stimuli, although only the auditory P300 has been used to detect MHE. This study aimed to compare the diagnostic features of auditory and visual P300 to detect MHE.Materials and methods: sixty patients with liver cirrhosis and thirty-five healthy controls completed the Psychometric Hepatic Encephalopathy Score (PHES), the critical flicker frequency (CFF), and auditory and visual P300 tests. MHE was diagnosed if PHES and CFF scores were abnormal.Results: fifty-three cirrhotic patients (aged 54.5 ± 8.6 years) completed all tests. Abnormal scores were obtained for PHES (49.1 %) and CFF (67.9 %). The proportion of MHE was 21.4 %. The area under the receiver operating (ROC) curves (AUROC) for auditory P300 was better than for visual P300 for distinguishing MHE from controls (AUROC: 0.792 vs 0.725; p < 0.005 for both; accuracy: 73.8 % vs 70.2 %; sensitivity: 72.2 % for both; specificity: 74.2 vs 69.7, respectively). Among cirrhotic patients, only auditory P300 was useful to detect MHE (AUROC: 0.723; p < 0.05; 77.4 % accuracy; 61.1 % sensitivity, and 81.8 % specificity). Conclusions: auditory P300 sensitivity, specificity, and accuracy were similar to those of CFF. Our results showed that only auditory P300 is useful to differentiate patients with MHE, although both modalities, auditory and visual, differentiated patients with cirrhosis from controls. Thus, we consider that visual P300 is not suitable for detecting MHE. (AU)