Astrocyte-to-neuron communication through integrin-engaged Thy-1/CBP/Csk/Src complex triggers neurite retraction via the RhoA/ROCK pathway.

Two key proteins for cellular communication between astrocytes and neurons are αvß3 integrin and the receptor Thy-1. Binding of these molecules in the same (cis) or on adjacent (trans) cellular membranes induces Thy-1 clustering, triggering actin cytoskeleton remodeling. Molecular events that could explain how the Thy-1-αvß3 integrin interaction signals have only been studied separately in different cell types, and the detailed transcellular communication and signal transduction pathways involved in neuronal cytoskeleton remodeling remain unresolved. Using biochemical and genetic approaches, single-molecule tracking, and high-resolution nanoscopy, we provide evidence that upon binding to αvß3 integrin, Thy-1 mobility decreased while Thy-1 nanocluster size increased. This occurred concomitantly with inactivation and exclusion of the non-receptor tyrosine kinase Src from the Thy-1/C-terminal Src kinase (Csk)-binding protein (CBP)/Csk complex. The Src inactivation decreased the p190Rho GTPase activating protein phosphorylation, promoting RhoA activation, cofilin, and myosin light chain II phosphorylation and, consequently, neurite shortening. Finally, silencing the adaptor CBP demonstrated that this protein was a key transducer in the Thy-1 signaling cascade. In conclusion, these data support the hypothesis that the Thy-1-CBP-Csk-Src-RhoA-ROCK axis transmitted signals from astrocytic integrin-engaged Thy-1 (trans) to the neuronal actin cytoskeleton. Importantly, the ß3 integrin in neurons (cis) was not found to be crucial for neurite shortening. This is the first study to detail the signaling pathway triggered by αvß3, the endogenous Thy-1 ligand, highlighting the role of membrane-bound integrins as trans acting ligands in astrocyte-neuron communication.

miR15a and miR16 in Chilean type 1 diabetes patients: possible association with apoptosis, inflammatory, or autoimmunity markers.

AIM: Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by the progressive destruction of ß cells, mediated by the interaction between T cells and several cytokines. The pathogenesis of T1D has established its possible relationship with miRNAs. In this study, we analyze the expression profile of miR-15a and miR-16 in peripheral blood mononuclear cells (PBMCs) and their possible association with apoptosis, inflammation, or autoimmunity markers. PATIENTS AND METHODOLOGY: 38 T1D patients and 41 control subjects were recruited. mRNAs were analyzed by means of qPCR and TaqMan probes. PBMCs were treated with different concentrations of glucose (baseline, 11 and 25 mM) with or without an inflammatory stimulus as TNF-α (10 ng/ml). RESULTS: A decrease in the levels of the miR-15a expression in basal conditions is observed in T1D patients compared to healthy control subjects (relative units 0.5 vs. 1.8, p < 0.05). This change in miR-15a and miR-16 is not affected by the addition of TNF-α. No association is observed with inflammatory markers (IL-6, TNF-α, vCAM) or apoptosis (bcl2 expression). The relationship with immunological markers shows an interaction effect between miR16 and IA-2 (p < 0.03). CONCLUSION: TNF-α does not affect the expression profile of miR-15a and miR16 in PBMCs. A weak correlation is observed between miR-16 and with the autoimmunity profile (IA-2 autoantibody).

miR15a and miR16 in Chilean type 1 diabetes patients: possible association with apoptosis, inflammatory, or autoimmunity markers.

AIM: Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by the progressive destruction of ß cells, mediated by the interaction between T cells and several cytokines. The pathogenesis of T1D has established its possible relationship with miRNAs. In this study, we analyze the expression profile of miR-15a and miR-16 in peripheral blood mononuclear cells (PBMCs) and their possible association with apoptosis, inflammation, or autoimmunity markers. PATIENTS AND METHODOLOGY: 38 T1D patients and 41 control subjects were recruited. mRNAs were analyzed by means of qPCR and TaqMan probes. PBMCs were treated with different concentrations of glucose (baseline, 11 and 25 mM) with or without an inflammatory stimulus as TNF-α (10 ng/ml). RESULTS: A decrease in the levels of the miR-15a expression in basal conditions is observed in T1D patients compared to healthy control subjects (relative units 0.5 vs. 1.8, p < 0.05). This change in miR-15a and miR-16 is not affected by the addition of TNF-α. No association is observed with inflammatory markers (IL-6, TNF-α, vCAM) or apoptosis (bcl2 expression). The relationship with immunological markers shows an interaction effect between miR16 and IA-2 (p < 0.03). CONCLUSION: TNF-α does not affect the expression profile of miR-15a and miR16 in PBMCs. A weak correlation is observed between miR-16 and with the autoimmunity profile (IA-2 autoantibody).

Grape seed proanthocyanidin supplementation reduces adipocyte size and increases adipocyte number in obese rats.

OBJECTIVES: White adipose tissue (WAT) expands through hypertrophy (increased adipocyte size) and/or hyperplasia (increased adipocyte number). Hypertrophy has been associated with insulin resistance and dyslipidemia independently of body composition and fat distribution. In contrast, hyperplasia protects against metabolic alterations. Proanthocyanidins, which are the most abundant flavonoids in the human diet, improve metabolic disturbances associated with diet-induced obesity without reducing body weight or adiposity. The aim of this study was to determine whether grape seed proanthocyanidin extract (GSPE) can modulate WAT expandability. Because GSPE also contains gallic acid, we also studied the capacity of gallic acid to remodel WAT. DESIGN: Male Wistar rats were fed a standard chow diet (n=6) or a cafeteria diet (CAF) for 11 weeks. After 8 weeks, the CAF-fed animals were supplemented with 25 mg GSPE/kg body weight (n=6), 7 mg gallic acid/kg body weight (n=6) or the vehicle (n=6) for 3 weeks. Histological analyses were performed in the retroperitoneal (rWAT) and inguinal (iWAT) WAT to determine adipocyte size and number. Specific markers for adipogenesis and WAT functionality were analysed in rWAT using quantitative RT-PCR. RESULTS: GSPE or gallic acid supplementation did not reduce weight gain or reverse and adiposity. However, GSPE reduced adipocyte size significantly in rWAT and moderately in iWAT and tripled the adipocyte number in rWAT. Gallic acid slightly reduced adipocyte size in rWAT and iWAT and doubled the adipocyte number in both WATs. In accordance with this adipogenic activity, Pref-1 and PPARγ tended to be overexpressed in rWAT of rats supplemented with GSPE. Moreover, GSPE supplementation increased Plin1 and Fabp4 expression and restored adiponectin expression completely, indicating a better functionality of visceral WAT. CONCLUSIONS: GSPE supplementation has anti-hypertrophic and hyperplasic activities in rats with established obesity, mainly in visceral WAT inducing a healthier expansion of WAT to match the surplus energy provided by the cafeteria diet.

The impact of chronic stress on the rat brain lipidome.

Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer's disease and depression. Lipids are a major constituent of the brain and specifically signaling lipids have been shown to regulate brain function. Here, we used a mass spectrometry-based lipidomic approach to evaluate the impact of a chronic unpredictable stress (CUS) paradigm on the rat brain in a region-specific manner. We found that the prefrontal cortex (PFC) was the area with the highest degree of changes induced by chronic stress. Although the hippocampus presented relevant lipidomic changes, the amygdala and, to a greater extent, the cerebellum presented few lipid changes upon chronic stress exposure. The sphingolipid and phospholipid metabolism were profoundly affected, showing an increase in ceramide (Cer) and a decrease in sphingomyelin (SM) and dihydrosphingomyelin (dhSM) levels, and a decrease in phosphatidylethanolamine (PE) and ether phosphatidylcholine (PCe) and increase in lysophosphatidylethanolamine (LPE) levels, respectively. Furthermore, the fatty-acyl profile of phospholipids and diacylglycerol revealed that chronic stressed rats had higher 38 carbon(38C)-lipid levels in the hippocampus and reduced 36C-lipid levels in the PFC. Finally, lysophosphatidylcholine (LPC) levels in the PFC were found to be correlated with blood corticosterone (CORT) levels. In summary, lipidomic profiling of the effect of chronic stress allowed the identification of dysregulated lipid pathways, revealing putative targets for pharmacological intervention that may potentially be used to modulate stress-induced deficits.

C-Reactive protein and insulin growth factor 1 serum levels during the menstrual cycle in adolescents with Type 1 diabetes.

AIMS: To evaluate C-reactive protein, insulin growth factor 1 and lipid levels during the follicular and luteal phases in adolescents with Type 1 diabetes. METHODS: Adolescents with Type 1 diabetes (N = 40) and healthy controls (C; N = 43) were studied during the follicular and luteal phases of their menstrual cycles. C-Reactive protein, insulin growth factor 1 and lipid levels were measured. RESULTS: Adolescents with Type 1 diabetes exhibited higher C-reactive protein levels than the C group during the follicular (P < 0.0001) and luteal phases (P < 0.01). The elevation of C-reactive protein levels was more pronounced in overweight adolescents with Type 1 diabetes than in adolescents in the C group. More adolescents with Type 1 diabetes were classified as having an elevated risk of cardiovascular disease (C-reactive protein > 3 mg/l) in the luteal phase than in the follicular phase (37.5% and 17.5%, respectively); half of the overweight adolescents with Type 1 diabetes in the luteal phase reached this level. BMI was the only significant factor affecting follicular and luteal phase C-reactive protein levels in adolescents with Type 1 diabetes. Lower insulin growth factor 1 levels were observed during both phases of the menstrual cycle in adolescents with Type 1 diabetes compared with controls. An elevation in insulin growth factor 1 levels in the luteal phase relative to the follicular phase was observed in controls, but not in adolescents with Type 1 diabetes. Luteal insulin growth factor 1 and C-reactive protein exhibited an inverse correlation (r = -0.4, P = 0.01). CONCLUSIONS: Adolescents with Type 1 diabetes have higher C-reactive protein levels and lower insulin growth factor 1 levels relative to controls, especially during the luteal phase. Type 1 diabetes diminishes the natural elevation in insulin growth factor 1 levels observed during the luteal phase in controls. Excess weight exacerbates the subclinical inflammatory state observed during both phases of the menstrual cycle in adolescents with Type 1 diabetes.

Prevalence of basilar artery dolichoectasia in patients with acute ischemic stroke or transient ischemic attack in a single center of Spain. / Prevalencia de la dolicoectasia de la arteria basilar en pacientes con ictus isquémico agudo o ataque isquémico transitorio en un centro español.

INTRODUCTION: Basilar artery dolichoectasia (BADE) refers to abnormal enlargement or displacement of the basilar artery (BA). The previously reported prevalence of BADE among patients with stroke is 0.3 to 33.1%, however, it might vary among studied populations. We aim is to determine the prevalence of BADE in patients presenting with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in a Stroke Unit in a single center in Spain. PATIENTS AND METHODS: Patients 50 years old or older presenting with AIS or TIA were eligible for inclusion. Demographic and clinical data were prospectively collected. Two neuroradiologists, blind to each other, assessed BA morphology. RESULTS: Among 126 patients, 34.1% fulfilled the criteria for BADE (ectasia or dolichosis). BADE was associated with advanced age (p = 0.04). Patients with fetal-type circle of Willis presented smaller BA diameters (2.9 ± 0.1 vs. 3.5 ± 0.1; p < 0.001), whereas patients with lacunar strokes presented a greater diameter than other stroke subtypes (3.8 ± 0.3 mm vs. 3.3 ± 0.1 mm; p = 0.04). DISCUSSION AND CONCLUSIONS: In this single-center study of patients presenting with AIS or TIA, the prevalence of BADE (ectasia or dolichosis) is high. Further studies focusing on Spaniards should confirm our results.

TITLE: Prevalencia de la dolicoectasia de la arteria basilar en pacientes con ictus isquémico agudo o ataque isquémico transitorio en un centro español.Introducción. La dolicoectasia de la arteria basilar (DEAB) es un término que se refiere a la dilatación o elongación anormal de la arteria basilar (AB). La prevalencia de DEAB notificada hasta la fecha en pacientes con ictus es del 0,3 al 33,1%; sin embargo, puede variar entre poblaciones. Se propuso determinar la prevalencia de DEAB en pacientes con ictus isquémico agudo (IIA) o ataque isquémico transitorio (AIT) en una unidad de ictus de España. Pacientes y métodos. Se consideró a pacientes de 50 años o más con IIA o AIT para ser incluidos. La información demográfica y clínica se obtuvo de forma prospectiva. Dos neurorradiólogos evaluaron la morfología de la AB de forma independiente. Resultados. De 126 pacientes, el 34,1% cumplió los criterios de DEAB (ectasia o dolicosis). La DEAB se asoció a mayor edad (p = 0,04). Los pacientes con la variante fetal del polígono de Willis presentaron menor diámetro de la AB (2,9 ± 0,1 frente a 3,5 ± 0,1; p < 0,001), mientras que pacientes con ictus lacunar presentaron diámetros mayores de la AB que otros subtipos de ictus (3,8 ± 0,3 mm frente a 3,3 ± 0,1 mm; p = 0,04). Discusión y conclusiones. En este estudio de centro único de pacientes con IIA o AIT, la prevalencia de DEAB (ectasia o dolicosis) fue alta. Estudios futuros enfocados en población española podrían confirmar nuestros resultados.

Characterization and classification of kinesthetic motor imagery levels.

Objective.Kinesthetic Motor Imagery (KMI) represents a robust brain paradigm intended for electroencephalography (EEG)-based commands in brain-computer interfaces (BCIs). However, ensuring high accuracy in multi-command execution remains challenging, with data from C3 and C4 electrodes reaching up to 92% accuracy. This paper aims to characterize and classify EEG-based KMI of multilevel muscle contraction without relying on primary motor cortex signals.Approach.A new method based on Hurst exponents is introduced to characterize EEG signals of multilevel KMI of muscle contraction from electrodes placed on the premotor, dorsolateral prefrontal, and inferior parietal cortices. EEG signals were recorded during a hand-grip task at four levels of muscle contraction (0%, 10%, 40%, and 70% of the maximal isometric voluntary contraction). The task was executed under two conditions: first, physically, to train subjects in achieving muscle contraction at each level, followed by mental imagery under the KMI paradigm for each contraction level. EMG signals were recorded in both conditions to correlate muscle contraction execution, whether correct or null accurately. Independent component analysis (ICA) maps EEG signals from the sensor to the source space for preprocessing. For characterization, three algorithms based on Hurst exponents were used: the original (HO), using partitions (HRS), and applying semivariogram (HV). Finally, seven classifiers were used: Bayes network (BN), naive Bayes (NB), support vector machine (SVM), random forest (RF), random tree (RT), multilayer perceptron (MP), and k-nearest neighbors (kNN).Main results.A combination of the three Hurst characterization algorithms produced the highest average accuracy of 96.42% from kNN, followed by MP (92.85%), SVM (92.85%), NB (91.07%), RF (91.07%), BN (91.07%), and RT (80.35%). of 96.42% for kNN.Significance.Results show the feasibility of KMI multilevel muscle contraction detection and, thus, the viability of non-binary EEG-based BCI applications without using signals from the motor cortex.

Rasch validation of the Keratoconus End-Points Assessment Questionnaire in a Spanish population with keratoconus.

OBJECTIVE: To carry out a methodologically complete validation of the Spanish version of the Keratoconus End-Points Assessment Questionnaire (KEPAQ) in a Spanish population with keratoconus. METHODS: Analytical, prospective study, including patients with keratoconus without previous surgical history, in which a measurement of quality of life was performed using the KEPAQ questionnaire, a complete exploration of the anterior pole and a corneal elevation topography with the Galilei G6 topographer. The evaluation of the psychometric characteristics of the scale in the studied population was carried out using Rasch modeling. RESULTS: A total of 140 patients with keratoconus were included, with a median age of 26.0 years, the majority (57.6%) being men. For the KEPAQ-E subscale, the median score was 69.3, with a reliability of 0.85 and an eigenvalue of the first contrast of 2.34. For the KEPAQ-F, the median score was 56.4, with a reliability of 0.88 and an eigenvalue of 2.00. All infit and outfit parameters were within normal limits for both subscales. A significant evaluation was found between the evaluations of both subscales (rho = 0.696; p < 0.001). The evaluations of the subscales and various clinical and tomographic characteristics showed a significant classification between them (p value between 0.048 y 0.001). CONCLUSION: The KEPAQ is a psychometrically robust and valid scale to evaluate quality of life in the Spanish population with keratoconus. This questionnaire can be easily used for both clinical and research aims.

Artificial Intelligence and new language models in Ophthalmology: Complications of the use of silicone oil in vitreoretinal surgery.

Artificial intelligence (AI) is an emerging technology that facilitates everyday tasks and automates tasks in various fields such as medicine. However, the emergence of a language model in academia has generated a lot of interest. This paper evaluates the potential of ChatGPT, a language model developed by OpenAI, and DALL-E 2, an image generator, in the writing of scientific articles in ophthalmology. The selected topic is the complications of the use of silicone oil in vitreoretinal surgery. ChatGPT was used to generate an abstract and a structured article, suggestions for a title and bibliographical references. In conclusion, despite the knowledge demonstrated by this tool, the scientific accuracy and reliability on specific topics is insufficient for the automatic generation of scientifically rigorous articles. In addition, scientists should be aware of the possible ethical and legal implications of these tools.

Effect of the high-pressure-release phase on the protein composition of the soluble milk fraction.

This paper describes a study on the influence of the high-pressure-release rate on the protein distribution between the soluble and colloidal fractions of milk. Skim milk, without or with sulfhydryl-blocking agents, was pressure treated at 250 and 350 MPa for 5 to 15 min at 25 °C, applying different pressure-release rates (pressure-release times between 0.07 to 10 min). The liberation of caseins to the soluble phase and the denaturation of whey proteins were assessed. A significantly higher increase in the content of soluble casein took place during the pressure-release phase as compared with a pressure-holding phase. Denaturation of ß-lactoglobulin mainly took place by -SH-S-S exchange reactions during the holding phase. The present results, thus, show a negligible influence of whey proteins on the increase in the content of nonsedimentable casein in pressure-treated milk and provide evidence for the importance of the pressure-release rate in this process, so that the slower the pressure release rate, the higher the level of soluble casein.

Intraocular metastasis as a systemic presentation of neuroendocrine differentiation of prostate carcinoma.

A 68 year-old male was referred for assessment of an amelanotic lesion in the right eye (RE) that was associated with a gradual loss of visual acuity (VA), of 2 months onset, as the main symptom. It was noted in his medical history, that 6 years ago, he had prostate cancer treated with prostatectomy, lymphadenectomy, and coadjuvant local radiotherapy (RT). He was asymptomatic until 6 months ago, when a metastasis was discovered in the left femur, which was treated with radiotherapy. There were no findings of interest in the left eye (LE). His AV was very low in his RE, and in the eye fundus examination a mass without pigment was observed in the posterior pole with an adjacent exudative retinal detachment. Due to his personal history and results of the complementary tests such as ultrasound and magnetic resonance, the most likely diagnostic option was metastasis of prostate carcinoma, subsequently being confirmed with the histopathology results. Despite 4 cycles of chemotherapy, the patient did not show any clinical or radiological response, worsening until his death 3 months later.

Bilateral ankyloblepharon: more than a simple malformation. / Anquilobléfaron bilateral: Algo más que una simple malformación.

"Ankyloblepharon filiforme adnatum" is a congenital anomaly characterized by partial or complete adhesion of upper and lower eyelids. The lid margins remain fused until the end of the fifth month of gestational age. Complete separation usually is completed about the seventh fetal month. Ankyloblepharon may be an isolated manifestation or may be associated with abnormalities in other organs and / or systems. The case is presented on a newborn male with family history of hypohydrotic ectodermal dysplasia (mother and maternal grandfather). It revealed extensible bands of skin in right and in left eye. Apart from this, he presented cleft lip, complete absence of palate, nail and ungueal dysplasia and supernumerary nipples.

Metastatic involvement of optic nerve in patient with breast and lung neoplasia.

Metastases are the most common adult intraocular tumors. However, those located in the optic nerve are very uncommon and are usually associated with spread to other locations such as the central nervous system, which darkens the prognosis. There is a case of a 67-year-old woman who reports progressive vision loss in the right eye of 15 days of evolution. The ophthalmological examination shows a relative afferent pupil defect in this eye and a pseudoedema of the papilla with retinal hemorrhages in the fundus. Personal history and characteristics of the optic nerve suggest the diagnosis of metastatic infiltration.

[Virulence factors and in vitro susceptibility of Plesiomonas shigelloides isolated from diarrhea episodes in Cuba]. / Caracterización de factores de virulencia y susceptibilidad antimicrobiana en cepas de Plesiomonas shigelloides aisladas de pacientes con diarrea aguda en Cuba.

Acute diarrhea is still one of the main causes of disease in developing countries. At the National Reference Laboratory for Acute Diarrhoeal Diseases, of the "Pedro Kourí" Tropical Medicine Institute, 54 Plesiomonas shigelloides strains were serotyped. As a result, the circulation of four new serotypes (O20:H2, 056:H18, 071 :H31,081 :H22) was detected. The most common antigenic variant was 094:H3. In addition, the susceptibility pattern to 21 antimicrobial agents (AA) was studied. Highest percentages of resistance were observed to ampicillin (77.7%), tetracycline (29.2%), and erythromycin (18.5%) while, to all other AA the resistance percentages were under 33%. There was no evidence of association between the serotypes and the multi-resistance patterns present in the strains under study. The frequency of virulence factors was determined: 21.15% of the strains turned out to be ss-haemolytic; 73.7% showed the presence of biofilm and 92.31% were hydrophobic. In 17.3% of the strains, the three virulence factors analysed were present. When establishing the relationship among the different virulence factors and the serotypes of the strains through cross reaction with the Shigella genus, there was evidence that 93.3% of the strains showed at least one of the virulence factors studied. Likewise, at least one of the virulence factors analysed was present in 90.9% of the multi-resistant strains.