Y Stent-Assisted Coiling Technique for Bifurcation Aneurysms Using Double Neuroform® Stent: a Large Restrospective Series.

BACKGROUND: Stent assisted coiling technique have shown to be an effective and safe endovascular strategy for wide neck bifurcation aneurysms in achieving greater packing, allowing the closure of the aneurysm and preserving the parent arteries, compared to simple coiling. MATERIAL AND METHODS: We conducted a retrospective analysis of 79 patients with cerebral aneurysms treated using 'Y'-configuration double Neuroform® stent-assisted coiling at our center from July 2009 to July 2022. RESULTS: Of the 79 patients, 76% (60/79) were incidental unruptured cerebral aneurysm and 24% were patients treated for aneurysm recanalization of a previous ruptured aneurysm (19/79). The most frequent locations were anterior communicating artery (AComA) 44.3% (35/79) and middle cerebral artery (MCA) 32.9% (26/79). We found a complete and almost complete aneurysm occlusion (Raymond-Roy occlusion classification (RROC) 1 and 2): in 100% (79/79) in the angiography after procedure, in 97.6% (42/43) at the first follow-up at 6-8 months and 100% (57/57) at the first 1-2 years of follow-up. No mortality related to treatment was detected. We registered 2.5% (2/79) major ipsilateral strokes, one due to acute in stent thrombosis (patient had a mRS: 0 in follow up at 90 days) and a spinal anterior artery occlusion (patient had a mRS: 3 in follow up at 90 days). CONCLUSION: The 'Y' stent-assisted coiling technique with double Neuroform® is a safe and effective technique for the treatment of wide-neck bifurcation aneurysms, with high rates of complete occlusion, preserving the permeability of the afferent and efferent arteries and low rate of complications.

Factors Associated With Mortality During the First Year Post Infarction: Survival Analysis of Patients With Acute Myocardial Infarction in Colombia.

INTRODUCTION: Cardiovascular diseases account for over 80% of global deaths. Risk factors and social determinants influence mortality in patients post acute myocardial infarction (AMI). OBJECTIVE: To evaluate factors associated with post-AMI mortality during the one-year follow-up. MATERIALS AND METHODS: The study is a prospective cohort study of adults aged 18 years and older with type 1 AMI conducted between October 2021 and January 2024. Intrahospital and outpatient information was collected. Statistical analyses included the Kaplan-Meier survival curve and Cox regression analysis. Proportional hazards and model predictive capacity were evaluated. RESULTS: A total of 1873 patients were included, with a 9.4% mortality rate in the first year. At one year, the estimated survival probability was 88.61% (95% CI: 86.82-90.18). Cox analysis identified several factors associated with mortality, highlighting age (HR = 1.04, 95% CI: 1.02-1.06, p = 0.001), diabetes (HR = 1.77, 95% CI: 1.09-2.87, p = 0.020), renal insufficiency (HR = 2.25, 95% CI: 1.32-3.84, p = 0.003), and type of intervention. The model evaluation showed strong predictive capacity. CONCLUSIONS: It is essential to emphasize the importance of comprehensive management in AMI patients with risk factors such as diabetes and chronic kidney disease, as they are significant predictors of mortality during the first year post infarction.

SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes.

Pancreatic ß-cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here we report that the succinate receptor (SUCNR1) is expressed in ß-cells and is up-regulated in hyperglycemic states in mice and humans. We found that succinate acts as a hormone-like metabolite and stimulates insulin secretion via a SUCNR1-Gq-PKC-dependent mechanism in human ß-cells. Mice with ß-cell-specific Sucnr1 deficiency exhibit impaired glucose tolerance and insulin secretion on a high-fat diet, indicating that SUCNR1 is essential for preserving insulin secretion in diet-induced insulin resistance. Patients with impaired glucose tolerance show an enhanced nutritional-related succinate response, which correlates with the potentiation of insulin secretion during intravenous glucose administration. These data demonstrate that the succinate/SUCNR1 axis is activated by high glucose and identify a GPCR-mediated amplifying pathway for insulin secretion relevant to the hyperinsulinemia of prediabetic states.

Time-Dependent Risk for Recurrence in Survivors of Major Adverse Cardiovascular Events.

INTRODUCTION: The prevalence of the population with a history of an occlusive cardiovascular event has been increasing in recent years, which means that a large number of patients will have a higher risk of presenting a fatal recurrence. The aim is to determine variables associated with time-to-recurrent cardiovascular events and analyze how changes in low-density lipoprotein cholesterol (LDL-C) levels during follow-up may be associated with this time-to-event. MATERIALS AND METHODS: This is a prospective observational cohort study of 727 adults with a history of at least one occlusive cardiovascular event recruited at a referral hospital in northeastern Colombia. Data from a follow-up period of a maximum of 33 months (median 26 months) (one death) were used to define how clinical and sociodemographic variables impact the recurrence of major adverse cardiovascular events (MACE). Analyses were performed based on proportional hazard models and time-dependent hazard models. RESULTS: Upon enrollment, 215 (30%) of the participants reported experiencing their most recent cardiovascular event within the preceding year. After two years, the recurrence rate was 12.38% (90/727). The risk of recurrence before two years was 3.9% (95% CI 2.7-5.6). In the multiple models, the presence of severe depression gives a Hazard Ratio of 8.25 (95% CI 2.98-22.86) and LDL ≥120 md/dl Hazard Ratio of 2.12 (95% CI 1.2 -3.9). It was found that LDL >120 mg/dl maintained over time increases the chances of recurrence by 1.7% (Hazard Ratio: 1.017, 95% CI 0.008-0.025). CONCLUSIONS: The present study allows us to identify a profile of patients who should be treated promptly in an interdisciplinary manner to avoid recurrences of coronary events.

Adaptation and Validation of the 3 × 2 Achievement Goals Questionnaire in a Population of Athletes.

(1) Background: Sport goals, although widely recognised as crucial for motivation and performance in sport, are multifaceted and can be difficult to measure directly. The present research aims to validate the 3 × 2 achievement goals questionnaire of Mascret in Spanish in a population of athletes. (2) Method: By using a latent factor approach, it is possible to identify the underlying dimensions of these goals and to better understand how they are structured. For this purpose, this questionnaire has been translated and compared with the life satisfaction scale. An exploration of the multifaceted nature of sport goals has been carried out using structural equation modelling. A total of 580 athletes (463 males and 216 females, M = 21.5, SD = 2.36) from different sport disciplines and from 12 autonomous communities in Spain participated in the research. (3) Results: The results show that the questionnaire presents a high scale reliability and that all items contribute significantly to the internal consistency of the scale. (4) Conclusions: The adaptation of this scale to the Spanish population of athletes can be a valid and useful tool to measure and understand motivation and goals in the sport context.

Implementation of a retinal stroke-code protocol results in visual recovery in patients receiving reperfusion therapies.

INTRODUCTION: Reperfusion therapies represent promising treatments for patients with Central Retinal Artery Occlusion (CRAO), but access is limited due to low incidence and lack of protocols. We aimed to describe the benefit of implementing a Retinal Stroke-Code protocol regarding access to reperfusion, visual acuity and aetiological assessment. PATIENTS AND METHODS: Prospective cohort study performed at a Comprehensive Stroke Centre. Criteria for activation were sudden monocular, painless vision loss within 6 h from onset. Eligible patients received IAT when immediately available and IVT otherwise. All patients were followed by ophthalmologists to assess best-corrected visual acuity (BCVA) and visual complications, and by neurologists for aetiological workup. Visual amelioration was defined as improvement of at least one Early Treatment Diabetic Retinopathy Study (ETDRS) letter from baseline to 1 week. RESULTS: Of 49 patients with CRAO, 15 (30.6%) received reperfusion therapies (12 IVT, 3 IAT). Presentation beyond 6 h was the main contraindication. Patients receiving reperfusion therapies had better rates of visual improvement (33.3% vs 5.9%, p = 0.022). There were no complications related to reperfusion therapies. Rates of neovascular glaucoma were non-significantly lower in patients receiving reperfusion therapies (13.3% vs 20.6%, p = 0.701). Similar rates of atherosclerotic, cardioembolic and undetermined aetiologies were observed, leading to 10 new diagnosed atrial fibrillation and five carotid revascularizations. CONCLUSION: A comprehensive acute management of CRAO is feasible despite low incidence. In our study, reperfusion therapies were safe and associated with higher rates of visual recovery. A similar etiological workup than ischemic stroke led to of high proportion of underlying aetiologies.

Mechanical thrombectomy with a new intermediate balloon catheter combining the BGC and DAC features: Initial clinical experience with the iNedit device.

INTRODUCTION: The iNedit balloon distal access catheter is a novel thrombectomy device. It has an inner diameter of 0.058″, proximal outer diameter of 2.13 mm, and distal outer diameter of 1.67mm. It is compatible with a 0.088″ guide catheter and includes a balloon located 5 cm from the catheter tip, enabling proximal flow restriction and combined therapy with stent retrievers. We investigate the appraisal of the use, safety, and efficacy of the iNedit catheter in the first-in-human study. METHODS: In the preliminary cases that demanded training on the product previous to a multicentric study, prospective data were collected on 22 consecutive patients treated with the iNedit catheter to perform thrombectomy for acute ischemic stroke due to large vessel occlusion within 24 h. The outcome measures consisted of several evaluations of user experience rated on a 5-point scale ranging from 1 (bad) to 5 (excellent), as well as assessments of procedural safety outcomes such as artery perforation and arterial occlusion, procedural efficacy outcomes including first-pass effect (Thrombolysis In Cerebral Infarction [TICI] 2c/3) and final recanalization (TICI 2b/3), and clinical efficacy outcomes such as a 3-month 0-2 modified Rankin Scale (mRS). RESULTS: The mean age was 72 ± 12 years old; median National Institute Health Stroke Scale was 17 (11-19). Sites of primary occlusion were: 2 internal carotid artery, 12 M1-MCA, 7 M2-MCA, and one P1. Median score evaluation of the appraisal of use was 4- IQR [4-5]. The median number of passes was 1 [IQR 1-2]. First pass complete recanalization rate was 50% and the final recanalization rate was 94.45%. No artery perforation and arterial occlusion. Good functional outcome mRS 0-2 was achieved in 50% of patients. CONCLUSIONS: In this initial clinical experience, iNedit device achieved a high rate of first-pass effect and final recanalization rate with no safety concerns, thus favoring a high percentage of good clinical outcomes.

miRNAs signature as potential biomarkers for cervical precancerous lesions in human papillomavirus positive women.

Biomarkers to identify women at risk of cervical cancer among those with high-risk HPV infection (hrHPV+) are needed. Deregulated expression of microRNAs (miRNAs) contributes to hrHPV-induced cervical carcinogenesis. We aimed at identifying miRNAs with the capacity to distinguish high (CIN2+) and low (≤ CIN1) grade cervical lesions. We sequenced miRNA libraries from Formalin-Fixed Paraffin-Embedded (FFPE) tissues from women with CIN2+ (n = 10) and age-matched women with ≤ CIN1 (n = 10), randomly and retrospectively selected from a trial that followed women for 24 months after a hrHPV+ test at the screening visit. Five miRNAs differentially expressed were validated by RT-qPCR in an independent set of FFPE tissues with a reviewed diagnosis of CIN2+ (n = 105) and ≤ CIN1 (n = 105). The Ingenuity Pathway Analysis (IPA) was conducted to identify mRNAs inversely correlated with the top 25 differentially expressed miRNAs. Inverse correlations with 401 unique mRNA targets were identified for fourteen of the top 25 differentially expressed miRNAs. Eleven of these miRNAs targeted 26 proteins of pathways deregulated by HPV E6 and E7 oncoproteins and two of them, miR-143-5p and miR-29a-3p, predicted CIN2+ and CIN3+ in the independent validation by RT-qPCR of FFPE tissues from hrHPV-positive women.

Identifying sustainability priorities among value chain actors in artisanal common octopus fisheries.

The United Nations (UN) Decade of Ocean Science highlights a need to improve the way in which scientific results effectively inform action and policies regarding the ocean. Our research contributes to achieving this goal by identifying practical actions, barriers, stakeholder contributions and resources required to increase the sustainability of activities carried out in the context of artisanal fisheries to meet UN Sustainable Development Goals (SDG) and International Year of Artisanal Fisheries and Aquaculture (IYAFA) Global Action Plan (GAP) Pillar targets. We conducted a novel 'social value chain analysis' via a participatory workshop to elicit perspectives of value chain actors and fisheries stakeholders associated with two Spanish artisanal common octopus (Octopus vulgaris) fisheries (western Asturias-Marine Stewardship Council [MSC] certified, and Galicia-non-MSC certified) about their priorities regarding sustainable octopus production and commercialization. Our adapted Rapfish sustainability framework emphasised the importance of economic, environmental, ethical, institutional, social, and technological indicators to different actors across the value chain. We mapped participants' shared sustainability priorities (e.g. integrated fisheries management, knowledge-based management, product traceability) to six Rapfish indicators, seven IYAFA Pillars and twelve SDGs to reveal how our results can inform ocean policy and actions. This identified how certification incentives and other cooperative approaches can facilitate environmental, economic and social sustainability (e.g. value-added products, price premiums for producers, gender inclusive organisations); support IYAFA priority outcomes (raised awareness, strengthened science-policy interface, empowered stakeholders, partnerships); and help to achieve UN SDG targets (e.g. SDG 14.b, SDG 17.17). The results can inform actors, stakeholders and policymakers about how different actors contribute to efforts to achieve the SDGs and how to manage priorities for sustainable actions within artisanal fisheries and their value chains. We recommend inclusive and equitable participatory knowledge transfer and governance platforms as part of the UN Decade of Ocean Science and beyond where participants can create theories of change towards sustainability involving the development of multi-sectoral ocean policies framed at the level of the value chain and supported by appropriate governance structures. Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-023-09768-5.

Tasa metabólica en reposo por calorimetría indirecta y ecuaciones de predicción en deportistas con amputación: Análisis de concordancia

La Tasa Metabólica en Reposo (TMR) suele calcularse utilizando ecuaciones de predicción por su fácil acceso y bajo costo. Sin embargo, estas ecuaciones no se encuentran validadas en población deportista con amputación. Objetivo: determinar la concordancia entre la medición de la TMR realizada por Calorimetría Indirecta (CI) y la calculada por ecuaciones de predicción en deportistas con amputación de miembros inferiores en Bogotá. Sujetos y métodos: Este estudio evaluó 16 deportistas adultos masculinos, con amputación de miembro inferior. La TMR se midió con CI y se calculó con las ecuaciones de predicción de Harris-Benedict, Cunningham, Mifflin -St. Jeor, Schofield y Oxford. Se utilizaron dos variables diferentes de masa corporal: masa corporal total (MCT) y masa magra (MM) determinada por Absorciometría de doble energía de rayos X (DEXA) y por el método antropométrico de fraccionamiento de masas en cinco componentes (5C). La concordancia se determinó a través del coeficiente de correlación intraclase (CCI) y se graficó mediante el método de Bland- Altman. Resultados y conclusión: La TMR determinada por la ecuación de Cunningham a partir de MM evaluada por DEXA, mostró la mejor concordancia con la CI (CCI= 0,709), seguida por Harris-Benedict con MCT (CCI= 0,697) y Cunningham con MM calculada por 5C (CCI= 0,693). La ecuación de Cunningham y Harris Benedict parecen ser las más adecuadas para calcular la TMR, sin embargo, se requieren más estudios con muestras mayores, lo cual permitirá obtener resultados más precisos.

Prediction equations for calculating resting metabolic rate (RMR) are widely used given their accessibility and low cost. However, they have not been yet validated in the amputee athlete population. Objective: to determine the concordance between the RMR measured by Indirect Calorimetry (IC) and that calculated by prediction equations in athletes with lower limb amputation in Bogota. Subjects and methods: sixteen adult male athletes with lower limb amputation were included. The RMR was measured with IC and calculated with the Harris-Benedict, Cunningham, Mifflin-St. Jeor, Schofield, and Oxford prediction equations. Three different body mass variables were used: total body mass (TBM) and lean body mass (LBM) determined by Dual Energy X-ray Absorptiometry (DEXA) and by the anthropometric method of mass fractionation into five components (5C). The agreement was determined by intraclass correlation coefficient (ICC) and plotted using the Bland-Altman method. Results and conclusions: RMR determined by the Cunningham equation from LBM assessed by DEXA showed the best agreement with CI (ICC= 0.709), followed by Harris-Benedict with MCT (ICC= 0.697) and Cunningham with LBM calculated by 5C (ICC= 0.693). The Cunningham and Harris-Benedict equation seems to be the most suitable for calculating RMR. However, more studies with larger samples are needed to obtain more accurate results.

Establishment of a reproducible and minimally invasive ischemic stroke model in swine.

The need for advances in the management/treatment options for ischemic stroke patients requires that upcoming preclinical research uses animals with more human-like brain characteristics. The porcine brain is considered appropriate, although the presence of the rete mirabile (RM) prevents direct catheterization of the intracranial arteries to produce focal cerebral ischemia. To develop a reproducible minimally invasive porcine stroke model, a guide catheter and guide wire were introduced through the femoral artery until reaching the left RM. Using the pressure cooker technique, Squid-12 embolization material was deposited to fill, overflow, and occlude the left RM, the left internal carotid artery, and left circle of Willis wing up to the origins of the middle cerebral arteries (MCAs), mimicking the occlusion produced in the filament model in rodents. Longitudinal multimodal cerebral MRI was conducted to assess the brain damage and cerebral blood supply. The technique we describe here occluded up to the origins of the MCAs in 7 of 8 swine, inducing early damage 90 minutes after occlusion that later evolved to a large cerebral infarction and producing no mortality during the intervention. This minimally invasive ischemic stroke model in swine produced reproducible infarcts and shows translational features common to human stroke.

An Overview of Inter-Tissue and Inter-Kingdom Communication Mediated by Extracellular Vesicles in the Regulation of Mammalian Metabolism.

Obesity and type 2 diabetes are associated with defects of insulin action in different tissues or alterations in ß-cell secretory capacity that may be triggered by environmental challenges, inadequate lifestyle choices, or an underlying genetic predisposition. In addition, recent data shows that obesity may also be caused by perturbations of the gut microbiota, which then affect metabolic function and energy homeostasis in the host. Maintenance of metabolic homeostasis in complex organisms such as mammals requires organismal-level communication, including between the different organs and the gut microbiota. Extracellular vesicles (EVs) have been identified in all domains of life and have emerged as crucial players in inter-organ and inter-kingdom crosstalk. Interestingly, EVs found in edible vegetables or in milk have been shown to influence gut microbiota or tissue function in mammals. Moreover, there is a multidirectional crosstalk mediated by EVs derived from gut microbiota and body organs that has implications for host health. Untangling this complex signaling network may help implement novel therapies for the treatment of metabolic disease.

Derivo embolization device for intracranial aneurysms: a Spanish multicenter retrospective study.

BACKGROUND: Flow diverters have emerged in recent years as a safe and effective treatment for intracranial aneurysms, with expanding indications. The Derivo embolization device (DED) is a second-generation flow diverter with a surface finish that may reduce thrombogenicity. We report our multicenter experience evaluating its safety and efficacy. METHODS: We retrospectively analyzed all patients treated with the DED in eight centers in Spain between 2016 and 2020. Demographics, clinical data, procedural complications, morbidity and aneurysm occlusion rates were collected. RESULTS: A total of 209 patients with 250 aneurysms were treated (77.5% women). The majority of aneurysms were located in the internal carotid artery (86.8%) and most (69.2%) were small (<10 mm) with a median maximum diameter of 5.85 mm and median neck size of 4 mm. DED deployment was successful in all cases, despite two malfunctioning devices (1%). Major complications occurred in nine patients (4.3%), while mild neurologic clinical events were registered in 23 (11%); four patients died (1.9%). A total of 194 aneurysms had an angiographic follow-up at 6 months and showed complete aneurysm occlusion in 75% of cases. Twelve-month follow-up was available for 112 of the treated aneurysms, with a total occlusion rate of 83%. CONCLUSION: The DED is a second-generation surface-modified flow diverter that presents an option for treatment of intracranial aneurysms with comparable safety and efficacy to other available flow diverter devices. Nonetheless, risks are not negligible, and must be balanced against the natural history risk of cerebral aneurysms, considering the tendency to widen indications for treatment of smaller and less complex lesions in day-to-day use.

First pass effect in posterior circulation occlusions: Analysis from the CICAT registry.

BACKGROUND: The first pass effect (FPE) is an independent predictor of functional independence in patients with large vessel occlusion in anterior circulation ischemic strokes. However, whether it predicts outcome in posterior circulation large vessel occlusion (PC-LVO) is uncertain. We aimed to study the frequency, characteristics, and predictors of FPE and its association with clinical outcomes in PC-LVO. METHOD: We performed an analysis from the prospective CICAT Registry. All patients with PC-LVO who underwent endovascular therapy between January 2016 and January 2020 were included. A centrally assessed clinical follow-up was performed at 3 months by blinded investigators. FPE was defined as the achievement of modified Thrombolysis In Cerebral Infarction 3 in a single pass of the endovascular thrombectomy device, and multi-pass effect (MPE) if it was achieved in more than one pass. A multivariable analysis was performed to identify whether FPE is an independent predictor of functional independence defined as a modified Rankin Score of 0-2. RESULTS: We analyzed data from 265 patients in who FPE was achieved in 105 (39.6%). Patients with FPE were more likely to achieve functional independence compared to the non-FPE group (52.4% vs 25.1%, p < .001) and the MPE group (52.4% vs 26.7%, p < .001). FPE was independently associated with functional independence (adjusted odds ratio (aOR): 2.10, 95% confidence interval (CI) 1.01-4.37) but MPE was not (aOR: 0.92, 95% CI 0.40-2.13). Independent predictors of FPE were the use of direct aspiration, embolic mechanism of stroke, and the absence of general anesthesia (GA) use. CONCLUSIONS: FPE is an independent predictor of functional independence in PC-LVO and was associated with a significantly better outcome than MPE.

Early and Delayed Infarct Growth in Patients Undergoing Mechanical Thrombectomy: A Prospective, Serial MRI Study.

BACKGROUND: We studied the evolution over time of diffusion weighted imaging (DWI) lesion volume and the factors involved on early and late infarct growth (EIG and LIG) in stroke patients undergoing endovascular treatment (EVT) according to the final revascularization grade. METHODS: This is a prospective cohort of patients with anterior large artery occlusion undergoing EVT arriving at 1 comprehensive stroke center. Magnetic resonance imaging was performed on arrival (pre-EVT), <2 hours after EVT (post-EVT), and on day 5. DWI lesions and perfusion maps were evaluated. Arterial revascularization was assessed according to the modified Thrombolysis in Cerebral Infarction (mTICI) grades. We recorded National Institutes of Health Stroke Scale at arrival and at day 7. EIG was defined as (DWI volume post-EVT-DWI volume pre-EVT), and LIG was defined as (DWI volume at 5d-DWI volume post-EVT). Factors involved in EIG and LIG were tested via multivariable lineal models. RESULTS: We included 98 patients (mean age 70, median National Institutes of Health Stroke Scale score 17, final mTICI≥2b 86%). Median EIG and LIG were 48 and 63.3 mL in patients with final mTICI<2b, and 3.6 and 3.9 cc in patients with final mTICI≥2b. Both EIG and LIG were associated with higher National Institutes of Health Stroke Scale at day 7 (ρ=0.667; P<0.01 and ρ=0.614; P<0.01, respectively). In patients with final mTICI≥2b, each 10% increase in the volume of DWI pre-EVT and each extra pass leaded to growths of 9% (95% CI, 7%-10%) and 14% (95% CI, 2%-28%) in the DWI volume post-EVT, respectively. Furthermore, each 10% increase in the volume of DWI post-EVT, each extra pass, and each 10 mL increase in TMax6s post-EVT were associated with growths of 8% (95% CI, 6%-9%), 9% (95% CI, 0%-19%), and 12% (95% CI, 5%-20%) in the volume of DWI post-EVT, respectively. CONCLUSIONS: Infarct grows during and after EVT, especially in nonrecanalizers but also to a lesser extent in recanalizers. In recanalizers, number of passes and DWI volume influence EIG, while number of passes, DWI, and hypoperfused volume after the procedure determine LIG.

Treatment with EV-miRNAs Alleviates Obesity-Associated Metabolic Dysfunction in Mice.

Most cells release extracellular vesicles (EVs) that can be detected circulating in blood. We and others have shown that the microRNA contents of these vesicles induce transcriptomic changes in acceptor cells, contributing to the adjustment of metabolic homeostasis in response to environmental demands. Here, we explore the potential for modulating obesity- and exercise-derived EV-microRNAs to treat the metabolic dysfunction associated with obesity in mice. Treatment with EV-miRNAs alleviated glucose intolerance and insulin resistance in obese mice to an extent similar to that of high-intensity interval training, although only exercise improved cardiorespiratory fitness and decreased body weight. Mechanistically, EV-miRNAs decreased fatty acid and cholesterol biosynthesis pathways in the liver, reducing hepatic steatosis and increasing insulin sensitivity, resulting in decreased glycemia and triglyceridemia. Our data suggest that manipulation of EV-miRNAs may be a viable strategy to alleviate metabolic dysfunction in obese and diabetic patients who are unable to exercise, although actual physical activity is needed to improve cardiorespiratory fitness.

Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue.

Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, proteomic, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most obesity and overnutrition-related pathological features were successfully reverted, we observed a high degree of metabolic dysfunction in visceral white adipose tissue, characterized by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and an apparent global healthy phenotype, obesity triggered a cascade of events in visceral adipose tissue progressing from mitochondrial metabolic and proteostatic alterations to widespread cellular stress, which compromises its biosynthetic and recycling capacity. In humans, weight loss after bariatric surgery showed a transcriptional signature in visceral adipose tissue similar to our mouse model of obesity reversion. Overall, our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in visceral adipose tissue.

Educación ambiental mediada desde las ecologías sociocuturales para el abordaje del territorio en contextos escolares / Environmental education mediated from socio-cultural ecologies for the approach to territory in school contexts

RESUMEN Desde la perspectiva de las ecologías socioculturales, como campo emergente interdisciplinario, se puede enriquecer de manera alternativa y complementaria la educación ambiental, puesto que permite un acercamiento comprensivo a las dinámicas de ocupación humana y las transformaciones en un territorio concreto desde una mirada histórica, política y sociocultural. Esta investigación, se llevó a cabo en el contexto territorial de la cuenca del río Quindío, en el centro-occidente de Colombia, con la participación de 144 estudiantes y 40 docentes, de cuatro Instituciones Educativas públicas. La metodología fue de enfoque cualitativo, donde se empleó como instrumento de recolección y análisis de información, una encuesta tipo cuestionario con preguntas abiertas, para indagar aspectos socioambientales, históricos y paisajísticos del contexto territorial de dicha cuenca. Los resultados develaron que estudiantes y docentes, en general, desconocen los procesos históricos de ocupación humana de la región; con relación a los principales cambios percibidos en el paisaje, los estudiantes señalaron el incremento de las urbanizaciones, la disminución de las zonas verdes y la contaminación, mientras que los docentes manifestaron cambios en los usos del suelo, el crecimiento urbanístico y el desarrollo basado en el turismo. Sin duda, estos hallazgos son importantes, como lectura del territorio, para ser tenidos en cuenta en la praxis de la educación ambiental de las instituciones educativas.

ABSTRACT From the perspective of socio-cultural ecologies as an emerging interdisciplinary field, environmental education can be enriched in an alternative and complementary way since they allow a comprehensive approach to the dynamics of human occupation and transformations in a specific territory from a historical perspective, political and socio-cultural. This research was carried out in the territorial context of the Quindío River basin in central-western Colombia, with the participation of 144 students and 40 teachers from four public educational institutions. The methodology was a qualitative approach, where a questionnaire-type survey with open questions was used as an instrument for collecting and analyzing information to investigate socio-environmental, historical, and landscape aspects of the territorial context of said basin. The results revealed that students and teachers, in general, are unaware of the historical processes of human occupation of the region; Concerning the main changes perceived in the landscape, the students pointed out the increase in urbanizations, the decrease in green areas, and pollution; while teachers expressed changes in land use, urban growth, and development based on tourism. Undoubtedly, these findings are important as a reading of the territory to be considered in the praxis of environmental education in educational institutions.

Central and Peripheral Immune Dysregulation in Posttraumatic Stress Disorder: Convergent Multi-Omics Evidence.

Posttraumatic stress disorder (PTSD) is a chronic and multifactorial disorder with a prevalence ranging between 6-10% in the general population and ~35% in individuals with high lifetime trauma exposure. Growing evidence indicates that the immune system may contribute to the etiology of PTSD, suggesting the inflammatory dysregulation as a hallmark feature of PTSD. However, the potential interplay between the central and peripheral immune system, as well as the biological mechanisms underlying this dysregulation remain poorly understood. The activation of the HPA axis after trauma exposure and the subsequent activation of the inflammatory system mediated by glucocorticoids is the most common mechanism that orchestrates an exacerbated immunological response in PTSD. Recent high-throughput analyses in peripheral and brain tissue from both humans with and animal models of PTSD have found that changes in gene regulation via epigenetic alterations may participate in the impaired inflammatory signaling in PTSD. The goal of this review is to assess the role of the inflammatory system in PTSD across tissue and species, with a particular focus on the genomics, transcriptomics, epigenomics, and proteomics domains. We conducted an integrative multi-omics approach identifying TNF (Tumor Necrosis Factor) signaling, interleukins, chemokines, Toll-like receptors and glucocorticoids among the common dysregulated pathways in both central and peripheral immune systems in PTSD and propose potential novel drug targets for PTSD treatment.

Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial.

Importance: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits. Objective: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion. Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3. Interventions: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52). Main Outcomes and Measures: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death. Results: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication. Trial Registration: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40.