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OBJECTIVE: To generate normative data for the Verbal Fluency Test (VFT) and the Boston Naming Test (BNT) in the Costa Rican population. METHOD: The sample consisted of 563 healthy older people (aged 59-90 years). Polynomial multiple regression analyses were run to evaluate the effects of the age, sex, and education variables on VFT and BNT scores. RESULTS: The results showed a significant linear effect of education on the four-letter VF scores and an effect of sex on the letter P score, with females performing better than males. The explained variance ranged from 20.9% to 28.3%. A linear effect of age and education was also found for the four semantic VF scores, with scores decreasing with increasing age and lower education. The sex variable was significant for all semantic categories, with females performing better than males except in the animal category. The explained variance ranged from 21.7% to 30.9%. In the BNT, a linear effect of education was found, so that the more education, the better the score. In addition, a sex effect was also found, with males having higher scores than females. The predictors of the model explained 9.6% of the variance. CONCLUSIONS: This is the first study that generates normative data for the VF and BNT in the Costa Rican population over 59 years of age based on demographic variables. The use of these normative data will help clinicians in Costa Rica to better understand language functioning in the elderly, allowing for better classification and diagnosis in the future.

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Mesenchymal stem cells (MSCs) are used in cell therapy; nonetheless, their application is limited by their poor survival after transplantation in a proinflammatory microenvironment. Macroautophagy/autophagy activation in MSCs constitutes a stress adaptation pathway, promoting cellular homeostasis. Our proteomics data indicate that RUBCNL/PACER (RUN and cysteine rich domain containing beclin 1 interacting protein like), a positive regulator of autophagy, is also involved in cell death. Hence, we screened MSC survival upon various cell death stimuli under loss or gain of function of RUBCNL. MSCs were protected from TNF (tumor necrosis factor)-induced regulated cell death when RUBCNL was expressed. TNF promotes inflammation by inducing RIPK1 kinase-dependent apoptosis or necroptosis. We determine that MSCs succumb to RIPK1 kinase-dependent apoptosis upon TNF sensing and necroptosis when caspases are inactivated. We show that RUBCNL is a negative regulator of both RIPK1-dependent apoptosis and necroptosis. Furthermore, RUBCNL mutants that lose the ability to regulate autophagy, retain their function in negatively regulating cell death. We also found that RUBCNL forms a complex with RIPK1, which disassembles in response to TNF. In line with this finding, RUBCNL expression limits assembly of RIPK1-TNFRSF1A/TNFR1 complex I, suggesting that complex formation between RUBCNL and RIPK1 represses TNF signaling. These results provide new insights into the crosstalk between the RIPK1-mediated cell death and autophagy machineries and suggest that RUBCNL, due to its functional duality in autophagy and apoptosis/necroptosis, could be targeted to improve the therapeutic efficacy of MSCs. Abbreviations: BAF: bafilomycin A1; CASP3: caspase 3; Caspases: cysteine-aspartic proteases; cCASP3: cleaved CASP3; CQ: chloroquine; CHX: cycloheximide; cPARP: cleaved poly (ADP-ribose) polymerase; DEPs: differential expressed proteins; ETO: etoposide; MEF: mouse embryonic fibroblast; MLKL: mixed lineage kinase domain-like; MSC: mesenchymal stem cell; MTORC1: mechanistic target of rapamycin kinase complex 1; Nec1s: necrostatin 1s; NFKB/NF-kB: nuclear factor of kappa light polypeptide gene enhancer in B cells; PLA: proximity ligation assay; RCD: regulated cell death; RIPK1: receptor (TNFRSF)-interacting serine-threonine kinase 1; RIPK3: receptor-interacting serine-threonine kinase 3; RUBCNL/PACER: RUN and cysteine rich domain containing beclin 1 interacting protein like; siCtrl: small interfering RNA nonsense; siRNA: small interfering RNA; TdT: terminal deoxynucleotidyl transferase; Tm: tunicamycin; TNF: tumor necrosis factor; TNFRSF1A/TNFR1: tumor necrosis factor receptor superfamily, member 1a.

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Parkinson's disease (PD) is the second most common late-onset neurodegenerative disease and the predominant cause of movement problems. PD is characterized by motor control impairment by extensive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). This selective dopaminergic neuronal loss is in part triggered by intracellular protein inclusions called Lewy bodies, which are composed mainly of misfolded alpha-synuclein (α-syn) protein. We previously reported insulin-like growth factor 2 (IGF2) as a key protein downregulated in PD patients. Here we demonstrated that IGF2 treatment or IGF2 overexpression reduced the α-syn aggregates and their toxicity by IGF2 receptor (IGF2R) activation in cellular PD models. Also, we observed IGF2 and its interaction with IGF2R enhance the α-syn secretion. To determine the possible IGF2 neuroprotective effect in vivo we used a gene therapy approach in an idiopathic PD model based on α-syn preformed fibrils intracerebral injection. IGF2 gene therapy revealed a significantly preventing of motor impairment in idiopathic PD model. Moreover, IGF2 expression prevents dopaminergic neuronal loss in the SN together with a decrease in α-syn accumulation (phospho-α-syn levels) in the striatum and SN brain region. Furthermore, the IGF2 neuroprotective effect was associated with the prevention of synaptic spines loss in dopaminergic neurons in vivo. The possible mechanism of IGF2 in cell survival effect could be associated with the decrease of the intracellular accumulation of α-syn and the improvement of dopaminergic synaptic function. Our results identify to IGF2 as a relevant factor for the prevention of α-syn toxicity in both in vitro and preclinical PD models.

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Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by protein accumulation in the brain as a main neuropathological hallmark. Among them, Aß42 peptides tend to aggregate and create oligomers and plaques. Macroautophagy, a form of autophagy characterized by a double-membrane vesicle, plays a crucial role in maintaining neuronal homeostasis by degrading protein aggregates and dysfunctional organelles as a quality control process. Recently, DEF8, a relatively uncharacterized protein, has been proposed as a participant in vesicular traffic and autophagy pathways. We have reported increased DEF8 levels in lymphocytes from mild cognitive impairment (MCI) and early-stage AD patients and a neuronal profile in a murine transgenic AD model. Here, we analyzed DEF8 localization and levels in the postmortem frontal cortex of AD patients, finding increased levels compared to healthy controls. To evaluate the potential function of DEF8 in the nervous system, we performed an in silico assessment of its expression and network profiles, followed by an in vivo evaluation of a neuronal Def8 deficient model using a Drosophila melanogaster model of AD based on Aß42 expression. Our findings show that DEF8 is an essential protein for maintaining cellular homeostasis in the nervous system, and it is upregulated under stress conditions generated by Aß42 aggregation. This study suggests DEF8 as a novel actor in the physiopathology of AD, and its exploration may lead to new treatment avenues.

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Objective: This study aimed to evaluate the psychometric properties of the Alexian Brother Urge to Self-Injure (ABUSI) in its Spanish version for Colombian adolescents. This instrument was created to measure cognitive and emotional aspects of the urge to self-injure by assessing the frequency, the urge, thoughts associated with time and place, the capacity for resistance, and thoughts associated with the urge to self-injure. Method: A total of 752 preadolescents and adolescents between 10 and 18 years of age, with a mean of 15.3 years (SD = 1.97), participated. The instruments used were The Alexian Brother Urge to Self-Injure ABUSI, ERS Suicide Risk Scale, Plutchik Suicide Risk Scale, and the Zimet The MSPSS Perceived Social Support Scale. Confirmatory factor analysis, inter-test correlations, to estimate cut-off point discriminant validity Receiver Operating Characteristics (ROC) and to determine convergent validity, a Pearson's coincidence analysis was performed between the ABUSI total score and the ERS Suicide Risk Scale, the Plutchik's Suicide Risk Scale and Zimet's Perceived Social Support Scale assessments. Results: The presence of a unidimensional model of the instrument is confirmed with adequate fit, reliability, and concurrent validity indices. The high score classification was determined from six (6) points for the total of the scale. These results show that ABUSI is a valid and reliable tool for the clinical assessment of self-injurious behavior in adolescents and preadolescents.

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BACKGROUND: Verbal fluency tests (VFT) are highly sensitive to cognitive deficits. Usually, the score on VFT is based on the number of correct words produced, yet it alone gives little information regarding underlying test performance. The implementation of different strategies (cluster and switching) to perform efficiently during the tasks provide more valuable information. However, normative data for clustering and switching strategies are scarce. Moreover, scoring criteria adapted to Colombian Spanish are missing. AIMS: (1) To describe the Colombian adaptation of the scoring system guidelines for clustering and switching strategies in VFT; (2) to determine its reliability; and (3) to provide normative data for Colombian children and adolescents aged 6-17 years. METHODS & PROCEDURES: A total of 691 children and adolescents from Colombia completed phonological (/f/, /a/, /s/, /m/, /r/ and /p/) and semantic (animals and fruits) VFT, and five scores were calculated: total score (TS), number of clusters (NC), cluster size (CS), mean cluster size (MCS) and number of switches (NS). The intraclass correlation coefficient was used for interrater reliability. Hierarchical multiple regressions were conducted to investigate which strategies were associated with VFT TS. Multiple regressions were conducted for each strategy, including as predictors age, age2 , sex, mean parents' education (MPE), MPE2 and type of school, to generate normative data. OUTCOMES & RESULTS: Reliability indexes were excellent. Age was associated with VFT TS, but weakly compared with strategies. For both VFT TS, NS was the strongest variable, followed by CS and NC. Regarding norms, age was the strongest predictor for all measures, while age2 was relevant for NC (/f/ phoneme) and NS (/m/ phoneme). Participants with higher MPE obtained more NC, and NS, and larger CS in several phonemes and categories. Children and adolescents from private school generated more NC, NS and larger CS in /s/ phoneme. CONCLUSIONS & IMPLICATIONS: This study provides new scoring guidelines and normative data for clustering and switching strategies for Colombian children and adolescents between 6 and 17 years old. Clinical neuropsychologists should include these measures as part of their everyday practice. WHAT THIS PAPER ADDS: What is already known on the subject VFT are widely used within the paediatric population due to its sensitivity to brain injury. Its score is based on the number of correct words produced; however, TS alone gives little information regarding underlying test performance. Several normative data for VFT TS in the paediatric population exist, but normative data for clustering and switching strategies are scarce. What this paper adds to existing knowledge The present study is the first to describe the Colombian adaptation of the scoring guidelines for clustering and switching strategies, and provided normative data for these strategies for children and adolescents between 6 and 17 years old. What are the potential or actual clinical implications of this work? Knowing VFT's performance, including strategy development and use in healthy children and adolescents, may be useful for clinical settings. We encourage clinicians to include not only TS, but also a careful analysis of strategies that may be more informative of the underlying cognitive processes failure than TS.

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RESUMEN Introducción : El Centro para el Control y Prevención de Enfermedades (CDC) define el suicidio como el acto de autoagresión con la intención de causar la muerte propia de manera voluntaria. En pueblos indígenas de países como Canadá, Australia, Groenlandia, Estados Unidos, Nueva Zelanda, Brasil y Siberia, se evidencia que este evento sucede con mayor frecuencia que en la población general, principalmente como consecuencia del colonialismo y las dificultades que enfrentan las comunidades indígenas, factores que se citan hoy como comunes a nivel mundial. Método : Estudio cuantitativo, descriptivo y retrospectivo en el que se analizaron 48 casos de suicidios de indígenas del suroccidente colombiano, ocurridos durante el período de prepandemia (2018-2019) y pandemia de la COVID-19 (2020-2021), registrados en el Instituto Nacional de Medicina Legal y Ciencias Forenses (INMLYCF) de los departamentos de Valle del Cauca, Cauca y Nariño. Resultados : En la región estudiada se suicidaron más personas durante el período pandémico (2020-2021). Las víctimas fueron, predominantemente, individuos del sexo masculino, de edad joven (entre 19 y 26 años), con estudios de primaria y bachillerato, que tenían ocupación de agricultores o estudiantes, que usaron el ahorcamiento como modalidad principal para acabar con su vida, y cuya razón de suicidio más frecuente era el conflicto con la pareja o expareja. Conclusiones : La tasa de suicidio en indígenas en el Valle del Cauca, Cauca y Nariño fue más alta que la registrada en la población general de los mismos departamentos durante la pandemia de la COVID-19 (2020-2021). Es necesario considerar factores socioculturales y trayectorias del evento suicida en el seno de cada comunidad distintivamente estudiada.

ABSTRACT Introduction : The Center for Disease Control and Prevention (CDC) defines suicide as an act of self-harm with the intent to cause a voluntary death. In indigenous peoples from countries such as Canada, Australia, Greenland, the United States, New Zealand, Brazil and Siberia, it is evident that this event occurs more frequently than in the general population, mainly as a consequence of colonialism and difficulties faced by indigenous communities, factors that are now considered as common throughout the world. Methods : A retrospective, descriptive, quantitative and retrospective study that analyzes 48 cases of suicide in indigenous people from Southwestern Colombia during the COVID-19 pre-pandemic (2018-2019) and pandemic (2020-2021) periods and registered in the National Institute of Legal Medicine and Forensic Sciences of the departments of Valle del Cauca, Cauca and Nariño. Results : In the studied region more people committed suicide during the pandemic period (2020-2021). The victims were, predominantly, males of young ages (between 19 and 26 years), with a primary and high school educational level, of primary and high school, with farmer or student occupations, use of hanging as the main modality, and conflict with partner or ex-partner as the most frequently cited reason. Conclusions : The suicide rate among indigenous people in the departments of Cauca Valley, Cauca and Nariño was higher than that recorded in the general population of the same departments during the COVID-19 pandemic (2020-2021). It is necessary to consider sociocultural factors and the trajectories of the suicide event within each distinctly studied community.

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BACKGROUND AND AIMS: Cardiometabolic diseases refer to a group of interrelated conditions, sharing metabolic dysfunctions like insulin resistance, obesity, dyslipidemia, and hypertension. The gut microbiota has been associated with CMD and related conditions. Alterations in the intestinal epithelium permeability triggered by chronic stress and diet could bridge gut microbiota with inflammation and CMD development. Here, we assessed the relationship between intestinal permeability and circulating SCFAs with cardiometabolic health status (CMHS) and gut microbiota in a sample of 116 Colombian adults. METHODS AND RESULTS: Plasma levels of lipopolysaccharide-binding protein (LBP), intestinal fatty acid-binding protein (I-FABP), claudin-3, and purported zonulin peptides (PZP) were measured by ELISA, whereas plasmatic levels of acetate, propionate, butyrate, isobutyrate, and valerate were measured by gas chromatography/mass spectrometry. In addition, for further statistical analysis, we took data previously published by us on this cohort, including gut microbiota and multiple CMD risk factors that served to categorize subjects as cardiometabolically healthy or cardiometabolically abnormal. From univariate and multivariate statistical analyses, we found the levels of I-FABP, LBP, and PZP increased in the plasma of cardiometabolically abnormal individuals, although only PZP reached statistical significance. CONCLUSIONS: Our results did not confirm the applicability of I-FABP, LBP, claudin-3, or SCFAs as biomarkers for associating intestinal permeability with the cardiometabolic health status in these subjects. On the other hand, the poorly characterized peptides detected with the ELISA kit branded as "zonulin" were inversely associated with cardiometabolic dysfunctions and gut microbiota. Further studies to confirm the true identity of these peptides are warranted.

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The concept of "politics of the end" assumes the catastrophe of living in a world that produces new forms of accumulation and allows symbolic and semiotic capital to create value. Currently, various far-right movements worldwide seem to appropriate this concept, employing radical communication strategies as a repertoire to contest the public agenda. These strategies include the massive creation of bots on social networks to spread hate speech and coordinate ideological manifestations. This article seeks to verify the use of these strategies by the Chilean far-right on Twitter. For the above, a social network analysis approach is proposed during the current socio-political crisis in Chile, which began with the massive protests of October 2019 and led to an unprecedented constituent process. For nine months, we studied five opinion leaders on Twitter from the Chilean far-right, who together have more than 600 thousand followers and almost 130 thousand followings. Through descriptive, quantitative, and qualitative techniques, an explicit political action "from the resistance" is revealed in the activity of the network, which includes hundreds of new users and coordinated bots to disseminate identifiable discourses with strongly ideological ideas. This coordination also presents identifiable differences in how opinion leaders interact and communicate with their network environment.

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Hypoglycemic encephalopathy constitutes a critical presentation of severely diminished glucose levels. We present the case of a 53-year-old male patient with a history of diabetes mellitus with hypoglycemic encephalopathy and MRI findings of bilateral middle cerebellar peduncle lesions. Common findings of hypoglycemic encephalopathy described in the literature consist of bilateral compromise of the cerebral cortex, basal ganglia, hippocampus, and long tracts of white matter. The cerebellum and brainstem are usually not affected. This is the ninth report of cerebellar peduncle compromise with hypoglycemia. As increasing evidence regarding prognosis estimation of lesion distribution arises, we consider it important to report the different cases of rare patterns of compromise.