Argentina-Alzheimer's Disease Neuroimaging Initiative: pioneering Alzheimer's Research in Latin America and its Implications for Regional Advancement.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) has fostered collaboration among researchers around the world, catalyzing innovation and accelerating progress in the field. In Latin America, this initiative advanced the validation and development of Alzheimer's disease biomarkers for the first time in our region. In 2011, as part of the international ADNI, Argentina-ADNI (Arg-ADNI) was founded. The following years were characterized by strong support from entities such as the Alzheimer's Association, transforming into the emergence of several multinational studies focusing on prevention and diagnosis, and treatment of dementias. These studies are heirs to the tradition of Arg-ADNI: the Dominantly Inherited Alzheimer Network, Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline, Longitudinal Early-Onset Alzheimer's Disease Study, and Initiative for the Study of Down Syndrome and Alzheimer's Disease. These initiatives have contributed significantly to the development of regional research and serve as essential tools for health policy planning in Latin America. HIGHLIGHTS: In Latin America, the Alzheimer's Disease Neuroimaging Initiative (ADNI) advanced the validation and development of Alzheimer's disease biomarkers for the first time in our region. ADNI has been the basis that boosted several multinational studies focusing on both prevention and diagnosis, and treatment of dementias (Dominantly Inherited Alzheimer Network, LatAm-FINGER, LEADS). These initiatives with the support from the Alzheimer's Association have contributed significantly to the development of regional research This is an example of collaboration between high-income countries with low- and middle-income countries aimed at global scientific development and inclusion.

Efectos de la pandemia por COVID-19 en la atención de pacientes con diabetes mellitus, Partido de General Pueyrredon, Argentina / Efectos de la pandemia por COVID-19 en la atención de pacientes con diabetes mellitus, Partido de General Pueyrredon, Argentina

INTRODUCCIÓN: La pandemia por COVID-19 condujo a la adopción de medidas de confinamiento con impacto en el control de la diabetes mellitus (DM). El objetivo fue evaluar el efecto de la pandemia en la atención de personas con DM del subsector público y privado de salud del Partido de General Pueyrredon (PGP). MÉTODOS: Se utilizó un diseño cuasiexperimental que comparó dos períodos: pandemia (3 de marzo de 2020 al 2 de marzo de 2021) y prepandemia (3 de marzo de 2019 al 2 de marzo de 2020). Se incluyó a personas de 18 años y más del PGP con diagnóstico de DM; se conformaron dos grupos según cobertura de salud. Los criterios de valoración principal fueron la hemoglobina glicosilada (HbA1c) y el control metabólico; los secundarios: glucemia basal, índice de masa corporal (IMC), triglicéridos, colesterol, consultas médicas, internación, fondo de ojo e índice albúmina/creatinina. Las diferencias con valor p<0,05 se consideraron estadísticamente significativas. Se ajustaron modelos multivariados. RESULTADOS: Se incluyeron 327 participantes (51,7% del subsector público). La mediana de HbA1c aumentó de 8,1% (rango intercuartílico [RIC] 2,7) a 8,8% (RIC 2,8). La pandemia, la atención en el subsector público y el tratamiento incompleto de la DM fueron predictores independientes del aumento de HbA1c; en tanto que el tratamiento con insulina lo fue del deterioro del control glucémico. DISCUSIÓN: La pandemia impactó negativamente en la atención de la DM, evidenciando desigualdades en los subsectores del sistema de salud.

Effectiveness of cognitive rehabilitation on mild cognitive impairment using teleneuropsychology.

The COVID-19 pandemic has affected the continuity of cognitive rehabilitation worldwide. However, the use of teleneuropsychology to provide cognitive rehabilitation has contributed significantly to the continuity of the treatment. Objectives: To measure the effects of cognitive telerehabilitation on cognition, neuropsychiatric symptoms, and memory strategies in a cohort of patients with mild cognitive impairment. Methods: A sample of 60 patients with mild cognitive impairment according to Petersen's criteria was randomly divided into two groups: 30 treatment cases and 30 controls (waiting list group). Subjects were matched by age, sex, and Montreal Cognitive Assessment. The treatment group received ten cognitive telerehabilitation sessions of 45 minutes duration once a week. Pre-treatment (week 0) and post-treatment (week 10) measures were assessed for both groups. Different linear mixed models were estimated to test treatment effect (cognitive telerehabilitation vs. controls) on each outcome of interest over time (pre/post-intervention). Results: A significant group (control/treatment) x time (pre/post) interaction revealed that the treatment group at week 10 had better scores in cognitive variables: memory (RAVLT learning trials p=0.030; RAVLT delayed recall p=0.029), phonological fluency (p=0.001), activities of daily living (FAQ p=0.001), satisfaction with memory performance (MMQ satisfaction p=0.004) and use of memory strategies (MMQ strategy p=0.000), as well as, and a significant reduction of affective symptomatology: depression (GDS p=0.000), neuropsychiatric symptoms (NPI-Q p=0.045), forgetfulness (EDO-10 p=0.000), and stress (DAS stress p=0.000). Conclusions: Our study suggests that CTR is an effective intervention.

A pandemia do COVID-19 afetou a continuidade da reabilitação cognitiva em todo o mundo. No entanto, o uso de tele neuropsicologia para a reabilitação cognitiva tem contribuído significativamente para a continuidade do tratamento. Objetivos: Medir os efeitos da tele reabilitação cognitiva na cognição, nos sintomas neuropsiquiátricos e nas estratégias de memória em uma coorte de pacientes com comprometimento cognitivo leve. Métodos: Uma amostra de 60 pacientes com comprometimento cognitivo leve de acordo com os critérios de Petersen foi dividida aleatoriamente em dois grupos: 30 casos de tratamento e 30 controles (grupo de lista de espera). Os assuntos foram pareados por idade, sexo e Avaliação Cognitiva de Montreal. O grupo de tratamento recebeu dez sessões de tele reabilitação cognitiva de 45 minutos de duração uma vez por semana. As medidas pré-tratamento (semana 0) e pós-tratamento (semana 10) foram avaliadas para ambos os grupos. Diferentes modelos lineares mistos foram estimados para testar o efeito do tratamento (tele reabilitação cognitiva vs. controles) em cada desfecho de interesse ao longo do tempo (pré-/pós-intervenção). Resultados: Uma interação significativa grupo (controle/tratamento) x tempo (pré/pós) revelou que o grupo de tratamento teve melhores pontuações em variáveis cognitivas na semana 10: memória (ensaios de aprendizagem RAVLT p = 0,030; RAVLT recordação tardia p=0,029), fluência fonológica (p=0,001), atividades da vida diária (FAQ p=0,001), satisfação com o desempenho da memória (satisfação MMQ p=0,004) e uso de estratégias de memória (estratégia MMQ p=0,000), bem como uma significativa redução da sintomatologia afetiva: depressão (GDS p=0,000), sintomas neuropsiquiátricos (NPI-Q p=0,045), esquecimento (EDO-10 p=0,000) e estresse (DAS estresse p=0,000). Conclusões: Nosso estudo sugere que a CTR é uma intervenção eficaz.

Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS): Study design and harmonization.

INTRODUCTION: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization. METHODS: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries. RESULTS: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome). DISCUSSION: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design.

Effectiveness of cognitive rehabilitation on mild cognitive impairment using teleneuropsychology / A eficácia da reabilitação cognitiva no comprometimento cognitivo leve usando tele neuropsicologia

ABSTRACT The COVID-19 pandemic has affected the continuity of cognitive rehabilitation worldwide. However, the use of teleneuropsychology to provide cognitive rehabilitation has contributed significantly to the continuity of the treatment. Objectives: To measure the effects of cognitive telerehabilitation on cognition, neuropsychiatric symptoms, and memory strategies in a cohort of patients with mild cognitive impairment. Methods: A sample of 60 patients with mild cognitive impairment according to Petersen's criteria was randomly divided into two groups: 30 treatment cases and 30 controls (waiting list group). Subjects were matched by age, sex, and Montreal Cognitive Assessment. The treatment group received ten cognitive telerehabilitation sessions of 45 minutes duration once a week. Pre-treatment (week 0) and post-treatment (week 10) measures were assessed for both groups. Different linear mixed models were estimated to test treatment effect (cognitive telerehabilitation vs. controls) on each outcome of interest over time (pre/post-intervention). Results: A significant group (control/treatment) x time (pre/post) interaction revealed that the treatment group at week 10 had better scores in cognitive variables: memory (RAVLT learning trials p=0.030; RAVLT delayed recall p=0.029), phonological fluency (p=0.001), activities of daily living (FAQ p=0.001), satisfaction with memory performance (MMQ satisfaction p=0.004) and use of memory strategies (MMQ strategy p=0.000), as well as, and a significant reduction of affective symptomatology: depression (GDS p=0.000), neuropsychiatric symptoms (NPI-Q p=0.045), forgetfulness (EDO-10 p=0.000), and stress (DAS stress p=0.000). Conclusions: Our study suggests that CTR is an effective intervention.

RESUMO A pandemia do COVID-19 afetou a continuidade da reabilitação cognitiva em todo o mundo. No entanto, o uso de tele neuropsicologia para a reabilitação cognitiva tem contribuído significativamente para a continuidade do tratamento. Objetivos: Medir os efeitos da tele reabilitação cognitiva na cognição, nos sintomas neuropsiquiátricos e nas estratégias de memória em uma coorte de pacientes com comprometimento cognitivo leve. Métodos: Uma amostra de 60 pacientes com comprometimento cognitivo leve de acordo com os critérios de Petersen foi dividida aleatoriamente em dois grupos: 30 casos de tratamento e 30 controles (grupo de lista de espera). Os assuntos foram pareados por idade, sexo e Avaliação Cognitiva de Montreal. O grupo de tratamento recebeu dez sessões de tele reabilitação cognitiva de 45 minutos de duração uma vez por semana. As medidas pré-tratamento (semana 0) e pós-tratamento (semana 10) foram avaliadas para ambos os grupos. Diferentes modelos lineares mistos foram estimados para testar o efeito do tratamento (tele reabilitação cognitiva vs. controles) em cada desfecho de interesse ao longo do tempo (pré-/pós-intervenção). Resultados: Uma interação significativa grupo (controle/tratamento) x tempo (pré/pós) revelou que o grupo de tratamento teve melhores pontuações em variáveis cognitivas na semana 10: memória (ensaios de aprendizagem RAVLT p = 0,030; RAVLT recordação tardia p=0,029), fluência fonológica (p=0,001), atividades da vida diária (FAQ p=0,001), satisfação com o desempenho da memória (satisfação MMQ p=0,004) e uso de estratégias de memória (estratégia MMQ p=0,000), bem como uma significativa redução da sintomatologia afetiva: depressão (GDS p=0,000), sintomas neuropsiquiátricos (NPI-Q p=0,045), esquecimento (EDO-10 p=0,000) e estresse (DAS estresse p=0,000). Conclusões: Nosso estudo sugere que a CTR é uma intervenção eficaz.

Clinical and genetic study of developmental and epileptic encephalopathy in Argentinean pediatric patients.

INTRODUCTION: The aim of this study was to extend our knowledge of the genetic background of Argentinean pediatric patients with developmental and epileptic encephalopathy (DEE) applying a next generation sequencing (NGS) panel. METHODS: Thirty one patients with DEE were studied, including these phenotypes: Dravet syndrome (n:7), Dravet like syndrome (n:3), West syndrome (WS) (n:6), WS that evolved to Lennox-Gastaut syndrome (LGS) (n:4), epilepsy of infancy with migrating focal seizures (n:2), continuous spikes and waves during slow sleep evolving to LGS (n:1), LGS (n:1), myoclonic status in non-progressive encephalopathy (n:1), myoclonic atonic epilepsy (n:1), epileptic encephalopathy with multifocal spikes (n:1) and unclassified epileptic encephalopathy (n:4). Fifty-two genes frequently associated with DEE were studied by NGS in genomic DNA from peripheral blood. RESULTS: Relevant variants were detected in 12 cases; 6 novel pathogenic or likely pathogenic variants, 6 previously reported as pathogenic and 1 variant of unknown significance. Single-nucleotide heterozygous variants were identified in the SCN1A (5), GABRG2 (1), STXBP1 (2) genes, a mosaic variant in SCN2A (1) and a homozygous variant in SCN1B (1). Additionally, a heterozygous deletion involving the SCN1A, SCN2A and SCN3A genes (1), and the most frequent triplet repeat expansion in the ARX gene (1) were detected. DISCUSSION: Genetic diagnosis was made in 39% of patients. We emphasize the importance of considering mosaic variants, copy number variants and hereditary forms when designing and interpreting molecular studies, to optimize diagnosis and management of patients. Approximately 42% of the detected variants were novel, expanding the knowledge of the molecular basis of DEEs in Latin-American patients.

Introducción: El objetivo del estudio fue ampliar el conocimiento de las bases moleculares de las encefalopatías epilépticas y del desarrollo (EED) en pacientes pediátricos argentinos aplicando un panel de secuenciación de nueva generación (NGS). Métodos: Se analizaron 31 pacientes con los fenotipos clínicos de síndrome de Dravet (n:7), síndrome símil Dravet (n:3), síndrome de West (SW) (n:6), SW que evoluciona a síndrome de Lennox Gastaut (SLG)(N:4), epilepsia de la infancia con crisis focales migratorias (n:2), actividad de punta onda continua durante el sueño que evolucionan a SLG (n:1), SLG (n:1), encefalopatía no progresiva con estatus mioclónico (n:1), epilepsia mioclónica atónica (n:1), encefalopatía epiléptica con espigas multifocales (n:1) y encefalopatía epiléptica indeterminada (n:4). Se estudiaron los 52 genes más frecuentemente asociados a EED a través de NGS, en ADN extraído de sangre periférica. Resultados: Se identificaron variantes relevantes en 12 casos, de las cuales 5 fueron nuevas y 6 previamente reportadas como patogénicas o posiblemente patogénicas, mientras que una variante fue clasificada como de significado incierto. Variantes heterocigotas, de nucleótido único, se identificaron en los genes SCN1A (5), GABRG2 (1), STXBP1 (2), una variante en mosaico en SCN2A (1) y otra homocigota en SCN1B (1). Además, se detectó una deleción que involucra a los genes SCN1A, SCN2A y SCN3A (1) y la expansión de repeticiones de tripletes más frecuente en el gen ARX (1). Discusión: Se alcanzó el diagnóstico molecular en el 39% de los pacientes. Remarcamos la importancia de considerar variantes en mosaico, variantes en el número de copias y formas heredadas al momento de diseñar e interpretar los estudios moleculares, de tal forma de optimizar el diagnóstico y seguimiento de los pacientes con EED. Cabe destacar, que el 42% de las variantes detectadas fueron nuevas, ampliando nuestro conocimiento sobre las bases moleculares de las EED en población latino americana.

Clinical and genetic study of developmental and epileptic encephalopathy in argentinean pediatric patients / Estudio clínico y genético de encefalopatía epiléptica y del desarrollo en pacientes pediátricos argentinos

Abstract Introduction: The aim of this study was to extend our knowledge of the genetic background of Argentinean pediatric patients with developmental and epileptic encephalopathy (DEE) applying a next generation sequencing (NGS) panel. Methods: Thirty one patients with DEE were studied, including these phenotypes: Dravet syndrome (n:7), Dravet like syndrome (n:3), West syndrome (WS) (n:6), WS that evolved to Lennox-Gastaut syndrome (LGS) (n:4), epilepsy of infancy with migrating focal seizures (n:2), continuous spikes and waves during slow sleep evolving to LGS (n:1), LGS (n:1), myoclonic status in non-progressive encephalopathy (n:1), myoclonic atonic epilepsy (n:1), epileptic encephalopathy with multifocal spikes (n:1) and unclassified epileptic encephalopathy (n:4). Fifty-two genes frequently associated with DEE were studied by NGS in genomic DNA from peripheral blood. Results: Relevant variants were detected in 12 cases; 6 novel pathogenic or likely pathogenic variants, 6 previously reported as pathogenic and 1 variant of unknown sig nificance. Single-nucleotide heterozygous variants were identified in the SCN1A (5), GABRG2 (1), STXBP1 (2) genes, a mosaic variant in SCN2A (1) and a homozygous variant in SCN1B (1). Additionally, a heterozygous deletion involving the SCN1A, SCN2A and SCN3A genes (1), and the most frequent triplet repeat expansion in the ARX gene (1) were detected. Discussion: Genetic diagnosis was made in 39% of patients. We emphasize the importance of considering mosaic variants, copy number variants and hereditary forms when designing and interpreting molecular studies, to optimize diagnosis and management of patients. Approximately 42% of the de tected variants were novel, expanding the knowledge of the molecular basis of DEEs in Latin-American patients.

Resumen Introducción: El objetivo del estudio fue ampliar el conocimiento de las bases moleculares de las encefalopatías epilépticas y del desarrollo (EED) en pacientes pediátricos argentinos aplicando un panel de secuenciación de nueva generación (NGS). Métodos: Se analizaron 31 pacientes con los fenotipos clínicos de síndrome de Dra vet (n:7), síndrome símil Dravet (n:3), síndrome de West (SW) (n:6), SW que evoluciona a síndrome de Lennox Gastaut (SLG)(N:4), epilepsia de la infancia con crisis focales migratorias (n:2), actividad de punta onda continua durante el sueño que evolucionan a SLG (n:1), SLG (n:1), encefalopatía no progresiva con estatus mioclónico (n:1), epilepsia mioclónica atónica (n:1), encefalopatía epiléptica con espigas multifocales (n:1) y encefalopatía epiléptica indeterminada (n:4). Se estudiaron los 52 genes más frecuentemente asociados a EED a través de NGS, en ADN extraído de sangre periférica. Resultados: Se identificaron variantes relevantes en 12 casos, de las cuales 5 fueron nuevas y 6 previamente reportadas como patogénicas o posiblemente patogénicas, mien tras que una variante fue clasificada como de significado incierto. Variantes heterocigotas, de nucleótido único, se identificaron en los genes SCN1A (5), GABRG2 (1), STXBP1 (2), una variante en mosaico en SCN2A (1) y otra homocigota en SCN1B (1). Además, se detectó una deleción que involucra a los genes SCN1A, SCN2A y SCN3A (1) y la expansión de repeticiones de tripletes más frecuente en el gen ARX (1). Discusión: Se alcanzó el diagnóstico molecular en el 39% de los pacientes. Remarcamos la importancia de considerar variantes en mosaico, variantes en el número de copias y formas heredadas al momento de diseñar e interpretar los estudios moleculares, de tal forma de optimizar el diagnóstico y seguimiento de los pacientes con EED. Cabe destacar, que el 42% de las variantes detectadas fueron nuevas, ampliando nuestro conocimiento sobre las bases mole culares de las EED en población latino americana.

Multicenter study of diffuse pleural mesothelioma. histopathological and immunohistochemical features / Estudio multicéntrico de características histopatológicas e inmunohistoquímicas del mesotelioma pleural difuso

Abstract The pathological diagnosis of diffuse pleural mesothelioma (DPM) contributes to treatment selection and clinical trials interpretation. To know its characteristics and evaluate the viability of comprehensive pathological diagnosis of DPM in Argentina we did a retrospective descriptive study of DPM cases reported from 2009 to 2018. We analyzed 398 cases corresponding to 238 (60%) men and 160 (40%) women, median age 66 years, from surgical biopsies (78%), small biopsies (16.5%) and surgical resections (5.5%). The 77% were epithelioid (E-DPM), 12% biphasic, 10% sarcomatoid, and 4 cases transitional variant. In E-DPM the main pattern was tubular in 36% and solid in 33%. There was a second pattern in 179 cases. Considering the main pattern and the second together, 48% presented tubular subtype and 48% solid subtype. Stroma, necrosis, and nuclear score showed significant differences between E-DPM and non-epithelioid mesotheliomas. Overall tumor grade was predominantly low in E-DPM, except for 42% of the solid main pattern. We recognized the transitional variant extensively in 4 cases and focally in 8. The immunohistochemical antibody panel used included pan-cytokeratin, calretinin, WT-1, cytokeratin 5, CEA and TTF-1. The expression of cytokeratin 5, calretinin and WT-1 was lower in the sarcomatoid type (43%, 87 and 37%) than in the epithelioid type (92%, 98% and 93%). This study highlights the tumor heterogeneity of DPM that shows the diagnostic difficulty, and the feasibility of evaluating histological aggressiveness in E-DPM, B-DPM and S-DPM in our country.

Resumen El diagnóstico patológico del mesotelioma pleural difuso (MPD) contribuye a la selección del tratamiento y a la interpretación de los ensayos clínicos. Para conocer sus características y evaluar la viabilidad del diagnóstico patológico de MPD en Argentina se realizó un estudio descriptivo retros pectivo de los casos de MPD informados de 2009 a 2018. Se analizaron 398 casos correspondientes a 238 (60%) hombres y 160 (40%) mujeres, mediana de edad de 66 años, a partir de biopsias quirúrgicas (78%), biopsias pequeñas (16.5%) y resecciones quirúrgicas (5.5%). El 77% fue epitelioide (E-MPD), 12% bifásicos, 10% sarcomatoides y 4 casos variante transicional. En E-MPD se encontró como patrón principal el tubular en 36% y el sólido en 33%. Hubo un segundo patrón en 179 casos. Considerando el principal y el segundo patrón en conjunto, el 48% presentó subtipo tubular y el 48% subtipo sólido. El estroma, la necrosis y el score nuclear mostraron diferencias significativas entre E-MPD y mesoteliomas no epitelioides. El grado general del tumor fue predominantemente bajo en E-MPD, a excepción del 42% del patrón principal sólido. Reconocimos la variante transicional en forma extensa en 4 casos y focalmente en 8. La expresión de citoqueratina 5, calretinina y WT-1 fue menor en el tipo sarcomatoide (43%, 87 y 37%) que en el tipo epitelioide (92%, 98% y 93%). Este estudio destaca la heterogeneidad tumoral de MPD que evidencia la dificu ltad en el diagnóstico y la viabilidad de evaluar la agresividad histológica en E-MPD, B-MPD y S-MPD en nuestro país.

Multicenter study of diffuse pleural mesothelioma. Histopathological and immunohistochemical features.

The pathological diagnosis of diffuse pleural mesothelioma (DPM) contributes to treatment selection and clinical trials interpretation. To know its characteristics and evaluate the viability of comprehensive pathological diagnosis of DPM in Argentina we did a retrospective descriptive study of DPM cases reported from 2009 to 2018. We analyzed 398 cases corresponding to 238 (60%) men and 160 (40%) women, median age 66 years, from surgical biopsies (78%), small biopsies (16.5%) and surgical resections (5.5%). The 77% were epithelioid (E-DPM), 12% biphasic, 10% sarcomatoid, and 4 cases transitional variant. In E-DPM the main pattern was tubular in 36% and solid in 33%. There was a second pattern in 179 cases. Considering the main pattern and the second together, 48% presented tubular subtype and 48% solid subtype. Stroma, necrosis, and nuclear score showed significant differences between E-DPM and non-epithelioid mesotheliomas. Overall tumor grade was predominantly low in E-DPM, except for 42% of the solid main pattern. We recognized the transitional variant extensively in 4 cases and focally in 8. The immunohistochemical antibody panel used included pan-cytokeratin, calretinin, WT-1, cytokeratin 5, CEA and TTF-1. The expression of cytokeratin 5, calretinin and WT-1 was lower in the sarcomatoid type (43%, 87 and 37%) than in the epithelioid type (92%, 98% and 93%). This study highlights the tumor heterogeneity of DPM that shows the diagnostic difficulty, and the feasibility of evaluating histological aggressiveness in E-DPM, B-DPM and S-DPM in our country.

El diagnóstico patológico del mesotelioma pleural difuso (MPD) contribuye a la selección del tratamiento y a la interpretación de los ensayos clínicos. Para conocer sus características y evaluar la viabilidad del diagnóstico patológico de MPD en Argentina se realizó un estudio descriptivo retrospectivo de los casos de MPD informados de 2009 a 2018. Se analizaron 398 casos correspondientes a 238 (60%) hombres y 160 (40%) mujeres, mediana de edad de 66 años, a partir de biopsias quirúrgicas (78%), biopsias pequeñas (16.5%) y resecciones quirúrgicas (5.5%). El 77% fue epitelioide (E-MPD), 12% bifásicos, 10% sarcomatoides y 4 casos variante transicional. En E-MPD se encontró como patrón principal el tubular en 36% y el sólido en 33%. Hubo un segundo patrón en 179 casos. Considerando el principal y el segundo patrón en conjunto, el 48% presentó subtipo tubular y el 48% subtipo sólido. El estroma, la necrosis y el score nuclear mostraron diferencias significativas entre E-MPD y mesoteliomas no epitelioides. El grado general del tumor fue predominantemente bajo en E-MPD, a excepción del 42% del patrón principal sólido. Reconocimos la variante transicional en forma extensa en 4 casos y focalmente en 8. La expresión de citoqueratina 5, calretinina y WT-1 fue menor en el tipo sarcomatoide (43%, 87 y 37%) que en el tipo epitelioide (92%, 98% y 93%). Este estudio destaca la heterogeneidad tumoral de MPD que evidencia la dificu ltad en el diagnóstico y la viabilidad de evaluar la agresividad histológica en E-MPD, B-MPD y S-MPD en nuestro país.

Neuropsychological profile of Alzheimer's disease based on amyloid biomarker findings results from a South American cohort.

OBJECTIVE: Increased life expectancy and exponential growth of adults suffering from Alzheimer's disease (AD) worldwide, has led to biomarkers incorporation for diagnosis in early stages. Use of neuropsychological testing remains limited. This study aimed to identify which neuropsychological tests best indicated underlying AD pathophysiology. METHODS: One hundred and forty-one patients with MCI (Mild Cognitive Impairment) were studied. A neuropsychological test battery based on the Uniform Data Set (UDS) from the Alzheimer's Disease Centers program of the National Institute on Aging (NIA) was performed and amyloid markers recorded; according to presence or absence of amyloid identified by positive PIB-PET findings, or low CSF Aß42 levels, patients were separated into MCI amyloid-(n:58) and MCI amyloid + (n = 83) cases. RESULTS: Statistical differences were found in all memory tests between groups. Delayed recall score at thirty minutes on the Rey Auditory Verbal Learning Test (AVLT) was the best predictor of amyloid pathology presence (AUC 0.68), followed by AVLT total learning (AUC 0.66) and AVLT Recognition (AUC 0.59) scores, providing useful cut off values in the clinical setting. CONCLUSIONS: Use of neuropsychological testing, specifically AVLT scores with cutoff values, contributed to the correct diagnosis of MCI due to AD in this SouthAmerican cohort.

Prospective cohort study in the early stage of the COVID-19 pandemic, General Pueyrredón, Argentina (INECOVID): infection dynamics and risk factors. / Estudio de cohortes prospectivo en etapa temprana de la pandemia COVID-19, Partido de General Pueyrredón, Argentina (INECOVID): dinámica de infección y factores de riesgo.

OBJECTIVE: To establish the magnitude and risk factors for SARS-CoV-2 infection in the General Pueyrredón, Buenos Aires, Argentina: the INECOVID study. METHODS: Prospective cohort designed with participants from the District general population. The follow-up period was from June 22nd to December 18th, 2020, with a minimum appointment interval of 21 days. Data were obtained via questionnaires and serum or plasma samples. The primary event was considered as the time to seroconversion (IgG) as evidence of SARS-CoV-2 infection. The accumulated risk of infection was estimated using the Kaplan Meier method. Cox models were built with time-dependent variables. RESULTS: 345 participants were recruited (n=222 women, 64.3%; 123 men, 35.7%), with a median age of 45 years in women (Interquartile range: 19) and 49 in men (Interquartile range: 26). 12.8% of participants (n=44) had evidence of SARS-CoV-2 infection [incidence density of 9.1 cases (women: 11.1, men: 5.1) per 10,000 person-day]. 36.4% of the cases (n=16) were asymptomatic. The following factors were associated to the risk of infection: being in close contact of a confirmed COVID-19 case (HR=5.56; 95%CI 2.85-10.83), being a health worker (HR=2.93; 95%CI 1.55-5.52), living in crowded conditions (HR=2.23; 95%CI 1.13-4.49), and age (HR=0.98; 95%CI 0.95-1.00). CONCLUSION: The identified risk factors endorse the protection policies and protocols adopted by the Argentinian sanitary authorities for the general population and the care programs for health workers in the pre-vaccination phase.

OBJETIVO: Establecer la magnitud y los factores de riesgo de infección por SARS-CoV-2 en el Partido de General Pueyrredón, Buenos Aires, Argentina: estudio INECOVID. MÉTODOS: Diseño de cohortes prospectivo con participantes de población general del partido. El período de seguimiento fue del 22 de junio al 18 de diciembre de 2020, con un intervalo mínimo de citación de 21 días. Los datos se obtuvieron mediante cuestionarios y muestras de suero o plasma. El evento primario fue el tiempo hasta la seroconversión (IgG) como evidencia de infección por SARS-CoV-2. Se estimó el riesgo acumulado de infección por el método de Kaplan Meier. Se construyeron modelos de Cox con variables tiempo-dependientes. RESULTADOS: Fueron reclutados 345 participantes (n=222 mujeres, 64,3%; 123 hombres, 35,7%), con una edad mediana de 45 años en mujeres (Rango intercuartílico: 19) y 49 en hombres (Rango intercuartílico: 26). El 12,8% de los participantes (n=44) tuvieron evidencia de infección por SARS-CoV-2 [densidad de incidencia de 9,1 casos (mujeres: 11,1, hombres: 5,1) por 10.000 personas-días]. El 36,4% de los casos (n=16) fueron asintomáticos. Se mostraron asociados al riesgo de infección: ser contacto estrecho de un caso confirmado de COVID-19 (HR=5,56; IC95% 2,85­10,83), ser trabajador de salud (HR=2,93; IC95% 1,55-5,52), vivir en hacinamiento (HR=2,23; IC95% 1,13­4,49) y edad (HR=0,98; IC95% 0,95­1,00). CONCLUSIÓN: Los factores de riesgo de infección hallados avalan las políticas y protocolos de protección adoptados por las autoridades sanitarias de Argentina para la población general y los programas de atención a los trabajadores de la salud en la etapa pre-vacunación.

[Spanish Norms for Mini-SEA (Mini Social Cognition and Emotional Assessment) in adults in Buenos Aires]. / Baremos en español del Mini-SEA (Mini Social Cognition and Emotional Assessment) en adultos normales de Buenos Aires.

INTRODUCTION AND OBJECTIVE: The Mini-SEA is a quick and brief cognitive assessment test developed to study social cognition. It consists of a modified version of the faux pas Test and an emotional recognition test based on Ekman's faces. The objective of this work was to obtain the first Spanish Speaking norms for the Mini-SEA test. MATERIAL AND METHODS: 64 healthy volunteers, between 35 and 80 years old, were recruited and evaluated with the Mini-SEA by specialized neuropsychologists from the Cities of Buenos Aires and La Plata, both in the Province of Buenos Aires, Argentina. RESULTS: The total mean (M) of the Mini-SEA was 25 +/- 4. The M of the faux pas Score was 12.5 +/- 2.4 and the M of the Emotional Recognition Score was 12.8 +/- 1.5. The sample was divided into 4 age groups: Group 1 (<50 years), Group 2 (50-59 years), Group 3 (60-69 years) and Group 4 (more than 70 years). Differences were found in the age continuum in the Emotional Recognition score between group 1 and 4 (p <0.05) and between group 3 and 4 (p <0.01), but not in the Faux Pas Score. CONCLUSION: This study presents the first normative values of the Mini-SEA Social Cognition test for a Spanish-speaking population. The Mini-SEA, being a quick and easy to administer test, allows the study of social cognition in an adequate and precise way, especially in prodromal stages of neurodegenerative diseases.

Estudio de cohortes prospectivo en etapa temprana de la pandemia COVID-19, Partido de General Pueyrredón, Argentina (INECOVID): dinámica de infección y factores de riesgo / Prospective cohort study in the early stage of the COVID-19 pandemic, General Pueyrredón, Argentina (INECOVID): infection dynamics and risk factors

RESUMEN: Objetivo: Establecer la magnitud y los factores de riesgo de infección por SARS-CoV-2 en el Partido de General Pueyrredón, Buenos Aires, Argentina: estudio INECOVID. Métodos: Diseño de cohortes prospectivo con participantes de población general del partido. El período de seguimiento fue del 22 de junio al 18 de diciembre de 2020, con un intervalo mínimo de citación de 21 días. Los datos se obtuvieron mediante cuestionarios y muestras de suero o plasma. El evento primario fue el tiempo hasta la seroconversión (IgG) como evidencia de infección por SARS-CoV-2. Se estimó el riesgo acumulado de infección por el método de Kaplan Meier. Se construyeron modelos de Cox con variables tiempo-dependientes. Resultados: Fueron reclutados 345 participantes (n=222 mujeres, 64,3%; 123 hombres, 35,7%), con una edad mediana de 45 años en mujeres (Rango intercuartílico: 19) y 49 en hombres (Rango intercuartílico: 26). El 12,8% de los participantes (n=44) tuvieron evidencia de infección por SARS-CoV-2 [densidad de incidencia de 9,1 casos (mujeres: 11,1, hombres: 5,1) por 10.000 personas-días]. El 36,4% de los casos (n=16) fueron asintomáticos. Se mostraron asociados al riesgo de infección: ser contacto estrecho de un caso confirmado de COVID-19 (HR=5,56; IC95% 2,85-10,83), ser trabajador de salud (HR=2,93; IC95% 1,55-5,52), vivir en hacinamiento (HR=2,23; IC95% 1,13-4,49) y edad (HR=0,98; IC95% 0,95-1,00). Conclusión: Los factores de riesgo de infección hallados avalan las políticas y protocolos de protección adoptados por las autoridades sanitarias de Argentina para la población general y los programas de atención a los trabajadores de la salud en la etapa pre-vacunación.

ABSTRACT Objective: To establish the magnitude and risk factors for SARS-CoV-2 infection in the General Pueyrredón, Buenos Aires, Argentina: the INECOVID study. Methods: Prospective cohort designed with participants from the District general population. The follow-up period was from June 22nd to December 18th, 2020, with a minimum appointment interval of 21 days. Data were obtained via questionnaires and serum or plasma samples. The primary event was considered as the time to seroconversion (IgG) as evidence of SARS-CoV-2 infection. The accumulated risk of infection was estimated using the Kaplan Meier method. Cox models were built with time-dependent variables. Results: 345 participants were recruited (n=222 women, 64.3%; 123 men, 35.7%), with a median age of 45 years in women (Interquartile range: 19) and 49 in men (Interquartile range: 26). 12.8% of participants (n=44) had evidence of SARS-CoV-2 infection [incidence density of 9.1 cases (women: 11.1, men: 5.1) per 10,000 person-day]. 36.4% of the cases (n=16) were asymptomatic. The following factors were associated to the risk of infection: being in close contact of a confirmed COVID-19 case (HR=5.56; 95%CI 2.85-10.83), being a health worker (HR=2.93; 95%CI 1.55-5.52), living in crowded conditions (HR=2.23; 95%CI 1.13-4.49), and age (HR=0.98; 95%CI 0.95-1.00). Conclusion: The identified risk factors endorse the protection policies and protocols adopted by the Argentinian sanitary authorities for the general population and the care programs for health workers in the pre-vaccination phase.

Abordaje epidemiológico en establecimiento de estancia prolongada de adultos mayores con antecedente de brote de COVID-19 / Epidemiological approach in a long-term care facility for the elderly with antecedent of COVID-19 outbreak

INTRODUCCIÓN: Durante la pandemia de enfermedad por el nuevo coronavirus (COVID-19) los adultos mayores residentes en instituciones semicerradas y su personal de salud constituyen una subpoblación vulnerable con riesgo elevado de hospitalización y muerte. OBJETIVO: Describir el abordaje epidemiológico efectuado en un establecimiento de estancia prolongada para adultos mayores bajo vigilancia activa, en el aglomerado urbano Mar del Plata-Batán, en diciembre de 2020. MÉTODOS: La estrategia de abordaje combinó la indicación de aislamiento de los casos sospechosos, la realización de reacción en cadena de la polimerasa en tiempo real (RT-PCR) y la detección de anticuerpos del tipo inmunoglobulina G (IgG). RESULTADOS: Se detectaron 4 casos de infección por el nuevo coronavirus (SARS-CoV-2) por RT-PCR en miembros del personal de salud; solo 1 tenía antecedente de detección por RT-PCR durante el brote inicial ocurrido 95 días antes; los resultados en los residentes fueron negativos. Se encontraron 40 casos con anticuerpos de tipo IgG (63,5%); 12 de ellos (30%) no tenían antecedente de detección mediante RT-PCR en ninguno de los brotes. DISCUSIÓN: Los hallazgos indican que el hecho de haber atravesado un primer episodio de brote en el establecimiento confirió inmunidad a personas que no habían tenido manifestaciones clínicas de la enfermedad, lo cual, probablemente, contribuyó a evitar la propagación del segundo brote entre los residentes

Environmental factors between normal and superagers in an Argentine cohort.

Normal aging usually brings age-related cognitive decline. However, there is a group of aged individuals who have exceptional memory performance: the superagers. OBJECTIVE: Our aim was to identify the environmental factors that could influence exceptional memory performance in a cohort of Argentine individuals. METHODS: Forty healthy volunteers >80 years of age were classified into two groups, superagers (SA, n=20) and normal agers (NA, n=20), according to the Northwestern SuperAging Program criteria. Participants were neuropsychologically tested and evaluated on environmental aspects: working status, education, bilingualism, cognitive reserve, physical activity, social networking, clinical comorbidities, and longevity of parents and siblings. RESULTS: Both groups were highly educated (NA=16.3±3 years; SA 15.85±2.6; p=0.6), 11.8% of the sample was still working without differences between groups. There were no differences in cognitive reserve inventory (p=0.7), physical activity engagement (p=0.423), or social network index (p=0.73). As for longevity, 44% of the siblings lived longer than 80 years of age (p=0.432) and maternal longevity was linked to SA (NA=46.7%; SA=80%; p=0.045). CONCLUSIONS: This study is a pilot approximation to the superaging population in Argentina. Our results suggest that environmental factors related to successful aging do not differentiate superaging. SA may depend on variables yet to be identified, probably of a genetic/metabolic order.

O envelhecimento normal geralmente traz declínio cognitivo relacionado à idade. No entanto, existe um grupo de idosos com desempenho excepcional de memória: os superidosos. OBJETIVO: Nosso objetivo foi identificar os fatores ambientais que podem influenciar o desempenho excepcional da memória em uma coorte de indivíduos argentinos. MÉTODOS: Quarenta voluntários saudáveis com idade >80 anos foram classificados em dois grupos: superidosos (SI, n=20) e idosos normais (IN, n=20), de acordo com os critérios do Programa de Superidosos da Universidade Northwestern. Os participantes foram testados neuropsicologicamente e avaliados nos aspectos ambientais: situação de trabalho, escolaridade, bilinguismo, reserva cognitiva, atividade física e rede social, comorbidades clínicas e longevidade de pais e irmãos. RESULTADOS: Ambos os grupos tinham alto nível de escolaridade (IN=16,3±3 anos; SI=15,85±2,6; p=0,6), 11,8% da amostra ainda trabalhava sem diferença entre os grupos. Não houve diferenças no inventário de reserva cognitiva (p=0,7), prática de atividade física (p=0,423) ou índice de rede social (p=0,73). Quanto à longevidade, 44% dos irmãos viviam mais de 80 anos (p=0,432) e a longevidade materna estava associada a SI (IN=46,7%; SI=80%; p=0,045). CONCLUSÕES: Este estudo é uma aproximação piloto ao super envelhecimento da população na Argentina. Nossos resultados sugerem que os fatores ambientais relacionados ao envelhecimento bem-sucedido não diferenciam os superidosos. Ser superidoso pode depender de variáveis ainda não identificadas, provavelmente de ordem genética/metabólica.

Environmental factors between normal and superagers in an Argentine cohort / Diferenças de fatores ambientais entre normais e superidosos em uma coorte argentina

ABSTRACT. Normal aging usually brings age-related cognitive decline. However, there is a group of aged individuals who have exceptional memory performance: the superagers. Objective: Our aim was to identify the environmental factors that could influence exceptional memory performance in a cohort of Argentine individuals. Methods: Forty healthy volunteers >80 years of age were classified into two groups, superagers (SA, n=20) and normal agers (NA, n=20), according to the Northwestern SuperAging Program criteria. Participants were neuropsychologically tested and evaluated on environmental aspects: working status, education, bilingualism, cognitive reserve, physical activity, social networking, clinical comorbidities, and longevity of parents and siblings. Results: Both groups were highly educated (NA=16.3±3 years; SA 15.85±2.6; p=0.6), 11.8% of the sample was still working without differences between groups. There were no differences in cognitive reserve inventory (p=0.7), physical activity engagement (p=0.423), or social network index (p=0.73). As for longevity, 44% of the siblings lived longer than 80 years of age (p=0.432) and maternal longevity was linked to SA (NA=46.7%; SA=80%; p=0.045). Conclusions: This study is a pilot approximation to the superaging population in Argentina. Our results suggest that environmental factors related to successful aging do not differentiate superaging. SA may depend on variables yet to be identified, probably of a genetic/metabolic order.

RESUMO. O envelhecimento normal geralmente traz declínio cognitivo relacionado à idade. No entanto, existe um grupo de idosos com desempenho excepcional de memória: os superidosos. Objetivo: Nosso objetivo foi identificar os fatores ambientais que podem influenciar o desempenho excepcional da memória em uma coorte de indivíduos argentinos. Métodos: Quarenta voluntários saudáveis com idade >80 anos foram classificados em dois grupos: superidosos (SI, n=20) e idosos normais (IN, n=20), de acordo com os critérios do Programa de Superidosos da Universidade Northwestern. Os participantes foram testados neuropsicologicamente e avaliados nos aspectos ambientais: situação de trabalho, escolaridade, bilinguismo, reserva cognitiva, atividade física e rede social, comorbidades clínicas e longevidade de pais e irmãos. Resultados: Ambos os grupos tinham alto nível de escolaridade (IN=16,3±3 anos; SI=15,85±2,6; p=0,6), 11,8% da amostra ainda trabalhava sem diferença entre os grupos. Não houve diferenças no inventário de reserva cognitiva (p=0,7), prática de atividade física (p=0,423) ou índice de rede social (p=0,73). Quanto à longevidade, 44% dos irmãos viviam mais de 80 anos (p=0,432) e a longevidade materna estava associada a SI (IN=46,7%; SI=80%; p=0,045). Conclusões: Este estudo é uma aproximação piloto ao super envelhecimento da população na Argentina. Nossos resultados sugerem que os fatores ambientais relacionados ao envelhecimento bem-sucedido não diferenciam os superidosos. Ser superidoso pode depender de variáveis ainda não identificadas, provavelmente de ordem genética/metabólica.

A new tool to sense pH changes at the neuromuscular junction synaptic cleft.

Synaptic transmission triggers transient acidification of the synaptic cleft. Recently, it has been shown that pH affects the opening of postsynaptic channels and therefore the production of tools that allow to study these behaviors should result of paramount value. We fused α-bungarotoxin, a neurotoxin derived from the snake Bungarus multicinctus that binds irreversibly to the acetylcholine receptor extracellular domain, to the pH sensitive GFP Super Ecliptic pHluorin, and efficiently expressed it in Pichia pastoris. This sensor allows synaptic changes in pH to be measured without the need of incorporating transgenes into animal cells. Here, we show that incubation of the mouse levator auris muscle with a solution containing this recombinant protein is enough to fluorescently label the endplate post synaptic membrane. Furthermore, we could physiologically alter and measure post synaptic pH by evaluating changes in the fluorescent signal of pHluorin molecules bound to acetylcholine receptors. In fact, using this tool we were able to detect a drop in 0.01 to 0.05 pH units in the vicinity of the acetylcholine receptors following vesicle exocytosis triggered by nerve electrical stimulation. Further experiments will allow to learn the precise changes in pH during and after synaptic activation.

Prognostic value of ATN Alzheimer biomarkers: 60-month follow-up results from the Argentine Alzheimer's Disease Neuroimaging Initiative.

PURPOSE: To describe results of the Amyloid, Tau, Neurodegeneration (ATN) research framework classification in the Argentine-Alzheimer's Disease Neuroimaging Initiative (arg-ADNI) cohort. METHODS: Twenty-three patients with mild cognitive impairment (MCI), 12 dementia of Alzheimer's type (DAT), and 14 normal controls were studied following the ADNI2 protocol. Patients were categorized according to presence or absence of the biomarkers for amyloid beta (Aß; A: amyloid positron emission tomography [PET] scan or cerebrospinal fluid [CSF] Aß42), tau (T: CSF phosphorylated-tau), and neurodegeneration (N: CSF total-tau, fluorodeoxyglucose [FDG]-PET scan, or structural magnetic resonance imaging [MRI] scan). RESULTS: A+T+N+ biomarker profile was identified at baseline in 91% of mild dementia patients, 20% of early MCI patients, 46% of late MCI patients, and 14% of control subjects. Suspected non-AD pathophysiology (SNAP, A-T-N+) was found in 8% of mild dementia, 20% of early MCI, 15% of late MCI, and 7% of control subjects. Conversion rates to dementia after 5-year follow-up were 85% in A+T+N+ MCI patients and 50% in A-T-N+ patients. CONCLUSIONS: We present initial 5-year follow-up results of a regional ADNI based on AD biomarkers and the ATN classification.

Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI): neuropsychological evolution profile after one-year follow up.

The Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI) study is a longitudinal prospective cohort of 50 participants at a single institution in Buenos Aires, Argentina. Longitudinal assessments on a neuropsychological test battery were performed on 15 controls, 24 mild cognitive impairment (MCI) patients and 12 Alzheimer's disease (AD) dementia patients. In our study population, there was a high prevalence of positive AD biomarkers in the AD group, 92.3% (12/13); and a low prevalence in the normal controls, 20%; almost half (48%) of the patients diagnosed with MCI had positive amyloid detection. After a one year, the significant differences found at baseline on neuropsychological testing were similar at the follow-up assessment even though the AD group had significantly altered its functional performance (FAQ and CDR). The exception was semantic fluency, which showed greater impairment between the AD group and MCI and normal controls respectively. For these tests, the addition of AD biomarkers as a variable did not significantly alter the variations previously found for the established clinical group's model. Finally, the one-year conversion rate to dementia was 20% in the MCI cohort.