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A Decline in Metabotropic Glutamate mGlu3 Receptor Levels Is Associated With Amyloid Plaques in Alzheimer's Disease and Is Detectable in Serum During Mild Cognitive Impairment

2026-04-01T00:00:00Z

A Decline in Metabotropic Glutamate mGlu3 Receptor Levels Is Associated With Amyloid Plaques in Alzheimer's Disease and Is Detectable in Serum During Mild Cognitive Impairment Olivera, Eugenia; Sáez, Albany; Castro, Micaela; Garaventa, Pilar; Novack, Gisela; Romero, Ana Clara; Bigi, Mercedes; Celaya, Daniela; Mezmezian, Mónica Beatriz; Sevlever, Gustavo Emilio; Saravia, Flavia; Lasaga, Mercedes; Caruso, Carla M.; Palumbo, María Laura; Durand, Daniela Subtype 3 metabotropic glutamate receptors (mGlu3R) play neuroprotective roles and are involved in superior executive functions and memory in humans. However, this target has been scarcely studied in the context of Alzheimer's disease (AD). Our previous results showed that astroglial mGlu3R promoted the non-amyloidogenic cleavage of amyloid precursor protein and triggered amyloid-β (Aβ) clearance by astrocytes. Remarkably, mGlu3R is downregulated in hippocampi from aged PDAPP-J20 mice, whereas the truncated isoform of the receptor, mGlu3Δ4, is early accumulated. Indeed, mGlu3Δ4 inhibited mGlu3R protective function in astrocytes. In the present paper, we aimed to investigate mGlu3Δ4/mGlu3R expression in AD brains and to assess whether changes in these proteins can be detected in human biofluids during mild cognitive impairment (MCI). Bioinformatics analysis of transcriptomic data from human brains indicated that mGlu3R expression was reduced in amyloid plaque-associated areas and in AD astrocytes. At the protein level, mGlu3R immunostaining was lower within the plaque niche in hippocampal slices from PDAPP-J20 mice, whereas cultured glial cells from these mice expressed lower mGlu3R than non-transgenic mice as early as 2 months-old of age. Furthermore, mGlu3R protein levels determined by western blot inversely correlated with histopathology in human AD hippocampi. Interestingly, mGlu3R (but not mGlu3Δ4) protein was detectable by western blot in serum samples from MCI and control subjects. We showed that mGlu3R levels were significantly reduced in MCI serum compared to those of cognitively intact individuals. Moreover, its levels positively correlated with serum Aβ. Our results showed changes in mGlu3R expression in AD brains that might reflect early glial receptor dysfunction, whereas reduced serum mGlu3R levels may be associated with mild cognitive impairment that precedes AD.

Prácticas de aislamiento en pacientes con enterobacterales productores de carbapenemasas : resultado de una encuesta nacional

2026-05-01T00:00:00Z

Prácticas de aislamiento en pacientes con enterobacterales productores de carbapenemasas : resultado de una encuesta nacional Huaier Arriazu, Emilio F.; Rodriguez, Viviana M.; Cudmani, Norma; Cornistein, Wanda; Scala, Gabriela; Edith, Carbone; Angeleri, Patricia; Abusamra, Lorena; Desse, Javier Eduardo; Del Castillo, Marcelo Ernesto; Echave, Cecilia; Sisto, Alicia Introducción: Los enterobacterales productores de carbapenemasas (EPC) representan un desafío creciente para los programas de control de infecciones. Las recomendaciones sobre duración y criterios de aislamiento varían entre guías y regiones. Este estudio buscó describir las prácticas de aislamiento en instituciones de salud de Argentina. Materiales y métodos: Estudio observacional, descriptivo y transversal basado en una encuesta autoadministrada, difundida por sociedades científicas nacionales entre marzo y abril de 2025. Se incluyeron instituciones públicas y privadas con programas de control de infecciones activos. Resultados: Se analizaron 190 encuestas válidas de 22 jurisdicciones. La mediana de camas fue 128 (IIQ 80-200). El 96.3% contaba con equipos de control de infecciones y el 95.3% realizaba vigilancia activa, principalmente en unidades críticas. El 81.6% de los hospitales reportó aplicar aislamiento individual como estrategia, aunque solo el 48.9% disponía de habitaciones individuales en todo momento. Asimismo, el 61.1% aplicaba cohorte de pacientes y el 13.7% cohorte de personal. La adherencia a la higiene de manos estuvo entre el 50 y 80%, ninguna institución superó el 90%. Un 28.4% informó criterios para suspender aislamiento, con marcada heterogeneidad entre centros. El sector privado mostró mayor disponibilidad de recursos, vigilancia en salas generales y normas escritas respecto del sector público. Conclusión: Las instituciones argentinas implementan medidas de aislamiento para EPC, aunque con variabilidad en recursos, adherencia y criterios de finalización. Se evidencian brechas entre políticas escritas y su aplicación efectiva, destacando la necesidad de protocolos nacionales estandarizados, adaptados a la realidad de cada Institución.

Global patterns of polypharmacy after acute heart failure hospitalization: Prevalence and outcomes from the REPORT-HF registry

2025-12-01T00:00:00Z

Global patterns of polypharmacy after acute heart failure hospitalization: Prevalence and outcomes from the REPORT-HF registry Wan Ting, Tay; Tiew-Hwa Katherine, Teng; Ouwerkerk, Wouter; John G.F., Cleland; Sean P., Collins; Christiane E., Angermann; Kenneth, Dickstein; Ulf, Dahlstrom; Anja, Schweizer; Achim, Obergfell; Kai-Hang, Yiu; Mathieu, Ghadanfar; Mahmoud, Hassanein; Qing-Wen, Ren; Wen-Li, Gu; Georg, Ertl; Sergio Víctor, Perrone; Gerasimos, Filippatos; Carolyn S.P., Lam; Jasper, Tromp Aims: Polypharmacy, defined as the concurrent use of ≥5 medications, is prevalent among older adults with heart failure (HF). While guideline-directed HF medications provide therapeutic benefits, non-HF polypharmacy, particularly involving inappropriate medications, may lead to adverse outcomes. The international REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure (REPORT-HF), the largest available global acute HF registry, was used to examine the prevalence, clinical correlates, and 1-year outcome associations of non-HF polypharmacy. Methods and results: Medication counts were classified as no polypharmacy (<5), polypharmacy (5-9), and hyper-polypharmacy (≥10). Potentially harmful medications were identified using the 2016 American Heart Association scientific statement. Multivariable regression models examined correlates of polypharmacy and 1-year mortality. Among 18 030 patients (66 ± 14 years, 39% women), 39% had polypharmacy and 9% had hyper-polypharmacy (63% and 25%, respectively, if including HF medications). Non-HF polypharmacy was more common in older white patients from high-income countries, with preserved ejection fraction and high comorbidity burden. Patients with greater non-HF medication use were less likely to receive guideline-directed HF medications and more likely to take medications that can worsen HF. Crude hazard ratios (HRs) for 1-year mortality were 1.16 (95% confidence interval [CI] 1.08-1.25) for polypharmacy and 1.46 (95% CI 1.31-1.63) for hyper-polypharmacy versus no polypharmacy. After adjustment, hyper-polypharmacy remained associated with increased mortality (HR 1.16, 95% CI 1.01-1.33). Conclusions: Non-HF polypharmacy in HF is common worldwide, particularly in high-income regions. Its association with reduced use of guideline-directed HF medications and higher usage of medications causing or worsening HF, as well as elevated 1-year mortality, underscores the importance of addressing polypharmacy in HF.

Frontotemporal dementia: Clinical aspects, genetics, and neuropathology of a family with a C9ORF72 expansion in Argentina

2026-01-07T00:00:00Z

Frontotemporal dementia: Clinical aspects, genetics, and neuropathology of a family with a C9ORF72 expansion in Argentina Román, Karen Daniela; Ardohain, Carolina Agata; Surace, Ezequiel Ignacio; Mezmezian, Mónica Beatriz; Levy, Alejandro; Baez Lovera, Alice; Turizo, Carlos; Sorbara, Marcos G.; Esnaola y Rojas, María M.; Graviotto, Gastón H.; Sevlever, Gustavo Emilio; Allegri, Ricardo Francisco; Serrano, Cecilia M.; Magrath Guimet, Nahuel Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia, typically manifesting before the age of 65, with a mean onset at 58 years. FTD may encompass a spectrum of neurodegenerative disorders resulting from frontotemporal lobar degeneration (FTLD), affecting behavior, language, and motor function. Among its clinical variants, the behavioral variant (bvFTD) is the most frequently inherited, often associated with mutations in MAPT, GRN, and C9ORF72, the latter being the most prevalent genetic cause of FTD and FTD-motor neuron disease (FTD-MND). While bvFTD is classically defined by profound behavioral changes and executive dysfunction, cases linked to C9ORF72 expansions exhibit atypical neuropsychiatric features. This study documents two cases within the same family presenting with bvFTD and atypical parkinsonism, associated with a C9ORF72 expansion. Neurocognitive assessments, genetic testing, and neuroimaging (MRI, SPECT) were performed to characterize the clinical phenotype. A detailed review of the familial aggregation of neurodegenerative and psychiatric disorders provided further insight into the genetic contributions to symptomatology. The findings highlight the phenotypic heterogeneity associated with C9ORF72 expansions, demonstrating a spectrum ranging from bvFTD to atypical parkinsonism, with variable neuropsychiatric involvement. While movement disorders in FTD have historically been underestimated, these cases reinforce the association between parkinsonism and familial bvFTD. Given the limited epidemiological data on genetic FTD in Latin America, this study underscores the importance of genetic testing in cases with prominent behavioral and psychiatric symptoms, supporting early identification and genetic counseling for affected families.