Microglia-mediated synaptic loss contributes to the development of cognitive impairments in Alzheimer’s disease (AD). However, the basis for this immune-mediated attack on synapses remains to be elucidated. Treatment with the metabotropic glutamate receptor 5 (mGluR5) silent allosteric modulator (SAM), BMS-984923, prevents β-amyloid oligomer–induced aberrant synaptic signaling while preserving physiological glutamate response. Here, we show that oral BMS-984923 effectively occupies brain mGluR5 sites visualized by [ 18 F]FPEB positron emission tomography (PET) at doses shown to be safe in rodents and nonhuman primates. In aged mouse models of AD ( APPswe/PS1 Δ E9 overexpressing transgenic and App NL-G-F / hMapt double knock-in), SAM treatment fully restored synaptic density as measured by [ 18 F]SynVesT-1 PET for SV2A and by histology, and the therapeutic benefit persisted after drug washout. Phospho-TAU accumulation in double knock-in mice was also reduced by SAM treatment. Single-nuclei transcriptomics demonstrated that SAM treatment in both models normalized expression patterns to a far greater extent in neurons than glia. Last, treatment prevented synaptic localization of the complement component C1Q and synaptic engulfment in AD mice. Thus, selective modulation of mGluR5 reversed neuronal gene expression changes to protect synapses from damage by microglial mediators in rodents.
BACKGROUND: Routinely obtaining intraoperative cultures for abdominal infections is not a currently recommended evidence-based practice. Yet, cultures are frequently sent from these infections when they are managed by image-guided percutaneous drains. OBJECTIVE: This study aimed to determine the utility of cultures from percutaneously drained intra-abdominal abscesses. DESIGN: Retrospective medical record review. SETTING: Single university-affiliated institution. PATIENTS: Inpatients with an intra-abdominal abscess secondary to diverticulitis or appendicitis between 2013 and 2021 managed with image-guided percutaneous drain, excluding those with active chemotherapy, HIV, or solid organ transplant, were included in the study. MAIN OUTCOME MEASURES: Frequency culture data from percutaneous drains changed antimicrobial therapy. RESULTS: There were 221 patients who met the inclusion criteria. Of these, 56% were admitted for diverticulitis and 44% for appendicitis. Patients were 54% female and had a median age of 62 years (range, 18–93), and 14% were active smokers. The median length of hospitalization was 8 days (range, 1–78) and the median antibiotics course was 8 days (range, 1–22). Culture data from percutaneous drains altered antimicrobial therapy in 8% of patients (16/211). A culture was obtained from 95% of drains, with 78% of cultures with growth. Cultures grew multiple bacteria in 66% and mixed variety without speciation in 13%. The most common pathogen was the Bacteroides family at 33% of all bacteria. The most common empiric antibiotic regimens were ceftriaxone used in 33% of patients and metronidazole used in 40% of patients. Female sex (p = 0.027) and presence of bacteria with any antibiotic resistance (p < 0.01) were associated with higher likelihood of cultures influencing antimicrobial therapy. LIMITATIONS: Retrospective and single institution’s microbiome. CONCLUSIONS: Microbiology data from image-guided percutaneous drains of abdominal abscesses altered antimicrobial therapy in 8% of patients, which is lower than reported in previously published literature on cultures obtained surgically. Given this low rate, similar to the recommendation regarding cultures obtained intraoperatively, routinely culturing material from drains placed in abdominal abscesses is not recommended. See Video Abstract at http://links.lww.com/DCR/C64. ¿LOS CULTIVOS DE ABSCESOS INTRA ABDOMINALES DRENADOS PERCUTÁNEAMENTE CAMBIAN EL TRATAMIENTO? UNA REVISIÓN RETROSPECTIVA ANTECEDENTES: La obtención rutinaria de cultivos intra-operatorios para infecciones abdominales no es una práctica basada en evidencia actualmente recomendada. Sin embargo, con frecuencia se envían cultivos de estas infecciones cuando se manejan con drenajes percutáneos guiados por imágenes. OBJETIVO: Determinar la utilidad de los cultivos de abscesos intra-abdominales drenados percutáneamente. DISEÑO: Revisión retrospectiva de gráficos. ESCENARIO: Institución única afiliada a la universidad. PACIENTES: Pacientes hospitalizados con absceso intr...
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