Treatment of pediatric extra-axial sinogenic infection: case series and literature review

PURPOSE: Analyze the clinical presentation, microbiology, outcomes, and medical and surgical treatment strategies of intracranial extension of sinogenic infection in pediatric patients. METHODS: A retrospective, single-center study of patients \u3c 18 years of age, presenting with intracranial extension of bacterial sinogenic infections requiring surgical intervention over a 5-year period, was conducted. Electronic medical records were reviewed for age, sex, primary symptoms, duration of symptoms, presence of sinusitis at initial presentation, microorganisms isolated, mode of surgery, timing of surgery, length of stay, and neurologic sequelae. RESULTS: Seventeen patients were identified; mean age was 10 years with 82.3% male predominance. Average duration of illness prior to presentation was 9.8 days, with 64.7% of patients displaying disease progression while on oral antibiotics prior to presentation. Sinusitis and intracranial extension were present in all patients upon admission. Simultaneous endoscopic endonasal drainage and craniotomy were performed on 70.5% of the patients, with the remaining 29.5% undergoing endonasal drainage only. Of the patients who underwent simultaneous endoscopic endonasal drainage and craniotomy, 17.6% required repeat craniotomy and 5.8% required repeat sinus surgery. The most commonly isolated organisms were S. intermedius (52.9%), S. anginosus (23.5%), and S. pyogenes (17.6%). All patients were treated postoperatively antibiotic on average 4-6 weeks. Frequently occurring long-lasting complications included seizures (29.4%) and focal motor deficits (17.6%); learning disability, anxiety disorders, impaired cognition, and sensory deficits occurred less frequently. CONCLUSION: In the case of intracranial extension of bacterial sinogenic infection, early identification and surgical treatment are crucial to avoid neurological sequelae

MicroRNA signatures associated with vulnerability to food addiction in mice and humans

Food addiction is characterized by a loss of behavioral control over food intake and is associated with obesity and other eating disorders. The mechanisms underlying this behavioral disorder are largely unknown. We aimed to investigate the changes in miRNA expression promoted by food addiction in animals and humans and their involvement in the mechanisms underlying the behavioral hallmarks of this disorder. We found sharp similitudes between miRNA signatures in the medial prefrontal cortex (mPFC) of our animal cohort and circulating miRNA levels in our human cohort, which allowed us to identify several miRNAs of potential interest in the development of this disorder. Tough decoy (TuD) inhibition of miRNA-29c-3p in the mouse mPFC promoted persistence of the response and enhanced vulnerability to developing food addiction, whereas miRNA-665-3p inhibition promoted compulsion-like behavior and also enhanced food addiction vulnerability. In contrast, we found that miRNA-137-3p inhibition in the mPFC did not lead to the development of food addiction. Therefore, miRNA-29c-3p and miRNA-665-3p could be acting as protective factors with regard to food addiction. We believe the elucidation of these epigenetic mechanisms will lead to advances toward identifying innovative biomarkers and possible future interventions for food addiction and related disorders based on the strategies now available to modify miRNA activity and expression

miRNA signatures associated with vulnerability to food addiction in mice and humans

Food addiction is characterized by a loss of behavioral control over food intake and is associated with obesity and other eating disorders. The mechanisms underlying this behavioral disorder are largely unknown. We aimed to investigate the changes in miRNA expression promoted by food addiction in animals and humans and their involvement in the mechanisms underlying the behavioral hallmarks of this disorder. We found sharp similitudes between miRNA signatures in the medial prefrontal cortex (mPFC) of our animal cohort and circulating miRNA levels in our human cohort, which allowed us to identify several miRNAs of potential interest in the development of this disorder. Tough decoy (TuD) inhibition of miRNA-29c-3p in the mouse mPFC promoted persistence of the response and enhanced vulnerability to developing food addiction, whereas miRNA-665-3p inhibition promoted compulsion-like behavior and also enhanced food addiction vulnerability. In contrast, we found that miRNA-137-3p inhibition in the mPFC did not lead to the development of food addiction. Therefore, miRNA-29c-3p and miRNA-665-3p could be acting as protective factors with regard to food addiction. We believe the elucidation of these epigenetic mechanisms will lead to advances toward identifying innovative biomarkers and possible future interventions for food addiction and related disorders based on the strategies now available to modify miRNA activity and expression.This work was supported by the Spanish “Ministerio de Ciencia e Innovación (MICIN), Agencia Estatal de Investigación (AEI)” (PID2020-120029GB-I00/MICIN/AEI/10.13039/501100011033, RD21/0009/0019, to RM; SAF2015-68341-R, RTI2018-100968-B-100, and PID2021-1277760B-100, to BC; and SAF2017-84060-R-AEI/FEDER-UE, to LD); the “Generalitat de Catalunya, AGAUR” (2017 SGR-669, to RM; 2017 SGR-734, to JMFR; 2017-SGR-738, to BC); the “ICREA-Acadèmia” (2020, to RM, 2021, to BC, and 2022, to JMFR); the “European Commission-DG Research” (PainFact, H2020-SC1-2019-2-RTD-848099, QSPain Relief, H2020-SC1-2019-2-RTD-848068, to RM; CoCA, H2020-667302, and Eat2beNICE, H2020-728018, to BC); the Spanish “Instituto de Salud Carlos III, RETICS-RTA” (RD16/0017/0020, to RM; FIS PI15/01934, PI18/01022, PI21/01361, to JMFR); the Spanish “Ministerio de Sanidad, Servicios Sociales e Igualdad, Plan Nacional Sobre Drogas” (PNSD- 2021I076, to RM; PNSD-2019I006, to EMG; PNSD-2017I050, to BC; PNSD-2020I042, to NFC); the “Fundació La Marató-TV3” (2016/20-30, to EMG); the European Regional Development Fund (project no. 01.2.2-LMT-K-718-03-0099) under a grant agreement with the Research Council of Lithuania (LMTLT), to AB; and the Project ThinkGut (EFA345/19), 65% co-financed by the European Regional Development Fund (ERDF) through the Interreg V-A Spain-France-Andorra programme (POCTEFA 2014-2020

Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food.

BACKGROUND: Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward. METHODS: We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons. We characterized the genetic deletion by histology, electrophysiology, and microdialysis; probed neuronal activation by c-Fos immunohistochemistry and resting-state functional magnetic resonance imaging; and investigated main behavioral responses to opiates, including motivation to obtain heroin and palatable food. RESULTS: Mutant mice showed MOR transcript deletion mainly in the striatum. In the ventral tegmental area, local MOR activity was intact, and reduced activity was only observed at the level of striatonigral afferents. Heroin-induced neuronal activation was modified at both sites, and whole-brain functional networks were altered in live animals. Morphine analgesia was not altered, and neither was physical dependence to chronic morphine. In contrast, locomotor effects of heroin were abolished, and heroin-induced catalepsy was increased. Place preference to heroin was not modified, but remarkably, motivation to obtain heroin and palatable food was enhanced in operant self-administration procedures. CONCLUSIONS: Our study reveals dissociable MOR functions across mesocorticolimbic networks. Thus, beyond a well-established role in reward processing, operating at the level of local ventral tegmental area neurons, MORs also moderate motivation for appetitive stimuli within forebrain circuits that drive motivated behaviors