Evaluating Providers’ Prescription Opioid Instructions to Pediatric Patients

Receiving an opioid prescription during childhood increases the risk of hazardous prescription opioid (PO) use during emerging adulthood. Instruction on how to safely use POs plays an essential role in pediatric patients’ capacity to utilize as well as to discontinue POs appropriately. This study aimed to evaluate pediatric PO label instructions provided to a large sample of pediatric outpatients. Data were extracted from the electronic healthcare records system identifying pediatric patients who received a PO between 2016 and 2019 from pediatric outpatient medical clinics were affiliated with a northwestern United States medical center and children’s hospital. Pediatric patients (n = 12,613) between 0–17 years old who received a PO during outpatient care were included. Patients with chronic health conditions (e.g., cancer) or who received their PO from an inpatient medical setting were excluded. Patient demographics, medication instructions, associated diagnoses, and other prescription information (e.g., name of medication, dose, and quantity dispensed) were examined using automated text classification. Many label instructions did not include any indication/reason for use (20.8%). Virtually none of the POs (\u3e99%) included instructions for how to reduce/wean off POs, contact information for questions about the POs, and/or instructions around how to dispose of the POs. Efforts are needed to ensure that pediatric PO instructions contain essential elements to improve comprehension of when and how to use POs for pediatric patients

Nat Metab

Hypothalamic AgRP and POMC neurons are conventionally viewed as the yin and yang of the body’s energy status, since they act in an opposite manner to modulate appetite and systemic energy metabolism. However, although AgRP neurons’ functions are comparatively well understood, a unifying theory of how POMC neuronal cells operate has remained elusive, probably due to their high level of heterogeneity, which suggests that their physiological roles might be more complex than initially thought. In this Perspective, we propose a conceptual framework that integrates POMC neuronal heterogeneity with appetite regulation, whole-body metabolic physiology and the development of obesity. We highlight emerging evidence indicating that POMC neurons respond to distinct combinations of interoceptive signals and food-related cues to fine-tune divergent metabolic pathways and behaviours necessary for survival. The new framework we propose reflects the high degree of developmental plasticity of this neuronal population and may enable progress towards understanding of both the aetiology and treatment of metabolic disorders.Bordeaux Region Aquitaine Initiative for NeuroscienceInnovations instrumentales et procédurales en psychopathologie expérimentale chez le rongeurLa signalisation des acides biliaires dans le cerveau et son rôle dans le contrôle métaboliqueRôle du récepteur aux cannabinoïdes de type 1 mitochondriale dans les circuits hypothalamiques et son interaction avec la voie mTORC1 dans l'obésité.Rôle de Tbx3 dans la détermination de l'identité fonctionnelle des neurones POMC dans l'obésitéEuropean Union Seventh Framework Programme FP7/2007-201

Mitochondrial Uncoupling Protein-2 (UCP2) Mediates Leptin Protection Against MPP+ Toxicity in Neuronal Cells

Mitochondrial dysfunction is involved in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). Uncoupling proteins (UCPs) delink ATP production from biofuel oxidation in mitochondria to reduce oxidative stress. UCP2 is expressed in brain, and has neuroprotective effects under various toxic insults. We observed induction of UCP2 expression by leptin in neuronal cultures, and hypothesize that leptin may preserve neuronal survival via UCP2. We showed that leptin preserved cell survival in neuronal SH-SY5Y cells against MPP+ toxicity (widely used in experimental Parkinsonian models) by maintaining ATP levels and mitochondrial membrane potential (MMP); these effects were accompanied by increased UCP2 expression. Leptin had no effect in modulating reactive oxygen species levels. Stable knockdown of UCP2 expression reduced ATP levels, and abolished leptin protection against MPP+-induced mitochondrial depolarization, ATP deficiency, and cell death, indicating that UCP2 is critical in mediating these neuroprotective effects of leptin against MPP+ toxicity. Interestingly, UCP2 knockdown increased UCP4 expression, but not of UCP5. Our findings show that leptin preserves cell survival by maintaining MMP and ATP levels mediated through UCP2 in MPP+-induced toxicity

Analysis of the Aspergillus fumigatus Proteome Reveals Metabolic Changes and the Activation of the Pseurotin A Biosynthesis Gene Cluster in Response to Hypoxia

The mold Aspergillus fumigatus is the most important airborne fungal pathogen. Adaptation to hypoxia represents an important virulence attribute for A. fumigatus. Therefore, we aimed at obtaining a comprehensive overview about this process on the proteome level. To ensure highly reproducible growth conditions, an oxygen-controlled, glucose-limited chemostat cultivation was established. Two-dimensional gel electrophoresis analysis of mycelial and mitochondrial proteins as well as two-dimensional Blue Native/SDS-gel separation of mitochondrial membrane proteins led to the identification of 117 proteins with an altered abundance under hypoxic in comparison to normoxic conditions. Hypoxia induced an increased activity of glycolysis, the TCA-cycle, respiration, and amino acid metabolism. Consistently, the cellular contents in heme, iron, copper, and zinc increased. Furthermore, hypoxia induced biosynthesis of the secondary metabolite pseurotin A as demonstrated at proteomic, transcriptional, and metabolite levels. The observed and so far not reported stimulation of the biosynthesis of a secondary metabolite by oxygen depletion may also affect the survival of A. fumigatus in hypoxic niches of the human host. Among the proteins so far not implicated in hypoxia adaptation, an NO-detoxifying flavohemoprotein was one of the most highly up-regulated proteins which indicates a link between hypoxia and the generation of nitrosative stress in A. fumigatus

Empleo de arcillas uruguayas pilareadas para el blanqueo de aceite de maiz.

In the present paper adsorptive capacity to remove carotenes from a com oil by an Uruguayan montmorillonite modified by different treatments: exchange with Na<sup>+</sup> ions (M-Na), acid-activation (Act), exchange with Ca<sup>2+</sup> and pillaring with Keggin ions (Pile-Act), acid-activation and pillaring (Act Pil-Ca), is studied. Bleaching action of the Uruguayan modified montmorillonites is compared with two commercial days: Tonsil Optimum (Süd-Chemie) and montmorillonite of type K 10 (Aldrich). Our results demonstrate that Act and Pilc-Ca samples are so efficient bleaching clays as commercials but M-Na sample Is lower. Also, mixtures of Pilc-Ca with commercial clays, added together in one step or consecutively in two steps, are studied. These procedures do not improved the bleaching action. As conclusion, the modified clay Pilc-Ca allows to bleach a neutralized and degummed corn oil, giving an end product similar to edible commercial oils. Such effect is improved with the simultaneous action with activated clays.<br><br>En este trabajo se estudia la capacidad de adsorción de los carotenos presentes en un aceite de maíz, de una montmorillonita uruguaya modificada por diferentes procedimientos: intercambiada con iones Na<sup>+</sup> (M-Na), activada por ácido (Act), intercambiada con iones Ca<sup>2+</sup> y pilareada con iones Keggin (Pilc-Ca), activada por ácidos y pilareada (Act Pilc-Ca) frente a dos arcillas comerciales: Tonsil Optimum de Süd-Chemie y una Montmorillonita tipo K 10 de Aldrich. Los resultados indican que la muestra Act y la Pilc-Ca son tan eficientes como las comerciales pero que la capacidad de la muestra M-Na es considerablemente menor. También se efectuó ensayos con mezclas de Pilc-Ca con las arcillas comerciales, colocadas simultáneamente (en una sola etapa) o agregadas de manera sucesiva (en dos etapas). Dichos procedimientos no mejoraron la eficiencia del blanqueo. En conclusión, la modificación Pilc-Ca permite blanquear un aceite de maíz neutralizado y desgomado a valores similares a los correspondientes a los aceites comestibles comerciales. Este efecto se mejora aún por la acción simultánea con arcillas activadas