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

The bisphenol a induced oxidative stress in non-alcoholic fatty liver disease male patients: A clinical strategy to antagonize the progression of the disease

Introduction: Bisphenol A (BPA) exposure has been correlated to non-alcoholic fatty liver disease (NAFLD) development and progression. We investigated, in a clinical model, the effects of the administration of 303 mg of silybin phospholipids complex, 10 μg of vitamin D, and 15 mg of vitamin E (RealSIL, 100D, IBI-Lorenzini, Aprilia, Italy) in male NAFLD patients exposed to BPA on metabolic, hormonal, and oxidative stress-related parameters. Methods: We enrolled 32 male patients with histologic diagnosis of NAFLD and treated them with Realsil 100D twice a day for six months. We performed at baseline clinical, biochemical, and food consumption assessments as well as the evaluation of physical exercise, thiobarbituric acid reactive substances (TBARS), plasmatic and urinary BPA and estrogen levels. The results obtained were compared with those of healthy control subjects and, in the NAFLD group, between baseline and the end of treatment. Results: A direct proportionality between TBARS levels and BPA exposure was shown (p < 0.0001). The therapy determined a reduction of TBARS levels (p = 0.011), an improvement of alanine aminotransferase, aspartate aminotransferase, insulinemia, homeostatic model assessment insulin resistance, C reactive protein, tumor necrosis factor alpha (p < 0.05), an increase of conjugated BPA urine amount, and a reduction of its free form (p < 0.0001; p = 0.0002). Moreover, the therapy caused an increase of plasmatic levels of the native form of estrogens (p = 0.03). Conclusions: We highlighted the potential role of BPA in estrogen oxidation and oxidative stress in NAFLD patients. The use of Realsil 100D could contribute to fast BPA detoxification and to improve cellular antioxidant power, defending the integrity of biological estrogen-dependent pathways

Developing K-2 Filipino children English language oral proficiency through concrete poetry teaching

The impact of concrete poetry as a strategy to increase word recognition in ten K-2 Filipino children with low oracy/literacy in English was examined in this six-month study utilizing the single-group pre-test/post-test method. Concrete poetry is a distinct form of poetry that comes in a variety of colors, textures, shapes, and even flavors. Either a static or dynamic poem is a concrete poem. These K-2 students, who were chosen at random from the preschools, were taught how to write their own concrete poetry and gained word recognition skills from them. It was believed that concrete poetry could aid increase word recognition by enhancing receptive and expressive oral vocabulary

Action Observation Areas Represent Intentions From Subtle Kinematic Features

Mirror neurons have been proposed to underlie humans’ ability to understand others’ actions and intentions. Despite 2 decades of research, however, the exact computational and neuronal mechanisms implied in this ability remain unclear. In the current study, we investigated whether, in the absence of contextual cues, regions considered to be part of the human mirror neuron system represent intention from movement kinematics. A total of 21 participants observed reach-to-grasp movements, performed with either the intention to drink or to pour while undergoing functional magnetic resonance imaging. Multivoxel pattern analysis revealed successful decoding of intentions from distributed patterns of activity in a network of structures comprising the inferior parietal lobule, the superior parietal lobule, the inferior frontal gyrus, and the middle frontal gyrus. Consistent with the proposal that parietal regions play a key role in intention understanding, classifier weights were higher in the inferior parietal region. These results provide the first demonstration that putative mirror neuron regions represent subtle differences in movement kinematics to read the intention of an observed motor act

Mitochondria and the regulation of free radical damage in the eye

Neuronal cell death can be determined by the overall level of reactive oxygen species (ROS) resulting from the combination of extrinsic sources and intrinsic production as a byproduct of oxidative phosphorylation. Key controllers of the intrinsic production of ROS are the mitochondrial uncoupling proteins (UCPs). By allowing a controlled leak of protons across the inner mitochondrial membrane activation of these proteins can decrease ROS and promote cell survival. In both primate models of Parkinson’s disease and mouse models of seizures, increased activity of UCP2 significantly increased neuronal cells survival. In the retina UCP2 is expressed in many neurons and glial cells, but was not detected in rod photoreceptors. Retinal ganglion cell survival following excitotoxic damage was much greater in animals overexpressing UCP2. Traditional Chinese medicines, such as an extract of Cistanche tubulosa, may provide benefit by altering mitochondrial metabolism

Modulation of presynaptic plasticity and learning by the H-ras/extracellular signal-regulated kinase/synapsin I signaling pathway

Molecular and cellular studies of the mechanisms underlying mammalian learning and memory have focused almost exclusively on postsynaptic function. We now reveal an experience-dependent presynaptic mechanism that modulates learning and synaptic plasticity in mice. Consistent with a presynapticfunctionfor endogenous H-ras/extracellular signal-regulated kinase (ERK) signaling, we observed that, under normal physiologic conditions in wild-type mice, hippocampus-dependent learning stimulated the ERK-dependent phosphorylation of synapsin I, and MEK (MAP kinase kinase)/ERK inhibition selectively decreased the frequency of miniature EPSCs. By generating transgenic mice expressing a constitutively active form of H-ras (H-rasG12V), which is abundantly localized in axon terminals, we were able to increase the ERK-dependent phosphorylation of synapsin I. This resulted in several presynaptic changes, including a higher density of docked neurotransmitter vesiclesin glutamatergicterminals, anincreasedfrequency of miniature EPSCs, andincreased paired-pulse facilitation. In addition, we observed facilitated neurotransmitter release selectively during high-frequency activity with consequent increases in long-term potentiation. Moreover, these mice showed dramatic enhancements in hippocampus-dependent learning. Importantly, deletion of synapsin I, an exclusively presynaptic protein, blocked the enhancements of learning, presynaptic plasticity, and long-term potentiation. Together with previous invertebrate studies, these results demonstrate that presynaptic plasticity represents an important evolutionarily conserved mechanism for modulating learning and memory

Impaired glymphatic system in genetic frontotemporal dementia: a GENFI study

The glymphatic system is an emerging target in neurodegenerative disorders. Here, we investigated the activity of the glymphatic system in genetic frontotemporal dementia with a diffusion-based technique called diffusion tensor image analysis along the perivascular space. We investigated 291 subjects with symptomatic or presymptomatic frontotemporal dementia (112 with chromosome 9 open reading frame 72 [C9orf72] expansion, 119 with granulin [GRN] mutations and 60 with microtubule-associated protein tau [MAPT] mutations) and 83 non-carriers (including 50 young and 33 old non-carriers). We computed the diffusion tensor image analysis along the perivascular space index by calculating diffusivities in the x-, y- and z-axes of the plane of the lateral ventricle body. Clinical stage and blood-based markers were considered. A subset of 180 participants underwent cognitive follow-ups for a total of 640 evaluations. The diffusion tensor image analysis along the perivascular space index was lower in symptomatic frontotemporal dementia (estimated marginal mean ± standard error, 1.21 ± 0.02) than in old non-carriers (1.29 ± 0.03, P = 0.009) and presymptomatic mutation carriers (1.30 ± 0.01, P < 0.001). In mutation carriers, lower diffusion tensor image analysis along the perivascular space was associated with worse disease severity (β = −1.16, P < 0.001), and a trend towards a significant association between lower diffusion tensor image analysis along the perivascular space and higher plasma neurofilament light chain was reported (β = −0.28, P = 0.063). Analysis of longitudinal data demonstrated that worsening of disease severity was faster in patients with low diffusion tensor image analysis along the perivascular space at baseline than in those with average (P = 0.009) or high (P = 0.006) diffusion tensor image analysis along the perivascular space index. Using a non-invasive imaging approach as a proxy for glymphatic system function, we demonstrated glymphatic system abnormalities in the symptomatic stages of genetic frontotemporal dementia. Such measures of the glymphatic system may elucidate pathophysiological processes in human frontotemporal dementia and facilitate early phase trials of genetic frontotemporal dementia

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