Perceptions of Rural Primary Care Providers in Caring for Infants Exposed to Opioids in Utero: A Qualitative Study

Vermont has one of the highest rates of substance use throughout pregnancy in the country, however there is limited research on the pediatric primary care of infants under one year of age who were exposed to opioids in utero. This project used qualitative interviewing and thematic coding to identify core themes in pediatric primary care for these infants. Core themes and their corresponding targeted areas of improvement and future directions were identifies.https://scholarworks.uvm.edu/fmclerk/1775/thumbnail.jp

Cannabinoids in the treatment of epilepsy: current status and future prospects

Cannabidiol (CBD) is one of the prominent phytocannabinoids found in Cannabis sativa, differentiating from Δ9-tetrahydrocannabinol (THC) for its non-intoxicating profile and its antianxiety/antipsychotic effects. CBD is a multi-target drug whose anti-convulsant properties are supposed to be independent of endocannabinoid receptor CB1 and might be related to several underlying mechanisms, such as antagonism on the orphan GPR55 receptor, regulation of adenosine tone, activation of 5HT1A receptors and modulation of calcium intracellular levels. CBD is a lipophilic compound with low oral bioavailability (6%) due to poor intestinal absorption and high first-pass metabolism. Its exposure parameters are greatly influenced by feeding status (ie, high fatcontaining meals). It is mainly metabolized by cytochrome P 450 (CYP) 3A4 and 2C19, which it strongly inhibits. A proprietary formulation of highly purified, plant-derived CBD has been recently licensed as an adjunctive treatment for Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), while it is being currently investigated in tuberous sclerosis complex. The regulatory agencies’ approval was granted based on four pivotal double-blind, placebocontrolled, randomized clinical trials (RCTs) on overall 154 DS patients and 396 LGS ones, receiving CBD 10 or 20 mg/kg/day BID as active treatment. The primary endpoint (reduction in monthly seizure frequency) was met by both CBD doses. Most patients reported adverse events (AEs), generally from mild to moderate and transient, which mainly consisted of somnolence, sedation, decreased appetite, diarrhea and elevation in aminotransferase levels, the last being documented only in subjects on concomitant valproate therapy. The interaction between CBD and clobazam, likely due to CYP2C19 inhibition, might contribute to some AEs, especially somnolence, but also to CBD clinical effectiveness. Cannabidivarin (CBDV), the propyl analogue of CBD, showed anti-convulsant properties in pre-clinical studies, but a plant-derived, purified proprietary formulation of CBDV recently failed the Phase II RCT in patients with uncontrolled focal seizures

Schwa reduction in low-proficiency L2 speakers: Learning and generalization

This paper investigated the learnability and generalizability of French schwa alternation by Dutch low-proficiency second language learners. We trained 40 participants on 24 new schwa words by exposing them equally often to the reduced and full forms of these words. We then assessed participants' accuracy and reaction times to these newly learnt words as well as 24 previously encountered schwa words with an auditory lexical decision task. Our results show learning of the new words in both forms. This suggests that lack of exposure is probably the main cause of learners' difficulties with reduced forms. Nevertheless, the full forms were slightly better recognized than the reduced ones, possibly due to phonetic and phonological properties of the reduced forms. We also observed no generalization to previously encountered words, suggesting that our participants stored both of the learnt word forms and did not create a rule that applies to all schwa words

Saving soil for sustainable land use

This paper experiments with some costs-benefit analyses, seeking a balance between soil-take and buildability due to land policy and management. The activities have been carried out inside the MITO lab (Lab for Multimedia Information for Territorial Objects) of the Polytechnic University of Bari. Reports have been produced about the Southern Italian Apulia Region, which is rich in farmland and coastline, often invaded by construction, with a severe loss of nature, a degradation of the soil, landscape, and ecosystem services. A methodological approach to the assessment of sustainability of urban expansion related, on one hand, to "plus values" deriving from the transformation of urban fringes and, on the other hand to the analysis of the transition of land-use, with the aim of "saving soil" against urban sprawl. The loss of natural and agricultural surfaces due to the expanding artificial lands is an unsustainable character of urban development, especially in the manner in which it was carried out in past decades. We try to assess how plus value can be considered "unearned", and to understand if the "land value recapture" can compensate for the negative environmental effects of urban expansion. We measured the transition from farmlands and natural habitat to urbanization with the support of the use of some Geographic Information Systems (GIS) tools, in favor of a new artificial land cover in the region of Apulia, Southern Italy. Data have been collected at the regional scale and at the local level, producing information about land use change and increases of property values due to improvements, referring to the 258 municipalities of the region. Looking at the results of our measurements, we started an interpretation of the driving forces that favor the plus values due to the transition of land-use. Compensation, easements, recapture of plus value, and improvement are, nowadays in Italy, discussed as major land-policy tools for managing environmental and landscape preservation. The interplay between urban economics and environmentally sound regulations reveals some controversial issues in urban governance and nature preservation: perhaps some abstract regulations, conjoined with non-case-oriented urban policies, consider these keywords as the old chemists considered the Philosopher's Stone. The analyses show criticality emerging themes in emblematic cases, studied in some municipal contexts

Shock and detonation modeling with the Mie-Grüneisen equation of state

We consider the numerical simulation of inviscid reactive flows with application to high density explosive detonation. The numerical model is based on the Euler equations and the Mie-Grüneisen equation of state extended to treat chemical energy release and expanded states. The equations are computed with a Roe-Glaister solver on a Cartesian mesh. We present results for two substances, a binder and an explosive. Our solution method is verified against the exact solution of the shock tube problem for solid materials. We show under what conditions a "physical" expansion shock can appear in this example. We then address the problem of modeling expanded states, and show results for a two-dimensional shock distraction around a sharp corner. In the last part of the paper, we introduce a detonation model that extends the Mie-Grüneisen equation of state to enable high explosive simulations without the complexity of mixture equations of state. We conclude with two examples of corner-turning computations carried out with a pressure-dependent reaction rate law

A FORTRESS BETWEEN ARTIFICE AND NATURE: THE LASER SCANNING SURVEY OF THE CASTLE OF PESCOPAGANO AS AN INSTRUMENT OF KNOWLEDGE, CONSERVATION AND ENHANCEMENT

Abstract. The castle of Pescopagano, a small village located on the border between Basilicata and Campania, is a complex of great historical and landscape value, for the inseparable combination that binds its stones to the rock where it stands. Founded perhaps in the Byzantine times, but certainly renovated and built in its current forms between the 11th and 12th century, the castle had considerable military importance under Frederick II of Swabia. Seriously damaged by the earthquake of 1694, the fortress underwent a partial reconstruction, but ended up suffering further collapses caused by the Irpinia earthquake of 1980, such as to motivate the first interventions of securing and, above all, the application of the listing process. Today the castle is still largely in ruins and is only partially accessible thanks to a limited intervention on the paths. The present research aims at deepening the knowledge of the state of conservation, the damage mechanisms and the previous restoration interventions of the castle, in order to define possible strategies for its restoration and enhancement. The analysis work uses the most advanced laser scanning and drone detection systems, in order to document, as accurately as possible, the complex patrimonial system of the castle. Thanks to the combined use of these techniques, the objective is also to define methods that can be replicated in other contexts where the relationship between geomorphology and construction is so relevant that it jeopardizes the use of any other traditional survey system

The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy: in vivo and in vitro evidence

Purpose: Interleukin (IL)-8 is a proinflammatory C-X-C chemokine involved in inflammation underling cardiac diseases, primary or in comorbid condition, such diabetic cardiomyopathy (DCM). The phosphodiesterase type 5 inhibitor sildenafil can ameliorate cardiac conditions by counteracting inflammation. The study aim is to evaluate the effect of sildenafil on serum IL-8 in DCM subjects vs. placebo, and on IL-8 release in human endothelial cells (Hfaec) and peripheral blood mononuclear cells (PBMC) under inflammatory stimuli. Methods: IL-8 was quantified: in sera of (30) DCM subjects before (baseline) and after sildenafil (100 mg/day, 3-months) vs. (16) placebo and (15) healthy subjects, by multiplatform array; in supernatants from inflammation-challenged cells after sildenafil (1 µM), by ELISA. Results: Baseline IL-8 was higher in DCM vs. healthy subjects (149.14 ± 46.89 vs. 16.17 ± 5.38 pg/ml, p < 0.01). Sildenafil, not placebo, significantly reduced serum IL-8 (23.7 ± 5.9 pg/ml, p < 0.05 vs. baseline). Receiver operating characteristic (ROC) curve for IL-8 was 0.945 (95% confidence interval of 0.772 to 1.0, p < 0.01), showing good capacity of discriminating the response in terms of drug-induced IL-8 decrease (sensitivity of 0.93, specificity of 0.90). Sildenafil significantly decreased IL-8 protein release by inflammation-induced Hfaec and PBMC and downregulated IL-8 mRNA in PBMC, without affecting cell number or PDE5 expression. Conclusion: Sildenafil might be suggested as potential novel pharmacological tool to control DCM progression through IL-8 targeting at systemic and cellular level

Normotensive offspring with non-dipper hypertensive parents have abnormal sleep pattern.

The objective of this study was to determine whether abnormal microstructure of sleep in non-dipper hypertensive patients was present in their offspring. Subjects included 11 normotensive offspring of non-dipper hypertensive parents (FH + ND), 6 of dipper hypertensive parents (FH + D) and 5 of normotensive parents (Controls). We measured blood pressure beat-to-beat by Finapres and all stages of sleep by polysomnographically recording simultaneously during spontaneous nocturnal sleep. We analysed blood pressure pattern for 4-min long random periods while the subjects were awake and during all stages of sleep; sleep efficiency (SE), sleep latency (SL), delta-sleep latency (delta-SL), REM sleep latency (REM-SL), Stage 1, Stage 2, Stage 3, Stage 4 and REM duration and percentage values, and microstructural aspects of sleep (arousal and microarousal temporization and features). FH + D and controls showed a fall in blood pressure greater than 10% in all stages of NREM sleep and in the FH + ND blood pressure fall in less than 10% of waking values in all NREM stages. REM sleep and heart rate were similar in the three groups during all stages of sleep. FH + ND showed the same number of arousals but more microarousals than FH + D and controls (p < 0.0001). Microarousals induced several stage shifts through lighter sleep. For this reason, FH + ND spent more time in stage 2 than FH + D and controls. In conclusion, offspring of non-dipper hypertension parents showed a greater number of microarousals than the other two groups

Ablation of smooth muscle myosin heavy chain SM2 increases smooth muscle contractility and results in postnatal death in mice

The smooth muscle myosin heavy chains (SMHC) are motor proteins powering smooth muscle contraction. Alternate splicing of SHMC gene at the C-terminus produces SM1, and SM2 myosin isoforms; SM2 (200 kDa) contains a unique 9-amino-acid sequence at the carboxyl terminus, whereas SM1 (204 kDa) has a 43 amino acid non-helical tail region. To date the functional difference between C-terminal isoforms has not been established; therefore, we used an exon-specific gene targeting strategy and generated a mouse model specifically deficient in SM2. Deletion of exon-41 of the SMHC gene resulted in a complete loss of SM2 in homozygous (_SM2^-/-^_) mice, accompanied by a concomitant down-regulation of SM1 in bladders. While heterozygous (_SM2^+/-^_) mice appeared normal and fertile, _SM2^-/-^_ mice died within 30 days after birth. The peri-mortal _SM2^-/-^_ mice showed reduced body weight, distention of the bladder and alimentary tract, and end-stage hydronephrosis. Interestingly, strips from _SM2^-/-^_ bladders showed increased contraction to K^+^ depolarization or M3 receptor activation. These results suggest that SM2 myosin has a distinct functional role in smooth muscle, and the deficiency of SM2 increases smooth muscle contractility, and causes dysfunctions of smooth muscle organs, including the bladder that leads to the end-stage hydronephrosis and postnatal death