Prenatal exposure to methadone or buprenorphine: Early childhood developmental outcomes.

BACKGROUND: Methadone and buprenorphine are recommended to treat opioid use disorders during pregnancy. However, the literature on the relationship between longer-term effects of prenatal exposure to these medications and childhood development is both spare and inconsistent. METHODS: Participants were 96 children and their mothers who participated in MOTHER, a randomized controlled trial of opioid-agonist pharmacotherapy during pregnancy. The present study examined child growth parameters, cognition, language abilities, sensory processing, and temperament from 0 to 36 months of the child\u27s life. Maternal perceptions of parenting stress, home environment, and addiction severity were also examined. RESULTS: Tests of mean differences between children prenatally exposed to methadone vs. buprenorphine over the three-year period yielded 2/37 significant findings for children. Similarly, tests of mean differences between children treated for NAS relative to those not treated for NAS yielded 1/37 significant finding. Changes over time occurred for 27/37 child outcomes including expected child increases in weight, head and height, and overall gains in cognitive development, language abilities, sensory processing, and temperament. For mothers, significant changes over time in parenting stress (9/17 scales) suggested increasing difficulties with their children, notably seen in increasing parenting stress, but also an increasingly enriched home environment (4/7 scales). CONCLUSIONS: Findings strongly suggest no deleterious effects of buprenorphine relative to methadone or of treatment for NAS severity relative to not-treated for NAS on growth, cognitive development, language abilities, sensory processing, and temperament. Moreover, findings suggest that prenatal opioid agonist exposure is not deleterious to normal physical and mental development

787-5 Systemic Effect of Ramipril on Endothelin, but not on Elcosanoid Levels in Patients with Coronary Artery Disease

Study aimNeurohumoral effects of ramipril (R) alone or in combination with isosorbide dinitrate (ISDN) compared to ISDN or placebo.Study designPlacebo-controlled double-blind parallel group trial.Methods32 patients with coronary artery disease (CAD) received placebo, R5mg, ISDN 20mg slow release b.i.d. or R+ISDN for one week. A 24 hour kinetic profile of ramipril and its metabolite, of ace activity (ACE-A) and of related hormones (renin and aldosterone), of endothelin and of prostaglandins (PG), thromboxane B2 (TXB2), PGF2a, 6-keto PGF1a, the stable metabolite of prostacyclin (PGI2-M) was studied after the first dose. Measurements were repeated after 8 days of treatment before and 3 hours after the morning dose.ResultsHormone measurements are presented as means of percent difference of patients treated with R (n=16) vs. those without ace-inhibitor (n=16).Time (hrs)0123468240–83–8Ramipril (mg/l)08543210.417Ramiprilat (mg/l)0611108751214ACE-A (%)-6-78-95-98-98-97-96-80-82-98Aldosteron (%)9-5-31-34-21-27-23-34--Renin (%)-9-771913175332--Endothelin (%)-17-13-25-19-16-15-40--TXB2 (%)41045-5012-3PGF2a (%)101700-8-22-9PGI2-M (%)70-38--59-1-713-=not done; significant differences are printed in italics (two-tailed t-test)A single oral dose of 5mg R reduced ACE activity (p<0.001), decreased aldosterone and increased renin (p<0.1). R did not influence plasma levels of the vasoconstricting (TXB2, PGF2a) or vasodilating (PGI2-M) eicosanoid mediators, but decreased endothelin (p<0.1).ConclusionR, in a dose that results in significant systemic inhibition of the renin angiotensin aldosteron system, does not induce measurable changes of circulating eicosanoid concentrations, but seems to diminish systemic release of endothelin

Hemodynamic effects of nitroglycerin in an experimental model of acute aortic regurgitation

AbstractAfterload reduction is an accepted therapeutic modality for the treatment of congestive heart failure caused by chronic aortic regurgitation. However, the role of vasodilator therapy in acute aortic incompetence has not been established. To investigate this, left ventricular volume overload was produced in 18 dogs by constructing a valved conduit from the descending thoracic aorta to the left ventricular apex. The time course of aortic, pulmonary and conduit flows was analyzed in eight control studies and established stability of the experimental model.In the remaining 10 dogs, intravenous nitroglycerin, titrated to reduce mean aortic blood pressure by 40%, and placebo (ethanol) were each infused for 20 min periods. Compared with placebo, nitroglycerin significantly reduced aortic flow (3,945 ± 324 to 3,397 ± 362 ml/min, p < 0.01), regurgitant flow (1,304 ± 131 to 764 ± 90 ml/min, p < 0.001), septal-lateral end-diastolic diameter (47.5 ± 1.8 to 46.5 ± 1.8 mm, p < 0.001), left ventricular end-diastolic pressure (6.9 ± 0.8 to 6.0 ± 0.6 mm Hg, p < 0.05), left ventricular stroke work (19.0 ± 2.6 to 10.8 ± 1.7 g-m/beat, p < 0.001) and systemic vascular resistance (2,253 ± 173 to 1,433 ± 117 dyne-s/cm5, p < 0.001). In contrast, pulmonary flow, left anterior descending coronary flow and subendocardial pH did not change during infusion of either nitroglycerin or placebo.These data indicate that by decreasing preload and afterload, and by preserving coronary flow and tissue pH, nitroglycerin effectively reduced ventricular and regurgitant volumes in the setting of acute volume overload. This study supports the clinical use of nitroglycerin in severe acute aortic incompetence

Novel UV-transparent 2-component polyurethane resin for chip-on-board LED micro lenses

In this work we present a novel optical polymer system based on polyurethane elastomer components, which combines excellent UV transparency with high thermal stability, good hardness, high surface tension and long pot life. The material looks very promising for encapsulation and microlensing applications for chip-on-board (CoB) light-emitting diodes (LED). The extinction coefficient k, refractive index n, and bandgap parameters were derived from transmission and reflection measurements in a wavelength range of 200-890 nm. Thermogravimetry and differential scanning calorimetry were used to provide glass transition and degradation temperatures. The surface tension was determined by means of contact angle measurements. As proof of concept, a commercial InGaN-CoB-LED is used to demonstrate the suitability of the new material for the production of microlenses. © 2020 Optical Society of America

CORUM: the comprehensive resource of mammalian protein complexes—2009

CORUM is a database that provides a manually curated repository of experimentally characterized protein complexes from mammalian organisms, mainly human (64%), mouse (16%) and rat (12%). Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. The new CORUM 2.0 release encompasses 2837 protein complexes offering the largest and most comprehensive publicly available dataset of mammalian protein complexes. The CORUM dataset is built from 3198 different genes, representing ∼16% of the protein coding genes in humans. Each protein complex is described by a protein complex name, subunit composition, function as well as the literature reference that characterizes the respective protein complex. Recent developments include mapping of functional annotation to Gene Ontology terms as well as cross-references to Entrez Gene identifiers. In addition, a ‘Phylogenetic Conservation’ analysis tool was implemented that analyses the potential occurrence of orthologous protein complex subunits in mammals and other selected groups of organisms. This allows one to predict the occurrence of protein complexes in different phylogenetic groups. CORUM is freely accessible at (http://mips.helmholtz-muenchen.de/genre/proj/corum/index.html)

Temporomandibular Joint Disorder Complaints in Tinnitus: Further Hints for a Putative Tinnitus Subtype

OBJECTIVE: Tinnitus is considered to be highly heterogeneous with respect to its etiology, its comorbidities and the response to specific interventions. Subtyping is recommended, but it remains to be determined which criteria are useful, since it has not yet been clearly demonstrated whether and to which extent etiologic factors, comorbid states and interventional response are related to each other and are thus applicable for subtyping tinnitus. Analyzing the Tinnitus Research Initiative Database we differentiated patients according to presence or absence of comorbid temporomandibular joint (TMJ) disorder complaints and compared the two groups with respect to etiologic factors. METHODS: 1204 Tinnitus patients from the Tinnitus Research Initiative (TRI) Database with and without subjective TMJ complaints were compared with respect to demographic, tinnitus and audiological characteristics, questionnaires, and numeric ratings. Data were analysed according to a predefined statistical analysis plan. RESULTS: Tinnitus patients with TMJ complaints (22% of the whole group) were significantly younger, had a lower age at tinnitus onset, and were more frequently female. They could modulate or mask their tinnitus more frequently by somatic maneuvers and by music or sound stimulation. Groups did not significantly differ for tinnitus duration, type of onset (gradual/abrupt), onset related events (whiplash etc.), character (pulsatile or not), hyperacusis, hearing impairment, tinnitus distress, depression, quality of life and subjective ratings (loudness etc.). CONCLUSION: Replicating previous work in tinnitus patients with TMJ complaints, classical risk factors for tinnitus like older age and male gender are less relevant in tinnitus patients with TMJ complaints. By demonstrating group differences for modulation of tinnitus by movements and sounds our data further support the notion that tinnitus with TMJ complaints represents a subgroup of tinnitus with clinical features that are highly relevant for specific therapeutic management

Relationship between Audiometric Slope and Tinnitus Pitch in Tinnitus Patients: Insights into the Mechanisms of Tinnitus Generation

BACKGROUND: Different mechanisms have been proposed to be involved in tinnitus generation, among them reduced lateral inhibition and homeostatic plasticity. On a perceptual level these different mechanisms should be reflected by the relationship between the individual audiometric slope and the perceived tinnitus pitch. Whereas some studies found the tinnitus pitch corresponding to the maximum hearing loss, others stressed the relevance of the edge frequency. This study investigates the relationship between tinnitus pitch and audiometric slope in a large sample. METHODOLOGY: This retrospective observational study analyzed 286 patients. The matched tinnitus pitch was compared to the frequency of maximum hearing loss and the edge of the audiogram (steepest hearing loss) by t-tests and correlation coefficients. These analyses were performed for the whole group and for sub-groups (uni- vs. bilateral (117 vs. 338 ears), pure-tone vs. narrow-band (340 vs. 115 ears), and low and high audiometric slope (114 vs. 113 ears)). FINDINGS: For the right ear, tinnitus pitch was in the same range and correlated significantly with the frequency of maximum hearing loss, but differed from and did not correlate with the edge frequency. For the left ear, similar results were found but the correlation between tinnitus pitch and maximum hearing loss did not reach significance. Sub-group analyses (bi- and unilateral, tinnitus character, slope steepness) revealed identical results except for the sub-group with high audiometric slope which revealed a higher frequency of maximum hearing loss as compared to the tinnitus pitch. CONCLUSION: The study-results confirm a relationship between tinnitus pitch and maximum hearing loss but not to the edge frequency, suggesting that tinnitus is rather a fill-in-phenomenon resulting from homeostatic mechanisms, than the result of deficient lateral inhibition. Sub-group analyses suggest that audiometric steepness and the side of affected ear affect this relationship. Future studies should control for these potential confounding factors

HIPPIE: Integrating Protein Interaction Networks with Experiment Based Quality Scores

Protein function is often modulated by protein-protein interactions (PPIs) and therefore defining the partners of a protein helps to understand its activity. PPIs can be detected through different experimental approaches and are collected in several expert curated databases. These databases are used by researchers interested in examining detailed information on particular proteins. In many analyses the reliability of the characterization of the interactions becomes important and it might be necessary to select sets of PPIs of different confidence levels. To this goal, we generated HIPPIE (Human Integrated Protein-Protein Interaction rEference), a human PPI dataset with a normalized scoring scheme that integrates multiple experimental PPI datasets. HIPPIE's scoring scheme has been optimized by human experts and a computer algorithm to reflect the amount and quality of evidence for a given PPI and we show that these scores correlate to the quality of the experimental characterization. The HIPPIE web tool (available at http://cbdm.mdc-berlin.de/tools/hippie) allows researchers to do network analyses focused on likely true PPI sets by generating subnetworks around proteins of interest at a specified confidence level

Chemical Diversity and Defence Metabolism: How Plants Cope with Pathogens and Ozone Pollution

Chemical defences represent a main trait of the plant innate immune system. Besides regulating the relationship between plants and their ecosystems, phytochemicals are involved both in resistance against pathogens and in tolerance towards abiotic stresses, such as atmospheric pollution. Plant defence metabolites arise from the main secondary metabolic routes, the phenylpropanoid, the isoprenoid and the alkaloid pathways. In plants, antibiotic compounds can be both preformed (phytoanticipins) and inducible (phytoalexins), the former including saponins, cyanogenic glycosides and glucosinolates. Chronic exposure to tropospheric ozone (O3) stimulates the carbon fluxes from the primary to the secondary metabolic pathways to a great extent, inducing a shift of the available resources in favour of the synthesis of secondary products. In some cases, the plant defence responses against pathogens and environmental pollutants may overlap, leading to the unspecific synthesis of similar molecules, such as phenylpropanoids. Exposure to ozone can also modify the pattern of biogenic volatile organic compounds (BVOC), emitted from plant in response to herbivore feeding, thus altering the tritrophic interaction among plant, phytophagy and their natural enemies. Finally, the synthesis of ethylene and polyamines can be regulated by ozone at level of S-adenosylmethionine (SAM), the biosynthetic precursor of both classes of hormones, which can, therefore, mutually inhibit their own biosynthesis with consequence on plant phenotype