The Drug Candidate BGP-15 Delays the Onset of Diastolic Dysfunction in the Goto-Kakizaki Rat Model of Diabetic Cardiomyopathy

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Negative Inotropic Effect of BGP-15 on the Human Right Atrial Myocardium

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Fused Deposition Modeling 3D Printing: Test Platforms for Evaluating Post-Fabrication Chemical Modifications and In-Vitro Biological Properties

3D printing is attracting considerable interest for its capacity to produce prototypes and small production runs rapidly. Fused deposit modeling (FDM) was used to produce polyvalent test plates for investigation of the physical, chemical, and in-vitro biological properties of printed materials. The polyvalent test plates (PVTPs) are poly-lactic acid cylinders, 14 mm in diameter and 3 mm in height. The polymer ester backbone was surface modified by a series of ramified and linear oligoamines to increase its hydrophilicity and introduce a positive charge. The chemical modification was verified by FT-IR spectroscopy, showing the introduction of amide and amine functions, and contact angle measurements confirmed increased hydrophilicity. Morphology studies (SEM, optical microscopy) indicated that the modification of PVTP possessed a planar morphology with small pits. Positron annihilation lifetime spectroscopy demonstrated that the polymeric free volume decreased on modification. An MTT-based prolonged cytotoxicity test using Caco-2 cells showed that the PVTPs are non-toxic at the cellular level. The presence of surface oligoamines on the PVTPs reduced biofilm formation by Candida albicans SC5314 significantly. The results demonstrate that 3D printed objects may be modified at their surface by a simple amidation reaction, resulting in a reduced propensity for biofilm colonization and cellular toxicity

‘Proactive’ use of cue-context congruence for building reinforcement learning’s reward function

Background: Reinforcement learning is a fundamental form of learning that may be formalized using the Bellman equation. Accordingly an agent determines the state value as the sum of immediate reward and of the discounted value of future states. Thus the value of state is determined by agent related attributes (action set, policy, discount factor) and the agent’s knowledge of the environment embodied by the reward function and hidden environmental factors given by the transition probability. The central objective of reinforcement learning is to solve these two functions outside the agent’s control either using, or not using a model.Results: In the present paper, using the proactive model of reinforcement learning we offer insight on how the brain creates simplified representations of the environment, and how these representations are organized to support the identification of relevant stimuli and action. Furthermore, we identify neurobiological correlates of our model by suggesting that the reward and policy functions, attributes of the Bellman equitation, are built by the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC), respectively. Conclusions: Based on this we propose that the OFC assesses cue-context congruence to activate the most context frame. Furthermore given the bidirectional neuroanatomical link between the OFC and model-free structures, we suggest that model-based input is incorporated into the reward prediction error (RPE) signal, and conversely RPE signal may be used to update the reward-related information of context frames and the policy underlying action selection in the OFC and ACC, respectively. Furthermore clinical implications for cognitive behavioral interventions are discussed

Impact of Drought, Heat, and Their Combination on Chlorophyll Fluorescence and Yield of Wild Barley (Hordeum spontaneum)

The impact of (long-term) drought acclimation and (short-term) heat stress and their combination on fast chlorophyll fluorescence induction curves (OJIP) and grain yield was tested using pot-grown plants of wild barley (Hordeum spontaneum) originating from Northern Egypt. Concerning agronomic traits, the main effect of drought was decreased biomass accumulation and grain yield, while heat specifically affected floral development. The treatments caused specific inhibitions of photosystem II (PSII) functionality. While heat stressed plants showed a reduction of maximum quantum efficiency of PSII (φP0), an indication of effects on oxygen evolving complex (OEC) functionality, and the connectivity of PSII units, these features were entirely missing in drought acclimated plants. Drought caused a reduction of the Performance Index (PIabs) and of the relative amplitude of the IP-phase of the OJIP induction curve (ΔVIP). Individuals suffering from a combination of drought and heat showed a better ability to recover photosynthetic electron transport after the relief of stress in comparison to heat stressed plants. However, this improved capacity to recover was not accompanied by an increased grain yield. Thus, we conclude that chlorophyll fluorescence measurements provide valuable physiological data; however, their use in agronomic studies for the prediction of agronomic traits should be done with some precaution

A Wide Spectrum of Ocular Manifestations Signify Patients with Systemic Sclerosis

Objectives: Systemic sclerosis (SSc) is a rare, chronic connective tissue disease involving multiple organ systems, including the eye. We evaluated the detailed clinical ocular manifestations of outpatients with SSc. Methods: Demographics, disease duration and subtype, nailfold capillaroscopy (NFC) patterns and laboratory parameters encompassing the autoantibody profile of 51 SSc patients were evaluated, and a general ocular examination was performed for each participant. Results: Twenty-nine patients (56.86%) had eyelid skin alterations, 26 (50.98%) had retinal abnormalities, 26 (50.98%) had cataracts, 8 (15.69%) had conjunctival changes, 7 (13.73%) had iris abnormalities, 33 (64.71%) suffered from dry eye disease (DED), and 11 (21.57%) suffered from glaucoma. Significant positive correlations were found between NFC data and both tear breakup time and Ocular Surface Disease Index test values. Conclusions: Eyelid skin abnormalities, DED and retinal abnormalities are among the most common SSc-related ocular involvements. Diverse ophthalmic findings are attributed to the heterogeneity of SSc

Altered irisin/BDNF axis parallels excessive daytime sleepiness in obstructive sleep apnea patients

Study objectives: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a sleep-related breathing disorder, characterized by excessive daytime sleepiness (EDS), paralleled by intermittent collapse of the upper airway. EDS may be the symptom of OSAHS per se but may also be due to the alteration of central circadian regulation. Irisin is a putative myokine and has been shown to induce BDNF expression in several sites of the brain. BDNF is a key factor regulating photic entrainment and consequent circadian alignment and adaptation to the environment. Therefore, we hypothesized that EDS accompanying OSAHS is reflected by alteration of irisin/BDNF axis. Methods: Case history, routine laboratory parameters, serum irisin and BDNF levels, polysomnographic measures and Epworth Sleepiness Scale questionnaire (ESS) were performed in a cohort of OSAHS patients (n=69). Simple and then multiple linear regression was used to evaluate data. Results: We found that EDS reflected by the ESS is associated with higher serum irisin and BDNF levels; β: 1.53; CI: 0.35, 6.15; p=0.012 and β: 0.014; CI: 0.0.005, 0.023; p=0.02, respectively. Furthermore, influence of irisin and BDNF was significant even if the model accounted for their interaction (p=0.006 for the terms serum irisin, serum BDNF and their interaction). Furthermore, a concentration-dependent effect of both serum irisin and BDNF was evidenced with respect to their influence on the ESS. Conclusions: These results suggest that the irisin-BDNF axis influences subjective daytime sleepiness in OSAS patients reflected by the ESS. These results further imply the possible disruption of the circadian regulation in OSAHS. Future interventional studies are needed to confirm this observation