In search of the behavioural effects of fear: a paradigm to assess conditioned suppression in humans

Conditioned fear can substantially reduce the likelihood that an individual will engage in reward- related behaviour - a phenomenon coined conditioned suppression. Despite the unmistakable relevance of conditioned suppression for excessive fears and their adverse consequences, the phenomenon has primarily been observed in animal models and is not yet well understood. Here, we aimed to develop a conditioned suppression paradigm that enables a robust quantification of the effect of Pavlovian aversive stimuli on subsequent reward-related behaviour in humans and assess its potential relation to physiological measures of fear. In phase 1, an instrumental response was incentivized with monetary rewards. In phase 2, one of two conditioned stimuli (CS+) was reinforced with an aversive unconditioned stimulus (US, i.e., electric stimulus). During aversive Pavlovian learning we assessed differential skin conductance (SCR) and fear potentiated startle responses (FPS). Lastly, we tested the effect of the aversively conditioned CS+ on the response rate of the instrumental response in a transfer phase. Despite strong aversive Pavlovian conditioning, as indicated by large effect sizes in differential SCR and FPS, we did not find any evidence for conditioned suppression: i.e., there was no significant reduction of instrumental responding in the presence of the CS+ compared to a new control stimulus. This lack of conditioned suppression is in line with previous studies that reported difficulties inducing conditioned suppression and points towards a general challenge in investigating conditioned suppression in humans. Implications and directions for future research on the highly relevant behavioural effects of fear and anxiety are discussed.

Flexoelectricity in soft elastomers and the molecular mechanisms underpinning the design and emergence of giant flexoelectricity

Soft robotics requires materials that are capable of large deformation and amenable to actuation with external stimuli such as electric fields. Energy harvesting, biomedical devices, flexible electronics, and sensors are some other applications enabled by electroactive soft materials. The phenomenon of flexoelectricity is an enticing alternative that refers to the development of electric polarization in dielectrics when subjected to strain gradients. In particular, flexoelectricity offers a direct linear coupling between a highly desirable deformation mode (flexure) and electric stimulus. Unfortunately, barring some exceptions, the flexoelectric effect is quite weak and rather substantial bending curvatures are required for an appreciable electromechanical response. Most experiments in the literature appear to confirm modest flexoelectricity in polymers although perplexingly, a singular work has measured a “giant” effect in elastomers under some specific conditions. Due to the lack of an understanding of the microscopic underpinnings of flexoelectricity in elastomers and a commensurate theory, it is not currently possible to either explain the contradictory experimental results on elastomers or pursue avenues for possible design of large flexoelectricity. In this work, we present a statistical-mechanics theory for the emergent flexoelectricity of elastomers consisting of polar monomers. The theory is shown to be valid in broad generality and leads to key insights regarding both giant flexoelectricity and material design. In particular, the theory shows that, in standard elastomer networks, combining stretching and bending is a mechanism for obtaining giant flexoelectricity, which also explains the aforementioned, surprising experimental discovery.

Effectiveness of spinal accessory intraoperative nerve monitoring during neck dissections

The aim of the study is to evaluate the efficiency and safety of intraoperative neuromonitoring (IONM) of accessory nerves during lateral lymphodissection (LLD). Materials and Methods. Main group consisted of 63 patients with thyroid cancer (TC) with confirmed metastatic spread into cervical lymph nodes of II-V groups, and which underwent IONM of accessory nerve during LLD. Control group consisted of 60 patients in which no IONM was performed during LLD. Main group consisted of 21 males (33.3%); 42 females (66.7%): mean age 50.7 ± 8,7. Control group consisted of 11 males (18.2%); 49 females (81.8%); mean age 47.2 ± 6,8. Results. All patients of main group responded to electric stimulation of accessory nerve during IONM. 58 (92.1%) patients did not present new symptom, whereas 4 (6.3%) noted a moderate pain while lifting and stretching the upper extremity during two weeks. In 1 (1.6%) - temporary difficulty in arm abduction up to 90° was observed. In control group, in 5 (8.3%) - damage to accessory nerve was found which manifested as lack of contraction of trapezius muscle in response to electric stimulus. In 12 (20%) - pain during lifting and abduction of upper extremity on respective side was observed up to 3-4 weeks after surgery. Conclusions. IONM of accessory nerve is a safe and effective way to reduce probability of accessory nerve damage, which, together with improvement in organ-preserving techniques, is demonstrated by decrease of functional loss in upper extremities from 13.3% to 1.6% during the period from 2000 to 2020.

Design of Powernet Knitted Fabrics from PET/BaTiO3 as Pressure Garments for Rehabilitation of Cerebral Palsy

In this study, powernet warp-knit fabrics were designed using polyethylene terephthalate (PET) yarns melt-spun with three different amounts (20, 25, and 30 wt.%) of barium titanate (BaTiO3) and 30 wt.% elastane yarns. The resulting fabrics were characterized by antimicrobial activity, cytotoxicity, electromagnetic shielding properties, differential scanning calorimetry (DSC) analyses, stiffness tests at MD and CD (machine and cross directions), and pressure measurements using wireless pressure sensors. According to the results, the newly-designed pressure garments would help in the rehabilitation of cerebral palsy patients to improve motor skills and to prevent complications by training muscles with the needed tight structure and electric stimulus onto limbs. They would also provide a hygienic environment during long physical therapy for future designs.

Functionally Tailored Electro-Sensitive Poly(Acrylamide)-g-Pectin Copolymer Hydrogel for Transdermal Drug Delivery Application: Synthesis, Characterization, In-vitro and Ex-vivo Evaluation

Background and Objectives: To develop electro-sensitive transdermal drug delivery systems (ETDDS) using polyacrylamide-grafted-pectin (PAAm-g-PCT) copolymer hydrogel for rivastigmine delivery. Methods: Free radical polymerization and alkaline hydrolysis technique was employed to synthesize PAAm-g-PCT copolymer hydrogel. The PAAm-g-PCT copolymeric hydrogel was used as a reservoir and cross-linked blend films of PCT and poly(vinyl alcohol) as rate-controlling membranes (RCMs) to prepare ETDDS. Results: The pH of the hydrogel reservoir was found to be in the range of 6.81 to 6.93 and drug content was 89.05 to 96.29%. The thickness of RCMs was in the range of 51 to 99 μ and RCMs showed permeability behavior against water vapors. There was a reduction in the water vapor transmission rate as the glutaraldehyde (GA) concentration was increased. The drug permeation rate from the ETDDS was enhanced under the influence of electric stimulus against the absence of an electric stimulus. The increase in flux by 1.5 fold was recorded with applied electric stimulus. The reduction in drug permeability observed when the concentration of GA was increased. Whereas, the permeability of the drug was augmented as an electric current was changed from 2 to 8 mA. The pulsatile drug release under “on– off” cycle of electric stimulus witnessed a faster drug release under ‘on’ condition and it was slow under ‘off’ condition. The alteration in skin composition after electrical stimulation was confirmed through histopathology studies. Conclusion: The PAAm-g-PCT copolymer hydrogel is a useful carrier for transdermal drug delivery activated by an electric signal to provide on-demand release of rivastigmine.