Cryogel-based neurostimulation electrodes to activate endogenous neural precursor cells.

The delivery of electrical pulses to the brain via penetrating electrodes, known as brain stimulation, has been recognized as an effective clinical approach for treating neurological disorders. Resident brain neural precursor cells (NPCs) are electrosensitive cells that respond to electrical stimulation by expanding in number, migrating and differentiating which are important characteristics that support neural repair. Here, we report the design of a conductive cryogel brain stimulation electrode specifically developed for NPC activation. The cryogel electrode has a modulus switching mechanism permitting facile penetration and reducing the mechanical mismatch between brain tissue and the penetrating electrode. The cryogel demonstrated good in vivo biocompatibility and reduced the interfacial impedance to deliver the stimulating electric field with lower voltage under charge-balanced current controlled stimulation. An ex vivo assay reveals that electrical stimulation using the cryogel electrodes results in significant expansion in the size of NPC pool. Hence, the cryogel electrodes have the potential to be used for NPC activation to support endogenous neural repair. STATEMENT OF SIGNIFICANCE: The objective of this study is to develop a cryogel-based stimulation electrode as an alternative to traditional electrode materials to be used in regenerative medicine applications for enhancing neural regeneration in brain. The electrode offers benefits such as adaptive modulus for implantation, high charge storage and injection capacities, and modulus matching with brain tissue, allowing for stable delivery of electric field for long-term neuromodulation. The electrochemical properties of cryogel electrodes were characterized in living tissue with an ex vivo set-up, providing a deeper understanding of stimulation capacity in brain environments. The cryogel electrode is biocompatible and enables low voltage, current-controlled stimulation for effective activation of endogenous neural precursor cells, revealing their potential utility in neural stem cell-mediated brain repair.

A MYCN-independent mechanism mediating secretome reprogramming and metastasis in MYCN-amplified neuroblastoma.

MYCN amplification (MNA) is a defining feature of high-risk neuroblastoma (NB) and predicts poor prognosis. However, whether genes within or in close proximity to the MYCN amplicon also contribute to MNA+ NB remains poorly understood. Here, we identify that GREB1, a transcription factor encoding gene neighboring the MYCN locus, is frequently coexpressed with MYCN and promotes cell survival in MNA+ NB. GREB1 controls gene expression independently of MYCN, among which we uncover myosin 1B (MYO1B) as being highly expressed in MNA+ NB and, using a chick chorioallantoic membrane (CAM) model, as a crucial regulator of invasion and metastasis. Global secretome and proteome profiling further delineates MYO1B in regulating secretome reprogramming in MNA+ NB cells, and the cytokine MIF as an important pro-invasive and pro-metastatic mediator of MYO1B activity. Together, we have identified a putative GREB1-MYO1B-MIF axis as an unconventional mechanism promoting aggressive behavior in MNA+ NB and independently of MYCN.

Loaded Inter-set Stretching for Muscular Adaptations in Trained Males: Is the Hype Real?

The study examined the effects of adding a loaded stretch in the inter-set rest period (ISS) compared to traditional resistance training (TR) on muscular adaptations in resistance-trained males. Twenty-six subjects were randomly assigned into two groups (ISS: n=12; TR: n=14) and underwent an 8-week training regimen. Subjects in ISS underwent an additional loaded stretch for 30 s at 15% of their working load from the prior set during the inter-set rest periods. Muscle thickness of the pectoralis major at the belly (BMT) and lateral (LMT) portions, One-repetition maximum (1RM) and repetitions-to-failure (RTF) on the bench press exercise were measured at baseline and post 8 weeks of training. Additionally, volume load and perceptual parameters for exertion and recovery were measured. Both groups had similar total volume load and average perceptual parameters (p>0.05). There was a main time effect (p<0.01) for all but one dependent variable indicating that both groups responded similarly across time [(∆BMT: ISS=2.7±1.7 mm; TR = 3.0±2.2 mm), (∆LMT: ISS=3.2±1.6 mm; TR=2.8±1.7 mm, (∆1RM: ISS=6.6±3.8 kg; TR=7.5±5.7 kg). Repetitions-to-failure did not change in either group (∆RTF: ISS=0.0±2.1 repetitions; TR=0.0±2.3 repetitions, p>0.05). Our results suggest that addition of a loaded ISS does not affect muscular adaptations either positively or negatively in resistance-trained males.

Electric Field Application In Vivo Regulates Neural Precursor Cell Behavior in the Adult Mammalian Forebrain.

Deep brain stimulation (DBS), which uses electrical stimulation, is a well-established neurosurgical technique used to treat neurologic disorders. Despite its broad therapeutic use, the effects of electrical stimulation on brain cells is not fully understood. Here, we examine the effects of electrical stimulation on neural stem and progenitor cells (collectively neural precursor cells; NPCs) from the subventricular zone in the adult forebrain of C57BL/6J mice. Previous work has demonstrated that adult-derived NPCs are electro sensitive and undergo rapid and directed migration in response to application of clinically relevant electric fields (EFs). We examine NPC proliferation kinetics and their differentiation profile following EF application using in vitro and in vivo assays. In vitro direct current electrical stimulation of 250 mV/mm is sufficient to elicit a 2-fold increase in the neural stem cell pool and increases neurogenesis and oligogenesis. In vivo, asymmetric biphasic electrical stimulation similarly increases the size of the NPC pool and alters neurogenesis. These findings provide insight into the effects of electrical stimulation on NPCs and suggest its potential use as a regenerative approach to neural repair.

Acute and daily effects of repeated voluntary hyperpnea on pulmonary function in healthy adults.

PURPOSE: Hyperpnea training has been used as a method for both improving exercise performance in healthy persons and improving ventilatory capacity in patients with pulmonary disease. However, voluntary hyperpnea causes acute declines in pulmonary function, but the effects of repeated days of hyperpnea on airway function are not known. The purpose of this study was to determine the effects of repeated normocapnic hyperpnea on daily and post-hyperpnea pulmonary function in healthy adults. METHODS: Ten healthy adults (21 years; 170 cm; 66 kg) completed ten hyperpnea training sessions within 17-days (TR). Training sessions consisted of 20-minutes of normocapnic hyperpnea with gradually increased minute ventilation over the 10 days. Spirometry was assessed at baseline and serially following hyperpnea during each experimental day. A control group (24 years; 171 cm; 66 kg) completed 10 days of spirometry with no hyperpnea training (CON). RESULTS: In both CON and TR subjects, baseline pulmonary function was unchanged during the 10 days. In TR subjects, pulmonary function was decreased at 5 mins after hyperpnea but thereafter increased to pre-hyperpnea values by 30 mins. Furthermore, these changes in pulmonary function were consistent during the 10 training days. In TR subjects, maximal voluntary ventilation decreased by 10.4 ± 8.9% (168-150 L min-1) over the 10 days (P < 0.05), whereas it was unchanged in CON subjects. CONCLUSIONS: These findings demonstrate that voluntary hyperpnea acutely decreases airway function in healthy subjects. However, there does not appear to be a cumulative effect of repeated hyperpnea, as daily pulmonary function was unchanged.

A 3D Printed Device for Low Cost Neural Stimulation in Mice.

Electrical stimulation of the brain through the implantation of electrodes is an effective treatment for certain diseases and the focus of a large body of research investigating new cell mechanisms, neurological phenomena, and treatments. Electrode devices developed for stimulation in rodents vary widely in size, cost, and functionality, with the majority of recent studies presenting complex, multi-functional designs. While some experiments require these added features, others are in greater need of reliable, low cost, and readily available devices that will allow surgeries to be scheduled and completed without delay. In this work, we utilize 3D printing and common electrical hardware to produce an effective 2-channel stimulation device that meets these requirements. Our stimulation electrode has not failed in over 60 consecutive surgeries, costs less than $1 USD, and can be assembled in less than 20 min. 3D printing minimizes the amount of material used in manufacturing the device and enables one to match the curvature of the connector's base with the curvature of the mouse skull, producing an ultra-lightweight, low size device with improved adhesion to the mouse skull. The range of the stimulation parameters used with the proposed device was: pulse amplitude 1-200 µA, pulse duration 50-500 µs and pulse frequency 1-285 Hz.

Self-Assembled Nanorod Structures on Nanofibers for Textile Electrochemical Capacitor Electrodes with Intrinsic Tactile Sensing Capabilities.

A novel polyaniline nanorod (PAniNR) three-dimensional structure was successfully grown on flexible polyacrylonitrile (PAN) nanofiber substrate as the electrode material for electrochemical capacitors (ECs), constructed via self-stabilized dispersion polymerization process. The electrode offered desired mechanical properties such as flexibility and bendability, whereas it maintained optimal electrochemical characteristics. The electrode and the assembled EC cell also achieved intrinsic piezoresistive sensing properties, leading to real-time monitoring of excess mechanical pressure and bending during cell operations. The PAniNR@PAN electrodes show an average diameter of 173.6 nm, with the PAniNR growth of 50.7 nm in length. Compared to the electrodes made from pristine PAni, the gravimetric capacitance increased by 39.8% to 629.6 F/g with aqueous acidic electrolyte. The electrode and the assembled EC cell with gel electrolyte were responsive to tensile, compressive, and bending stresses with a sensitivity of 0.95 MPa-1.

No effect of elevated operating lung volumes on airway function during variable workrate exercise in asthmatic humans.

In asthmatic adults, airway caliber fluctuates during variable intensity exercise such that bronchodilation (BD) occurs with increased workrate whereas bronchoconstriction (BC) occurs with decreased workrate. We hypothesized that increased lung mechanical stretch would prevent BC during such variable workrate exercise. Ten asthmatic and ten nonasthmatic subjects completed two exercise trials on a cycle ergometer. Both trials included a 28-min exercise bout consisting of alternating four min periods at workloads equal to 40 % (Low) and 70% (High) peak power output. During one trial, subjects breathed spontaneously throughout exercise (SVT), such that tidal volume (VT) and end-inspiratory lung volume (EILV) were increased by 0.5 and 0.6 liters during the high compared with the low workload in nonasthmatic and asthmatic subjects, respectively. During the second trial (MVT), VT and EILV were maintained constant when transitioning from the high to the low workload. Forced exhalations from total lung capacity were performed during each exercise workload. In asthmatic subjects, forced expiratory volume 1.0 s (FEV1.0) increased and decreased with the increases and decreases in workrate during both SVT (Low, 3.3 ± 0.3 liters; High, 3.6 ± 0.2 liters; P < 0.05) and MVT (Low, 3.3 ± 0.3 liters; High, 3.5 ± 0.2 liters; P < 0.05). Thus increased lung stretch during MVT did not prevent decreases in airway caliber when workload was reduced. We conclude that neural factors controlling airway smooth muscle (ASM) contractile activity during whole body exercise are more robust determinants of airway caliber than the ability of lung stretch to alter ASM actin-myosin binding and contraction.

The relationship between prenatal control, expectations, experienced control, and birth satisfaction among primiparous women.

OBJECTIVES: This paper explores the relationship between perceptions of prenatal control, expectations for childbirth, and experienced control in labour and birth and how they individually and collectively affect birth satisfaction. DESIGN: A repeated measures exploratory study was conducted with 31 primiparous women between 26 and 40 weeks pregnant. Standardised interviews were conducted prior to birth to assess levels of prenatal control and expectations for control during childbirth. Six weeks after the birth, women were interviewed again to assess experiences of control and birth satisfaction. SETTING: Prenatal clinic, North Carolina, USA. FINDINGS: Results show experienced control to be a significant predictor of birth satisfaction, with high levels of control correlating with high satisfaction levels. However, no correlations were found between the three aspects of control, and both prenatal control and birth expectations were found to have no significant effect on birth satisfaction. Findings also indicate that women cared for by midwives have significantly higher experienced control and birth satisfaction than women whose care was provided by obstetricians, while incidence of caesarean birth did not affect either measure. CONCLUSIONS: Experienced control during labour and birth is an important predictor of birth satisfaction. Health care providers should collaborate with the women they care for to use techniques that maximize the experience of control especially during labour and birth.