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Background: Application time and viscosity are factors that can significantly affect the properties of bone cement and implant fixation. The aim of this study was to investigate the influence of different application times of 2 different cements on mechanical parameters, cement interdigitation, and cement distribution. Methods: P.F.C. Sigma tibial trays were cemented with high-viscous Palacos R and medium- to low-viscous Simplex P in an open-cell model. The application was performed at different times within the manufacturer’s specifications. Cement interdigitation and micromotion were measured with computed tomography scan using a novel method. Results: Significant differences of insertion forces were found at all times of cement application. Cement penetration decreased with increasing pressure and viscosity. No significant differences were shown for micromotion between Palacos R and Simplex P except for an increase for Simplex P from 3 to 7 minutes at the bone-cement interface. Simplex P appeared to trap air at the implant-cement interface at 3 minutes and increased at 7 minutes. Conclusions: Cement distribution and intrusion of Palacos R and Simplex P decreased with time. Simplex P trapped air at the implant-cement interface, decreasing the amount of contact at the implant-cement interface, which is worrisome for long-term implant fixation. Given the significant changes in cement properties after mixing, it is necessary for surgeons to understand the viscosity and timing of cement application to achieve optimal cement penetration and surface contact area to potentially decrease implant loosening. High-viscous Palacos R should be applicated immediately with doughing time and medium-viscous Simplex P for about 4 minutes considering a threshold of minimum pressure.

Current in vivo disease models and analysis methods for cardiac drug development have been insufficient in providing accurate and reliable predictions of drug efficacy and safety. Here, we propose a custom optical flow-based analysis method to quantitatively measure recordings of contracting cardiomyocytes on polydimethylsiloxane (PDMS), compatible with medium-throughput systems.Movement of the PDMS was examined by covalently bound fluorescent beads on the PDMS surface, differences caused by increased substrate stiffness were compared, and cells were stimulated with β-agonist. We further validated the system using cardiomyocytes treated with endothelin-1 and compared their contractions against control and cells incubated with receptor antagonist bosentan. After validation we examined two MYBPC3-mutant patient-derived cell lines.Recordings showed that higher substrate stiffness resulted in higher contractile pressure, while beating frequency remained similar to control. β-agonist stimulation resulted in both higher beating frequency as well as higher pressure values during contraction and relaxation. Cells treated with endothelin-1 showed an increased beating frequency, but a lower contraction pressure. Cells treated with both endothelin-1 and bosentan remained at control level of beating frequency and pressure. Lastly, both MYBPC3-mutant lines showed a higher beating frequency and lower contraction pressure.Our validated method is capable of automatically quantifying contraction of hiPSC-derived cardiomyocytes on a PDMS substrate of known shear modulus, returning an absolute value. Our method could have major benefits in a medium-throughput setting.

Introduction: The transcranial direct current stimulation (tDCS) is a neuromodulatory technique with the potential to decrease pain scores and to improve chronic pain treatment. Although age is an essential factor that might impact the tDCS effect, most studies are solely conducted in adults. Therefore, the age limitation presents a critical research gap in this field and can be shown by only a handful of studies that have included other age groups. To examine the evidence upon the tDCS effect on pain scores on children, adolescents, or elderly, and indirectly, to infer the age-dependent impact on tDCS effects, we conducted a systematic review and meta-analysis.Methods: A systematic review searching the following databases: PubMed, EMBASE, and Science Direct using the following search terms adapted according to MeSh or Entree: [(“Adolescent” OR “Children” OR “Elderly”) AND (“tDCS”) AND (“Pain” OR “Pain threshold”) AND (“dorsolateral prefrontal cortex” OR “Motor cortex)] up to April 20th, 2020. We retrieved 228 articles, 13 were included in the systematic review, and five studies with elderly subjects that had their outcomes assessed by pain score or pain threshold were included in the meta-analysis.Results: For the analysis of pain score, 96 individuals received active stimulation, and we found a favorable effect for active tDCS to reduce pain score compared to sham (P = 0.002). The standardized difference was −0.76 (CI 95% = −1.24 to −0.28). For the pain threshold, the analysis showed no significant difference between active and sham tDCS. We reviewed two studies with adolescents: one study using anodal tDCS over the prefrontal cortex reported a reduction in pain scores. However, the second study reported an increase in pain sensitivity for the dorsolateral prefrontal cortex (DLPFC) stimulation.Conclusion: Our findings suggest tDCS may reduce pain levels in the elderly group. Nevertheless, the small number of studies included in this review—and the considerable heterogeneity for clinical conditions and protocols of stimulation present—limits the support of tDCS use for pain treatment in elderly people. Larger studies on the tDCS effect on pain are needed to be conducted in elderly and adolescents, also evaluating different montages and electrical current intensity.

Background: Age is an important factor that impacts the variability of tDCS effects.Objective/Hypothesis: To compare effects of anodal (a)-tDCS over the left dorsolateral prefrontal cortex (DLPFC), and primary motor cortex (M1) in adolescents, adults, and elderly on heat pain threshold (HPT; primary outcome) and the working memory (WM; secondary outcome). We hypothesized that the effect of tDCS on HPT and WM performance would be the largest in adolescents because their pre-frontal cortex is more prone to neuroplasticity.Methods: We included 30 healthy women within the age ranges of 15–16 (adolescents, n = 10), 30–40 (adults, n = 10), and 60–70 (elderly, n = 10) years. In this crossover single-blinded study, participants received three interventions applied over the DLPF and M1. The active stimulation intensity was two mA for 30 min. From 20 min of stimulation onset, the tDCS session was coupled with an online n-back task. The a-tDCS and sham were applied in a random sequence, with a washout time of a minimum 7 days between each trial. HPT was evaluated before and after stimulation. The WM performance with an n-back task was assessed after the tDCS session.Results: A Generalized Estimating Equation (GEE) model revealed a significant effect of the a-tDCS over the left DLPFC to reduce the HPT in adolescents compared with sham. It increased the pain perception significantly [a large effect size (ES) of 1.09)]. In the adults, a-tDCS over M1 enhanced the HPT significantly (a large ES of 1.25) compared to sham. No significant effect for HPT was found in the elderly. Response time for hits was reduced for a-tDCS over the DLPFC in adolescents, as compared to the other two age groups.Conclusions: These findings suggest that a-tDCS modulates pain perception and WM differentially according to age and target area of stimulation. In adolescents, anodal stimulation over the DLPFC increased the pain perception, while in adults, the stimulation over the M1 increased the pain threshold. Thus, they elucidate the impact of tDCS for different age groups and can help to define what is the appropriate intervention according to age in further clinical trials.Clinical Trial Registration:www.ClinicalTrials.gov, Identifier: NCT04328545.

Abstract Cognitive dysfunction in fibromyalgia has been reported, especially memory. Anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) has been effective in enhancing this function. We tested the effects of eight sessions of tDCS and cognitive training on immediate and delayed memory, verbal fluency and working memory and its association with brain-derived neurotrophic factor (BDNF) levels. Forty females with fibromyalgia were randomized to receive eight sessions of active or sham tDCS. Anodal stimulation (2 mA) was applied over the DLPFC and online combined with a working memory training (WMT) for 20 minutes. Pre and post-treatment neurocognitive tests were administered. Data analysis on deltas considering years of education and BDNF as covariates, indicated active-tDCS + WMT significantly increased immediate memory indexed by Rey Auditory Verbal Learning Test score when compared to sham. This effect was dependent on basal BDNF levels. In addition, the model showed active stimulation increased orthographic and semantic verbal fluency scores (Controlled Oral Word Association Test) and short-term memory (Forward Digit Span). The combination of both techniques seemed to produce effects on specific cognitive functions related to short-term and long-term episodic memory and executive functions, which has clinical relevance for top-down treatment approaches in FM.