Decoding temporal muscle synergy patterns based on brain activity for upper extremity in ADL movements.

Muscle synergies have been hypothesized as specific predefined motor primitives that the central nervous system can reduce the complexity of motor control by using them, but how these are expressed in brain activity is ambiguous yet. The main purpose of this paper is to develop synergy-based neural decoding of motor primitives, so for the first time, brain activity and muscle synergy map of the upper extremity was investigated in the activity of daily living movements. To find the relationship between brain activities and muscle synergies, electroencephalogram (EEG) and electromyogram (EMG) signals were acquired simultaneously during activities of daily living. To extract the maximum correlation of neural commands with muscle synergies, application of a combined partial least squares and canonical correlation analysis (PLS-CCA) method was proposed. The Elman neural network was used to decode the relationship between extracted motor commands and muscle synergies. The performance of proposed method was evaluated with tenfold cross-validation and muscle synergy estimation of brain activity with R, VAF, and MSE of 84 ± 2.6%, 70 ± 4.7%, and 0.00011 ± 0.00002 were quantified respectively. Furthermore, the similarity between actual and reconstructed muscle activations was achieved more than 92% for correlation coefficient. To compare with the existing methods, our results showed significantly more accuracy of the model performance. Our results confirm that use of the expression of muscle synergies in brain activity can estimate the neural decoding performance for motor control that can be used to develop neurorehabilitation tools such as neuroprosthesis.

In Vitro Evaluation of Pore Size Graded Bone Scaffolds with Different Material Composition.

The demand for biomimetic and biocompatible scaffolds in equivalence of structure and material composition for the regeneration of bone tissue is relevantly high. This article is investigating a novel three-dimensional (3D) printed porous structure called bone bricks with a gradient pore size mimicking the structure of the bone tissue. Poly-ɛ-caprolactone (PCL) combined with ceramics such as hydroxyapatite (HA), ß-tricalcium phosphate (TCP), and bioglass 45S5 were successfully mixed using a melt blending method and fabricated with the use of screw-assisted extrusion-based additive manufacturing system. Bone bricks containing the same material concentration (20 wt%) were biologically characterized through proliferation and differentiation tests. Scanning electron microscopy (SEM) was used to investigate the morphology of cells on the surface of bone bricks, whereas energy dispersive X-ray (EDX) spectroscopy was used to investigate the element composition on the surface of the bone bricks. Confocal imaging was used to investigate the number of differentiated cells on the surface of bone bricks. Proliferation results showed that bone bricks containing PCL/HA content are presenting higher proliferation properties, whereas differentiation results showed that bone bricks containing PCL/Bioglass 45S5 are presenting higher differentiation properties. Confocal imaging results showed that bone bricks containing PCL/Bioglass 45S5 are presenting a higher number of differentiated cells on their surface compared with the other material contents.

Exosomes from SHED-MSC regulate polarization and stress oxidative indexes in THP-1 derived M1 macrophages.

OBJECTIVE: The inhibition of M1 macrophages may be interesting for targeted therapy with mesenchymal stem cell-derived Exosomes (MSC-EXOs). This study aimed to investigate the stem cells of human exfoliated deciduous teeth-derived EXOs (SHED-MSC-EXOs) effect on regulating the pro- and anti-oxidant indexes and inhibiting M1 macrophage polarization. Besides, an in-silico analysis of SHED-MSC-EXO miRNAs as the highest frequency of small RNAs in the exosomes was performed to discover the possible mechanism. METHODS: The flow cytometry analysis of CD80 and CD86 as M1-specific markers confirmed the polarization of macrophages derived from THP-1 cells. After exosome isolation, characterization, and internalization, THP-1-derived M1 macrophages were treated with SHED-MSC-EXOs. M1-specific markers and pro- and anti-oxidant indexes were evaluated. For in-silico analysis of SHED-MSC-EXOs miRNAs, initial miRNA array data of SHED-EXOs is collected from GEO, and the interaction of the miRNAs in M1 macrophage polarization (M1P), mitochondrial oxidative stress (MOS) and LPS-induced oxidative stress (LOS) were analyzed by miRWalk 3.0 server. Outcomes were filtered by 75th percentile signal intensity, score cut-off ≥0.95, minimum free energy (MEF)≤ -20 kcal/mol, and seed = 1. RESULTS: It shows a decrease in the expression of CD80 and CD81, a reduction in pro-oxidant indicators, and an increase in the anti-oxidant indexes (P < 0.05). Computational analysis showed that eight microRNAs of SHED-MSC-EXO miRNAs can bind to and interfere with the expression of candidate genes in the M1P, MOS, and LOS pathways simultaneously. CONCLUSION: SHED-MSCs-EXOs can be utilized to treat conditions related to M1 macrophage-induced diseases (M1IDs) due to their unique physical properties and ability to penetrate target cells easily.

Brain Connectivity Estimation Pitfall in Multiple Trials of Electroencephalography Data.

Introduction: The electroencephalography signal is well suited to calculate brain connectivity due to its high temporal resolution. When the purpose is to compute connectivity from multi-trial electroencephalography (EEG) data, confusion arises about how these trials involved in calculating the connectivity. The purpose of this paper is to study this confusing issue using simulated and experimental data. Methods: To this end, Granger causality-based connectivity measures were considered. Using simulations, two signals were generated with known AR (auto-regressive) coefficients and then simple multivariate autoregressive (MVAR) models based on different numbers of trials were extracted. For accurate estimation of the MVAR model, the data samples should be sufficient. Two Granger causality-based connectivity, granger causality (GC) and Partial directed coherence (PDC) were estimated. Results: Estimating connectivity corresponding to small trial numbers (5 and 10 trials) resulted in an average value of connectivity that is significantly higher and also more variable over different estimates. By increasing the number of trials, the MVAR model has fitted more appropriately to the data and the connectivity values were converged. This procedure was implemented on real EEG data. The obtained results agreed well with the findings of simulated data. Conclusion: The results showed that the brain connectivity should calculate for each trial, and then average the connectivity values on all trials. Also, the larger the trial numbers, the MVAR model has fitted more appropriately to the data, and connectivity estimations are more reliable. Highlights: The average of connectivity values on trials is considered brain connectivity.Connectivity estimations are more reliable for larger trial numbers.Estimations of connectivity for small trial numbers are not valid. Plain Language Summary: Several different techniques can be utilized to evaluate brain connectivity such as functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), electroencephalography (EEG) and etc. Connectivity estimation methods are associated with computing the correspondence of neural signals over time, therefore modalities such as EEG due to their fine temporal resolution are well suited to calculate such connectivity. When the purpose is to compute connectivity from multi-trial data, confusion arises about how these trials and how many trials are involved in calculating the connectivity. During calculating brain connectivity from data with many observation epochs, the question arises whether brain connectivity is calculated for each trial and then average or for the averaged trials. The target of this paper is to study the abovementioned issue using simulated data and realistic EEG data. Our analysis indicated that the brain connectivity should calculate for each trial, and then average the connectivity values on all trials. It was also found that estimating connectivity corresponding to small trial numbers resulted in an average value of connectivity that is significantly higher and also more variable over different estimates and is not valid. These findings can help us in the correct estimation of brain connectivity.

Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.

Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment outcomes for metastatic and recurrent disease still pose a major concern for both basic and clinical scientists. The treatment strategies for rhabdomyosarcoma include multi-agent chemotherapies after surgical resection with or without ionization radiotherapy. In this comprehensive review, we first provide a detailed clinical understanding of rhabdomyosarcoma including its classification and subtypes, diagnosis, and treatment strategies. Later, we focus on chemotherapy strategies for this childhood sarcoma and discuss the impact of three mechanisms that are involved in the chemotherapy response including apoptosis, macro-autophagy, and the unfolded protein response. Finally, we discuss in vivo mouse and zebrafish models and in vitro three-dimensional bioengineering models of rhabdomyosarcoma to screen future therapeutic approaches and promote muscle regeneration.

Fluoxetine enhances the antitumor effect of olfactory ensheathing cell-thymidine kinase/ganciclovir gene therapy in human glioblastoma multiforme cells through upregulation of Connexin43 levels.

Glioblastoma multiforme (GBM) is the most invasive form of primary brain astrocytoma, resulting in poor clinical outcomes. Herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy is considered a promising strategy for GBM treatment. Since Connexin43 (Cx43) expression is reduced in GBM cells, increasing Cx43 levels could enhance the effectiveness of gene therapy. The present study aims to examine the impact of fluoxetine on HSV-TK/GCV gene therapy in human GBM cells using human olfactory ensheathing cells (OECs) as vectors. The effect of fluoxetine on Cx43 levels was assessed using the western blot technique. GBM-derived astrocytes and OECs-TK were Cocultured, and the effect of fluoxetine on the Antitumor effect of OEC-TK/GCV gene therapy was evaluated using MTT assay and flow cytometry. Our results showed that fluoxetine increased Cx43 levels in OECs and GBM cells and augmented the killing effect of OECs-TK on GBM cells. Western blot data revealed that fluoxetine enhanced the Bax/Bcl2 ratio and the levels of cleaved caspase-3 in the coculture of OECs-TK and GBM cells. Moreover, flow cytometry data indicated that fluoxetine increased the percentage of apoptotic cells in the coculture system. This study suggests that fluoxetine, by upregulating Cx43 levels, could strengthen the Antitumor effect of OEC-TK/GCV gene therapy on GBM cells.

Design and 3D Printing of Personalized Hybrid and Gradient Structures for Critical Size Bone Defects.

Treating critical-size bone defects with autografts, allografts, or standardized implants is challenging since the healing of the defect area necessitates patient-specific grafts with mechanically and physiologically relevant structures. Three-dimensional (3D) printing using computer-aided design (CAD) is a promising approach for bone tissue engineering applications by producing constructs with customized designs and biomechanical compositions. In this study, we propose 3D printing of personalized and implantable hybrid active scaffolds with a unique architecture and biomaterial composition for critical-size bone defects. The proposed 3D hybrid construct was designed to have a gradient cell-laden poly(ethylene glycol) (PEG) hydrogel, which was surrounded by a porous polycaprolactone (PCL) cage structure to recapitulate the anatomical structure of the defective area. The optimized PCL cage design not only provides improved mechanical properties but also allows the diffusion of nutrients and medium through the scaffold. Three different designs including zigzag, zigzag/spiral, and zigzag/spiral with shifting the zigzag layers were evaluated to find an optimal architecture from a mechanical point of view and permeability that can provide the necessary mechanical strength and oxygen/nutrient diffusion, respectively. Mechanical properties were investigated experimentally and analytically using finite element analysis (FEA), and computational fluid dynamics (CFD) simulation was used to determine the permeability of the structures. A hybrid scaffold was fabricated via 3D printing of the PCL cage structure and a PEG-based bioink comprising a varying number of human bone marrow mesenchymal stem cells (hBMSCs). The gradient bioink was deposited inside the PCL cage through a microcapillary extrusion to generate a mineralized gradient structure. The zigzag/spiral design for the PCL cage was found to be mechanically strong with sufficient and optimum nutrient/gas axial and radial diffusion while the PEG-based hydrogel provided a biocompatible environment for hBMSC viability, differentiation, and mineralization. This study promises the production of personalized constructs for critical-size bone defects by printing different biomaterials and gradient cells with a hybrid design depending on the need for a donor site for implantation.

Accelerated Degradation of Poly-ε-caprolactone Composite Scaffolds for Large Bone Defects.

This research investigates the accelerated hydrolytic degradation process of both anatomically designed bone scaffolds with a pore size gradient and a rectangular shape (biomimetically designed scaffolds or bone bricks). The effect of material composition is investigated considering poly-ε-caprolactone (PCL) as the main scaffold material, reinforced with ceramics such as hydroxyapatite (HA), ß-tricalcium phosphate (TCP) and bioglass at a concentration of 20 wt%. In the case of rectangular scaffolds, the effect of pore size (200 µm, 300 µm and 500 µm) is also investigated. The degradation process (accelerated degradation) was investigated during a period of 5 days in a sodium hydroxide (NaOH) medium. Degraded bone bricks and rectangular scaffolds were measured each day to evaluate the weight loss of the samples, which were also morphologically, thermally, chemically and mechanically assessed. The results show that the PCL/bioglass bone brick scaffolds exhibited faster degradation kinetics in comparison with the PCL, PCL/HA and PCL/TCP bone bricks. Furthermore, the degradation kinetics of rectangular scaffolds increased by increasing the pore size from 500 µm to 200 µm. The results also indicate that, for the same material composition, bone bricks degrade slower compared with rectangular scaffolds. The scanning electron microscopy (SEM) images show that the degradation process was faster on the external regions of the bone brick scaffolds (600 µm pore size) compared with the internal regions (200 µm pore size). The thermal gravimetric analysis (TGA) results show that the ceramic concentration remained constant throughout the degradation process, while differential scanning calorimetry (DSC) results show that all scaffolds exhibited a reduction in crystallinity (Xc), enthalpy (Δm) and melting temperature (Tm) throughout the degradation process, while the glass transition temperature (Tg) slightly increased. Finally, the compression results show that the mechanical properties decreased during the degradation process, with PCL/bioglass bone bricks and rectangular scaffolds presenting higher mechanical properties with the same design in comparison with the other materials.

3D printed scaffold design for bone defects with improved mechanical and biological properties.

Bone defect treatment is still a challenge in clinics, and synthetic bone scaffolds with adequate mechanical and biological properties are highly needed. Adequate waste and nutrient exchange of the implanted scaffold with the surrounded tissue is a major concern. Moreover, the risk of mechanical instability in the defect area during regular activity increases as the defect size increases. Thus, scaffolds with better mass transportation and mechanical properties are desired. This study introduces 3D printed polymeric scaffolds with a continuous pattern, ZigZag-Spiral pattern, for bone defects treatments. This pattern has a uniform distribution of pore size, which leads to uniform distribution of wall shear stress which is crucial for uniform differentiation of cells attached to the scaffolds. The mechanical, mass transportation, and biological properties of the 3D printed scaffolds are evaluated. The results show that the presented scaffolds have permeability similar to natural bone and, with the same porosity level, have higher mechanical properties than scaffolds with conventional lay-down patterns 0-90° and 0-45°. Finally, human mesenchymal stem cells are seeded on the scaffolds to determine the effects of geometrical microstructure on cell attachment and morphology. The results show that cells in scaffold with ZigZag-Spiral pattern infilled pores gradually, while the other patterns need more time to fill the pores. Considering mechanical, transportation, and biological properties of the considered patterns, scaffolds with ZigZag-Spiral patterns can mimic the properties of cancellous bones and be a better choice for treatments of bone defects.

ß2-Adrenergic receptor agonist enhances the bystander effect of HSV-TK/GCV gene therapy in glioblastoma multiforme via upregulation of connexin 43 expression.

Glioblastoma multiforme (GBM) is the most invasive form of primary brain astrocytoma. Gene therapy using the herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) is a new strategy for GBM treatment. As the connexin 43 (Cx43) levels are downregulated in GBM cells, it seems that the upregulation of Cx43 could improve the efficacy of the gene therapy. This study aims to evaluate the effect of clenbuterol hydrochloride (Cln) as a ß2-adrenergic receptor agonist on HSV-TK/GCV gene therapy efficacy in human GBM cells using olfactory ensheathing cells (OECs) as vectors. The lentivirus containing the thymidine kinase gene was transduced to OECs and the effective dose of GCV on cells was measured by MTT assay. We found that Cln upregulated Cx43 expression in human GBM cells and OECs and promoted the cytotoxic effect of GCV on the co-culture cells. Western blot results showed that Cln increased the cleaved caspase-3 expression and the Bax/Bcl2 ratio in the co-culture of GBM cells and OEC-TK. Also, the flow cytometry results revealed that Cln increased apoptosis in the co-culture of GBM cells and OEC-TK cells. This study showed that Cln via upregulation of Cx43 expression could enhance the bystander effect of HSVTK-GCV gene therapy in human GBM cells.

Bone Bricks: The Effect of Architecture and Material Composition on the Mechanical and Biological Performance of Bone Scaffolds.

Large bone loss injuries require high-performance scaffolds with an architecture and material composition resembling native bone. However, most bone scaffold studies focus on three-dimensional (3D) structures with simple rectangular or circular geometries and uniform pores, not able to recapitulate the geometric characteristics of the native tissue. This paper addresses this limitation by proposing novel anatomically designed scaffolds (bone bricks) with nonuniform pore dimensions (pore size gradients) designed based on new lay-dawn pattern strategies. The gradient design allows one to tailor the properties of the bricks and together with the incorporation of ceramic materials allows one to obtain structures with high mechanical properties (higher than reported in the literature for the same material composition) and improved biological characteristics.

Novel 3D Bioglass Scaffolds for Bone Tissue Regeneration.

The design of scaffolds with optimal biomechanical properties for load-bearing applications is an important topic of research. Most studies have addressed this problem by focusing on the material composition and not on the coupled effect between the material composition and the scaffold architecture. Polymer-bioglass scaffolds have been investigated due to the excellent bioactivity properties of bioglass, which release ions that activate osteogenesis. However, material preparation methods usually require the use of organic solvents that induce surface modifications on the bioglass particles, compromising the adhesion with the polymeric material thus compromising mechanical properties. In this paper, we used a simple melt blending approach to produce polycaprolactone/bioglass pellets to construct scaffolds with pore size gradient. The results show that the addition of bioglass particles improved the mechanical properties of the scaffolds and, due to the selected architecture, all scaffolds presented mechanical properties in the cortical bone region. Moreover, the addition of bioglass indicated a positive long-term effect on the biological performance of the scaffolds. The pore size gradient also induced a cell spreading gradient.

Neural decoding of continuous upper limb movements: a meta-analysis.

OBJECTIVE: EEG-based motion trajectory decoding makes a promising approach for neurotechnology which can be used for neural control of motion reconstruction and neurorehabilitation tools. However, the feasibility and validity of continuous motion decoding by non-invasive brain activity are not clear. The main aim of this study was to perform a meta-analysis across studies that examined the ability of EEG-based continuous motion decoding of upper limb movements. APPROACH: Pearson's correlation coefficient (CC) was used to evaluate the model performance of the studies and considered as an effect size. To estimate the overall effect size of neural decoding of motion trajectory across studies, characteristics of included studies were addressed and the random effect model was applied to the heterogeneous studies which estimated overall effect size distribution. Furthermore, the significant difference between the two subgroups of imagined and executed movements was analysed. MAIN RESULTS: The mean of the overall effect size was computed 0.46 across the nonhomogeneous studies. The results showed no significant difference between imagined and executed movements (Chi2=0.28, df = 1, p = 0.60). SIGNIFICANCE: Meta-analysis results confirm that imagination like execution movements can be used for neural decoding of motion trajectory in neural motor control systems. Also, nonlinear compare with linear model statistically confirmed to be more beneficial for complex movements. Furthermore, a new approach of synergy-based motion decoding can be significantly effective to increase model performance and more research needs to evaluate this method for different levels of complexity of movements.IMPLICATIONS FOR REHABILITATIONNeural decoding methods base on EEG as a non-invasive brain activity, are more user friendly for neurorehabilitation than invasive methods that developing of it makes it more applicable for reconstructing activities of daily living.Neurotechnology for neural control of motion reconstruction, makes the rehabilitation tools to be more synchrony with human intentional movement that can be used to improve the brain neuroplastisity in stroke or other paralysed people.The feasibility and validity of imagined movements equal with executed movements show that amputee people also can benefit EEG-based motion decoding for controling rehabilitation tools just by imagination of their intentional movements.For neurorehabilitation tools, comparing the study outcomes illucidate that the approach of synergy-based motor control in brain activities concluded significantly high performance that highlighted the need it to more investigated in future research.

An improved saliency model of visual attention dependent on image content.

Many visual attention models have been presented to obtain the saliency of a scene, i.e., the visually significant parts of a scene. However, some mechanisms are still not taken into account in these models, and the models do not fit the human data accurately. These mechanisms include which visual features are informative enough to be incorporated into the model, how the conspicuity of different features and scales of an image may integrate to obtain the saliency map of the image, and how the structure of an image affects the strategy of our attention system. We integrate such mechanisms in the presented model more efficiently compared to previous models. First, besides low-level features commonly employed in state-of-the-art models, we also apply medium-level features as the combination of orientations and colors based on the visual system behavior. Second, we use a variable number of center-surround difference maps instead of the fixed number used in the other models, suggesting that human visual attention operates differently for diverse images with different structures. Third, we integrate the information of different scales and different features based on their weighted sum, defining the weights according to each component's contribution, and presenting both the local and global saliency of the image. To test the model's performance in fitting human data, we compared it to other models using the CAT2000 dataset and the Area Under Curve (AUC) metric. Our results show that the model has high performance compared to the other models (AUC = 0.79 and sAUC = 0.58) and suggest that the proposed mechanisms can be applied to the existing models to improve them.

Features of Pathobiology and Clinical Translation of Approved Treatments for Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently the most important etiological agent of acute respiratory distress syndrome (ARDS) with millions of infections and deaths in the last 2 years worldwide. Several reasons and parameters are responsible for the difficult management of coronavirus disease-2019 (COVID-19) patients; the first is virus behavioral factors such as high transmission rate, and the different molecular and cellular mechanisms of pathogenesis remain a matter of controversy, which is another factor. SUMMARY: In the present review, we attempted to explain about features of SARS-COV-2, particularly focusing on the various aspects of pathogenesis and treatment strategies. KEY MESSAGES: We note evidence for the understanding of the precise molecular and cellular mechanisms of SARS-CoV-2 pathogenesis, which can help design the appropriate drug or vaccine. Additionally, and importantly, we reported the updated issues associated with the history and development of treatment strategies such as, drugs, vaccines, and other medications that have been approved or under consideration in clinics and markets worldwide.

Exploiting Urazole's Acidity for Fabrication of Hydrogels and Ion-Exchange Materials.

In this study, the acidity of urazole (pKa 5-6) was exploited to fabricate a hydrogel in two simple and scalable steps. Commercially available poly(hexamethylene)diisocyanate was used as a precursor to synthesize an urazole containing gel. The formation of urazole was confirmed by FT-IR and 1H-NMR spectroscopy. The hydrogel was characterized by microscopy imaging as well as spectroscopic and thermo-gravimetric analyses. Mechanical analysis and cell viability tests were performed for its initial biocompatibility evaluation. The prepared hydrogel is a highly porous hydrogel with a Young's modulus of 0.91 MPa, has a swelling ratio of 87%, and is capable of exchanging ions in a medium. Finally, a general strategy was demonstrated to embed urazole groups directly into a crosslinked material.

A neuro-computational model of visual attention with multiple attentional control sets.

In numerous activities, humans need to attend to multiple sources of visual information at the same time. Although several recent studies support the evidence of this ability, the mechanism of multi-item attentional processing is still a matter of debate and has not been investigated much by previous computational models. Here, we present a neuro-computational model aiming to address specifically the question of how subjects attend to two items that deviate defined by feature and location. We simulate the experiment of Adamo et al. (2010) which required subjects to use two different attentional control sets, each a combination of color and location. The structure of our model is composed of two components "attention" and "decision-making". The important aspect of our model is its dynamic equations that allow us to simulate the time course of processes at a neural level that occur during different stages until a decision is made. We analyze in detail the conditions under which our model matches the behavioral and EEG data from human subjects. Consistent with experimental findings, our model supports the hypothesis of attending to two control settings concurrently. In particular, our model proposes that initially, feature-based attention operates in parallel across the scene, and only in ongoing processing, a selection by the location takes place.

Bioactivity and Antibacterial Behaviors of Nanostructured Lithium-Doped Hydroxyapatite for Bone Scaffold Application.

The material for bone scaffold replacement should be biocompatible and antibacterial to prevent scaffold-associated infection. We biofunctionalized the hydroxyapatite (HA) properties by doping it with lithium (Li). The HA and 4 Li-doped HA (0.5, 1.0, 2.0, 4.0 wt.%) samples were investigated to find the most suitable Li content for both aspects. The synthesized nanoparticles, by the mechanical alloying method, were cold-pressed uniaxially and then sintered for 2 h at 1250 °C. Characterization using field-emission scanning electron microscopy (FE-SEM) revealed particle sizes in the range of 60 to 120 nm. The XRD analysis proved the formation of HA and Li-doped HA nanoparticles with crystal sizes ranging from 59 to 89 nm. The bioactivity of samples was investigated in simulated body fluid (SBF), and the growth of apatite formed on surfaces was evaluated using SEM and EDS. Cellular behavior was estimated by MG63 osteoblast-like cells. The results of apatite growth and cell analysis showed that 1.0 wt.% Li doping was optimal to maximize the bioactivity of HA. Antibacterial characteristics against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were performed by colony-forming unit (CFU) tests. The results showed that Li in the structure of HA increases its antibacterial properties. HA biofunctionalized by Li doping can be considered a suitable option for the fabrication of bone scaffolds due to its antibacterial and unique bioactivity properties.

Brain connectivity analysis in fathers of children with autism.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in which changes in brain connectivity, associated with autistic-like traits in some individuals. First-degree relatives of children with autism may show mild deficits in social interaction. The present study investigates electroencephalography (EEG) brain connectivity patterns of the fathers who have children with autism while performing facial emotion labeling task. Fifteen biological fathers of children with the diagnosis of autism (Test Group) and fifteen fathers of neurotypical children with no personal or family history of autism (Control Group) participated in this study. Facial emotion labeling task was evaluated using a set of photos consisting of six categories (mild and extreme: anger, happiness, and sadness). Group Independent Component Analysis method was applied to EEG data to extract neural sources. Dynamic causal connectivity of neural sources signals was estimated using the multivariate autoregressive model and quantified by using the Granger causality-based methods. Statistical analysis showed significant differences (p value < 0.01) in the connectivity of neural sources in recognition of some emotions in two groups, which the most differences observed in the mild anger and mild sadness emotions. Short-range connectivity appeared in Test Group and conversely, long-range and interhemispheric connections are observed in Control Group. Finally, it can be concluded that the Test Group showed abnormal activity and connectivity in the brain network for the processing of emotional faces compared to the Control Group. We conclude that neural source connectivity analysis in fathers may be considered as a potential and promising biomarker of ASD.

HSV-TK Expressing Mesenchymal Stem Cells Exert Inhibitory Effect on Cervical Cancer Model.

A growing area of research is focused on cancer therapy, and new therapeutic approaches are welcomed. Mesenchymal stem cell (MSC)-based gene therapy is a promising strategy in oncology. Intrinsic tropism and migration to tumor microenvironment with off lights are attractive features of this type of cell carrier. In this way, suicide genes have also found a good platform for better performance and have shown a stronger anti-tumor mechanism by riding on mesenchymal cells. In this study, we investigated the anti-tumor activity of intratumoral injected MSCs transduced with a lentivector expressing the HSV/TK in a mouse cervical cancer model. Following the injection of MSCs transduced with lentivector carrying TK, MSCs alone or PBS into the mice tumor, ganciclovir was administered intraperitoneally during 14 days, and tumor size, survival time, natural killer (NK) cells and cytotoxic T lymphocyte (CTL) activities were assessed. We demonstrated that combination of suicide therapy and cell therapy leading m,to successful tumor inhibition. Significant reduction in tumor size was detected in test group in comparison with controls. Also, potent antitumor NK and CTL activity was seen in treatment group in comparison with controls. Our data demonstrated that the mesenchymal cells expressing TK had inhibitory effect on cervical cancer model.