Construction of BaTiO3-TiO2 hollow sphere heterojunctions for enhanced microwave dynamic therapy in cancer treatment.

Cancer is one of the primary health concerns among humans due to its high incidence rate and lack of effective treatment. Currently, medical techniques to achieve the precise elimination of local cancer lesions with negligible damage to normal tissues are still intensely desired. Herein, we synthesized BaTiO3-TiO2 hollow spheres (BTHSs) for use in microwave dynamic therapy (MWDT) for cancer. Under UV irradiation, BTHSs can mediate the production of multiple reactive oxygen species (ROS), mainly 1O2, which results in a rapid photocatalytic degradation rate (97%), 1.6-fold that of commercial P25. Importantly, the ROS production process can be triggered by microwaves to effectively execute MWDT for cancer. Under microwave irradiation, BTHSs exhibit a remarkable therapeutic effect and slight cytotoxicity. In terms of mechanism, the enhanced ROS production efficiency of BTHSs can be attributed to their unique hollow structure and the formation of a type-II heterojunction by the incorporation of BaTiO3. The hollow structure increases the availability of active sites and enhances light scattering, while the BaTiO3-TiO2 heterojunction enhances the photocatalytic activity of TiO2 through charge transfer and electron-hole separation. Overall, this study provides important insights into the design and optimization of sensitizers for MWDT applications.

Biomimetic piezoelectric nanomaterial-modified oral microrobots for targeted catalytic and immunotherapy of colorectal cancer.

Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective tumor immunotherapy. Here, an intelligent tumor treatment microrobot based on the unique physiological structure and metabolic characteristics of Veillonella atypica (VA) is proposed by loading Staphylococcus aureus cell membrane-coating BaTiO3 nanocubes (SAM@BTO) on the surface of VA cells (VA-SAM@BTO) via click chemical reaction. Following oral administration, VA-SAM@BTO accurately targeted orthotopic colorectal cancer through inflammatory targeting of SAM and hypoxic targeting of VA. Under in vitro ultrasonic stimulation, BTO catalyzed two reduction reactions (O2 → •O2- and CO2 → CO) and three oxidation reactions (H2O → •OH, GSH → GSSG, and LA → PA) simultaneously, effectively inducing immunogenic death of tumor cells. BTO catalyzed the oxidative coupling of VA cells metabolized LA, effectively disrupting the immunosuppressive microenvironment, improving dendritic cell maturation and macrophage M1 polarization, and increasing effector T cell proportions while decreasing regulatory T cell numbers, which facilitates synergetic catalysis and immunotherapy.

Confinement Enrichment Effect in HoMS-BaTiO3 Microwave Gas Sensors for the Detection of 10 ppb-0.55 v/v% Ammonia at Room Temperature.

The construction of ammonia gas sensors with wide detection ranges is important for exhalation diagnosis and environmental pollution monitoring. To achieve a wide detection range, sensitive materials must possess excellent spatial confinement and large active surfaces to enhance gas adsorption. In this study, an ammonia microwave gas sensor with a wide detection range of 10 ppb-0.55 v/v% at room temperature was fabricated by incorporating hollow multishelled-structured BaTiO3 (HoMS-BaTiO3). The effect of the number of shells and the quantity of the sensitive material on the gas-sensing performance was investigated, and two-layered HoMS-BaTiO3 demonstrated the best response at high concentrations (0.15-0.55 v/v%). Conversely, single-layered HoMS-BaTiO3 displayed outstanding performance at low concentrations (10 ppb-0.15 v/v%). The lower the quantity of the sensitive material, the higher the response. This study offers a method for preparing room-temperature ammonia sensors with a wide detection range and reveals the link between the structure and quantity of sensitive materials and gas-sensing performance.

Biophotonic sensor for swift detection of malignant brain tissues by using nanocomposite YBa2Cu3O7/dielectric material as a 1D defective photonic crystal.

In the present research work we have theoretically examined the biosensing capabilities of proposed one dimensional defective photonic crystal for swift detection of malignant brain tissues. The transfer matrix formulation and MATLAB computational tool have been used to examine the transmission properties of proposed structure. The identical buffer layers of nanocomposite superconducting material have been used either side of cavity region to enhance the interaction between incident light and different brain tissue samples poured into the cavity region. All the investigations have been carried out under normal incidence to suppress the experimental liabilities involved. We have investigated the biosensing performance of the proposed design by changing the values of two internal parameters (1) the cavity layer thickness (d4) and (2) volume fraction (η) of nanocomposite buffer layers one by one to get the optimum biosensing performance from the structure. It has been found that the sensitivity of the proposed design becomes 1.42607 µm/RIU when the cavity region of thickness 15dd is loaded with lymphoma brain tissue. This value of sensitivity can be further increased to 2.66136 µm/RIU with η = 0.8. The findings of this work are very beneficial for designing of various bio-sensing structures composed of nanocomposite materials of diversified biomedical applications.

Membrane reactor based synthesis of biodiesel from Toona ciliata seed oil using barium oxide nano catalyst.

Membrane technology has been embraced as a feasible and promising substitute to the traditional technologies employed for biodiesel synthesis which are energy and time consuming. It needs less energy, has high stability, is environmentally friendly, and is simple to operate and control. Therefore, in our current study membrane technology was employed to synthesize biodiesel from Toona ciliate novel and non-edible seed oil. Since Toona ciliata has affluent oil content (33.8%) and is effortlessly and extensively available. In fact, we intended to scrutinize the effects of green synthesized barium oxide nanoparticles for one step transesterification of biodiesel production using membrane technology followed by characterization of prepared catalyst via innovative techniques. Optimal yield of biodiesel attained was 94% at 90 °C for 150 min with methanol to oil molar ratio of 9:1 and amount of about 0.39 wt %. Quantitative analysis of synthesized Toona ciliata oil biodiesel was carried out by advance techniques of Gas chromatography mass spectrometry (GC-MS), Fourier-transform infrared (FTIR) spectroscopy and Nuclear magnetic resonance (NMR) which authorize the synthesis of fatty acid methyl ester compounds using oil from Toona ciliata seeds. Values of Toona ciliata fuel properties for instance flash point (70°C), density (0.89 kg/m3), viscosity (5.25 mm2/s), cloud point (-8°C) and pour point (-11°C) met the specifications of international standards i. e American (ASTM D-6751), European (EN-14214) and China (GB/T 20,828). Subsequently, it is concluded that membrane technology is environmentally friendly and efficient technique for mass-production of sustainable biodiesel using green nano catalyst of barium oxide.

Biocompatibility and colorectal anti-cancer activity study of nanosized BaTiO3 coated spinel ferrites.

In the present work, different nanoparticles spinel ferrite series (MFe2O4, Co0.5M0.5Fe2O4; M = Co, Mn, Ni, Mg, Cu, or Zn) have been obtained via sonochemical approach. Then, sol-gel method was employed to design core-shell magnetoelectric nanocomposites by coating these nanoparticles with BaTiO3 (BTO). The structure and morphology of the prepared samples were examined by X-ray powder diffraction (XRD), scanning electron microscope (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscope (HR-TEM), and zeta potential. XRD analysis showed the presence of spinel ferrite and BTO phases without any trace of a secondary phase. Both phases crystallized in the cubic structure. SEM micrographs illustrated an agglomeration of spherical grains with nonuniformly diphase orientation and different degrees of agglomeration. Moreover, HR-TEM revealed interplanar d-spacing planes that are in good agreement with those of the spinel ferrite phase and BTO phase. These techniques along with EDX analyses confirmed the successful formation of the desired nanocomposites. Zeta potential was also investigated. The biological influence of (MFe2O4, CoMFe) MNPs and core-shell (MFe2O4@BTO, CoMFe@BTO) magnetoelectric nanocomposites were examined by MTT and DAPI assays. Post 48 h of treatments, the anticancer activity of MNPs and MENCs was investigated on human colorectal carcinoma cells (HCT-116) against the cytocompatibility of normal non-cancerous cells (HEK-293). It was established that MNPs possess anti-colon cancer capability while MENCs exhibited a recovery effect due to the presence of a protective biocompatible BTO layer. RBCs hemolytic effect of NPs has ranged from non- to low-hemolytic effect. This effect that could be attributed to the surface charge from zeta potential, also the CoMnFe possesses the stable and lowest zeta potential in comparison with CoFe2O4 and MnFe2O4 also to the protective effect of shell. These findings open up wide prospects for biomedical applications of MNPs as anticancer and MENCs as promising drug nanocarriers.

Electrical stimulation waveform-dependent osteogenesis on PVDF/BaTiO3 composite using a customized and programmable cell stimulator.

Directing cellular functionalities using biomaterial-based bioelectronic stimulation remains a significant constraint in translating research outcomes to address specific clinical needs. Electrical stimulation is now being clinically used as a therapeutic treatment option to promote bone tissue regeneration and to improve neuromuscular functionalities. However, the nature of the electrical waveforms during the stimulation and underlying biophysical rationale are still not scientifically well explored. Furthermore, bone-mimicking implant-based bioelectrical regulation of osteoinductivity has not been translated to clinics. The present study demonstrates the role of the electrical stimulation waveform to direct differentiation of stem cells on an electroactive polymeric substrate, using monophasic direct current (DC), square waveform, and biphasic waveform. In this regard, an in-house electrical stimulation device has been fabricated for the uninterrupted delivery of programmed electrical signals to stem cells in culture. To provide a functional platform for stem cells to differentiate, barium titanate (BaTiO3 , BT) reinforced poly(vinylidene difluoride) (PVDF) has been developed with mechanical properties similar to bone. The electrical stimulation of human mesenchymal stem cells (hMSCs) on PVDF/BT composite inhibited proliferation rate at day 7, indicating early commitment for differentiation. The phenotypical characteristics of DC stimulated hMSCs provided signatures of differentiation towards osteogenic lineage, which was subsequently confirmed using alkaline phosphatase assay, collagen deposition, matrix mineralization, and genetic expression. Our findings suggest that DC stimulation induced early osteogenesis in hMSCs with a higher level of intracellular reactive oxygen species (ROS), whereas the stimulation with square wave directed late osteogenesis with a lower ROS regeneration. In summary, the present study critically analyzes the role of electrical stimulation waveforms in regulating osteogenesis, without external biochemical differentiation inducers, on a bone-mimicking functional biomaterial substrate. Such a strategy can potentially be adopted to develop orthopedic implant-based bioelectronic medicine for bone regeneration.

Neuron Compatibility and Antioxidant Activity of Barium Titanate and Lithium Niobate Nanoparticles.

The biocompatibility and the antioxidant activity of barium titanate (BaTiO3) and lithium niobate (LiNbO3) were investigated on a neuronal cell line, the PC12, to explore the possibility of using piezoelectric nanoparticles in the treatment of inner ear diseases, avoiding damage to neurons, the most delicate and sensitive human cells. The cytocompatibility of the compounds was verified by analysing cell viability, cell morphology, apoptotic markers, oxidative stress and neurite outgrowth. The results showed that BaTiO3 and LiNbO3 nanoparticles do not affect the viability, morphological features, cytochrome c distribution and production of reactive oxygen species (ROS) by PC12 cells, and stimulate neurite branching. These data suggest the biocompatibility of BaTiO3 and LiNbO3 nanoparticles, and that they could be suitable candidates to improve the efficiency of new implantable hearing devices without damaging the neuronal cells.

Myeloid mineralocorticoid receptors contribute to skeletal muscle repair in muscular dystrophy and acute muscle injury.

Suppressing mineralocorticoid receptor (MR) activity with MR antagonists is therapeutic for chronic skeletal muscle pathology in Duchenne muscular dystrophy (DMD) mouse models. Although mechanisms underlying clinical MR antagonist efficacy for DMD cardiomyopathy and other cardiac diseases are defined, mechanisms in skeletal muscles are not fully elucidated. Myofiber MR knockout improves skeletal muscle force and a subset of dystrophic pathology. However, MR signaling in myeloid cells is known to be a major contributor to cardiac efficacy. To define contributions of myeloid MR in skeletal muscle function and disease, we performed parallel assessments of muscle pathology, cytokine levels, and myeloid cell populations resulting from myeloid MR genetic knockout in muscular dystrophy and acute muscle injury. Myeloid MR knockout led to lower levels of C-C motif chemokine receptor 2 (CCR2)-expressing macrophages, resulting in sustained myofiber damage after acute injury of normal muscle. In acute injury, myeloid MR knockout also led to increased local muscle levels of the enzyme that produces the endogenous MR agonist aldosterone, further supporting important contributions of MR signaling in normal muscle repair. In muscular dystrophy, myeloid MR knockout altered cytokine levels differentially between quadriceps and diaphragm muscles, which contain different myeloid populations. Myeloid MR knockout led to higher levels of fibrosis in dystrophic diaphragm. These results support important contributions of myeloid MR signaling to skeletal muscle repair in acute and chronic injuries and highlight the useful information gained from cell-specific genetic knockouts to delineate mechanisms of pharmacological efficacy.

3-Aminopyrazolo[3,4-b]pyridine: Effective Precursor for Barium Hydroxide-Mediated Three Components Synthesis of New Mono- and Bis(pyrimidines) with Potential Cytotoxic Activity.

In this study, an efficient one-pot procedure for preparing a new series of pyrazolo[3,4-b]pyridine-fused pyrimidines was described. The target hybrids were developed through a three-component reaction of 3-amino-1H-pyrazolo[3,4-b]pyridine, benzaldehydes, and acetophenones (molar ratio 1 : 1 : 1). The best conditions for the previous reaction were 2.5 equivalents of barium hydroxide in DMF at 150 °C for 6 h. New bis(pyrimidines) were synthesized in high yields using a similar one-pot reaction protocol with some modifications. Thus, two equivalents of each of the appropriate acetophenones and 3-aminopyrazolopyridine were reacted with one equivalent of the appropriate bis(aldehydes). The reaction was carried out at 150 °C for 8 h using 4.5 equivalents of barium hydroxide in DMF. Repeating the previous reaction with the appropriate bis(acetyl) derivatives and benzaldehydes resulted in good yields of the target bis(pyrimidines). The in vitro cytotoxic activity of new pyrimidines against the MCF-7, HEPG2, and Caco2 cell lines was evaluated using the reference doxorubicin (IC50 values of 4.34-6.97 µM). Hybrid 6h had the best activity against Caco2 and MCF-7 cell lines, IC50 values of 12.62 and 14.50 µM, respectively. The IC50 values for hybrids 6c, 6e, and 6f against MCF-7 and Caco2 cell lines were 23.99-41.69 and 33.14-43.33 µM, respectively. Furthermore, hybrid 6e displayed IC50 value of 20.06 µM HEPG2 cell lines, while the hybrids 6c, 6f and 6h exhibited IC50 values ranging between 26.29-50.51 µM. Furthermore, hybrid 6e had an IC50 value of 20.06 µM for the HEPG2 cell lines, whereas hybrids 6c, 6f, and 6h had IC50 values ranging from 26.29 to 50.51 µM.

In Vitro Study on the Piezodynamic Therapy with a BaTiO3-Coating Titanium Scaffold under Low-Intensity Pulsed Ultrasound Stimulation.

To solve the poor sustainability of electroactive stimulation in clinical therapy, a strategy of combining a piezoelectric BaTiO3-coated Ti6Al4V scaffold and low-intensity pulsed ultrasound (LIPUS) was unveiled and named here as piezodynamic therapy. Thus, cell behavior could be regulated phenomenally by force and electricity simultaneously. First, BaTiO3 was deposited uniformly on the surface of the three-dimensional (3D) printed porous Ti6Al4V scaffold, which endowed the scaffold with excellent force-electricity responsiveness under pulsed ultrasound exposure. The results of live/dead staining, cell scanning electron microscopy, and F-actin staining showed that cells had better viability, better pseudo-foot adhesion, and more muscular actin bundles when they underwent the piezodynamic effect of ultrasound and piezoelectric coating. This piezodynamic therapy activated more mitochondria at the initial stage that intervened in the cell cycle by promoting cells' proliferation and weakened the apoptotic damage. The quantitative real-time polymerase chain reaction data further confirmed that the costimulation of the ultrasound and the piezoelectric scaffolds could trigger adequate current to upregulated the expression of osteogenic-related genes. The continuous electric cues could be generated by the BaTiO3-coated scaffold and intermittent LIPUS stimulation; thereon, more efficient bone healing would be promoted by piezodynamic therapy in future treatment.

"Green" Flexible Electronics: Biodegradable and Mechanically Strong Soy Protein-Based Nanocomposite Films for Human Motion Monitoring.

Soy protein isolate (SPI) is envisioned as a promising alternative to fabricate "green" flexible electronics, showing great potential in the field of flexible wearable electronics. However, it is challenging to simultaneously achieve conductive film-based human motion-monitoring strain sensors with reliable fatigue resistance, robust mechanical property, environmental degradability, and sensing capability of human motions. Herein, we prepared a series of SPI-based nanocomposite films by embedding a surface-hydroxylated high-dielectric constant inorganic filler, BaTiO3, (HBT) as interspersed nanoparticles into a biodegradable SPI substrate. In particular, the fabricated film comprising 0.5 wt % HBT and glycerin (GL), namely, SPI-HBT0.5-GL0.5, presents multifunctional properties, including a combination of excellent toughness, tensile strength, conductivity, translucence, recyclability, and excellent thermal stability. Meanwhile, this multifunctional film could be simply degraded in phosphate buffered saline solution and does not cause any pollution to the environment. Attractively, wearable sensors prepared with this particular material (SPI-HBT0.5-GL0.5) displayed excellent biocompatibility, prevented the occurrence of an immune response, and could accurately monitor various types of human joint motions and successfully remain operable after 10,000 cycles. These properties make the developed SPI-based film a great candidate in formulating biobased and multifunctional wearable electronics.

Application of iron/barium ferrite/carbon-coated iron nanocrystal composites in transcatheter arterial chemoembolization of hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) has been widely used in clinical practice as a first-line treatment for unresectable hepatocellular carcinoma (HCC). However, the current therapeuticeffect of TACE is far from satisfactory and thus requires further improvement. TACE combined with multifunctional magnetic particles may be a promising approach for the treatment of HCC. In this study, we designed a new magnetic drug carrier system consisting of micron-sized iron powder, barium ferrite (BaFe12O19), and carbon-coated iron nanocrystals (CCINs). CCINs possess properties, such as high drug loading and sustained release. BaFe12O19 could attract both CCINs and iron powder to form larger clusters after magnetization. Altogether, the triple therapeutic effects of chemotherapeutic enhancement, embolization, and thermal ablation could be realized herein. Further experiments indicate that the system has a high drug-loading capacity, good controlled-release effect, and no significant cytotoxicity. Under the action of a medium-frequency magnetic induction device, the magnetic induction temperature could reach 43 °C in one min while the maximum temperature of 70.8 °C could be reached in 2.5 h. Overall, this new carrier system displayed excellent antitumor effects in a mouse model. Our findings demonstrate the great application prospects of this system in TACE for HCC.

Dual response of osteoblast activity and antibacterial properties of polarized strontium substituted hydroxyapatite-Barium strontium titanate composites with controlled strontium substitution.

To mimic the electrical properties of natural bone, controlled strontium substitution of both hydroxyapatite and ferroelectric barium titanate were achieved by mixing in the ratio 30:70 by weight. The composites were characterized by X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy to investigate the phase composition and microstructure of the composites. Unpolarized and polarized strontium hydroxyapatite (SrHA)-barium strontium titanate (BST) composites with controlled degree of Sr substitution were examined, including 5SrHA-5BST (5% Sr substitution in both components) and 10SrHA-10BST composites. The 10SrHA-10BST composite showed a higher osteoblast activity, as observed from the cell viability studies performed using CCK-8 assay. The polarized composites showed promise against Staphylococcus aureus bacteria by minimizing the adhesion and growth of bacteria, as compared with their unpolarized counterparts. The polarized 10SrHA-10BST was found to be superior than all other composites. As a result, the approach of polarization of SrHA-BST composites has been found to be an effective bone substitute material in controlled enhancement of osteoblast growth with simultaneous reduction of bacterial infection.

Different types of dysphagia alleviated by the chin-down position.

OBJECTIVE: Retrospective videofluoroscopic swallowing study (VFSS) evaluations of pharyngeal swallowing were used to evaluate the types of dysphagia alleviated by the chin-down maneuver. MATERIALS AND METHODS: The study population consisted of 64 patients who underwent VFSS evaluations during neutral and chin-down maneuvers presenting specifically penetration or aspiration. The assessment of the VFSS movie clips of each maneuver was performed using parameters of the Modified Barium Swallow Impairment Profile (MBSImP) and the presence and degree of airway invasion(PDAI) by three blinded raters in the following five subcategorized groups, 1. patietns presenting penetration or aspiration during swallow 2. after swallow, patients of 3. head and neck, 4. digestive and 5. neuromuscular disorders, respectively. The scores registered for the two maneuvers were statistically compared. Additionally, we examined statistically which factors had the impact on the improvement of the PDAI using fisher's exact test. RESULTS: Compared with the neutral position, PDAI, pharyngeal constriction, anterior hyoid movement, pharyngeal constriction, laryngeal elevation, laryngeal closure, upper esophageal sphincter opening, initiation of the pharyngeal swallow, and pharyngeal clearance in pyriform sinus were significantly (p < 0.01-0.05) improved with the chin-down maneuver. In a subcategory comparison with group 1, 3 and 4, the PDAI improved significantly (p < 0.01) with the chin-down maneuver, in which laryngeal elevation and laryngeal closure had statistically the impact (p < 0.01-0.05) on improvement of PDAI. CONCLUSION: The chin-down maneuver was most effective in improving swallow function when the impairment included penetration and aspiration during swallow caused by inadequate laryngeal elevation and laryngeal closure.

Multiple rapid swallows and rapid drink challenge in patients with esophagogastric junction outflow obstruction on high-resolution manometry.

BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) as defined by Chicago Classification of esophageal motility disorders (CCv3.0) encompasses a broad range of diagnoses, thus posing clinical challenges. Our aims were to evaluate multiple rapid swallow (MRS) and rapid drink challenge (RDC) during high-resolution manometry (HRM) to aid identifying clinically relevant EGJOO. METHODS: Patients with a HRM diagnosis of EGJOO based on CCv3.0 that also completed MRS and RDC during HRM and barium esophagram were retrospectively identified. Radiographic EGJOO (RAD-EGJOO) was defined by either liquid barium retention or delayed passage of a barium tablet on barium esophagram. Thirty healthy asymptomatic controls that completed HRM were also included. MRS involved drinking 2 mL for 5 successive swallows. RDC involved rapid drinking of 200 mL liquid. Integrated relaxation pressure (IRP) and presence of panesophageal pressurization (PEP) during MRS and RDC were assessed. KEY RESULTS: One hundred one patients, mean (SD) age 56 (16) years, were included; 32% had RAD-EGJOO, 68% did not. RAD-EGJOO patients more frequently had elevated (>12 mmHg) upright IRP (100%), MRS-IRP (56%), RDC-IRP (53%), and PEP during RDC (66%) than both controls [17%; 0%; 7%; 3%] and patients without RAD-EGJOO [83%; 35%; 39%; 41%] Having IRP >12 mmHg during both MRS and RDC was twice as likely to be associated with RAD-EGJOO (19%) than those without RAD-EGJOO (9%) among patients with upright IRP >12 mmHg. CONCLUSIONS AND INFERENCES: Adjunctive HRM maneuvers MRS and RDC appear to help identify clinically significant EGJOO. While future outcome studies are needed, comprehensive multimodal evaluation helps clarify relevance of EGJOO on HRM.

Timed barium swallow for assessing long-term treatment response in patients with achalasia: Absolute cutoff versus percent change - A cross-sectional analytic study.

BACKGROUND: Timed barium swallow (TBS) assesses esophageal emptying before and after therapy in patients with achalasia. Our aim was to compare the accuracy of percent change in barium height with traditional absolute cutoff of <5 cm on post-treatment TBS. MATERIALS AND METHODS: Consecutive patients with treatment naïve achalasia treated with either PD, HM, or POEM between 1/2012 and 7/2017 were eligible for inclusion. The accuracy of percent change in pre- and post-treatment barium height at 5 minutes versus an absolute <5 cm cutoff for assessing treatment response was assessed using the receiver operating curve analysis (ROC). RESULTS: Eighty-one patients met the inclusion criteria. The median percent change in barium heights at five minutes in patients who did not improve was 6 percent increase (n = 10; mean 10.6) versus 78 percent decrease (n = 71; mean 64) in patients who improved (P = 0.0001). The AUC for percent change in TBS 5 minutes height was 76% (95% CI 48% to 90%), and a 3% decrease from baseline as a cutoff had a sensitivity of 60% and specificity of 99%. The AUC for post-treatment TBS 5 minutes height was 79% (95% CI 53% to 91%), and the 5 cm cutoff had a sensitivity of 70% and specificity of 75%. CONCLUSIONS: The results show that 3% percent improvement in pre- and post-treatment barium height at 5 minutes rather than absolute cutoff value of <5 cm on post-treatment TBS is a better indicator of treatment success in achalasia patients. These findings indicate the need for reassessment of tools to identify treatment response.

Hypercontractile Esophagus From Pathophysiology to Management: Proceedings of the Pisa Symposium.

Hypercontractile esophagus (HE) is a heterogeneous major motility disorder diagnosed when ≥20% hypercontractile peristaltic sequences (distal contractile integral >8,000 mm Hg*s*cm) are present within the context of normal lower esophageal sphincter (LES) relaxation (integrated relaxation pressure < upper limit of normal) on esophageal high-resolution manometry (HRM). HE can manifest with dysphagia and chest pain, with unclear mechanisms of symptom generation. The pathophysiology of HE may entail an excessive cholinergic drive with temporal asynchrony of circular and longitudinal muscle contractions; provocative testing during HRM has also demonstrated abnormal inhibition. Hypercontractility can be limited to the esophageal body or can include the LES; rarely, the process is limited to the LES. Hypercontractility can sometimes be associated with esophagogastric junction (EGJ) outflow obstruction and increased muscle thickness. Provocative tests during HRM can increase detection of HE, reproduce symptoms, and predict delayed esophageal emptying. Regarding therapy, an empiric trial of a proton pump inhibitor, should be first considered, given the overlap with gastroesophageal reflux disease. Calcium channel blockers, nitrates, and phosphodiesterase inhibitors have been used to reduce contraction vigor but with suboptimal symptomatic response. Endoscopic treatment with botulinum toxin injection or pneumatic dilation is associated with variable response. Per-oral endoscopic myotomy may be superior to laparoscopic Heller myotomy in relieving dysphagia, but available data are scant. The presence of EGJ outflow obstruction in HE discriminates a subset of patients who may benefit from endoscopic treatment targeting the EGJ.

Field-controlled magnetoelectric core-shell CoFe2O4@BaTiO3 nanoparticles as effective drug carriers and drug release in vitro.

The targeted drug release at tumor cells while sparing normal cells is a huge challenge. Core-shell magnetoelectric (ME) nanoparticles have addressed this problem using shape-dependent magneto-electric attributes. The colloidally stable, core-shell cobalt ferrite@barium titanate (CFO@BTO) ME nanoparticles (NPs) used for in vitro study were synthesized using sonochemical method. The structural characteristics and core-shell morphology were analyzed by X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) respectively. Further magnetic and exchange coupling between two phases of ME nanostructures were studied at room temperature. Colloidal stability was studied in different suspension solutions (Water, SBB, PBS, and DMEM) using dynamic light scattering. Subsequently, the synthesized nanoparticles were functionalized with anticancer drugs including doxorubicin and methotrexate up to 80% via (EDC) chemistry. In vitro cytotoxicity studies carried out on human hepatocellular carcinoma (HepG2) and human malignant melanoma (HT144), cells validated the magneto-electric property of CFO@BTO nano-carriers in the presence of external magnetic field (5 mT), with significantly enhanced cytotoxicity when compared to free drugs and without field replicates. The resulted IC50 values ranging from 5.3-7.3 µg/ml compared to 30.1-43.1 µg/ml in the absence of a magnetic field also confirmed the involved physical attributes of magnetoelectric nanostructures. The fluorescent microscopy results also indicated the increased apoptosis in magnetic field-assisted samples. Finally, hemolysis assay indicated the suitability of CFO@BTO nano-carriers for intravenous applications at IC50 concentration.

Tunable Substrate Functionalities Direct Stem Cell Fate toward Electrophysiologically Distinguishable Neuron-like and Glial-like Cells.

Engineering cellular microenvironment on a functional platform using various biophysical cues to modulate stem cell fate has been the central theme in regenerative engineering. Among the various biophysical cues to direct stem cell differentiation, the critical role of physiologically relevant electric field (EF) stimulation was established in the recent past. The present study is the first to report the strategy to switch EF-mediated differentiation of human mesenchymal stem cells (hMSCs) between neuronal and glial pathways, using tailored functional properties of the biomaterial substrate. We have examined the combinatorial effect of substrate functionalities (conductivity, electroactivity, and topography) on the EF-mediated stem cell differentiation on polyvinylidene-difluoride (PVDF) nanocomposites in vitro, without any biochemical inducers. The functionalities of PVDF have been tailored using conducting nanofiller (multiwall-carbon nanotube, MWNT) and piezoceramic (BaTiO3, BT) by an optimized processing approach (melt mixing-compression molding-rolling). The DC conductivity of PVDF nanocomposites was tuned from ∼10-11 to ∼10-4 S/cm and the dielectric constant from ∼10 to ∼300. The phenotypical changes and genotypical expression of hMSCs revealed the signatures of early differentiation toward neuronal pathway on rolled-PVDF/MWNT and late differentiation toward glial lineage on rolled-PVDF/BT/MWNT. Moreover, we were able to distinguish the physiological properties of differentiated neuron-like and glial-like cells using membrane depolarization and mechanical stimulation. The excitability of the EF-stimulated hMSCs was also determined using whole-cell patch-clamp recordings. Mechanistically, the roles of intracellular reactive oxygen species (ROS), Ca2+ oscillations, and synaptic and gap junction proteins in directing the cellular fate have been established. Therefore, the present work critically unveils complex yet synergistic interaction of substrate functional properties to direct EF-mediated differentiation toward neuron-like and glial-like cells, with distinguishable electrophysiological responses.