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Hypothesis: Magnetic Sphincter Augmentation device causes fibrosis at the distal esophagus which prevents reflux even after device removal Background: Gastroesophageal reflux disease (GERD) affects over 20 million people in the United States. If left untreated, chronic reflux of gastric contents into the distal esophagus may result in benign or malignant esophageal strictures, causing varying degrees of dysphagia. We currently offer interventions which artificially create a narrowing at the distal esophagus to prevent complications of GERD. Magnetic Sphincter Augmentation device (MSA), or LINX, creates such a narrowing of the distal esophagus at the level of the LES. Individuals intolerant of this device need surgical removal which leaves scarring at the site of implantation. Methods: There were 118 MSA devices placed at our institution between 2017 and 2021. During this time, 8 out of 118 (6.7%) patients needed to have their LINX removed due to side effects attributed to the implant. Causes for removal included esophageal perforation, dysphagia or hypersensitivity related chest pressure presumably caused by the device. Patients, who have had the LINX device removed, were followed for recurrence of reflux using Barium Swallow imaging, endoscopic findings and GERD-HRQL scores. Results: The longer the MSA implants remained before removal, the more extensive the scar tissue encountered at site of excision. Five of eight patients (62%) experienced improvement in their GERD-HRQL scores after removal of the MSA device when compared to results before LINX implantation. The residual band of scar tissue observed after device removal appeared to control reflux by restricting the relaxation of the esophageal outlet. Conclusions: These results indicate that fibrosis at the site of MSA device removal improves heartburn symptoms in a majority of patients. We do not recommend fundoplication at time of LINX removal as symptoms of GERD may be adequately controlled by scar tissue at the LES.

Among the various cross coupling reactions, C−C cross coupling reaction has attracted many researchers to investigate in the last four decades. The continuous, constant, and consistent progress in this field fetched a Noble prize in 2010, showing the importance of this reaction in diversified fields. Among the various transition metals studied for this reaction, Pd is one of the metals that has exhibited the highest activity due to its unique features and reactivity. Although Pd-based homogeneous catalyst was the preferred choice for many researchers, the field slowly diverted towards the development of Pd-based heterogeneous catalysts for C−C coupling reactions. This is obviously due to the high cost of Pd precursor, its self-deactivation. In this context, metal organic frameworks (MOFs) are one of the solid catalysts frequently employed as host matrix for the deposition of Pd(II) salts and Pd nanoparticles. This is due to the widespread possibilities available for the functionalization of MOFs and their stability during the synthetic procedure. This review provides the design and development of Pd-based MOFs as heterogeneous catalysts for the C−C cross coupling reactions. After a brief introduction on MOFs and the importance of C−C coupling reactions, the main part of the review summarizes the catalytic data with respect to Pd(II) and Pd nanoparticles as active sites. The last section provides our views in this field for the further development in the near future.

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of Technology-aided assessments of sensorimotor function: current use, barriers and future directions in the view of different stakeholders

Questionnaire. (PDF 2623 kb)

This article deals with the identification and characterization of process-related impurities of trans-resveratrol (3,5,4'-trihydroxystilbene), which exhibits several health benefits, including cancer prevention. During the synthesis of the bulk drug resveratrol, three new impurities were observed. The impurities were detected using the high-performance liquid chromatographic (HPLC) method, whose area percentages ranged from 0.05 to 0.3%. A systematic study was carried out to characterize them. These impurities were isolated by preparative HPLC and characterized by spectral data, subjected to co-injection in HPLC, and were found to be matching with the impurities present in the sample. LC-MS was performed to identify the mass of these impurities. Based on their spectral data (IR, NMR, and Mass), these impurities were characterized as 2-benzyl-5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol [Impurity-B], 3-(benzyloxy)-5-[(E)-2-(4-hydroxyphenyl)ethenyl]phenol [Impurity-C], 5-{(E)-2-[4-(benzyloxy)phenyl]ethenyl}benzene-1,3-diol [Impurity-D). These compounds are not reported earlier as process-related impurities.

A multifunctional nanoparticle based on carboxymethyl cellulose was developed. Folate group was attached to nanoparticle for specific recognition of cancerous cells and 5FU was encapsulated for delivering cytotoxicity. The whole system was able to track by the semiconductor quantum dots that were attached to the nanoparticle. The multifunctional nanoparticle was characterized by UV-VIS spectra, PL spectra, FTIR, TEM, SEM etc and was targeted to human breast cancer cell, MCF7. The biocompatibility of nanoparticle without drug and cytotoxicity rendered by nanoparticle with drug was studied with MCF7 and L929 cell lines. The epifluorescent images suggest that the folate-conjugated nanoparticles were more internalized by folate receptor positive cell line, MCF7 than the noncancerous L929 cells.

Appendix. This additional file includes the details of the SPARC measure development and the analysis of its properties. (PDF 474 kb)

Two unknown impurities were detected in the cefazolin sodium bulk drug substance using gradient reversed-phase high-performance liquid chromate-graphy (HPLC). These impurities were isolated by preparative HPLC and characterized by using spectroscopic techniques like LC-MS, LC-MS/MS, 1D, 2D NMR, and FT-IR. Based on the spectral data, the impurities have been characterized as N-(2,2-dihydroxyethyl)-2-(1H-tetrazol-1-yl)acetamide (Impu rity-I) and 2-{carboxy[(1H-tetrazol-1-ylacetyl)amino]methyl}-5-methylidene-5,6-dihydro-2H-1,3-thiazine-4-carboxylic acid (Impurity-II). The structures of these impurities were also established unambiguously by co-injection into HPLC to confirm the retention time. To the best of our knowledge, these two impurities were not reported elsewhere.

In an era where rehabilitation services are diminishing under the weight of the growing demands and fewer therapists, home-based telerehabilitation offers a way of increasing duration and intensity of post-stroke training. Novel systems that guide the therapist and patient in planning, executing, and assessing the training can reduce the burden on the healthcare system while maintaining or improving the quality of care. To achieve this effectively, a unified approach is needed that can address the diverse needs of the users and adequately assess the level of mobility deficits remotely. This document presents a methodology and prototype system for assessment and training adaptation within a telerehabilitation framework targeting home-based rehabilitation of the upper limbs after stroke. The framework uses 4 games for assessment of motor performance based on measures of range and control of movement. Assessment games include range of motion, range of force, control of motion, and control of force. The initial assessment games are used to tune the deficit-specific parameters in each successive game for assessment and training. Games are administered over the web-based TeleREHA platform through a novel arm rehabilitation device called the ArmAssist. An overview of the developments in each project is presented including the basic assessment parameters and a methodology for making patient-specific adaptation to game levels. Preliminary feedback from an ongoing usability evaluation is also presented and discussed.

In this work, self-assembled core/shell nanostructures of CdS/CoFe2O4 (CFO) have been synthesized using a chemical solution method to include magnetic and fluorescent properties in a single composite material for bioapplications. Successful synthesis of the core/shell nanostructure has been evidenced from the transmission electron microscopy and x-ray diffraction results. Alternating gradient magnetometer and photoluminescence spectroscopy results confirm good magnetic and luminescent characteristics of the core/shell nanostructure. The in vitro biocompatibility of the CFO and CdS/CFO nanostructures has been studied in the Alamar blue assay in four different cell lines (MIAPaCa-2, MCF-7, KUSA-A1, and L929 cells) at different concentrations of nanostructures. The CdS/CFO nanostructure shows improved biocompatibility in all the cell lines as compared to bare CFO nanostructures at all concentrations. However, the biocompatibility for both the nanostructures is found to decrease in the KUSA-A1 cell line at higher concentrations of the nanostructures, which is due to the higher sensitivity of the KUSA-A1 cell line to the nanostructures at higher concentrations than other cell lines. Biocompatibility studies show the potentiality of these core/shell nanostructures for bio-applications.

The single-crystal X-ray diffraction study of the title mol­ecule [alternative name: N(2)-acetyl-1,3-di­phenyl-1,2,3,4-tetra­hydro­benzo­[b][1,6]naphthyridine], C26H22N2O, confirms that it is a 1,6-naphthyridine derivative whose structural characterization was not possible from 1H, 13C NMR and mass spectral data. The tetra­hydro-1,6-napthyridine ring has a boat conformation. The equatorial and axial orientations of the two phenyl groups and the coplanarity of the acetyl group with the tetra­hydro­naphthyridine ring are also confirmed.

A major limitation of the clinical efficacy of the 7-ethyl-10-hydroxycamptothecin (SN38) therapy is its facile conversion of the active lactone form into a less active carboxylate species at physiological pH and limited aqueous solubility. The present manuscript embodies a detailed description of several physicochemical properties of SN38 and further details the thermodynamic basis for its poor aqueous solubility. The ionization and increased solubility of the drug in highly acidic media were subsequently employed to efficiently load the positively charged drug in its biologically active lactone form into mesoporous silica material of type MCM-41, achieving a maximum loading of 250 mg of SN38 per gram of silicate. It was also found that the equilibrium association constant K(A) varies with the extent of drug adsorption. At low and high drug load, corresponding to one SN38 molecule bound for every 70 and 13 -SiO(2)-, K(A) was determined to be 1253.5 and 127.39 M(-1), respectively.

Pancreatic cancer is the fifth leading cause of cancer related deaths worldwide. Currently, finding an effective drug delivery strategy in pancreatic cancer treatment is a major challenge. Nanotechnology offers an indispensible function by precisely delivering anticancer therapeutics in a targeted method to the cancer specific cells thus sparing normal healthy cells and hence resulting in an enhanced efficiency. The development of designer multifunctional therapeutics with magnetic nanoparticles (MNP) is a promising approach to selectively deliver therapeutics and image them in cancer cells. This study explored the preparation, characterization and application of a targeted nanosystem represented by an aptamer conjugated dual drug (curcumin and gemcitabine-loaded) and MNP encapsulated PLGA nanoparticles (Apt-Cur-Gem-PLGA- MNPs) for pancreatic cancer therapy. The aptamer targeted NPs exhibited excellent antiproliferative activity leading to apoptosis owing to enhanced cellular uptake. The presence of MNP in the nanoconjugate was exploited for magnetic hyperthermia and magnetic ablation of cancer cells by a rotating magnetic field. Thus, Apt-Cur-Gem-PLGA-MNPs is able to deliver an effective and targeted delivery of therapeutics for pancreatic cancer treatment. Refereed/Peer-reviewed

Background: Electrospun fibers are widely studied in regenerative medicine for their ability to mimic the extracellular matrix (ECM) and provide mechanical support. In vitro studies indicated that cell adhesion and migration is superior on smooth poly(L-lactic acid) (PLLA) electrospun scaffolds and porous scaffolds once biofunctionalized with collagen. Methods: The in vivo performance of PLLA scaffolds with modified topology and collagen biofunctionalization in full-thickness mouse wounds was assessed by cellular infiltration, wound closure and re-epithelialization and ECM deposition. Results: Early indications suggested unmodified, smooth PLLA scaffolds perform poorly, with limited cellular infiltration and matrix deposition around the scaffold, the largest wound area, a significantly larger panniculus gape, and lowest re-epithelialization; however, by day 14, no significant differences were observed. Collagen biofunctionalization may improve healing, as collagen-functionalized smooth scaffolds were smallest overall, and collagen-functionalized porous scaffolds were smaller than non-functionalized porous scaffolds; the highest re-epithelialization was observed in wounds treated with collagen-functionalized scaffolds. Conclusion: Our results suggest that limited incorporation of smooth PLLA scaffolds into the healing wound occurs, and that altering surface topology, particularly by utilizing collagen biofunctionalization, may improve healing. The differing performance of the unmodified scaffolds in the in vitro versus in vivo studies demonstrates the importance of preclinical testing. Refereed/Peer-reviewed

Electrospun polymer fibers have garnered substantial importance in regenerative medicine owing to their intrinsic 3D topography, extracellular matrix microenvironment, biochemical flexibility, and mechanical support. In particular, a material's nano-topography can have a significant effect on cellular responses, including adhesion, proliferation, differentiation, and migration. In this study, poly(l-lactic acid) (PLLA), a biodegradable polymer with excellent biocompatibility was electrospun into fibers with either smooth or porous topologies. The scaffolds were further modified and biofunctionalized with 0.01% and 0.1% collagen to enhance bioactivity and improve cellular interactions. Human keratinocytes (HaCaTs) and fibroblasts (human foreskin fibroblasts-HFF) were cultured on the scaffolds using a modified co-culture technique, where keratinocytes were grown on the dorsal plane for 5 days, followed by flipping, seeding with fibroblasts on the ventral plane and culturing for a further 5 days. Following this, cellular adhesion of the skin cells on both the unmodified and collagen-modified scaffolds (smooth and porous) was performed using scanning electron microscopy (SEM) and immunofluorescence. Distinct outcomes were observed with the unmodified smooth scaffolds showing superior cell adhesion than the porous scaffolds. Modification of the porous and smooth scaffolds with 0.1% collagen enhanced the adhesion and migration of both keratinocytes and fibroblasts to these scaffolds. Further, the collagen-modified scaffolds (both porous and smooth) produced confluent and uniform epidermal sheets of keratinocytes on one plane with healthy fibroblasts populated within the scaffolds. Thus, presenting a vast potential to serve as a self-organized skin substitute this may be a promising biomaterial for development as a dressing for patients suffering from wounds Refereed/Peer-reviewed

Theragnostics is considered as an emerging treatment strategy that integrates therapeutics and diagnostics thus allowing delivery of therapeutics and simultaneous monitoring of the progression of treatment. Among the different types of inorganic nanomaterials that are being used for nanomedicine, core shell mesoporous silica nanoparticles have emerged as promising multifunctional nanoplatform for theragnostic application. Research in the design of core/shell mesoporous silica nanoparticles is steadily diversifying owing to the various interesting properties of these nanomaterials that are advantageous for advanced biomedical applications. Core/shell mesoporous silica nanoparticles, have garnered substantial attention in recent years because of their exceptional properties including large surface area, low density, ease of functionalization, high loading capacity of drugs, control of the morphology, particle size, tunable hollow interior space and mesoporous shell and possibility of incorporating multifunctional interior core material. In the past decade researcher’s demonstrated tremendous development in design of functionalized core/shell mesoporous silica nanoparticles with different inorganic functional nanomaterial incorporated into mesoporous nanosystem for simultaneous therapeutic and diagnostic (theragnostic) applications in cancer. In this review, we recapitulate the progress in commonly used synthetic strategies and theragnostic applications of core/shell mesoporous silica nanoparticles with special emphasis on therapeutic and diagnostic modalities. Finally, we discuss the challenges and some perspectives on the future research and development of theragnostic core/shell mesoporous silica nanoparticles. Refereed/Peer-reviewed