CUX1 regulates human hematopoietic stem cell chromatin accessibility via the BAF complex.

CUX1 is a homeodomain-containing transcription factor that is essential for the development and differentiation of multiple tissues. CUX1 is recurrently mutated or deleted in cancer, particularly in myeloid malignancies. However, the mechanism by which CUX1 regulates gene expression and differentiation remains poorly understood, creating a barrier to understanding the tumor-suppressive functions of CUX1. Here, we demonstrate that CUX1 directs the BAF chromatin remodeling complex to DNA to increase chromatin accessibility in hematopoietic cells. CUX1 preferentially regulates lineage-specific enhancers, and CUX1 target genes are predictive of cell fate in vivo. These data indicate that CUX1 regulates hematopoietic lineage commitment and homeostasis via pioneer factor activity, and CUX1 deficiency disrupts these processes in stem and progenitor cells, facilitating transformation.

Comparative study of hydroxyapatite synthesized using Schiff base and wet chemical precipitation methods.

Hydroxyapatite (HAp) exists as an inorganic and crystalline composition present in bones and dental enamel, and hence can be utilized as a direct element or as part of the composition of biomaterials and implants for dental and orthopaedic applications. Listed below are a few synthesis techniques for HAp that are listed in the literature: solid-state and mechano-chemical methods (dry methods), wet chemical precipitation and sol-gel methods (wet methods), and combustion and pyrolysis methods (high-temperature processes). Nevertheless, there are new and more productive techniques that result in HAp with a regulated morphology, such as the Schiff base method, which, on reaction with calcium and phosphate precursors, forms chelating complexes to produce HAp nuclei. This research paper presents the comparison in characteristics between HAp synthesized using Schiff base (HAp-SB), wet chemical precipitation (HAp-WC) methods, and commercial HAp (HAp-CM) in their powdered and pelleted form. The average size of HAp-WC particles in the spherical form was found to be 603 nm ± 176, HAp-SB were found to have rod-like morphology, which is very similar to human bone-like HAp, with an average length and width of 1522 nm ± 759 and 400 nm ± 112, respectively, and HAp-CM were found to have spherical morphology with dimensions of 52 nm ± 25. Biological studies show that cell viability of HAp-SB pellet (202.01% ± 8.16) seemed to have higher cell proliferation properties than HAp-WC pellet (145.7% ± 5.11) and HAp-CM pellet (71.53% ± 3.61) due to its higher aspect ratio, and hence higher surface area for the cells to adhere. In a detailed study, it is observed that both techniques had their advantages, and there were no significant disadvantages observed.

Investigation of Giant Cell Tumor of Bone and Tissue Engineering Approaches for the Treatment of Giant Cell Tumor of Bone.

Primary bone tumors such as Ewing sarcoma, osteosarcoma, and chondrosarcoma, secondary bone tumors developed from progressive malignancies, and metastasized bone tumors are more prevalent and studied descriptively through biology and medical research. Less than 0.2% of cancer diagnoses are caused by rare bone-originating tumors, which despite being rare are particularly difficult due to their high death rates and substantial disease burden. A giant cell tumor of bone (GCTB) is an intramurally invasive but rare and benign type of bone tumor, which seldom metastasizes. The most often prescribed medication for GCTB is Denosumab, a RANKL (receptor activator of nuclear factor κB ligand) inhibitor. Because pharmaceutical drug companies rely on two-dimensional and animal models, current approaches for investigating the diverse nature of tumors are insufficient. Cell line based medication effectiveness and toxicity studies cannot predict tumor response to antitumor medicines. It has already been investigated in detail why molecular pathways do not reproduce in vitro, a phenomenon known as flat biology. Due to physiological differences between human beings and animals, animal models do not succeed in identifying side effects of the treatment, emulating metastatic growth, and establishing the link between cancer and the immune system. This review summarizes and discusses GCTB, the disease, its cellular composition, various bone tumor models, and their properties and utilization in research. As a result, this study delves deep into in vitro testing, which is vital for scientists and physicians in various fields, including pharmacology, preclinical investigations, tissue engineering, and regenerative medicine.

Factors Affecting Post-Anesthesia Care Unit Length of Stay in Pediatric Patients after an Adenotonsillectomy.

OBJECTIVES: (1) To identify clinical factors and perioperative practices that correlate with longer length of stay (LOS) in the post-anesthesia care unit (PACU) after adenotonsillectomy (T&A) in pediatric populations.(2) To understand the relationship between family presence and PACU LOS for pediatric patients after T&A. METHODS: Pediatric patients (ages 3-17) who underwent T&A between February 2016 and December 2016 were retrospectively reviewed. Factors assessed for impact on PACU LOS included BMI, preoperative medications, intraoperative medications/narcotics, postoperative medications/narcotics, method of postoperative medication administration, and family presence in the PACU. Kruskal-Wallis and Spearman tests were used to assess correlations. Statistical significance was set a priori at P < .05. RESULTS: Our cohort included 500 patients. Patients were in the PACU for an average of 135.4 minutes (±65.8). Subset analyses of the type of medications administered intra-operatively and in the PACU show that the intraoperative administration of sedatives is associated with increased LOS (P = .014). Postoperative administration of any medications (P < .001), and specifically, postoperative administration of narcotics (P < .001), analgesics (P = .043), antihistamines (P < .001), and dopamine antagonists (P = .011), are associated with increased LOS. Administration of PACU medications by IV was also correlated with shorter LOS compared to oral administration of PACU medications (P = .016). A comparison of patients who received PACU medications to those who did not demonstrated that intraoperative administration of acetaminophen was associated with a reduced need for PACU medication administration (P = .012). Shorter waiting times for family arrival in the PACU was also associated with shorter LOS (P < .001). CONCLUSION: Our results suggest that postoperative medication administration and time until family arrival in the PACU are associated with significant differences in LOS. We also find that intraoperative administration of acetaminophen is correlated with reduced need for postoperative medication administration. Standardizing postoperative practices to minimize PACU LOS could result in a more efficient recovery for pediatric patients undergoing T&A.

Transdiaphragmatic tunneled Broviac catheters: Cost-effective perioperative central venous access in infants undergoing cardiac surgery.

OBJECTIVES: Infants undergoing congenital heart surgery require central venous lines which can be achieved by various combinations of transthoracic lines, percutaneous-indwelling central catheters and tunneled Broviac catheters. Transthoracic lines are removed by protocol prior to cardiac intensive care unit discharge (risk of bleeding), at which time percutaneous-indwelling central catheters are placed. Transdiaphragmatic tunneled Broviac catheters placed at the time of sternotomy, remain in place until hospital discharge, when they are safely removed at bedside. We characterized actual cost profiles associated with strategies that do versus do not include tunneled Broviac catheters. METHODS: From January 2014 to December 2016, we identified a study population of 220 consecutive patients under 1 year of age undergoing congenital heart surgery. Cost data were acquired from our electronic patient system interface database and office of finance. Our cohort was divided into 2 groups, tunneled Broviac catheter and nontunneled Broviac catheter. We calculated the total cost associated with each groups' central venous lines, propensity matched, and used the Mann-Whitney U test to analyze the results. RESULTS: Eighty-three (37.7%) of the 220 patients had tunneled Broviac catheters. The tunneled Broviac catheter group had 4 percutaneous-indwelling central catheter insertions and 6 radiological interventions while the nontunneled Broviac catheter group had 90 percutaneous-indwelling central catheters and 203 radiologic interventions. After propensity score matching, both groups were reduced to 82 patients and sum, median and interquartile range cost for tunneled Broviac catheters and nontunneled Broviac catheters was $17,351.84, $159.76 (128-159.76) versus $72,809.32, $1277.26 (31.76-1277.26), P < .02 respectively. CONCLUSIONS: Tunneled Broviac catheters, placed routinely at cardiac surgery, incur lower costs than the conventional combination of transthoracic lines and percutaneous-indwelling central catheters. The cost-effectiveness is achieved by reducing the number of percutaneous-indwelling central catheters and associated radiologic interventions.

Crosslinking of gum-based composite scaffolds for enhanced strength and stability: A comparative study between sodium trimetaphosphate and glutaraldehyde.

Tissue engineering is one of the potential fields in the domain of regenerative medicine. Engineered scaffolds are an excellent substitute for the conventional use of bone grafts as they are biocompatible, economic, and provide limitless supply with no risk of disease transmission. Gum-based scaffolds present a good scope for studying tissue-engineering models and analyzing controlled drug delivery. Uniform blending of the gums and the presence of the optimal concentration of appropriate crosslinkers are very crucial for biodegradability nature. Gum-based scaffolds containing gellan gum, xanthan gum, polyvinyl alcohol, and hydroxyapatite, cross-linked with either glutaraldehyde (GA) or sodium trimetaphosphate (STMP) were fabricated to study the efficiency of crosslinkers and were characterized for degradation profile, swelling capacity, porosity, mechanical strength, morphology, X-ray diffraction, Fourier-transform infrared, and in vitro biocompatibility. Scaffolds crosslinked with STMP exhibited higher degradation rate at Day 21 than scaffolds crosslinked with GA. However, higher compressive strength was obtained for scaffolds cross-linked with STMP signifying that they have a better ability to resist compressive forces. Superior cell viability was observed in STMP-crosslinked scaffolds. In conclusion, STMP serves as a better crosslinker in comparison to GA and can be used in the fabrication of scaffolds for bone tissue engineering.

Gum based 3D composite scaffolds for bone tissue engineering applications.

The increase in population, greater life expectancy, and lifestyle choices have caused a drastic increase in the number of bone diseases such as bone tumours, osteoarthritis and bone fractures. This results in the dire need for treatment options such as suitable bone grafts that can be easily fabricated, and are economical. In this study, fabricated composite scaffolds are made from polysaccharide biopolymers, namely gellan and guar gum, and hydroxyapatite by freeze drying method. The developed scaffolds of optimum concentration showed a maximum percentage degradation of 13.7% only until 21 days in phosphate buffered saline solution, and minimum swelling capacity. The mechanically stable scaffolds (compressive strength equivalent to cancellous bone region, ˜3-30 MPa) amongst them were then subjected to characterization tests-scanning electron microscopy, fourier transform infrared spectroscopy, X-ray diffraction, swelling ratio percentage determination, degradation profile study and water vapour transmission study. The cytotoxic evaluation of the optimised scaffolds was performed using MTT assay with murine fibroblast (L929) cells and osteosarcoma (MG63) cells. It was found that the scaffolds were non-cytotoxic and additionally, the cells had proliferated well within the scaffolds, which was confirmed by MTT assay at 1, 4 and 7 days after cell seeding onto the scaffolds.

Development of mechanically compliant 3D composite scaffolds for bone tissue engineering applications.

Cancellous bone region of the human native bone has the potential to bear significant mechanical loads. However, due to the following parameters such as low trabecular volume, more porosity, less thickness and more interconnectivity, cancellous bone is accessible to damage in accidents or when aging. This research led to the effective fabrication and engineering of cancellous region of the bone for its application in reconstruction or filling of bone voids after resection of large tumor mass. Scaffolds containing hydroxyapatite (HAp), polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) (5% polymer and HAp concentrations) at different HAp: polymer composite ratios (50:50, 70:30 and 80:20), were fabricated by freeze-drying method using only water as solvent and ribose as crosslinker for the scaffolds. The fabricated scaffolds were characterized for its mechanical (compressive) strength, chemical properties using FT-IR and XRD analyses, swelling and degradation studies, confirmation of mineralization process by immersion in simulated body fluid (SBF) for 7, 15 and 30 days, morphological analysis using scanning electron microscopy (SEM), and biocompatibility properties by performing MTT analysis. From the combined interpretation of the above mentioned tests, it was proven that 80:20 ratio of HAp to polymers was found to be the most suitable scaffold in terms of its optimal properties for its use as bone graft material for trabecular bone. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3267-3274, 2018.