Clinical Associations of Bitter Taste Perception and Bitter Taste Receptor Variants and the Potential for Personalized Healthcare.

Bitter taste receptors (T2Rs) consist of 25 functional receptors that can be found in various types of cells throughout the human body with responses ranging from detecting bitter taste to suppressing pathogen-induced inflammation upon activation. Numerous studies have observed clinical associations with genetic or phenotypic variants in bitter taste receptors, most notably that of the receptor isoform T2R38. With genetic variants playing a role in the response of the body to bacterial quorum-sensing molecules, bacterial metabolites, medicinal agonists and nutrients, we examine how T2R polymorphisms, expression levels and bitter taste perception can lead to varying clinical associations. From these genetic and phenotypic differences, healthcare management can potentially be individualized through appropriately administering drugs with bitter masking to increase compliance; optimizing nutritional strategies and diets; avoiding the use of T2R agonists if this pathway is already activated from bacterial infections; adjusting drug regimens based on differing prognoses; or adjusting drug regimens based on T2R expression levels in the target cell type and bodily region.

Efficacy and safety of vancomycin-loaded calcium sulfate versus conventional surgical debridement for pediatric acute osteomyelitis: a retrospective study.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of vancomycin-loaded calcium sulfate beads and negative-pressure wound therapy (NPWT) in treating children with acute hematogenous osteomyelitis (AHOM). METHODS: A retrospective cohort study was conducted from January 2017 to January 2020 examining children (n = 60) with AHOM who were treated with surgical debridement followed by vancomycin-loaded calcium sulfate beads and NPWT (n = 32) and compared to treatment by conventional surgical debridement (n = 28) followed by NPWT. Conventional surgical treatment consisted of fenestration of necrotic infected bone, debridement of surrounding soft tissue, and washing of the medullary canal before the application of NPWT. In the vancomycin group, the antibiotic-loaded beads were implanted after washing the medullary canal and before the application of NPWT. Epidemiological factors, complications during the procedure, outcomes at last follow-up (30.0 ± 11.7 months, range 13-58 months), and laboratory parameters were documented and compared between the two groups. RESULTS: Good outcomes were achieved at last follow-up in 71.4% of the conventional treatment group and 75% of the vancomycin group. In the vancomycin group, it took a mean of 4.8 ± 2.5 days for CRP levels to decrease to 50% of initial inflammatory levels compared to 13 ± 9.6 days for the conventional treatment group (p = 0.001, t-test). The conventional group also had seven patients who underwent four or more surgeries whereas no patients in the vancomycin group underwent more than three surgeries (p = 0.013, chi-square test). CONCLUSION: Localized vancomycin delivery with NPWT effective for treating cases of AHOM that required. No perioperative adverse reactions or complications occurred from this treatment method. Based on the shortened recovery period of CRP levels, prolonged administration of post-operational parenteral antibiotics can possibly be reduced with this treatment method.

Six-Year Follow-Up of a Rare Bifid Talus and Eight-Toed Central Polydactyly: A Case Report.

Eight-toed central polydactyly is a rare congenital foot deformity and no other case with a bifid talus has been reported in the literature. We present a 6-year follow-up of a male child who had eight-toed central polydactyly with a duplicate cuneiform bone and bifid talus in his right foot. During preoperative planning, CT scans were conducted to evaluate the duplicate tarsals and to assist in reaching surgical decisions. In 2013, when the child was 1 year and 8 months old, the fourth, fifth and sixth phalanges and metatarsals as well as the duplicate cuneiform bone were excised. A portion of the malformed talus was also resected. This case report discusses functional and aesthetic outcomes after 6 years and provides an analysis on relevant reconstructive follow-up practices.

Contact force sensors in minimally invasive catheters: current and future applications.

INTRODUCTION: Advances in catheter design for minimally invasive surgery have brought about the incorporation of contact force (CF) sensors in catheters. Two main approaches to achieve CF sensing at the catheter end-effector consist of fiber optic or magnetic solutions. CF sensing feedback can be used to assist in ablation procedures, mapping cardiac regions, identifying tissue characteristics, and enhancing robotic catheter control. AREAS COVERED: This review covers the technological and clinical aspects of CFS in catheters. Contact force and force-time integral thresholds for ablation procedures, procedural complications, and electroanatomical mapping strategies are discussed. Future applications of improving catheter control, minimizing complications, and enhancing mapping techniques through CF are examined. EXPERT OPINION: Fiber optic CF catheters may be more desirable compared to magnetic modalities due to the lower cost, compactness, and higher accuracy. In ablation procedures, complications due to higher ablation duration, power, contact force, and force time can be reduced through practical experience and informed training for catheter operators. Future prospects consist of the incorporation of CF sensors with remote catheter systems to assist in catheter control. We propose that CF can also be used in machine learning decision-making algorithms to prevent complications or improve tissue characterization.

MRI recovery of the Achilles tendon after percutaneous tenotomy in older children.

BACKGROUND: An observational study was conducted to evaluate the recovery of older children with relapsed congenital clubfoot who underwent an Achilles tenotomy for the second time as part of the Ponseti treatment. METHODS: Thirteen patients (19 feet) with congenital clubfoot underwent Achilles tenotomy where magnetic resonance images of the severed tendons were taken after 1, 3, and 6 weeks post-procedure. The participants were categorized into older children who underwent tenotomy for the first time (group A: mean, 4.9±1.8, and range, 2.8-7 years old) and older children who underwent tenotomy for a second time (group B: mean, 4.9±1.5, and range, 3-6.8 years old). The area of high signal intensity between the severed tendons on MRI scans was computed using Python programming language and compared with clinical assessment. RESULTS: Three weeks after Achilles tenotomy, groups A and B had clinically intact tendons in 9 out of 11 and 2 out of 8 feet, respectively, according to both clinical and MRI assessment. From week 1 to week 3 post-tenotomy, computational analysis showed that the mean high signal intensity area of group A decreased by 88.5±15.2%, which was significantly different (P .048 < .05) than the percent reduction of high signal intensity area of group B (69.0±24.9%). CONCLUSION: Children who underwent Achilles tenotomy for the second time showed slower tendon recovery on the third week post-procedure. A possible reason for slower healing times may be due to the location of tenotomy in being further away from the musculotendinous junction where extrinsic healing mechanisms take place.

Bitter Taste Receptor as a Therapeutic Target in Orthopaedic Disorders.

Non-gustatory, extraoral bitter taste receptors (T2Rs) are G-protein coupled receptors that are expressed throughout the body and have various functional responses when stimulated by bitter agonists. Presently, T2Rs have been found to be expressed in osteoclasts and osteocytes where osteoclasts were capable of detecting bacterial quorum-sensing molecules through the T2R38 isoform. In the innate immune system, stimulating T2Rs induces anti-inflammatory and anti-pathogenic effects through the phospholipase C/inositol triphosphate pathway, which leads to intracellular calcium release from the endoplasmic reticulum. The immune cells with functional responses to T2R activation also play a role in bone inflammation and orthopaedic disorders. Furthermore, increasing intracellular calcium levels in bone cells through T2R activation can potentially influence bone formation and resorption. With recent studies finding T2R expression in bone cells, we examine the potential of targeting this receptor to treat bone inflammation and to promote bone anabolism.

Progress in Photobiomodulation for Bone Fractures: A Narrative Review.

Objective: The aim of this article is to examine current concepts and the future direction of implementing photobiomodulation (PBM) for fracture treatment. Background data: The effectiveness of PBM for bone regeneration has been demonstrated throughout in vitro studies and animal models. Yet, insufficient clinical trials have been reported on treating fractures with PBM. Materials and methods: A narrative review was composed on the basis of a literary search. Inclusion criteria consisted of studies between 2000 and 2019 using animal or human fracture models. Exclusion criteria consisted of studies that did not pertain to complete fractures or used other forms of intervention. Results: Ten animal studies on rats and rabbits and four clinical trials were found on using PBM for complete fractures. Conclusions: Based on positive outcomes in animal trials, parameter optimization of PBM for human fractures still requires extensive research on factors such as dosage, wavelength, penetration depth, treatment frequency, and the use of pulsed waves.

The effect of mechanical stretch stress on the differentiation and apoptosis of human growth plate chondrocytes.

The study is aimed to investigate the effect of stretch stress with different intensities on the differentiation and apoptosis of human plate chondrocytes. In the present study, the human epiphyseal plate chondrocytes were isolated and cultured in vitro. Toluidine blue staining and type II collagen immunohistochemical staining were used to identify the chondrocytes. Mechanical stretch stresses with different intensities were applied to intervene cells at 0-, 2000-, and 4000-µ strain for 6 h via a four-point bending system. The expression levels of COL2, COL10, Bax, Bcl-2, and PTHrp were detected by quantitative RT-PCR. Under the intervention of 2000-µ strain, the expression levels of COL2, COL10, and PTHrp increased significantly compared with the control group (P < 0.05), and the expression level of PCNA was also increased, but the difference was not statistically significant (P > 0.05). Under 4000-µ strain, however, the expression levels of PCNA, COL2, and PTHrp decreased significantly compared with the control group (P < 0.05), and the expression level of COL10 decreased slightly (P > 0.05). The ratio of Bcl-2/Bax gradually increased with the increase of stimulus intensity; both of the differences were detected to be statistically significant (P < 0.05). In conclusion, the apoptosis of growth plate chondrocytes is regulated by mechanical stretch stress. Appropriate stretch stress can effectively promote the cells' proliferation and differentiation, while excessive stretch stress inhibits the cells' proliferation and differentiation, even promotes their apoptosis. PTHrp may play an important role in this process.

Ossotide promotes cell differentiation of human osteoblasts from osteogenesis imperfecta patients by up-regulating miR-145.

Ossotide as an effective bone formation compound preparation has been proved to promote osteoblasts differentiation. MiR-145 is significantly decreased in osteogenesis imperfecta (OI) patients, but it is still unknown whether ossotide performed its effect by regulating miR-145. In this study, we investigated the effect of ossotide on regulating miR-145 expression and osteoblasts differentiation. The primary osteoblasts cells were isolated from OI patients and then cultured with different concentrations (0, 25, 50, 100, 200µg/l) of ossotide. The cell proliferation was detected with CCK-8 Elisa kit after ossotide treatment. The level of miR-145 expression was determined using qRT-PCR. In order to study whether ossotide up regulated miR-145, miR-145 mimic and miR-145 inhibitor were used to up regulate and down regulate the miR-145 levels in osteoblasts. The expressions of Runx2, Osx, ß-catenin, TCF-1 were detected using Western blot and qRT-PCR. We observed that miR-145 was up regulated by ossotide treatment in miR-145 mimic or miR-145 inhibitor treated osteoblasts. What's more, up regulated miR-145 increased the expression of osteoblasts differentiation regulated protein Runx2 and Osx. In addition, Wnt signaling related ß-catenin, TCF-1 were activated by up-regulated miR-145 which was induced by ossotide treatment. In summary, ossotide induced cell differentiation and Wnt signaling activation in osteoblasts by up regulating miR-145.