Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.     

Towards a Better Prediction of Cell Settling on Nanostructure Arrays—Simple Means to Complicated Ends

Vertical arrays of nanostructures (NSs) are emerging as promising platforms for probing and manipulating live mammalian cells. The broad range of applications requires different types of interfaces, but cell settling on NS arrays is not yet fully controlled and understood. Cells are both seen to deform completely into NS arrays and to stay suspended like tiny fakirs, which have hitherto been explained with differences in NS spacing or density. Here, a better understanding of this phenomenon is provided by using a model that takes into account the extreme membrane deformation needed for a cell to settle into a NS array. It is shown that, in addition to the NS density, cell settling depends strongly on the dimensions of the single NS, and that the settling can be predicted for a given NS array geometry. The predictive power of the model is confirmed by experiments and good agreement with cases from the literature. Furthermore, the influence of cell‐related parameters is evaluated theoretically and a generic method of tuning cell settling through surface coating is demonstrated experimentally. These findings allow a more rational design of NS arrays for the numerous exciting biological applications where the mode of cell settling is crucial.     

Electrospun microporous gelatin–polycaprolactone blend tubular scaffold as a potential vascular biomaterial

The work reported involved the fabrication of an electrospun tubular conduit of a gelatin and polycaprolactone (PCL) blend as an adventitia‐equivalent construct. Gelatin was included as the matrix for increased biocompatibility with the addition of PCL for durability. This is contrary to most of the literature available for biomaterials based on blends of gelatin and PCL where PCL is the major matrix. The work includes the assiduous selection of key electrospinning parameters to obtain smooth bead‐free fibres with a narrow distribution of pore size and fibre diameter. Few reports elucidate the optimization of all electrospinning parameters to fabricate tubular conduits with a focus on obtaining homogeneous pores and fibres. This stepwise investigation would be unique for the fabrication of gelatin–PCL electrospun tubular constructs. The fabricated microfibrous gelatin–PCL constructs had pores of size ca 50–100 μm reportedly conducive for cell infiltration. The measured value of surface roughness of 57.99 ± 17.4 nm is reported to be favourable for protein adhesion and cell adhesion. The elastic modulus was observed to be similar to that of the tunica adventitia of the native artery. Preliminary in vitro and in vivo biocompatibility tests suggest safe applicability as a biomaterial. Minimal cytotoxicity was observed using MTT assay. Subcutaneous implantation of the scaffold demonstrated acute inflammation which decreased by day 15. The findings of this study could enable the fabrication of smooth bead‐free microfibrous gelatin–PCL tubular construct as viable biomaterial which can be included in a bilayer or a trilayer scaffold for vascular tissue engineering. © 2019 Society of Chemical Industry     

5-Benzylidene-4-Oxazolidinones Are Synergistic with Antibiotics for the Treatment of Staphylococcus aureus Biofilms

The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative approaches to treatment so as to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms, and, in combination with common antibiotics, are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.     

日本应用预应力混凝土预制件建造公路防灾构筑物的情况

本文介绍了日本公路工程利用预应力混凝土预制件修建防灾构筑物的情况。防灾构筑物可分为:防雪灾和防落石、塌方两种。也可分为预防工程和防护工程构筑物,如防风雪掩道、防雪崩栅栏、防雪崩安全隧道、防雪崩栏杆、防落石、防塌方安全隧道和防落石栏杆,以及用FRP的吊栅栏、用泡沫苯乙烯的悬臂梁防落石栏杆等。     

Unperturbed dimension of poly(4-acetoxystyrene) measured in good and theta solvents

In order to obtain the additional data concerning the unperturbed dimension of poly-4-substituted styrene, light scattering measurements are performed on the twenty-two fractions with molecular weight of (0.91–352)·10⁴ of poly(4-acetoxystyrene) in dioxan at 25°C, from which the molecular weight obtained was found easily to be evaluated with the gel permeation chromatography using THF. Phase separation experiments for this polymer indicate that the theta state is attained in isopropyl acetate at 19.7°C and butyl acetate at 26.8°C. By making viscosity measurements at that state, the value of K_Θ is directly evaluated as 5.4·10^?4 dl g^?1. The limiting viscosity number is also obtained in good solvents, THF and dioxan, at 25°C and constants of the Mark-Houwink-Sakurada equation in each solvent are determined. Further, approximately the same K_Θ as above is obtained from these data with the Stockmayer-Fixman plot. The calculated value of steric factor, 2.37, on this polymer may be plausible, compared with those of polyvinylaromatic derivatives.     

The relationship between bioelectrical impedance phase angle and subjective global assessment in advanced colorectal cancer

Background  

Bioelectrical Impedance (BIA) derived phase angle is increasingly being used as an objective indicator of nutritional status in advanced cancer. Subjective Global Assessment (SGA) is a subjective method of nutritional status. The objective of this study was to investigate the association between BIA derived phase angle and SGA in advanced colorectal cancer.     

Infrequent mutation of the H-cadherin gene on chromosome 16q24 in human breast cancers

To investigate the molecular basis of altered expression of the H-cadherin gene, we used polymerase chain reaction-single strand conformation polymorphism and DNA sequencing to examine the H-cadherin gene in 48 primary breast cancers in which loss of the long arm of chromosome 16 had been detected. We identified no mutations other than somatic 5-bp deletion within the coding region in a single tumor. The very low frequency of mutation found in these experiments suggests that H-cadherin is usually not a primary target for carcinogenesis in human breast cancers, and that reduction of its expression is likely to be a consequence of some other genetic event(s).