Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification

The term heterotopic ossification (HO) describes bone formation in tissues where bone is normally not present. Musculoskeletal trauma induces signalling events that in turn trigger cells, probably of mesenchymal origin, to differentiate into bone. The aetiology of HO includes extremely rare but severe, generalised and fatal monogenic forms of the disease; and as a common complex disorder in response to musculoskeletal, neurological or burn trauma. The resulting bone forms through a combination of endochondral and intramembranous ossification, depending on the aetiology, initiating stimulus and affected tissue. Given the heterogeneity of the disease, many cell types and biological pathways have been studied in efforts to find effective therapeutic strategies for the disorder. Cells of mesenchymal, haematopoietic and neuroectodermal lineages have all been implicated in the pathogenesis of HO, and the emerging dominant signalling pathways are thought to occur through the bone morphogenetic proteins (BMP), mammalian target of rapamycin (mTOR), and retinoic acid receptor pathways. Increased understanding of these disease mechanisms has resulted in the emergence of several novel investigational therapeutic avenues, including palovarotene and other retinoic acid receptor agonists and activin A inhibitors that target both canonical and non-canonical signalling downstream of the BMP type 1 receptor. In this article we aim to illustrate the key cellular and molecular mechanisms involved in the pathogenesis of HO and outline recent advances in emerging molecular therapies to treat and prevent HO that have had early success in the monogenic disease and are currently being explored in the common complex forms of HO.     

Background Radiation Measurement and the Assessment of Radiological Impacts due to Natural Radioactivity Around Itakpe Iron-Ore Mines

Mining activity and metal extraction processes have been identified as one of the major pathways through which natural radionuclides are accumulated in the terrestrial environment. Exposure to excessive radiation from natural radionuclides can cause deleterious health hazards to man. In this study therefore, the activity concentrations of primordial radionuclides (⁴⁰K, ²³⁸U and ²³²Th) were measured in rock, soil, tailings and water samples collected from abandoned iron ore mines in order to estimate the radiological impacts associated with the previous mining and metal extraction activities within the environment of abandoned Itakpe iron-ore mines. Gamma spectrometry utilizing a well calibrated NaI(Tl) detector was employed for the measurements. Results show that the average activity concentrations of ⁴⁰K, ²³⁸U and ²³²Th are 1084?±?581, 11.0?±?7.7 and 5.0?±?1.8 Bq kg^?1 respectively for rock samples and 415.6?±?197.5, 12.8?±?5.7 and 8.8?±?5.8 Bq kg^?1, respectively for soil samples. The activity concentrations of the three radionuclides are much lower in water samples compared to rocks and soil. Radiological hazard indices calculated from the activity concentrations show that the mining activities have little or no negative impacts on the environment as the radiological risk indices obtained are all lower than their permissible limits.     

Influence of process conditions on the sulfonation of methyl ester synthesized from used cooking oil: Optimization by Taguchi approach

Developing a robust and facile process route for fatty acid methyl ester sulfonate (MES) synthesis is of importance for industrial applications. Herein, Taguchi orthogonal array (OA) approach was used for the first time to establish the optimum process condition for the sulfonation of methyl esters (ME) with chlorosulfonic acid (CSA). According to the experimental design, the most significant parameter was sulfonation temperature, followed by CSA/ME molar ratio. Under the optimum sulfonation conditions (that is, 70°C sulfonation temperature, 2.0 h sulfonation time, 1.5:1 mol/mol CSA/ME molar ratio and 2.0 h aging time), the MES yield and the corresponding signal/noise ratio were 92.08 ± 0.28% and 39.28, respectively. The obtained FTIR and ¹H NMR data revealed spectra associated with methyl (CH₂ asymmetric and CH₂ symmetric stretching vibrations), esters (CO, C O, and O CH₃), and sulfonate (SO) groups in the MES sample synthesized under optimal conditions, thus confirming the target MES product. Surface tension measurements revealed that the optimal MES sample had a low critical miscelle concentration of 0.082 g/L at a surface tension of 51.2 mN/m, implying the possibility of better performance.     

Parametric studies of mixed convective fluid flow around cylinders of different cross-sections

A numerical study of mixed convective heat transfer in a lid-driven square enclosure containing a hot elliptic cylinder is conducted. The impacts of the Grashof number $({10}^3\le \mathit{Gr}\le 10^6)$, Reynolds number $(1.0\le Re\le 100)$, cylinder tilt angle $(0^{°}\le \varphi \le {90}^{°})$, and aspect ratio $(1.0\le AR\le 3.0)$ have been examined for a fluid of $Pr$ of 0.71. The horizontal enclosure walls are insulated, while its vertical walls are restricted to a nonvarying temperature T_c, whereas a sinusoidal temperature of $T_h+∆T\sin (\pi x/L)$ is imposed on the wall of the elliptical cylinder. The governing equations are solved using COMSOL Multiphysics 5.6 software. The fluid dynamic and the heat transport profiles between the enclosure and the elliptical cylinder walls are represented by the stream function, isothermal contours, and average Nusselt number. Results established that for all the considered aspect ratios, the thermal heating range of ${10}^3\le \mathit{Gr}\le 10^4$ is predominantly a conduction mechanism. The critical position of the ellipse where the inclination effect becomes insignificant is determined by the Grashof number and aspect ratio when the Re = 100. The strength of vortices and cell numbers are significantly influenced by the aspect ratio, particularly when the $\mathit{Gr}=10^4$. When $AR=1.0$, the average heat transfer from the cylinder remains the same regardless of the cylinder's orientation. The impact of cylinder orientation on heat transfer from the cylinder wall is minimal for $1.5\le AR\le 2.0$. For AR values of $2.5\le AR\le 3.0$, increasing the inclination angle does not result in improved heat transfer. The influence of the increasing inclination angle on the right wall diminishes as the angle increases, except when the Grashof number is greater than 10⁵, where the rate of heat transfer is enhanced for inclination angles beyond 45°.