VISCOELASTIC BEHAVIOUR OF THE CANINE CRANIAL CRUCIATE LIGAMENT COMPLEX

The canine stifle joint is one of the most vulnerable joints within the musculoskeletal system and the cranial cruciate ligament (CCL) is the most susceptible ligament to rupture within the joint. When this ligament is damaged, the stifle joint becomes mechanically unstable leading to abnormal load distribution within the joint. This physiological change is associated with osteophyte formation at the joint margins, thickening of the medial aspect of the joint capsule and the medial collateral ligament, softening of the articular cartilage resulting in osteoarthritis (OA). Ligament injury can be either purely traumatic or a degenerative non-contact form. The aetiopathogenesis of non-contact cranial cruciate ligament rupture (CCLR) is unclear, however alterations in the composition of the extracellular matrix (ECM) has been implicated as one of its causes. This thesis aimed to advance the current understanding of the biomechanical behaviour of the canine CCL and investigated the contribution of proteoglycans (PGs) to the viscoelastic behaviour of the CCL. The objectives comprise of experimental and numerical studies, including the development and utilisation of a novel full-field three-dimensional digital image correlation method (3D DIC) and a representative FEM of the whole canine stifle joint. Experimental Study I on the canine CCLs was the first to focus on characterising slow strain rate sensitivity and hysteresis behaviour of the ligament at the toe-region of stress-strain behaviour. This study showed that arranging mechanical tests in different orders of strain rates resulted in different tissue response, such that tensile responses of the CCL during the ascending (increasing order of strain rates from 0.1 to 1%/min, and 1 to 10%/min) tests were significantly different from the descending tests (decreasing order of strain rates from 10 to 1%/min, and 1 to 0.1%/min). Only during ascending tests were the CCLs strain rate sensitive and hysteresis was strain rate dependent. The different tensile responses of the CCLs during the ascending and descending order of strain rate may be associated with strain history of the tissue. In Experimental Study II, two groups of the CCLs (control and treatment (PG depletion)) were tested under tensile load at slow strain rates (0.1, 1 and 10%/min). PG content in the treatment group was depleted by 21.11 ± 14.51% (p=0.45). Water content in the treatment group reduced by approximately 5.2% (p=0.048). Although there were no statistically significant values; stress-strain, tangent modulus, hysteresis and creep behaviour in the treatment was different from the control groups. Stress relaxation rate was significantly higher in the control than the treatment group (p=0.039). The lower relaxation rate in the treatment group could be associated with sGAGs which provides cross-links between collagen molecules. Hence, it is possible that an efficient depletion of PGs in canine CCLs could result in significant mechanical changes in the tissue. A full-field 3D DIC method was developed to generate five CCL-specific FEM and provide load-deformation behaviour across the middle region of the CCLs. This information was utilised to predict stress-strain behaviour of the CCLs through inverse analysis. In addition, an anatomically representative FEM of the canine stifle joint was developed and employed to investigate the joint when PGs in the CCL were depleted. Results showed reduction in joint stability in joints with depleted CCLs (p=0.56). Hence, PG content in the CCL could be one of the ECM components contributing to the mechanical behaviour of the ligament, and affecting the stability in canine stifle joints. This research leads to a better understanding of the biomechanical behaviour of canine CCL, and it is useful for researchers in the field of biomechanics and biomedical science who are seeking advanced experimental and numerical works in tissue mechanics

Phytotoxic characterization of various fractions of Launaea procumbens

Allelopathic screening of various fractions of Launaea procumbens, collected from Wah Cantt (Punjab) Pakistan, was conceded to identify potent allelopathic fraction for future phytochemical analyses. For this purpose, radish root inhibition method was used to test allelopathic potential. Two different concentrations of 100 ppm and 1000 ppm of Launaea procumbens were used in this study. Methanolic and ethyl acetate fraction potently inhibited root and radical growth; comparative to other fractions, it might be due to the presence of bioactive allelochemicals. Based on this screening, both of these fractions were recommended for future bioassay guided isolation of allelochemicals.Key words: Launaea procumbens, radish seeds, root inhibition, Launaea procumbens methanolic fraction

Formalization of Transform Methods using HOL Light

Transform methods, like Laplace and Fourier, are frequently used for analyzing the dynamical behaviour of engineering and physical systems, based on their transfer function, and frequency response or the solutions of their corresponding differential equations. In this paper, we present an ongoing project, which focuses on the higher-order logic formalization of transform methods using HOL Light theorem prover. In particular, we present the motivation of the formalization, which is followed by the related work. Next, we present the task completed so far while highlighting some of the challenges faced during the formalization. Finally, we present a roadmap to achieve our objectives, the current status and the future goals for this project.Comment: 15 Pages, CICM 201

Adalimumab or Etanercept as first line biologic therapy in Enthesitis related arthritis (ERA) - a drug-survival single centre study spanning 10 years

Objectives: To analyse and compare drug-survival of adalimumab and etanercept (and their biosimilars) in biologic-naïve patients with ERA (Enthesitis-Related Arthritis). // Methods: In this retrospective observational study, conventional statistics and machine-learning were applied to compare drug-survival (adalimumab, etanercept and their biosimilars initiated: 2009–2019) in ERA and identify determinants. The primary outcome was discontinuation of treatment due to primary- or secondary-failure and adverse drug-reactions. // Results: During the observation period, 99 of 188 patients with ERA on first-line TNF inhibitors (etanercept-n=108, adalimumab-n=80) discontinued their treatment (median survival-time 3.9years, 95%CI 2.6-4.9years). Adalimumab was associated with longer drug-survival compared to etanercept especially after an initial positive response, with the median time to treatment discontinuation 4.9years (95% CI 3.9–5.7) for adalimumab, compared to 2years (95%CI 1.4–4.0) for etanercept (HR of treatment-discontinuation-0.49, 95%CI 0.32–-0.75, p=0.001). Adjusted by propensity-score, adalimumab-methotrexate combination was associated with longer drug survival, compared to adalimumab-monotherapy (HR-0.41, 95%CI 0.20–0.85), etanercept-monotherapy (HR-0.28, 95%CI 0.15–0.53), and etanercept-methotrexate combination (HR-0.39, 95%CI 0.21–0.73). The presence of HLA-B27 was associated with longer drug-survival (HR-0.50, 95%CI 0.29–0.87) following an initial positive response. Higher-CRP at baseline was associated with higher rate of primary-failure (HR-1.68, 95%CI 1.08–2.62). Axial-ERA (sacroiliitis±spinal-involvement) was associated with poorer drug-survival for both primary- and secondary-failure (overall HR-2.03, 95%CI 1.22–3.40). Adjusted by propensity-score, shorter drug-survival was observed in patients with baseline-CRP≥12.15 mg/L, but only in the context of axial-ERA, not in peripheral-ERA (no sacroiliitis/spinal-involvement) (HR-2.28, 95%CI 1.13–-3.64). // Conclusion: Following an initial positive primary response, continuing methotrexate with adalimumab was associated with the longest drug-survival compared to adalimumab-monotherapy or etanercept-based regimens. Axial-ERA was associated with a poorer drug-survival. A CRP >12.15 in patients with axial-ERA was associated with a higher rate of primary-failure. Further prospective studies are required to confirm these findings

Occurrence of testicular microlithiasis in androgen insensitive hypogonadal mice

<b>Background</b>: Testicular microliths are calcifications found within the seminiferous tubules. In humans, testicular microlithiasis (TM) has an unknown etiology but may be significantly associated with testicular germ cell tumors. Factors inducing microlith development may also, therefore, act as susceptibility factors for malignant testicular conditions. Studies to identify the mechanisms of microlith development have been hampered by the lack of suitable animal models for TM.<BR/> <b>Methods</b>: This was an observational study of the testicular phenotype of different mouse models. The mouse models were: cryptorchid mice, mice lacking androgen receptors (ARs) on the Sertoli cells (SCARKO), mice with a ubiquitous loss of androgen ARs (ARKO), hypogonadal (hpg) mice which lack circulating gonadotrophins, and hpg mice crossed with SCARKO (hpg.SCARKO) and ARKO (hpg.ARKO) mice.<BR/> <b>Results</b>: Microscopic TM was seen in 94% of hpg.ARKO mice (n=16) and the mean number of microliths per testis was 81 +/- 54. Occasional small microliths were seen in 36% (n=11) of hpg testes (mean 2 +/- 0.5 per testis) and 30% (n=10) of hpg.SCARKO testes (mean 8 +/- 6 per testis). No microliths were seen in cryptorchid, ARKO or SCARKO mice. There was no significant effect of FSH or androgen on TM in hpg.ARKO mice.<BR/> <b>Conclusions</b>: We have identified a mouse model of TM and show that lack of endocrine stimulation is a cause of TM. Importantly, this model will provide a means with which to identify the mechanisms of TM development and the underlying changes in protein and gene expression

Acute mesenteric ischemia and duodenal ulcer perforation: a unique double pathology

Background: Acute mesenteric ischaemia and duodenal perforation are surgical emergencies with serious consequences. Patients presenting with acute mesenteric ischaemia alone face a high mortality rate as high as 60% whereas those presenting with peptic ulcer perforation the mortality rates range from 6-14%. There are very few reported cases of patients presenting with this dual pathology. Case presentation: We report a unique case of a 53 year old Italian lady who presented with acute mesenteric ischaemia and duodenal perforation. This is the first report of massive bowel ischaemia and duodenal perforation with no apparent underlying common pathophysiology leading to this presentation. Conclusion: Early management in the intensive care unit and appropriate surgical intervention maximised the patient’s chances of survival despite the poor prognosis associated with her dual pathology. The rare pathology of the patient described can be explained by two possible hypotheses: peptic ulcer disease causing duodenal ulceration, which precipitated ischaemic infarction of the small bowel. The second hypothesis is the patient developed a stress related ulcer following ischaemic bowel infarction secondary to arterial thrombosis

Nanoscale Structural and Emission Properties within - Russian Doll- - Type InGaN/AlGaN Quantum Wells

Due to the increasing desire for nanoscale optoelectronic devices with green light emission capability and high efficiency, ternary III- N- based nanorods are extensively studied. Many efforts have been taken on the planar device configuration, which lead to unavoided defects and strains. With selective- area molecular- beam epitaxy, new - Russian Doll- - type InGaN/AlGaN quantum wells (QWs) have been developed, which could largely alleviate this issue. This work combines multiple nanoscale characterization methods and k- p theory calculations so that the crystalline structure, chemical compositions, strain effects, and light emission properties can be quantitatively correlated and understood. The 3D structure and atomic composition of these QWs are retrieved with transmission electron microscopy and atom probe tomography while their green light emission has been demonstrated with room- temperature cathodoluminescence experiments. k- p theory calculations, with the consideration of strain effects, are used to derive the light emission characteristics that are compared with the local measurements. Thus, the structural properties of the newly designed nanorods are quantitatively characterized and the relationship with their outstanding optical properties is described. This combined approach provides an innovative way for analyzing nano- optical- devices and new strategies for the structure design of light- emitting diodes.The chemical components of the nanorods, shape effects and strain effects given by this unique - Russian Doll- - type geometry of InGaN/AlGaN quantum wells are quantitatively related with the optical properties. This combined approach reported here provides an innovative way for analyzing nano- optical- devices and new strategies for the structure design of light- emitting diodes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162759/3/adom202000481_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162759/2/adom202000481.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162759/1/adom202000481-sup-0001-SuppMat.pd

Evaluation of phenolic contents and antioxidant activity of various solvent extracts of Sonchus asper (L.) Hill

<p>Abstract</p> <p>Background</p> <p><it>Sonchus asper </it>(SA) is traditionally used for the treatment of various ailments associated with liver, lungs and kidneys. This study was aimed to investigate the therapeutic potential of nonpolar (hexane, SAHE; ethyl acetate, SAEE and chloroform, SACE) and polar (methanol, SAME) crude extracts of the whole plant.</p> <p>Methods</p> <p>To achieve these goals, several parameters including free-radical (DPPH^•, ABTS^•+, H₂O₂and ^•OH) scavenging, iron chelating activity, scavenging of superoxide radicals, total flavonoids and total phenolic content (TPC) were examined.</p> <p>Results</p> <p>The SA extracts presented a remarkable capacity to scavenge all the tested reactive species with IC₅₀values being found at the μg ⁄ ml level. The SAME was shown to have the highest TPCs while lowest IC₅₀values for the DPPH^•, ABTS^•+radical scavenging capacities and iron chelating scavenging efficiency, moreover, SAME had best activities in scavenging of superoxide radicals and hydrogen peroxide as well as potently scavenged the hydroxyl radicals.</p> <p>Conclusion</p> <p>These results suggest the potential of <it>S. asper </it>as a medicine against free-radical-associated oxidative damage.</p