Browsing by Subject "Biomedicine"
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- ItemOpen AccessComparison of resting state functional networks in HIV infected and uninfected children at age 9 years(2018) Stoltsz, Werner Heinrich; Meintjes, Ernesta M; du Plessis, LindieOver 2.5 million children are infected with HIV, the majority of whom reside in Sub-Saharan Africa. Treatment coverage is steadily gaining momentum, reducing mortality and morbidity. Yet little is known about brain development in HIV-infected (HIV+) children who are on highly-active antiretroviral therapy (ART), with viral load suppression from a young age. Here, we use resting state fMRI (rs-fMRI) to examine the impact of HIV and ART on the development of functional networks in 9-year-old vertically HIV-infected children compared to age-matched controls of similar socioeconomic status. We present analyses for a sample of 40 HIV+ (9.2 ± 0.20 years; 16 males) children from the Children with HIV Early Antiretroviral (CHER) clinical trial (Cotton et al. 2013; Violari et al. 2008) and 24 uninfected (12 exposed; 12 males; 9.6 ± 0.52 years) controls from an interlinking vaccine trial (Madhi et al. 2010). Scans were performed at the Cape Universities Body Imaging Centre (CUBIC) in Cape Town, South Africa. We investigated HIV-related differences in within- and between-network functional connectivity (FC) using independent component analysis(ICA) and seed-based correlation analysis (SCA). For SCA, seeds were placed in the structural core, in regions implicated in HIV-related between-group differences at age 7 years, and in regions associated with neuropsychological domains impaired in our cohort. In addition, we evaluated associations of past and present immune health measures with within-network connectivity using ICA. We found no HIV-related intra-network FC differences within any ICA-generated RSNs at age 9 years, perhaps as a result of within-network connectivity not being sufficiently robust at this age. We found a positive association of CD4%, both current and in infancy, with functional integration of left lobule 7 into the cerebellum network at age 9 years. Long-term impact of early immune health supports recently-revised policies of commencing ART immediately in HIV+ neonates. ii Compared to uninfected children, HIV+ children had increased FC to several seeds. Firstly, to seeds associated with the planning and visual perception neuropsychological domains. Secondly, to structural core seeds in the extrastriate visual cortex (of the medial visual network) and the right angular gyrus (of the temporoparietal network). Finally, to left paracentral (somatosensory network) and right precuneus (posterior DMN) seeds previously revealing between-group differences at age 7 years. The connections with greater FC in HIV+ children may variously indicate functional recruitment of additional brain capacity, immature excess of short-range connections, and/or immature excess of between-network connections. In conclusion, despite early ART and early virologic suppression, HIV+ children demonstrate instances of abnormal FC at age 9 years. Disruption to visual cortex is marked, consistent with indications from neuropsychological testing that visual perception is disrupted. The profile of HIV- and/or ART-related effects on FC differs considerably between the two ages of 7 and 9 years, but both show characteristics of immature functional organisation compared with age-matched controls.
- ItemOpen AccessEvolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes(2017) Hockman, Dorit; Burns, Alan J; Schlosser, Gerhard; Gates, Keith P; Jevans, Benjamin; Mongera, Alessandro; Fisher, Shannon; Unlu, Gokhan; Knapik, Ela W; Kaufman, Charles K; Mosimann, Christian; Zon, Leonard I; Lancman, Joseph J; Dong, P Duc S; Lickert, Heiko; Tucker, Abigail S; Baker, Clare V HThe evolutionary origins of the hypoxia-sensitive cells that trigger amniote respiratory reflexes – carotid body glomus cells, and ‘pulmonary neuroendocrine cells’ (PNECs) - are obscure. Homology has been proposed between glomus cells, which are neural crest-derived, and the hypoxia-sensitive ‘neuroepithelial cells’ (NECs) of fish gills, whose embryonic origin is unknown. NECs have also been likened to PNECs, which differentiate in situ within lung airway epithelia. Using genetic lineage-tracing and neural crest-deficient mutants in zebrafish, and physical fate-mapping in frog and lamprey, we find that NECs are not neural crest-derived, but endoderm-derived, like PNECs, whose endodermal origin we confirm. We discover neural crest-derived catecholaminergic cells associated with zebrafish pharyngeal arch blood vessels, and propose a new model for amniote hypoxia-sensitive cell evolution: endoderm-derived NECs were retained as PNECs, while the carotid body evolved via the aggregation of neural crest-derived catecholaminergic (chromaffin) cells already associated with blood vessels in anamniote pharyngeal arches.
- ItemOpen AccessGenome-wide DNA methylation in mixed ancestry individuals with diabetes and prediabetes from South Africa(2016) Matsha, Tandi E; Pheiffer, Carmen; Humphries, Stephen E; Gamieldien, Junaid; Erasmus, Rajiv T; Kengne, Andre PAims. To conduct a genome-wide DNA methylation in individuals with type 2 diabetes, individuals with prediabetes, and control mixed ancestry individuals from South Africa. Methods. We used peripheral blood to perform genome-wide DNA methylation analysis in 3 individuals with screen detected diabetes, 3 individuals with prediabetes, and 3 individuals with normoglycaemia from the Bellville South Community, Cape Town, South Africa, who were age-, gender-, body mass index-, and duration of residency-matched. Methylated DNA immunoprecipitation (MeDIP) was performed by Arraystar Inc. (Rockville, MD, USA). Results. Hypermethylated DMRs were 1160 (81.97%) and 124 (43.20%), respectively, in individuals with diabetes and prediabetes when both were compared to subjects with normoglycaemia. Our data shows that genes related to the immune system, signal transduction, glucose transport, and pancreas development have altered DNA methylation in subjects with prediabetes and diabetes. Pathway analysis based on the functional analysis mapping of genes to KEGG pathways suggested that the linoleic acid metabolism and arachidonic acid metabolism pathways are hypomethylated in prediabetes and diabetes. Conclusions. Our study suggests that epigenetic changes are likely to be an early process that occurs before the onset of overt diabetes. Detailed analysis of DMRs that shows gradual methylation differences from control versus prediabetes to prediabetes versus diabetes in a larger sample size is required to confirm these findings.
- ItemOpen AccessOptimisation of insertion point during latissimus dorsi tendon transfer(2018) Thompson, Seth Mkhanyisi; Sivarasu, Sudesh; Roche, StephenProblem and Motivation: Posterior rotator cuff injuries are common (Yamaguchi et al., 2006), (Neri et al., 2009) and often debilitating and irreparable (Sim et al., 2001). Latissimus dorsi (LD) tendon transfers have been shown to be an effective treatment for these massive or irreparable tears (Habermeyer, 2006), (De Casas et al., 2014). This procedure can have unpredictable outcomes (Ling et al., 2009). This is partially caused by discrepancies in the suggested insertion site for the LD tendon during transfers. The current literature is composed of in-silico studies which ignore the practicalities of the human body (Magermans et al., 2004), in-vivo studies which use subjective pain scores, and small scale cadaver trials. For these reasons, a study is needed that uses the power of in-silico modeling in a way that is verified using in-vitro testing on cadavers. Aims and Objectives: The aim of this study is to determine the effects of varying the insertion point of the LD tendon on the humeral head to treat posterior rotator cuff tears in terms of the effects on strength, primarily in rotation and in flexion over a range of motion. The objectives are to use an in-silico model to define the effects of various insertion points and validate this model using a cadaver trial before presenting the final findings. Methods: In-silico Model The Upper Extremity Model (Holzbaur et al., 2005) was used to simulate tendon transfers. The moment arms in flexion and rotation were measured and recorded at angles of 0° and 90° of forward ix elevation. The moment arms at each point were then projected onto humeral maps to display the results. Cadaver Trial Four fresh frozen cadaver torsos (eight shoulders) were mounted into a specifically designed rig. The LD was transferred to 7 points illustrative of the humeral head. The strain generated by the humerus in rotation on the clamps was measured at 0° and 90° of forward flexion for each point. These were then compared. Results In-silico Model The in-silico moment arm maps were generated and analysed. The optimal point for external rotation at 0° of flexion was the lesser tuberosity. Moment arms to produce external rotation were found over the entire greater tuberosity. Flexion was only generated on the posterior edge of the greater tuberosity. At 90° of flexion, little to no rotation generating moment arms were found in the lesser tuberosity and the anterior ridge of the greater tuberosity. Rotation generating moment arms were not significantly different between the posterior edge and the face of the greater tuberosity. No areas generated flexion moment arms. Cadaver Trial At 0° of flexion, the lesser tuberosity (point 1) generated the most flexion, with the greater tuberosity (points 2-7) also generating external rotation, but at reduced levels. At 90° of flexion, the lesser tuberosity and the anterior ridges of the greater tuberosty (points 1-3) generated no significant rotation. The posterior ridge and face of the greater tuberosity generated similar amounts of flexion, greater than points 1-3 Conclusions: The in-silico model was validated in rotation by the cadaver trials and this validation was extended to flexion. For maximum rotation strength at 0° of flexion and no flexion strength, the x lesser tuberosity is the optimal point. For maximum rotation strength and no flexion throughout the motion of flexion, the middle of the face of the greater tuberosity is the optimal area. For maximum rotation throughout the motion of flexion, points 4 and 5 (the posterior edge of the greater tuberosity) represent the optimal area for insertion. This area represents the optimal compromise in terms of range of motion and strength.
- ItemOpen AccessPromoting equality for ethnic minority NHS staff—what works?(2015) Priest, Naomi; Esmail, Aneez; Kline, Roger; Rao, Mala; Coghill, Yvonne; Williams, David RNHS organisations are now being judged on indicators of ethnic diversity. Naomi Priest and colleagues look at the international evidence on how they should tackle discrimination