Adolescents and Young Adults (AYAs) with chronic kidney disease (CKD) have challenges unique to this developmental period, with increased rates of high‐risk behavior and non‐adherence to therapy ...which may impact the progression of kidney disease and their requirement for kidney replacement therapy (KRT). Successful transition of AYA patients are particularly important in low‐ and middle‐income countries (LMICs) where KRT is limited, rationed or not available. Kidney AYA transition clinics have the potential to improve clinical outcomes but there is a paucity of data on the clinical translational impact of these clinics in Africa. This review is a reflection of the 20‐year growth and development of the first South African kidney AYA transition clinic. We describe a model of care for patients with CKD, irrespective of etiology, aged 10–25 years, transitioning from pediatric to adult nephrology services. This unique service was established in 2002 and re‐designed in 2015. This multidisciplinary integrated transition model has improved patient outcomes, created peer support groups and formed a training platform for future pediatric and adult nephrologists. In addition, an Adolescent Centre of Excellence has been created to compliment the kidney AYA transition model of care. The development of this transition pathway challenges and solutions are explored in this article. This is the first kidney AYA transition clinic in Africa. The scope of this service has expanded over the last two decades. With limited resources in LMICs, such as KRT, the structured transition of AYAs with kidney disease is not only possible but essential. It is imperative to preserve residual kidney function, maximize the kidney allograft lifespan and improve adherence, to enable young individuals an opportunity to lead productive lives.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Understanding the effects of microgravity on human organs is crucial to exploration of low-earth orbit, the moon, and beyond. Drosophila can be sent to space in large numbers to examine the effects ...of microgravity on heart structure and function, which is fundamentally conserved from flies to humans. Flies reared in microgravity exhibit cardiac constriction with myofibrillar remodeling and diminished output. RNA sequencing (RNA-seq) in isolated hearts revealed reduced expression of sarcomeric/extracellular matrix (ECM) genes and dramatically increased proteasomal gene expression, consistent with the observed compromised, smaller hearts and suggesting abnormal proteostasis. This was examined further on a second flight in which we found dramatically elevated proteasome aggregates co-localizing with increased amyloid and polyQ deposits. Remarkably, in long-QT causing sei/hERG mutants, proteasomal gene expression at 1g, although less than the wild-type expression, was nevertheless increased in microgravity. Therefore, cardiac remodeling and proteostatic stress may be a fundamental response of heart muscle to microgravity.
Display omitted
•Flies in microgravity exhibit cardiac constriction, remodeling, and diminished output•Heart defects correlate with reduced sarcomeric and extracellular matrix gene expression•Proteosome gene or protein expression is upregulated, suggesting proteostasis imbalance
Walls et al. find that exposure to microgravity aboard the ISS causes heart dysfunction in a fly cardiac model. Hearts are less contractile and exhibit changes in genes and proteins that maintain heart structure and function. Effects are seen in several lines of flies, suggesting a common response to microgravity.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Analysis of tumour-infiltrating T cells in colorectal cancer can predict disease-free survival. The Immunoscore, obtained by quantifying tumour-infiltrating CD3
+
and CD8
+
T cells, may improve ...current staging. Effector regulatory T cells are a potently suppressive subset in mice and, while present in human colorectal cancer, their role in patient outcome is unknown. Immunofluorescence was used to analyse immune cell infiltrates in patients with early (stage II) colorectal cancer with (
n
= 13) and without (
n
= 19) recurrent disease. CD3 and CD8 were used for the Immunoscore; FOXP3, BLIMP-1 and CD3 to identify effector regulatory T cells. Patients with high Immunoscores had increased disease-free survival compared to patients with low Immunoscores (Log-rank test
p
< 0.01). Prediction of outcome was further improved by stratifying patients with a low Immunoscore according to CD3
+
FOXP3
+
BLIMP-1
+
cell infiltration at the invasive margin. Patients with a low Immunoscore and high infiltrate of CD3
+
FOXP3
+
BLIMP-1
+
cells tended to have better disease-free survival than patients with low Immunoscore and low infiltrate of CD3
+
FOXP3
+
BLIMP-1
+
cells. Patients with a high Immunoscore had better disease-free survival than patients with a low Immunoscore and low infiltrate of CD3+ FOXP3+ BLIMP-1+ cells (Log-rank test
p
< 0.001). These results indicate that tumour infiltration with effector regulatory T cells improves the prognostic value of the Immunoscore and implies that these cells may play a role in colorectal cancer patient outcome.
Full text
Available for:
EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Staging of patients with colorectal cancer is currently based on tumour morphology and does not take into account the complexity of the anti-tumour immune response. Early-stage colorectal ...patients are usually treated with surgery alone and are not recommended additional adjuvant therapy. Up to twenty-five percent of these patients have relapse of disease, indicating that the current staging does not accurately predict disease-free survival. The Immunoscore has been proposed to incorporate the T cell infiltrate in the tumour into current staging protocols to improve estimates of disease-free survival. However, T cell subsets are complex and therefore may have different effects on patient outcome. Immunofluorescence was used to analyse immune cell infiltrates in early stage (II) colorectal cancer patients and to compare those with recurrent and non-recurrent disease (n=33). CD3 and CD8 were used for the Immunoscore. FoxP3, Blimp-1 and CD3 were used to identify effector regulatory T cells. Patients with a high Immunoscore (high T cell infiltrate) had increased disease-free survival than patients with a low Immunoscore (low T cell infiltrate, Log-rank test p>0.001). The ability to predict patient outcome was improved by measuring the infiltrate of CD4+FoxP3+Blimp-1+ cells (effector regulatory T cells, Log-rank test p>0.001). Patients with a low Immunoscore but high infiltrate of CD4+FoxP3+Blimp-1+ cells at the centre of the tumour had increased disease-free survival than those with a low Immunoscore and a low infiltrate of CD4+FoxP3+Blimp-1+ cells. These results show that incorporating the complexity of the local immune response into current practice may improve prediction of patient outcome in colorectal cancer.
Sidelying hip abduction (SHA) is a common exercise utilized in rehabilitation to strengthen the gluteus medius (GMed). Alterations in the exercise can produce different patterns of muscular activity. ...No studies have examined the effect of mechanical pelvic stabilization during SHA. This study enrolled 19 participants (male = 11, female = 8) who performed the same SHA exercise under two randomized conditions: standard and with a mechanical block to prevent frontal-plane movement. Electromyographic amplitudes during exercise were obtained through surface electrodes and compared against maximum voluntary isometric contraction (MVIC) testing: GMed, gluteus maximus, biceps femoris, tensor fascia latae, quadratus lumborum, and vastus lateralis. While no significant differences were found in GMed activity during SHA with or without pelvic stabilization, reduced concomitant activation of other musculature was observed, potentially producing a more isolated exercise for the GMed with less compensatory activity.
PDF
