Skin deep: is curriculum reform a responsibility of the student?

In the current climate of persisting racial injustice, which extends far beyond the confines of the United States (US), addressing racial inequalities in the field of medicine has re-emerged as a priority. In 2020 alone, the US witnessed multiple homicides of innocent Black individuals, including the deaths of George Floyd and Breonna Taylor. In no way exempt from racial injustice, Ireland witnessed the death of George Nkencho in December 2020. The undeniable injustice surrounding each of these events sparked civil unrest and a collective anger with a calibre reminiscent of the peace protests of the 1960s. However, when challenged to reflect on the racial injustice that persists in our modern day society, it became abundantly clear that the deaths of innocent Black men and women should not have been necessary as a catalyst for equality. Indeed, the status quo remains rife with racial injustice, and change is long overdue. Medicine is no exception.</p

MyD88 expression and survival (Kaplan-Meier curves: median survival time shown in months).

<p>MyD88 positive tumours (n = 12) had significantly reduced progression-free survival (A) and overall survival (B) (p = 0.018 and p = 0.008, respectively).</p

Heterogeneous expression of monoclonal anti-TLR4.

<p>A: variable staining observed in adjacent epithelium within a benign serous cystadenoma (20x). B: focal strong staining within a serous carcinoma (40x).</p

The effect of silencing MyD88 and TLR4 mRNA on the chemoresponsive properties of SKOV-3 cells.

<p>SKOV-3 cells were left untransfected (Unt), transfected with negative control siRNA (siNeg), MyD88 targeting siRNA (siMyD88) or TLR4 targeting siRNA (siTLR4). The transfected cells were incubated for 72 hrs before either harvesting for mRNA analysis (A), for protein analysis (B) or treatment with paclitaxel (C). (A) MyD88 and TLR4 mRNA expression levels were evaluated by TaqMan RT-PCR. MyD88 and TLR4 mRNA expression was normalised to that of an endogenous control, B2M, and calibrated to that of untreated cells to establish the relative percentage of mRNA expression (n = 3, mean +SD). (B) MyD88 and TLR4 mRNA expression levels were evaluated by western blot analysis. GAPDH was used as a loading control. (C) Transfected cells were either left untreated, treated with DMSO (vehicle control) or 3.5 nM of paclitaxel (IC25). 48 hrs post treatment, cell viability was assessed by means of the CCK-8 assay. % cell viability rate was calculated by comparing the absorbance values for the vehicle control to the corresponding paclitaxel treated samples. Results are expressed as mean +SD, n = 3; *p<0.05, **p<0.01 (un-paired Student's t-test).</p

TLR4/MyD88 and progression-free survival (Kaplan-Meier curves; median survival shown in months).

<p>TLR4 (A) or MyD88 (B) negative cases had significantly better PFS (15 & 18 months longer; p<0.05).</p

TLR4/MyD88 and overall survival (Kaplan-Meier curves; median survival shown in months).

<p>Survival was longer in MyD88 (B) negative cases (by 19 months; p<0.05). The difference in survival associated with TLR4 (A) is not significant (p>0.5).</p

Quantification of immunohistochemical staining of TLR4 and MyD88 (0 = no staining, 1 = weak staining, 2 = moderate staining, 3 = strong staining).

<p>Quantification of immunohistochemical staining of TLR4 and MyD88 (0 =  no staining, 1 =  weak staining, 2 =  moderate staining, 3 =  strong staining).</p

MiR-21 & miR-146a expression in the test series.

<p>Scatter plots showing relative microRNA expression with standard deviation (fold changes calculated via the 2^−ΔΔCt method). 20 EOC cases (serous carcinomas) grouped as MyD88+ or MyD88- based on protein expression; data shown relative to each group. Average expression of miR-21 & miR-146a increased in MyD88 negative EOC (p<0.05).</p

Distribution of TLR4 & MyD88 protein expression in all patient samples.

<p>Abbreviations: SD, standard deviation; FIGO, Federation International of Gynecology & Obstetrics; NOSE, normal ovarian surface epithelium.</p>†<p>TLR4, MyD88 expression by immunohistochemistry (score >4 =  positive).</p

miR-21 (A) and miR-146a (B) expression in chemosensitive and chemoresistant cancer cells.

<p>Data are expressed as fold change in expression with respect to A2780 cancer cells (with standard deviation).</p