Racism, Discrimination, Harressement in Medical Schools in the UK: A Scoping Review

Background: Discrimination, racism, harassment, stereotyping, and bullying are a significant issue for medical students as they create a hostile environment with detrimental effect on student wellbeing and educational experience. Findings suggest that though prevalent, reporting of these experiences is rare and perceived as ineffective. Objectives: This scoping review aims to map the trends, types, and nature of discrimination, harassment, bullying, stereotyping, intimidation, and racism reports in undergraduate medical education in the UK since 2010 and to determine areas of focus for undertaking full systematic reviews in the future. Method: A search was conducted using the MEDLINE, AHMED, CINHL, and EMBASE electronic databases from 2010 up to February 2022 in English. Only primary research papers (e.g., cohort studies, cross-sectional studies, and case series) that report the words/phrases discrimination (including gender and racial), harassment (including verbal, sexual, academic, and physical), bullying, stereotype, intimidation, and racism within medical education in the UK after 2010, following the Equity Act 2010, were eligible for inclusion. Results: Five relevant articles relating to discrimination, harassment, bullying, stereotyping, intimidation, and racism in medical schools in the UK were included. Three themes were identified across these studies. Conclusions: The data suggest that there is a high prevalence rate of discrimination, harassment, and stereotyping being experienced by ethnic minority undergraduate medical students in the UK. There is underreporting due to perceived and structural barriers. The identified studies suggest that less progress has been made in these areas.</jats:p

Well-matchedness in Euler and Linear Diagrams

A key feature of diagrams is well-matchedness, referred to as iconicity in philosophy. A well-matched diagram has a structural resemblance to its semantics and is believed to be an effective representation. In this paper, we view well-matchedness as a feature of diagrams' meaning carriers -- syntactic relationships that convey meaning. Each meaning carrier may or may not structurally resemble, i.e. be well-matched to, its semantics. This paper provides the first empirical study that evaluates the impact of well-matched meaning carriers on effectiveness in Euler diagrams and linear diagrams. There are two key take-away messages: using only well-matched meaning carriers led to the best task performance and using both well-matched and non-well-matched meaning carriers in a single diagram should be approached with caution

SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification.

The C. elegans AWC olfactory neuron pair communicates to specify asymmetric subtypes AWCOFF and AWCON in a stochastic manner. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes voltage-activated calcium channels, UNC-2 (CaV2) and EGL-19 (CaV1), in the AWCON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood. Here, we show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that slo-1 BK channels act downstream of NSY-5 gap junctions to inhibit calcium channel-mediated signaling in the specification of AWCON. We also show for the first time that slo-2 BK channels are important for AWC asymmetry and act redundantly with slo-1 to inhibit calcium signaling. In addition, nsy-5-dependent asymmetric expression of slo-1 and slo-2 in the AWCON neuron is necessary and sufficient for AWC asymmetry. SLO-1 and SLO-2 localize close to UNC-2 and EGL-19 in AWC, suggesting a role of possible functional coupling between SLO BK channels and voltage-activated calcium channels in AWC asymmetry. Furthermore, slo-1 and slo-2 regulate the localization of synaptic markers, UNC-2 and RAB-3, in AWC neurons to control AWC asymmetry. We also identify the requirement of bkip-1, which encodes a previously identified auxiliary subunit of SLO-1, for slo-1 and slo-2 function in AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal differentiation of olfactory neurons

SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification

<div><p>The <i>C</i>. <i>elegans</i> AWC olfactory neuron pair communicates to specify asymmetric subtypes AWC^OFF and AWC^ON in a stochastic manner. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes voltage-activated calcium channels, UNC-2 (CaV2) and EGL-19 (CaV1), in the AWC^ON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood. Here, we show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that <i>slo-1</i> BK channels act downstream of NSY-5 gap junctions to inhibit calcium channel-mediated signaling in the specification of AWC^ON. We also show for the first time that <i>slo-2</i> BK channels are important for AWC asymmetry and act redundantly with <i>slo-1</i> to inhibit calcium signaling. In addition, <i>nsy-5</i>-dependent asymmetric expression of <i>slo-1</i> and <i>slo-2</i> in the AWC^ON neuron is necessary and sufficient for AWC asymmetry. SLO-1 and SLO-2 localize close to UNC-2 and EGL-19 in AWC, suggesting a role of possible functional coupling between SLO BK channels and voltage-activated calcium channels in AWC asymmetry. Furthermore, <i>slo-1</i> and <i>slo-2</i> regulate the localization of synaptic markers, UNC-2 and RAB-3, in AWC neurons to control AWC asymmetry. We also identify the requirement of <i>bkip-1</i>, which encodes a previously identified auxiliary subunit of SLO-1, for <i>slo-1</i> and <i>slo-2</i> function in AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal differentiation of olfactory neurons.</p></div

<i>slo-1</i> and <i>slo-2</i> act downstream of <i>nsy-5</i> to antagonize the function of voltage-gated calcium channel-activated kinase cascade in promoting AWC^ON.

<p>(<b>A</b>) Double and triple mutant analysis of <i>slo-1(ky389gf)</i>, <i>slo-1(ky399gf)</i>, and <i>slo-1(eg142lf); slo-1(ok2214lf)</i> animals with mutants of known genes involved in establishment of AWC asymmetry. 2AWC^ON, both AWC cells express <i>str-2</i>; 1AWC^OFF/AWC^ON, only one of the two AWC cells expresses <i>str-2</i>; 2AWC^OFF, neither AWC cell expresses <i>str-2</i>. (<b>B</b>) The genetic pathway that demonstrates possible relationships between <i>slo-1</i>, <i>slo-2</i> and other genes required for AWC asymmetry. Genes in green represent AWC^OFF promoting, genes in red represent AWC^ON promoting, and those in grey represent less active or inactive genes.</p

Model of <i>slo-1</i> and <i>slo-2</i> function in AWC asymmetry.

<p>AWC asymmetry is stochastic, and this figure illustrates the case when AWC^ON is on the left side of the head. Molecules in green represent AWC^OFF promoting, molecules in red represent AWC^ON promoting, and those in grey represent less active or inactive molecules. In the AWC^OFF neuron (right), calcium enters the cell through voltage-gated calcium channels (UNC-2/UNC-36 and EGL-19/UNC-36) and stimulates a MAP kinase cascade consisting of UNC-43 (CaMKII), TIR-1 (Sarm1) adaptor protein, and NSY-1 (MAPKKK). This leads to expression of the AWC^OFF marker <i>srsx-3</i> and suppression of the AWC^ON marker <i>str-2</i>. In the AWC^ON cell (left), NSY-5 gap junctions activate SLO-1 and SLO-2 voltage- and calcium-activated potassium channels, which antagonize the function of UNC-2/UNC-36 and EGL-19/UNC-36 calcium channels by suppressing the calcium-activated CaMKII-MAP kinase cascade. NSY-4 (claudin) acts in parallel with NSY-5, SLO-1, and SLO-2 to inhibit calcium channel-mediated signaling, resulting in de-repression of <i>str-2</i> expression.</p

SLO-1 and SLO-2 BK potassium channels are localized in the vicinity of UNC-2 voltage-gated calcium channels in AWC axons.

<p>(<b>A-C</b>) Images of wild-type L1 animals expressing single copy insertion transgenes <i>odr-3p</i>::<i>slo-1</i>::<i>TagRFP</i> and <i>odr-3p</i>::<i>GFP</i>::<i>unc-2</i> (A), <i>odr-3p</i>::<i>slo-2</i>::<i>TagRFP</i> and <i>odr-3p</i>::<i>GFP</i>::<i>unc-2</i> (B), as well as <i>odr-3p</i>::<i>slo-2</i>::<i>TagRFP</i> and <i>odr-3p</i>::<i>slo-1</i>::<i>GFP</i> (C) in AWC neurons. SLO-1::TagRFP (A), SLO-1::GFP (C), SLO-2::TagRFP (B, C), and GFP::UNC-2 (A, B) were localized in AWC cell bodies (arrows) and in a punctate pattern along AWC axons (arrowheads). In AWC axons, SLO-1::TagRFP was localized next to GFP::UNC-2 (A); SLO-2::TagRFP was adjacent to GFP::UNC-2 (B); and SLO-2::TagRFP was localized near SLO-1::GFP (C). Insets show higher magnification of the outlined areas that exemplify localization of two translational reporters in close proximity. Scale bar, 5 μm. Anterior is at left and ventral is at bottom. (D) Quantification of mean correlation coefficient between SLO-1 and UNC-2, SLO-2 and UNC-2, as well as SLO-1 and SLO-2 using three algorithms of the Coloc 2 plugin in Fiji: Pearson’s correlation coefficient, Spearman’s rank correlation coefficient, and Li’s ICQ. For each colocalization class, images of three animals were used for quantification. Positive values of each coefficient indicate positive correlation, values close to zero indicate no correlation, and negative values indicate anti-correlation. Pearson's correlation coefficient ranges from -1 to +1; Spearman’s rank correlation coefficient ranges from -1 to +1; Li's ICQ value ranges from -0.5 to +0.5. A schematic diagram of the AWC cell body, axon, dendrite, and cilia that represents the approximate region of images in A-C is shown in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005654#pgen.1005654.s002" target="_blank">S2D Fig</a>.</p