Dyslexic doctors, an observation on current United Kingdom practice

Issue: Dyslexia is a common learning difficulty with an estimated prevalence of ten percent within the general population and two percent among junior doctors training in the United Kingdom. Despite dyslexia being common, there are still many challenges sufferers face in modern medical practice. Evidence: Multiple case studies have found there to be barriers that dyslexic doctors face throughout their training. Common activities that required reading or writing in time pressured situations in front of an audience can impose an additional pressure for dyslexic doctors. In addition to the difficulties with day to day work, criticism and mockery from other staff members can make suffers of dyslexia feel undermined. From personal experiences, the authors of this article have found barriers are particularly present with regards to sitting post- graduate examinations and getting support in a modern time pressure health service. Implications: The discrepancy in the prevalence of learning difficulties between the general population and doctors in training might be due to barriers in training and difficulties when starting work. Addressing challenges will help support current dyslexic doctors and also help support future generations. Rapidly developing technology in health care makes it easier to accommodate doctors with additional needs but the impact of this are yet to be studied. If the barriers are addressed it is likely to support not only doctors with dyslexia diagnosis but all health care professionals

Engaging with conspiracy believers

Conspiracy theories abound in social and political discourse, believed by millions of people around the world. In this article, we highlight when it is important to engage with people who believe in conspiracy theories and review recent literature highlighting how best to do so. We first summarise research on the potentially damaging consequences of conspiracy beliefs for individuals, including consequences related to psychopathology. We also focus on the consequences for groups, and societies, and the importance of understanding and addressing conspiracy beliefs. We then review recent literature on how to engage with people who believe in conspiracy theories, specifically with the goal to reduce susceptibility to conspiracy theories and other types of misinformation. We focus on interpersonal strategies to communicate with individuals who believe in conspiracy theories, and large-scale strategies designed to reduce conspiracy beliefs within broader communities

Enhanced snoMEN Vectors Facilitate Establishment of GFP–HIF-1α Protein Replacement Human Cell Lines

The snoMEN (snoRNA Modulator of gene ExpressioN) vector technology was developed from a human box C/D snoRNA, HBII-180C, which contains an internal sequence that can be manipulated to make it complementary to RNA targets, allowing knock-down of targeted genes. Here we have screened additional human nucleolar snoRNAs and assessed their application for gene specific knock-downs to improve the efficiency of snoMEN vectors. We identify and characterise a new snoMEN vector, termed 47snoMEN, that is derived from box C/D snoRNA U47, demonstrating its use for knock-down of both endogenous cellular proteins and G/YFP-fusion proteins. Using multiplex 47snoMEM vectors that co-express multiple 47snoMEN in a single transcript, each of which can target different sites in the same mRNA, we document >3-fold increase in knock-down efficiency when compared with the original HBII-180C based snoMEN. The multiplex 47snoMEM vector allowed the construction of human protein replacement cell lines with improved efficiency, including the establishment of novel GFP–HIF-1α replacement cells. Quantitative mass spectrometry analysis confirmed the enhanced efficiency and specificity of protein replacement using the 47snoMEN-PR vectors. The 47snoMEN vectors expand the potential applications for snoMEN technology in gene expression studies, target validation and gene therapy

Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium

AbstractBarrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α. A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4α were ectopically expressed by adenoviral infection. The phenotype following infection was determined by a combination of PCR, immunohistochemical and morphological analyses. We demonstrate the expression of CDX2 and HNF4α in human biopsy samples. Our oesophageal organ culture system expressed markers characteristic of the normal SSQE: p63, K14, K4 and loricrin. Ectopic expression of HNF4α, but not of Cdx2 induced expression of Tff3, villin, K8 and E-cadherin. HNF4α is sufficient to induce a columnar-like phenotype in adult mouse oesophageal epithelium and is present in the human condition. These data suggest that induction of HNF4α is a key early step in the formation of Barrett's metaplasia and are consistent with an origin of Barrett's metaplasia from the oesophageal epithelium

Adiponectin-Mediated Analgesia and AntiInflammatory Effects in Rat

The adipose tissue-derived protein, adiponectin, has significant anti-inflammatory properties in a variety of disease conditions. Recent evidence that adiponectin and its receptors (AdipoR1 and AdipoR2) are expressed in central nervous system, suggests that it may also have a central modulatory role in pain and inflammation. This study set out to investigate the effects of exogenously applied recombinant adiponectin (via intrathecal and intraplantar routes; 10–5000 ng) on the development of peripheral inflammation (paw oedema) and pain hypersensitivity in the rat carrageenan model of inflammation. Expression of adiponectin, AdipoR1 and AdipoR2 mRNA and protein was characterised in dorsal spinal cord using real-time polymerase chain reaction (PCR) and Western blotting. AdipoR1 and AdipoR2 mRNA and protein were found to be constitutively expressed in dorsal spinal cord, but no change in mRNA expression levels was detected in response to carrageenan-induced inflammation. Adiponectin mRNA, but not protein, was detected in dorsal spinal cord, although levels were very low. Intrathecal administration of adiponectin, both pre- and 3 hours post-carrageenan, significantly attenuated thermal hyperalgesia and mechanical hypersensitivity. Intrathecal administration of adiponectin post-carrageenan also reduced peripheral inflammation. Intraplantar administration of adiponectin pre-carrageenan dose-dependently reduced thermal hyperalgesia but had no effect on mechanical hypersensitivity and peripheral inflammation. These results show that adiponectin functions both peripherally and centrally at the spinal cord level, likely through activation of AdipoRs to modulate pain and peripheral inflammation. These data suggest that adiponectin receptors may be a novel therapeutic target for pain modulation

Once (but not twice) upon a time: Narrative inoculation against conjunction errors indirectly reduces conspiracy beliefs and improves truth discernment

Psychological inoculation has proven effective at reducing susceptibility to misinformation. We present a novel storytelling approach to inoculation against susceptibility to the conjunction fallacy (dmeta‐analysis = 0.82), a known cognitive predictor of conspiracy beliefs. In Study 1 (Pilot; N = 161), a narrative inoculation (vs. control) reduced susceptibility to conjunction errors, and in turn, conspiracy beliefs regarding government malfeasance. In Study 2 (main experiment; N = 141; pre‐registered), two separate narrative inoculations (vs. control) directly reduced susceptibility to conjunction errors, and indirectly reduced conspiracy beliefs regarding extra‐terrestrial cover‐ups. In addition, the inoculation messages improved detection of both real and fake news (‘truth discernment’). We discuss theoretical and practical implications, including the use of inoculation to induce critical thinking styles, and tailoring inoculations that may suit storytelling mediums

The selective metabotropic glutamate receptor 7 allosteric agonist AMN082 inhibits inflammatory pain-induced and incision-induced hypersensitivity in rat

This study characterized the contribution of metabotropic glutamate receptor 7 (mGlu7 receptor) activation to the development of inflammatory hyperalgesia and allodynia, using a novel, systemically active mGlu7 receptor allosteric agonist, N, N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082). The effects of AMN082 (0.1, 1 or 5 mg/kg, intraperitoneally; 5 or 50 nmol, intrathecally) or diclofenac (5 mg/kg, intraperitoneally) administered 30 min preprocedure or 3 h postprocedure on hindpaw withdrawal latency (in seconds) to thermal stimulation, and response threshold (in grams) to mechanical stimulation, were measured in adult rats (n = 6-8 per group) before and up to 24 h after intradermal injection of carrageenan into the hindpaw or hindpaw incision. Precarrageenan injection of 1 and 5 mg/kg AMN082, but not diclofenac inhibited thermal hyperalgesia, whereas postcarrageenan, both AMN082 and diclofenac attenuated thermal hyperalgesia and allodynia. In the paw incision model, presurgical and postsurgical administration of 1 and 5 mg/kg AMN082 inhibited thermal hyperalgesia, but not allodynia, whereas diclofenac was effective in attenuating both thermal hyperalgesia and allodynia but only when administered postsurgically. Intrathecal injection of AMN082 postcarrageenan and postsurgery also significantly attenuated thermal hyperalgesia. Enhancing endogenous mGlu7 receptor activity inhibits postinjury stimulus-evoked hypersensitivity and may be of therapeutic benefit for the treatment of inflammatory and incision-induced pain