A Scoping Review of Universal Design for Learning in United States Allied Health & Medical Education

Background: Universal design for learning (UDL) is considered best-practice for embracing inclusion for students with disabilities and there is growing evidence of its effectiveness in primary, secondary, and postsecondary education. However, little is known about if and how UDL is being implemented into United States graduate allied health and medical school curriculum as well as evidence of its benefits. Method: We used Arksey and O’Malley’s (2005) methodological framework. Search engines were: PubMed, CINAHL Complete, ERIC, GoogleScholar, and Scopus. Data were analyzed by the research team using Covidence to organize articles, screen, and complete a full-text review. Data extraction was completed by identifying key themes in the manuscripts and categorizing articles accordingly. Results: Six studies were eligible: three intervention and three descriptive articles. Findings identify a need for UDL in these programs but research regarding the effect of implementation of this framework into medical and allied health programs is lacking. Conclusion: There is a scarcity of research on UDL in graduate education from the United States. Much of the literature found on use of UDL in medical and allied health graduate level programs is non-experimental or descriptive. Future research is recommended to examine the impact of UDL in graduate education

Longitudinal association between child emotion regulation and aggression, and the role of parenting: a comparison of three cultures

Background: The ability to regulate emotions is a key developmental achievement acquired during social interactions and associated with better behavioral and social outcomes. We examined the influence of culture on child emotion regulation (ER) and aggression and on early parenting practices, and the role of parenting in child ER. Methods: We assessed 48 mother-infant dyads from three cultures (1 UK, 2 South African) at infant age of 3 months for maternal sensitivity during face-to-face interactions and responses to infant distress during daily life, and at 2 years for child ER strategies and maternally reported aggression. Results: There were cultural differences in child ER, and these were associated with differences in levels of aggression. Maternal strategies in response to early infant distress also differed by culture and predicted later child ER. Maternal sensitivity during face-to-face interactions was not associated with culture and showed no clear relationship with child ER. Conclusion: Cultural differences in maternal responses to infant distress mediated differences in child ER that are, in turn, related to differences in child aggression

AKR1D1 knockout mice have impaired intestinal health with evidence of gut dybiosis and increased gut permeability and have increased incidence of colon cancer in females

AKR1D1 knockout mice have impaired intestinal health with evidence of gut dybiosis and increased gut permeability and have increased incidence of colon cancer in female

An educational leaflet improves response to invitation for screening for arthritis in patients with psoriasis in primary care, but only in practices in the most deprived areas

This study hypothesises that an educational leaflet about psoriatic arthritis (PsA) will improve psoriasis patients’ attendance for screening for PsA. A random sample of patients ≥18 years old with a coded diagnosis of psoriasis and no diagnosis of PsA, rheumatoid arthritis or ankylosing spondylitis were identified from five GP surgeries in Yorkshire, UK. Patients were randomised 1:1 to receive study information alone or with the educational leaflet, with an invitation to attend for a screening examination by a dermatologist and rheumatologist. Nine hundred thirty-two invitation packs were sent to recruit 191 (20.5%) participants. One hundred sixty-nine (88.5%) had current or previous psoriasis and 17 (10.1%) had previously undiagnosed PsA. The estimated prevalence of PsA was 18.1% (95% CI: 16.2, 20.1%). The response rate was lower than expected and was not significantly higher when patients received the educational leaflet (22.8 vs 18.3%, p = 0.08). Response rates varied by practice (14.7 to 30.6%). However, deprivation scores for each practice revealed a significant increase in response with the leaflet for deprivation decile of 3 (p < 0.001) but no significant differences in the other practices. An educational leaflet about PsA improves attendance for screening in primary care, but only in those practices with higher levels of socioeconomic deprivation

The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management

Pathogenic germline exonuclease domain (ED) variants of POLE and POLD1 cause the Mendelian dominant condition polymerase proof-reading associated polyposis (PPAP). We aimed to describe the clinical features of all PPAP patients with probably pathogenic variants. We identified patients with a variants mapping to the EDs of POLE or POLD1 from cancer genetics clinics, a colorectal cancer (CRC) clinical trial, and systematic review of the literature. We used multiple evidence sources to separate ED variants into those with strong evidence of pathogenicity and those of uncertain importance. We performed quantitative analysis of the risk of CRC, colorectal adenomas, endometrial cancer or any cancer in the former group. 132 individuals carried a probably pathogenic ED variant (105 POLE, 27 POLD1). The earliest malignancy was colorectal cancer at 14. The most common tumour types were colorectal, followed by endometrial in POLD1 heterozygotes and duodenal in POLE heterozygotes. POLD1-mutant cases were at a significantly higher risk of endometrial cancer than POLE heterozygotes. Five individuals with a POLE pathogenic variant, but none with a POLD1 pathogenic variant, developed ovarian cancer. Nine patients with POLE pathogenic variants and one with a POLD1 pathogenic variant developed brain tumours. Our data provide important evidence for PPAP management. Colonoscopic surveillance is recommended from age 14 and upper-gastrointestinal surveillance from age 25. The management of other tumour risks remains uncertain, but surveillance should be considered. In the absence of strong genotype–phenotype associations, these recommendations should apply to all PPAP patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10689-021-00256-y

Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatophepatitis

OBJECTIVE: Insulin resistance and lipotoxicity are pathognomonic in non-alcoholic steatohepatitis (NASH). Glucagon-like peptide-1 (GLP-1) analogues are licensed for type 2 diabetes, but no prospective experimental data exists in NASH. This study determined the effect of a long-acting GLP-1 analogue, liraglutide, on organ-specific insulin sensitivity, hepatic lipid handling and adipose dysfunction in biopsy-proven NASH.DESIGN: 14 patients were randomised to 1.8mg liraglutide or placebo for 12-weeks of the mechanistic component of a double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov-NCT01237119). Patients underwent paired hyperinsulinaemic euglycaemic clamps, stable isotope tracers, adipose microdialysis and serum adipocytokine/metabolic profiling. In vitro isotope experiments on lipid flux were performed on primary human hepatocytes.RESULTS: Liraglutide reduced BMI (-1.9 vs. +0.04 kg/m2;p&lt;0.001), HbA1c (-0.3 vs. +0.3%;p&lt;0.01), cholesterol-LDL (-0.7 vs. +0.05 mmol/L;p&lt;0.01), ALT (-54 vs -4.0 IU/L;p&lt;0.01) and serum leptin, adiponectin, and CCL-2 (all p&lt;0.05). Liraglutide increased hepatic insulin sensitivity (-9.36 vs. -2.54% suppression of hepatic endogenous glucose production with low-dose insulin;p&lt;0.05). Liraglutide increased adipose tissue insulin sensitivity enhancing the ability of insulin to suppress lipolysis both globally (-24.9 vs. +54.8 pmol/L insulin required to ½ maximally suppress serum NEFA; p&lt;0.05), and specifically within subcutaneous adipose tissue (p&lt;0.05). In addition, liraglutide decreased hepatic DNL in-vivo (-1.26 vs. +1.30%; p&lt;0.05); a finding endorsed by the effect of GLP-1 receptor agonist on primary human hepatocytes (24.6% decrease in lipogenesis vs. untreated controls; p&lt;0.01).CONCLUSIONS: Liraglutide reduces metabolic dysfunction, insulin resistance and lipotoxicity in the key metabolic organs in the pathogenesis of NASH. Liraglutide may offer the potential for a disease-modifying intervention in NASH.</p

Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatophepatitis

Background & AimsInsulin resistance and lipotoxicity are pathognomonic in non-alcoholic steatohepatitis (NASH). Glucagon-like peptide-1 (GLP-1) analogues are licensed for type 2 diabetes, but no prospective experimental data exists in NASH. This study determined the effect of a long-acting GLP-1 analogue, liraglutide, on organ-specific insulin sensitivity, hepatic lipid handling and adipose dysfunction in biopsy-proven NASH.MethodsFourteen patients were randomised to 1.8mg liraglutide or placebo for 12-weeks of the mechanistic component of a double-blind, randomised, placebo-controlled trial (ClinicalTrials.gov-NCT01237119). Patients underwent paired hyperinsulinaemic euglycaemic clamps, stable isotope tracers, adipose microdialysis and serum adipocytokine/metabolic profiling. In vitro isotope experiments on lipid flux were performed on primary human hepatocytes.ResultsLiraglutide reduced BMI (−1.9 vs. +0.04kg/m2; p<0.001), HbA1c (−0.3 vs. +0.3%; p<0.01), cholesterol-LDL (−0.7 vs. +0.05mmol/L; p<0.01), ALT (−54 vs. −4.0IU/L; p<0.01) and serum leptin, adiponectin, and CCL-2 (all p<0.05). Liraglutide increased hepatic insulin sensitivity (−9.36 vs. −2.54% suppression of hepatic endogenous glucose production with low-dose insulin; p<0.05). Liraglutide increased adipose tissue insulin sensitivity enhancing the ability of insulin to suppress lipolysis both globally (−24.9 vs. +54.8pmol/L insulin required to ½ maximally suppress serum non-esterified fatty acids; p<0.05), and specifically within subcutaneous adipose tissue (p<0.05). In addition, liraglutide decreased hepatic de novo lipogenesis in vivo (−1.26 vs. +1.30%; p<0.05); a finding endorsed by the effect of GLP-1 receptor agonist on primary human hepatocytes (24.6% decrease in lipogenesis vs. untreated controls; p<0.01).ConclusionsLiraglutide reduces metabolic dysfunction, insulin resistance and lipotoxicity in the key metabolic organs in the pathogenesis of NASH. Liraglutide may offer the potential for a disease-modifying intervention in NASH

Differential activity and expression of human 5β-reductase (AKR1D1) splice variants

Steroid hormones, including glucocorticoids and androgens, exert a wide variety of effects in the body across almost all tissues. The steroid A-ring 5beta-reductase (AKR1D1) is expressed in human liver and testes, and three splice variants have been identified (AKR1D1-001, AKR1D1-002, AKR1D1-006). Amongst these, AKR1D1-002 is the best described; it modulates steroid hormone availability and catalyses an important step in bile acid biosynthesis. However, specific activity and expression of AKR1D1-001 and AKR1D1-006 are unknown. Expression of AKR1D1 variants were measured in human liver biopsies and hepatoma cell lines by qPCR. Their three-dimensional (3D) structures were predicted using in silico approaches. AKR1D1 variants were over-expressed in HEK293 cells, and successful overexpression confirmed by qPCR and western blotting. Cells were treated with either cortisol, dexamethasone, prednisolone, testosterone or androstenedione, and steroid hormone clearance was measured by mass spectrometry. Glucocorticoid and androgen receptor activation were determined by luciferase reporter assays. AKR1D1-002 and AKR1D1-001 are expressed in human liver, and only AKR1D1-006 is expressed in human testes. Following over-expression, AKR1D1-001 and AKR1D1-006 protein levels were lower than AKR1D1-002, but significantly increased following treatment with the proteasomal inhibitor, MG-132. AKR1D1-002 efficiently metabolised glucocorticoids and androgens and decreased receptor activation. AKR1D1-001 and AKR1D1-006 poorly metabolised dexamethasone, but neither protein metabolised cortisol, prednisolone, testosterone or androstenedione. We have demonstrated the differential expression and role of AKR1D1 variants in steroid hormone clearance and receptor activation in vitro. AKR1D1-002 is the predominant functional protein in steroidogenic and metabolic tissues. In addition, AKR1D1-001 and AKR1D1-006 may have a limited, steroid-specific role in the regulation of dexamethasone action

Patient and Public Involvement Toolkit : Involving LGBTQ+ Unpaid Carers

Impactful social care research that achieves to influence policy and practice needs to draw upon and be informed by the very social groups it wishes to benefit. There is a gap in a resource for co-productions in research and practice when it comes to LGBTQ+ people, and especially when these are unpaid carers – this is a unique challenge because current best practice indicates that the carer and the person cared for need to be perceived and considered as a unit. Therefore researchers and policy makers need to consider intersectional impacts and implications, that reflect the needs of the LGBTQ+ person and that of the person they care for, who may or may not be LGBTQ+, too. The leadership of LGBTQ+ individuals and communities in research, policy and practice that concerns those being impacted upon is vital. This project aimed to address a gap in the resources available to support co-production in research and practice. Its focus was on the vital role of unpaid carers as equal partners in developing research that addresses how to provide more tailored support. Our philosophy aimed to take account of the many different identities held by LGBTQ+ unpaid carers and to capitalise on the assets, knowledge and skills that they bring to caring and how best to improve it. The development of the toolkit involved developing processes and outcomes in relation to: Community engagement and consultation Identifying and building capacity for research collaboration Resources for training, supervision and support of LGBTQ+ unpaid carers; Peer networking and peer support Evaluation and capturing best practices Community knowledge exchang

Non-Lynch Familial and Early-Onset Colorectal Cancer Explained by Accumulation of Low-Risk Genetic Variants

A large proportion of familial and/or early-onset cancer patients do not carry pathogenic variants in known cancer predisposing genes. We aimed to assess the contribution of previously validated low-risk colorectal cancer (CRC) alleles to familial/early-onset CRC (fCRC) and to serrated polyposis. We estimated the association of CRC with a 92-variant-based weighted polygenic risk score (wPRS) using 417 fCRC patients, 80 serrated polyposis patients, 1077 hospital-based incident CRC patients, and 1642 controls. The mean wPRS was significantly higher in fCRC than in controls or sporadic CRC patients. fCRC patients in the highest (20th) wPRS quantile were at four-fold greater CRC risk than those in the middle quantile (10th). Compared to low-wPRS fCRC, a higher number of high-wPRS fCRC patients had developed multiple primary CRCs, had CRC family history, and were diagnosed at age ≥50. No association with wPRS was observed for serrated polyposis. In conclusion, a relevant proportion of mismatch repair (MMR)-proficient fCRC cases might be explained by the accumulation of low-risk CRC alleles. Validation in independent cohorts and development of predictive models that include polygenic risk score (PRS) data and other CRC predisposing factors will determine the implementation of PRS into genetic testing and counselling in familial and early-onset CRC