Structure and mechanism of acetolactate decarboxylase

Acetolactate decarboxylase catalyzes the conversion of both enantiomers of acetolactate to the (R)-enantiomer of acetoin, via a mechanism that has been shown to involve a prior rearrangement of the non-natural (R)-enantiomer substrate to the natural (S)-enantiomer. In this paper, a series of crystal structures of ALDC complex with designed transition state mimics are reported. These structures, coupled with inhibition studies and site-directed mutagenesis provide an improved understanding of the molecular processes involved in the stereoselective decarboxylation/protonation events. A mechanism for the transformation of each enantiomer of acetolactate is proposed

Development and initial validation of the Influences on Patient Safety Behaviours Questionnaire

YesBackground: Understanding the factors that make it more or less likely that healthcare practitioners (HCPs) will perform certain patient safety behaviors is important in developing effective intervention strategies. A questionnaire to identify determinants of HCP patient safety behaviors does not currently exist. This study reports the development and initial validation of the Influences on Patient Safety Behaviors Questionnaire (IPSBQ) based on the Theoretical Domains Framework. Methods: Two hundred and thirty-three HCPs from three acute National Health Service Hospital Trusts in the United Kingdom completed the 34-item measure focusing on one specific patient safety behavior (using pH as the first line method for checking the position of a nasogastric tube). Confirmatory factor analysis (CFA) was undertaken to generate the model of best fit. Results: The final questionnaire consisted of 11 factors and 23 items, and CFA produced a reasonable fit: χ2 (175) = 345.7, p < 0.001; CMIN/DF = 1.98; GFI = 0.90 and RMSEA = 0.06, as well as adequate levels of discriminant validity, and internal consistency (r = 0.21 to 0.64). Conclusions: A reliable and valid theoretically underpinned measure of determinants of HCP patient safety behavior has been developed. The criterion validity of the measure is still unknown and further work is necessary to confirm the reliability and validity of this measure for other patient safety behaviors

Role of Primary Care Clinician Concern During Screening for Early Identification of Autism

ObjectiveThe aim of this study was to evaluate the added value of primary care clinician (PCC)-indicated concern during primary care universal standardized screening in early identification of autism.MethodsToddlers were screened for autism during primary care checkups (n = 7,039, aged 14.24-22.43 months) in 2 studies. Parents completed the Modified Checklist for Autism in Toddlers, Revised, with Follow-Up. For each participant, PCCs indicated whether they had autism concerns (optional in 1 study-before or after viewing screening results, required before viewing screen results in the other). Children at high likelihood for autism from screen result and/or PCC concern (n = 615) were invited for a diagnostic evaluation; 283 children attended the evaluation.ResultsRates of PCC-indicated autism concerns were similar whether PCCs were required or encouraged to indicate concerns. High likelihood of autism indication on both screen and PCC concern resulted in the highest positive predictive value for autism and positive predictive value for any developmental disorder, as well as the highest evaluation attendance, with no significant difference between the positive screen-only and PCC concern-only groups. Although the frequency of PCC-indicated autism concern did not differ significantly based on the child's cognitive level, PCCs were more likely to identify children with more obvious autism characteristics compared with more subtle autism characteristics as having autism.ConclusionThe findings support the recommendation of the American Academy of Pediatrics that both screening and surveillance for autism be incorporated into well-child visits. High likelihood of autism on either screen or PCC concern should trigger a referral for an evaluation

Sex differences in early autism screening using the Modified Checklist for Autism in Toddlers, Revised, with Follow-Up (M-CHAT-R/F)

Lay abstractThis study examined a widely used autism screening tool, the Modified Checklist for Autism in Toddlers, Revised, with Follow-Up to identify differences in screening for autism between toddler males and females. Examining sex differences in screening for autism in toddlerhood is important as it determines who will be referred for evaluations and receive diagnoses, which is critical for access to autism-specific early intervention. This study found that females were less likely to screen positive and be invited for evaluations compared with males. Females at high likelihood for autism were less likely to be diagnosed with autism, which decreases confidence in the screener's results. Importantly, the Modified Checklist for Autism in Toddlers, Revised, with Follow-Up accurately identified both males and females with autism. Future research should examine ways to improve accuracy in screening results for females

Critical Examination of Autism Screening Tools: A Reply to Øien

We thank Dr. Øien for his comments on the relevance and implications of our cluster randomized controlled trial (RCT) in his editorial, "Editorial: The Critical Examination of Autism Screening Tools: A Call for Addressing False Negatives."1

Eight-fold increased COVID-19 mortality in autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations: an observational study

Background: MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD-MUC1 patients produce approximately 50% of normal mucin-1. Methods: To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths. Results: Surveys were emailed to 637 individuals, with responses from 89 ADTKD-MUC1 and 132 ADTKD-UMOD individuals. 19/83 (23%) ADTKD-MUC1 survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD-UMOD respondents (odds ratio (OR) 2.35 (95%CI 1.60–3.11, P = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD-MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD-UMOD, with OR 9.21 (95%CI 1.22–69.32), P = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD-MUC1 individuals was 7.06 ± 4.12 vs. 10.21 ± 4.02 U/mL (P = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD-MUC1 individuals (5%) vs. 3 deaths in 478 ADTKD-UMOD individuals (0.6%) (P = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD-MUC1 8.4 (2.9–29.5), kidney transplant 5.5 (1.6–9.1), body mass index (kg/m2) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1). Conclusions: Individuals with ADTKD-MUC1 are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD-UMOD individuals. Haplo-insufficient production of mucin-1 may be responsible

Cardiovascular risk factors among Chamorros

BACKGROUND: Little is known regarding the cardiovascular disease risk factors among Chamorros residing in the United States. METHODS: The Chamorro Directory International and the CDC's Behavioral Risk Factor Surveillance System Questionnaire (BRFSS) were used to assess the health related practices and needs of a random sample of 228 Chamorros. RESULTS: Inactivity, hypertension, elevated cholesterol and diabetes mellitus were more prevalent in this Chamorro sample compared to the US average. Participants who were 50-and-older or unemployed were more likely to report hypertension, diabetes and inactivity, but they were also more likely to consume more fruits and vegetables than their younger and employed counterparts. Women were more likely to report hypertension and diabetes, whereas men were more likely to have elevated BMI and to have never had their blood cholesterol checked. CONCLUSION: The study provides data that will help healthcare providers, public health workers and community leaders identify where to focus their health improvement efforts for Chamorros and create culturally competent programs to promote health in this community

Genetic and Clinical Predictors of Age of ESKD in Individuals With Autosomal Dominant Tubulointerstitial Kidney Disease Due to UMOD Mutations

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2016 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1003/thumbnail.jp

Pain Neuroscience Education: State of the Art and Application in Pediatrics

Chronic pain is a widespread problem in the field of pediatrics. Many interventions to ameliorate pain-related dysfunction have a biobehavioral focus. As treatments for chronic pain (e.g., increased movement) often stand in stark contrast to treatments for an acute injury (e.g., rest), providing a solid rationale for treatment is necessary to gain patient and parent buy-in. Most pain treatment interventions incorporate psychoeducation, or pain neuroscience education (PNE), as an essential component, and in some cases, as a stand-alone approach. The current topical review focuses on the state of pain neuroscience education and its application to pediatric chronic pain. As very little research has examined pain neuroscience education in pediatrics, we aim to describe this emerging area and catalyze further work on this important topic. As the present literature has generally focused on adults with chronic pain, pain neuroscience education merits further attention in the realm of pediatric pain in order to be tailored and implemented in this population