Evaluation of Real-time Feedback to Train Caregivers to Conduct Early Intensive Behavioral Interventions

Mounting empirical support for early intensive behavioral intervention (EIBI) has increased demand for these types of treatments for children diagnosed with autism spectrum disorder (ASD). Many caregivers are now learning EIBI techniques and becoming active agents in their child’s ASD treatment. Behavioral skills training (BST) has been frequently used to teach individuals to perform a variety of skills correctly, including discrete-trial instruction (DTI; Lafasakis & Sturmey, 2007). In this study, caregivers were trained to conduct a DTI procedure. A single-component BST method (i.e., real-time feedback) was examined. A concurrent, multiple baseline across caregivers design was used to demonstrate experimental control. Results showed that a single-component BST was associated with short training time and few sessions to mastery. In addition, caregivers expressed high satisfaction with the real-time feedback training method

Population genetic structure associated with a landscape barrier in the Western Grasswren (Amytornis textilis textilis)

Dispersal patterns can dictate genetic population structure and, ultimately, population resilience, through maintaining gene flow and genetic diversity. However, geographical landforms, such as peninsulas, can impact dispersal patterns and thus be a barrier to gene flow. Here, we use 13 375 genome-wide single-nucleotide polymorphisms (SNPs) to evaluate genetic population structure and infer dispersal patterns of the Western Grasswren Amytornis textilis textilis (WGW, n = 140) in the Shark Bay region of Western Australia. We found high levels of genetic divergence between subpopulations on the mainland (Hamelin) and narrow peninsula (Peron). In addition, we found evidence of further genetic sub-structuring within the Hamelin subpopulation, with individuals collected from the western and eastern regions of a conservation reserve forming separate genetic clusters. Spatial autocorrelation analysis within each subpopulation revealed significant local-scale genetic structure up to 35 km at Hamelin and 20 km at Peron. In addition, there was evidence of male philopatry in both subpopulations. Our results suggest a narrow strip of land may be acting as a geographical barrier in the WGW, limiting dispersal between a peninsula and mainland subpopulation. In addition, heterogeneous habitat within Hamelin may be restricting dispersal at the local scale. Furthermore, there is evidence to suggest that the limited gene flow is asymmetrical, with directional dispersal occurring from the bounded peninsula subpopulation to the mainland. This study highlights the genetic structure existing within and between some of the few remaining WGW subpopulations, and shows a need to place equal importance on conservation efforts to maintain them in the future

Observational Study Design in Veterinary Pathology, Part 1: Study Design

Observational studies are the basis for much of our knowledge of veterinary pathology and are highly relevant to the daily practice of pathology. However, recommendations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offer advice on planning and conducting an observational study with examples from the veterinary pathology literature. Investigators should recognize the importance of creativity, insight, and innovation in devising studies that solve problems and fill important gaps in knowledge. Studies should focus on specific and testable hypotheses, questions, or objectives. The methodology is developed to support these goals. We consider the merits and limitations of different types of analytic and descriptive studies, as well as of prospective vs retrospective enrollment. Investigators should define clear inclusion and exclusion criteria and select adequate numbers of study subjects, including careful selection of the most appropriate controls. Studies of causality must consider the temporal relationships between variables and the advantages of measuring incident cases rather than prevalent cases. Investigators must consider unique aspects of studies based on archived laboratory case material and take particular care to consider and mitigate the potential for selection bias and information bias. We close by discussing approaches to adding value and impact to observational studies. Part 2 of the series focuses on methodology and validation of methods

Re-sensitization of Mycobacterium smegmatis to Rifampicin Using CRISPR Interference Demonstrates Its Utility for the Study of Non-essential Drug Resistance Traits

© 2021 Faulkner, Cox, Goh, van Bohemen, Gibson, Liebster, Wren, Willcocks and Kendall. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/A greater understanding of the genes involved in antibiotic resistance in Mycobacterium tuberculosis (Mtb) is necessary for the design of improved therapies. Clustered regularly interspaced short palindromic repeat interference (CRISPRi) has been previously utilized in mycobacteria to identify novel drug targets by the demonstration of gene essentiality. The work presented here shows that it can also be usefully applied to the study of non-essential genes involved in antibiotic resistance. The expression of an ADP-ribosyltransferase (Arr) involved in rifampicin resistance in Mycobacterium smegmatis was silenced using CRISPRi and the impact on rifampicin susceptibility was measured. Gene silencing resulted in a decrease in the minimum inhibitory concentration (MIC) similar to that previously reported in an arr deletion mutant. There is contradictory evidence for the toxicity of Streptococcus pyogenes dCas9 (dCas9 Spy) in the literature. In this study the expression of dCas9 Spy in M. smegmatis showed no impact on viability. Silencing was achieved with concentrations of the aTc inducer lower than previously described and with shorter induction times. Finally, designing small guide RNAs (sgRNAs) that target transcription initiation, or the early stages of elongation had the most impact on rifampicin susceptibility. This study demonstrates that CRISPRi based gene silencing can be as impactful as gene deletion for the study of non-essential genes and further contributes to the knowledge on the design and induction of sgRNAs for CRISPRi. This approach can be applied to other non-essential antimicrobial resistance genes such as drug efflux pumps.Peer reviewe

Selective Role of the Catalytic PI3K Subunit p110β in Impaired Higher Order Cognition in Fragile X Syndrome

SummaryDistinct isoforms of the PI3K catalytic subunit have specialized functions in the brain, but their role in cognition is unknown. Here, we show that the catalytic subunit p110β plays an important role in prefrontal cortex (PFC)-dependent cognitive defects in mouse models of Fragile X syndrome (FXS), an inherited intellectual disability. FXS is caused by loss of function of the fragile X mental retardation protein (FMRP), which binds and translationally represses mRNAs. PFC-selective knockdown of p110β, an FMRP target that is translationally upregulated in FXS, reverses deficits in higher cognition in Fmr1 knockout mice. Genetic full-body reduction of p110β in Fmr1 knockout mice normalizes excessive PI3K activity, restores stimulus-induced protein synthesis, and corrects increased dendritic spine density and behavior. Notably, adult-onset PFC-selective Fmr1 knockdown mice show impaired cognition, which is rescued by simultaneous p110β knockdown. Our results suggest that FMRP-mediated control of p110β is crucial for neuronal protein synthesis and cognition

Plasma p-tau181, neurofilament light chain and association with cognition in Parkinson's disease

Early identification of cognitive impairment in Parkinson’s disease (PD) has important clinical and research implications. The aim of our study was to investigate the role of plasma tau phosphorylated at amino acid 181 (p-tau181) and plasma neurofilament light chain (NfL) as biomarkers of cognition in PD. Baseline concentrations of plasma p-tau181 and NfL were measured in a cohort of 136 patients with PD and 63 healthy controls (HC). Forty-seven PD patients were followed up for up to 2 years. Cross-sectional and longitudinal associations between baseline plasma biomarkers and cognitive progression were investigated using linear regression and linear mixed effects models. At baseline, plasma p-tau181 concentration was significantly higher in PD subjects compared with HC (p = 0.026). In PD patients, higher plasma NfL was associated with lower MMSE score at baseline, after adjusting for age, sex and education (p = 0.027). Baseline plasma NfL also predicted MMSE decline over time in the PD group (p = 0.020). No significant association between plasma p-tau181 concentration and baseline or longitudinal cognitive performance was found. While the role of p-tau181 as a diagnostic biomarker for PD and its relationship with cognition need further elucidation, plasma NfL may serve as a feasible, non-invasive biomarker of cognitive progression in PD

Plasma Neurofilament Light and p-tau181 and Risk of Psychosis in Parkinson's Disease

BACKGROUND: Neuropsychiatric symptoms are common and important to people with Parkinson's disease (PD), but their etiology is poorly understood. Plasma neurofilament light (NfL) and p-tau181 are biomarkers of neuro-axonal degeneration and tau pathology respectively which have yet to be explored in association with the affective and psychotic symptoms in PD. OBJECTIVE: To investigate the relationship between plasma NfL and p-tau181 with the affective and psychotic symptoms in PD. METHODS: We assessed the baseline concentration of plasma NfL and p-tau181 in a cohort of 108 patients with PD and 38 healthy controls. A subgroup of patients (n = 63) was assessed annually with clinical measures for up to 7 years. Psychotic symptoms were assessed using Non-Motor Symptom Scale with affective symptoms measured in the Hospital Anxiety and Depression Scale. RESULTS: Baseline plasma NfL was a significant predictor of psychotic symptoms longitudinally across the study adjusted for age, Hoehn and Yahr stage, duration of follow up, duration of disease, baseline levodopa and dopamine agonist medication, and baseline cognition: (OR 8.15 [95% CI 1.40-47.4], p = 0.020). There was no association between NfL concentration and the cumulative prevalence of affective symptoms. Plasma p-tau181 concentration was not associated with psychotic or affective symptoms. CONCLUSION: These findings suggest psychotic symptoms are associated with greater neurodegeneration in PD. Further studies are needed to explore NfL as a potential biomarker for psychosis in PD

NMDA Receptor Antibodies and Neuropsychiatric Symptoms in Parkinson's Disease

OBJECTIVE: N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoantibody-mediated neurological syndrome with prominent cognitive and neuropsychiatric symptoms. The clinical relevance of NMDAR antibodies outside the context of encephalitis was assessed in this study. METHODS: Plasma from patients with Parkinson's disease (PD) (N=108) and healthy control subjects (N=89) was screened at baseline for immunoglobulin A (IgA), IgM, and IgG NMDAR antibodies, phosphorylated tau 181 (p-tau181), and the neuroaxonal injury marker neurofilament light (NfL). Clinical assessment of the patients included measures of cognition (Mini-Mental State Examination [MMSE]) and neuropsychiatric symptoms (Hospital Anxiety and Depression Scale; Non-Motor Symptoms Scale for Parkinson's Disease). A subgroup of patients (N=61) was followed annually for up to 6 years. RESULTS: Ten (9%) patients with PD tested positive for NMDAR antibodies (IgA, N=5; IgM, N=6; IgG, N=0), and three (3%) healthy control subjects had IgM NMDAR antibodies; IgA NMDAR antibodies were detected significantly more commonly among patients with PD than healthy control subjects (χ2=4.23, df=1, p=0.04). Age, gender, and disease duration were not associated with NMDAR antibody positivity. Longitudinally, antibody-positive patients had significantly greater decline in annual MMSE scores when the analyses were adjusted for education, age, disease duration, p-tau181, NfL, and follow-up duration (adjusted R2=0.26, p=0.01). Neuropsychiatric symptoms were not associated with antibody status, and no associations were seen between NMDAR antibodies and p-tau181 or NfL levels. CONCLUSIONS: NMDAR antibodies were associated with greater cognitive impairment over time in patients with PD, independent of other pathological biomarkers, suggesting a potential contribution of these antibodies to cognitive decline in PD

Introducing Interprofessional Education (IPE) Grand Rounds: Lessons from a New Student-led IPE Initiative

Learning Objectives • Describe 2-3 benefits for enhancing student exposure to real world collaborative practice teams • Develop an action plan for starting an IPE Interest Group at your institution • Describe 3 practical tips for implementing an IPE Grand Round

A 360 Degree View of the Jefferson Health Mentors Program: Students, Administrator and Faculty Weigh in on Seven Years of Interprofessional Education

Learning Objectives •List three strategies for successful implementation of an Interprofessional Education (IPE) curriculum •Develop a roadmap for starting, expanding or evaluating an existing IPE program •Discuss challenges and shared lessons learned with CQI in implementing IPE with a panel hosted by HMP students, administrator and facult