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Implementation of evidence-based practices for autistic students must be informed by robust research literature. Randomized-controlled trials (RCTs) are often considered a "gold standard" methodology for determining the effectiveness of interventions. However, the complex nature of schools presents challenges for implementing successful RCTs. We review common challenges that researchers may face when implementing RCTs of interventions for autistic students in school settings. Additionally, we provide recommendations to researchers for avoiding and addressing such challenges, based on our own experience conducting a school-based RCT. Limitations and directions for future research are also discussed.

New school transitions can be challenging for students on the autism spectrum. No published, evidence-based interventions exist to support families and teachers of students transitioning to elementary and secondary school during this critical period. Using Community Partnered Participatory Research, we developed Building Better Bridges (BBB), a caregiver coaching intervention that includes training on effective school communication, educational rights, advocacy, and child preparation strategies. We compared BBB (n = 83) to a module/resources-only comparison (n = 87) in a four-site randomized controlled trial in racially and ethnically diverse, under-resourced communities. In our intent-to-treat analysis, caregivers and teachers in BBB rated students' transitions to the new classroom as more positive, relative to the comparison group. Results suggest this low-cost intervention can improve the transition process for families and students at high risk of poor transitions.

As the prevalence of autistic children receiving special education continues to increase, educators are expected to identify and implement evidence-based interventions for autistic students. Unfortunately, there are numerous barriers to implementation of evidence-based interventions in schools and educators report a lack of adequate training regarding the needs of autistic students and appropriate intervention approaches. Modular approaches to intervention are a promising but untested strategy for helping educators receive training on evidence-based interventions and support with implementation. This study uses mixed methods to explore the initial feasibility of the Modular Approach to Autism Programs in Schools (MAAPS) in typical school settings. Key indicators of feasibility are presented using the RE-AIM framework (Glasgow et al. "American journal of public health," 89(9), 1322-1327, Glasgow et al., 1999), with emphasis on intervention fidelity, social validity, and promise of efficacy. Additionally, directions for future research are discussed.

BackgroundThere are a growing number of evidence-based interventions (EBIs) for autistic individuals, but few are successfully implemented with fidelity in under-resourced communities and with families from traditionally disenfranchised groups. Implementation science offers tools to increase EBI use in communities, but most implementation strategies are designed specific to a single EBI. It is not feasible to develop a new implementation strategy each time a new EBI is introduced in the community. Therefore, to test the effectiveness and generalizability of implementation strategies we are developing and testing a multifaceted implementation strategy with three EBIs concurrently. The goal of this protocol paper is to describe the randomized field trial of an implementation strategy for use across autism EBIs, diverse settings and participants, with the goal of increasing rapid uptake of effective practices to reach our most vulnerable children.MethodsWe developed a multifaceted implementation strategy called Using Novel Implementation Tools for Evidence-based intervention Delivery (UNITED) to facilitate the implementation and sustainment of three EBIs in under-resourced settings. We will compare fidelity to, and effectiveness of, each intervention [Mind the Gap (MTG), Remaking Recess (RR), Self-Determined Learning Model of Instruction (SDLMI)] with and without UNITED in a randomized field trial. Randomization will be stratified using a minimization allocation method. We will train community practitioners using remote delivery of modules specific to the intervention, and active coaching via Zoom for at least 6 sessions and up to 12 as dictated by each EBI. Our primary outcome is fidelity to each EBI, and our secondary outcome is at the child or family level (family empowerment for MTG, child peer social engagement for RR, and adolescent self-determination for SDLMI, respectively). We will measure progress through the implementation phases using the Stages of Implementation Completion and cost-effectiveness of UNITED.DiscussionThe results of this study will provide rigorous data on the effectiveness and generalizability of one relatively light-touch implementation strategy in increasing use of autism EBIs and associated outcomes in diverse under resourced public service settings for underrepresented autistic youth.Trial registrationMind the Gap: Clinicaltrials.gov Identifier:  NCT04972825 (Date registered July 22, 2021); Remaking Recess: Clinicaltrials.gov Identifier:  NCT04972838 (Date registered July 22, 2021); Self-Determined Learning Model of Instruction: Clinicaltrials.gov Identifier:  NCT04972851 (Date registered July 22, 2021).

The present paper aims to broaden the field of application of the phenomenological model proposed by the authors in a previous study (ICP model) and to assess the shear properties of a recycled 30 wt.% talc-filled polypropylene (TFPP) and a recycled 30 wt.% short glass fiber-reinforced polypropylene (SGFPP), used in the automotive industry. The materials were produced by injection molding employing post-industrial mechanical shredding of recycled materials. In particular, Iosipescu shear tests adopting the American Standard for Testing Materials (ASTM D5379) at three different operating temperatures (−40, 23 and 85 °C) were performed. The strain was acquired using a Digital Image Correlation (DIC) system to determine the map of the strain in the area of interest before failure. Lower operating temperatures led to higher shear chord moduli and higher strengths. Recycled SGFPP material showed higher mechanical properties and smaller strains at failure with respect to recycled TFPP. Finally, the ICP model also proved to be suitable and accurate for the prediction of the shear behavior of 30 wt.% SGFPP and 30 wt.% TFPP across different operating temperatures.

The cure kinetics of various epoxy resin mixtures, comprising a bisphenol epoxy, two epoxy modifiers, and two hardening agents derived from cardanol technology, were investigated through differential scanning calorimetry (DSC). The development of these mixtures aimed to achieve epoxy materials with a substantial bio-content up to 50% for potential automotive applications, aligning with the 2019 European Regulation on climate neutrality and CO2 emission. The Friedman isoconversional method was employed to determine key kinetic parameters, such as activation energy and pre-exponential factor, providing insights into the cross-linking process and the Kamal–Sourour model was used to describe and predict the kinetics of the chemical reactions. This empirical approach was implemented to forecast the curing process for the specific oven curing cycle utilised. Additionally, tensile tests revealed promising results showcasing materials’ viability against conventional counterparts. Overall, this investigation offers a comprehensive understanding of the cure kinetics, mechanical behaviour, and thermal properties of the novel epoxy–novolac blends, contributing to the development of high-performance materials for sustainable automotive applications.

While COVID-19’s urgency has diminished since its emergence in late 2019, it remains a significant public health challenge. Recent research reveals that the molecular intricacies of this virus are far more complex than initially understood, with numerous post-translational modifications leading to diverse proteoforms and viral particle heterogeneity. Mass spectrometry-based proteomics of patient serum/plasma emerges as a promising complementary approach to traditional diagnostic methods, offering insights into SARS-CoV-2 protein dynamics and enhancing understanding of the disease and its long-term consequences. This article highlights key findings from three years of pandemic-era proteomics research. It delves into biomarker discovery, diagnostic advancements, and drug development efforts aimed at monitoring COVID-19 onset and progression and exploring treatment options. Additionally, it examines global protein abundance and post-translational modification profiling to elucidate signaling pathway alterations and protein-protein interactions during infection. Finally, it explores the potential of emerging multi-omics analytic strategies in combatting SARS-CoV-2.

IntroductionPotential advantages of home dialysis remained a questionable issue. Three main factors have to be considered: the progressive reduction in the cost of consumables for in-Center hemodialysis (IC-HD), the widespread use of incremental Peritoneal Dialysis (PD), and the renewed interest in home hemodialysis (H-HD) in the pandemic era. Registries data on prevalence of dialysis modalities generally report widespread underemployment of home dialysis despite PD and H-HD could potentially provide clinical benefits, improve quality of life, and contrast the diffusion of new infection among immunocompromised patients.MethodsWe examined the economic impact of home dialysis by comparing the direct and indirect costs of PD (53 patients), H-HD (21 patients) and IC-HD (180 patients) in a single hospital of North-west Italy. In order to achieve comparable weekly costs, the average weekly frequency of dialysis sessions based on the dialysis modality was calculated, the cost of individual sessions per patient per week normalized, and the monthly and yearly costs were derived.ResultsAs expected, PD resulted the least expensive procedure (€ 23,314.79 per patient per year), but, notably, H-HD has a lower average cost than IC-HD (€ 35,535.00 vs. € 40,798.98). A cost analysis of the different dialysis procedures confirms the lower cost of PD, especially continuous ambulatory PD, compared to any extracorporeal technique.DiscussionAmong the hemodialysis techniques, home bicarbonate HD showed the lowest costs, while the weekly cost of Frequent Home Hemodialysis was found to be comparable to In-Center Bicarbonate Hemodialysis.

Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested whether three-month FOLFOX or XELOX therapy produced changes in plasma amino acid levels (PAAL) (an estimation of whole-body amino acid metabolism) and in plasma levels of malondialdehyde (MDA), a marker of lipid hyper oxidation. Fourteen ambulatory, resected patients with colorectal cancer scheduled to receive FOLFOX (n = 9) or XELOX (n = 5) therapy, after overnight fasting, underwent peripheral venous blood sampling, to determine PAAL and MDA before, during, and at the end of three-month therapy. Fifteen healthy matched subjects (controls) only underwent measures of PAAL at baseline. The results showed changes in 87.5% of plasma essential amino acids (EAAs) and 38.4% of non-EAAs in patients treated with FOLFOX or XELOX. These changes in EAAs occurred in two opposite directions: EAAs decreased with FOLFOX and increased or did not decrease with XELOX (interactions: from p = 0.034 to p = 0.003). Baseline plasma MDA levels in both FOLFOX and XELOX patients were above the normal range of values, and increased, albeit not significantly, during therapy. In conclusion, three-month FOLFOX or XELOX therapy affected plasma EAAs differently but not the baseline MDA levels, which were already high.

Background: Numerous studies have shown that racial/ethnic minority and under-resourced families face barriers that delay timely access to autism services. These barriers include lack of resources and information about autism, financial hardship, mistrust in the service system, cultural and language mismatch, and other factors that have yet to be identified. Method: The current study aimed to examine additional caregiver and system-level factors that could be associated with early service access using a diverse sample from four study sites (Los Angeles, CA; Philadelphia, PA; Sacramento, CA; and Rochester, NY). Partnering with community agencies that serve traditionally underrepresented groups, the research team recruited 118 caregivers of young children with autism who were low-income, English, Spanish or Korean speaking and had not accessed autism-specific services. Results: Regression analyses revealed that the total number of services accessed were associated with caregiver social network size (p = 0.011) but not by race, autism knowledge and caregiver agency. Among families receiving at least one non-autism specific service, a marginally significant interaction effect of site and primary language on total services received was observed (p = 0.06). Conclusion: Findings suggest that caregivers’ social network connections are crucial in early service access, and future interventions could target increasing social networks to improve families’ service engagement. More attention for non-English speaking families, especially those living in areas with few supports in their native languages, is needed.

Background: Although many interventions have empirical support in improving the outcomes of students with autism spectrum disorders (ASD), schools struggle with implementation of these interventions. Method and materials: We conducted 13 focus groups with 69 participants who included parents, educators, and administrators across three states to examine the challenges schools face in implementing evidence-based interventions (EBIs) and to evaluate the acceptability and contextual fit of the Modular Approach to Autism Programs for Schools (MAAPS). MAAPS is a comprehensive modular intervention that uses an active coaching process to guide school-based teams in selecting, planning, and implementing EBIs that are customised to meet individual student needs. Results: Results suggest that when implementing EBIs, schools face considerable challenges including limited resources (eg funding, personnel, materials, time) and personnel training. MAAPS was considered highly acceptable primarily due to the involvement of a coach who would support the teacher. Specifically, participants indicated that the physical presence of the coach actively providing support could help relieve the stressors and burdens of the teacher. Conclusions: Interpretations of these findings are discussed in terms of their implications on understanding the challenges schools face when adopting and implementing EBIs.

This Special Issue, “Mass Spectrometric Proteomics 2 [...]

ObjectiveDementias and mild cognitive impairment (MCI) are associated with variously combined changes in the neurotransmitter system and signaling, from neurotransmitter synthesis to synaptic binding. The study tested the hypothesis that different dementia subtypes and MCI may share similar reductions of brain availability in amino acid precursors (AAPs) of neurotransmitter synthesis and concomitant similar impairment in energy production and increase of oxidative stress, i.e., two important metabolic alterations that impact neurotransmission.Materials and methodsSixty-five demented patients (Alzheimer’s disease, AD, n = 44; frontotemporal disease, FTD, n = 13; vascular disease, VaD, n = 8), 10 subjects with MCI and 15 control subjects (CTRL) were recruited for this study. Cerebrospinal fluid (CSF) and plasma levels of AAPs, energy substrates (lactate, pyruvate), and an oxidative stress marker (malondialdehyde, MDA) were measured in all participants.ResultsDemented patients and subjects with MCI were similar for age, anthropometric parameters, biohumoral variables, insulin resistance (HOMA index model), and CSF neuropathology markers. Compared to age-matched CTRL, both demented patients and MCI subjects showed low CSF AAP tyrosine (precursor of dopamine and catecholamines), tryptophan (precursor of serotonin), methionine (precursor of acetylcholine) limited to AD and FTD, and phenylalanine (an essential amino acid largely used for protein synthesis) (p = 0.03 to

IntroductionChildren with autism spectrum disorder (ASD) benefit when their caregivers can effectively advocate for appropriate services. Barriers to caregiver engagement such as provider mistrust, cultural differences, stigma, and lack of knowledge can interfere with timely service access. We describe Mind the Gap (MTG), an intervention that provides education about ASD, service navigation, and other topics relevant to families whose children have a new ASD diagnosis. MTG was developed via community partnerships and is explicitly structured to reduce engagement barriers (e.g., through peer matching, meeting flexibility, culturally-informed practices). We also present on the results of a pilot of MTG, conducted in preparation for a randomized controlled trial.MethodsMTG was evaluated using mixed methods that included qualitative analysis and pre/post-test without concurrent comparison group. Participants (n=9) were primary caregivers of children (ages 2-7 years) with a recent ASD diagnosis and whose annual income was at or below 185% of the federal poverty level. In order to facilitate trust and relationship building, peer coaches delivered MTG. The coaches were parents of children with ASD who we trained to deliver the intervention. MTG consisted of up to 12 meetings between coaches and caregivers over the course of 18 weeks. Coaches delivered the intervention in homes and other community locations. Coaches shared information about various "modules," which were topics identified as important for families with a new ASD diagnosis. Coaches worked with families to answer questions, set weekly goals, assess progress, and offer guidance. For the pilot, we focused on three primary outcomes: feasibility, engagement, and satisfaction. Feasibility was measured via enrollment and retention data, as well as coach fidelity (i.e., implementation of MTG procedures). Engagement was measured via number of sessions attended and percentage completion of the selected outcome measures. For completers (n=7), satisfaction was measured via a questionnaire (completed by caregivers) and open-ended interviews (completed by caregivers and coaches).ResultsWe enrolled 56% of referred caregivers and 100% of eligible families. Retention was high (78%). Coaches could deliver the intervention with fidelity, completing, on average, 83% of program components. Engagement also was high; caregivers attended an average of 85% of total possible sessions and completed 100% of their measures. Caregivers indicated moderately high satisfaction with MTG. Qualitative data indicated that caregivers and coaches were positive about intervention content, and the coach-caregiver relationship was important. They also had suggestions for changes.ConclusionMind the Gap demonstrates evidence of feasibility, and data from the pilot suggest that it addresses intervention engagement barriers for a population that is under-represented in research. The results and suggestions from participants were used to inform a large-scale RCT, which is currently underway. Overall, MTG shows promise as an intervention that can be feasibly implemented with under-resourced and ethnic minority families of children with ASD.Trial registrationThis study is registered with ClinicalTrials.gov: NCT03711799.

Abstract Alzheimer’s disease (AD) is characterized by genetic and multifactorial risk factors. Many studies correlate AD to sleep disorders. In this study, we performed and validated a mouse model of AD and sleep fragmentation, which properly mimics a real condition of intermittent awakening. We noticed that sleep fragmentation induces a general acceleration of AD progression in 5xFAD mice, while in wild type mice it affects cognitive behaviors in particular learning and memory. Both these events may be correlated to aquaporin-4 (AQP4) modulation, a crucial player of the glymphatic system activity. In particular, sleep fragmentation differentially affects aquaporin-4 channel (AQP4) expression according to the stage of the disease, with an up-regulation in younger animals, while such change cannot be detected in older ones. Moreover, in wild type mice sleep fragmentation affects cognitive behaviors, in particular learning and memory, by compromising the glymphatic system through the decrease of AQP4. Nevertheless, an in-depth study is needed to better understand the mechanism by which AQP4 is modulated and whether it could be considered a risk factor for the disease development in wild type mice. If our hypotheses are going to be confirmed, AQP4 modulation may represent the convergence point between AD and sleep disorder pathogenic mechanisms.

Keenan A Ramsey,1 Suey SY Yeung,1 Anna GM Rojer,1 Noémie Gensous,2 Evans A Asamane,3 Justin Avery Aunger,3 Dmitriy Bondarev,4 Andrea Cabbia,5 Paul Doody,3 Barbara Iadarola,6,7 Belina Rodrigues,8,9 Muhammad R Tahir,10 Victor Kallen,10 Paola Pazienza,6,7 Nadine Correia Santos,8,9 Sarianna Sipilä,4 Janice L Thompson,3 Carel GM Meskers,1,11 Marijke C Trappenburg,12,13 Anna C Whittaker,15 Andrea B Maier1,14,16,17 1Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Vrije Universiteit, Faculty of Behavioural and Human Movement Sciences, Amsterdam, the Netherlands; 2Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy; 3School of Sport, Exercise & Rehabilitation Sciences, University of Birmingham, Birmingham, UK; 4Gerontology Research Center & Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland; 5Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; 6Personal Genomics s.r.l., Verona, Italy; 7Department of Biotechnology, University of Verona, Verona, Italy; 8Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; 9ICVS/3B’s, PT Government Associate Laboratory, Guimarães, Portugal; 10Department of Microbiology and System Biology, The Netherlands Organization for Applied Scientific Research, Zeist, the Netherlands; 11Department of Rehabilitation Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; 12Department of Internal Medicine, Section of Gerontology and Geriatrics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; 13Department of Internal Medicine, Amstelland Hospital, Amstelveen, the Netherlands; 14Department of Medicine and Aged Care, @Age, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria, Australia; 15Faculty of Health Sciences and Sport, University of Stirling, Scotland, UK; 16Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 17Centre for Healthy Longevity, @AgeSingapore, National University Health System, SingaporeCorrespondence: Andrea B Maier, Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Vrije Universiteit, Faculty of Behavioural and Human Movement Sciences, Van der Boechorststraat 7, Amsterdam, 1081 BT, the Netherlands, Tel +31 20 59 82000, Email a.b.maier@vu.nlPurpose: Evidence-based guidelines on nutrition and physical activity are used to increase knowledge in order to promote a healthy lifestyle. However, actual knowledge of guidelines is limited and whether it is associated with health outcomes is unclear.Participants and Methods: This inception cohort study aimed to investigate the association of knowledge of nutrition and physical activity guidelines with objective measures of physical function and physical activity in community-dwelling older adults attending a public engagement event in Amsterdam, The Netherlands. Knowledge of nutrition and physical activity according to Dutch guidelines was assessed using customized questionnaires. Gait speed and handgrip strength were proxies of physical function and the Minnesota Leisure Time Physical Activity Questionnaire was used to assess physical activity in minutes/week. Linear regression analysis, stratified by gender and adjusted for age, was used to study the association between continuous and categorical knowledge scores with outcomes.Results: In 106 older adults (mean age=70.1 SD=6.6, years) who were highly educated, well-functioning, and generally healthy, there were distinct knowledge gaps in nutrition and physical activity which did not correlate with one another (R2=0.013, p=0.245). Knowledge of nutrition or physical activity guidelines was not associated with physical function or physical activity. However, before age-adjustment nutrition knowledge was positively associated with HGS in males (B= 0.64 (95% CI: 0.05, 1.22)) and having knowledge above the median was associated with faster gait speed in females (B=0.10 (95% CI: 0.01, 0.19)).Conclusion: Our findings may represent a ceiling effect of the impact knowledge has on physical function and activity in the this high performing and educated population and that there may be other determinants of behavior leading to health status such as attitude and perception to consider in future studies.Keywords: health knowledge, attitudes, practice, lifestyle, physical performance, aged

Abstract Electron clouds forming inside the beam vacuum chamber due to photoemission and secondary emission may limit the accelerator performance. Specifically, the electron clouds can blow up the vertical emittance of a positron beam, through a head-tail-type single-bunch instability, if the central electron density exceeds a certain threshold value, that can be estimated analytically. Using the codes PyECLOUD and VSim, we carried out detailed simulations of the electron-cloud build up for the main arcs and the damping ring of the FCC-ee collider, in order to identify the effective photoemission rate and secondary emission yield required for achieving and maintaining the design emittance. To this end, we present the simulated electron density at the centre of the beam pipe for various bunch spacings, secondary emission yields, and photoemission parameters, in the damping ring and in the arcs of the collider positron ring. To gain further insight into the underlying dynamics, the obtained spatial and energy distributions of the cloud electrons are illustrated as a function of time. In addition, we compare results obtained for two different secondary emission models (“Furman–Pivi” and “ECLOUD”), thereby indicating the uncertainty inherent in this type of study, without any prototype vacuum chambers yet available. We also point out a few situations where the two secondary-emission models yield similar density values. Finally, based on our simulation results for two different design variants, we conclude that the new parameter baseline of the FCC-ee will facilitate electron-cloud mitigation.

Summary: Response to multiple microenvironmental cues and resilience to mechanical stress are essential features of trafficking leukocytes. Here, we describe unexpected role of titin (TTN), the largest protein encoded by the human genome, in the regulation of mechanisms of lymphocyte trafficking. Human T and B lymphocytes express five TTN isoforms, exhibiting cell-specific expression, distinct localization to plasma membrane microdomains, and different distribution to cytosolic versus nuclear compartments. In T lymphocytes, the LTTN1 isoform governs the morphogenesis of plasma membrane microvilli independently of ERM protein phosphorylation status, thus allowing selectin-mediated capturing and rolling adhesions. Likewise, LTTN1 controls chemokine-triggered integrin activation. Accordingly, LTTN1 mediates rho and rap small GTPases activation, but not actin polymerization. In contrast, chemotaxis is facilitated by LTTN1 degradation. Finally, LTTN1 controls resilience to passive cell deformation and ensures T lymphocyte survival in the blood stream. LTTN1 is, thus, a critical and versatile housekeeping regulator of T lymphocyte trafficking.

Decades of research have established that racial ethnic minority, low-income, and/or non-English speaking children with autism spectrum disorder (ASD) are diagnosed later than white children, and their families experience greater difficulty accessing services in the USA. Delayed access to timely diagnosis and early intervention may impact child outcomes and family quality of life. Despite their cognition of these disparities and their significant impact on the lives of those affected, explanations for the barriers experienced by underserved families are elusive, likely due to the complex interaction between structural and family factors. This study used qualitative methods to gather family and provider perspectives of perceived barriers and facilitators to obtaining an ASD diagnosis and accessing ASD-related services for underserved families. Themes from focus groups and interviews with families from three cultural groups (black, Hispanic/Latino, and Korean) and three primary languages (English, Korean, and Spanish) highlight specific barriers related to family, community, and systemic challenges as well as facilitators to accessing care for these populations. Family experiences are expanded upon with viewpoints from the providers who work with them. Recommendations are made for reducing disparities in the existing ASD service system including increasing professional, family, and community education; increasing culturally responsive care; improving provider-family partnerships; and addressing practical challenges to service access.

Decades of research have established that racial ethnic minority, low-income, and/or non-English speaking children with autism spectrum disorder (ASD) are diagnosed later than white children, and their families experience greater difficulty accessing services in the USA. Delayed access to timely diagnosis and early intervention may impact child outcomes and family quality of life. Despite their cognition of these disparities and their significant impact on the lives of those affected, explanations for the barriers experienced by underserved families are elusive, likely due to the complex interaction between structural and family factors. This study used qualitative methods to gather family and provider perspectives of perceived barriers and facilitators to obtaining an ASD diagnosis and accessing ASD-related services for underserved families. Themes from focus groups and interviews with families from three cultural groups (black, Hispanic/Latino, and Korean) and three primary languages (English, Korean, and Spanish) highlight specific barriers related to family, community, and systemic challenges as well as facilitators to accessing care for these populations. Family experiences are expanded upon with viewpoints from the providers who work with them. Recommendations are made for reducing disparities in the existing ASD service system including increasing professional, family, and community education; increasing culturally responsive care; improving provider-family partnerships; and addressing practical challenges to service access.

Abstract Background There are a growing number of evidence-based interventions (EBIs) for autistic individuals, but few are successfully implemented with fidelity in under-resourced communities and with families from traditionally disenfranchised groups. Implementation science offers tools to increase EBI use in communities, but most implementation strategies are designed specific to a single EBI. It is not feasible to develop a new implementation strategy each time a new EBI is introduced in the community. Therefore, to test the effectiveness and generalizability of implementation strategies we are developing and testing a multifaceted implementation strategy with three EBIs concurrently. The goal of this protocol paper is to describe the randomized field trial of an implementation strategy for use across autism EBIs, diverse settings and participants, with the goal of increasing rapid uptake of effective practices to reach our most vulnerable children. Methods We developed a multifaceted implementation strategy called Using Novel Implementation Tools for Evidence-based intervention Delivery (UNITED) to facilitate the implementation and sustainment of three EBIs in under-resourced settings. We will compare fidelity to, and effectiveness of, each intervention [Mind the Gap (MTG), Remaking Recess (RR), Self-Determined Learning Model of Instruction (SDLMI)] with and without UNITED in a randomized field trial. Randomization will be stratified using a minimization allocation method. We will train community practitioners using remote delivery of modules specific to the intervention, and active coaching via Zoom for at least 6 sessions and up to 12 as dictated by each EBI. Our primary outcome is fidelity to each EBI, and our secondary outcome is at the child or family level (family empowerment for MTG, child peer social engagement for RR, and adolescent self-determination for SDLMI, respectively). We will measure progress through the implementation phases using the Stages of Implementation Completion and cost-effectiveness of UNITED. Discussion The results of this study will provide rigorous data on the effectiveness and generalizability of one relatively light-touch implementation strategy in increasing use of autism EBIs and associated outcomes in diverse under resourced public service settings for underrepresented autistic youth. Trial registration Mind the Gap: Clinicaltrials.gov Identifier: NCT04972825 (Date registered July 22, 2021); Remaking Recess: Clinicaltrials.gov Identifier: NCT04972838 (Date registered July 22, 2021); Self-Determined Learning Model of Instruction: Clinicaltrials.gov Identifier: NCT04972851 (Date registered July 22, 2021).

Neutrophils play a pathogenic role in COVID-19 by releasing Neutrophils Extracellular Traps (NETs) or human neutrophil elastase (HNE). Given that HNE is inhibited by α1-antitrypsin (AAT), we aimed to assess the content of HNE, α1-antitrypsin (AAT) and HNE–AAT complexes (the AAT/HNE balance) in 33 bronchoalveolar lavage fluid (BALf) samples from COVID-19 patients. These samples were submitted for Gel-Electrophoresis, Western Blot and ELISA, and proteins (bound to AAT or HNE) were identified by Liquid Chromatography-Mass Spectrometry. NETs’ release was analyzed by confocal microscopy. Both HNE and AAT were clearly detectable in BALf at high levels. Contrary to what was previously observed in other settings, the formation of HNE–AAT complex was not detected in COVID-19. Rather, HNE was found to be bound to acute phase proteins, histones and C3. Due to the relevant role of NETs, we assessed the ability of free AAT to bind to histones. While confirming this binding, AAT was not able to inhibit NET formation. In conclusion, despite the finding of a high burden of free and bound HNE, the lack of the HNE–AAT inhibitory complex in COVID-19 BALf demonstrates that AAT is not able to block HNE activity. Furthermore, while binding to histones, AAT does not prevent NET formation nor their noxious activity.

Malnutrition is a common condition in cancer patients which is usually associated with functional limitations, as well as increased morbidity and mortality. Based on the support of the young sections of Italian Association of Medical Oncology (AIOM), Italian Association of Radiotherapy and Clinical Oncology (AIRO) and Italian Society of Surgical Oncology (SICO) merged into the NutriOnc Research Group, we performed a multidisciplinary national survey with the aim to define the awareness of nutritional issues among healthcare professionals delivering anticancer care. The questionnaire was organized in four sections, as follows: Knowledge and practices regarding Nutritional Management of cancer patients; Timing of screening and assessment of Nutritional Status; Nutritional Treatment and prescription criteria; Immunonutrition and educational topics. The modules focused on esophagogastric, hepato-bilio-pancreatic and colorectal malignancies. Overall, 215 physicians completed the survey. As regards the management of Nutritional Status of cancer patients, many responders adopted the ERAS program (49.3%), while a consistent number of professionals did not follow a specific validated nutritional care protocol (41.8%), mainly due to lack of educational courses (14.5%) and financial support (15.3%). Nearly all the included institutions had a multidisciplinary team (92%) to finalize the treatment decision-making. Cancer patients routinely underwent nutritional screening according to 57.2% of interviewed physicians. The timing of nutritional assessment was at diagnosis (37.8%), before surgery (25.9%), after surgery (16.7%), before radiochemotherapy (13.5%) and after radiochemotherapy (7%). Most of the responders reported that nutritional status was assessed throughout the duration of cancer treatments (55.6%). An important gap between current delivery and need of nutritional assessment persists. The development of specific and defined care protocols and the adherence to these tools may be the key to improving nutritional support management in clinical practice.

To date there are no evidence-based comprehensive interventions for use in school settings. There are numerous barriers to delivery of high-quality interventions in schools that have limited the transfer of research-based interventions to school settings. "Modular Approach to Autism Programing for Schools (MAAPS)" is a framework for implementation of evidence-based interventions in school settings that is designed to address these barriers. The development and initial evaluation of MAAPS was conducted using an implementation-science framework and results indicate that MAAPS is aligned with needs and resources available in schools, that it had excellent social validity, and that there is good evidence that MAAPS is effective for addressing core and associated features of autism in educational settings. [For the corresponding grantee submission, see ED605688.]

Abstract Pathological sensations caused by peripheral painful neuropathy occurring in Type 2 diabetes mellitus (T2DM) are often described as ‘sharp’ and ‘burning’ and are commonly spontaneous in origin. Proposed etiologies implicate dysfunction of nociceptive sensory neurons in dorsal root ganglia (DRG) induced by generation of reactive oxygen species, microvascular defects, and ongoing axonal degeneration and regeneration. To investigate the molecular mechanisms contributing to diabetic pain, DRGs were acquired postmortem from patients who had been experiencing painful diabetic peripheral neuropathy (DPN) and subjected to transcriptome analyses to identify genes contributing to pathological processes and neuropathic pain. DPN occurs in distal extremities resulting in the characteristic “glove and stocking” pattern. Accordingly, the L4 and L5 DRGs, which contain the perikarya of primary afferent neurons innervating the foot, were analyzed from five DPN patients and compared with seven controls. Transcriptome analyses identified 844 differentially expressed genes. We observed increases in levels of inflammation-associated transcripts from macrophages in DPN patients that may contribute to pain hypersensitivity and, conversely, there were frequent decreases in neuronally-related genes. The elevated inflammatory gene profile and the accompanying downregulation of multiple neuronal genes provide new insights into intraganglionic pathology and mechanisms causing neuropathic pain in DPN patients with T2DM.

The language used by teachers, school staff, and parents to talk about autistic students can send either positive or negative messages to other school staff, parents, and all students—with or without autism—about autistic students. Ultimately, these messages also extend to autistic people. Using qualitative focus group methods, we talked to parents, teachers, administrators, and other school staff to better understand how people speak about the inclusion of autistic students in general education classrooms in public schools. Overall, we found that many of our participants thought (1) autistic students need to earn their way into general education classrooms, unlike their peers without disabilities, (2) segregating students with disabilities away from their peers without disabilities is acceptable, and sometimes preferable, in school settings, and (3) there is power in inclusive education opportunities for students with and without disabilities in school settings. The findings from this study suggest that inclusive opportunities for autistic students were largely driven by stakeholder mindsets. These results should encourage school staff to think about and reflect on how they talk about autistic students in inclusive settings with the ultimate goal of creating more welcoming inclusive environments for autistic students.

Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE–AAT) in which the two proteins are covalently bound. The lack of this complex, together with the detection of HNE activity in BALf/plasma samples of COVID-19 patients, leads us to hypothesize that potential functional deficiencies should necessarily be attributed to possible structural modifications of AAT. These could greatly diminish its ability to inhibit neutrophil elastase, thus reducing lung protection. The aim of this work was to explore the oxidation state of AAT in BALf/plasma samples from these patients so as to understand whether the deficient inhibitory activity of AAT was somehow related to possible conformational changes caused by the presence of abnormally oxidized residues.

In Antarctica, ice-free areas can be found along the coast, on mountain peaks, and in the McMurdo Dry Valleys, where microorganisms well-adapted to harsh conditions can survive and reproduce. Metabolic analyses can shed light on the survival mechanisms of Antarctic soil communities from both coastal sites, under different plant coverage stages, and inner sites where slow-growing or dormant microorganisms, low water availability, salt accumulation, and a limited number of primary producers make metabolomic profiling difficult. Here, we report, for the first time, an efficient protocol for the extraction and the metabolic profiling of Antarctic soils based on the combination of NMR spectroscopy and mass spectrometry (MS). This approach was set up on samples harvested along different localities of Victoria Land, in continental Antarctica, devoid of or covered by differently developed biological crusts. NMR allowed for the identification of thirty metabolites (mainly sugars, amino acids, and organic acids) and the quantification of just over twenty of them. UPLC-MS analysis identified more than twenty other metabolites, in particular flavonoids, medium- and long-chain fatty acids, benzoic acid derivatives, anthracenes, and quinones. Our results highlighted the complementarity of the two analytical techniques. Moreover, we demonstrated that their combined use represents the “gold standard” for the qualitative and quantitative analysis of little-explored samples, such as those collected from Antarctic soils.

Abstract GPR120 (encoded by FFAR4 gene) is a receptor for long chain fatty acids, activated by ω-3 Polyunsaturated Fatty Acids (PUFAs), and expressed in many cell types. Its role in the context of colorectal cancer (CRC) is still puzzling with many controversial evidences. Here, we explored the involvement of epithelial GPR120 in the CRC development. Both in vitro and in vivo experiments were conducted to mimic the conditional deletion of the receptor from gut epithelium. Intestinal permeability and integrity of mucus layer were assessed by using Evans blue dye and immunofluorescence for MUC-2 protein, respectively. Microbiota composition, presence of lipid mediators and short chain fatty acids were analyzed in the stools of conditional GPR120 and wild type (WT) mice. Incidence and grade of tumors were evaluated in all groups of mice before and after colitis-associated cancer. Finally, GPR120 expression was analyzed in 9 human normal tissues, 9 adenomas, and 17 primary adenocarcinomas. Our work for the first time highlights the role of the receptor in the progression of colorectal cancer. We observed that the loss of epithelial GPR120 in the gut results into increased intestinal permeability, microbiota translocation and dysbiosis, which turns into hyperproliferation of epithelial cells, likely through the activation of β -catenin signaling. Therefore, the loss of GPR120 represents an early event of CRC, but avoid its progression as invasive cancer. these results demonstrate that the epithelial GPR120 receptor is essential to maintain the mucosal barrier integrity and to prevent CRC developing. Therefore, our data pave the way to GPR120 as an useful marker for the phenotypic characterization of CRC lesions and as new potential target for CRC prevention.

BackgroundDisparities in COVID-19 information and vaccine access have emerged during the pandemic. Individuals from historically excluded communities (eg, Black and Latin American) experience disproportionately negative health outcomes related to COVID-19. Community gaps in COVID-19 education, social, and health care services (including vaccines) should be prioritized as a critical effort to end the pandemic. Misinformation created by the politicization of COVID-19 and related public health measures has magnified the pandemic’s challenges, including access to health care, vaccination and testing efforts, as well as personal protective equipment. Information and Communication Technology (ICT) has been demonstrated to reduce the gaps of marginalization in education and access among communities. Chatbots are an increasingly present example of ICTs, particularly in health care and in relation to the COVID-19 pandemic. ObjectiveThis project aimed to (1) follow an inclusive and theoretically driven design process to develop and test a COVID-19 information ICT bilingual (English and Spanish) chatbot tool named “Ana” and (2) characterize and evaluate user experiences of these innovative technologies. MethodsAna was developed following a multitheoretical framework, and the project team was comprised of public health experts, behavioral scientists, community members, and medical team. A total of 7 iterations of ß chatbots were tested, and a total of 22 ß testers participated in this process. Content was curated primarily to provide users with factual answers to common questions about COVID-19. To ensure relevance of the content, topics were driven by community concerns and questions, as ascertained through research. Ana’s repository of educational content was based on national and international organizations as well as interdisciplinary experts. In the context of this development and pilot project, we identified an evaluation framework to explore reach, engagement, and satisfaction. ResultsA total of 626 community members used Ana from August 2021 to March 2022. Among those participants, 346 used the English version, with an average of 43 users per month; and 280 participants used the Spanish version, with an average of 40 users monthly. Across all users, 63.87% (n=221) of English users and 22.14% (n=62) of Spanish users returned to use Ana at least once; 18.49% (n=64) among the English version users and 18.57% (n=52) among the Spanish version users reported their ranking. Positive ranking comprised the “smiley” and “loved” emojis, and negative ranking comprised the “neutral,” “sad,” and “mad” emojis. When comparing negative and positive experiences, the latter was higher across Ana’s platforms (English: n=41, 64.06%; Spanish: n=41, 77.35%) versus the former (English: n=23, 35.93%; Spanish: n=12, 22.64%). ConclusionsThis pilot project demonstrated the feasibility and capacity of an innovative ICT to share COVID-19 information within diverse communities. Creating a chatbot like Ana with bilingual content contributed to an equitable approach to address the lack of accessible COVID-19–related information.