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Despite considerable progress in using lipid nanoparticle (LNP) vehicles for gene delivery, achieving selective transfection of specific cell types remains a significant challenge, hindering the advancement of new gene or gene-editing therapies. Although LNPs have been equipped with ligands aimed at targeting specific cellular receptors, achieving complete selectivity continues to be elusive. The exact reasons for this limited selectivity are not fully understood, as cell targeting involves a complex interplay of various cellular factors. Assessing how much ligand/receptor binding contributes to selectivity is challenging due to these additional influencing factors. Nonetheless, such data are important for developing new nanocarriers and setting realistic expectations for selectivity. Here, we have quantified the selective, targeted transfection using two uniquely engineered cell lines that eliminate unpredictable and interfering cellular influences. We have compared the targeted transfection of Chinese ovary hamster (CHO) cells engineered to express the human transferrin receptor 1 (hTfR1), CHO-TRVb-hTfR1, with CHO cells that completely lack any transferrin receptor, CHO-TRVb-neo cells (negative control). Thus, the two cell lines differ only in the presence/absence of hTfR1. The transfection was performed with pDNA-encapsulating LNPs equipped with the DT7 peptide ligand that specifically binds to hTfR1 and enables targeted transfection. The LNPs pDNA encoded for the monomeric GreenLantern (mGL) reporter protein, whose fluorescence was used to quantify transfection. We report a novel LNP composition designed to achieve an optimal particle size and ζ-potential, efficient pDNA encapsulation, hTfR1-targeting capability, and sufficient polyethylene glycol sheltering to minimize random cell targeting. The transfection efficiency was quantified in both cell lines separately through flow cytometry based on the expression of the fluorescent gene product. Our results demonstrated an LNP dose-dependent mGL expression, with a 5-fold preference for the CHO-TRVb-hTfR1 when compared to CHO-TRVb-neo. In another experiment, when both cell lines were mixed at a 1:1 ratio, the DT7-decorated LNP achieved a 3-fold higher transfection of the CHO-TRVb-hTfR1 over the CHO-TRVb-neo cells. Based on the low-level transfection of the CHO-TRVb-neo cells in both experiments, our results suggest that 17-25% of the transfection occurred in a nonspecific manner. The observed transfection selectivity for the CHO-TRVb-hTfR1 cells was based entirely on the hTfR1/DT7 interaction. This work showed that the platform of two engineered cell lines which differ only in the hTfR1 can greatly facilitate the development of LNPs with hTfR1-targeting ligands.

BackgroundPreoperative anxiety is a common occurrence among children and is associated with a host of maladaptive postoperative behaviors. Consequently, increased attention has been placed on interventions to reduce preoperative anxiety and its associated outcomes. Child Life preparation prior to surgery includes evidence-based practices such as age-appropriate distraction and therapeutic play. Virtual reality (VR) is a promising addition to the Child Life toolbox to address anxiety prior to surgery. The current study evaluates the implementation and feasibility of a VR experience, “Doc McStuffins: Doctor for a Day Virtual Reality Experience” (DocVR), developed by Disney Junior in collaboration with Children’s Hospital Los Angeles, to target pediatric preoperative anxiety. ObjectiveThe primary aim of this study was to examine the feasibility and efficacy of DocVR for preoperative anxiety. A secondary aim was to improve patient, caregiver, and health care provider satisfaction with the preoperative experience. MethodsIn this study, 51 patients (age 6-14 years) scheduled for surgery in the ambulatory surgery center and the main operating room at Children’s Hospital Los Angeles were approached to participate in Disney’s DocVR experience. The patients played the DocVR experience for an average of 18 minutes (3-55 minutes). Irrespective of surgical procedure, patients and their families were eligible, as long as they had no known marked cognitive or visual impairments that would interfere with completing the survey and engaging in the DocVR experience. ResultsPatients who tried the DocVR experience (n=51) responded overwhelmingly positively to both the VR technology and to the game itself. Patients experienced a statistically significant decrease in anxiety following DocVR game play (Z=–3.26, P=.001). On the Facial Affective Scale, the percentage of patients who chose the face with the most positive facial expression to represent their affect increased from 23% (12/51) pre-VR to 49% (25/47) post-VR. Furthermore, 97% (38/39) of patients reported feeling more comfortable at the hospital, and 74% (28/38) reported feeling less scared at the hospital after playing the game. The game was enjoyed by 94% (46/49) of patients, and 88% (30/34) of patients reported feeling both “Interested” and “Involved” in the game. ConclusionsDocVR is a feasible and beneficial VR experience to relieve pediatric preoperative anxiety and improve satisfaction in the preoperative area. The VR experience resulted in a decrease in overall anxiety and an increase in overall positive affect during the preoperative time. Patients also responded positively to the game, confirming their interest in the content and affirming the quality of the DocVR experience. The positive response to the game indicates that DocVR has the potential to make the overall preoperative experience less anxiety-producing and more comfortable, which leads to improved patient satisfaction. Naturally, improved patient outcomes lead to improved caregiver and health care provider satisfaction.

The coronavirus disease 2019 (COVID-19) outbreak has required institutions to rapidly adapt to changing public health circumstances. The Centers for Disease Control and Prevention has encouraged health care facilities to explore novel health care delivery modes. However, many institutions may not be prepared to begin offering digital health and telehealth services. Chatbots are one digital health tool that can help evolve triage and screening processes in a scalable manner. Here, we present a decision-making and implementation framework for deploying COVID-19 screening chatbots at pediatric health care facilities.

BackgroundA composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.MethodsWe assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.ResultsThe analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.ConclusionThe GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

OBJECTIVE: The objective of this scoping review is to identify and describe the literature on the use of geospatial data in pediatric asthma research. INTRODUCTION: Asthma is one of the most common pediatric chronic diseases in the United States, disproportionately affecting low-income patients. Asthma exacerbations may be triggered by local environmental factors, such as air pollution or exposure to indoor allergens. Geographic information systems are increasingly recognized as tools that use geospatial data to enhance understanding of the link between environmental exposure, social determinants of health, and clinical outcomes. Geospatial data in pediatric asthma may help inform risk factors for asthma severity, and guide targeted clinical and social interventions. INCLUSION CRITERIA: This review will consider studies that utilize geospatial data in the evaluation of pediatric patients with asthma, ages 2 to 18 years, in the United States. Mixed samples of adults and children will also be considered. Geospatial data will include any external non-clinical geographic-based data source that uses a patients environment or context. METHODS: The following databases will be searched: PubMed, Embase, Cochrane CENTRAL, CINAHL, ERIC, Web of Science, and IEEE. Gray literature will be searched in DBLP, the US Environmental Protection Agency, Google Scholar, Google search, and a hand search of recent abstracts from relevant conferences. Articles published in English, Spanish, and French from 2010 to the present will be included. Study screening and selection will be performed independently by 2 reviewers. Data extraction will be performed by a trained research team member following pilot testing.

Diabetes Technology Society hosted its annual Diabetes Technology Meeting on November 12 to November 14, 2020. This meeting brought together speakers to cover various perspectives about the field of diabetes technology. The meeting topics included artificial intelligence, digital health, telemedicine, glucose monitoring, regulatory trends, metrics for expressing glycemia, pharmaceuticals, automated insulin delivery systems, novel insulins, metrics for diabetes monitoring, and discriminatory aspects of diabetes technology. A live demonstration was presented.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has rapidly involved the entire world and exposed the pressing need for collaboration between public health and other stakeholders from the clinical, scientific, regulatory, pharmaceutical, and medical device and technology communities. To discuss how to best protect people with diabetes from serious outcomes from COVID-19, Diabetes Technology Society, in collaboration with Sansum Diabetes Research Institute, hosted the "International COVID-19 and Diabetes Virtual Summit" on August 26-27, 2020. This unique, unprecedented real-time conference brought together physicians, scientists, government officials, regulatory experts, industry representatives, and people with diabetes from six continents to review and analyze relationships between COVID-19 and diabetes. Over 800 attendees logged in. The summit consisted of five sessions: (I) Keynotes, (II) Preparedness, (III) Response, (IV) Recovery, and (V) Surveillance; eight parts: (A) Background, (B) Resilience, (C) Outpatient Care, (D) Inpatient Care, (E) Resources, (F) High-Risk Groups, (G) Regulation, and (H) The Future; and 24 sections: (1) Historic Pandemics and Impact on Society, (2) Pathophysiology/Risk Factors for COVID-19, (3) Social Determinants of COVID-19, (4) Preparing for the Future, (5) Medications and Vaccines, (6) Psychology of Patients and Caregivers, (7) Outpatient Treatment of Diabetes Mellitus and Non-Pharmacologic Intervention, (8) Technology and Telehealth for Diabetes Outpatients, (9) Technology for Inpatients, (10) Management of Diabetes Inpatients with COVID-19, (11) Ethics, (12) Accuracy of Diagnostic Tests, (13) Children, (14) Pregnancy, (15) Economics of Care for COVID-19, (16) Role of Industry, (17) Protection of Healthcare Workers, (18) People with Diabetes, (19) International Responses to COVID-19, (20) Government Policy, (21) Regulation of Tests and Treatments, (22) Digital Health Technology, (23) Big Data Statistics, and 24) Patient Surveillance and Privacy. The two keynote speeches were entitled (1) COVID-19 and Diabetes-Meeting the Challenge and (2) Knowledge Gaps and Research Opportunities for Diabetes and COVID-19. While there was an emphasis on diabetes and its interactions with COVID-19, the panelists also discussed the COVID-19 pandemic in general. The meeting generated many novel ideas for collaboration between experts in medicine, science, government, and industry to develop new technologies and disease treatment paradigms to fight this global pandemic.

ObjectiveThe purpose of this report is to provide insight from pediatric stakeholders with a shared desire to facilitate a revision of the current United States regulatory pathways for the development of pediatric healthcare devices.MethodsOn August 5, 2020, a group of innovators, engineers, professors and clinicians met to discuss challenges and opportunities for the development of new medical devices for pediatric health and the importance of creating a regulatory environment that encourages and accelerates the research and development of such devices. On January 6, 2021, this group joined regulatory experts at a follow-up meeting.ResultsOne of the primary issues identified was the need to present decision-makers with opportunities that change the return-on-investment balance between adult and pediatric devices to promote investment in pediatric devices.Discussion/conclusionSeveral proposed strategies were discussed, and these strategies can be divided into two broad categories: 1. Removal of real and perceived barriers to pediatric device innovation; 2. Increasing incentives for pediatric device innovation.

Digital health is a rapidly developing field which is positioned to transform the manner in which healthcare is delivered, especially amongst adolescents and young adults. In order to assess the efficacy of novel medical devices, clinicians and researchers often turn to the literature for guidance. Randomized control trials and the systematic reviews and meta-analyses that they inform are considered to be at the top of the evidence hierarchy. While they are excellent tools to identify and to summarize the best available evidence to answer a specific research question, they are poorly equipped to provide a more expansive understanding of the body of relevant literature in a timely manner. In this letter we discuss the utility of the scoping review, an underutilized style of academic writing designed to map key concepts in a body of literature. This method is ideal when reporting on the fast-paced field of digital medicine, as it allows for rapid synthesis of the available literature.

In the present work, manganese cobaltite (MnCo2O4) spinel (MCO) was synthetized by Pechini and hydrothermal method, characterized and photocatalytically evaluated toward H2 production through water splitting under visible-light irradiation. Characterization consisted in Thermogravimetry analysis (TGA), X-ray diffraction (XRD), X-ray photoelectron spectroscopy, scattering transmission electronic microscopy, BET surface area, UV-Vis spectroscopy, cyclic voltammetry, Hall effect, and photoluminescence. The MCO were evaluated as photocatalyst using an artificial visible light lamp and monitored by gas chromatography. XRD analysis found a pure spinel phase MCO. The surface area was ∼5 m2·g−1 for the MCO synthetized by Pechini and increased to 155 m2·g−1 with the hydrothermal method with acetates as precursors. The Pechini MCO showed higher carrier mobility but the fastest recombination. Photocatalytic evaluation of the MCOs showed that the highest photocatalytic activity generated was 12 μmol H2/gcat at 8 h with the MCO obtained by hydrothermal method with the acetates.

Children with autism spectrum disorder are at increased risk for obesity compared to typically developing children. Many obesity intervention programs exclude children with autism spectrum disorder. There is little research on developmentally inclusive approaches to pediatric weight management. We examined the outcomes of children and families with autism spectrum disorder in an inclusive, comprehensive behavioral family-based lifestyle intervention. A secondary analysis of a randomized controlled trial on families enrolled in a comprehensive behavioral family-based lifestyle intervention was conducted. Analyses included chi-square or Fisher's exact tests to examine family and child differences in program completion rates and multivariate regression analysis using generalized estimating equation to further examine differences in weight outcomes between children with autism spectrum disorder versus no autism spectrum disorder accounting for other covariates. There were 158 families; 15 families had children with autism spectrum disorder. There were no significant differences in demographics, program completion, or weight outcomes between the two groups. Children who completed the intervention had a significant decrease in body mass index Z-scores, but no change in their percentage of the 95th percentiles. Families of children with autism spectrum disorder participated in a comprehensive behavioral family-based lifestyle intervention alongside children without autism spectrum disorder with similar outcomes. Comprehensive behavioral family-based lifestyle intervention can meet the weight management needs of children with autism spectrum disorder using an inclusive approach, expanding access to needed obesity interventions.

Biofouling in membrane filtration systems poses significant operational challenges, leading to decreased permeate flux. The aim of this work was to study the anti-biofilm properties of new nanofiltration membranes produced via layer-by-layer, LBL, assembly by coating a polyvinylidene fluoride (PVDF) support with a polyethylenimine (PEI) and poly(acrylic acid)/graphene oxide (PAA-GO) mixture. The membranes were characterized according to contact angle, scanning electron microscopy (SEM), atomic force microscopy and their Z-potential. Biofilm quantification and characterization were carried out using crystal violet staining and SEM, while bacterial viability was assessed by using colony-forming units. The membrane with three bilayers ((PAA-PEI)3/PVDF) showed a roughness of 77.78 nm. The incorporation of GO ((GO/PAA-PEI)3/PVDF) produced a membrane with a smoother surface (roughness of 26.92 nm) and showed salt rejections of 16% and 68% for NaCl and Na2SO4, respectively. A significant reduction, ranging from 82.37 to 77.30%, in biofilm formation produced by S. aureus and E. coli were observed on modified membranes. Additionally, the bacterial viability on the modified membranes was markedly reduced (67.42–99.98%). Our results show that the modified membranes exhibited both antibiofilm and antimicrobial capacities, suggesting that these properties mainly depend on the properties of the modifying agents, as the initial adherence on the membrane surface was not totally suppressed, but the proliferation and formation of EPSs were prevented. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of zero-valent iron nanoparticles (NZVI) on the anaerobic digestion of swine manure. A wide range of doses of NZVI was evaluated (5, 10, 15, 20, 25, 50, and 100 mgFe°/gVS). The maximum methane yield of 0.4506 L/gVSremoved was obtained with the concentration of 10 mgFe°/gVS representing an increase of 58.99% than the control system with 0.2834 L/gVSremoved, indicating that Fe° improves the methanogenic activity. However, when using doses greater than 20 mgFe°/gVS, there were decreases in the methane yield of 34.4–47.98%. Also, to observe the effect of NZVI in anaerobes was evaluated the activity in the electron transport system (ETS), where the control reactor showed an activity of 31.91 μg INTred/gVS•h, while in reactors with NZVI showed values of 39.48 μg INTred/gVS•h (10 Fe°mg/gVS), observing a stimulation of Fe° in microbial activity. However, the dose of 100 mgFe°/gVS showed the greatest decrease in methane yield (0.1474 L/gVSremoved) and a reduction in ETS was observed by 8.5% compared to the control. The effect on the composition of the volatile fatty acids was observed, where the control system obtained a maximum production of acetic acid of 639 mg/L, which was exceeded with the dose of 10 mg Fe°/gVS by 215% and a decrease of 41.15% with the inhibitory concentration of 100 mg Fe°/gVS. As a result, higher doses of NZVI affect the metabolic activity of anaerobes as well as the acetoclastic pathway causing a decrease in the methane production. [ABSTRACT FROM AUTHOR]

In response to the water contamination problem, this study presents a novel method to remove methylene blue (MB), a typical water pollutant, using synthesized porous silicon dioxide (SiO2). The SiO2 was synthesized via a cost-effective sol–gel method and characterized for its thermal stability, structural, textural, morphological properties, and elemental composition using techniques such as TGA, FT-IR, XRD, BET-BJH, SEM, TEM, and STEM-EDS. A unique aspect of this study is the evaluation of SiO2 reusability in MB removal through multiple adsorption and thermal regeneration cycles, a critical factor for practical applications. The results demonstrated the successful synthesis of thermally stable, amorphous, porous SiO2 with a surface area of 811 m2g−1 initially, reducing to 600 m2g−1 after the adsorption and regeneration cycles, indicating its stability and durability. The removal efficiency of MB was consistent across cycles, achieving 71.19 ± 0.94%, 75.55 ± 0.69%, and 73.49 ± 0.15% after 20 min, and the adsorption capacity at equilibrium was 3.73 ± 0.025, 4.08 ± 0.045, and 3.48 ± 0.021 mgMB gads−1 during the first, second, and third cycles, respectively. These findings highlight the potential of the synthesized porous SiO2 as a reusable and efficient adsorbent for MB removal in water treatment, contributing to the advancement of sustainable and effective solutions for water pollution. [ABSTRACT FROM AUTHOR]