ABSTRACT
Taylor Swift is arguably one of the most popular and influential celebrities. Of particular interest is her power as a role model for millions of fans across the world. Swift has spoken openly about different cultural issues, including her struggles with disordered eating and diet culture. Thus, the purpose of this paper was to explore whether Swift's disclosures of her own eating and body image struggles influenced her fans. Over 200 TikTok and Reddit posts related to Swift and eating disorders or body image, as well as their associated comments, were qualitatively coded to examine relevant themes. Key themes included: 1) Swift as a role model for disordered eating recovery; 2) use of or identification with specific Swift songs to illustrate struggles with eating or body image; 3) continued objectification of Swift's body; and 4) conflicted reaction to a scene in Swift's video for 'Anti-Hero' that depicted the word 'fat' on a scale. Overall, Swift's disclosures of her own eating/body image struggles positively influenced her fans' relationships with their eating behaviors and body image. This analysis illustrates the positive influence celebrities can have while also highlighting the limitations of personal disclosures to impact understanding of systemic issues like anti-fat bias.
ABSTRACT
Due to the pervasiveness of trauma, it is likely that many children and families seen in pediatric health settings have incurred traumatic experiences. These experiences can lead to a variety of negative medical, psychological, and social health outcomes. Therefore, a provider's focus on supporting resilience is integral. The use of trauma-informed care (TIC) is one way providers can work toward promoting a family's resilience. TIC is considered an organizational, attitudinal shift to understanding the broad impacts of trauma. This shift can contribute to changes in policies and procedures to make each system more welcoming to all those accessing the health system. This review will discuss the current pervasiveness of trauma, its associated impacts, the importance of TIC, and practical applications of TIC based on guiding principles provided by the Substance Abuse and Mental Health Services Administration. [Pediatr Ann. 2024;53(8):e299-e304.].
Subject(s)
Resilience, Psychological , Humans , Child , Adolescent , Family/psychology , Inpatients/psychology , Pediatrics/methodsABSTRACT
Scincidae is one of the most species-rich and cosmopolitan clades of squamate reptiles. Abundant disarticulated fossil material has also been attributed to this group, however, no complete pre-Cenozoic crown-scincid specimens have been found. A specimen in Burmite (99 MYA) is the first fossil that can be unambiguously referred to this clade. Our analyses place it as nested within extant skinks, supported by the presence of compound osteoderms formed by articulated small ostedermites. The specimen has a combination of dorsal and ventral compound osteoderms and overlapping cycloid scales that is limited to skinks. We propose that this type of osteoderm evolved as a response to an increased overlap of scales, and to reduced stiffness of the dermal armour. Compound osteoderms could be a key innovation that facilitated diversification in this megadiverse family.
Subject(s)
Amber , Fossils , Animals , Fossils/anatomy & histology , Lizards/anatomy & histology , Phylogeny , Biological EvolutionABSTRACT
Variants in SCN2A are a known risk factor for developing autism spectrum disorder (ASD). Catatonia is a complex neuropsychiatric syndrome, which occurs at a higher rate in individuals with ASD. Catatonia has also been associated with COVID-19 infection, though the majority of these cases are associated with increased serum inflammatory markers. We present a case of a 15-year-old female with ASD and corticosteroid responsive stuporous catatonia to explore the relationship between SCN2A variants, ASD, COVID-19 exposure, and treatment refractory catatonia. Despite a lack of significantly elevated serum or CSF inflammatory markers, this patient showed significant improvement following initiation of corticosteroid therapy. This case presents a novel approach to the work-up and treatment of catatonia in individuals with SCN2A variants independent of elevated inflammatory markers.
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PURPOSE: The presence of wheals or hives has been viewed as a hallmark symptom of urticaria, a highly debilitating disease. This study explores our experience with omalizumab in patients with apparent mast-cell mediated pruritus in the absence of hives. MATERIALS AND METHODS: This is a retrospective case series examining all patients with mast cell-mediated pruritus in the absence of hives from April 2022 to May 2024 at a tertiary referral clinic at Icahn School of Medicine at Mount Sinai in New York. Peak pruritus-numerical rating scale (PP-NRS) itch score changes over time were recorded and analyzed. RESULTS: Six patients (67% women; mean [SD] age, 47.67 [13.52] years) were included in the analysis. The median [IQR] pruritus PP-NRS itch score before omalizumab injection was 9 [6 - 10] and the final median [IQR] PP-NRS itch score was 2.5 [0 - 5]. The mean [SD] reduction in the PP-NRS itch score was 6 [3.16]. CONCLUSIONS: This study suggests that patients with evidence of mast cell-mediated pruritus can be identified based on clinical features and may benefit from omalizumab therapy.
Subject(s)
Mast Cells , Omalizumab , Pruritus , Humans , Omalizumab/therapeutic use , Omalizumab/administration & dosage , Female , Pruritus/drug therapy , Pruritus/etiology , Male , Middle Aged , Retrospective Studies , Adult , Mast Cells/drug effects , Mast Cells/immunology , Anti-Allergic Agents/therapeutic use , Anti-Allergic Agents/administration & dosage , Treatment Outcome , Severity of Illness Index , Urticaria/drug therapyABSTRACT
mRNA-based gene editing platforms have tremendous promise in the treatment of genetic diseases. However, for this potential to be realized in vivo, these nucleic acid cargos must be delivered safely and effectively to cells of interest. Ionizable lipid nanoparticles (LNPs), the most clinically advanced non-viral RNA delivery system, have been well-studied for the delivery of mRNA but have not been systematically optimized for the delivery of mRNA-based CRISPR-Cas9 platforms. In this study, we investigated the effect of microfluidic and lipid excipient parameters on LNP gene editing efficacy. Through in vitro screening in liver cells, we discovered distinct trends in delivery based on phospholipid, cholesterol, and lipid-PEG structure in LNP formulations. Combination of top-performing lipid excipients produced an LNP formulation that resulted in 3-fold greater gene editing in vitro and facilitated 3-fold greater reduction of a therapeutically-relevant protein in vivo relative to the unoptimized LNP formulation. Thus, systematic optimization of LNP formulation parameters revealed a novel LNP formulation that has strong potential for delivery of gene editors to the liver to treat metabolic disease.
Subject(s)
Gene Editing , Lipids , Nanoparticles , Nanoparticles/chemistry , Lipids/chemistry , Humans , Animals , Excipients/chemistry , CRISPR-Cas Systems , Mice , Lab-On-A-Chip Devices , LiposomesABSTRACT
Monogenic blood diseases are among the most common genetic disorders worldwide. These diseases result in significant pediatric and adult morbidity, and some can result in death prior to birth. Novel ex vivo hematopoietic stem cell (HSC) gene editing therapies hold tremendous promise to alter the therapeutic landscape but are not without potential limitations. In vivo gene editing therapies offer a potentially safer and more accessible treatment for these diseases but are hindered by a lack of delivery vectors targeting HSCs, which reside in the difficult-to-access bone marrow niche. Here, we propose that this biological barrier can be overcome by taking advantage of HSC residence in the easily accessible liver during fetal development. To facilitate the delivery of gene editing cargo to fetal HSCs, we developed an ionizable lipid nanoparticle (LNP) platform targeting the CD45 receptor on the surface of HSCs. After validating that targeted LNPs improved messenger ribonucleic acid (mRNA) delivery to hematopoietic lineage cells via a CD45-specific mechanism in vitro, we demonstrated that this platform mediated safe, potent, and long-term gene modulation of HSCs in vivo in multiple mouse models. We further optimized this LNP platform in vitro to encapsulate and deliver CRISPR-based nucleic acid cargos. Finally, we showed that optimized and targeted LNPs enhanced gene editing at a proof-of-concept locus in fetal HSCs after a single in utero intravenous injection. By targeting HSCs in vivo during fetal development, our Systematically optimized Targeted Editing Machinery (STEM) LNPs may provide a translatable strategy to treat monogenic blood diseases before birth.
Subject(s)
Gene Editing , Hematopoietic Stem Cells , Nanoparticles , Animals , Hematopoietic Stem Cells/metabolism , Gene Editing/methods , Nanoparticles/chemistry , Mice , Female , Pregnancy , Lipids/chemistry , Leukocyte Common Antigens/metabolism , Leukocyte Common Antigens/genetics , Humans , Genetic Therapy/methods , CRISPR-Cas Systems , LiposomesABSTRACT
BACKGROUND: Less moderate to vigorous physical activity (MVPA), more sedentary time (ST), and higher perceived stress are related to type 2 diabetes mellitus (T2DM) occurrence, but observational evidence addressing the interaction of these factors is lacking in youth. This pilot study investigated momentary stress as a moderator in the acute associations of MVPA and ST with subsequent glucose in healthy adolescents. METHODS: Participants (N=15, Mage=13.1±1.0 years, 10 girls, 5 with overweight/obesity) simultaneously wore a continuous glucose monitor (CGM), thigh-mounted accelerometer, and reported momentary stress via random ecological momentary assessments (EMA; Time T) for 7-14 days. MVPA and ST (min) were calculated for 60- and 120-minute time windows before each EMA prompt (Time T-1). Mean CGM-measured interstitial glucose (mg/dL) was calculated after each prompt (Mmin=120.0±25.4; Time T+1). Multilevel models assessed whether within-subject MVPA and ST (Time T-1) predicted mean glucose (Time T+1), with momentary stress as a moderator (Time T). RESULTS: There were 513 time-matched EMA reports of stress, accelerometer, and CGM data. Momentary stress moderated the effects of MVPA 60 (ß=-0.22, p=.001) and 120 min (ß=-0.08, p=.02) before the prompt on subsequent glucose levels. When youth spent more time in MVPA than their average and when momentary stress was higher than their average, subsequent glucose was lower. Stress did not moderate associations of ST with glucose (p>.05). CONCLUSIONS: Higher momentary stress may interact with higher MVPA to lower subsequent glucose in youth. Accelerometers, EMA, and CGMs can be integrated in future studies to further understand these associations in free-living environments.
Subject(s)
Accelerometry , Exercise , Sedentary Behavior , Stress, Psychological , Humans , Female , Adolescent , Male , Stress, Psychological/physiopathology , Stress, Psychological/metabolism , Exercise/physiology , Exercise/psychology , Pilot Projects , Ecological Momentary Assessment , Blood Glucose/metabolism , Child , Glucose/metabolismABSTRACT
Metals are important cofactors in the metabolic processes of cyanobacteria, including photosynthesis, cellular respiration, DNA replication, and the biosynthesis of primary and secondary metabolites. In adaptation to the marine environment, cyanobacteria use metallophores to acquire trace metals when necessary as well as to reduce potential toxicity from excessive metal concentrations. Leptochelins A-C were identified as structurally novel metallophores from three geographically dispersed cyanobacteria of the genus Leptothoe. Determination of the complex structures of these metabolites presented numerous challenges, but they were ultimately solved using integrated data from NMR, mass spectrometry and deductions from the biosynthetic gene cluster. The leptochelins are comprised of halogenated linear NRPS-PKS hybrid products with multiple heterocycles that have potential for hexadentate and tetradentate coordination with metal ions. The genomes of the three leptochelin producers were sequenced, and retrobiosynthetic analysis revealed one candidate biosynthetic gene cluster (BGC) consistent with the structure of leptochelin. The putative BGC is highly homologous in all three Leptothoe strains, and all possess genetic signatures associated with metallophores. Postcolumn infusion of metals using an LC-MS metabolomics workflow performed with leptochelins A and B revealed promiscuous binding of iron, copper, cobalt, and zinc, with greatest preference for copper. Iron depletion and copper toxicity experiments support the hypothesis that leptochelin metallophores may play key ecological roles in iron acquisition and in copper detoxification. In addition, the leptochelins possess significant cytotoxicity against several cancer cell lines.
Subject(s)
Cyanobacteria , Cyanobacteria/metabolism , Cyanobacteria/chemistry , Cyanobacteria/genetics , Humans , Multigene Family , Cell Line, Tumor , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/metabolismABSTRACT
PURPOSE: Because some stakeholders within medicine seek to diversify and attain greater workforce equity, it is critical to understand gender-based divisions within specialization. Radiation oncology (RO) has one of the smallest proportions of women representation of all specialties, and to our knowledge, no prior studies have investigated gender differences in all the disease site specializations within RO. Thus, we analyzed the relationship between gender and disease site(s) treated in academic RO (ARO). METHODS AND MATERIALS: Faculty gender and disease site(s) treated by faculty from ARO departments were collected via publicly available department websites in January 2020. X2 analyses were conducted to assess differences between the proportions of women faculty treating each disease site. RESULTS: Of 1337 ARO faculty, 408 (30.5%) were identified as women. Breast, gynecology, and pediatrics had the largest proportions of women faculty (all >40%; P < .001). A majority (53%; P < .001) of women ARO faculty treated breast. Genitourinary, thoracic, and head and neck had the smallest proportions of women faculty (all <25%; P < .001). Women ARO faculty were twice as likely to treat breast and gynecologic malignancies compared with men faculty (risk ratio [RR] with 95% CI, 2.01 [1.75-2.50]; P < .001 and RR [95% CI], 2.06 [1.72-2.79]; P <.001, respectively). Men ARO faculty were 3 times more likely to treat genitourinary cancer compared with women faculty (RR [95% CI], 0.40 [0.34-0.48]; P < .001). There was no difference in the mean number of disease sites treated between women and men ARO faculty (2.63 vs 2.53; P = .29). CONCLUSIONS: Gender differences in disease site specialization were observed in ARO. Future research into the drivers of disease site selection should be explored.
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The triarchic model posits that distinct trait constructs of boldness, meanness, and disinhibition underlie psychopathy. The triarchic model traits are conceptualized as biobehavioral dimensions that can be assessed using different sets of indicators from alternative measurement modalities; as such, the triarchic model would hypothesize that these traits are not confined to any one item set. The present study tested whether the triarchic model dimensions would emerge from a hierarchical-structural analysis of the facet scales of the Elemental Psychopathy Assessment (EPA), an inventory designed to comprehensively index psychopathy according to the five-factor personality model. Study participants (Ns = 811, 170) completed the EPA and three different scale sets assessing the triarchic traits along with criterion measures of antisocial/externalizing behaviors. Bass-ackwards modeling of the EPA facet scales revealed a four-level structure, with factors at the third level appearing similar to the triarchic trait dimensions. An analysis in which scores for the Level-3 EPA factors were regressed onto corresponding latent-trait dimensions defined using the different triarchic scale sets revealed extremely high convergence (ßs = .84-.91). The Level-3 EPA factors also evidenced validity in relation to relevant criteria, approximating and sometimes exceeding that evident for the Level-4 EPA factors. Together, these results indicate that the triarchic trait constructs are embedded in a psychopathy inventory designed to align with a general personality model and effectively predict pertinent external criteria. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Subject(s)
Antisocial Personality Disorder , Models, Psychological , Humans , Male , Female , Adult , Antisocial Personality Disorder/psychology , Antisocial Personality Disorder/diagnosis , Young Adult , Adolescent , Psychometrics , Personality Inventory , Middle Aged , PersonalityABSTRACT
PURPOSE: Patients with cervical cancer undergoing chemoradiation have high symptom burden. We performed an analysis of prospectively collected data on patient-reported outcomes to determine characteristics predictive of poor treatment experience. METHODS AND MATERIALS: Between 2021 and 2023, we prospectively collected data on patient-reported outcomes from patients with cervical cancer undergoing definitive chemoradiation. The European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Question-Core 30 and the EORTC-Quality of Life Question-Cervical Cancer module were completed at baseline (BL) and at the end of treatment (EOT). Poor treatment experience was defined as EOT poor health-related quality of life (HRQOL), low physical function, or significant overall symptom burden. Predictive factors analyzed included demographic, clinical, and disease-specific factors and BL financial toxicity, depression, social function, and emotional function. Receiver operating characteristic analysis provided appropriate predictive cutoff values. Univariable and multivariable (MVA) linear regression analyses were performed. RESULTS: Forty-nine patients completed BL and EOT questionnaires. Median age was 43 years (range, 18-85 years). Most patients (59%) had stage III disease. BL financial toxicity ≥66.7, depression ≥66.7, social function ≤50, and emotional function ≤58 on the EORTC linear transformed scale of 0 to 100 were significant predictors for poor treatment experience (p ≤ .04) based on receiver operating characteristic analysis. On MVA, poor BL social function was associated with reduced EOT HRQOL (ß, -9.3; 95% CI, -16.1 to -2.6; p < .008), decreased physical function (ß, -24.4; 95% CI, -36.3 to -12.6; p < .001), and high symptom burden (ß, 26.9; 95% CI, 17.5-36.3; p < .001). Earlier disease stage predicted decreased symptom burden (ß, -6.7; 95% CI, -13.1 to -0.3; p = .039). BL financial toxicity was a significant predictor in univariable analysis (p = .001-.044) and showed a significant interaction term on MVA (p = .024-.041) for all 3 domains of poor treatment experience. Demographic and treatment-related factors were not predictive. CONCLUSIONS: Patients with cervical cancer with poor BL social function or high financial toxicity were at risk for increased symptom burden and poor HRQOL. Screening for these factors provides an opportunity for early intervention to improve treatment experience.
ABSTRACT
Immune modulation through the intracellular delivery of nucleoside-modified mRNA to immune cells is an attractive approach for in vivo immunoengineering, with applications in infectious disease, cancer immunotherapy, and beyond. Lipid nanoparticles (LNPs) have come to the fore as a promising nucleic acid delivery platform, but LNP design criteria remain poorly defined, making the rate-limiting step for LNP discovery the screening process. In this study, we employed high-throughput in vivo LNP screening based on molecular barcoding to investigate the influence of LNP composition on immune tropism with applications in vaccines and systemic immunotherapies. Screening a large LNP library under both intramuscular (i.m.) and intravenous (i.v.) injection, we observed differential influences on LNP uptake by immune populations across the two administration routes, gleaning insight into LNP design criteria for in vivo immunoengineering. In validation studies, the lead LNP formulation for i.m. administration demonstrated substantial mRNA translation in the spleen and draining lymph nodes with a more favorable biodistribution profile than LNPs formulated with the clinical standard ionizable lipid DLin-MC3-DMA (MC3). The lead LNP formulations for i.v. administration displayed potent immune transfection in the spleen and peripheral blood, with one lead LNP demonstrating substantial transfection of splenic dendritic cells and another inducing substantial transfection of circulating monocytes. Altogether, the immunotropic LNPs identified by high-throughput in vivo screening demonstrated significant promise for both locally- and systemically-delivered mRNA and confirmed the value of the LNP design criteria gleaned from our screening process, which could potentially inform future endeavors in mRNA vaccine and immunotherapy applications.
Subject(s)
Lipids , Mice, Inbred C57BL , Nanoparticles , RNA, Messenger , Animals , Nanoparticles/chemistry , RNA, Messenger/genetics , Mice , Lipids/chemistry , High-Throughput Screening Assays , Female , Injections, Intramuscular , Dendritic Cells/immunology , Dendritic Cells/metabolism , Injections, Intravenous , Immunotherapy , LiposomesABSTRACT
BACKGROUND: Parents commonly seek online sources of information on the important complementary feeding period, but the accuracy of these sources varies. The 21st Century Integrated Digital Experience Act (IDEA) states federal government resources should be accurate and user-friendly; however, the quantity, quality, and accuracy of federal resources on complementary feeding is unknown. METHODS: An environmental scan of online federal, parent-facing resources about complementary feeding was conducted. The authors reviewed federal resources for concordance of information with the Dietary Guidelines for Americans (DGA). Quality was evaluated using the Patient Education Materials Assessment Tool. RESULTS: A total of 112 resources across 2 federal government departments. Overall quality was high as was concordance with recommendations from the DGA for age of complementary food introduction, foods to introduce, and foods to avoid. Allergenic food introduction and textured food progression recommendations were less consistent. Recommendations for improvements to federal resources are made. CLINICAL IMPLICATIONS: This environmental scan only included federal resources for CF. Parents may be accessing other, non-federal resources online. However, given the enactment of IDEA, it is expected that these federal resources will be up-to-date and user-friendly, which was not always the case. Nurses should review the DGA guidelines for complementary feeding and provide evidence-based anticipatory guidance to families, focusing especially on allergenic food introduction and textured food progression. Future complementary feeding interventions may benefit from directing families to online exemplars from federal sources.
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BACKGROUND: Disease outbreaks present a significant challenge to horse health and welfare and the economic stability of horse industries internationally. This is a particular concern in Ontario, Canada, where there have been frequent outbreaks of respiratory infectious diseases among horses. Despite these risks, there has been limited research on whether Ontario horse owners engage in biosecurity measures sufficient to mitigate risk of equine diseases, and whether current events such as the COVID-19 pandemic influence attitudes towards equine biosecurity practices. OBJECTIVE: To explore Ontario horse owners' perceptions, attitudes and experiences relating to on-farm biosecurity during the COVID-19 pandemic. STUDY DESIGN: Qualitative study using virtual semi-structured interviews. METHODS: Participants (horse owners, frequent horse riders and part boarders) were recruited using social media snowball sampling where advertisements were shared by equine and veterinary organisations. Interviews were conducted virtually between June and September 2022 and were analysed using reflexive thematic analysis. RESULTS: Three key themes relating to biosecurity perceptions among the 14 participants were identified. Participants relied on minimal preventative measures (such as vaccines) where perceived risk of disease was low, but implemented additional measures including quarantine and handwashing when perceived risk of disease was high. Participants' choice of biosecurity practices often mirrored those recommended by the barn manager. Moreover, participants felt that responsibility for biosecurity was not shared equally across horse owners, with more emphasis placed on those engaging in high-risk situations for disease spread. Despite experiencing biosecurity during the COVID-19 pandemic, horse owners were not consistently applying these practices to their horse care routines. MAIN LIMITATIONS: The perspectives reported here are from a small sample of horse owners and may not be generalisable to all populations. CONCLUSIONS: Our findings indicate that horse owners need improved access to and engagement with educational initiatives that emphasise the importance and purpose of all biosecurity measures.
ABSTRACT
People often interact with groups (i.e., ensembles) during social interactions. Given that group-level information is important in navigating social environments, we expect perceptual sensitivity to aspects of groups that are relevant for personal threat as well as social belonging. Most ensemble perception research has focused on visual ensembles, with little research looking at auditory or vocal ensembles. Across four studies, we present evidence that (i) perceivers accurately extract the sex composition of a group from voices alone, (ii) judgments of threat increase concomitantly with the number of men, and (iii) listeners' sense of belonging depends on the number of same-sex others in the group. This work advances our understanding of social cognition, interpersonal communication, and ensemble coding to include auditory information, and reveals people's ability to extract relevant social information from brief exposures to vocalizing groups.
Subject(s)
Voice , Humans , Male , Female , Adult , Sex Ratio , Social Perception , Young Adult , Auditory Perception/physiology , Interpersonal Relations , Social InteractionABSTRACT
This economic evaluation estimates the out-of-pocket cost savings patients could achieve if generic drugs were purchased directly from the Mark Cuban Cost Plus Drug Company rather than using their health insurance.
Subject(s)
Drug Industry , Drugs, Generic , Drugs, Generic/economics , Drugs, Generic/therapeutic use , Humans , Cuba , Drug Industry/economics , Cost Savings , Drug Costs , Female , MaleABSTRACT
BACKGROUND: In the United States, caregivers of people living with Alzheimer disease and Alzheimer disease-related dementias (AD/ADRD) provide >16 billion hours of unpaid care annually. These caregivers experience high levels of stress and burden related to the challenges associated with providing care. Social media is an emerging space for individuals to seek various forms of support. OBJECTIVE: We aimed to explore the primary topics of conversation on the social media site Reddit related to AD/ADRD. We then aimed to explore these topics in depth, specifically examining elements of social support and behavioral symptomology discussed by users. METHODS: We first generated an unsupervised topic model from 6563 posts made to 2 dementia-specific subreddit forums (r/Alzheimers and r/dementia). Then, we conducted a manual qualitative content analysis of a random subset of these data to further explore salient themes in the corpus. RESULTS: The topic model with the highest overall coherence score (0.38) included 10 topics, including caregiver burden, anxiety, support-seeking, and AD/ADRD behavioral symptomology. Qualitative analyses provided added context, wherein users sought emotional and informational support for many aspects of the care experience, including assistance in making key care-related decisions. Users expressed challenging and complex emotions on Reddit, which may be taboo to express in person. CONCLUSIONS: Reddit users seek many different forms of support, including emotional and specific informational support, from others on the internet. Users expressed a variety of concerns, challenges, and behavioral symptoms to manage as part of the care experience. The unique (ie, anonymous and moderated) nature of the forum allowed for a safe space to express emotions free from documented caregiver stigma. Additional support structures are needed to assist caregivers of people living with AD/ADRD.
Subject(s)
Alzheimer Disease , Caregivers , Qualitative Research , Social Media , Humans , Caregivers/psychology , Alzheimer Disease/psychology , Alzheimer Disease/nursing , Aged , Social Support , Female , Male , Dementia/psychology , Dementia/nursing , United States/epidemiology , Caregiver Burden/psychologyABSTRACT
The full potential of ionizable lipid nanoparticles (LNPs) as an in vivo nucleic acid delivery platform has not yet been realized given that LNPs primarily accumulate in the liver following systemic administration, limiting their success to liver-centric conditions. The engineering of LNPs with antibody targeting moieties can enable extrahepatic tropism by facilitating site-specific LNP tethering and driving preferential LNP uptake into receptor-expressing cell types via receptor-mediated endocytosis. Obstetric conditions stemming from placental dysfunction, such as preeclampsia, are characterized by overexpression of cellular receptors, including the epidermal growth factor receptor (EGFR), making targeted LNP platforms an exciting potential treatment strategy for placental dysfunction during pregnancy. Herein, an EGFR antibody-conjugated LNP (aEGFR-LNP) platform was developed by engineering LNPs with increasing densities of antibody functionalization. aEGFR-LNPs were screened in vitro in immortalized placental trophoblasts and in vivo in non-pregnant and pregnant mice and compared to non-targeted formulations for extrahepatic, antibody-targeted mRNA LNP delivery to the placenta. Our top performing LNP with an intermediate density of antibody functionalization (1:5 aEGFR-LNP) mediated a â¼twofold increase in mRNA delivery in murine placentas and a â¼twofold increase in LNP uptake in EGFR-expressing trophoblasts compared to non-targeted counterparts. These results demonstrate the potential of antibody-conjugated LNPs for achieving extrahepatic tropism, and the ability of aEGFR-LNPs in promoting mRNA delivery to EGFR-expressing cell types in the placenta.
Subject(s)
ErbB Receptors , Lipids , Nanoparticles , Placenta , RNA, Messenger , Female , Animals , ErbB Receptors/metabolism , Pregnancy , Placenta/metabolism , Nanoparticles/chemistry , RNA, Messenger/administration & dosage , Lipids/chemistry , Humans , Mice , Trophoblasts/metabolism , LiposomesABSTRACT
BACKGROUND: Pediatric feeding disorder (PFD) is increasingly common and is often treated by speech language pathologists (SLPs) and occupational therapists (OTs) in the community setting. However, the preparedness of these disciplines to effectively address PFD is relatively unknown. METHODS: A national (US), online survey was disseminated to providers who assess and treat PFD. For the present analysis, the responses of SLPs (N = 418) and OTs (N = 195) related to their clinical background, educational background, post-graduate training, and self-rated clinical effectiveness were statistically analyzed and compared across the two disciplines. RESULTS: Both SLPs and OTs report feeling underprepared to work with PFD clients immediately following their academic training, but time spent in post-graduate training and years of clinical practice both significantly (p < 0.0001) increased feelings of effectiveness in assessing and treating PFD. Most SLPs and OTs pursued self-directed learning activities to increase competence, with the most common activities being article review, podcasts, and peer case review, although SLPs were significantly more likely to use podcasts (p < 0.0001) and peer review (p = 0.0004) than OTs. The most common barriers for providers were financial, time, travel, and institutional support barriers. CONCLUSIONS: While PFD is a key practice area of both SLPs and OTs, both provider groups feel unprepared and under-supported in providing competent care to these patients upon graduation. Future research and policy should support advancements in training for current SLPs and OTs related to PFD and address current barriers to a specialized educational pathway.