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CO2-based aliphatic polycarbonates (aPCs), produced through the alternating copolymerization of epoxides with CO2, present an appealing option for sustainable polymeric materials owing to their renewable feedstock and degradable characteristics. An ongoing challenge in working with aPCs is modifying their mechanical properties to meet specific demands. Herein, we report that monomer ratio and polymer architecture of aPCs impact not only printability by digital light processing (DLP) additive manufacturing, but also dictate the thermomechanical and degradation properties of the printed objects. We found that block copolymers exhibit tailorable thermomechanical properties ranging from soft elastomeric to strong and brittle as the proportion of hard blocks increases, whereas the homopolymer blend failed to print objects and statistical copolymers delaminated or overcured, displaying the weakest mechanical properties. In addition, the hydrolytic degradation of the prints was demonstrated under various conditions, revealing that BCP prints containing a higher proportion of hard blocks had slower degradation and that statistical copolymer prints degraded more slowly than their BCP counterparts. This study underscores that polymer composition and architecture both play key roles in resin printability and bulk properties, offering significant prospects for advancing sustainable materials in additive manufacturing through polymer design.
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CASE HISTORY: In spring 2021, on a seasonally calving, pastorally based, Taranaki dairy farm, 12 first-calving heifers (≤ 30 days post-calving) developed similar dry, red to black, crusting lesions on the medial aspect of the teat udder junction extending down the medial teat. Some cows had multiple teats affected. Treatment was initially unrewarding and did not slow the progression of the disease. Overall, 8/12 cows recovered, and 4/12 cows were culled, with three of the cows culled after a teat sloughed and the fourth after surgical amputation of a teat. Outbreaks of the same condition, on the same farm but affecting fewer animals, occurred in spring 2022 (n = 6) and spring 2023 (n = 3). CLINICAL FINDINGS: An initial scab-like or crusting lesion progressed to resemble a thick eschar consisting of very dry and hard dead tissue. The unaffected areas of the teat felt normal but immediately under the dead tissue, there was a warm, firmer area consistent with an inflammatory reaction. Removing the scab led to profuse bleeding, with no visible bed of granulation underneath the scab. There was no leaking of milk in those cows that lost a teat, and no smell to the lesions themselves. Serology and virology ruled out the involvement of bovine alphaherpesvirus (BoHV-2) bovine gammaherpesvirus (BoHV-4), orthopoxviruses (cowpox) and parapoxviruses (pseudocowpox). Histopathology of an affected and surgically amputated teat showed multifocal erosion and ulceration of the epidermis, covered by a thick serocellular crust. In areas of ulceration, there were numerous neutrophils, and the dermis was expanded by granulation tissue with variable numbers of neutrophils, eosinophils, and lymphocytes around small blood vessels. DIAGNOSIS: Based on the similarity of the history, presentation, and histopathological changes to those described for a novel disease reported in the UK, a diagnosis of ischaemic teat necrosis (ITN) was made. CLINICAL RELEVANCE: If ITN is an emerging condition in New Zealand and becomes as prevalent as it has in the UK, clinicians will be confronted with a significant new welfare problem in dairy cows. Anecdotally, there have been reports of other ITN outbreaks in New Zealand, and the Ministry for Primary Industries would be interested in collating reports from other New Zealand veterinarians.
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Control of algal blooms and associated biologically-induced water quality risks in drinking reservoirs is problematic. Copper sulphate (CuSO4) treatment is one intervention that has been utilised for >100 years. Evidence indicates a favourable short-term reduction in Cyanobacterial biomass (e.g. bloom termination), but here we indicate that it may also increase longer-term water quality risk. In 2022, we investigated the impacts of CuSO4 spraying on Cyanobacterial communities and nutrient levels within a drinking water supply reservoir using environmental DNA (eDNA) to assess community shifts, alongside monitoring nutrient fractions, orthophosphate (OP) and total phosphate (TP), post-treatment. CuSO4 application successfully reduced Cyanobacterial abundance, however elimination of Cyanobacteria resulted in a shift in bacterial dominance favouring Planctomycetota throughout the summer and a combination of Actinobacteriota and Verrucomicrobiota, throughout autumn. As Cyanobacterial abundance recovered post-treatment, Cyanobacterial genera demonstrated greater diversity compared to only three Cyanobacterial genera present across samples pre-treatment, and included taxa associated with water quality risk (e.g. taste and odour (T&O) metabolite and toxin producers). The increase in Cyanobacteria post-treatment was attributed to an increase in biologically available nutrients, primarily a significant increase in OP. Overall, findings suggest that the significant shift in biodiversity likely induces a less stable ecosystem with greater plasticity of response to changing environmental and biogeochemical variables. Legacy implications of CuSO4 spraying, in terms of shifts in ecosystem and nutrient balance over time, may have implications for drinking water quality, but importantly also for reservoir management options. As such, the effects of CuSO4 spraying should be considered carefully before consideration as a contender for in-reservoir biological control.
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Sulfato de Cobre , Cianobactérias , Qualidade da Água , Cianobactérias/efeitos dos fármacos , EutrofizaçãoRESUMO
BACKGROUND: Despite a glaring need and proven efficacy, prospective surgical registries are lacking in low- and middle-income countries. The objective of this study was to design and implement a comprehensive prospective perioperative registry in a low-income country. METHODS: This study was conducted at Hawassa University Comprehensive Specialized Hospital in Hawassa, Ethiopia. Design of the registry occurred from June 2021 to May 2022 and pilot implementation from May 2022 to May 2023. All patients undergoing elective or emergent general surgery were included. Following one year, operability and fidelity of the registry were analyzed by assessing capture rate, incidence of missing data, and accuracy. RESULTS: A total of 67 variables were included in the registry including demographics, preoperative, operative, post-operative, and 30-day data. Of 440 eligible patients, 226 (51.4%) were successfully captured. Overall incidence of missing data and accuracy was 5.4% and 90.2% respectively. Post pilot modifications enhanced capture rate to 70.5% and further optimized data collection processes. CONCLUSION: The establishment of a low-cost electronic prospective perioperative registry in a low-income country represents a significant step forward in enhancing surgical care in under-resourced settings. The initial success of this registry highlights the feasibility of such endeavors when strong partnerships and local context are at the center of implementation. Continuous efforts to refine this registry are ongoing, which will ultimately lead to enhanced surgical quality, research output, and expansion to other sites.
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Melhoria de Qualidade , Sistema de Registros , Etiópia , Humanos , Estudos Prospectivos , Feminino , Masculino , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/normas , Adulto , Pessoa de Meia-Idade , Países em Desenvolvimento , Projetos Piloto , Assistência Perioperatória/normasRESUMO
OBJECTIVE: This study examined associations of school readiness measures obtained before school entry with academic achievement at early school age in children born very preterm (VPT, gestational age ≤ 30 weeks) and children born full term (FT, GA ≥ 37 weeks). METHOD: The sample included 38 children born VPT and 30 born FT recruited at age 4 years and followed to early school age. Measures of readiness included tests of global cognition, executive function, motor abilities, and preacademic skills, as well as caregiver behavior ratings. Tests of math, reading, and spelling were administered to assess school-age achievement. Analyses that controlled for socioeconomic status and accounted for inclusion of siblings compared the groups on the achievement tests and identified measures of readiness related to school-age achievement. RESULTS: Achievement difficulties were more pronounced in the VPT group and associated with problems in multiple readiness domains. Effect sizes for these associations were largest for measures of spatial ability, executive function, and preacademic skills. Some associations remained significant when controlling for global cognitive ability at age 4 years, and others were significant only for the VPT group. CONCLUSION: Findings suggest that deficits on tests in multiple readiness domains assessed before school entry in children born VPT or FT are associated with early school-age achievement. The most pronounced readiness deficits in the VPT group at age 4 years were also among those most closely associated with later difficulties in achievement. Further research is needed to refine assessment of school readiness in children born VPT.
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Sucesso Acadêmico , Desenvolvimento Infantil , Lactente Extremamente Prematuro , Humanos , Masculino , Feminino , Pré-Escolar , Lactente Extremamente Prematuro/fisiologia , Desenvolvimento Infantil/fisiologia , Função Executiva/fisiologia , CriançaRESUMO
CASE HISTORY: A line of 25 cull cows were all found to have ulcerative lesions of the tongue at post-mortem inspection in a New Zealand slaughter plant. A further 9 of 10 cows inspected at the farm of origin had similar oral lesions. There were no other clinical signs or indicators of ill-health observed at ante-mortem inspection in the abattoir or on the farm. The cows had been fed baleage for 3 weeks prior to slaughter, made from pasture in paddocks heavily contaminated with yellow bristle grass (Setaria pumila). CLINICAL FINDINGS: There was extensive and deep transverse linear ulceration in the lingual fossa immediately rostral to the torus linguae. At histological examination, full-thickness ulceration of the stratified squamous epithelium was observed with a bed of disorganised collagenous tissue and extensive mixed inflammatory infiltrate extending into the sub-epithelial connective tissue and skeletal muscle. Barbed plant fragments were embedded in both the superficial and deeper areas of inflammation. Detailed examination of the baleage also found that yellow bristle grass seedheads were present. DIAGNOSIS: Based on the presence of barbed plant material in the tongue and yellow bristle grass seeds in the baleage, a diagnosis of ulcerative stomatitis associated with yellow bristle grass was made. CLINICAL RELEVANCE: Clinicians should be aware of the potential for hay or baleage contaminated with yellow bristle grass to cause oral lesions in cattle.
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Doenças dos Bovinos , Animais , Bovinos , Nova Zelândia/epidemiologia , Feminino , Doenças dos Bovinos/patologia , Doenças dos Bovinos/epidemiologia , Estomatite/veterinária , Estomatite/patologia , Poaceae , Língua/patologia , Ração Animal/análiseRESUMO
Urinary tract infection (UTI) is one of the most common bacterial infections worldwide. The main causative agent of UTI is uropathogenic Escherichia coli (UPEC). There is an immediate need for novel prophylactic and treatment strategies against UTI because of the increasing incidence of antimicrobial resistance among uropathogens. ABU 83972, an asymptomatic bacteriuria-causing E. coli strain, prevents UTI by suppressing the colonization of UPEC. However, the nature of competition and growth repression of UPEC by ABU 83972 is unclear and is the subject of our investigation. Here, we characterized the growth kinetics of ABU 83972 and uropathogens in human urine and laboratory media. Next, we performed a series of competitive co-culture experiments where ABU 83972 and uropathogens were inoculated at a 1:1 ratio in human urine and in various media, and their relative abundance was determined. In human urine, ABU 83972 outcompeted UPEC and additional uropathogens, reaching up to 90% of the total population after 24 hours of incubation. In contrast, UPEC outcompeted ABU 83972 in LB and M9 minimal media and exhibited superior colonization than ABU 83972 in the mouse urinary bladder. Since engineered living materials (ELMs) can be used to retain an organism of interest in a particular location, we developed ABU 83972-containing ELMs that effectively outcompeted UPEC in human urine. In summary, our work establishes that ABU 83972 outcompetes UPEC in a milieu- and cell-density-dependent manner, highlighting the importance of the metabolites and nutrients found in the human urine as determinants of the competitive fitness of ABU 83972.
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Bacteriúria , Infecções por Escherichia coli , Infecções Urinárias , Escherichia coli Uropatogênica , Humanos , Bacteriúria/microbiologia , Animais , Escherichia coli Uropatogênica/genética , Escherichia coli Uropatogênica/efeitos dos fármacos , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/urina , Infecções Urinárias/microbiologia , Camundongos , Feminino , Urina/microbiologia , Escherichia coli/genética , Escherichia coli/efeitos dos fármacosRESUMO
Background: Gender-affirming breast augmentation comprises an increasing portion of breast augmentations performed by plastic surgeons. Satisfaction and breast implant illness (BII) symptoms in this population have not been well studied. This study aimed to evaluate satisfaction and BII symptoms in transwomen who received nontextured implants as part of their breast reconstruction. Methods: We conducted a retrospective review of transwomen who underwent breast augmentation for gender-affirming surgery. We performed telephone survey evaluation using the BREAST-Q questionnaire preoperatively, 6 months and 1 year after breast implant placement. Survey evaluation asking about BII symptoms was also administered at the same time points. Results: Twenty-six patients completed the BREAST-Q survey, which demonstrated significantly improved satisfaction postoperatively at 6 and 12 months when compared with median preoperative scores for psychosocial (P < 0.001; P < 0.001), sexual (P < 0.001; P < 0.001), and overall satisfaction with breasts (P < 0.001; P < 0.001). Physical well-being of the chest decreased at 6 months (P < 0.001) but improved in comparison with 12 months (P < 0.001). Thirty-four patients completed the BII survey, with 18% reporting symptoms at 3 months and 29% at 1 year. Zero patients requested explantation. Conclusions: Transwomen exhibit a significant increase in breast, psychosocial, and sexual well-being after breast augmentation. However, patients experienced a decreased physical well-being, and many report symptoms associated with BII. These results can be used to better counsel these individuals preoperatively and set reasonable postoperative expectations. Further studies investigating long-term satisfaction in larger cohorts are needed.
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This study examined the nature, variability, and predictors of school readiness difficulties in young children with critical congenital heart disease (CCHD). We hypothesized that, compared to a community control (CC) group, children with CCHD would score less well on measures of readiness and that readiness would be associated with CCHD-related risk factors. Children (60 CCHD and 60 CC) were 4 to 5 years of age and not yet attending kindergarten. Readiness measures included tests of cognition, executive function, motor ability, and pre-academic skills. Caregivers provided child behavior ratings. Analyses examined group differences in readiness, readiness profiles, and associations of readiness with CCHD-related medical risk factors. The CCHD group had lower scores than the CC group on testing and higher caregiver ratings of problems in social communication, as well as higher rates of deficits on several of the measures. Latent class analysis provided evidence for different readiness profiles, with more children with CCHD displaying profiles characterized by weaknesses in readiness. CCHD-related medical risk factors associated with readiness problems in the CCHD group included a co-morbid genetic disorder, postnatal diagnosis of CCHD, major perioperative complication, and longer periods of hospitalizations, cardiopulmonary bypass, and aortic cross-clamp placements. Findings document multiple problems in school readiness in young children with CCHD. Deficits vary across individuals and are associated with higher medical risk. Results confirm the importance of screening for school readiness in these children and suggest areas to target in designing screening measures and providing early childhood interventions.
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The primary aim of this study was to evaluate the convergent validity of the Motor domain (MOT) of PediaTracTM v3.0, an online developmental tracking instrument based on caregiver reports, with fine and gross motor domains (ASQ-FM and ASQ-GM) of the Ages and Stages Questionnaire (ASQ-3) in infants between 2- and 9 months of age. Participants were caregivers of 571 infants born term or preterm (gestational age <37 weeks) enrolled in a multi-site psychometric study of PediaTracTM. Findings revealed significant correlations between MOT and ASQ-3 scores at 2, 4, 6, and 9 months across time periods, term-preterm status, and biological sex. A significantly higher percentage of infants born preterm, compared with those born at term, was identified as a moderate or high risk on both the ASQ-3 and PediaTrac. Future investigations are warranted to further examine the psychometric properties of the MOT domain, including sensitivity, specificity, and positive and negative predictive value.
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Consumer wearables have been successful at measuring sleep and may be useful in predicting changes in mental health measures such as stress. A key challenge remains in quantifying the relationship between sleep measures associated with physiologic stress and a user's experience of stress. Students from a public university enrolled in the Lived Experiences Measured Using Rings Study (LEMURS) provided continuous biometric data and answered weekly surveys during their first semester of college between October-December 2022. We analyzed weekly associations between estimated sleep measures and perceived stress for participants (N = 525). Through mixed-effects regression models, we identified consistent associations between perceived stress scores and average nightly total sleep time (TST), resting heart rate (RHR), heart rate variability (HRV), and respiratory rate (ARR). These effects persisted after controlling for gender and week of the semester. Specifically, for every additional hour of TST, the odds of experiencing moderate-to-high stress decreased by 0.617 or by 38.3% (p<0.01). For each 1 beat per minute increase in RHR, the odds of experiencing moderate-to-high stress increased by 1.036 or by 3.6% (p<0.01). For each 1 millisecond increase in HRV, the odds of experiencing moderate-to-high stress decreased by 0.988 or by 1.2% (p<0.05). For each additional breath per minute increase in ARR, the odds of experiencing moderate-to-high stress increased by 1.230 or by 23.0% (p<0.01). Consistent with previous research, participants who did not identify as male (i.e., female, nonbinary, and transgender participants) had significantly higher self-reported stress throughout the study. The week of the semester was also a significant predictor of stress. Sleep data from wearable devices may help us understand and to better predict stress, a strong signal of the ongoing mental health epidemic among college students.
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OBJECTIVE: Assess residual disability in youth with traumatic brain injury (TBI) treated in a pediatric inpatient rehabilitation unit and examine associations of disability with inpatient status and measures of concurrent functioning. SETTING: Large, urban, quaternary care children's hospital in the Midwestern United States. PARTICIPANTS: Forty-five youth aged 6 to 18 years treated in an inpatient rehabilitation unit for mild-complicated to severe TBI at a minimum of 12 months postdischarge (mean = 3.5 years). DESIGN: Retrospective chart review of clinical data collected from standard clinical care at admission and discharge combined with follow-up data examining current functioning at the time of study enrollment. MAIN OUTCOME MEASURES: Glasgow Outcome Scale-Extended, Pediatric Revision (GOS-E Peds), Neurology Quality of Life Measurement System Short Form (NeuroQOL) Social Interaction with Peers and Cognitive Short Forms, Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale, Strengths and Difficulties Questionnaire, and the Behavior Rating Inventory of Executive Function, 2nd Edition (BRIEF-2). RESULTS: Based on parent report at follow-up, 62% of the children had residual TBI-related disabilities on the GOS-E Peds, while 38% reported "good recovery." Children with residual disability also reported more long-term problems in overall health, social relationships, emotional regulation, behaviors, and executive functioning than those with no residual disability. Measures of functional independence and cognitive recovery at discharge were associated with these impairments. CONCLUSIONS: More than half of the children with TBI in this study had residual disability more than 1 year after inpatient rehabilitation. Findings highlight the associations between measures of functional independence and cognitive recovery during inpatient rehabilitation with later outcomes and underscore the need for continued services to support the needs of children with TBI following their inpatient rehabilitation stay.
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Lesões Encefálicas Traumáticas , Pacientes Internados , Adolescente , Humanos , Criança , Estudos Retrospectivos , Qualidade de Vida , Assistência ao Convalescente , Alta do Paciente , Lesões Encefálicas Traumáticas/psicologia , Recuperação de Função FisiológicaRESUMO
Ecosystem change can profoundly affect human well-being and health, including through changes in exposure to vector-borne diseases. Deforestation has increased human exposure to mosquito vectors and malaria risk in Africa, but there is little understanding of how socioeconomic and ecological factors influence the relationship between deforestation and malaria risk. We examined these interrelationships in six sub-Saharan African countries using demographic and health survey data linked to remotely sensed environmental variables for 11,746 children under 5 years old. We found that the relationship between deforestation and malaria prevalence varies by wealth levels. Deforestation is associated with increased malaria prevalence in the poorest households, but there was not significantly increased malaria prevalence in the richest households, suggesting that deforestation has disproportionate negative health impacts on the poor. In poorer households, malaria prevalence was 27%-33% larger for one standard deviation increase in deforestation across urban and rural populations. Deforestation is also associated with increased malaria prevalence in regions where Anopheles gambiae and Anopheles funestus are dominant vectors, but not in areas of Anopheles arabiensis. These findings indicate that deforestation is an important driver of malaria risk among the world's most vulnerable children, and its impact depends critically on often-overlooked social and biological factors. An in-depth understanding of the links between ecosystems and human health is crucial in designing conservation policies that benefit people and the environment.
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BACKGROUND: Traumatic brain injury (TBI) is a leading cause of disability in children. Cognitive rehabilitation for this population is critical for their long-term health outcomes. This trial aims to evaluate the efficacy of a virtual reality-based program (VICT) for training executive functions in children with TBI. METHODS: A parallel group randomized controlled trial will be conducted among up to 32 children with TBI. Children in the intervention group will receive the VICT training while children in the control group will play a comparable VR game without executive function training. Each participant will be assessed at baseline, post-intervention, and 1-month follow-up. Outcomes will include core executive functions, attention, and health-related quality of life measured by computerized tasks or standardized questionnaires. DISCUSSION: Cognitive rehabilitation is among the top healthcare needs for pediatric TBI patients. Virtual reality-based training is promising due to its versatile content, flexibility, and potential cost savings for both patients and providers. Findings of this trial will provide data on the efficacy of the VICT program on core executive functions, attention problems, and health-related quality of life and serve as the empirical foundation for future larger multi-site effectiveness trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04526639 . Registered on August 18, 2020.
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Lesões Encefálicas Traumáticas , Realidade Virtual , Humanos , Criança , Qualidade de Vida , Treino Cognitivo , Resultado do Tratamento , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/terapia , Cognição , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Microbial community dynamics arise through interspecies interactions, including resource competition, cross-feeding and pH modulation. The individual contributions of these mechanisms to community structure are challenging to untangle. Here we develop a framework to estimate multispecies niche overlaps by combining metabolomics data of individual species, growth measurements in spent media and mathematical models. We applied our framework to an in vitro model system comprising 15 human gut commensals in complex media and showed that a simple model of resource competition accounted for most pairwise interactions. Next, we built a coarse-grained consumer-resource model by grouping metabolomic features depleted by the same set of species and showed that this model predicted the composition of 2-member to 15-member communities with reasonable accuracy. Furthermore, we found that incorporation of cross-feeding and pH-mediated interactions improved model predictions of species coexistence. Our theoretical model and experimental framework can be applied to characterize interspecies interactions in bacterial communities in vitro.
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Microbioma Gastrointestinal , Microbiota , Humanos , Bactérias , Modelos Teóricos , MetabolômicaRESUMO
Predicting survival is essential to tailoring treatment for patients diagnosed with brain metastases. We have evaluated the performance of widely used, validated prognostic scoring systems (Graded Prognostic Assessment and diagnosis-specific Graded Prognostic Assessment) in over 1000 'real-world' patients treated with stereotactic radiosurgery to the brain, selected according to National Health Service commissioning criteria. Survival outcomes from our dataset were consistent with those predicted by the prognostic systems, but with certain cancer subtypes showing a significantly better survival than predicted. Although performance status remains the simplest tool for prediction, total brain tumour volume emerges as an independent prognostic factor, and a new, improved, prognostic scoring system incorporating this has been developed.
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Neoplasias Encefálicas , Radiocirurgia , Humanos , Prognóstico , Medicina Estatal , Estudos Retrospectivos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgiaRESUMO
Deficits in executive functioning (EF) behaviors are very common following pediatric traumatic brain injury (TBI) and can linger well after acute injury recovery. Raters from multiple settings provide information that may not be appreciated otherwise. We examined differences between parent and teacher ratings of EF using data examining longitudinal outcomes following pediatric TBI in comparison to orthopedic injury (OI). We used linear mixed models to determine the association of rater type and injury type with scores on the Behavior Rating Inventory of Executive Functioning (BRIEF). After controlling for demographic variables, rater type and injury type accounted for a small but significant proportion of the variance in EF. Teachers' ratings on the BRIEF were significantly higher than parent ratings for global EF and metacognition, but not for behavior regulation, regardless of injury type, indicating greater EF concerns. All BRIEF ratings, whether from teachers or parents, were higher for children with TBI than for those with OI. Results suggest that parents and teachers provide unique information regarding EF following traumatic injuries and that obtaining ratings from persons who observe children at school as well as at home can result in a better understanding of situation-specific variability in outcomes.
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OBJECTIVE: Early relational health (ERH) is a key developmental predictor and outcome in infancy and early childhood that reflects social-emotional well-being and promotes resilience throughout childhood. Currently, there is no gold-standard developmental screening tool for ERH in pediatric care settings. This study examined the psychometric properties of items assessing ERH that are part of a web-based, caregiver-report screening tool called PediaTrac TM . It was hypothesized that ERH could be reliably estimated and that second-order factors would be revealed within the latent construct ERH. METHOD: Participants included 571 caregivers of term (n = 331; ≥37 weeks) and preterm (n = 240; <37 weeks) infants recruited shortly after birth from several academic medical centers and a community health clinic. Caregivers completed PediaTrac modules at birth and 2, 4, 6, 9, 12, 15, and 18 months; data for this study are from the newborn through 12-month periods. RESULTS: Results from Item Response Theory Graded Response Modeling revealed excellent reliability for the PediaTrac ERH domain at all time points, ranging from 0.96 to 0.98. Exploratory factor analyses revealed 4 to 5 second-order factors, representing Parent-Child Relationship, Parent Distress, Parenting Stress, Parenting Efficacy, Sensitivity, and Perceptions of Child, depending on period. CONCLUSION: The caregiver-report developmental screening tool, PediaTrac, reliably measures ERH during the first year of life. The measure has promising clinical utility in pediatric clinic settings for tracking ERH over time to ensure early social-emotional well-being and to identify concerns as early as possible.
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Psicometria , Humanos , Feminino , Lactente , Masculino , Psicometria/normas , Psicometria/instrumentação , Relações Pais-Filho , Cuidadores , Recém-Nascido , Adulto , Recém-Nascido Prematuro/fisiologia , Desenvolvimento Infantil/fisiologia , Reprodutibilidade dos TestesRESUMO
Lipid nanoparticle (LNP)-encapsulated mRNA has been used for in vivo production of several secreted protein classes, such as IgG, and has enabled the development of personalized vaccines in oncology. Establishing the feasibility of delivering complex multispecific modalities that require higher-order structures important for their function could help expand the use of mRNA/LNP biologic formulations. Here, we evaluated whether in vivo administration of mRNA/LNP formulations of SIRPα-Fc-CD40L and TIGIT-Fc-LIGHT could achieve oligomerization and extend exposure, on-target activity, and antitumor responses comparable with that of the corresponding recombinant fusion proteins. Intravenous infusion of the formulated LNP-encapsulated mRNAs led to rapid and sustained production of functional hexameric proteins in vivo, which increased the overall exposure relative to the recombinant protein controls by â¼28 to 140 fold over 96 hours. High concentrations of the mRNA-encoded proteins were also observed in secondary lymphoid organs and within implanted tumors, with protein concentrations in tumors up to 134-fold greater than with the recombinant protein controls 24 hours after treatment. In addition, SIRPα-Fc-CD40L and TIGIT-Fc-LIGHT mRNAs induced a greater increase in antigen-specific CD8+ T cells in the tumors. These mRNA/LNP formulations were well tolerated and led to a rapid increase in serum and intratumoral IL2, delayed tumor growth, extended survival, and outperformed the activities of benchmark mAb controls. Furthermore, the mRNA/LNPs demonstrated improved efficacy in combination with anti-PD-L1 relative to the recombinant fusion proteins. These data support the delivery of complex oligomeric biologics as mRNA/LNP formulations, where high therapeutic expression and exposure could translate into improved patient outcomes. SIGNIFICANCE: Lipid nanoparticle-encapsulated mRNA can efficiently encode complex fusion proteins encompassing immune checkpoint blockers and costimulators that functionally oligomerize in vivo with extended pharmacokinetics and durable exposure to induce potent antitumor immunity.
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Nanopartículas , RNA Mensageiro , Proteínas Recombinantes de Fusão , Animais , Camundongos , RNA Mensageiro/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/imunologia , Nanopartículas/química , Humanos , Feminino , Camundongos Endogâmicos C57BL , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/genética , Lipídeos/química , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Linhagem Celular TumoralRESUMO
Some animals form transient, responsive and solid-like ensembles through dynamic structural interactions. These ensembles demonstrate emergent responses such as spontaneous self-assembly, which are difficult to achieve in synthetic soft matter. Here we use shape-morphing units comprising responsive polymers to create solids that self-assemble, modulate their volume and disassemble on demand. The ensemble is composed of a responsive hydrogel, liquid crystal elastomer or semicrystalline polymer ribbons that reversibly bend or twist. The dispersions of these ribbons mechanically interlock, inducing reversible aggregation. The aggregated liquid crystal elastomer ribbons have a 12-fold increase in the yield stress compared with cooled dispersion and contract by 34% on heating. Ribbon type, concentration and shape dictate the aggregation and govern the global mechanical properties of the solid that forms. Coating liquid crystal elastomer ribbons with a liquid metal begets photoresponsive and electrically conductive aggregates, whereas seeding cells on hydrogel ribbons enables self-assembling three-dimensional scaffolds, providing a versatile platform for the design of dynamic materials.