Potent Engineered PLGA Nanoparticles by Virtue of Exceptionally High Chemotherapeutic Loadings

Herein we report the fabrication of engineered poly(lactic acid-co-glycolic acid) nanoparticles via the PRINT® (Particle Replication In Non-wetting Templates) process with high and efficient loadings of docetaxel, up to 40% (w/w) with encapsulation efficiencies >90%. The PRINT process enables independent control of particle properties leading to a higher degree of tailorability than traditional methods. Particles with 40% loading display better in vitro efficacy than particles with lower loadings and the clinical formulation of docetaxel, Taxotere®

Medical factors associated with caregiver intention to vaccinate their children against COVID-19

Objective: To describe medical factors that are associated with caregiver intention to vaccinate their children against COVID-19. Methods: We conducted a cross-sectional study of families receiving primary care in a mid-Atlantic pediatric healthcare system, linking caregiver-reported data from a survey completed March 19 to April 16, 2021 to comprehensive data from the child\u27s EHR. Results: 513 families were included (28% Black, 16% Hispanic, 44% public insurance, 21% rural, child age range 0-21 years). 44% of caregivers intended to vaccinate their children against COVID-19, while 41% were not sure and 15% would not. After adjusting for socio-demographics, the only medical factors that were associated with caregiver COVID-19 vaccine hesitancy were caregiver COVID-19 vaccination status at the time of the survey (aOR 3.0 if the caregiver did not receive the vaccine compared to those who did, 95% CI 1.7-5.3) and child seasonal influenza immunization history (aOR 3.3 if the child had not received the influenza vaccine in the 2020-2021 season compared to those who did, 95% CI 2.0-5.4). Other medical factors, including family medical experiences with COVID-19, other child immunization history, child health conditions like obesity and asthma, and family engagement with the healthcare system were not associated with caregiver intention to vaccinate their children against COVID-19. Conclusions: This study highlights important factors, such as general attitudes towards vaccines and understanding of COVID-19 morbidity risk factors, that healthcare providers should address when having conversations with families about the COVID-19 vaccine

Disparities in Delaware Caregiver Beliefs about the COVID-19 Vaccine for their Children

Objective: To describe sociodemographic disparities in caregiver beliefs about the COVID-19 vaccine for their children. Methods: This was a cross-sectional study, linking caregiver-reported data to geocoded sociodemographic data from child EHRs. Caregivers of children receiving care in a Delaware pediatric healthcare system were invited to complete a survey about COVID-19 vaccine beliefs from March 19 to April 16, 2021. Results: 1499 caregivers participated (18% Black, 11% Hispanic, 32% public insurance, 12% rural). 54% of caregivers intended to vaccinate their children, while 34% were unsure and 12% would not. Caregivers of younger children (aOR 3.70, CI 2.36-5.79), Black children (aOR 2.11, CI 1.50-2.96), and from disadvantaged communities (aOR 1.59, CI 1.05-2.42) were more likely to be unsure and not vaccinate their children. Caregivers from rural communities were more likely not to vaccinate their children (aOR 2.51, CI 1.56-4.05). Fewer caregivers of younger children, Black children, and from disadvantaged communities believed in the safety or efficacy of the vaccines (p \u3c 0.001), while fewer caregivers of younger children and from rural communities believed in their children’s susceptibility to COVID-19 or risk of getting severe disease from COVID-19 (p \u3c 0.05). While the majority (72%) of caregivers were influenced by health experts, fewer from communities of color and disadvantaged communities were (p\u3c0.001). Conclusions: Caregivers of younger children and from communities of color, rural communities, and disadvantaged communities in Delaware expressed more COVID-19 vaccine hesitancy. Policy implications: This study explores beliefs of different communities in Delaware, which are important to tailoring public health messaging and strategies to increase vaccine uptake in these communities

Plasma, tumor and tissue pharmacokinetics of Docetaxel delivered via nanoparticles of different sizes and shapes in mice bearing SKOV-3 human ovarian carcinoma xenograft

The particle fabrication technique PRINT® was used to fabricate monodisperse size and shape specific poly(lactide-co-glycolide) particles loaded with the chemotherapeutic Docetaxel. The pharmacokinetics of two cylindrical shaped particles with diameter=80nm; height=320nm (PRINT-Doc-80×320) and d=200nm; h=200nm (PRINT-Doc-200×200) were compared to Docetaxel in mice bearing human ovarian carcinoma SKOV-3 flank xenografts. The Docetaxel plasma exposure was ~20-fold higher for both particles compared to docetaxel. Additionally, the volume of distribution (Vd) of Docetaxel in PRINT formulations was ~18-fold (PRINT-Doc-80×320) and ~33-fold (PRINT-Doc-200×200) lower than Docetaxel. The prolonged duration of Docetaxel in plasma when dosed with PRINT formulations subsequently lead to increased tumor exposure of Docetaxel from 0-168 hours (~53% higher for PRINT-Doc-80×320 and ~76% higher for PRINT-Doc-200×200 particles). PRINT-Doc-80×320 had lower exposures in the liver, spleen and lung compared with PRINT-Doc-200×200. Thus, the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system

A longitudinal study of adolescents’ judgments of the attractiveness of facial symmetry, averageness and sexual dimorphism

Adolescents have been found to differ by age in their attraction to facial symmetry, averageness, and sexual dimorphism. However, it has not been demonstrated that attraction to these facial characters changes over time as a consequence of age-linked development. We aimed to extend previous cross-sectional findings by examining whether facial attractiveness judgments change over time during adolescence as a consequence of increasing age, in a within-subjects study of two cohorts of adolescents aged 11–16. Consistent with previous findings, we find that adolescents (often particularly females) judged faces with increased averageness, symmetry and femininity to be more attractive than original, asymmetric and masculine faces, respectively. However, we do not find longitudinal changes in face preference judgments across the course of a year, leading us to question the extent to which some of the previously reported differences in facial attractiveness judgments between younger and older adolescents were due to age-linked changes

The phylogenetic origin and evolution of acellular bone in teleost fishes: insights into osteocyte function in bone metabolism

Vertebrate bone is composed of three main cell types: osteoblasts, osteoclasts and osteocytes, the latter being by far the most numerous. Osteocytes are thought to play a fundamental role in bone physiology and homeostasis, however they are entirely absent in most extant species of teleosts, a group that comprises the vast majority of bony ‘fishes’, and approximately half of vertebrates. Understanding how this acellular (anosteocytic) bone appeared and was maintained in such an important vertebrate group has important implications for our understanding of the function and evolution of osteocytes. Nevertheless, although it is clear that cellular bone is ancestral for teleosts, it has not been clear in which specific subgroup the osteocytes were lost. This review aims to clarify the phylogenetic distribution of cellular and acellular bone in teleosts, to identify its precise origin, reversals to cellularity, and their implications. We surveyed the bone type for more than 600 fossil and extant ray‐finned fish species and optimised the results on recent large‐scale molecular phylogenetic trees, estimating ancestral states. We find that acellular bone is a probable synapomorphy of Euteleostei, a group uniting approximately two‐thirds of teleost species. We also confirm homoplasy in these traits: acellular bone occurs in some non‐euteleosts (although rarely), and cellular bone was reacquired several times independently within euteleosts, in salmons and relatives, tunas and the opah (Lampris sp.). The occurrence of peculiar ecological (e.g. anadromous migration) and physiological (e.g. red‐muscle endothermy) strategies in these lineages might explain the reacquisition of osteocytes. Our review supports that the main contribution of osteocytes in teleost bone is to mineral homeostasis (via osteocytic osteolysis) and not to strain detection or bone remodelling, helping to clarify their role in bone physiology

Development and Psychometric Validation of the Pandemic-Related Traumatic Stress Scale for Children and Adults

To assess the public health impact of the COVID-19 pandemic on mental health, investigators from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) research program developed the Pandemic-Related Traumatic Stress Scale (PTSS). Based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) acute stress disorder symptom criteria, the PTSS is designed for adolescent (13–21 years) and adult self-report and caregiver-report on 3–12-year-olds. To evaluate psychometric properties, we used PTSS data collected between April 2020 and August 2021 from non-pregnant adult caregivers (n = 11,483), pregnant/postpartum individuals (n = 1,656), adolescents (n = 1,795), and caregivers reporting on 3–12-year-olds (n = 2,896). We used Mokken scale analysis to examine unidimensionality and reliability, Pearson correlations to evaluate relationships with other relevant variables, and analyses of variance to identify regional, age, and sex differences. Mokken analysis resulted in a moderately strong, unidimensional scale that retained nine of the original 10 items. We detected small to moderate positive associations with depression, anxiety, and general stress, and negative associations with life satisfaction. Adult caregivers had the highest PTSS scores, followed by adolescents, pregnant/postpartum individuals, and children. Caregivers of younger children, females, and older youth had higher PTSS scores compared to caregivers of older children, males, and younger youth, respectively

Recommendations for Enhancing Psychosocial Support of NICU Parents through Staff Education and Support

Providing psychosocial support to parents whose infants are hospitalized in the neonatal intensive care unit (NICU) can improve parents’ functioning as well as their relationships with their babies. Yet, few NICUs offer staff education that teaches optimal methods of communication with parents in distress. Limited staff education in how to best provide psychosocial support to families is one factor that may render those who work in the NICU at risk for burnout, compassion fatigue and secondary traumatic stress syndrome. Staff who develop burnout may have further reduced ability to provide effective support to parents and babies. Recommendations for providing NICU staff with education and support are discussed. The goal is to deliver care that exemplifies the belief that providing psychosocial care and support to the family is equal in importance to providing medical care and developmental support to the baby

Human Remains from the Pleistocene-Holocene Transition of Southwest China Suggest a Complex Evolutionary History for East Asians

BACKGROUND: Later Pleistocene human evolution in East Asia remains poorly understood owing to a scarcity of well described, reliably classified and accurately dated fossils. Southwest China has been identified from genetic research as a hotspot of human diversity, containing ancient mtDNA and Y-DNA lineages, and has yielded a number of human remains thought to derive from Pleistocene deposits. We have prepared, reconstructed, described and dated a new partial skull from a consolidated sediment block collected in 1979 from the site of Longlin Cave (Guangxi Province). We also undertook new excavations at Maludong (Yunnan Province) to clarify the stratigraphy and dating of a large sample of mostly undescribed human remains from the site. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a detailed comparison of cranial, including a virtual endocast for the Maludong calotte, mandibular and dental remains from these two localities. Both samples probably derive from the same population, exhibiting an unusual mixture of modern human traits, characters probably plesiomorphic for later Homo, and some unusual features. We dated charcoal with AMS radiocarbon dating and speleothem with the Uranium-series technique and the results show both samples to be from the Pleistocene-Holocene transition: ∼14.3-11.5 ka. CONCLUSIONS/SIGNIFICANCE: Our analysis suggests two plausible explanations for the morphology sampled at Longlin Cave and Maludong. First, it may represent a late-surviving archaic population, perhaps paralleling the situation seen in North Africa as indicated by remains from Dar-es-Soltane and Temara, and maybe also in southern China at Zhirendong. Alternatively, East Asia may have been colonised during multiple waves during the Pleistocene, with the Longlin-Maludong morphology possibly reflecting deep population substructure in Africa prior to modern humans dispersing into Eurasia