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Biomaterials Science Jun 2024PEGylation is currently used for the synthesis of stealth liposomes and to enhance the pharmacokinetic and biopharmaceutical properties of payloads. PEGylated dendron...
PEGylation is currently used for the synthesis of stealth liposomes and to enhance the pharmacokinetic and biopharmaceutical properties of payloads. PEGylated dendron phospholipids can decrease the detachment of polyethylene glycol (PEG) from the liposomal surface owing to an increased hydrophobic anchoring effect on the phospholipid bilayer of liposomes and thus generating super stealth liposomes that are suitable for the systemic delivery of anticancer drugs. Herein, doxorubicin hydrochloride-loaded super stealth liposomes were studied for the treatment of breast cancer lung metastasis in an animal model. The results demonstrated that the super stealth liposomes had suitable physicochemical properties for administration and could significantly increase the efficacy of doxorubicin in breast cancer lung metastasis tumor-bearing mice compared to the free drug. The super stealth liposomes also increased doxorubicin accumulation inside the tumor tissue. The permanence of PEG on the surface of the super stealth liposomes favored the formation of a depot of therapeutic nanocarriers inside the tumor tissue by improving their permanence after stopping treatment. The doxorubicin-loaded super stealth liposomes increased the survival of the mouse tumor model. These promising results demonstrate that the doxorubicin-loaded super stealth liposomes could be an effective nanomedicine to treat metastatic breast cancer.
PubMed: 38940612
DOI: 10.1039/d4bm00478g -
The Journal of Physical Chemistry... Jun 2024This work reports the observation and characterization of heterobinuclear transition-metal main-group metal oxide carbonyl complex anions, RuGeO(CO) ( = 3-5), by...
This work reports the observation and characterization of heterobinuclear transition-metal main-group metal oxide carbonyl complex anions, RuGeO(CO) ( = 3-5), by combining mass-selected photoelectron velocity map imaging spectroscopy and quantum chemistry calculations. The experimentally determined vertical electron detachment energy of RuGeO(CO) surpasses those of RuGeO(CO) and RuGeO(CO), which is attributed to distinctive bonding features. RuGeO(CO) manifests one covalent σ and two Ru-to-Ge dative π bonds, contrasting with the sole covalent σ bond present in RuGeO(CO) and RuGeO(CO). Unpaired spin density distribution analysis reveals a 17-electron configuration at the Ru center in RuGeO(CO) and an 18-electron configuration in RuGeO(CO) and RuGeO(CO). This work closes a gap in the quantitative physicochemical characterization of heteronuclear oxide carbonyl complexes, enhancing our insights into catalytic processes of CO/GeO on the metal surface at the molecular level.
PubMed: 38940497
DOI: 10.1021/acs.jpclett.4c01532 -
Frontiers in Immunology 2024TRIM21 is a pivotal effector in the immune system, orchestrating antibody-mediated responses and modulating immune signaling. In this comprehensive study, we focus on...
TRIM21 is a pivotal effector in the immune system, orchestrating antibody-mediated responses and modulating immune signaling. In this comprehensive study, we focus on the interaction of TRIM21 with Fc engineered antibodies and subsequent implications for viral neutralization. Through a series of analytical techniques, including biosensor assays, mass photometry, and electron microscopy, along with structure predictions, we unravel the intricate mechanisms governing the interplay between TRIM21 and antibodies. Our investigations reveal that the TRIM21 capacity to recognize, bind, and facilitate the proteasomal degradation of antibody-coated viruses is critically dependent on the affinity and avidity interplay of its interactions with antibody Fc regions. We suggest a novel binding mechanism, where TRIM21 binding to one Fc site results in the detachment of PRYSPRY from the coiled-coil domain, enhancing mobility due to its flexible linker, thereby facilitating the engagement of the second site, resulting in avidity due to bivalent engagement. These findings shed light on the dual role of TRIM21 in antiviral immunity, both in recognizing and directing viruses for intracellular degradation, and demonstrate its potential for therapeutic exploitation. The study advances our understanding of intracellular immune responses and opens new avenues for the development of antiviral strategies and innovation in tailored effector functions designed to leverage TRIM21s unique binding mode.
Topics: Humans; Ribonucleoproteins; Protein Binding; Antibodies, Neutralizing; Immunoglobulin Fc Fragments; Protein Engineering; Antibodies, Viral; Antibody Affinity; Animals
PubMed: 38938560
DOI: 10.3389/fimmu.2024.1401471 -
Medical Education Jun 2024The awarding gap between White and Black students in UK health curricula is well established. Critical race theory (CRT) is a lens to deconstruct pedagogic practice and...
INTRODUCTION
The awarding gap between White and Black students in UK health curricula is well established. Critical race theory (CRT) is a lens to deconstruct pedagogic practice and consider the intersectionality of Black student lived experience to provide a realist critique of the phenomenon of Whiteness in higher education and the impact this has on Black attainment. Using one UK pharmacy programme as a case study, this paper aims to explore Black lived experience as a means of problematising and disrupting structural oppressions.
METHODS
Sixteen Black students from one UK pharmacy degree programme were purposively recruited to the study. Love and breakup letter methodology (LBM) was used to facilitate sharing experiences of intersectionality in relation to their undergraduate education, with data thematically analysed through the lens of CRT.
RESULTS
Two meta-themes (identity and inclusion; and cultural capital) and four subthemes (social capital; access; family expectations; and help-seeking) were identified. The intersectionality of Black students was articulated as not possessing the social capital and the 'language' to succeed within the White structures of the curriculum. The conflict of capital and the absence of Black culture gave rise to confined help-seeking behaviours. Whilst Black students experienced equality of access to the curriculum, an absence of rights to legitimate involvement (inclusion) worked to diminish participation in the curriculum.
DISCUSSION
This is the first study to consider the intersectionality of Black pharmacy students in relation to academic awarding gaps and has found that oppressive educational structures marginalise and other Black experience. Black students experience the curriculum as a place where their social and cultural capital is undervalued, and as a White space where they lack the artefacts to succeed, leading to peripheral participation and detachment. The approach used in this study can be adopted across medical and health education as a means to problematise racial inequality through the exemplar of White:Black awarding gaps.
PubMed: 38938192
DOI: 10.1111/medu.15460 -
Clinical & Experimental Ophthalmology Jun 2024Paediatric vitreoretinal pathology is distinct from adult cases in both presentation and surgical planning. Here we aim to report the aetiology and epidemiology in...
BACKGROUND
Paediatric vitreoretinal pathology is distinct from adult cases in both presentation and surgical planning. Here we aim to report the aetiology and epidemiology in children 0-18 years requiring vitreoretinal surgery at a major tertiary paediatric hospital in Queensland, Australia.
METHODS
Retrospective review of cases requiring vitreoretinal surgery between May 2015 and October 2022 was conducted. Demographics, ocular and medical history, surgical pathology, procedures performed, and epidemiology data were retrieved. Patients were grouped into three main aetiologies: traumatic, syndromic, or secondary.
RESULTS
A total of 124 patients, the majority male (87, 70.2%) with a mean age of 10.3 years underwent vitreoretinal surgery. Trauma accounted for 32.3% of cases requiring surgery of which 47% were due to a penetrating eye injury. 35.5% were associated with a syndromic cause with common aetiology including coats, congenital cataract, sticklers, and retinopathy of prematurity. 32.3% developed secondary pathology and retinal detachment was the primary cause for surgery (55%). The average time from symptom onset to presentation was 30 days (SD 56.88) with patients living an average of 306.2 km (SD 558.9) away from the Queensland Children's Hospital. Older age was significantly associated with increased days to presentation in the traumatic group (p < 0.05).
CONCLUSIONS
This study provides an insight into the aetiology and epidemiology of paediatric vitreoretinal presentations in Queensland, Australia.
PubMed: 38937978
DOI: 10.1111/ceo.14413 -
BMC Public Health Jun 2024More knowledge is needed on the risk of developing chronic obstructive pulmonary disease (COPD) associated with housing conditions and indoor environment based on cohort...
BACKGROUND
More knowledge is needed on the risk of developing chronic obstructive pulmonary disease (COPD) associated with housing conditions and indoor environment based on cohort studies with a long follow-up time.
OBJECTIVE
To examine the association between housing conditions and indoor environment and the risk of developing COPD.
METHODS
In this cohort study, we followed 11,590 individuals aged ≥ 30 years free of COPD at baseline. Information on incident COPD and housing conditions and indoor environment was obtained from the Danish national registers and the Danish Health and Morbidity Survey year 2000. Poisson regression of incidence rates (IRs) were used to estimate incidence rate ratios (IRRs) of COPD.
RESULTS
The overall IR of COPD was 8.6 per 1,000 person-years. Individuals living outside the biggest cities vs. living in the biggest cities (≥ 50,000) had a lower risk of COPD (200-4,999; IRR 0.77 (95% CI 0.65-0.90). Individuals living in semi-detached houses had a higher risk compared to individuals living in detached houses (IRR 1.29 (95% CI 1.07-1.55)). Likewise, individuals living in rented homes had a higher risk (IRR 1.47 (95% CI 1.27-1.70)) compared to individuals living in owned homes. The IR of COPD was 17% higher among individuals living in dwellings build > 1982 compared with individuals living in older dwellings (< 1962), not statistically significant though (IRR 0.83 (95% CI 0.68-1.03)). Likewise, the IR of COPD was 15% higher among individuals living in the densest households compared with individuals living in the least dense households, not statistically significant though (IRR 1.15 (95% CI 0.92-1.45)). This was primary seen among smokers. There was no difference in risk among individuals with different perceived indoor environments. Overall, similar patterns were seen when stratified by smoking status with exception of perceived indoor environment, where opposite patterns were seen for smokers and never smokers.
CONCLUSION
Individuals living in semi-detached houses or rented homes had a higher risk of developing COPD compared to individuals living in detached or owned homes. Individuals living in cities with < 50.000 residents had a lower risk of COPD compared to individuals living in cities with ≥ 50.000 residents.
Topics: Humans; Denmark; Pulmonary Disease, Chronic Obstructive; Housing; Male; Female; Middle Aged; Adult; Incidence; Cohort Studies; Aged; Risk Factors
PubMed: 38937765
DOI: 10.1186/s12889-024-19131-3 -
Ophthalmology. Retina Jun 2024To describe common referral diagnoses of FEVR (Familial Exudative Vitreoretinopathy) DESIGN: Retrospective case series.
PURPOSE
To describe common referral diagnoses of FEVR (Familial Exudative Vitreoretinopathy) DESIGN: Retrospective case series.
SUBJECTS
Patients with phenotypic FEVR evaluated by the pediatric retina service at Bascom Palmer Eye Institute from March 1, 2019 to May 31, 2023.
METHODS
A retrospective detailed review of history, imaging, and genetic testing was performed for all patients included in the study.
MAIN OUTCOME MEASURES
The primary outcome measures included genetic evaluation, clinical imaging and characteristics. Secondary outcome measures were age and stage of disease at diagnosis.
RESULTS
Fifty-five patients with phenotypic and genetically confirmed FEVR were identified. Of these, the initial diagnosis was incorrect upon referral in 33 cases (60%). The referral diagnoses included Coats disease (n =2, 7%), toxoplasmosis (n=2, 7%), retinal detachment (n=6, 18%), persistent fetal vasculature (PFV) (n =5, 15%), suspected inherited retinal disease (n=2, 7%), myopia (n=3, 9%), retinopathy of prematurity (ROP) with preterm gestational age (n=7, 21%), and ROP at moderate to late preterm gestational age (n=6, 18%). The mean age at diagnosis was 8.78 years and 6.42 years for patients with revised diagnosis versus initial diagnosis of FEVR, respectively (p =0.4). There was no correlation between age of diagnosis and stage of disease (p =0.8).
CONCLUSIONS
A high index of suspicion for FEVR must be maintained given the heterogeneity of phenotypes. Atypical cases of PFV, Coats disease, and ROP should prompt fluorescein angiography and genetic evaluation.
PubMed: 38936772
DOI: 10.1016/j.oret.2024.06.010 -
ACS Applied Materials & Interfaces Jun 2024Icing has been seen as an economic and safety hazard due to its threats to aviation, power generation, offshore platforms, etc., where passive icephobic surfaces with a...
Icing has been seen as an economic and safety hazard due to its threats to aviation, power generation, offshore platforms, etc., where passive icephobic surfaces with a surface texturing design have the potential to address this problem. However, the intrinsic icephobic principles associated with the surface textures, energy, elasticity, and hybrid effects are still unclear. To explore the anisotropic wettability, ice nucleation, and ice detaching behaviors, a series of textured poly(dimethylsiloxane) (PDMS)-based coatings with various texture orientations were proposed through a simple stamping method with surface functionalization. The anisotropic hydrophobic/icephobic phenomena and mechanisms were discovered from wettability evaluation, experimentally studied by icing/deicing experiments, and finally verified by microscopic numerical simulations. One-way analysis of variance (one-way ANOVA analysis) was used to analyze the effect of surface textures on hydrophobic/icephobic properties, which assisted in understanding anisotropic phenomena. Typical anisotropic ice nucleation and growth on the textured coatings were clarified using in situ environmental scanning electron microscope (ESEM) characterization. The ice/coating interfacial stress responses were studied by numerical stimulation at the microscopic level, further verifying the localized, amplified, and propagated stress at the ice/coating interface. The theoretical anisotropic responses, barrier effect, and accelerating effect were verified to interpret the anisotropic wettability and icephobicity, depending on the specific surface conditions. This study revealed the basics of the anisotropic icephobic mechanisms of textured icephobic surfaces, further facilitating the R&D of passive icephobic surfaces.
PubMed: 38934333
DOI: 10.1021/acsami.4c08004 -
Scandinavian Journal of Child and... Jan 2024The experience of several adverse childhood experiences (ACEs) has been shown to be associated with Post-Traumatic Stress Disorder (PTSD) and Disturbances in...
BACKGROUND
The experience of several adverse childhood experiences (ACEs) has been shown to be associated with Post-Traumatic Stress Disorder (PTSD) and Disturbances in Self-Organization (DSO) symptoms among adolescents. Defense mechanisms and coping styles are psychological processes involved in the association of ACEs with PTSD and DSO symptoms. However, there is a lack of research on the joint association of these variables among Faroese adolescents.
AIM
The aim of this study was to analyze the effect of exposure to ACEs on PTSD and DSO symptoms trough the indirect effect of defense mechanisms and coping styles in a sample of Faroese adolescents.
METHOD
Six hundred and eighty-seven Faroese adolescents were recruited from 19 schools. Participants responded to validated self-report questionnaires. A multiple step mediation and a serial mediation methodology were conducted through structural equation modeling.
RESULTS
Exposure to ACEs was linked to PTSD and DSO symptoms through the indirect effect of immature defense mechanisms, emotional coping, and detachment coping. Exposure to ACEs was linked to PTSD symptoms through rational coping.
CONCLUSIONS
The results suggest a mutual relationship between defense mechanisms and coping styles in coping with multiple adversity among adolescents.
PubMed: 38933756
DOI: 10.2478/sjcapp-2024-0004 -
Materials Horizons Jun 2024Reversible adhesion with on-demand attachment and detachment is used by many animals for their locomotion. However, achieving robust and switchable adhesion on rough...
Reversible adhesion with on-demand attachment and detachment is used by many animals for their locomotion. However, achieving robust and switchable adhesion on rough surfaces in artificial adhesives remains a significant challenge. Here, we present a snail mucus-inspired touch-initiate adhesive (TIA), showing robust adhesions on various surfaces. TIA is a polymeric hydrogel photo-cured with the presence of supersaturated sodium acetate (NaAc) in the precursor solution. TIA is soft and flexible at room temperature, allowing it to form conformal contact with objects with various surfaces. The contact with the target surface immediately initiates the crystallization of TIA, increasing the elastic modulus of TIA by an order of magnitude. The increased modulus and the interlocking with the target surfaces thus results in an adhesion strength up to 465.56 ± 84.05 kPa. TIA can be easily detached from the surface by heating to a temperature above 58 °C, showing an adhesion strength of 12.71 ± 2.73 kPa. The detached TIA, even cooled down to and kept at room temperature, is readily used for the subsequent adhesion. The study here not only provides a highly adhesive material for on-demand attachment to various surfaces, but also proposes a new design strategy to compose smart materials.
PubMed: 38932648
DOI: 10.1039/d4mh00331d