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Glioblastoma (GBM) is the most common form of brain cancer. Even with aggressive treatment, tumor recurrence is almost universal and patient prognosis is poor because many GBM cell subpopulations, especially the mesenchymal and glioma stem cell populations, are resistant to temozolomide (TMZ), the most commonly used chemotherapeutic in GBM. For this reason, there is an urgent need for the development of new therapies that can more effectively treat GBM. Several recent studies have indicated that high expression of connexin 43 (Cx43) in GBM is associated with poor patient outcomes. It has been hypothesized that inhibition of the Cx43 hemichannels could prevent TMZ efflux and sensitize otherwise resistance cells to the treatment. In this study, we use a 3-dimensional organoid model of GBM to demonstrate that combinatorial treatment with TMZ and αCT1, a Cx43 mimetic peptide, significantly improves treatment efficacy in certain populations of GBM. Confocal imaging was used to visualize changes in Cx43 expression in response to combinatorial treatment. These results indicate that Cx43 inhibition should be pursued further as an improved treatment for GBM. This article is protected by copyright. All rights reserved.

A droplet generator has been developed that interfaces with a barrier-on-chip platform for temporal analyte compartmentalisation and analysis. Droplets are generated every 20 minutes in 8 separate parallel microchannels, with an average droplet volume of 9.47 ± 0.6 μL, allowing simultaneous analysis of 8 different experiments. The device was tested using an epithelial barrier model by monitoring the diffusion of a fluorescent high molecular weight dextran molecule. The epithelial barrier was perturbed using detergent leading to a peak at 3–4 hours, correlating with simulations. For the untreated (control) a constant, very low level of dextran diffusion was observed. The epithelial cell barrier properties were also continuously measured using electrical impedance spectroscopy to extract an equivalent trans epithelial resistance.

This study demonstrated successful encapsulation of polymerized hemoglobin in the tense quaternary state inside a nanoparticle comprised of zeolite imidazole framework precursors with antioxidant properties.

Anorexia nervosa (AN) is a severe psychiatric illness with complex etiology. Recently, we found elevated striatal brain response to sweet taste stimuli in adolescents and young adults with AN. Here, we tested the hypothesis that nutritional rehabilitation normalizes prediction error activation, a measure for dopamine-related reward circuit response, to salient caloric taste stimuli in AN.A total of 28 individuals with AN (age = 16 ± 2 years; body mass index [BMI] = 16 ± 1) who previously underwent brain imaging while performing a taste prediction error task using sucrose as salient caloric stimulus, participated in a second brain imaging scan (BMI = 18 ± 1) after intensive specialized eating disorder treatment (41 ± 15 days). A total of 31 healthy controls (age = 16 ± 3 years; BMI = 21 ± 2) were also studied on two occasions.At baseline, individuals with AN demonstrated an elevated salience response in bilateral caudate head and nucleus accumbens, and right ventral striatum. At the second scan, elevated response was only found in the right nucleus accumbens. A moderator analysis indicated that greater increase in BMI and greater decrease in sweetness perception predicted lesser prediction error response at the second scan in AN.Consistent with the previously reported monetary stimulus-response, elevated taste prediction error response in AN was largely absent after weight restoration. This study indicates that changes in BMI and sweet taste perception are independent moderators of change of brain salience response in adolescents and young adults with AN. The study points toward dynamic changes in the brain reward circuitry in AN and highlights the importance of nutrition and weight restoration in that process.AN is a severe psychiatric illness. Biological factors that integrate neurobiology and behavior could become important targets to improve treatment outcome. This study highlights the importance of weight normalization and taste perception the normalization of brain function, and food type or taste-specific interventions could help in the recovery process. Furthermore, the study suggests that food-related and nonfood-related reward processing adapts to illness state in AN.

Anxious traits are elevated in eating disorders (EDs), are considered risk factors for ED development, and trait anxiety has been linked to ED psychopathology. How trait anxiety relates to ED neurobiology is not well understood. In this study 197 individuals across the ED spectrum (anorexia nervosa n = 91; other specified EDs n = 34; bulimia nervosa n = 56; binge ED n = 16), and 120 healthy controls were assessed for anxious traits and learned to expect and receive caloric or neutral taste stimuli during brain imaging. Amygdala sucrose expectation response differed across groups (Wilk’s lambda = 0.945, p = 0.023), and was higher on the left in anorexia nervosa compared to healthy controls (p = 0.002). Expected sucrose receipt response across taste reward regions was not different between groups. In the ED sample, trait anxiety negatively moderated the relationship between amygdala expectation and right dorsal (p = 0.0062) and ventral (p = 0.0046) anterior insula receipt response. A subgroup analysis showed similar results for anorexia nervosa, and partially in bulimia nervosa. Across EDs, appetitive motivation correlated positively with bilateral orbitofrontal cortex, caudate head, and ventral striatal sucrose receipt response (r = 0.215 to 0.179, p = 0.002 to 0.012). Across the study sample, trait anxiety showed an inverted-U-shaped relationship with right (r = 0.147, p = 0.034) and left (r = 0.162, p = 0.016) amygdala expectation response. Amygdala sucrose expectation response is elevated in anorexia nervosa, correlates with sucrose receipt response, and this relationship is negatively moderated by trait anxiety across EDs. Trait anxiety may have an important role in how expectation drives taste stimulus receipt brain response and perhaps food approach in individuals with EDs.

In this IMR Country Report, we draw attention to Costa Rica as a strategic location for expanding research and theory on migrants in need of protection (MNP), who have migrated abroad primarily to evade an imminent threat to their survival. MNP constitute an increasing share of all international migrants in Costa Rica and worldwide, yet research on these migrants and their migration dynamics remains comparatively underdeveloped relative to research on migrants who relocate abroad primarily in pursuit of material gains, social status, or family reunification. As we highlight, Costa Rica is an instrumental site to deepen understandings of MNP populations and migration dynamics because its large and rapidly growing MNP population is incredibly diverse with respect to national origins, demographic characteristics, and underlying motivations for migration. This diversity presents ample opportunities to better understand heterogeneity in the different types of threats MNP seek to evade; how and why MNP incorporation is shaped by individuals’ demographic attributes and pre-migration threats; and how the social networks of various MNP subpopulations develop and overlap with time. Moreover, the geographic concentration of MNP in two regions in Costa Rica lends itself to primary data collection among this population and generates opportunities for estimating local MNPs’ demographic characterization, even in the absence of a reliable sampling frame.

Globally, age-related macular degeneration (AMD) is the third most common visual impairment. Most often attributed to cellular fatigue with aging, over expression of reactive oxygen species (ROS) causes ROS accumulation in the retina, leading to chronic inflammatory immune signaling, cellular and tissue damage, and eventual blindness. If left uncontrolled, the disease will progress from the dry form of AMD to more severe forms such as geographic atrophy or wet AMD, hallmarked by choroidal neovascularization. There is no cure for AMD and treatment options are limited. Treatment options for wet AMD require invasive ocular injections or implants, yet fail to address the disease progressing factors. To provide more complete treatment of AMD, the application of a novel anti-inflammatory heme-bound human serum albumin (heme-albumin) protein complex delivered by antioxidant ROS scavenging polydopamine (PDA) nanoparticles (NPs) for sustained treatment of AMD was investigated. Through the induction of heme oxygenase-1 (HO-1) by heme-albumin in retinal pigment epithelial (RPE) cells, anti-inflammatory protection may be provided through the generation of carbon monoxide (CO) and biliverdin during heme catabolism. Our results show that the novel protein complex has negligible cytotoxicity towards RPE cells (ARPE-19), reduces oxidative stress in both inflammatory and ROS

The A2P2S6 (A = Ba and Pb) system provides a good platform to study how the polymorph effect and lone pair effect influence an acentric structure.

Municipalities in central Oklahoma, U.S.A. increasingly rely on water drawn from the Central Oklahoma Aquifer (COA) as surface water resources have not grown in proportion to population and current water demands. However, water drawn from certain regions of the COA frequently contains elevated levels of naturally occurring hexavalent chromium. Rock samples from the Norman Arsenic Test Hole Core (NATHC) were investigated to identify the mineralogic host(s) of Cr and mechanisms of Cr(VI) release

Supplemental material, sj-pdf-1-cat-10.1177_10760296231186144 for Extracellular Vesicle Size Reveals Cargo Specific to Coagulation and Inflammation in Pediatric and Adult Sickle Cell Disease by Kiruphagaran Thangaraju, Saini Setua, Christina Lisk, Delaney Swindle, Daniel Stephenson, Monika Dzieciatkowska, Derek R. Lamb, Parikshit Moitra, David Pak, Kathryn Hassell, Gemlyn George, Rachelle Nuss, Pavel Davizon-Castillo and Kurt R. Stenmark, Angelo D’Alessandro, David C. Irwin, Paul W. Buehler in Clinical and Applied Thrombosis/Hemostasis

Child Sexual Abuse (CSA) is both a global and national social issue, as well as an epidemic in various societies. Non-disclosure of CSA only worsens and extends survivors’ suffering, and CSA’s long-term effects can be devastating. Several studies have been done in the field of CSA and its health implications but rarely have previous studies addressed child sexual abuse disclosure (CSAD). The current study aimed at examining child factors of CSAD at Thika Level 5 Hospital (TL5H) in Kiambu County, Kenya. The study is a case study using a phenomenology approach where the primary data was collected from the sexual abuse survivors and caregivers using a mixed-method analysis. Interviews were conducted with 30 CSA survivors, 25 girls, and 5 boys: 5-17 years. The study utilised the convergent QUAL (investigative open-ended questions and storytelling) design with a Quan component (structured survey) to identify CSA survivors’ experiences while receiving medical treatment and therapeutic intervention at TL5H. Descriptive and thematic approaches were applied to analyse qualitative data that revealed survivors’ lived experiences with CSA. Informed by Bronfenbrenner’s Socio-Ecological Model (SEM), saliency analysis was applied to code the recurring and important themes from the data in order to identify which child factors. Survivors gave detailed accounts of types of threats and manipulation applied by perpetrators to stop them from disclosing abuse. Survivors said disclosing or not disclosing helped them cope with abuse trauma. Quantitative results revealed that 58% of the survivors who completed the disclosure process aged between 9-13 years, 83.3% were female, and 70% had achieved a lower level of education.

We present a comprehensive petrological and geochronological study of a single granulite sample from the lithosphere-scale Beraketa shear zone in southern Madagascar to constrain the orogenic history of Gondwana assembly in this region. The studied sample provides a panoply of data constraining the prograde, retrograde, and late metasomatic history of the region via the application of Ti-in-quartz, Ti-in-zircon, Zr-in-rutile, and Al-in-orthopyroxene thermobarometry; phase-equilibrium modeling; U–Pb monazite, zircon, and rutile petrochronology; and trace element diffusion chronometry in rutile methods. Our results reveal five stages of metamorphism along a clockwise P-T path that may have begun as early as 620–600 Ma and certainly by 580–560 Ma, based on the oldest concordant zircon dates. The rock heated to >725 °C at less than 7.5 kbar (stage 1) before burial to ~8 kbar (stage 2). By c. 540 Ma, the rock had heated to ~970 °C at ~9 kbar, and lost approximately 12% melt (stage 3), before decompressing and cooling to the solidus at ~860 °C and 6.5 kbar within 10 Myr (stage 4). The vast majority of monazite and zircon dates record stage 4 cooling and exhumation. Monazite and zircon rim dates as young as c. 510 Ma record subsolidus cooling (stage 5) and associated symplectite formation around garnet. U–Pb rutile dates record partial resetting at c. 460 Ma; Zr- and Nb-in-rutile diffusion chronometry link these dates to a metasomatic event that lasted

Single-cell RNA sequencing (scRNA-seq) of the bronchial epithelium enables examination of cellular subtypes and their responses to viral infections. Here, an optimized method for the isolation of virally infected primary bronchial epithelial cells using a commercially available microfluidic device is presented. Using this method single cells can be rapidly isolated with minimal equipment available in most laboratories. Isolation can be carried out inside biological safety cabinets, permitting the use of virally infected cells. Both cell-line and primary cells isolated using the device retained sufficient RNA integrity for the generation of short-read sequencing-compatible cDNA libraries to facilitate scRNA-seq.

Individuals with anorexia (AN) or bulimia nervosa (BN) often present with fear of loss of control in the context of eating. It is unclear whether this fear of loss of control, which has been associated with fear of failure and a sense of not being in charge of one’s own life in eating disorders, can be distinguished from self-perceived maintained control over food intake in AN. Further, anxious traits are elevated across eating disorders and could contribute to this fear of loss of control. We recruited 113 adult women: restricting type AN (n = 26), BN (n = 28), and healthy controls (CW, n = 59). Participants completed the Eating Expectancies Inventory (EEI), which assesses learned expectations on the effects of eating, including whether Eating Leads to Feeling out of Control, and the Trait Food Craving Questionnaire (FCQ-T), which measures food craving and the ability to withstand those cravings, including self-perceived Lack of Control Over Eating. Eating Leads to Feeling out of Control was elevated in AN and BN compared to CW. Lack of Control Over Eating was similar between AN and CW but elevated in BN. Intolerance of uncertainty correlated with those measures in CW only. Individuals with restricting-type AN experience feeling out of control when eating while maintaining self-perceived control over eating. The EEI’s eating leads to feeling out of control is associated with negative self-improvement expectations. Targeting self-improvement through more functional strategies could be an important aspect in psychotherapy in AN and reduce the perceived need to restrict food intake. Level III, Evidence obtained from well-designed cohort or case–control analytic studies.

Mast cells (MCs) are classically associated with allergic asthma but their role in antiviral immunity is unclear. Human rhinoviruses (HRVs) are a major cause of asthma exacerbations and can infect and replicate within MCs. The primary site of HRV infection is the airway epithelium and MCs localise to this site with increasing asthma severity. The asthma susceptibility gene, IL-33, encodes an epithelial-derived cytokine released following HRV infection but its impact on MC antiviral responses has yet to be determined. In this study we investigated the global response of LAD2 MCs to IL-33 stimulation using RNA sequencing and identified genes involved in antiviral immunity. In spite of this, IL-33 treatment increased permissiveness of MCs to HRV16 infection which, from the RNA-Seq data, we attributed to upregulation of ICAM1. Flow cytometric analysis confirmed an IL-33-dependent increase in ICAM1 surface expression as well as LDLR, the receptors used by major and minor group HRVs for cellular entry. Neutralisation of ICAM1 reduced the IL-33-dependent enhancement in HRV16 replication and release in both LAD2 MCs and cord blood derived MCs. These findings demonstrate that although IL-33 induces an antiviral signature in MCs, it also upregulates the receptors for HRV entry to enhance infection. This highlights the potential for a gene-environment interaction involving IL33 and HRV in MCs to contribute to virus-induced asthma exacerbations.

Identifying which patients can receive immediate intramedullary nailing (IMN) after bilateral femoral shaft fracture may improve health-related quality of life outcomes and decrease healthcare costs. This retrospective study evaluated the perioperative factors that guided emergency department transfer of patients to the operating room (OR) where IMN or temporizing external fixation (TEF) was performed, to the intensive care unit (ICU), or to the orthopedic ward. The hypothesis was that patients referred initially to the OR or to the ICU had more serious co-morbidities, complications, or orthopedic polytrauma, increasing the likelihood that they would benefit from "damage control orthopedics" and TEF use.A Level I Trauma Center database (2010-2020) review identified the records of 23 patients that met study inclusion and exclusion criteria. Most sustained their injury in a motor vehicle accident (87%) and were not wearing a seatbelt.Patients transferred to the operating room had a greater body mass index and shorter times between admission and surgery. Those transferred to the OR or ICU had higher injury severity scores (ISS), higher arterial blood OPatients with higher BMI, ISS, greater RBCU transfusion needs, with pneumothorax, rib fractures, or acute complications requiring exploratory laparotomy were more likely to be initially transferred to the OR or ICU. Patients transferred to the orthopedic ward represented a more heterogenous group with greater possibility for benefitting from earlier definitive IMN.

Breast milk is essential for facilitating the growth and development of infants and for providing immune protection against viral infections in the infant’s airways. Yet, regulation of inflammation by milk components may be needed to reduce immune pathology. While milk-derived extracellular vesicles (EVs) are bestowed with immunomodulatory capacities, their role in bronchial epithelial barrier function and inflammation has not yet been examined. We hypothesised that during feeding, milk is not only ingested, but aerosols containing milk EVs are inhaled and locally delivered to the infant’s airways to suppress aberrant inflammation. A bronchial epithelial model of viral infection was used to explore the direct effect of milk EVs on cellular barrier function and cytokine release during stimulation with a viral dsRNA analogue (Poly I:C). We demonstrate that milk EVs improved the dsRNA-mediated decrease in ionic barrier integrity, limited tight junction reorganisation and reduced inflammatory cytokine production (IL-6, IL-8 and TNF-α). This protective response was EV-mediated, could be successfully titrated and exhibited a time-dependent response. The results indicate that if EV-containing milk aerosols are inhaled during feeding, this may lead to protection of the airway integrity from adverse inflammatory effects.

As a mid-size international pharmaceutical company, we initiated 4 years ago the launch of a dedicated high-throughput computing platform supporting drug discovery. The platform named 'Specifically,We report our achievements, but also our challenges in implementing data access and governance processes, building up hardware and user interfaces, and acculturing scientists to use predictive models to inform decisions.

Background Family carers of persons living with dementia who are residing in long term care (LTC), often experience significant changes in their roles and relationships which affects mental and physical health. Research has focused on describing the carers’ experience, but not on how they deal with these changes or their perceptions of support needs. The purpose of this study was to explore how family carers of persons living with dementia residing in LTC deal with significant changes and to understand how best to support these carers. Methods Eight face-to-face audio-recorded focus group interviews were conducted with 45 participants from September 2019 to January 2020, as part of a larger study aimed at guiding the adaptation of an online toolkit to support family carers of persons living with dementia residing in LTC. Applied thematic analysis was used to analyze the focus group data. Findings/results Carers dealt with the significant changes they experienced through the process of “building a new life” consisting of two sub-processes: a) building new relationships (with their family member, LTC staff and others outside of LTC), and b) finding space for themselves (sharing of care and finding balance). Understanding dementia, support from others (staff, family and friends), connecting with resources, and being included in care decisions helped carers build a new life. Conclusion The process of building a new life describes the ways that family carers deal with the life-altering changes they experienced when a family member is admitted to LTC. Carers may be supported in building their new life, by providing them with information about dementia and how to relate to staff and their family member living with dementia. The quality of care being provided and the LTC environment may also play an important role in how carers deal with the significant changes they experience.

Introduction: The few studies that have investigated patterns of routine checkup (hereafter routine checkups) among Saudis have found overall low rates of use. Those studies focused mainly on understanding the influence of individual characteristics on use of routine checkup. Aims: The main purpose of this study was to consider a wider array of factors beyond individual characteristics, including system-based factors, beliefs, attitudes, and satisfaction, and to examine their influence on use of routine checkup among Saudi students studying in the United States. Methods: A cross-sectional survey targeting Saudi students studying in the United States aged 19 years or older was conducted to gather information about their sociodemographic characteristics, needs for healthcare, use of routine checkup and satisfaction with access to primary care services. Descriptive statistics and logistic regression analysis were conducted to determine factors influencing use of routine checkup among Saudis. Results: 381 surveys were eligible to be included in the analyses. Among the included participants, only 25.5% had a routine checkup after the age of 18 years. The likelihood of having routine checkup after the age of 18 was significantly higher among those who trusted provided primary care, believed in the importance of routine checkup, had health insurance, had chronic conditions and were physically active, and was significantly lower among married individuals. Conclusions: The use of routine checkup is low among Saudis and this study has laid the foundation for future research that can inform policy and decision-making related to improving use of routine care in Saudi Arabia.

This paper brings together both theoretically and empirically two strands of social science research: migration and developmental idealism. The paper is motivated by the fact that there are extensive bodies of research about migration and about developmental idealism, but almost no discussion in the literature about how they might be interconnected. We present theoretical arguments concerning the influence of migration in distributing developmental idealism around the world and in developmental idealism being a force influencing the migration decisions of people. We also provide an empirical investigation of how variation in developmental idealism may have been an influence on migration and choice of migration destinations in Nepal. Thus, we extend the developmental idealism literature to include migration and the migration literature to include developmental idealism.

Older persons with serious illnesses living in rural communities are an underserved population. They often live with heavy symptom burden and poor quality of life with limited access to resources. Nav-CARE (Navigation: Connecting Accessing Resourcing and Engaging) was developed to specially train and mentor volunteer navigators who help connect older persons with serious illness to the resources and information they need. Aims: This mixed methods longitudinal study evaluated Nav-CARE for feasibility, acceptability, ease of use, and satisfaction by older persons and volunteers. Methods: Nine volunteer navigators visited 23 older persons with serious illness every 3 to 4 weeks for 1 year. Data were collected from volunteer navigators, and older person participants at baseline, during the year- long implementation and post implementation. Results: Volunteer navigators and older persons reported Nav-CARE was easy to use, feasible and acceptable. The majority of older persons agreed or strongly agreed that they were satisfied with the navigation services (100%; 8/8), that navigation services were important to them (87%; 7/8), that they would recommend the program to someone else (87%; 7/8), and would participate in the program again (75%; 6/8). Similarly, volunteer navigators reported 100% (9/9) satisfaction with the program, 100% (9/9) would recommend it to others, and 67% (6/8) would participate again. Conclusions: Nav-CARE appears to be a feasible, acceptable, and satisfactory program for older persons with serious illness and volunteer navigators.

The majority of prostate cancer diagnoses are facilitated by testing serum Prostate Specific Antigen (PSA) levels. Despite this, there are limitations to the diagnostic accuracy of PSA. Consideration of patient demographic factors and biochemical adjuncts to PSA may improve prostate cancer risk stratification. We aimed to develop a contemporary, accurate and cost-effective model based on objective measures to improve the accuracy of prostate cancer risk stratification. Data were collated from a local institution and combined with patient data retrieved from the Prostate, Lung, Colorectal and Ovarian Cancer screening Trial (PLCO) database. Using a dataset of 4548 patients, a machine learning model was developed and trained using PSA, free-PSA, age and free-PSA to total PSA (FTR) ratio. The model was trained on a dataset involving 3638 patients and was then tested on a separate set of 910 patients. The model improved prediction for prostate cancer (AUC 0.72) compared to PSA alone (AUC 0.63), age (AUC 0.52), free-PSA (AUC 0.50) and FTR alone (AUC 0.65). When an operating point is chosen such that the sensitivity of the model is 80% the specificity of the model is 45.3%. The benefit in AUC secondary to the model was related to sample size, with AUC of 0.64 observed when a subset of the cohort was assessed. Development of a dense neural network model improved the diagnostic accuracy in screening for prostate cancer. These results demonstrate an additional utility of machine learning methods in prostate cancer risk stratification when using biochemical parameters.

OBJECTIVE: To determine if children’s “pester power” related to a classroom-based nutrition program, Together, We Inspire Smart Eating (WISE), is related to familial dietary habits and parental food purchases and practices. METHODS: Classroom teachers delivered weekly WISE lessons at seven Head Start sites across two states in the Southern United States. Pre- and post-intervention, parents were interviewed on consumption of WISE fruits and vegetables, intake of nutrient-poor foods, parenting practices related to food, and exposure to WISE through the child’s “pester power”. RESULTS: After controlling for baseline levels of outcome variables, child willingness to try new foods at baseline, and the effect of state, “pester power” predicated significant variance in the outcomes of consumption of WISE foods [F(3, 229) = 34.7, p

The study of social capital has been one of the strongest areas of recent advance in migration research, but there are still many questions about how it works and why it has varying effects in studies of different places. In this article, we address the contextual variation in social capital’s effects on migration by considering migration brokers. We argue that destinations for which migration is logistically difficult to arrange give rise to brokerage industries and hypothesize that brokers, in turn, substitute for the informational capital typically provided by social networks. Our empirical tests in Nepal support this narrative, showing that social networks matter for migration to destinations where brokers are not available and have little discernible effect on migration to brokered destinations. Our results suggest that migration research should consider the growing role of brokerage agencies, that theorizations of social capital more broadly must contend with how it is delimited by brokers, and that social scientists might also consider other consequences that can arise from these migration brokers that are increasingly common in many countries and provide a marketized replacement for social capital in some cases.

The current therapy for treating neovascular age-related macular degeneration requires monthly intravitreal injection of angiogenesis inhibitors such as bevacizumab or ranibizumab via a 31-gauge needle to inhibit choroidal neovascularization. However, repeated intravitreal injections are associated with poor patient compliance and potential side effects. Microparticle-based injectable devices have shown great promise to address this issue by sustained delivery of protein therapeutics, but critical barriers remain, including limited loading capacity and steady long-term release without compromising the anti-angiogenic activity of drugs. Addressing these challenges, we developed a unique method for synthesizing biodegradable polymer-based core-shell microparticles with sizes around 10 μm, high physical integrity, and uniform size. Subsequent electrostatic and physical interactions to control protein diffusion were designed for the core-shell microparticles to effectively increase the capacity of drug loading to 25%, reduce burst release by almost 30%, and extend the period of drug release from 3 to 6 months. Remarkably, the microparticles enabled a longer-term drug administration and maintained high drug potency up to 6 months in vitro, representing significant advancement compared to conventional microparticle-based delivery platforms or currently commercialized devices. Additionally, the microparticles presented minimal toxicity to human retinal cells in vitro with over 90% cell viability, and they also exhibited good injection feasibility through 31-gauge needles in an ex vivo porcine eye model. These results warrant further studies to evaluate the clinical potential for treating posterior ophthalmic diseases as well as other conditions or injuries requiring long-term local drug administration.

Vascular endothelial growth factor (VEGF) is a key regulator of abnormal blood vessel growth. As such, bevacizumab-based inhibition of VEGF has been the clinically adopted strategy to treat colorectal and breast cancers as well as age-related macular degeneration (AMD). However, as the treatment of vascular diseases often requires a high drug concentration for a long period, the burst release of bevacizumab remains a critical limitation in anti-VEGF-based therapies. Maintaining bevacizumab at high concentrations over extended periods remains challenging due to insufficient drug loading capacity and drug-device interactions. We report the development of a polymeric based bi-layered capsule that could address these challenges by extending the release over one year, thereby providing an effective platform enabling treatment of chronic vascular diseases. Remarkably, the developed capsules have a bi-layered structure which ensures the structural integrity of the injectable capsules and appropriate diffusion of bevacizumab by providing optimal physical trapping and electrostatic interaction. Meanwhile, the central hollow design enables a higher drug loading to meet the need for long-term release of bevacizumab for several months to one year. Using an in vitro drug release assay, we demonstrated that the bi-layered capsule could produce longer-term local drug administration by intravitreal injection compared to previously reported devices. The capsules also present minimal toxicity and maintain anti-VEGF potency, suggesting that our approach may have the potential to treat vascular-related diseases using bevacizumab.

Ultra-low-level measurements of radionuclides in air have been conducted at the Savannah River National Laboratory (SRNL) to determine the atmospheric concentration of fission products released following the Fukushima Daiichi reactor accident on March 11, 2011. Air filter samples were acquired from two high-volume collection systems (a traditional filter-based system and an electrostatic precipitator-based system) to monitor airborne radionuclide concentrations in the period covering from 2 weeks to 3 years after the disaster. The world-wide spread of low-level concentrations of airborne fission products from the Fukushima event provided a unique opportunity to demonstrate SRNL's electrostatic particle collection technology and other improvements in environmental monitoring developed at the Savannah River Site (SRS). Detecting and analyzing the release allowed a comprehensive test of SRS systems for monitoring environmental radioactivity. Gamma-ray-emitting fission products (