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Philip JT Reardon,1,* Maryam Parhizkar,2,* Anthony H Harker,3 Richard J Browning,4 Vessela Vassileva,5 Eleanor Stride,4 R Barbara Pedley,5 Mohan Edirisinghe,2 Jonathan C Knowles1 1Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, 2Department of Mechanical Engineering, 3Department of Physics & Astronomy, University College London, London, 4Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, 5Department of Oncology, UCL Cancer Institute, University College London, London, UK *These authors contributed equally to this work Abstract: Increasing the clinical efficacy of toxic chemotherapy drugs such as cisplatin (CDDP), via targeted drug delivery, is a key area of research in cancer treatment. In this study, CDDP-loaded poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles (NPs) were successfully prepared using electrohydrodynamic atomization (EHDA). The configuration was varied to control the distribution of CDDP within the particles, and high encapsulation efficiency (>70%) of the drug was achieved. NPs were produced with either a core–shell (CS) or a matrix (uniform) structure. It was shown that CS NPs had the most sustained release of the 2 formulations, demonstrating a slower linear release post initial “burst” and longer duration. The role of particle architecture on the rate of drug release in vitro was confirmed by fitting the experimental data with various kinetic models. This indicated that the release process was a simple diffusion mechanism. The CS NPs were effectively internalized into the endolysosomal compartments of cancer cells and demonstrated an increased cytotoxic efficacy (concentration of a drug that gives half maximal response [EC50] reaching 6.2 µM) compared to free drug (EC50 =9 µM) and uniform CDDP-distributed NPs (EC50 =7.6 µM) in vitro. Thus, these experiments indicate that engineering the structure of PLGA NPs can be exploited to control both the dosage and the release characteristics for improved clinical chemotherapy treatment. Keywords: cisplatin, drug delivery, cancer chemotherapy, polymer, poly(lactic-co-glycolic acid), nanoparticles, electrohydrodynamic atomization, controlled release

Colombia currently hosts nearly three million Venezuelan refugees and migrants and is home to seven million internally displaced Colombians. For forcibly displaced populations in Colombia, and especially for women, gender-based violence (GBV) poses a threat during transit and in their new homes where xenophobia, lack of accessible and adequate services, limited safe economic opportunities, and lack of information on access to services, further increase risk. The dearth of livelihood opportunities also affects forcibly displaced populations, especially women. This study will conduct a randomized-controlled trial (RCT) of HIAS' Entrepreneurship School with Gender Lens (ESGL), a program that targets forcibly displaced GBV survivors and women at-risk to help them develop business ideas, access needed support for the prevention of and response to GBV, and improve overall self-reliance. The RCT will be conducted within three cities in Colombia; approximately 80 eligible participants will be enrolled in each city and randomized to a treatment or control arm. Survey questionnaires will be administered to participants at baseline, eight months following baseline (endline), and 3-4 months after endline. Outcomes of interest include household self-reliance, mental health, resilience, empowerment, utilization of GBV services, and social support., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Stark et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Colombia, which hosts over 3 million of the Venezuelan diaspora, is lauded for its progressive approach to social integration, including providing migrants access to its universal health coverage system. However, barriers to healthcare persist for both migrant and host populations, with poorly understood disparities in healthcare-seeking behaviors and associated costs. This is the first study to link healthcare-seeking behaviors with costs for Venezuelan migrants in Colombia, encompassing costs of missing work or usual activities due to healthcare events., Methods: We use self-reported survey data from Venezuelan migrants and Colombians living in Colombia (September-November 2020) to compare healthcare-seeking behaviors and cost variables by nationality using two-sampled t-tests or Chi-square tests (X 2 ). The International Classification of Diseases was used to compare reported household illnesses for both populations. Average health service direct costs were estimated using the Colombian Government's Suficiencia database and self-reported out-of-pocket (OOP) payments for laboratory and pharmacy services. Indirect costs were calculated by multiplying self-reported days of missed work or usual activities with estimated income levels, derived by matching characteristics using the Gran Enquesta Integrada de Hogares database. We calculate economic burdens for both populations, combining self-reported healthcare-seeking behaviors and estimated healthcare service unit costs across six healthcare-seeking behavior categories., Results: Despite similar disease profiles, Venezuelan migrants are 21.3% more likely to forego formal care than Colombians, with 746.3% more Venezuelans reporting lack of health insurance as their primary reason. Venezuelan women and uninsured report the greatest difficulties in accessing health services, with accessing medications becoming more difficult for Venezuelan women during the COVID-19 pandemic. Colombians cost the health system more per treated illness event (US$40) than Venezuelans (US$26) in our sample, over a thirty-day period. Venezuelans incur higher costs for emergency department visits (123.5% more) and laboratory/ pharmacy OOP payments (24.7% more)., Conclusions: While Colombians and Venezuelans share similar disease burdens, significant differences exist in access, cost, and health-seeking behaviors. Increasing Venezuelan health insurance enrollment and tackling accessibility barriers are crucial for ensuring healthcare equity and effectively integrating the migrant population. Findings suggest that improving migrant access to primary healthcare would produce savings in Colombian healthcare expenditures., (© 2024. The Author(s).)

Background: Violence against children and youth poses public health risks regarding mental health symptoms and substance use. Less studied is the relationship between violence and mental health/substance abuse in the Latin American context. This study explored sex-stratified relationships between violence and mental health/substance use among Colombian youth., Methods: We analyzed the 2018 Colombian Violence Against Children and Youth Survey, which collected cross-sectional data from Colombian youth (13-24 years) (n = 2705). Exposure variables were (i) binary sexual, emotional, and physical victimization and (ii) poly-victimization. The outcomes were binary suicidal thoughts, self-harm, past-month psychological distress, binge drinking, smoking, and drug use. Sex-stratified, logistic regressions were adjusted for age, primary school, parental presence, relationship status, and witnessing community violence., Results: For females, (i) emotional violence (compared to being unexposed) was associated with greater odds of suicidal thoughts, self-harm, and psychological distress and (ii) sexual violence was associated with suicidal thoughts and self-harm. For males, (i) emotional violence (compared to being unexposed) was associated with greater odds of suicidal thoughts and psychological distress, but not self-harm and (ii) sexual violence exposure was associated with suicidal thoughts and self-harm. Physical violence was generally not associated with internalized mental health outcomes for females/males, when emotional and sexual violence were held constant. Poly-victimization was consistently and positively associated with internalized mental health symptoms among females, and to a lesser degree for males. Substance use outcomes for males or females were not associated with violence., Conclusions: Findings highlight the internalized mental health burden of emotional and sexual violence., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Exposure to protracted public violence is increasingly referenced as a risk factor for domestic violence, but limited quantitative evidence has demonstrated this association to date. This study analyzes associations in Colombia between lifetime experiences of external violence, including the Colombia civil conflict and community interpersonal violence, and experiences of household violence, including intimate partner and caregiver violence., Methods and Findings: We use the 2018 Colombia Violence Against Children and Youth Survey, employing multi-variable logistic regressions to determine the association between exposure to external violence and household violence victimization for females aged 13-24 (n = 1406). Adjusted models controlled for age, ever married, currently in school, and past 12-mo work experience and standard errors were adjusted to account for the multi-stage sampling design. Females who had ever witnessed community violence (39.23 %) faced increased risks of experiencing both physical violence (aOR = 2.81; 95 % CIs: 1.54-5.14; p < 0.001) and emotional violence (aOR: 2.48; 95 % CIs: 1.29-4.75; p < 0.01) from caregivers. Females who had ever witnessed internal conflict (15.99 %) had a greater likelihood of experiencing emotional violence from caregivers (aOR: 5.24; 95 % CIs: 1.86-14.76; p < 0.01) as well as physical violence perpetrated by intimate partners (aOR: 3.31; 95 % CIs: 1.22-8.95; p < 0.05)., Conclusions: This study demonstrates the connection between exposure to community violence and internal conflict and household violence victimization among adolescent and young adult females in Colombia. Findings build the evidence base for more holistic and coordinated policy and programming efforts and foreground the need to identify and support vulnerable populations across socioecological domains in contexts of chronic violence., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: There is a paucity of research examining the contextual factors that shape the violence experienced by those engaged in transactional sex, particularly among adolescent boys and young men. Recognizing the acute vulnerability among youth engaged in transactional sex, this analysis examined the associations between lifetime transactional sex and experience of violence among 13- to 24-year-old males., Methods: Using data from two strata of the 2018 Violence Against Children and Youth Survey from Colombia, logistic regressions were used to estimate the association between engagement in transactional sex and violence exposure. Three groups of violence outcomes were examined: violence victimization, violence perpetration, and witnessing violence., Results: Violence victimization and witnessing violence were widespread. Adolescent boys and young men with a lifetime history of transactional sex were significantly more likely to experience violence victimization than those without a lifetime history of transactional sex, particularly intimate partner violence (adjusted odds ratio [aOR]: 5.23 and 5.41) and caregiver emotional violence (aOR: 7.23 and 8.74). In the national and priority samples respectively, those with a lifetime history of transactional sex were also significantly more likely to witness violence within the home (aOR: 4.42 and 4.99) and outside of the home (aOR: 7.24 and 28.32)., Discussion: Although research is needed to determine causal pathways, our findings highlight the ubiquity of violence and the criticality of supporting this group of adolescent boys and young men. Interventions for those with a history of transactional sex should address factors that may contribute to drivers of violence and transactional sex., (Copyright © 2022 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Hypothesis: Developing oral formulations to enable effective release of poorly water-soluble drugs like progesterone is a major challenge in pharmaceutics. Coaxial electrospray can generate drug-loaded nanoparticles of strategic compositions and configurations to enhance physiological dissolution and bioavailability of poorly water-soluble drug progesterone., Experiments: Six formulations comprising nanoparticles encapsulating progesterone in different poly(lactide-co-glycolide) (PLGA) matrix configurations and compositions were fabricated and characterized in terms of morphology, molecular crystallinity, drug encapsulation efficiency and release behavior., Findings: A protocol of fabrication conditions to achieve 100% drug encapsulation efficiency in nanoparticles was developed. Scanning electron microscopy shows smooth and spherical morphology of 472.1±54.8 to 588.0±92.1 nm in diameter. Multiphoton Airyscan super-resolution confocal microscopy revealed core-shell nanoparticle configuration. Fourier transform infrared spectroscopy confirmed presence of PLGA and progesterone in all formulations. Diffractometry indicated amorphous state of the encapsulated drug. UV-vis spectroscopy showed drug release increased with hydrophilic copolymer glycolide ratio while core-shell formulations with progesterone co-dissolved in PLGA core exhibited enhanced release over five hours at 79.9±1.4% and 70.7±3.5% for LA:GA 50:50 and 75:25 in comparison with pure progesterone without polymer matrix in the core at 67.0±1.7% and 57.5±2.8%, respectively. Computational modeling showed good agreement with the experimental drug release behavior in vitro., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Zhang et al.)

There are several limitations with monodrug cancer therapy, including poor bioavailability, rapid clearance and drug resistance. Combination therapy addresses these by exploiting synergism between different drugs against cancer cells. In particular, the combination of epigenetic therapies with conventional chemotherapeutic agents can improve the initial tumour response and overcome acquired drug resistance. Co-encapsulation of multiple therapeutic agents into a single polymeric nanoparticle is one of the many approaches taken to enhance therapeutic effect and improve the pharmacokinetic profile. In this study, different types of poly(lactic- co -glycolic acid) (PLGA) nanoparticles (NPs), matrix and core-shell (CS), were investigated for simultaneous encapsulation of a demethylating drug, decitabine, and a potent anticancer agent, cisplatin. It was shown that by altering the configuration of the CS structure, the release profile could be tuned. In order to investigate whether this could enhance the anticancer effect compared to cisplatin, human ovarian carcinoma cell line (A2780) and its cisplatin resistant variant (A2780cis) were exposed to free cisplatin and the CS-NPs. A better response was obtained in both cell lines (11% and 51% viability of A2780 and A2780cis, respectively) using CS-NPs than cisplatin alone (27%, 82% viability of A2780 and A2780cis, respectively) or in combination with decitabine (22%, 96% viability of A2780 and A2780cis, respectively) at equivalent doses (10 μM)., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Co-axial electrohydrodynamic atomization was used to prepare core/shell polymethylsilsesquioxane particles for co-delivery of metformin and glibenclamide in a sustained release manner. The drug-loaded microparticles were mostly spherical and uniformly distributed in size, with average diameters between 3 and 5 µm across various batches. FTIR was used to confirm the presence of drugs within the particles while X-ray diffraction studies revealed drugs encapsulated existed predominantly in the amorphous state. Intended as systems that potentially can act as depot formulations for long-term release of antidiabetics, a detailed analysis of drug release from these particles was necessary. Drugs of different solubilities were selected in order to study the effects of drug solubility from a core/shell particle system. Further analyses to determine how conditions such as release into a limited volume of media, sampling rate and partitioning of drug between the core and shell layers influenced drug release were conducted by comparing experimental and mathematically modelled outcomes. It was found that while the solubility of drug may affect release from such systems, rate of removal of drug (sampling frequency) which upsets local equilibrium at the particle/solution interface prompting a rapid release to redress the equilibrium influenced release more.

Background: Research examining the interrelated drivers of household violence against women and violence against children is nascent, particularly in humanitarian settings. Gaps remain in understanding how relocation, displacement and ongoing insecurity affect families and may exacerbate household violence., Methods: Employing purposive sampling, we used photo elicitation methods to facilitate semi-structured, in-depth interviews with female and male adolescents and adults aged 13-75 ( n  = 73) in two districts in Colombia from May to August of 2017. Participants were displaced and/or residing in neighborhoods characterized by high levels of insecurity from armed groups., Results: Using inductive thematic analysis and situating the analysis within a feminist socioecological framework, we found several shared drivers of household violence. Intersections among drivers at all socioecological levels occurred among societal gender norms, substance use, attempts to regulate women's and children's behavior with violence, and daily stressors associated with numerous community problems. A central theme of relocation was of family compositions that were in continual flux and of family members confronted by economic insecurity and increased access to substances., Conclusions: Findings suggest interventions that systemically consider families' struggles with relocation and violence with multifaceted attention to socioecological intersections., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Single and coaxial electrospraying was used to prepare Eudragit L100-55 polymer microparticles containing prednisolone as the active pharmaceutical ingredient. Different compositions of prednisolone and Eudragit L100-55 were used to develop five different formulations with different polymer : drug ratios. The resultant microparticles had a toroidal shape with a narrow size distribution. Prednisolone was present in an amorphous physical state, as confirmed by X-ray diffraction analysis. Dissolution studies were carried out in order to investigate the feasibility of the proposed system for site-specific release of prednisolone. The release rates were interpreted in terms of diffusion-controlled release. It was shown that utilization of pH-responsive Eudragit L100-55 could minimize the release of prednisolone in the acidic conditions of the stomach, which was followed by rapid release as the pH of the release medium was adjusted to 6.8 after the first 2 h. This is especially desirable for the treatment of conditions including inflammatory bowel disease and colon cancer., (© 2018 The Authors.)

Targeted delivery of potent, toxic chemotherapy drugs, such as cisplatin, is a significant area of research in cancer treatment. In this study, cisplatin was successfully encapsulated with high efficiency (>70%) in poly (lactic-co-glycolic acid) polymeric nanoparticles by using electrohydrodynamic atomization (EHDA) where applied voltage and solution flow rate as well as the concentration of cisplatin and polymer were varied to control the size of the particles. Thus, nanoparticles were produced with three different drug:polymer ratios (2.5, 5 and 10wt% cisplatin). It was shown that smaller nanoparticles were produced with 10wt% cisplatin. Furthermore, these demonstrated the best sustained release (smallest burst release). By fitting the experimental data with various kinetic models it was concluded that the release is dependent upon the particle morphology and the drug concentration. Thus, these particles have significant potential for cisplatin delivery with controlled dosage and release period that are crucial chemotherapy parameters., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Polymer-coated pores play a crucial role in nucleo-cytoplasmic transport and in a number of biomimetic and nanotechnological applications. Here we present Monte Carlo and Density Functional Theory approaches to identify different collective phases of end-grafted polymers in a nanopore and to study their relative stability as a function of intermolecular interactions. Over a range of system parameters that is relevant for nuclear pore complexes, we observe two distinct phases: one with the bulk of the polymers condensed at the wall of the pore, and the other with the polymers condensed along its central axis. The relative stability of these two phases depends on the interpolymer interactions. The existence the two phases suggests a mechanism in which marginal changes in these interactions, possibly induced by nuclear transport receptors, cause the pore to transform between open and closed configurations, which will influence transport through the pore.

Understanding how structural features determine specific biological activities has often proved elusive. With over 161,000 steroid structures described, an algorithm able to predict activity from structural attributes would provide manifest benefits. Molecular simulations of a range of 35 corticosteroids show striking correlations between conformational mobility and biological specificity. Thus steroid ring A is important for glucocorticoid action, and is rigid in the most specific (and potent) examples, such as dexamethasone. By contrast, ring C conformation is important for the mineralocorticoids, and is rigid in aldosterone. Other steroids that are less specific, or have mixed functions, or none at all, are more flexible. One unexpected example is 11-deoxycorticosterone, which the methods predict (and our activity studies confirm) is not only a specific mineralocorticoid, but also has significant glucocorticoid activity. These methods may guide the design of new corticosteroid agonists and antagonists. They will also have application in other examples of ligand-receptor interactions.

We assess routes to a diamond-based quantum computer, where we specifically look towards scalable devices, with at least 10 linked quantum gates. Such a computer should satisfy the deVincenzo rules and might be used at convenient temperatures. The specific examples that we examine are based on the optical control of electron spins. For some such devices, nuclear spins give additional advantages. Since there have already been demonstrations of basic initialization and readout, our emphasis is on routes to two-qubit quantum gate operations and the linking of perhaps 10-20 such gates. We analyse the dopant properties necessary, especially centres containing N and P, and give results using simple scoping calculations for the key interactions determining gate performance. Our conclusions are cautiously optimistic: it may be possible to develop a useful quantum information processor that works above cryogenic temperatures.

Our ab initio calculations of the hyperfine parameters for negatively charged vacancy-hydrogen and nitrogen-vacancy-hydrogen complexes in diamond compare static defect models and models which account for the quantum tunneling behavior of hydrogen. The static models give rise to hyperfine splittings that are inconsistent with the experimental electron paramagnetic resonance data. In contrast, the hyperfine parameters for the quantum dynamical models are in agreement with the experimental observations. We show that the quantum motion of the proton is crucial to the prediction of symmetry and hyperfine constants for two simple defect centers in diamond. Static a priori methods fail for these systems.

Experimental measurements have been made of the ultrasonic velocity and attenuation in some simple suspensions of, mainly, silicon carbide in water and in ethylene glycol. These are compared with theoretical predictions based on a novel hydrodynamic model. Predicted ultrasonic velocities are in excellent agreement with the measured values. Predicted and measured ultrasonic attenuations do not agree as well. However, the suspensions give rise to excess attenuations rising to a few hundred nepers per metre and special experimental techniques were needed to measure ultrasonic properties. To predict attenuations to within, say, 20% for mixtures such as these is a major achievement.