Characterization of metabolic alterations of chronic lymphocytic leukemia in the lymph node microenvironment.

Altered metabolism is a hallmark of both cell division and cancer. Chronic lymphocytic leukemia (CLL) cells circulate between peripheral blood (PB) and lymph nodes (LNs), where they receive proliferative and prosurvival signals from surrounding cells. However, insight into the metabolism of LN CLL and how this may relate to therapeutic response is lacking. To obtain insight into CLL LN metabolism, we applied a 2-tiered strategy. First, we sampled PB from 8 patients at baseline and after 3-month ibrutinib (IBR) treatment, which forces egress of CLL cells from LNs. Second, we applied in vitro B-cell receptor (BCR) or CD40 stimulation to mimic the LN microenvironment and performed metabolomic and transcriptomic analyses. The combined analyses indicated prominent changes in purine, glucose, and glutamate metabolism occurring in the LNs. CD40 signaling mostly regulated amino acid metabolism, tricarboxylic acid cycle (TCA), and energy production. BCR signaling preferably engaged glucose and glycerol metabolism and several biosynthesis routes. Pathway analyses demonstrated opposite effects of in vitro stimulation vs IBR treatment. In agreement, the metabolic regulator MYC and its target genes were induced after BCR/CD40 stimulation and suppressed by IBR. Next, 13C fluxomics performed on CD40/BCR-stimulated cells confirmed a strong contribution of glutamine as fuel for the TCA cycle, whereas glucose was mainly converted into lactate and ribose-5-phosphate. Finally, inhibition of glutamine import with V9302 attenuated CD40/BCR-induced resistance to venetoclax. Together, these data provide insight into crucial metabolic changes driven by the CLL LN microenvironment. The prominent use of amino acids as fuel for the TCA cycle suggests new therapeutic vulnerabilities.

Neurodevelopment in the Congenital Heart Disease Population as Framed by the Life Course Health Development Framework.

BACKGROUND: Adverse neurodevelopment is a common comorbidity associated with congenital heart disease (CHD). The consequences of adverse neurodevelopment are seen across the life course. The cause of adverse neurodevelopment is multifactorial, and use of a life course perspective can assist with understanding and enhancing neurodevelopment in individuals with CHD. PURPOSE: The purposes of this article are to (1) apply the Life Course Health Development framework to neurodevelopment in the population with CHD and (2) discuss how exposure to the pediatric cardiac intensive care unit (PCICU) environment during infancy is a point of intervention for improving neurodevelopmental outcomes. CONCLUSION: Individuals with CHD are at an increased risk for adverse neurodevelopment across the life course. The PCICU environment is a point of intervention for improving neurodevelopmental outcomes. Stress can lead to changes in brain structure and function that are associated with negative outcomes in terms of outward behavioral and functional capacity, and the PCICU environment is a source of stressful stimuli. Infancy is a period of rapid brain growth, and the brain is more susceptible to stress during this period of the life course, putting infants receiving care in the PCICU at an increased risk of adverse neurodevelopment. CLINICAL IMPLICATIONS: Interventions to support optimal neurodevelopment should focus on the PCICU environment during infancy. Developmentally supportive care models should be explored as a means of modifying the PCICU environment. In addition, more research is needed on the relationship between the PCICU and neurodevelopment. The conceptual model introduced can serve as a starting point for this research.

Intersections of phenomenology, voice beliefs and distress in bipolar disorder: a comparison with schizophrenia.

BACKGROUND: Auditory verbal hallucinations (AVH), or voice-hearing, can be a prominent symptom during fluctuating mood states in bipolar disorder (BD). AIMS: The current study aimed to: (i) compare AVH-related distress in BD relative to schizophrenia (SCZ), (ii) examine correlations between phenomenology and voice beliefs across each group, and (iii) explore how voice beliefs may uniquely contribute to distress in BD and SCZ. METHOD: Participants were recruited from two international sites in Australia (BD=31; SCZ=50) and the UK (BD=17). Basic demographic-clinical information was collected, and mood symptoms were assessed. To document AVH characteristics, a 4-factor model of the Psychotic Symptoms Rating Scale and the Beliefs about Voices Questionnaire-Revised were used. Statistical analyses consisted of group-wise comparisons, Pearson's correlations and multiple hierarchical regressions. RESULTS: It was found that AVH-related distress was not significantly higher in BD than SCZ, but those with BD made significantly more internal attributions for their voices. In the BD group, AVH-related distress was significantly positively correlated with malevolence, omnipotence and resistance, However, only resistance, alongside mania and depressive symptoms, significantly contributed to AVH-related distress in BD. DISCUSSION: Our findings have several clinical implications, including identification of voice resistance as a potential therapeutic target to prioritise in BD. Factoring in the influence of mood symptoms on AVH-related distress as well as adopting more acceptance-oriented therapies may also be of benefit.

A study of disparities in access to genetic care pre- and post-pandemic.

We aimed to explore the delivery of pediatric genetic care before and during the COVID-19 pandemic and assess if disparities in care existed or emerged. We retrospectively reviewed the electronic medical record for patients 18 years old or younger seen in the Division of Pediatric Genetics between September 2019-March 2020 and April-October 2020. Outcomes included time between referral and new visit, recommendation and completion of genetic testing and/or follow-up visit within 6 months, and telemedicine versus in-person format. Outcomes were compared pre- and post-COVID-19 emergence across ethnicity, race, age, health insurance, socioeconomic status (SES), and use of medical interpretation services. Three hundred thirteen total records were reviewed with comparable demographics between cohorts. Cohort 2 had shorter times between referral and new visit, greater telemedicine utilization, and a greater proportion of testing completed. Younger patients tended to have shorter times between referral and initial visit. In Cohort 1, those with Medicaid insurance or no coverage had longer referral-initial visit times. In Cohort 2, there were differences in testing recommendation based on age. For all outcomes, no disparities were observed across ethnicity, race, SES, or use of medical interpretation services. This study characterizes the impact of the pandemic on pediatric genetics care delivery at our center and may have wider implications.

Association between outpatient follow-up and incidence of revision after knee and hip replacements: a population-based cohort study.

BACKGROUND: Follow-up visits 5 or 7 years after surgery were recommended for people having primary hip or knee replacement. The benefits of this practice to patients and the healthcare system, however, have not yet been specifically examined. The aim of this study was to investigate the association between long-term follow-up outpatient hospital visits and revision rates for patients who undergo primary knee or hip replacement surgery. METHODS: Cohorts were identified for patients undergoing knee or hip replacement surgery using medical records from primary care practices within the UK Clinical Practice Research Datalink (CPRD) GOLD dataset linked to hospital records from the English Hospital Episodes Statistics (HES) data. Two groups of patients were compared in terms of revision and mortality rates: those with at least one long-term (between five and 10 years since primary surgery) follow-up visit at the orthopaedic department ('Follow-up' group), and those without ('No follow-up' group). RESULTS: A total of 9856 (4349 in the Follow-up group) patients with knee replacement and 10,837 (4870 in the Follow-up group) with hip replacement were included in the analysis. For knee replacement, the incidence of revision was 3.6% for those followed-up and 0.6% for those not followed-up. An adjusted regression model confirmed the difference in the hazard ratio (HR) for revision was statistically significant (HR: 5.65 [95% CI 3.62 to 8.81]). Mortality at 4 years was lower for the Follow-up (17%) compared to the No follow-up group (21%), but this difference was not statistically significant (HR: 0.95 [0.84 to 1.07]). For hip replacement, the incidence of revision rates were 3.2 and 1.4% for the follow-up and not follow-up groups, respectively, the difference being statistically significant (HR: 2.34 [1.71 to 3.20]). Mortality was lower for the Follow-up (15%) compared to the No follow-up group (21%), but the difference was not statistically significant (HR: 0.91 [0.81 to 1.02]). CONCLUSION: Patients attending follow-up orthopaedic consultations show a higher risk of revision surgery compared to those who are not followed-up. A cause for this difference could not be identified in this study but a likely explanation is that surgeons play an effective role as ultimate arbitrators when identifying patients to be included in long-term follow-up lists.

Viewing Then Doing?: Problem-Solving Court Coordinators' Perceptions of Medications for Opioid Use Disorders from a Nationally Representative Survey in the United States.

Background. Overdose deaths in the United States (U.S.) surpassed 100,000 in 2021. Problem-solving courts (PSCs), which originally began as drug courts, divert people with nonviolent felonies and underlying social issues (e.g. opioid use disorders (OUDs)) from the carceral system to a community-based treatment court program. PSCs are operated by a collaborative court staff team including a judge that supervises PSC clients, local court coordinators that manage PSC operations, among other staff. Based on staff recommendations, medications for opioid use disorders (MOUDs) can be integrated into court clients' treatment plans. MOUDs are an evidence-based treatment option. However, MOUDs remain widely underutilized within criminal justice settings partially due to negative perceptions of MOUDs held by staff. Objective. PSCs are an understudied justice setting where MOUD usage would be beneficial. This study sought to understand how court coordinators' perceptions and attitudes about MOUDs influenced their uptake and utilization in PSCs. Methods. A nationally representative survey of 849 local and 42 state PSC coordinators in the U.S. was conducted to understand how coordinators' perceptions influenced MOUD utilization. Results. Generally, court coordinators hold positive views of MOUDs, especially naltrexone. While state and local coordinators' views do not differ greatly, their stronger attitudes align with different aspects of and issues in PSCs such as medication diversion (i.e. misuse). Conclusions. This study has implications for PSCs and their staff, treatment providers, and other community supervision staff (e.g. probation/parole officers, court staff) who can promote and encourage the use of MOUDs by clients.

Medication-Assisted Treatment in Problem-solving Courts: A National Survey of State and Local Court Coordinators.

Problem-solving courts (PSCs) are a critical part of a societal effort to mitigate the opioid epidemic's devastating consequences. This paper reports on a national survey of PSCs (N = 42 state-wide court coordinators; N = 849 local court coordinators) and examines the structural factors that could explain the likelihood of a local PSC authorizing medication-assisted treatment (MAT) and MAT utilization. Results of the analyses indicate that MAT availability at the county level was a significant predictor of the likelihood of local courts authorizing MAT. The court's location in a Medicaid expansion state was also a significant predictor of local courts allowing buprenorphine and methadone, but not naltrexone. Problem-solving courts are in the early stages of supporting the use of medications, even when funding is available through Medicaid expansion policies. Adoption and use of treatment innovations like MAT are affected by coordinators' perceptions of MAT as well as structural factors such as the availability of the medications in the community and funding resources. The study has important implications for researchers, policymakers, and practitioners.

Pandemic Procedures: Adapting Problem-Solving Court (PSC) Operations and Treatment Protocols During COVID-19.

With an ongoing pandemic claiming hundreds of lives a day, it is unclear how COVID-19 has affected court operations, particularly problem-solving courts (PSCs) which have goals rooted in rehabilitation for participants in their programs. Even with practical recommendations from national organizations directing courts on how to manage COVID-19, whether and how PSCs met the needs of PSC participants during this time is underexplored. This study, drawn from a larger national study using a survey of PSC coordinators, examines the COVID-19 responses of PSCs to remain safely operational for participants. A sub-sample of survey respondents (n = 82 PSC coordinators) detailed how the COVID-19 pandemic led to changes to their court and treatment operations amidst the constraints of the pandemic. The courts' shifts in policy and practice have important impacts for court participants' treatment retention and success in the PSC program, and these shifts need more in-depth research in the future.

Adolescent experience of radically open dialectical behaviour therapy: a qualitative study.

BACKGROUND: Radically Open Dialectical Behaviour Therapy (RO DBT) is a novel transdiagnostic treatment that targets 'maladaptive overcontrol'; a transdiagnostic cluster of traits associated with excessive emotional and behavioural inhibitory control. Outcomes are promising for adults with a range of psychiatric disorders. No study to date has explored the adolescent experience of RO DBT. METHODS: Of the 25 eligible adolescents who received RO DBT between March 2015 and April 2017, 15 (14-17 years) consented and completed a semi-structured interview about their experience of treatment within 1 month of discharge. Interviews were recorded and then transcribed manually. Free text responses were analysed using reflexive thematic analysis. RESULTS: The majority (n = 13) had a primary diagnosis of anorexia nervosa, although comorbidity was the norm, with 80.0% having two or more predicted comorbid psychiatric diagnoses. All had received some prior psychological treatment. Four themes were identified from analysis of transcripts: 1) Broadening Horizons, 2) Building Connections, 3) Flexibility, 4) Information Overload. Generally, RO DBT was perceived as helpful in both content and process. The focus on social and broader well-being, rather than specific mental health symptoms, was considered beneficial by many. Adolescents appreciated the group-based format of skills classes and reported benefiting from learning and practicing skills each week. The fourth theme, Information Overload, highlighted that for some, the amount of content felt overwhelming and that it was hard to remember and digest all the information, suggesting that adaptations, or simplifications, may be required to ensure accessibility for adolescents. CONCLUSIONS: RO DBT is perceived as a relevant and beneficial new treatment for adolescents with maladaptive overcontrol. The broad treatment focus is perceived as unique and of particular benefit. It is reported to help with general and social functioning and foster cognitive and behavioural flexibility. Nevertheless, the amount and complexity of material was felt to be very large by some and may suggest the need for modified adolescent-specific materials.

Learning continuous chaotic attractors with a reservoir computer.

Neural systems are well known for their ability to learn and store information as memories. Even more impressive is their ability to abstract these memories to create complex internal representations, enabling advanced functions such as the spatial manipulation of mental representations. While recurrent neural networks (RNNs) are capable of representing complex information, the exact mechanisms of how dynamical neural systems perform abstraction are still not well-understood, thereby hindering the development of more advanced functions. Here, we train a 1000-neuron RNN-a reservoir computer (RC)-to abstract a continuous dynamical attractor memory from isolated examples of dynamical attractor memories. Furthermore, we explain the abstraction mechanism with a new theory. By training the RC on isolated and shifted examples of either stable limit cycles or chaotic Lorenz attractors, the RC learns a continuum of attractors as quantified by an extra Lyapunov exponent equal to zero. We propose a theoretical mechanism of this abstraction by combining ideas from differentiable generalized synchronization and feedback dynamics. Our results quantify abstraction in simple neural systems, enabling us to design artificial RNNs for abstraction and leading us toward a neural basis of abstraction.

Insights into wild-type dynamin 2 and the consequences of DNM2 mutations from transgenic zebrafish.

Dynamin 2 (DNM2) encodes a ubiquitously expressed large GTPase with membrane fission capabilities that participates in the endocytosis of clathrin-coated vesicles. Heterozygous mutations in DNM2 are associated with two distinct neuromuscular disorders, Charcot-Marie-Tooth disease (CMT) and autosomal dominant centronuclear myopathy (CNM). Despite extensive investigations in cell culture, the role of dynamin 2 in normal muscle development is poorly understood and the consequences of DNM2 mutations at the molecular level in vivo are not known. To address these gaps in knowledge, we developed transgenic zebrafish expressing either wild-type dynamin 2 or dynamin 2 with either a CNM or CMT mutation. Taking advantage of the live imaging capabilities of the zebrafish embryo, we establish the localization of wild-type and mutant dynamin 2 in vivo, showing for the first time distinctive dynamin 2 subcellular compartments. Additionally, we demonstrate that CNM-related DNM2 mutations are associated with protein mislocalization and aggregation. Lastly, we define core phenotypes associated with our transgenic mutant fish, including impaired motor function and altered muscle ultrastructure, making them the ideal platform for drug screening. Overall, using the power of the zebrafish, we establish novel insights into dynamin 2 localization and dynamics and provide the necessary groundwork for future studies examining dynamin 2 pathomechanisms and therapy development.

The severe epilepsy syndromes of infancy: A population-based study.

OBJECTIVE: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes. METHODS: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined. RESULTS: Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased. SIGNIFICANCE: Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, initial treatment, and prognostication.

Ethical issues in participatory arts methods for young people with adverse childhood experiences.

CONTEXT: Participatory arts-based methods such as photovoice, drama and music have increasingly been used to engage young people who are exposed to psychosocial risks. These methods have the potential to empower youth and provide them with an accessible and welcoming environment to express and manage difficult feelings and experiences. These effects are, however, dependent on the way these methods are implemented and how potential ethical concerns are handled. OBJECTIVE: Using the current literature on arts-based health research as a foundation, this paper examines ethical issues emerging from participatory arts methods with young people with traumatic experiences. RESULTS: We present a typology covering relevant issues such as power, accessibility, communication, trust and ownership, across the domains of partnership working, project entry, participation and dissemination. Drawing on our extensive clinical and research experiences, existing research and novel in-practice examples, we offer guidance for ethical dilemmas that might arise at different phases of research. CONCLUSION: Adequate anticipation and consideration of ethical issues, together with the involvement of young people, will help ensure that arts methods are implemented in research and practice with young people in a fair, meaningful and empowering way. PATIENT OR PUBLIC CONTRIBUTION: The issues reviewed are largely based on the authors' experience conducting participatory research. Each of the projects referenced has its own systems for PPI including, variously, consultations with advisory groups, coproduction, youth ambassadors and mentor schemes. One of the coauthors, Josita Kavitha Thirumalai, is a young person trained in peer support and has provided extensive input across all stages.

Factors Associated With Psychosocial Illness Impact Among Black/African American and Hispanic Older Women Living With HIV.

BACKGROUND: In 2018, one in six newly diagnosed individuals with HIV in the United States were adults aged 50 years and older, 24% were women, and 60% were Black/African American and Hispanic (42% and 18%, respectively). OBJECTIVES: This study aims to examine the factors associated with HIV psychosocial illness impact among Black/African American and Hispanic older women living with HIV. METHOD: Guided by the socioecological model, a secondary data analysis design with cross-sectional data that included 138 Black/African American and Hispanic women aged 50 years and older was conducted. RESULTS: Higher levels of avoidant coping, depressive symptoms, negative self-perception of health, and decreased social support were significant factors associated with HIV psychosocial illness impact among this sample. CONCLUSIONS: Findings from this study can contribute to identifying solutions to prevent and decrease these negative factors associated with HIV psychosocial illness impact among Black/African American and Hispanic older women.

Exploring patient willingness to accept hepatitis C-infected kidneys for transplantation.

BACKGROUND: As organs infected with Hepatitis C virus (HCV) provide an opportunity to expand the donor pool, the primary aim of this study is to explore patient willingness to accept a kidney from HCV-infected donors compared to other high-risk donors. METHODS: An anonymous, electronic survey was sent to all active kidney transplant waitlist patients at a single large volume transplant center. Patients were asked to respond to three hypothetical organ offers from the following: 1) HCV-infected donor 2) Donor with active intravenous drug use and 3) Donor with longstanding diabetes and hypertension. RESULTS: The survey was sent to 435 patients of which 125 responded (29% response rate). While 86 out of 125 patients (69%) were willing to accept an HCV-infected kidney, only a minority of respondents were willing to accept a kidney from other high-risk donors. In contrast to other studies, by multivariable logistic regression, age and race were not associated with willingness to accept an HCV-infected kidney. CONCLUSIONS: In this exploratory study, utilization of kidneys from HCV-infected donors to expand the donor pool appears to be an acceptable option to patients.

Setting up an arthroplasty care practitioner-led virtual clinic for follow-up of orthopaedic patients.

This article provides an overview of the set up for an arthroplasty care practitioner (ACP)-led virtual orthopaedic clinic (VOC). Suitable patients attend a local hospital for an X-ray and complete a questionnaire, but do not physically attend a clinic. This has been running successfully in a university teaching hospital and has led to cost savings, a reduction in outpatient waiting times and high levels of patient satisfaction. Similar clinics have the potential to become normal practice across the NHS. This article outlines the steps necessary to implement a successful VOC. The lessons learnt during this exercise may be useful for other ACPs when setting up a VOC.

Ice and anti-nucleating activities of an ice-binding protein from the annual grass, Brachypodium distachyon.

Plants exposed to sub-zero temperatures face unique challenges that threaten their survival. The growth of ice crystals in the extracellular space can cause cellular dehydration, plasma membrane rupture and eventual cell death. Additionally, some pathogenic bacteria cause tissue damage by initiating ice crystal growth at high sub-zero temperatures through the use of ice-nucleating proteins (INPs), presumably to access nutrients from lysed cells. An annual species of brome grass, Brachypodium distachyon (Bd), produces an ice-binding protein (IBP) that shapes ice with a modest depression of the freezing point (~0.1 °C at 1 mg/mL), but high ice-recrystallization inhibition (IRI) activity, allowing ice crystals to remain small at near melting temperatures. This IBP, known as BdIRI, is unlike other characterized IBPs with a single ice-binding face, as mutational analysis indicates that BdIRI adsorbs to ice on two faces. BdIRI also dramatically attenuates the nucleation of ice by bacterial INPs (up to -2.26 °C). This 'anti-nucleating' activity is significantly higher than previously documented for any IBP.

IL-4 enhances expression and function of surface IgM in CLL cells.

Kinase inhibitors targeting the B-cell receptor (BCR) are now prominent in the treatment of chronic lymphocytic leukemia (CLL). We have focused here on interleukin 4 (IL-4), a cytokine that protects normal and malignant B cells from apoptosis and increases surface immunoglobulin M (sIgM) expression on murine splenic B cells. First, we have demonstrated that IL-4 treatment increased sIgM expression in vitro on peripheral blood B cells obtained from healthy individuals. In CLL, IL-4 target genes are overexpressed in cells purified from the lymph nodes of patients compared with cells derived from matched blood and bone marrow samples. As for normal B cells, IL-4 increased sIgM expression on CLL cells in vitro, especially in samples expressing unmutated V-genes. IL-4-induced sIgM expression was associated with increased receptor signalling activity, measured by anti-IgM-induced calcium mobilization, and with increased expression of CD79B messenger RNA and protein, and the "mature" glycoform of sIgM. Importantly, the ability of the BCR-associated kinase inhibitors idelalisib and ibrutinib, approved for treatment of CLL and other B-cell malignancies, to inhibit anti-IgM-induced signalling was reduced following IL-4 pretreatment in samples from the majority of patients. In contrast to stimulatory effects on sIgM, IL-4 decreased CXCR4 and CXCR5 expression; therefore, CLL cells, particularly within the progressive unmutated V-gene subset, may harness the ability of IL-4 to promote BCR signalling and B-cell retention within lymph nodes. Effects of IL-4 were mediated via JAK3/STAT6 and we propose a potential role for JAK inhibitors in combination with BCR kinase inhibitors for the treatment of CLL.

Orally Bioavailable and Effective Buparvaquone Lipid-Based Nanomedicines for Visceral Leishmaniasis.

Nanoenabled lipid-based drug delivery systems offer a platform to overcome challenges encountered with current failed leads in the treatment of parasitic and infectious diseases. When prepared with FDA or EMA approved excipients, they can be readily translated without the need for further toxicological studies, while they remain affordable and amenable to scale-up. Buparvaquone (BPQ), a hydroxynapthoquinone with in vitro activity in the nanomolar range, failed to clinically translate as a viable treatment for visceral leishmaniasis due to its poor oral bioavailability limited by its poor aqueous solubility (BCS Class II drug). Here we describe a self-nanoemulsifying system (SNEDDS) with high loading and thermal stability up to 6 months in tropical conditions and the ability to enhance the solubilization capacity of BPQ in gastrointestinal media as demonstrated by flow-through cell and dynamic in vitro lipolysis studies. BPQ SNEDDS demonstrated an enhanced oral bioavailability compared to aqueous BPQ dispersions (probe-sonicated), resulting in an increased plasma AUC0-24 by 55% that is 4-fold higher than any previous reported values for BPQ formulations. BPQ SNEDDS can be adsorbed on low molecular glycol chitosan polymers forming solid dispersions that when compressed into tablets allow the complete dissolution of BPQ in gastrointestinal media. BPQ SNEDDS and BPQ solid SNEDDS demonstrated potent in vitro efficacy in the nanomolar range (<37 nM) and were able to near completely inhibit parasite replication in the spleen while also demonstrating 48 ± 48 and 56 ± 23% inhibition of the parasite replication in the liver, respectively, compared to oral miltefosine after daily administration over 10 days. The proposed platform technology can be used to elicit a range of cost-effective and orally bioavailable noninvasive formulations for a range of antiparasitic and infectious disease drugs that are needed for closing the global health innovation gap.