Integrative oncology: Addressing the global challenges of cancer prevention and treatment.

The increase in cancer incidence and mortality is challenging current cancer care delivery globally, disproportionally affecting low- and middle-income countries (LMICs) when it comes to receiving evidence-based cancer prevention, treatment, and palliative and survivorship care. Patients in LMICs often rely on traditional, complementary, and integrative medicine (TCIM) that is more familiar, less costly, and widely available. However, spheres of influence and tensions between conventional medicine and TCIM can further disrupt efforts in evidence-based cancer care. Integrative oncology provides a framework to research and integrate safe, effective TCIM alongside conventional cancer treatment and can help bridge health care gaps in delivering evidence-informed, patient-centered care. This growing field uses lifestyle modifications, mind and body therapies (eg, acupuncture, massage, meditation, and yoga), and natural products to improve symptom management and quality of life among patients with cancer. On the basis of this review of the global challenges of cancer control and the current status of integrative oncology, the authors recommend: 1) educating and integrating TCIM providers into the cancer control workforce to promote risk reduction and culturally salient healthy life styles; 2) developing and testing TCIM interventions to address cancer symptoms or treatment-related adverse effects (eg, pain, insomnia, fatigue); and 3) disseminating and implementing evidence-based TCIM interventions as part of comprehensive palliative and survivorship care so patients from all cultures can live with or beyond cancer with respect, dignity, and vitality. With conventional medicine and TCIM united under a cohesive framework, integrative oncology may provide citizens of the world with access to safe, effective, evidence-informed, and culturally sensitive cancer care.

A Novel Endocrine Role for the BAT-Released Lipokine 12,13-diHOME to Mediate Cardiac Function.

BACKGROUND: Brown adipose tissue (BAT) is an important tissue for thermogenesis, making it a potential target to decrease the risks of obesity, type 2 diabetes, and cardiovascular disease, and recent studies have also identified BAT as an endocrine organ. Although BAT has been implicated to be protective in cardiovascular disease, to this point there are no studies that identify a direct role for BAT to mediate cardiac function. METHODS: To determine the role of BAT on cardiac function, we utilized a model of BAT transplantation. We then performed lipidomics and identified an increase in the lipokine 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME). We utilized a mouse model with sustained overexpression of 12,13-diHOME and investigated the role of 12,13-diHOME in a nitric oxide synthase type 1 deficient (NOS1-/-) mouse and in isolated cardiomyocytes to determine effects on function and respiration. We also investigated 12,13-diHOME in a cohort of human patients with heart disease. RESULTS: Here, we determined that transplantation of BAT (+BAT) improves cardiac function via the release of the lipokine 12,13-diHOME. Sustained overexpression of 12,13-diHOME using tissue nanotransfection negated the deleterious effects of a high-fat diet on cardiac function and remodeling, and acute injection of 12,13-diHOME increased cardiac hemodynamics via direct effects on the cardiomyocyte. Furthermore, incubation of cardiomyocytes with 12,13-diHOME increased mitochondrial respiration. The effects of 12,13-diHOME were absent in NOS1-/- mice and cardiomyocytes. We also provide the first evidence that 12,13-diHOME is decreased in human patients with heart disease. CONCLUSIONS: Our results identify an endocrine role for BAT to enhance cardiac function that is mediated by regulation of calcium cycling via 12,13-diHOME and NOS1.

Equity, intercultural approaches, and access to information on traditional, complementary, and integrative medicines in the Americas.

Access to information and intercultural approaches in the field of health are essential for the elimination of inequities in health access and care. Intercultural models such as traditional, complementary, and integrative medicine (TCIM) are an important part of health care in most countries and often contribute to expanding access to primary health care. Despite legal recognition and policies to integrate TCIM into health systems, their contribution to health, well-being, and people-centered care to achieve universal health is still underestimated. This article presents the progress (2017-2020) achieved by the Virtual Health Library specialized in the TCIM (VHL TCIM Americas), an initiative created as a tool to reduce the gaps in the production and access to validated information on TCIM. Through collaborative network work, VHL TCIM Americas contributes to the democratization of health, access to verified scientific data, visibility of non-conventional knowledge, strengthening of research capacities, and exchange of experiences for informed decision-making.

El acceso a la información y los abordajes interculturales en el ámbito de la salud son esenciales para la eliminación de inequidades en el acceso a los servicios de salud y la atención sanitaria. Los modelos interculturales, como las medicinas tradicionales, complementarias e integrativas (MTCI) son una parte importante del cuidado de la salud en la mayoría de los países y frecuentemente contribuyen a ampliar el acceso a la atención primaria de salud. A pesar del reconocimiento legal y de la existencia de políticas para la integración de las MTCI en los sistemas de salud, aún se subestima su contribución a la salud, el bienestar y la atención de la salud centrada en las personas para alcanzar la salud universal. En este artículo se presentan los avances (2017-2020) alcanzados por la Biblioteca Virtual en Salud especializada en las MTCI (BVS MTCI Américas), iniciativa creada como herramienta para disminuir las brechas en la producción y el acceso a la información validada sobre las MTCI. Mediante el trabajo colaborativo en red, la BVS MTCI Américas contribuye a la democratización de la salud, el acceso a datos científicos verificados disponibles, la visibilización de conocimientos no convencionales, el fortalecimiento de capacidades de investigación y el intercambio de experiencias para la toma informada de decisiones.

O acesso à informação e as abordagens interculturais no setor da saúde são essenciais para eliminar as desigualdades no acesso aos serviços de saúde. Os modelos interculturais, como as medicinas tradicionais, complementares e integrativas (MTCI), são uma parte importante da atenção à saúde na maioria dos países e frequentemente contribuem para ampliar o acesso à atenção primária. Apesar do reconhecimento legal e da existência de políticas para a integração das MTCI nos sistemas de saúde, a sua contribuição para a saúde, o bem-estar e a atenção centrada nas pessoas para alcançar a saúde universal ainda é subestimada. Este artigo apresenta o progresso (de 2017 a 2020) alcançado pela Biblioteca Virtual em Saúde especializada em MTCI (BVS MTCI Américas), uma iniciativa criada como ferramenta para reduzir as disparidades na produção e no acesso a informações validadas sobre as MTCI. Realizando um trabalho colaborativo em rede, a BVS MTCI Américas contribui para a democratização da saúde, o acesso a dados científicos verificados, a visibilidade dos conhecimentos não convencionais, o fortalecimento das capacidades de pesquisa e a troca de experiências para a tomada de decisões bem informada.

Neurogenic tissue nanotransfection in the management of cutaneous diabetic polyneuropathy.

This work rests on our recent report on the successful use of tissue nanotransfection (TNT) delivery of Ascl1, Brn2, and Myt1l (TNTABM) to directly convert skin fibroblasts into electrophysiologically active induced neuronal cells (iN) in vivo. Here we report that in addition to successful neurogenic conversion of cells, TNTABM caused neurotrophic enrichment of the skin stroma. Thus, we asked whether such neurotrophic milieu of the skin can be leveraged to rescue pre-existing nerve fibers under chronic diabetic conditions. Topical cutaneous TNTABM caused elevation of endogenous NGF and other co-regulated neurotrophic factors such as Nt3. TNTABM spared loss of cutaneous PGP9.5+ mature nerve fibers in db/db diabetic mice. This is the first study demonstrating that under conditions of in vivo reprogramming, changes in the tissue microenvironment can be leveraged for therapeutic purposes such as the rescue of pre-existing nerve fibers from its predictable path of loss under conditions of diabetes.

[Equity, intercultural approaches and access to information on traditional, complementary and integrative medicines in the AmericasEquidade, abordagens interculturais e acesso a informações sobre medicinas tradicionais, complementares e integrativas nas Américas]. / Equidad, abordajes interculturales y acceso a la información sobre las medicinas tradicionales, complementarias e integrativas en las Américas.

Access to information and intercultural approaches in the field of health are essential for the elimination of inequities in health access and care. Intercultural models such as traditional, complementary and integrative medicine (TCIM) are an important part of health care in most countries and often contribute to expanding access to primary health care. Despite legal recognition and policies to integrate TCIM into health systems, their contribution to health, well-being, and people-centered care to achieve universal health is still underestimated. This article presents the progress (2017-2020) achieved by the Virtual Health Library specialized in the TCIM (VHL TCIM Americas), an initiative created as a tool to reduce the gaps in the production and access to validated information on TCIM. Through collaborative network work, the VHL TCIM Americas contributes to the democratization of health, access to verified scientific data, visibility of non-conventional knowledge, strengthening of research capacities, and exchange of experiences for informed decision-making.

O acesso à informação e as abordagens interculturais no setor da saúde são essenciais para eliminar as desigualdades no acesso aos serviços de saúde. Os modelos interculturais, como as medicinas tradicionais, complementares e integrativas (MTCI), são uma parte importante da atenção à saúde na maioria dos países e frequentemente contribuem para ampliar o acesso à atenção primária. Apesar do reconhecimento legal e da existência de políticas para a integração das MTCI nos sistemas de saúde, a sua contribuição para a saúde, o bem-estar e a atenção centrada nas pessoas para alcançar a saúde universal ainda é subestimada. Este artigo apresenta o progresso (de 2017 a 2020) alcançado pela Biblioteca Virtual em Saúde especializada em MTCI (BVS MTCI Américas), uma iniciativa criada como ferramenta para reduzir as disparidades na produção e no acesso a informações validadas sobre as MTCI. Realizando um trabalho colaborativo em rede, a BVS MTCI Américas contribui para a democratização da saúde, o acesso a dados científicos verificados, a visibilidade dos conhecimentos não convencionais, o fortalecimento das capacidades de pesquisa e a troca de experiências para a tomada de decisões bem informada.
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The human PMR1 endonuclease stimulates cell motility by down regulating miR-200 family microRNAs.

The motility of MCF-7 cells increases following expression of a human PMR1 transgene and the current study sought to identify the molecular basis for this phenotypic change. Ensemble and single cell analyses show increased motility is dependent on the endonuclease activity of hPMR1, and cells expressing active but not inactive hPMR1 invade extracellular matrix. Nanostring profiling identified 14 microRNAs that are downregulated by hPMR1, including all five members of the miR-200 family and others that also regulate invasive growth. miR-200 levels increase following hPMR1 knockdown, and changes in miR-200 family microRNAs were matched by corresponding changes in miR-200 targets and reporter expression. PMR1 preferentially cleaves between UG dinucleotides within a consensus YUGR element when present in the unpaired loop of a stem-loop structure. This motif is present in the apical loop of precursors to most of the downregulated microRNAs, and hPMR1 targeting of pre-miRs was confirmed by their loss following induced expression and increase following hPMR1 knockdown. Introduction of miR-200c into hPMR1-expressing cells reduced motility and miR-200 target gene expression, confirming hPMR1 acts upstream of Dicer processing. These findings identify a new role for hPMR1 in the post-transcriptional regulation of microRNAs in breast cancer cells.

On-Chip Clonal Analysis of Glioma-Stem-Cell Motility and Therapy Resistance.

Enhanced glioma-stem-cell (GSC) motility and therapy resistance are considered to play key roles in tumor cell dissemination and recurrence. As such, a better understanding of the mechanisms by which these cells disseminate and withstand therapy could lead to more efficacious treatments. Here, we introduce a novel micro-/nanotechnology-enabled chip platform for performing live-cell interrogation of patient-derived GSCs with single-clone resolution. On-chip analysis revealed marked intertumoral differences (>10-fold) in single-clone motility profiles between two populations of GSCs, which correlated well with results from tumor-xenograft experiments and gene-expression analyses. Further chip-based examination of the more-aggressive GSC population revealed pronounced interclonal variations in motility capabilities (up to ∼4-fold) as well as gene-expression profiles at the single-cell level. Chip-supported therapy resistance studies with a chemotherapeutic agent (i.e., temozolomide) and an oligo RNA (anti-miR363) revealed a subpopulation of CD44-high GSCs with strong antiapoptotic behavior as well as enhanced motility capabilities. The living-cell-interrogation chip platform described herein enables thorough and large-scale live monitoring of heterogeneous cancer-cell populations with single-cell resolution, which is not achievable by any other existing technology and thus has the potential to provide new insights into the cellular and molecular mechanisms modulating glioma-stem-cell dissemination and therapy resistance.

Dietary patterns in Liberian refugees in Buduburam, Ghana.

Previous research suggests that acculturation (i.e., exposure and assimilation to local culture) is associated with changes in dietary patterns among immigrants. This study investigates this association in a refugee population using time in refugee settlement as a proxy for acculturation. A cross-sectional survey was conducted among a systematic sample to (a) identify dietary patterns in Liberian refugees and Ghanaians living in or near a refugee settlement, (b) compare adherence to these dietary patterns between groups, and (c) investigate the association between acculturation and dietary patterns in Liberian refugees. Participants were Liberian and Ghanaian women with young children living in the Buduburam refugee settlement or Awutu in Ghana (n = 480; 50% Liberian; mean age 28, SD 6.3, range 16-48 years). Time in settlement was assessed by self-report; food consumption was assessed by food frequency questionnaire. Principal component analysis was used to identify dietary patterns; a generalized linear model was used to test the association of interest. Three distinct dietary patterns emerged: Healthy, Sweets, and Fats. Ghanaians were more adherent to the Healthy pattern than Liberians (p < 0.05). Liberians were more adherent to the Sweets and Fats patterns than Ghanaians (p < 0.05). There were no significant differences in dietary pattern adherence among the Liberians based on time in settlement. Ghanaians living in Awutu were more adherent to the Healthy pattern than Ghanaians who lived in settlement (p < 0.05). Differences in dietary patterns were observed between Liberian refugees and Ghanaians. These differences were not associated with acculturation and may be related to the food environment in the settlement.

Length of time in Ghana is associated with the likelihood of exclusive breastfeeding among Liberian refugees living in Buduburam.

While literature describing immigrant's breastfeeding practices exists, especially among those living within developed countries, there is a significant gap in knowledge on how the host culture may influence the EBF behaviors of refugees, especially those living in protracted situations within sub-Saharan Africa. A cross-sectional study was conducted in the Buduburam Refugee Settlement in Ghana from July-August 2008 to explore the association between the amount of time living in Ghana and exclusive breastfeeding practices among Liberian refugees and Ghanaians in surround villages. The study included 480 women: 239 Liberians living in 12 settlement zones (in two of which Liberians and Ghanaians co-exist), 121 Ghanaians living in two settlement zones, and 120 Ghanaians living in nearby urban village of Awutu. Liberian mothers who lived in Ghana at least eight years were significantly more likely to exclusively breastfeed (OR: 1.78, 95% CI: 1.02, 3.09) compared to Ghanaian mothers living in Awutu. These findings suggest that increased time living in Buduburam improved the chances of EBF success among Liberians, perhaps as a result of unique EBF education/support opportunities offered in the settlement to Liberian refugees that were not readily available to Ghanaians. Further research to understand the "mechanisms" explaining exclusive breastfeeding differences as a function of time spent in host country is needed for improving breastfeeding support in refugee settlements and host communities.

Controllable Large-Scale Transfection of Primary Mammalian Cardiomyocytes on a Nanochannel Array Platform.

While electroporation has been widely used as a physical method for gene transfection in vitro and in vivo, its application in gene therapy of cardiovascular cells remains challenging. Due to the high concentration of ion-transport proteins in the sarcolemma, conventional electroporation of primary cardiomyocytes tends to cause ion-channel activation and abnormal ion flux, resulting in low transfection efficiency and high mortality. In this work, a high-throughput nanoelectroporation technique based on a nanochannel array platform is reported, which enables massively parallel delivery of genetic cargo (microRNA, plasmids) into mouse primary cardiomyocytes in a controllable, highly efficient, and benign manner. A simple "dipping-trap" approach was implemented to precisely position a large number of cells on the nanoelectroporation platform. With dosage control, our device precisely titrates the level of miR-29, a potential therapeutic agent for cardiac fibrosis, and determines the minimum concentration of miR-29 causing side effects in mouse primary cardiomyocytes. Moreover, the dose-dependent effect of miR-29 on mitochondrial potential and homeostasis is monitored. Altogether, our nanochannel array platform provides efficient trapping and transfection of primary mouse cardiomyocyte, which can improve the quality control for future microRNA therapy in heart diseases.

Deterministic transfection drives efficient nonviral reprogramming and uncovers reprogramming barriers.

Safety concerns and/or the stochastic nature of current transduction approaches have hampered nuclear reprogramming's clinical translation. We report a novel non-viral nanotechnology-based platform permitting deterministic large-scale transfection with single-cell resolution. The superior capabilities of our technology are demonstrated by modification of the well-established direct neuronal reprogramming paradigm using overexpression of the transcription factors Brn2, Ascl1, and Myt1l (BAM). Reprogramming efficiencies were comparable to viral methodologies (up to ~9-12%) without the constraints of capsid size and with the ability to control plasmid dosage, in addition to showing superior performance relative to existing non-viral methods. Furthermore, increased neuronal complexity could be tailored by varying BAM ratio and by including additional proneural genes to the BAM cocktail. Furthermore, high-throughput NEP allowed easy interrogation of the reprogramming process. We discovered that BAM-mediated reprogramming is regulated by AsclI dosage, the S-phase cyclin CCNA2, and that some induced neurons passed through a nestin-positive cell stage. FROM THE CLINICAL EDITOR: In the field of regenerative medicine, the ability to direct cell fate by nuclear reprogramming is an important facet in terms of clinical application. In this article, the authors described their novel technique of cell reprogramming through overexpression of the transcription factors Brn2, Ascl1, and Myt1l (BAM) by in situ electroporation through nanochannels. This new technique could provide a platform for further future designs.

Effect of nonendocytic uptake of nanoparticles on human bronchial epithelial cells.

The toxicity of artificial nanoparticles is a major concern in industrial applications. Cellular uptake of hard nanoparticles could follow either endocytic or nonendocytic pathways, leading to different stimuli to the cells. Yet the cellular responses to nanoparticles following different pathways have not been compared due to the lack of an independent nonendocytic delivery method. We applied a unique delivery method, nanochannel electroporation (NEP), to produce predominantly nonendocytic uptakes of quantum dots (Q-dots) and multiwalled carbon nanotubes (MWCNTs) with different chemical modifications. NEP delivery bypassed endocytosis by electrophoretic injection of nanoparticles into human bronchial epithelial (BEAS-2B) cells at different dosages. Conventional exposure by direct nanoparticle suspending in cell culture medium was also performed as control. The dosage-dependent responses to nanoparticles under different uptake pathways were compared. Fluorescence colocalization demonstrated that nanoparticles followed both endocytic and nonendocytic pathways for cell entry in contact exposure, whereas NEP delivery of nanoparticles bypassed endocytosis. Nonendocytic entry resulted in much higher oxidation stress and, for MWCNTs, more cell death in BEAS-2B cells. Despite the observation that most nanoparticles were taken up by cells through endocytosis, the minor nonendocytic entry of nanoparticles seemed to dominate the overall cellular response in conventional contact exposure. Our finding suggests that prevention against nonendocytic uptake could help reduce the toxicity of hard nanoparticles.

Magnetic tweezers-based 3D microchannel electroporation for high-throughput gene transfection in living cells.

A novel high-throughput magnetic tweezers-based 3D microchannel electroporation system capable of transfecting 40 000 cells/cm(2) on a single chip for gene therapy, regenerative medicine, and intracellular detection of target mRNA for screening cellular heterogeneity is reported. A single cell or an ordered array of individual cells are remotely guided by programmable magnetic fields to poration sites with high (>90%) cell alignment efficiency to enable various transfection reagents to be delivered simultaneously into the cells. The present technique, in contrast to the conventional vacuum-based approach, is significantly gentler on the cellular membrane yielding >90% cell viability and, moreover, allows transfected cells to be transported for further analysis. Illustrating the versatility of the system, the GATA2 molecular beacon is delivered into leukemia cells to detect the regulation level of the GATA2 gene that is associated with the initiation of leukemia. The uniform delivery and a sharp contrast of fluorescence intensity between GATA2 positive and negative cells demonstrate key aspects of the platform for gene transfer, screening and detection of targeted intracellular markers in living cells.

Single clonal tracking on biomimetic microtextured platforms for real-time guided migration analysis of myeloid-derived suppressor cell dissemination characteristics ex vivo.

Current strategies to undermine the deleterious influence of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME) are lacking effective clinical solutions, in large part, due to insufficient knowledge on susceptible cellular and molecular targets. We describe here the application of biomimetic microfabricated platforms designed to analyze migratory phenotypes of MDSCs in the tumor niche ex vivo, which may enable accelerated therapeutic discovery. By mimicking the guided structural cues present in the physiological architecture of the TME, aligned microtopography substrates can elucidate potential interventions on migratory phenotypes of MDSCs at the single clonal level. Coupled with cellular and molecular biology analysis tools, our approach employs real-time tracking analysis of cell motility to probe the dissemination characteristics of MDSCs under guided migration conditions. These methods allow us to identify cellular subpopulations of interest based on their disseminative and suppressive capabilities. By doing so, we illustrate the potential of applying microscale engineering tools, in concert with dynamic live cell imaging and bioanalysis methods to uncover novel exploitable motility targets for advancing cancer therapy discovery. The inherent simplicity and extended application to a variety of contexts in tumor-associated cell migration render this method widely accessible to existing biological laboratory conditions and interests.

A review of the WHO strategy on traditional, complementary, and integrative medicine from the perspective of academic consortia for integrative medicine and health.

Despite important progress in modern medicine, widely regarded as an indispensable foundation of healthcare in all highly advanced nations and regions, not all patients respond well to available treatments in biomedicine alone. Additionally, there are concerns about side effects of many medications and interventions, the unsustainable cost of healthcare and the low resolution of chronic non-communicable diseases and mental disorders whose incidence has risen in the last decades. Besides, the chronic stress and burnout of many healthcare professionals impairs the therapeutic relationship. These circumstances call for a change in the current paradigm and practices of biomedicine healthcare. Most of the world population (80%) uses some form of traditional, complementary, and integrative medicine (T&CM), usually alongside biomedicine. Patients seem equally satisfied with biomedicine and T&CM, but in the field of T&CM there are also many challenges, such as unsupported claims for safety and/or efficacy, contamination of herbal medicines and problems with regulation and quality standards. As biomedicine and T&CM seem to have different strengths and weaknesses, integration of both approaches may be beneficial. Indeed, WHO has repeatedly called upon member states to work on the integration of T&CM into healthcare systems. Integrative medicine (IM) is an approach that offers a paradigm for doing so. It combines the best of both worlds (biomedicine and T&CM), based on evidence for efficacy and safety, adopting a holistic personalized approach, focused on health. In the last decades academic health centers are increasingly supportive of IM, as evidenced by the foundation of national academic consortia for integrative medicine in Brazil (2017), the Netherlands (2018), and Germany (2024) besides the pioneering American consortium (1998). However, the integration process is slow and sometimes met with criticism and even hostility. The WHO T&CM strategies (2002-2005 and 2014-2023) have provided incipient guidance on the integration process, but several challenges are yet to be addressed. This policy review proposes several possible solutions, including the establishment of a global matrix of academic consortia for IM, to update and extend the WHO T&CM strategy, that is currently under review.

Gene delivery to cultured embryonic stem cells using nanofiber-based sandwich electroporation.

Multiple gene transfections are often required to control the differentiation of embryonic stem cells. This is typically done by removing the cells from the culture substrate and conducting gene transfection via bulk electroporation (in suspension), which is then followed by further culture. Such repetitive processes could affect the growth and behavior of delicate/scarce adherent cells. We have developed a novel nanofiber-based sandwich electroporation device capable of in situ and in culture gene transfection. Electrospinning was used to deposit poly(ε-caprolactone)/gelatin nanofibers on the Al(2)O(3) nanoporous support membrane, on top of which a polystyrene microspacer was thermally bonded to control embryonic stem cell colony formation. The applicability of this system was demonstrated by culturing and transfecting mouse embryonic stem cells. Measurements of secreted alkaline phosphatase protein and metabolic activity showed higher transfection efficacy and cell viability compared to the conventional bulk electroporation approach.

Surface-mediated nucleic acid delivery by lipoplexes prepared in microwell arrays.

Many delivery methods have been developed to improve the therapeutic efficacy and facilitate the clinical translation of nucleic acid-based therapeutics. A facile surface-mediated nucleic acid delivery by lipoplexes is prepared in a microwell array, which combines the advantages of lipoplexes as an efficient carrier system, surface-mediated delivery, and the control of surface topography. Uniform disc-like lipoplexes containing nucleic acids are formed in the microwell array with a diameter of ∼818 nm and thickness of ∼195 nm. The microwell array-mediated delivery of lipoplexes containing FAM-oligodeoxynucleotides is ∼18.6 and ∼10.6 times more efficient than the conventional transfection method in an adherent cell line (A549 non-small cell lung cancer cells) and a suspension cell line (KG-1a acute myelogenous leukemia cells), respectively. MicroRNA-29b is then used as a model nucleic acid to investigate the therapeutic efficacy of lipoplexes delivered by the microwell array. Compared to conventional transfection methods, the effective therapeutic dosage of microRNA-29b is reduced from the microgram level to the nanogram level by lipoplexes prepared in the microwell array. The microwell array is also a very flexible platform. Both nucleic acid therapeutics and imaging reagents are incorporated in lipoplexes and successfully delivered to A549 cells, demonstrating its potential applications in theranostic medicine.

Untimely care: How the modern logics of coverage and medicine compromise children's health and development.

How do families manage when health care systems do not "cover" and clinicians do not acknowledge their children's condition? This article presents an ethnographic study in the Northeastern region of the United States with 20 families with children diagnosed with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)/Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). Two of the 20 families had moved to the U.S. seeking care. The for-profit structure of the U.S. health care system resulted in costly and lengthy therapeutic journeys to access a diagnosis and adequate treatments. In the U.S., PANS/PANDAS coverage depends on legislation, advocacy, clinical characteristics of each child, and how for-profit insurance companies react to an increased demand for a given service. Many medical professionals, both in the U.S. and in other countries, refuse to acknowledge the condition or offer effective treatments that lack "acceptable" evidence. We argue that the financial logic behind coverage exists across modern health care systems and imposes restrictions and exclusions that impede access to care. Thus, untimely care, the time gap from PANS/PANDAS symptoms to diagnosis and treatment is the result of the modern logics that structure medicine and coverage. The results of this study illustrate how modern medicine and coverage fail to protect families with children with PANS/PANDAS against catastrophic expenses and often block care that would prevent developmental disruptions and losses, avoid much suffering, and even save costs to health care systems. New and controversial conditions like PANS/PANDAS highlight the importance of separating the financial logics behind proposals such as "universal health coverage" from the provision of comprehensive forms of care that acknowledge uncertainty and prioritize action and flexibility.

Characterizing Therapeutic Pluralism Policies in Latin America: A Qualitative Content Analysis.

Introduction: The 1978 Alma Ata Declaration initiated international recognition of non-biomedical healing systems and their relevance for primary health. World Health Assembly (WHA) resolutions have called for the study and inclusion of traditional and complementary medicine (T&CM) into national health systems through policy development. The increased public, political, and scholarly attention given to T&CM has focused on clinical efficacy, cost-effectiveness, mechanisms of action, consumer demand, and supply-side regulation. Although >50% of WHO member states have T&CM policies, scant research has focused on these policies and their public health implications. This paper defines a novel term "therapeutic pluralism," and it aims at characterizing related policies in Latin America. Methods: A qualitative content analysis of Latin American therapeutic pluralism policies was performed. Policies' characteristics and the reported social, political, and economic forces that have made possible their development were assessed. Pre-defined policy features were categorized on an MS-Excel; in-depth text analyses were conducted in NVivo. Analyses followed the steps described by Bengtsson: decontextualization, recontextualization, categorization, and compilation. Results: Seventy-four (74) policy documents from 16 of the 20 sovereign Latin American countries were included. Mechanisms for policy enactment included: Constitution, National Law, National Policy, National Healthcare Model, National Program Guideline, Specific Regulatory Norms, and Supporting Legislation, Policies, and Norms. We propose a four-category typology of policy approaches in Latin America: Health Services-centered, Model of Care-based, Participatory, and Indigenous People-focused. Common themes countries used when justifying developing these policies included: benefits to the health system, legal and political mandates, supply and demand, and culture and identity. Social forces these policies referenced as influencing their development included: pluralism, self-determination and autonomy, anticapitalism and decolonization, safeguarding cultural identity, bridging cultural barriers, and sustainability. Conclusion: Policy approaches to therapeutic pluralism in Latin America go beyond integrating non-biomedical interventions into health services; they offer perspectives for transforming health systems. Characterizing these approaches has implications for policy development, implementation, evaluation, international collaboration, the development of technical cooperation tools and frameworks, and research.

Building Bridges Toward Common Goals - A Call for Greater Collaboration Between Public Health and Integrative, Complementary and Traditional Health Providers.

This commentary makes the case for greater collaboration between public health professionals and integrative, complementary and traditional health practitioners (ICTHP). Previous partnerships have been successful, and more such collaborative work is needed to help overcome division, enhance the health workforce, and move all involved toward shared goals. ICTHP providers may be uniquely able to work across ideological differences and engage individuals and communities who are less trusting of public health, including those who are vaccine hesitant. Diverse partnerships can be difficult to maintain, but the application of equitable processes may aid their success. In the face of highly complex public health challenges, partnerships with ICTHP are critical.