Human-induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation.

STUDY QUESTION: Can in vitro maturation (IVM) and developmental competence of human oocytes be improved by co-culture with ovarian support cells (OSCs) derived from human-induced pluripotent stem cells (hiPSCs)? SUMMARY ANSWER: OSC-IVM significantly improves the rates of metaphase II (MII) formation and euploid Day 5 or 6 blastocyst formation, when compared to a commercially available IVM system. WHAT IS KNOWN ALREADY: IVM has historically shown highly variable performance in maturing oocytes and generating oocytes with strong developmental capacity, while limited studies have shown a positive benefit of primary granulosa cell co-culture for IVM. We recently reported the development of OSCs generated from hiPSCs that recapitulate dynamic ovarian function in vitro. STUDY DESIGN, SIZE, DURATION: The study was designed as a basic science study, using randomized sibling oocyte specimen allocation. Using pilot study data, a prospective sample size of 20 donors or at least 65 oocytes per condition were used for subsequent experiments. A total of 67 oocyte donors were recruited to undergo abbreviated gonadotropin stimulation with or without hCG triggers and retrieved cumulus-oocyte complexes (COCs) were allocated between the OSC-IVM or control conditions (fetal-like OSC (FOSC)-IVM or media-only IVM) in three independent experimental design formats. The total study duration was 1 April 2022 to 1 July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Oocyte donors between the ages of 19 and 37 years were recruited for retrieval after informed consent, with assessment of anti-Mullerian hormone, antral follicle count, age, BMI and ovarian pathology used for inclusion and exclusion criteria. In experiment 1, 27 oocyte donors were recruited, in experiment 2, 23 oocyte donors were recruited, and in experiment 3, 17 oocyte donors and 3 sperm donors were recruited. The OSC-IVM culture condition was composed of 100 000 OSCs in suspension culture with hCG, recombinant FSH, androstenedione, and doxycycline supplementation. IVM controls lacked OSCs and contained either the same supplementation, FSH and hCG only (a commercial IVM control), or FOSCs with the same supplementation (Media control). Experiment 1 compared OSC-IVM, FOSC-IVM, and a Media control, while experiments 2 and 3 compared OSC-IVM and a commercial IVM control. Primary endpoints in the first two experiments were the MII formation (i.e. maturation) rate and morphological quality assessment. In the third experiment, the fertilization and embryo formation rates were assessed with genetic testing for aneuploidy and epigenetic quality in blastocysts. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a statistically significant improvement (∼1.5×) in maturation outcomes for oocytes that underwent IVM with OSCs compared to control Media-IVM and FOSC-IVM in experiment 1. More specifically, the OSC-IVM group yielded a MII formation rate of 68% ± 6.83% SEM versus 46% ± 8.51% SEM in the Media control (P = 0.02592, unpaired t-test). FOSC-IVM yielded a 51% ± 9.23% SEM MII formation rate which did not significantly differ from the media control (P = 0.77 unpaired t-test). Additionally, OSC-IVM yielded a statistically significant ∼1.6× higher average MII formation rate at 68% ± 6.74% when compared to 43% ± 7.90% in the commercially available IVM control condition (P = 0.0349, paired t-test) in experiment 2. Oocyte morphological quality between OSC-IVM and the controls did not significantly differ. In experiment 3, OSC-IVM oocytes demonstrated a statistically significant improvement in Day 5 or 6 euploid blastocyst formation per COC compared to the commercial IVM control (25% ± 7.47% vs 11% ± 3.82%, P = 0.0349 logistic regression). Also in experiment 3, the OSC-treated oocytes generated blastocysts with similar global and germline differentially methylated region epigenetic profiles compared commercial IVM controls or blastocysts after either conventional ovarian stimulation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: While the findings of this study are compelling, the cohort size remains limited and was powered on preliminary pilot studies, and the basic research nature of the study limits generalizability compared to randomized control trials. Additionally, use of hCG-triggered cycles results in a heterogenous oocyte cohort, and potential differences in the underlying maturation state of oocytes pre-IVM may limit or bias findings. Further research is needed to clarify and characterize the precise mechanism of action of the OSC-IVM system. Further research is also needed to establish whether these embryos are capable of implantation and further development, a key indication of their clinical utility. WIDER IMPLICATIONS OF THE FINDINGS: Together, these findings demonstrate a novel approach to IVM with broad applicability to modern ART practice. The controls used in this study are in line with and have produced similar to findings to those in the literature, and the outcome of this study supports findings from previous co-culture studies that found benefits of primary granulosa cells on IVM outcomes. The OSC-IVM system shows promise as a highly flexible IVM approach that can complement a broad range of stimulation styles and patient populations. Particularly for patients who cannot or prefer not to undergo conventional gonadotropin stimulation, OSC-IVM may present a viable path for obtaining developmentally competent, mature oocytes. STUDY FUNDING/COMPETING INTEREST(S): A.D.N., A.B.F., A.G., B.P., C.A., C.C.K., F.B., G.R., K.S.P., K.W., M.M., P.C., S.P., and M.-J.F.-G. are shareholders in the for-profit biotechnology company Gameto Inc. P.R.J.F. declares paid consultancy for Gameto Inc. P.C. also declares paid consultancy for the Scientific Advisory Board for Gameto Inc. D.H.M. has received consulting services from Granata Bio, Sanford Fertility and Reproductive Medicine, Gameto, and Buffalo IVF, and travel support from the Upper Egypt Assisted Reproduction Society. C.C.K., S.P., M.M., A.G., B.P., K.S.P., G.R., and A.D.N. are listed on a patent covering the use of OSCs for IVM: U.S. Provisional Patent Application No. 63/492,210. Additionally, C.C.K. and K.W. are listed on three patents covering the use of OSCs for IVM: U.S. Patent Application No. 17/846,725, U.S Patent Application No. 17/846,845, and International Patent Application No.: PCT/US2023/026012. C.C.K., M.P.S., and P.C. additionally are listed on three patents for the transcription factor-directed production of granulosa-like cells from stem cells: International Patent Application No.: PCT/US2023/065140, U.S. Provisional Application No. 63/326,640, and U.S. Provisional Application No. 63/444,108. The remaining authors have no conflicts of interest to declare.

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.

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.

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.

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.

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

[ABSTRACT]. 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.

[RESUMEN]. 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.

[RESUMO]. 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.

A randomized control trial to test a peer support group approach for reducing social isolation and depression among female Mexican immigrants.

BACKGROUND: Female Mexican Immigrants (FMIs) experience high rates of depression compared with other populations. For this population, depression is often exacerbated by social isolation associated with the experience of immigration. Aim 1. To measure whether a culturally situated peer group intervention will reduce depression and stress associated with the experience of immigration. Aim 2. To test whether an intervention using a "women's funds of knowledge" approach results in improved resilience, knowledge and empowerment. Aim 3. To investigate whether a culturally situated peer group intervention using a women's funds of knowledge approach can give participants a sense and experience of social and physical connection ("emplacement") that is lost in the process of immigration. METHODS: This mixed-methods study will implement "Tertulias" ("conversational gatherings" in Spanish), a peer support group intervention designed to improve health outcomes for FMI participants in Albuquerque, New Mexico. We will document results of the intervention on our primary hypotheses of a decrease in depression, and increases in resilience and social support, as well as on our secondary hypotheses of decreased stress (including testing of hair cortisol as a biomarker for chronic stress), and an increase in social connectedness and positive assessment of knowledge and empowerment. DISCUSSION: This project will address mental health disparities in an underserved population that experiences high rates of social isolation. Successful completion of this project will demonstrate that health challenges that may appear too complex and too hard to address can be using a multi-level, holistic approach. Our use of hair samples to test for the 3-month average levels of systemic cortisol will contribute to the literature on an emerging biomarker for analyzing chronic stress. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov on 2/3/20, Identifier # NCT04254198 .

Experiências e reflexões sobre medicinas tradicionais, complementares e integrativas em sistemas de saúde nas Américas / Experiencias y reflexiones sobre medicinas tradicionales, complementarias e integradoras en los sistemas de salud de las Américas / Experiences and reflections on traditional, complementary and integrative medicine in health systems in the Americas

O objetivo é apresentar sob diferentes perspectivas e dimensões da atuação das MTCI nas Américas, a fim de que, com a troca de experiências, possamos enriquecer e fortalecer tais saberes e práticas nos diferentes países. O livro e seus dez capítulos estão divididos em duas partes. Na primeira, Modelos, sistemas e políticas de saúde, relata as experiências com essas medicinas no Peru, Colômbia e Brasil. Na segunda parte, Experiências de Gestão, Formação e Cuidado, são apresentados estudos de caso e experiências com problemas específicos e reflexões acerca das MTCI. Os autores abordam temas relacionados à gestão, formação e cuidado, farmacovigilância em Cuba, a pediatria integrativa na Argentina e experiências no Nordeste do Brasil. Um desafio enfrentado pelo livro foi o reconhecimento e a adequação das diferenças e das similaridades acerca das denominações sobre o tema entre os países da América Latina. Atualmente, a OMS denomina esses saberes e práticas/intervenções de Medicinas Tradicionais, Complementares e Integrativas (MTCI), mas em cada país elas recebem uma denominação distinta. No entanto, apesar das diferentes denominações, os fundamentos são similares, principalmente no que se refere à adoção do paradigma vitalista e ao modo de intervir nos processos de adoecimento. O termo Tradicional pode adquirir múltiplos sentidos, devendo ser compreendido de acordo com o contexto a que se refere. Os sistemas de saúde tradicionais indígenas estão presentes entre os povos originários e se mantêm em alguns locais sem interação com a biomedicina e/ou com as MTCI, como visto nas experiências de alguns países. Essa convivência não está isenta de tensões históricas, que se refletem nos próprios conceitos denominados pluralismo terapêutico na região, bem como nos marcos legais e nas abordagens práticas para a inclusão (ou exclusão) do referido pluralismo nos sistemas nacionais de saúde.

El objetivo es brindar al lector una aproximación a las MTCI en las Américas, desde las diferentes perspectivas y dimensiones de actuación de estas, para que, con el intercambio de experiencias, podamos enriquecer y fortalecer dichos conocimientos y prácticas en diferentes países. Construir un libro sobre el mismo tema, pero a partir de experiencias en diferentes países, fue un rico experimento que requirió tiempo, y el cual trajo reflejos de diversos matices. El primer desafío fue el reconocimiento y adecuación de las diferencias y similitudes en cuanto a las denominaciones sobre el tema entre los países de América Latina. Actualmente, la OMS denomina a estos conocimientos y prácticas/intervenciones como Medicinas Tradicionales, Complementarias e Integrativas (MTCI), pero en cada país reciben un nombre diferente. En el caso de Brasil, por ejemplo, las Medicinas Tradicionales, Complementarias e Integrativas se denominan Prácticas de Salud Integrativas y Complementarias (PICS); en Perú se les llama Medicinas Alternativas y Complementarias; en Ecuador, Medicinas Tradicionales y Complementarias; en Colombia, Medicinas Alternativas y Terapias Alternativas y Complementarias; en Cuba se adopta el término Medicina Natural y Tradicional. Sin embargo, a pesar de las diferentes denominaciones, los fundamentos son similares, principalmente en lo que respecta a la adopción del paradigma vitalista y la forma de intervenir en los procesos de la enfermedad. En este libro, adoptaremos el término MTCI para una mejor comprensión internacional. Si bien las nomenclaturas van cambiando con el tiempo, no podemos perder de vista el hecho de que en América Latina han convivido muchos sistemas terapéuticos a lo largo de los siglos. El término Tradicional puede adquirir múltiples significados, y debe entenderse según el contexto al que se refiere. Los sistemas tradicionales de salud indígena están presentes entre los pueblos originarios, y se mantienen en algunos lugares sin interacción con la biomedicina y/o con las MTCI, como se ve en las experiencias de algunos países. Esta convivencia no está exenta de tensiones históricas, que se reflejan en los propios conceptos que se denomina pluralismo terapéutico en la región, así como en los marcos legales y enfoques prácticos para la inclusión (o exclusión) de dicho pluralismo en los sistemas nacionales de salud.

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

ABSTRACT 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.

RESUMEN 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.

RESUMO 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.

[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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Equidad, abordajes interculturales y acceso a la información sobre las medicinas tradicionales, complementarias e integrativas en las Américas

[RESUMEN]. 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.

[ABSTRACT]. 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.

[RESUMO]. 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.

Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy.

Like normal hematopoietic stem cells, leukemic stem cells depend on their bone marrow (BM) microenvironment for survival, but the underlying mechanisms remain largely unknown. We have studied the contribution of nestin+ BM mesenchymal stem cells (BMSCs) to MLL-AF9-driven acute myeloid leukemia (AML) development and chemoresistance in vivo. Unlike bulk stroma, nestin+ BMSC numbers are not reduced in AML, but their function changes to support AML cells, at the expense of non-mutated hematopoietic stem cells (HSCs). Nestin+ cell depletion delays leukemogenesis in primary AML mice and selectively decreases AML, but not normal, cells in chimeric mice. Nestin+ BMSCs support survival and chemotherapy relapse of AML through increased oxidative phosphorylation, tricarboxylic acid (TCA) cycle activity, and glutathione (GSH)-mediated antioxidant defense. Therefore, AML cells co-opt energy sources and antioxidant defense mechanisms from BMSCs to survive chemotherapy.

First in Literature Intraneuronal Sacral Nerve Stimulation for Fecal Incontinence After Robotic-Assisted En-Bloc Sacrectomy with Transection of Nerve Roots.

BACKGROUND: En-bloc sacrectomy is the treatment of choice for patients affected by sacral chordoma. It is a radical surgical procedure, which has to face the problem of handling fragile anatomic structures, such as the internal iliac vessels and the sacral nerve roots, with the risk of causing bowel, bladder, and sexual dysfunction. The combined anterior-posterior approach allows for a safer dissection of the tumor from the mesorectal fascia than the mere posterior approach, especially for tumors extending proximally to S3. Robotic surgery can improve the safety of the procedure. Sacral nerve stimulation is an accepted therapeutic option for fecal incontinence and may be used to treat postoperative incontinence. CASE PRESENTATION: We report on a patient affected by sacral chordoma with en-bloc sacrectomy preceded by a robotic-assisted dissection of the mesorectal fascia and on managing the postoperative fecal incontinence by implanting a sacral nerve stimulator on the first postoperative day. To our knowledge this is the first such procedure in the literature. CONCLUSIONS: From our experience, a robotic anterior approach increases safety for the organs in the pelvis when performing a sacrectomy. Moreover, a sacral nerve stimulator should be considered to manage neurologic complications following transection of nerve roots after sacrectomy.

Empiric use of oxygen for acute atraumatic, unilateral, retro-orbital headaches.

This article describes a man who presented with a 2-week history of atraumatic, unilateral, retro-orbital cranio-facial pain, ipsilateral diaphoresis, and facial flushing. He was diagnosed with cluster headaches after a positive response to oxygen therapy. Early consideration for oxygen therapy in the acute setting should be considered in all patients with an acute, unilateral, retro-orbital headache.

Evaluation of contaminants spreading from sludge piles, applying geochemical fractionation and attenuation of concentrations model in a tropical reservoir.

Drinking water production may generate significant amounts of sludge, which may be contaminated with various metals. For the first time, the mobility/lability of contaminants from two water treatment sludge piles in the Juturnaíba Reservoir was evaluated by applying two geochemical approaches: sequential extractions and attenuation of concentrations model. Both procedures were applied to evaluate the mobility/lability of Al, Cr, Cu, Fe, Mn, and Zn on samples collected in the sludge piles and in the neighborhood of both water treatment plants. The results show that aluminum presents considerably higher concentrations in the sediments close to the sludge piles, with more labile phases; however, the attenuation of concentrations model indicates little spreading of this contaminant in the reservoir. Manganese was shown to be severely depleted in the sludge, indicating that it can be leached away, due to the reducing conditions of the pile. The other elements showed low concentrations and were shown not to affect the concentrations in the reservoir. While the geochemical fractionation indicates the possibility of dissolution to the water column, the attenuation of concentrations model gives information on the spatial dispersion of the contaminants, constituting interesting complementary approaches.

Flexibility In Vitro of Amino Acid 226 in the Receptor-Binding Site of an H9 Subtype Influenza A Virus and Its Effect In Vivo on Virus Replication, Tropism, and Transmission.

Influenza A viruses (IAVs) remain a significant public health threat, causing more than 300,000 hospitalizations in the United States during the 2015-2016 season alone. While only a few IAVs of avian origin have been associated with human infections, the ability of these viruses to cause zoonotic infections further increases the public health risk of influenza. Of these, H9N2 viruses in Asia are of particular importance as they have contributed internal gene segments to other emerging zoonotic IAVs. Notably, recent H9N2 viruses have acquired molecular markers that allow for a transition from avian-like to human-like terminal sialic acid (SA) receptor recognition via a single amino acid change at position 226 (H3 numbering), from glutamine (Q226) to leucine (L226), within the hemagglutinin (HA) receptor-binding site (RBS). We sought to determine the plasticity of amino acid 226 and the biological effects of alternative amino acids on variant viruses. We created a library of viruses with the potential of having any of the 20 amino acids at position 226 on a prototypic H9 HA subtype IAV. We isolated H9 viruses that carried naturally occurring amino acids, variants found in other subtypes, and variants not found in any subtype at position 226. Fitness studies in quails revealed that some natural amino acids conferred an in vivo replication advantage. This study shows the flexibility of position 226 of the HA of H9 influenza viruses and the resulting effect of single amino acid changes on the phenotype of variants in vivo and in vitroIMPORTANCE A single amino acid change at position 226 in the hemagglutinin (HA) from glutamine (Q) to leucine (L) has been shown to play a key role in receptor specificity switching in various influenza virus HA subtypes, including H9. We tested the flexibility of amino acid usage and determined the effects of such changes. The results reveal that amino acids other than L226 and Q226 are well tolerated and that some amino acids allow for the recognition of both avian and human influenza virus receptors in the absence of other changes. Our results can inform better avian influenza virus surveillance efforts as well as contribute to rational vaccine design and improve structural molecular dynamics algorithms.

Dose-response study for the highly aggressive and metastatic primary F3II mammary carcinoma under direct current.

Electrochemical treatment has been suggested as an effective alternative to local cancer therapy. Nevertheless, its effectiveness decreases when highly aggressive primary tumors are treated. The aim of this research was to understand the growth kinetics of the highly aggressive and metastatic primary F3II tumor growing in male and female BALB/c/Cenp mice under electrochemical treatment. Different amounts of electric charge (6, 9, and 18 C) were used. Two electrodes were inserted into the base, perpendicular to the tumor's long axis, keeping about 1 cm distance between them. Results have shown that the F3II tumor is highly sensitive to direct current. The overall effectiveness (complete response + partial response) of this physical agent was ≥75.0% and observed in 59.3% (16/27) of treated F3II tumors. Complete remission of treated tumors was observed in 22.2% (6/27). An unexpected result was the death of 11 direct current-treated animals (eight females and three males). It is concluded that direct current may be addressed to significantly affect highly aggressive and metastatic primary tumor growth kinetics, including the tumor complete response. Bioelectromagnetics. 39:460-475, 2018. © 2018 Wiley Periodicals, Inc.

Evidence-based treatment for gynoid lipodystrophy: A review of the recent literature.

Gynoid lipodystrophy (GLD) is a structural, inflammatory, and biochemical disorder of the subcutaneous tissue causing alterations in the topography of the skin. Commonly known as "cellulite," GLD affects up to 90% of women, practically in all stages of the life cycle, beginning in puberty. It is a clinical condition that considerably affects the patients' quality of life. It is a frequent reason for consultation, although the patients resort to empirical, improvised, nonevidence-based treatments which discourage and can be a source of frustration not only because of the lack of results but also due to the complications derived from those treatments. In this article, a panel of experts from different specialties involved in the management of this clinical skin disorder presents the results of a systematic literature search and of the consensus discussion of the evidence obtained from different treatments currently available. The analysis was divided into topical, systemic, noninvasive, and minimally invasive treatments.

Subtly Modulating Glycogen Synthase Kinase 3 ß: Allosteric Inhibitor Development and Their Potential for the Treatment of Chronic Diseases.

Glycogen synthase kinase 3 ß (GSK-3ß) is a central target in several unmet diseases. To increase the specificity of GSK-3ß inhibitors in chronic treatments, we developed small molecules allowing subtle modulation of GSK-3ß activity. Design synthesis, structure-activity relationships, and binding mode of quinoline-3-carbohydrazide derivatives as allosteric modulators of GSK-3ß are presented here. Furthermore, we show how allosteric binders may overcome the ß-catenin side effects associated with strong GSK-3ß inhibition. The therapeutic potential of some of these modulators has been tested in human samples from patients with congenital myotonic dystrophy type 1 (CDM1) and spinal muscular atrophy (SMA) patients. We found that compound 53 improves delayed myogenesis in CDM1 myoblasts, while compounds 1 and 53 have neuroprotective properties in SMA-derived cells. These findings suggest that the allosteric modulators of GSK-3ß may be used for future development of drugs for DM1, SMA, and other chronic diseases where GSK-3ß inhibition exhibits therapeutic effects.