The association between obesity and malignant progression of Barrett's Esophagus: a systematic review and dose-response meta-analysis.

BACKGROUND AND AIM: Obesity is a risk factor for both Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). However, it is unclear whether obesity drives the malignant progression of BE. We aimed to assess whether obesity is associated with high-grade dysplasia (HGD) or cancer in patients with BE. METHODS: We searched MEDLINE and EMBASE from inception through April 2024 for studies reporting the effect of body mass index (BMI) on the progression of non-dysplastic BE or low-grade dysplasia (LGD) to HGD or EAC. A two-stage dose response meta-analysis was performed to estimate the dose-response relationship between BMI with malignant progression. Study quality was appraised using a modified Newcastle-Ottawa scale. The review was registered (PROSPERO ID CRD42017051046). RESULTS: Twenty studies reported data on 38565 patients (74.4% male) in total, of whom 1684 patients were diagnosed with HGD/cancer. Nineteen studies were considered moderate to high quality. Eight cohort studies reported data on 6647 male patients with baseline NDBE/LGD, of whom 555 progressed to HGD/EAC (pooled annual rate of progression 0.02%; 95% CI 0.01%-0.03%) and 1992 female patients with baseline NDBE/LGD with 110 progressors (pooled annual rate of progression 0.01%; 95% CI 0.01%-0.02%). There was no significant difference in pooled annual rate of progression between males and females (p=0.15). Each 5kg/m2 increase in BMI was associated with a 6% increase in the risk of malignant progression (adjusted OR 1.06; 95% CI 1.02-1.10; p<0.001; I2=0%). CONCLUSION: Our meta-analysis provides some evidence that obesity as measured by BMI is associated with malignant progression of BE with a dose-response relationship. This finding requires confirmation in future high-quality cohort studies. Future risk prediction models could incorporate measures of obesity to potentially improve risk stratification in patients with BE.

Doxorubicin and folic acid-loaded zinc oxide nanoparticles-based combined anti-tumor and anti-inflammatory approach for enhanced anti-cancer therapy.

BACKGROUND: Zinc oxide nanoparticles (ZnONPs) have impressively shown their efficacy in targeting and therapy of cancer. The present research was designated to investigate the potential of ZnONP nanocomposites as a cancer chemotherapeutic-based drug delivery system and to assess the anti-tumor and anti-inflammatory effectiveness of ZnONP nanocomposites combination with systemic chemotherapeutic drugs doxorubicin (DOX) and folic acid (FA) in Ehrlich ascites carcinoma (EAC) tumor cell line both in vitro and in vivo. METHODS: Anti-tumor potential of ZnONP nanocomposites: ZnONPs, ZnONPs/FA, ZnONPs/DOX and ZnONPs/DOX/FA against EAC tumor cell line was evaluated in vitro by MTT assay. Anti-tumor and anti-inflammatory efficacy of ZnONP nanocomposites were analyzed in vivo by examination of the proliferation rate and apoptosis rate of EAC tumor cells by flow cytometry, splenocytes count, level of inflammatory markers interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), as well as liver and kidney function in EAC-challenged mice. RESULTS: In vitro results showed that ZnONP nanocomposites showed a high anti-proliferative potency against EAC tumor cells. Furthermore, the in vivo study revealed that the treatment EAC-challenged mice with ZnONPs, ZnONPs/DOX, ZnONPs/FA and ZnONPs/DOX/FA hindered the proliferation rate of implanted EAC tumor cells through lowering their number and increasing their apoptosis rate. Moreover, the treatment of EAC-challenged mice with ZnONPs/DOX/FA markedly decreased the level of IL-6 and TNF-α and remarkably ameliorated the liver and kidney damages that were elevated by implantation of EAC tumor cells, restoring the liver and kidney functions to be close to the naïve mice control. CONCLUSION: ZnONP nanocomposites may be useful as a cancer chemotherapeutic-based drug delivery system. ZnONP nanocomposites: ZnONPs/DOX, ZnONPs/FA and ZnONPs/DOX/FA regimen may have anti-inflammatory approaches and a great potential to increase anti-tumor effect of conventional chemotherapy, overcoming resistance to cancer systemic chemotherapeutics and reducing their side effects, offering a promising regimen for cancer therapy.

Rapid regional mobile laboratory response and genomic monkeypox virus (MPXV) surveillance in seven East African Community partner states, August 2024: preparedness activities for the ongoing outbreak.

The East African Community (EAC) is experiencing an unprecedented, emerging mpox outbreak since July 2024 in five of eight partner states. We highlight rapid regional response measures, initiated August 2024 coordinated by EAC: field deployment of six mobile laboratories in Burundi, Rwanda, Uganda, Tanzania, Kenya, South Sudan to high-risk areas, donation of one mobile laboratory to Democratic Republic of the Congo and genomic monkeypox virus (MPXV) surveillance support. These interventions aim to limit local mpox spread and support international containment.

Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights.

Esophageal cancer (EC) remains a formidable malignancy with limited treatment options and high mortality rates, necessitating the exploration of innovative therapeutic avenues. Through a systematic analysis of a multitude of studies, we synthesize the diverse findings related to metformin's influence on EC. This review comprehensively elucidates the intricate metabolic pathways and molecular mechanisms through which metformin may exert its anti-cancer effects. Key focus areas include its impact on insulin signaling, AMP-activated protein kinase (AMPK) activation, and the mTOR pathway, which collectively contribute to its role in mitigating esophageal cancer progression. This review critically examines the body of clinical and preclinical evidence surrounding the potential role of metformin, a widely prescribed anti-diabetic medication, in EC management. Our examination extends to the modulation of inflammation, oxidative stress and angiogenesis, revealing metformin's potential as a metabolic intervention in esophageal cancer pathogenesis. By consolidating epidemiological and clinical data, we assess the evidence that supports metformin's candidacy as an adjuvant therapy for esophageal cancer. By summarizing clinical and preclinical findings, our review aims to enhance our understanding of metformin's role in EC management, potentially improving patient care and outcomes.

Conservation priorities for endangered trees facing multiple threats around the world.

Trees are vital to the survival of numerous species and to forest ecosystem functioning. However, the current distribution, vulnerability to extinction, and conservation priorities of globally endangered trees are not well known. We mapped the global distribution of 1686 tree species listed as endangered on the International Union for the Conservation of Nature Red List and identified conservation priority for them based on species richness, life-history traits, evolutionary distinctiveness, future climate change, and intensity of human activities. We also evaluated the impacts of various threats to these endangered tree species and evaluated the effectiveness of their protection based on the percentage of the species' range inside protected areas. The worldwide distribution of endangered trees, from the tropics through temperate zones, was uneven. Most endangered tree species were not protected in their native ranges, and only 153 species were fully protected. Hotspots of tree diversity occurred primarily in the tropics, and 79.06% of these were highly vulnerable to threats. We identified 253 areas of high priority for the conservation of endangered trees that are highly threatened and insufficiently protected. In particular, 43.42% of unprotected tree species in priority areas lacked recommended conservation measures or had no associated conservation plan. The priority conservation areas and unprotected trees we identified serve as a guideline for future management underpinning the post-2020 global biodiversity framework.

Prioridades de conservación para los árboles amenazados que enfrentan múltiples amenazas en todo el mundo Resumen Los árboles son vitales para la supervivencia de numerosas especies y para el funcionamiento de los ecosistemas forestales. Sin embargo, no se conoce muy bien la distribución actual, vulnerabilidad a la extinción y prioridades de conservación de los árboles amenazados a nivel mundial. Mapeamos la distribución global de 1686 especies de árboles catalogadas como en peligro por la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza e identificamos su prioridad de conservación con base en la riqueza de especies, características de historia de vida, singularidad evolutiva, cambio climático futuro e intensidad de las actividades humanas. También evaluamos el impacto de varias amenazas sobre estas especies y analizamos la efectividad de su protección con base en el porcentaje de la distribución de la especie ubicado dentro de un área protegida. La distribución mundial de árboles en peligro, desde los trópicos y hasta las zonas templadas, fue desigual. La mayoría de las especies no estaban protegidas dentro de su distribución nativa y sólo 153 especies contaban con protección completa. Los puntos calientes de diversidad de árboles se ubicaron principalmente en los trópicos, y el 79.06% de estos tenían una vulnerabilidad alta ante las amenazas. Identificamos 253 áreas de gran prioridad para la conservación de los árboles en peligro que están amenazados y con poca protección. En particular, el 43.42% de las áreas sin protección dentro de las áreas prioritarias no contaban con las medidas recomendadas de conservación o no tenían asociado un plan de conservación. Las áreas prioritarias de conservación y los árboles sin protección que identificamos son una pauta para futuros manejos que apuntalan el marco de trabajo post-2020 para la biodiversidad.

Facilitating biodiversity conservation through partnerships to achieve transformative outcomes.

Conservation biology is a mission-driven discipline that must navigate a new relationship between conservation and science. Because conservation is a social and political as well as an ecological project, conservation biologists must practice interdisciplinarity and collaboration. In a comparative study of 7 cases (Jaguars in the Chaco, Grevy's zebra in Kenya, Beekeeping in Tanzania, Andean cats in Argentina, Jaguars in Mexico, Lobster fishing, and Black bears in Mexico), we examined motivations for collaboration in conservation, who can collaborate in conservation, and how conservation professionals can work well together. In 5 case studies, successful conservation outcomes were prioritized over livelihood benefits. In the other 2 cases, livelihoods were prioritized. All case studies employed participatory approaches. There were multiple external actors, including local and Indigenous communities, nongovernmental organizations, agencies, regional and national governments, and international organizations, which enhanced conservation and wider sustainability outcomes. Key collaboration aspects considered across the case studies were time (mismatch between relationship building and project schedules), trust required for meaningful partnerships, tools employed, and transformative potential for people, nature, and the discipline of conservation biology. We developed guidelines for successful collaboration, including long-term commitment, knowledge integration, multiscalar and plural approaches, cultivation of trust, appropriate engagement, evaluation, supporting students, and efforts for transformation.

Facilitación de la conservación de la biodiversidad a través de colaboraciones para lograr resultados transformadores Resumen La biología de la conservación es una disciplina impulsada por sus objetivos que debe navegar una nueva relación entre la conservación y la ciencia. Dado que la conservación es un proyecto social y político así como ecológico, los biólogos de la conservación deben practicar la interdisciplinariedad y la colaboración. En un estudio comparativo de siete casos (jaguares en el Chaco, cebras de Grevy en Kenia, apicultura en Tanzania, gatos andinos en Argentina, jaguares en México, pesca de langosta, osos negros en México), analizamos las motivaciones para colaborar en la conservación, quién puede colaborar en la conservación y cómo los profesionales de la conservación pueden trabajar bien juntos. En cinco estudios de caso, se priorizaron los resultados satisfactorios de la conservación sobre los beneficios para los medios de subsistencia. En los otros 2 casos, se dio prioridad a los medios de sustento. Todos los estudios de caso emplearon enfoques participativos. Hubo múltiples actores externos, como comunidades locales e indígenas, organizaciones no gubernamentales, agencias, gobiernos regionales y nacionales y organizaciones internacionales, que mejoraron los resultados de conservación y sostenibilidad en general. Los aspectos clave de la colaboración considerados en los estudios de caso fueron el tiempo (desajuste entre el establecimiento de relaciones y los calendarios de los proyectos), la confianza necesaria para establecer colaboraciones significativas, las herramientas empleadas y el potencial transformador para las personas, la naturaleza y la disciplina de la biología de la conservación. Se elaboraron directrices para el éxito de la colaboración, como el compromiso a largo plazo, la integración de conocimientos, los enfoques multiescalares y plurales, el fomento de la confianza, la participación adecuada, la evaluación, el apoyo a los estudiantes y los esfuerzos de transformación. Facilitación de la conservación de la biodiversidad a través de colaboraciones para lograr resultados transformadores.

3,5,7-trihydroxyflavone restricts proliferation of androgen-independent human prostate adenocarcinoma cells by inducing ROS-mediated apoptosis and reduces tumour growth.

Flavonoids are among the largest groups of secondary metabolites. Studies suggest that dietary intake of flavonoids reduces the risk of cancer. 3,5,7-trihydroxyflavone (THF) belongs to the flavone class of flavonoids and potentially inhibits the growth of many cancers; however, it is unexplored in prostate cancer. This study reports the antiproliferative potential of THF in prostate cancer cell line via reactive oxygen species (ROS)-mediated cascades and examines the tumour reduction potential in swiss albino mice. The potency of THF was evaluated by employing cytotoxicity assays and wound healing assays. Cell cycle, ROS, mitochondrial membrane potential (MMP), and Annexin-V-FITC assay were performed using a flow cytometer. In vivo, anticancer potential was achieved using the mice Ehrlich Ascites Carcinoma (EAC) model. THF inhibits cell growth with IC50 of 64.30 µM (MTT), 81.22 µM (NRU) and 25.81 µM (SRB), substantiated by cell migration assay. Cell-cycle analysis revealed that THF increases the subdiploid population. Furthermore, the Annexin-V-FITC assay evoked a significant induction of late apoptosis at a higher concentration of THF. THF also disrupts MMP, caused by an increased generation of ROS. In the EAC model, THF significantly inhibits tumour growth and increases the percent survival of mice and ROS levels in EAC cells. Hence, it may be concluded that THF might execute its antiproliferative effect via inducing ROS generation and could be a promising lead for preclinical and clinical validations.

Regulatory performance of the East African Community joint assessment procedure: The way forward for regulatory systems strengthening.

BACKGROUND: Seven national medicines regulatory authorities in the East African Community (EAC) have embraced regulatory reliance, harmonization and work sharing through the EAC Medicines Regulatory Harmonization programme. Measuring the performance of regulatory systems provides key baseline information to build on regulatory system-strengthening strategies. Therefore, the aim of the study was to evaluate the regulatory performance of the EAC joint scientific assessment of applications approved between 2018 and 2021. METHODS: Utilising a data metrics tool, information was collected reflecting timelines for various milestones including submission to screening, scientific assessment and communication of regional recommendations for biologicals and pharmaceuticals that received a positive regional recommendation for product registration from 2018 to 2021. RESULTS: Several challenges as well as possible solutions were identified, including median overall approval times exceeding the EAC 465-day target and median times to issue marketing authorisation following EAC joint assessment recommendation that far exceeded the 116-day target. Recommendations included establishment of an integrated information management system and automation of the capture of regulatory timelines through the EAC metric tool. CONCLUSIONS: Despite initiative progress, work is required to improve the EAC joint regulatory procedure to achieve regulatory systems-strengthening and ensure patients' timely access to safe, efficacious and quality medicines.

Regional regulatory harmonisation initiatives: Their potential contribution to the newly established African Medicines Agency.

BACKGROUND: Key regulatory entities can serve as building blocks for the African Medicines Agency (AMA). The aim of this study is to demonstrate how the regional medicines regulatory harmonisation programmes could contribute to AMA's effectiveness and efficiency. METHODS: A literature search was conducted using key words to identify publications about the AMA, African Medicines Regulatory Harmonisation (AMRH) and East African Community Medicines Regulatory Harmonisation programmes (EAC-MRH) from 2009 to 2023. The EAC-MRH programme experience was used to highlight the benefits and challenges of African regulatory harmonisation. RESULTS: As the foundation for the AMA, the AMRH has established structures and workstreams to support its operationalisation, including 10 Technical Committees (TCs) and 5 Regional Economic Committees (RECs). Lessons learned from the EAC-MRH 10-year experience are being used to scale up regulatory harmonisation and could be of value to AMA harmonisation experience. CONCLUSIONS: As of June 2023, 35 of 55 countries have either signed and/or ratified the AMA Treaty, whilst 20 have neither signed nor ratified it. An effective AMA will need strong National Medicines Regulatory Authorities as well as Regional programmes and it is imperative for more well-resourced countries to ratify the treaty to ensure access to essential medical products and technologies for the African people.

Long-term analysis of prognostic risk factors impacting surgical outcomes in patients with external auditory canal carcinoma.

BACKGROUND: Malignant neoplasms of the external auditory canal (EAC) are rare. No consensus on management has emerged. OBJECTIVE: To determine possible risk factors influencing tumorgenesis and prognosis of EAC carcinoma. MATERIALS AND METHODS: 108 patients (87 men/21 women) with an average age of 74 ± 13.8 years were recruited from 2005 to 2019 at Department of Otorhinolaryngology, Head and Neck Surgery Heidelberg. The follow-up interval was 43.62 ± 55.39 months. Partial and (sub)total ablative otis, supplementary surgery (petrosectomy, parotidectomy, neck dissection, mastoidectomy) and adjuvant radio(chemo)therapy belonged to treatment options. TNM status was determined at time of diagnosis using the AJCC staging system. RESULTS: 63.9% of patients underwent a total ablative otis. Tumor recurrence was seen in 24.1%. The 1-year survival rate was 87%, the 5-year survival rate was 52%, the mean overall survival (OS) was 3.82 ± 4.6 years. Male EAC carcinoma patients had a better OS (p < 0.001), PFS (p < 0.001) and DSS (p = 0.02) than females. T1 patients had a better OS (p = 0.01), PFS (p = 0.01) and DSS (p < 0.001) than T4 patients. Lymph node but not distant metastasis, tumor grading, perineural, venous and lymphatic invasion, histology, age and tumor localization influenced the OS in EAC carcinoma patients (p = 0.04). The more radical the ablative otis, the worse the OS (p = 0.002), PFS (p = 0.02) and DSS (p < 0.001). Radio(chemo)therapy did not improve the OS. CONCLUSIONS: EAC carcinoma are difficult to treat and benefit from early diagnosis so that a radical combined treatment approach does not need to be used.

Molecular Docking and In Vivo Biological Studies of Sodium Salt of 3-(4-Methyl-2-oxo-2-H-quinoline-7-yloxy)-3-phenylacrylic Acid As Anticancer Agent.

Quinoline derivatives possess several therapeutic properties. Aim: studying the anticancer effect of 3-(4-methyl-2-oxo-2-H-quinoline-7-yloxy)-3-phenylacrylic acid's sodium solution on the Ehrlich ascites carcinoma (EAC). Median lethal dose (LD50) and dose response curve was determined for sodium salt solution of 3-(4-methyl-2-oxo-2-H-quinoline-7-yloxy)-3-phenylacrylic acid, then diving a group of one hundred Swiss albino mice, which are all females, into five groups: group 1: (negative control) where intraperitoneally injected with saline into mice for 10 successive days; group 2 (positive control), also namely (EAC-bearing group): where the EAC cells were intraperitoneally injected into mice (2.5 × 106 cells/mouse) only one time on the first day; group 3 which is defined as the (therapeutic group) where the Na+ salt of the synthetic compound was injected into the peritoneum of the mice (2.5 mg/kg) the very first day after the injection of the EAC, then the compound was injected every two days for a period of 10 days; group 4 which is the (preventive group) where the sodium salt of the synthetic compound (2.5 mg/kg) was injected in the peritoneum of the mice the day before the injection of the EAC, then the compound was successively injected every day for a period of ten days; and group 5 which is the (drug group) in which mice were repeatedly injected) in their peritoneum with the sodium salt of the synthetic compound (2.5 mg/kg on a daily basis over a period of ten days. On the eleventh day of the trial, EAC cells were harvested from each mouse in a heparinized saline, in addition to blood samples, liver and kidney tissues which are also collected. Molecular docking showed that compound's sodium salt was docked into (PDB: 2R7G) and (PDB: 2R3I), which are the retinoblastoma protein receptor and the cyclin D-1 receptor respectively. Compared to those in the positive control group, mice in both the therapeutic and preventive groups, has shown a significant decrease in MDA, cyclin D-1 levels in the tissues of both liver and kidney tissues, in addition to the serum ALT, AST, CK-MB, and LDH activities, and the serum urea and creatinine concentration. However, mice in the formerly mentioned groups, both therapeutic and preventive groups, have shown an increase in the serum albumin, total protein, retinoblastoma protein in both liver and kidney tissues as well as the total antioxidant capacity, when compared to mice in the positive control group. It is worth mentioning that histopathological findings have confirmed that. Sodium salt of 3-(4-methyl-2-oxo-2H-quinoline-7-yloxy)-3-phenylacrylic acid showed potential in vivo anticancer and antioxidant effects against Ehrlich ascites carcinoma cells; (EAC cells).

Substituted Thiazole Derivatives Provide Corrective Anti-tumour and Anti-oxidant Activities against Ehrlich Ascites Carcinoma.

Novel and effective treatments are urgently needed for cancer, which is still the leading cause of death in the world. Biological characteristics linked to thiazole derivatives span a wide range. Thiazole derivatives are used in the creation of medications for therapy as well. The aim of current study is to evaluate the anticancer and antioxidant properties of the newly synthesized thiazole derivatives, compounds 1 and 2, on Ehrlich ascites carcinoma (EAC) cells in female mice. Our findings indicated that thiazole derivatives, compounds 1 and 2 have anticancer activity by elevating the p53 expression and cytochrome c levels in groups treated with compounds 1 and 2 compared to the positive control group. Furthermore, thiazole derivatives compounds 1 and 2 showed a potent antioxidant effect by increasing enzymatic antioxidants, catalase (CAT) activity, and non-enzymatic antioxidants, GSH, and lowering Malondialdehyde (MDA) in hepatic and renal tissues of treated groups. Additionally, the target compounds were capable of providing corrective effects against EAC-induced biochemical and histopathological changes without harmful side effects. CONCLUSION: The target studied thiazol derivatives compounds were capable of providing corrective effects against EAC-induced without harmful side effects.

Between Regional Recommendations and National Implementation: An Analysis of the East African Community Partner States' Legislative Responses to TRIPS Obligations.

With the access-to-medicines conundrum facing its populations, the East African Community has adopted a policy framework which promotes a collective approach to resolving the access gap in the region. To this end, crucial policy documents on the implementation of TRIPS obligations, harmonisation of drug regulation and boosting regional manufacturing capacity have been adopted. This paper is a case study of the regional policy on the implementation of TRIPS obligations, specifically examining the extent to which partner states' implementation of TRIPS obligations mirrors the regional recommendations. The paper finds that, while many partner states follow the regional recommendations on implementing TRIPS obligations, coherence remains a big challenge. This, the paper concludes, may affect the overall usefulness of a regional approach to solving the access conundrum.

The Optimal Age to Stop Endoscopic Surveillance of Patients With Barrett's Esophagus Based on Sex and Comorbidity: A Comparative Cost-Effectiveness Analysis.

BACKGROUND AND AIMS: Current guidelines recommend surveillance for patients with nondysplastic Barrett's esophagus (NDBE) but do not include a recommended age for discontinuing surveillance. This study aimed to determine the optimal age for last surveillance of NDBE patients stratified by sex and level of comorbidity. METHODS: We used 3 independently developed models to simulate patients diagnosed with NDBE, varying in age, sex, and comorbidity level (no, mild, moderate, and severe). All patients had received regular surveillance until their current age. We calculated incremental costs and quality-adjusted life-years (QALYs) gained from 1 additional endoscopic surveillance at the current age versus not performing surveillance at that age. We determined the optimal age to end surveillance as the age at which incremental cost-effectiveness ratio of 1 more surveillance was just less than the willingness-to-pay threshold of $100,000/QALY. RESULTS: The benefit of having 1 more surveillance endoscopy strongly depended on age, sex, and comorbidity. For men with NDBE and severe comorbidity, 1 additional surveillance at age 80 years provided 4 more QALYs per 1000 patients with BE at an additional cost of $1.2 million, whereas for women with severe comorbidity the benefit at that age was 7 QALYs at a cost of $1.3 million. For men with no, mild, moderate, and severe comorbidity, the optimal ages of last surveillance were 81, 80, 77, and 73 years, respectively. For women, these ages were younger: 75, 73, 73, and 69 years, respectively. CONCLUSIONS: Our comparative modeling analysis illustrates the importance of considering comorbidity status and sex when deciding on the age to discontinue surveillance in patients with NDBE.

Identifying and developing effective post-2020 conservation bridging leaders.

Effective bridging leaders interact within and outside their group to facilitate collaboration required in multistakeholder contexts. This is particularly crucial to community-based conservation interventions that strive to achieve both ecological and social objectives by actively engaging or devolving decision-making and management authority to local communities. Although a viable approach in many contexts, achieving "unprecedented collaboration" called for by the Post-2020 Global Biodiversity Framework in community-based conservation is problematic given the multiple and diverse actors affecting and affected by these interventions. Therefore, effective leadership becomes crucial to implementing necessary strategies to engage actors and resolve conflict inclusively. Yet, weak leadership commonly constrains these interventions. I reviewed relevant literature and devised a framework of effective bridging leadership characteristics. I then used this framework to appraise bridging leadership in two African coastal-marine community-based conservation cases. I employed social network analysis and semistructured and group interviews in the two cases. Several local leaders emerged as key (potential) bridging leaders. Furthermore, I found that effective bridging leaders require not only legal recognition but also perceived legitimacy resulting from building trust with other actors. Additionally, the inclusive collaboration required multiple sources of emotionally intelligent bridging leaders with the integrity, humility, empathy, and cultural awareness necessary to mitigate elite capture, effectively communicate, and empower and provide support to others. Because emotional intelligence in conservation leadership remains a knowledge gap, particularly in community-based conservation research, insights from this study should be useful to diverse conservation actors.

Los líderes vinculantes efectivos interactúan dentro y fuera de su grupo para facilitar la colaboración requerida en contextos con múltiples actores. Esto es crucial para las intervenciones de conservación basada en la comunidad que buscan alcanzar objetivos ecológicos y sociales mediante la participación y transferencia de la autoridad gestora y la toma de decisiones a la comunidad local. Aunque es una estrategia viable, es problemático lograr la "colaboración sin precedentes" en la conservación basada en la comunidad que exige el Marco Mundial de Biodiversidad Post-2020 debido a los múltiples y diversos actores que afectan y han sido afectados por estas intervenciones. Por lo tanto, el liderazgo efectivo se vuelve crucial para la implementación de las estrategias necesarias para involucrar a los actores y resolver los conflictos de manera inclusiva. Sin embargo, es común que el liderazgo deficiente limite estas intervenciones. Revisé la literatura relevante y diseñé un marco de trabajo de las características del liderazgo vinculante efectivo. Después usé este marco para valorar el liderazgo vinculante en dos casos de conservación costera-marina basada en la comunidad en África. Analicé las redes sociales y realicé entrevistas grupales y semiestructuradas en ambos casos. Además, descubrí que los líderes vinculantes efectivos requieren no sólo de un reconocimiento legal, sino también de la legitimidad resultante de la construcción de la confianza con otros actores. Asimismo, la colaboración inclusiva requirió de líderes vinculantes de múltiples orígenes con inteligencia emocional y con la integridad, humildad, empatía y conciencia cultural para mitigar la captura elite, comunicar efectivamente y empoderar y proporcionarles apoyo a los demás. Ya que la inteligencia emocional todavía es un vacío de conocimiento en el liderazgo de la conservación, particularmente en la investigación sobre la conservación basada en la comunidad, el conocimiento que brinda este estudio debería ser útil para diversificar a los actores de la conservación.

Integration of qualitative and quantitative methods for land-use-change modeling in a deforestation frontier.

Development and implementation of effective protected area management to reduce deforestation depend in part on identifying factors contributing to forest loss and areas at risk of conversion, but standard land-use-change modeling may not fully capture contextual factors that are not easily quantified. To better understand deforestation and agricultural expansion in Amazonian protected areas, we combined quantitative land-use-change modeling with qualitative discourse analysis in a case study of Brazil's Jamanxim National Forest. We modeled land-use change from 2008 to 2018 and projected deforestation through 2028. We used variables identified in a review of studies that modeled land-use change in the Amazon (e.g., variables related to agricultural suitability and economic accessibility) and from a critical discourse analysis that examined documents produced by different actors (e.g., government agencies and conservation nonprofit organizations) at various spatial scales. As measured by analysis of variance, McFadden's adjusted pseudo R2 , and quantity and allocation disagreement, we found that including variables in the model identified as important to deforestation dynamics through the qualitative discourse analysis (e.g., the proportion of unallocated public land, distance to proposed infrastructure developments, and density of recent fires) alongside more traditional variables (e.g., elevation, distance to roads, and protection status) improved the predictive ability of these models. Models that included discourse analysis variables and traditional variables explained up to 19.3% more of the observed variation in deforestation probability than a model that included only traditional variables and 4.1% more variation than a model with only discourse analysis variables. Our approach of integrating qualitative and quantitative methods in land-use-change modeling provides a framework for future interdisciplinary work in land-use change.

El desarrollo y la implementación de la gestión efectiva de las áreas protegidas para reducir la deforestación dependen parcialmente de la identificación de los factores que contribuyen a la pérdida del bosque y de las áreas en riesgo de ser convertidas, pero el modelado estándar del cambio de uso de suelo puede no capturar completamente los factores contextuales que no se cuantifican fácilmente. Combinamos el modelado cuantitativo del cambio de uso de suelo con el análisis cualitativo del discurso en un estudio de caso del Bosque Nacional Jamanxim de Brasil para entender de mejor manera la deforestación y la expansión agrícola en las áreas protegidas del Amazonas. Modelamos el cambio de uso de suelo entre 2008 y 2018 y lo proyectamos hasta 2028. Usamos las variables identificadas en una revisión de estudios que modelaron el cambio de uso de suelo en el Amazonas (p. ej.: variables relacionadas con la idoneidad agrícola y la accesibilidad económica) y en el análisis crítico del discurso que examinó documentos producidos por diferentes actores (p. ej.: agencias gubernamentales y organizaciones sin fines de lucro para la conservación) a varias escalas espaciales. Conforme a las medidas del análisis de varianza, la pseudo-R2 ajustada de McFadden y el desacuerdo en la cantidad y la asignación, descubrimos que la inclusión dentro del modelo de las variables identificadas como importantes para las dinámicas de deforestación mediante el análisis cualitativo del discurso (p. ej.: la proporción de terrenos públicos sin asignar, la distancia hacia los desarrollos propuestos de infraestructura y la densidad de incendios recientes) junto con variables más tradicionales (p. ej.: elevación, distancia a las carreteras y estado de protección) mejoró la habilidad predictiva de dichos modelos. Los modelos que incluyeron la mezcla de variables explicaron hasta 19.3% más de la variación observada en la probabilidad de deforestación que un modelo que solamente incluyó las variables tradicionales y 4.1% más variación que un modelo con las variables del análisis del discurso. Nuestra estrategia de integrar los métodos cualitativos y cuantitativos dentro del modelado del cambio de uso de suelo proporciona un marco para futuros trabajos interdisciplinarios sobre el cambio de uso de suelo.

The right of access to healthcare: an analysis of how legal and institutional frameworks constrain or facilitate access to healthcare for residents in border areas in the East African Community.

BACKGROUND: Despite many countries working hard to attain Universal Health Coverage (UHC) and the Health-related Sustainable Development Goals, access to healthcare services has remained a challenge for communities residing along national borders in the East Africa Community (EAC). Unlike the communities in the interior, those along national borders are more likely to face access barriers and exclusion due to low health investments and inter-state rules for non-citizens. This study explored the legal and institutional frameworks that facilitate or constrain access to healthcare services for communities residing along the national borders in EAC. METHODS: This study is part of a broader research implemented in East Africa (2018-2020), employing mixed methods. For this paper, we report data from a literature review, key informant interviews and sub-national dialogues with officials involved in planning and implementing health and migration services in EAC. The documents reviewed included regional and national treaties, conventions, policies and access rules, regulations and guidelines that affect border crossing and access to healthcare services. These were retrieved from official online and physical libraries and archives. RESULTS: Overall, the existing laws, policies and guidelines at all levels do not explicitly deal with cross border healthcare access especially for border residents, but address citizen rights and entitlements including health within national frameworks. There is no clarity on whether these rights can be enjoyed beyond one's country of citizenship. The review found examples of investments in shared health infrastructure to benefit all EAC member countries - a signal of closer cooperation for specialized health care, this had not been accompanied by access rule for citizens outside the host country. The focus on specialized care is unlikely to contribute to the every-day health care needs of border resident communities in remote areas of EAC. Nevertheless, the establishment of the EAC entail opportunities for increased collaboration and integration beyond the trade and customs union to included health care and other social services. The study established active cooperation aimed at disease surveillance and epidemic control among sub-national officials responsible for health and migration services across borders. Health insurance cards, national identification cards and official travel documents were found to constrain access to health services across the borders in EAC. CONCLUSION: In the era of UHC, there is need to take advantage of the EAC integration to revise legal and policy frameworks to leverage existing investments and facilitate cross-border access to healthcare services for communities residing along EAC borders.

Genetically engineered mouse models of esophageal cancer.

BACKGROUND: Esophageal cancer is the most common cause of cancer-related death worldwide with a diverse geographical distribution, poor prognosis, and diagnosis in advanced stages of the disease. Identification of the mechanisms involved in esophageal cancer development is evaluative to improve outcomes for patients. Genetically engineered mouse models (GEMMs) of cancer provide the physiologic, molecular, and histologic features of the human tumors to determine the pathogenesis and treatments for cancer, hence exhibiting a source of tremendous potential for oncology research. The advancement of cancer modeling in mice has improved to the extent that researchers can observe and manipulate the disease process in a specific manner. Despite the significant differences between mice and humans, mice can be great models for human oncology researches due to similarities between them at the molecular and physiological levels. Due to most of the existing esophageal cancer GEMMs do not propose an ideal system for pathogenesis of the disease, genetic risks, and microenvironment exposure, so identification of challenges in GEM modeling and well-developed technologies are required to obtain the most value for patients. In this review, we describe the biology of human and mouse, followed by the exciting esophageal cancer mouse models with a discussion of applicability and challenges of these models for generating new GEMMs in future studies.

In vivo biological evaluation of sodium salt of ethyl (E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxoquinoline-1(2H)-yl)-3-(4-hydroxyphenyl) acrylate as anticancer agent.

Nowadays, quinoline scaffold is among the most vital construction compounds for the development of new drugs. The purpose of this research is to evaluate the anti-cancer activity of sodium salt of ethyl (E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxoquinoline-1(2H)-yl)-3-(4-hydroxyphenyl) acrylate against Ehrlich ascites carcinoma (EAC) cells residing in female mice's peritoneal cavity. The docking study exhibited a favourable interaction between the compound and the receptors 1MOY and 3KJF of osteopontin and caspase 3, respectively. The compound's sodium salt showed potential antioxidant and anti-cancer effects against Ehrlich ascites carcinoma (EAC) cells in vivo. Herein, the results elucidated that treatment with the compound's sodium salt exerted significant chemopreventive and chemotherapeutic effects, which reduced both EAC cell volume and count. Our results revealed that treatment with the sodium salt of the compound demonstrated a remarkable in vivo apoptotic effect through elevation of the expression of caspase 3 and reduction of osteopontin levels. Histopathological examination confirmed that the compound's sodium salt improved liver and kidney tissues without any apparent adverse effects.

Lean mass and strength profile of women submitted to bariatric surgery: comparison of the EWGSOP2 and FNIH classification for sarcopenia - ASBS program phase II.

Aim: To assess the effect of bariatric surgery on the lean mass of women after one year of the procedure, comparing its outcomes upon the classification from both the Foundation of the National Institutes of Health (FNIH) and the European Working Group on Sarcopenia in the Elderly People (EWGSOP). Material and methods: Twenty-eight obese women aged 40.5 ± 9.8 yrs who underwent Roux-en-Y gastric bypass (RYGB) were included. 27 of them were reassessed after 6 months of surgery, and 16 completed the one-year follow-up. Pre-sarcopenia condition was assessed through a handgrip strength test and body composition by dual-energy X-ray absorptiometry (DXA). Total body mass, body mass index, and lean mass (LM) were collected prior to, 6 and 12 months after RYGB surgery. Results: All subjects reassessed after 12 months were diagnosed with pre-sarcopenia according to the FNIH classification criteria, while according to the EWGSOP2 Consensus they presented normal values. LM represented 14% of the influence on handgrip strength (p = .049) after 6 months of surgery; however, its influence on strength after 12 months increased to 30% (p = .028). Conclusion: The FNIH classification is the most effective criteria since it uses LM content as the first test, considering that strength capacity needs more time to be affected by the surgical procedure. On the other hand, the EWGSOP2 classification should not be applied to determine the loss of LM in younger populations regardless of what may have caused such changes.