Effect of Mucuna pruriens seed extract on depression-like behavior derived from mild traumatic brain injury in rats.

Background: Traumatic brain injury (TBI) is a severe health problem for which there is no specific treatment, leading to neurological or neuropsychological consequences. One of the most described disorders, even after mild TBI (mTBI), is depression, related to mechanisms involving reactive oxygen species (ROS). The Mucuna pruriens (M. pruriens) plant has various antioxidant, neuroprotective, and anti-inflammatory properties. Purpose: There is insufficient evidence of M. pruriens use for the treatment of neurobehavioral and depressive impairments induced by TBI and of the mechanisms underlying this effect, so we aimed to evaluate the ability of shortterm administration of M. pruriens extract to prevent neurobehavioral impairment and depression-like behaviors in a murine model of mTBI as well as evaluate the role of oxidative stress. Methods: Male Wistar rats underwent mTBI or sham surgery. Immediately after, they were treated with vehicle or M. pruriens extract (50 mg/kg ip/day for five days). We evaluated neurobehavioral recovery using the Neurobehavioral Severity Scale-Revised (NSS-R) and the immobility time in the forced swimming test 3, 7, 15, 30, and 60 days after mTBI. In addition, lipid peroxidation (LP) and GSH concentrations were determined in some brain areas (motor cortex, striatum, midbrain, and nucleus accumbens). Results: M. pruriens extract did not decrease neurobehavioral impairment caused by mTBI. Nevertheless, it prevented depression-like behaviors starting three days after mTBI, reduced LP, and increased GSH in some brain areas. Conclusions: M. pruriens may prevent depression-like behaviors and reduce oxidative stress by decreasing LP and increasing concentrations of antioxidant compounds.

The Anatomy, Histology, and Function of the Major Pelvic Ganglion.

This review provides a comprehensive analysis of the pelvic plexus and its regulation across various mammalian species, including rats, cats, dogs, and pigs. The pelvic and hypogastric nerves play crucial roles in regulating pelvic functions such as micturition, defecation, and erection. The anatomical organization of these nerves varies, forming either well-defined ganglia or complex plexuses. Despite these variations, the neurons within these structures are consistently regulated by key neurotransmitters, norepinephrine and acetylcholine. These neurons also possess receptors for testosterone and prolactin, particularly in rats, indicating the significant role of these hormones in neuronal function and development. Moreover, neuropeptides such as vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY), somatostatin (SOM), galanin (GAL), and calcitonin gene-related peptide (CGRP) are co-released with neurotransmitters to modulate pelvic functions. This review highlights the complex interplay between neurotransmitters, neuropeptides, and hormones in regulating pelvic physiology and emphasizes the importance of hormonal regulation in maintaining the functionality and health of the pelvic plexus across different species.

Dysregulation of the dopaminergic system secondary to traumatic brain injury: implications for mood and anxiety disorders.

Traumatic brain injury (TBI) represents a public health issue with a high mortality rate and severe neurological and psychiatric consequences. Mood and anxiety disorders are some of the most frequently reported. Primary and secondary damage can cause a loss of neurons and glial cells, leading to dysfunction of neuronal circuits, which can induce imbalances in many neurotransmitter systems. Monoaminergic systems, especially the dopaminergic system, are some of the most involved in the pathogenesis of neuropsychiatric and cognitive symptoms after TBI. In this work, we summarize the studies carried out in patients who have suffered TBI and describe alterations in the dopaminergic system, highlighting (1) dysfunction of the dopaminergic neuronal circuits caused by TBI, where modifications are shown in the dopamine transporter (DAT) and alterations in the expression of dopamine receptor 2 (D2R) in brain areas with dopaminergic innervation, thus establishing a hypodopaminergic state and (2) variations in the concentration of dopamine and its metabolites in biological fluids of post-TBI patients, such as elevated dopamine (DA) and alterations in homovanillic acid (HVA). On the other hand, we show a large number of reports of alterations in the dopaminergic system after a TBI in animal models, in which modifications in the levels of DA, DAT, and HVA have been reported, as well as alterations in the expression of tyrosine hydroxylase (TH). We also describe the biological pathways, neuronal circuits, and molecular mechanisms potentially involved in mood and anxiety disorders that occur after TBI and are associated with alterations of the dopaminergic system in clinical studies and animal models. We describe the changes that occur in the clinical picture of post-TBI patients, such as alterations in mood and anxiety associated with DAT activity in the striatum, the relationship between post-TBI major depressive disorders (MDD) with lower availability of the DA receptors D2R and D3R in the caudate and thalamus, as well as a decrease in the volume of the substantia nigra (SN) associated with anxiety symptoms. With these findings, we discuss the possible relationship between the disorders caused by alterations in the dopaminergic system in patients with TBI.

Neoadjuvant cabozantinib restores CD8+ T cells in patients with locally advanced non-metastatic clear cell renal cell carcinoma: a phase 2 trial.

Cabozantinib is an oral multikinase inhibitor approved for treatment in metastatic renal cell carcinoma (RCC). We hypothesized that neoadjuvant cabozantinib could downstage localized tumors, facilitating partial nephrectomy, and facilitating surgery in patients with locally advanced tumors that would require significant adjacent organ resection. We, therefore, conducted a phase 2, single-arm trial of cabozantinib treatment for 12 weeks in 17 patients with locally advanced biopsy-proven non-metastatic clear cell RCC before surgical resection. Six patients (35%) experienced a partial response, and 11 patients (65%) had stable disease. We identified that plasma cell-free DNA (cfDNA), VEGF, c-MET, Gas6, and AXL were significantly increased while VEGFR2 decreased during cabozantinib treatments. There was a trend towards CD8+ T cells becoming activated in the blood, expressing the proliferation marker Ki67 and activation markers HLA-DR and CD38. Cabozantinib treatment depleted myeloid populations acutely. Importantly, immune niches made up of the stem-like CD8+ T cells and antigen presenting cells were increased in every patient. These data suggest that cabozantinib treatment was clinically active and safe in the neoadjuvant setting in patients with locally advanced non-metastatic clear cell RCC and activated the anti-tumor CD8+ T cell response. The trial is registered at ClinicalTrials.gov under registration no. NCT04022343.

TiO2-ZnPc nanoparticles functionalized with folic acid as a target photosensitizer for photodynamic therapy against glioblastoma cells.

The use of TiO2 as a photosensitizer in photodynamic therapy is limited due to TiO2 generates reactive oxygen species only under UV irradiation. The TiO2 surface has been modified with different functional groups to achieve activation at longer wavelengths (visible light). This work reports the synthesis, characterization, and biological toxicity assay of TiO2 nanoparticles functionalized with folic acid and combined with a zinc phthalocyanine to obtain a nano-photosensitizer for its application in photodynamic therapy for glioblastoma cancer treatment. The nano-photosensitizer was prepared using the sol-gel method. Folic acid and zinc phthalocyanine were added during the hydrolysis and condensation of titanium butoxide, which was the TiO2 precursor. The samples obtained were characterized by several microscopy and spectroscopy techniques. An in vitro toxicity test was performed using the MTT assay and the C6 cellular line. The results of the characterization showed that the structure of the nanoparticles corresponds mainly to the anatase phase. Successful functionalization with folic acid and an excellent combination with phthalocyanine was also achieved. Both folic acid-functionalized TiO2 and phthalocyanine-functionalized TiO2 had no cytotoxic effect on C6 cells (even at high concentrations) in comparison to Cis-Pt, which was very toxic to C6 cells. The materials behaved similarly to the control (untreated cells). The cell viability and light microscopy images suggest that both materials could be considered biocompatible and mildly phototoxic in these cells when activated by light.

Theoretical and experimental studies of cephalexin adsorption on aluminium as a new alternative of removal from wastewater.

Cephalexin (CPX) is an antibiotic widely used to treat many infections. CPX has become an emerging pollutant present in wastewater. On the other hand, it is well known that organic compounds can be adsorbed over metal surfaces when the metal is in active state such as when it is rusting. This work proposes an alternative for the elimination of CPX from wastewater, applying electrochemical principles using a conventional and cheap substrate, aluminium. The first part consisted of obtaining the active states of aluminium electrodes carrying out voltametric curves at different pH (4, 7 and 9) to find the particular condition of interaction between CPX and metal surface. The potential was used in the potentiostatic tests to set the activation potential of metal at different times. After the treatment, electrolyte solutions were analysed using UV-vis spectra, and the aluminium surfaces were studied by optical micrographs and X-ray diffraction. In addition, aluminium-CPX interactions were corroborated by quantum-chemical calculations and adsorption isotherms. All results indicate that it was possible for the CPX removal at basic pH conditions, where the molecule adsorption on the aluminium substrate occurs due to a strong electrostatic interaction.

Multinational evaluation of genetic diversity indicators for the Kunming-Montreal Global Biodiversity Framework.

Under the recently adopted Kunming-Montreal Global Biodiversity Framework, 196 Parties committed to reporting the status of genetic diversity for all species. To facilitate reporting, three genetic diversity indicators were developed, two of which focus on processes contributing to genetic diversity conservation: maintaining genetically distinct populations and ensuring populations are large enough to maintain genetic diversity. The major advantage of these indicators is that they can be estimated with or without DNA-based data. However, demonstrating their feasibility requires addressing the methodological challenges of using data gathered from diverse sources, across diverse taxonomic groups, and for countries of varying socio-economic status and biodiversity levels. Here, we assess the genetic indicators for 919 taxa, representing 5271 populations across nine countries, including megadiverse countries and developing economies. Eighty-three percent of the taxa assessed had data available to calculate at least one indicator. Our results show that although the majority of species maintain most populations, 58% of species have populations too small to maintain genetic diversity. Moreover, genetic indicator values suggest that IUCN Red List status and other initiatives fail to assess genetic status, highlighting the critical importance of genetic indicators.

Efficacy of pain management strategies in adults with Amyotrophic Lateral Sclerosis (ALS): A Systematic Review.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle weakness. Presence of pain in ALS patients is heterogeneously reported in studies, and mostly underrepresented in symptom scales. The aim of this study is to evaluate the efficacy of pharmacological and non-pharmacological therapeutic modalities for pain management in patients with ALS. A systematic review was conducted in four databases; PubMed, Scopus, Clinicaltrials.gov, and Cochrane-Ovid. Five randomized controlled clinical trials were included regarding pharmacological and non-pharmacological pain management interventions in adult patients with confirmed diagnosis of ALS in whom pain was objectively evaluated. Risk of bias assessment was evaluated using the RoB2.0 tool. Eligible studies were reported as a descriptive analysis. This systematic review was registered with PROSPERO ID: CRD42024495009. Five clinical trials regarding pain management strategies in ALS were eligible for analysis. Two out of five were non-pharmacological approaches whilst the remaining three provided pharmacological therapies. Of these, Mexiletine was efficient in terms of pain relief, particularly between 600 and 900 mg per day, whereas Mecasin showed no pain relief at both, high and low doses. Non-pharmacological therapies, such as exercise and osteopathic manual treatment also lacked efficacy in regard to pain management. Clinical trials focusing on pain management strategies for ALS patients are limited. Medical professionals, understandably focused on immediate life-threatening aspects, may inadvertently sideline the nuanced and intricate dimension of pain experienced by patients with ALS.

Alzheimer's Disease: Cellular and Pharmacological Aspects.

Alzheimer's disease was described more than 100 years ago and despite the fact that several molecules are being tested for its treatment, which are in phase III trials, the disease continues to progress. The main problem is that these molecules function properly in healthy neurons, while neuronal pathology includes plasma membrane disruption, malfunction of various organelles, and hyperphosphorylation of Tau and amyloid plaques. The main objective of this article is the discussion of a neuronal restoration therapy, where molecules designed for the treatment of Alzheimer's disease would probably be more effective, and the quality of life of people would be better.

Real-World Use of Hybrid Closed-Loop Systems during Diabetes Camp: A Preliminary Study for Secure Configuration Strategies in Children and Adolescents.

The introduction of closed-loop systems in the pediatric population has been a revolution in the management and evolution of diabetes. However, there are not many published studies in situations in which the feeding, schedules, and activities of the children deviate from the routine for which the systems were programmed, as in the case of a summer camp for children and adolescents with diabetes, where the specific programming of this device is not well known. It was a single-center prospective preliminary study. A total of twenty-seven patients (mean age 11.9 ± 1.9 years, 40% male, duration of diabetes 6.44 ± 2.83 years) were included (twenty with Medtronic MiniMed 780G system and seven with Tandem Control-IQ). Glucometric variables and pump functionality were monitored during the 7-day camp and in the following 3 weeks. There was no decrease from the objective TIR 70% at any moment. The worst results in Time Below Range were at 72 h from starting the camp, and the worst results in Time Above Range were in the first 24 h, with a progressive improvement after that. No episodes of level 3 hypoglycemia or ketoacidosis occurred. The use of specific programming in two integrated systems, with complex blood glucose regulation algorithms and not-prepared-for situations with increased levels of physical activity or abrupt changes in feeding routines, did not result in an increased risk of level 3 hypoglycemia and ketoacidosis for our pediatric type 1 diabetes (T1D) patients, regardless of the closed-loop device.

Detection of cerebrospinal fluid biomarkers changes of Alzheimer's disease using a cognitive stress test in persons with subjective cognitive decline and mild cognitive impairment.

Introduction: Timely and accurate diagnosis of the earliest manifestations of Alzheimer's disease (AD) is critically important. Cognitive challenge tests such as the Loewenstein Acevedo Scales for Semantic Interference and Learning (LASSI-L) have shown favorable diagnostic properties in a number of previous investigations using amyloid or FDG PET. However, no studies have examined LASSI-L performance against cerebrospinal fluid biomarkers of AD, which can be affected before the distribution of fibrillar amyloid and other changes that can be observed in brain neuroimaging. Therefore, we aimed to evaluate the relationship between LASSI-L scores and CSF biomarkers and the capacity of the cognitive challenge test to detect the presence of amyloid and tau deposition in patients with subjective cognitive decline and amnestic mild cognitive impairment (MCI). Methods: One hundred and seventy-nine patients consulting for memory loss without functional impairment were enrolled. Patients were examined using comprehensive neuropsychological assessment, the LASSI-L, and cerebrospinal fluid (CSF) biomarkers (Aß1-42/Aß1-40 and ptau181). Means comparisons, correlations, effect sizes, and ROC curves were calculated. Results: LASSI-L scores were significantly associated with CSF biomarkers Aß1-42/Aß1-40 in patients diagnosed with MCI and subjective cognitive decline, especially those scores evaluating the capacity to recover from proactive semantic interference effects and delayed recall. A logistic regression model for the entire sample including LASSI-L and age showed an accuracy of 0.749 and an area under the curve of 0.785 to detect abnormal amyloid deposition. Conclusion: Our study supports the biological validity of the LASSI-L and its semantic interference paradigm in the context of the early stages of AD. These findings emphasize the utility and the convenience of including sensitive cognitive challenge tests in the assessment of patients with suspicion of early stages of AD.

COVID-19: Medical education from the point of view of medical students using the participatory Delphi method.

BACKGROUND: The COVID-19 pandemic has prompted a transformation of medical training. Although there were obvious medical education and social interaction challenges, e-learning presented some advantages, which may have generated medical curricula innovation and adjustments to novel technological methodologies. This study aims to generate consensuses among medical students regarding medical education provided during the pandemic in the resource-limited context of a Global South university. METHODS: The implementation of a participatory Delphi method included a recruitment campaign, training, constitution of Delphi panels and questions, and development of the Delphi exercises. Students from the second to the sixth year of medicine of a university in Quito, Ecuador, constituted two Delphi panels, developed questions about the education received during the pandemic, and answered them over 3.5 rounds. FINDINGS: Twenty-two medical students participated in the Delphi exercises about their perception of medical education during the COVID-19 pandemic. The analysis consisted of a total of 22 Delphi questions divided into five distinct categories: adaptations and innovations, curriculum and assessment changes, virtual clinical practice, time management, and mental health. The authors established high, medium, and low consensuses for analysis. CONCLUSIONS: Consensuses were reached based on students' academic year and focused on the changes in lecture delivery, the usage of new technologies, patient care skills, the impact of the educational routine, and the mental health of the COVID-19 pandemic. The way the pandemic affected medical education in the Global South set the stage for the need for a comprehensive review of tools, skills, and curricula for students from culturally diverse backgrounds. This study offers a highly replicable methodology to generate consensuses and introduce students to academic research.

Distinct SIV-specific CD8+ T cells in the lymph node exhibit simultaneous effector and stem-like profiles and are associated with limited SIV persistence.

Human immunodeficiency virus (HIV) cure efforts are increasingly focused on harnessing CD8+ T cell functions, which requires a deeper understanding of CD8+ T cells promoting HIV control. Here we identifiy an antigen-responsive TOXhiTCF1+CD39+CD8+ T cell population with high expression of inhibitory receptors and low expression of canonical cytolytic molecules. Transcriptional analysis of simian immunodeficiency virus (SIV)-specific CD8+ T cells and proteomic analysis of purified CD8+ T cell subsets identified TOXhiTCF1+CD39+CD8+ T cells as intermediate effectors that retained stem-like features with a lineage relationship with terminal effector T cells. TOXhiTCF1+CD39+CD8+ T cells were found at higher frequency than TCF1-CD39+CD8+ T cells in follicular microenvironments and were preferentially located in proximity of SIV-RNA+ cells. Their frequency was associated with reduced plasma viremia and lower SIV reservoir size. Highly similar TOXhiTCF1+CD39+CD8+ T cells were detected in lymph nodes from antiretroviral therapy-naive and antiretroviral therapy-suppressed people living with HIV, suggesting this population of CD8+ T cells contributes to limiting SIV and HIV persistence.

An Exploratory Approach of Clinically Useful Biomarkers of Cvid by Logistic Regression.

Despite advancements in genetic and functional studies, the timely diagnosis of common variable immunodeficiency (CVID) remains a significant challenge. This exploratory study was designed to assess the diagnostic performance of a novel panel of biomarkers for CVID, incorporating the sum of κ+λ light chains, soluble B-cell maturation antigen (sBCMA) levels, switched memory B cells (smB) and the VISUAL score. Comparative analyses utilizing logistic regression were performed against established gold-standard tests, specifically antibody responses. Our research encompassed 88 subjects, comprising 27 CVID, 23 selective IgA deficiency (SIgAD), 20 secondary immunodeficiency (SID) patients and 18 healthy controls. We established the diagnostic accuracy of sBCMA and the sum κ+λ, achieving sensitivity (Se) and specificity (Spe) of 89% and 89%, and 90% and 99%, respectively. Importantly, sBCMA showed strong correlations with all evaluated biomarkers (sum κ+λ, smB cell and VISUAL), whereas the sum κ+λ was uniquely independent from smB cells or VISUAL, suggesting its additional diagnostic value. Through a multivariate tree decision model, specific antibody responses and the sum κ+λ emerged as independent, signature biomarkers for CVID, with the model showcasing an area under the curve (AUC) of 0.946, Se 0.85, and Spe 0.95. This tree-decision model promises to enhance diagnostic efficiency for CVID, underscoring the sum κ+λ as a superior CVID classifier and potential diagnostic criterion within the panel.

Local adaptation of Pinus leiophylla under climate and land use change models in the Avocado Belt of Michoacán.

Climate change and land use change are two main drivers of global biodiversity decline, decreasing the genetic diversity that populations harbour and altering patterns of local adaptation. Landscape genomics allows measuring the effect of these anthropogenic disturbances on the adaptation of populations. However, both factors have rarely been considered simultaneously. Based on a set of 3660 SNPs from which 130 were identified as outliers by a genome-environment association analysis (LFMM), we modelled the spatial turnover of allele frequencies in 19 localities of Pinus leiophylla across the Avocado Belt in Michoacán state, Mexico. Then, we evaluated the effect of climate change and land use change scenarios, in addition to evaluating assisted gene flow strategies and connectivity metrics across the landscape to identify priority conservation areas for the species. We found that localities in the centre-east of the Avocado Belt would be more vulnerable to climate change, while localities in the western area are more threatened by land conversion to avocado orchards. Assisted gene flow actions could aid in mitigating both threats. Connectivity patterns among forest patches will also be modified by future habitat loss, with central and eastern parts of the Avocado Belt maintaining the highest connectivity. These results suggest that areas with the highest priority for conservation are in the eastern part of the Avocado Belt, including the Monarch Butterfly Biosphere Reserve. This work is useful as a framework that incorporates distinct layers of information to provide a more robust representation of the response of tree populations to anthropogenic disturbances.

Eosinophilic esophagitis: Does age matter?

OBJECTIVES: Eosinophilic esophagitis (EoE) is often diagnosed in school-age children between 6- and 9-year-old. There is less known about those who are diagnosed with EoE that are younger than 6 years old. The objective of this study is to compare clinical presentation, comorbidities, and outcomes based on age at diagnosis of EoE. METHODS: Single-center retrospective chart review of children (<18 years) diagnosed with EoE between 2005 and 2020. We recorded demographics, clinical presentation, family history, past medical history, treatment, and endoscopic findings. Children in this cohort were classified based on age into three age groups: <2 years, 2-<6 years, and 6-<18 years. RESULTS: We identified 256 children with EoE, the mean age (SD) at the time of diagnosis was 9 (5.2) years and 184 (72%) were male. We had 164 (64%) patients with available follow-up esophagogastroduodenoscopies (EGDs) data (495 EGDs in total) of those 99/164 (60%) reached mucosal remission. In the very young children (<2 years) vomiting was the most common presentation, while poor weight gain was seen more in the 2-<6-year group in comparison to the >6-years. Food impaction and abdominal pain were most likely to present in older children 6-18 years. Combination therapy, as opposed to a single therapy, induced remission at a higher frequency in the <6-year group in comparison to the 6-<18-year group (85% vs. 66%). CONCLUSION: EoE should be considered in younger children presenting with feeding difficulty and poor weight gain. Combination therapy seems to be more effective in younger children with EoE, but further studies with bigger sample size are needed to study the efficacy of the different combination therapies.

Armodafinil as a Potential Pharmacological Treatment for Attention Deficit Hyperactivity Disorder in Adults: A Review.

INTRODUCTION: Armodafinil is a psychostimulant that promotes alertness, and it has been shown to improve attention, memory, and fatigue in healthy adults and adults with neurodevelopmental conditions that share symptoms with Attention Deficit Hyperactivity Disorder (ADHD). It is generally well tolerated and safe, and most of the adverse events reported are considered not serious. However, the available evidence on the efficacy of armodafinil for the treatment of ADHD in adults is scarce. OBJECTIVE: The present review aims to perform a systematized search of the available evidence on the possible therapeutic benefit of armodafinil treatment in adult patients with ADHD. METHODS: A literature review using PubMed was conducted to compile and summarize the available clinical and scientific evidence on the possible use of armodafinil as a pharmacological treatment in adult patients with ADHD. RESULTS: From the 86 articles reviewed, the available evidence showed that both acute and chronic treatment with armodafinil can improve wakefulness, memory, impulse control, and executive functions in adults with sleep disorders and other conditions. In addition, evidence of improvement in cognitive functions and mood alterations in other neuropsychiatric conditions was shown. CONCLUSION: Armodafinil could be useful for the treatment of ADHD in adults, according to the review of the literature from both pre-clinical and clinical studies.

Genomic and global gene expression profiling in pediatric and young adult acute leukemia with PICALM::MLLT10 Fusion.

PICALM: MLLT10 fusion is a rare but recurrent genetic driver in acute leukemias. To better understand the genomic landscape of PICALM::MLLT10 (PM) positive acute leukemia, we performed genomic profiling and gene expression profiling in twenty PM-positive patients, including AML (n = 10), T-ALL/LLy (n = 8), Mixed-phenotype acute leukemia (MPAL), T/B (n = 1) and acute undifferentiated leukemia (AUL) (n = 1). Besides confirming the known activation of HOXA, differential gene expression analysis compared to hematopoietic stem cells demonstrated the enrichment of genes associated with cell proliferation-related pathways and relatively high expression of XPO1 in PM-AML and PM-T-ALL/LLy. Our study also suggested PHF6 disruption as a key cooperating event in PICALM::MLLT10-positive leukemias. In addition, we demonstrated differences in gene expression profiles as well as remarkably different spectra of co-occurring mutations between PM-AML and PM-T-ALL/LLy. Alterations affecting TP53 and NF1, hallmarks of PM-AML, are strongly associated with disease progression and relapse, whereas EZH2 alterations are highly enriched in PM-T-ALL/LLy. This comprehensive genomic and transcriptomic profiling provides insights into the pathogenesis and development of PICALM::MLLT10 positive acute leukemia.

Novel MED15::ATF1 fusion in a pediatric melanoma with spitzoid features and aggressive presentation.

Childhood melanoma is a rare and biologically heterogeneous pediatric malignancy. The differential diagnosis of pediatric melanoma is usually broad, including a wide variety of spindle cell or epithelioid neoplasms. Different molecular alterations affecting the MAPK and PI3K/AKT/mTOR pathways, tumor suppressor genes, and telomerase reactivation have been implicated in melanoma tumorigenesis and progression. Here, we report a novel MED15::ATF1 fusion in a pediatric melanoma with spitzoid features and an aggressive clinical course.

Co-creation process of an intervention to implement a multiparameter point-of-care testing device in a primary healthcare setting for non-communicable diseases in Peru.

BACKGROUND: Point-of-care testing (POCT) devices are diagnostic tools that can provide quick and accurate results within minutes, making them suitable for diagnosing non-communicable diseases (NCDs). However, these devices are not widely implemented in healthcare systems and for this reason is relevant to understand the implementation process. AIM: To describe the process and define a strategy to implement a multiparameter POCT device for diagnosing and managing NCDs in one region of Peru. METHODS: A descriptive and non-experimental study, using the participatory methodologies of co-creation process. It was conducted in one region of Peru (Tumbes) to design an intervention for implementing a multiparameter POCT device. Two co-creation sessions were conducted involving five groups: community members, primary healthcare workers, these groups in both rural and urban settings, and regional decision-makers. These sessions included activities to understand patient journeys in receiving care for NCDs, identify facilitators and barriers to POCT devices usage, and define an implementation strategy for POCT devices in both rural and urban settings of Tumbes. The research team analysed the data and summarized key topics for discussion after each session. RESULTS: A total of 78 participants were enrolled across the five groups. Among community members: 22.2% had only diabetes, 24.1% had only hypertension, and 18.5% had both diagnoses. In the patient journey, community members mentioned that it took at least three days to receive a diagnosis and treatment for an NCD. Most of the participants agreed that the POCT devices would be beneficial for their communities, but they also identified some concerns. The strategy for POCT devices implementation included healthcare workers training, POCT devices must be placed in the laboratory area and must be able to perform tests for glucose, glycated haemoglobin, cholesterol, and creatinine. Advertising about POCT devices should be displayed at the healthcare centres and the municipality using billboards and flyers. CONCLUSIONS: The co-creation process was useful to develop strategies for the implementation of multiparameter POCT devices for NCDs, involving the participation of different groups of stakeholders guided by moderators in both, rural and urban, settings in Peru.