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1.
Neurol Sci ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967881

ABSTRACT

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.

2.
Front Psychol ; 15: 1373541, 2024.
Article in English | MEDLINE | ID: mdl-38988382

ABSTRACT

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.

3.
Ecol Lett ; 27(7): e14461, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38953253

ABSTRACT

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.


Subject(s)
Biodiversity , Conservation of Natural Resources , Genetic Variation , Animals
4.
PLoS One ; 19(7): e0297602, 2024.
Article in English | MEDLINE | ID: mdl-38968213

ABSTRACT

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.


Subject(s)
COVID-19 , Curriculum , Delphi Technique , Education, Medical , Students, Medical , COVID-19/epidemiology , Humans , Students, Medical/psychology , Education, Medical/methods , SARS-CoV-2/isolation & purification , Pandemics , Female , Male , Ecuador/epidemiology , Education, Distance/methods , Adult
5.
Nat Immunol ; 25(7): 1245-1256, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38886592

ABSTRACT

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.


Subject(s)
CD8-Positive T-Lymphocytes , Lymph Nodes , Simian Acquired Immunodeficiency Syndrome , Simian Immunodeficiency Virus , Simian Immunodeficiency Virus/immunology , CD8-Positive T-Lymphocytes/immunology , Animals , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Acquired Immunodeficiency Syndrome/virology , Lymph Nodes/immunology , Humans , Macaca mulatta , HIV Infections/immunology , HIV Infections/virology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism
6.
J Clin Immunol ; 44(6): 143, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847936

ABSTRACT

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.


Subject(s)
Biomarkers , Common Variable Immunodeficiency , Humans , Common Variable Immunodeficiency/diagnosis , Common Variable Immunodeficiency/immunology , Male , Female , Adult , Middle Aged , Logistic Models , Young Adult , Adolescent , Aged , Immunoglobulin kappa-Chains/blood , Immunoglobulin kappa-Chains/genetics , Sensitivity and Specificity , B-Lymphocytes/immunology , Immunoglobulin lambda-Chains , Memory B Cells/immunology
7.
Mol Ecol ; 33(13): e17424, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38813851

ABSTRACT

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.


Subject(s)
Climate Change , Gene Flow , Persea , Pinus , Polymorphism, Single Nucleotide , Pinus/genetics , Persea/genetics , Mexico , Gene Frequency , Adaptation, Physiological/genetics , Genetics, Population , Conservation of Natural Resources , Ecosystem , Genetic Variation
8.
J Pediatr Gastroenterol Nutr ; 78(6): 1329-1336, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38562024

ABSTRACT

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.


Subject(s)
Eosinophilic Esophagitis , Humans , Eosinophilic Esophagitis/epidemiology , Eosinophilic Esophagitis/therapy , Eosinophilic Esophagitis/diagnosis , Child , Male , Female , Retrospective Studies , Child, Preschool , Adolescent , Age Factors , Infant , Endoscopy, Digestive System/statistics & numerical data
9.
Res Sq ; 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38496632

ABSTRACT

Radiotherapy (RT) and anti-PD-L1 synergize to enhance local and distant (abscopal) tumor control. However, clinical results in humans have been variable. With the goal of improving clinical outcomes, we investigated the underlying synergistic mechanism focusing on a CD8+ PD-1+ Tcf-1+ stem-like T cell subset in the tumor-draining lymph node (TdLN). Using murine melanoma models, we found that RT + anti-PD-L1 induces a novel differentiation program in the TdLN stem-like population which leads to their expansion and differentiation into effector cells within the tumor. Our data indicate that optimal synergy between RT + anti-PD-L1 is dependent on the TdLN stem-like T cell population as either blockade of TdLN egress or specific stem-like T cell depletion reduced tumor control. Together, these data demonstrate a multistep stimulation of stem-like T cells following combination therapy which is initiated in the TdLN and completed in the tumor.

10.
Curr Neuropharmacol ; 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38486390

ABSTRACT

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.

11.
Leukemia ; 38(5): 981-990, 2024 May.
Article in English | MEDLINE | ID: mdl-38429501

ABSTRACT

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.


Subject(s)
Gene Expression Profiling , Oncogene Proteins, Fusion , Humans , Oncogene Proteins, Fusion/genetics , Child , Adolescent , Male , Female , Young Adult , Adult , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Genomics/methods , Transcription Factors/genetics , Child, Preschool , Biomarkers, Tumor/genetics , Gene Expression Regulation, Leukemic , Prognosis , Transcriptome
12.
BMC Health Serv Res ; 24(1): 401, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38553724

ABSTRACT

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.


Subject(s)
Diabetes Mellitus , Noncommunicable Diseases , Humans , Noncommunicable Diseases/epidemiology , Noncommunicable Diseases/therapy , Peru , Point-of-Care Testing , Diabetes Mellitus/diagnosis , Diabetes Mellitus/therapy , Primary Health Care , Point-of-Care Systems
13.
Genes Chromosomes Cancer ; 63(3): e23230, 2024 03.
Article in English | MEDLINE | ID: mdl-38459940

ABSTRACT

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.


Subject(s)
Glycine , Melanoma , Nevus, Epithelioid and Spindle Cell , Oncogene Proteins, Fusion , Pyrroles , Skin Neoplasms , Child , Humans , Diagnosis, Differential , Glycine/analogs & derivatives , Mediator Complex , Melanoma/diagnosis , Melanoma/genetics , Melanoma/pathology , Nevus, Epithelioid and Spindle Cell/diagnosis , Phosphatidylinositol 3-Kinases , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Oncogene Proteins, Fusion/genetics
14.
Res Sq ; 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38410458

ABSTRACT

Virus specific PD-1+ TCF-1+ TOX+ stem-like CD8+ T cells are essential for maintaining T cell responses during chronic infection and are also critical for PD-1 directed immunotherapy. In this study we have used the mouse model of chronic LCMV infection to examine when these virus specific stem-like CD8+ T cells are generated during the course of chronic infection and what is the role of antigen in maintaining the stem-like program. We found that these stem-like CD8+ T cells are generated early (day 5) during chronic infection and that antigen is essential for maintaining their stem-like program. This early generation of stem-like CD8+ T cells suggested that the fate commitment to this cell population was agnostic to the eventual outcome of infection and the immune system prepares a priori for a potential chronic infection. Indeed, we found that an identical virus specific stem-cell like CD8+ T cell population was also generated during acute LCMV infection but these cells were lost once the virus was cleared. To determine the fate of these early PD-1+TCF-1+TOX+ stem-like CD8+ T cells that are generated during both acute and chronic LCMV infection we set up two reciprocal adoptive transfer experiments. In the first experiment we transferred day 5 stem-like CD8+ T cells from chronically infected into acutely infected mice and examined their differentiation after viral clearance. We found that these early stem-like CD8+ T cells downregulated canonical markers of the chronic stem-like CD8+ T cells and expressed markers (CD127 and CD62L) associated with central memory CD8+ T cells. In the second experiment, we transferred day 5 stem-like cells from acutely infected mice into chronically infected mice and found that these CD8+ T cells could function like resource cells after transfer into a chronic environment by generating effector CD8+ T cells in both lymphoid and non-lymphoid tissues while also maintaining the number of stem-like CD8+ T cells. These findings provide insight into the generation and maintenance of virus specific stem-like CD8+ T cells that play a critical role in chronic viral infection. In particular, our study highlights the early generation of stem-like CD8+ T cells and their ability to adapt to either an acute or chronic infection. These findings are of broad significance since these novel stem-like CD8+ T cells play an important role in not only viral infections but also in cancer and autoimmunity.

15.
PLoS Pathog ; 20(2): e1011990, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38324589

ABSTRACT

BACKGROUND: Hofbauer cells (HBCs) and cytotrophoblasts (CTBs) are major cell populations in placenta. The indirect impact of maternal SARS-CoV-2 disease on these cells that are not directly infected has not been extensively studied. Herein, we profiled gene expression in HBCs and CTBs isolated from placentae of recovered pregnant subjects infected with SARS-CoV-2 during all trimesters of pregnancy, placentae from subjects with active infection, SARS-CoV-2 vaccinated subjects, and those who were unexposed to the virus. METHODS: Placentae were collected within 4 h post-delivery and membrane-free tissues were enzymatically digested for the isolation of HBCs and CTBs. RNA extracted from HBCs and CTBs were sequenced using 150bp paired-end reads. Differentially expressed genes (DEGs) were identified by DESeq2 package in R and enriched in GO Biological Processes, KEGG Pathway, Reactome Gene Sets, Hallmark Gene Sets, and Canonical Pathways. Protein-protein interactions among the DEGs were modelled using STRING and BioGrid. RESULTS: Pregnant subjects (n = 30) were recruited and categorized into six groups: infected with SARS-CoV-2 in i) the first (1T, n = 4), ii) second (2T, n = 5), iii) third (3T, n = 5) trimester, iv) tested positive at delivery (Delivery, n = 5), v) never infected (Control, n = 6), and vi) fully mRNA-vaccinated by delivery (Vaccinated, n = 5). Compared to the Control group, gene expression analysis showed that HBCs from infected subjects had significantly altered gene expression profiles, with the 2T group having the highest number of DEGs (1,696), followed by 3T and 1T groups (1,656 and 958 DEGs, respectively). These DEGs were enriched for pathways involved in immune regulation for host defense, including production of cytokines, chemokines, antimicrobial proteins, ribosomal assembly, neutrophil degranulation inflammation, morphogenesis, and cell migration/adhesion. Protein-protein interaction analysis mapped these DEGs with oxidative phosphorylation, translation, extracellular matrix organization, and type I interferon signaling. Only 95, 23, and 8 DEGs were identified in CTBs of 1T, 2T, and 3T groups, respectively. Similarly, 11 and 3 DEGs were identified in CTBs and HBCs of vaccinated subjects, respectively. Reassuringly, mRNA vaccination did not induce an inflammatory response in placental cells. CONCLUSIONS: Our studies demonstrate a significant impact of indirect SARS-CoV-2 infection on gene expression of inner mesenchymal HBCs, with limited effect on lining CTB cells isolated from pregnant subjects infected and recovered from SARS-CoV-2. The pathways associated with these DEGs identify potential targets for therapeutic intervention.


Subject(s)
COVID-19 , Placenta , Pregnancy , Female , Humans , COVID-19/genetics , COVID-19/metabolism , SARS-CoV-2/genetics , Trophoblasts/metabolism , Transcriptome , RNA, Messenger/metabolism
16.
CNS Neurosci Ther ; 30(2): e14382, 2024 02.
Article in English | MEDLINE | ID: mdl-37501389

ABSTRACT

AIMS: The AT(N) classification system not only improved the biological characterization of Alzheimer's disease (AD) but also raised challenges for its clinical application. Unbiased, data-driven techniques such as clustering may help optimize it, rendering informative categories on biomarkers' values. METHODS: We compared the diagnostic and prognostic abilities of CSF biomarkers clustering results against their AT(N) classification. We studied clinical (patients from our center) and research (Alzheimer's Disease Neuroimaging Initiative) cohorts. The studied CSF biomarkers included Aß(1-42), Aß(1-42)/Aß(1-40) ratio, tTau, and pTau. RESULTS: The optimal solution yielded three clusters in both cohorts, significantly different in diagnosis, AT(N) classification, values distribution, and survival. We defined these three CSF groups as (i) non-defined or unrelated to AD, (ii) early stages and/or more delayed risk of conversion to dementia, and (iii) more severe cognitive impairment subjects with faster progression to dementia. CONCLUSION: We propose this data-driven three-group classification as a meaningful and straightforward approach to evaluating the risk of conversion to dementia, complementary to the AT(N) system classification.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/diagnostic imaging , Amyloid beta-Peptides , tau Proteins , Cognitive Dysfunction/diagnostic imaging , Biomarkers , Peptide Fragments , Disease Progression
17.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1559789

ABSTRACT

Introducción: La diabetes mellitus tipo 2 se caracteriza por la hiperglucemia debido a la insuficiente producción de insulina de las células β. La mieloperoxidasa promueve el estrés oxidativo durante la inflamación y la ceruloplasmina se considera su inhibidor endógeno. Objetivo: Evaluar la relación entre la ceruloplasmina y la mieloperoxidasa, determinadas simultáneamente en el suero de pacientes diabéticos tipo 2. Métodos: Se estudiaron 362 pacientes diabéticos tipo 2 y 110 sujetos sanos. La actividad sérica de la ceruloplasmina se determinó por el método de Siotto; y el de la mieloperoxidasa, por el de Kraeisz. Resultados: El 72 % de los pacientes diabéticos tenían hiperglucemia y el 77 % presentaba obesidad abdominal. Las actividades de ambas enzimas se incrementaron significativamente en relación con el grupo control. El coeficiente de correlación de la actividad enzimática resultó bajo. El cociente RMPO/CP de los pacientes diabéticos superó el de los controles. La ceruloplasmina no inhibió la mieloperoxidasa. Conclusiones: Predominó la mieloperoxidasa, por tanto, no se manifestó el efecto inhibitorio de la ceruloplasmina. La elevada actividad de la mieloperoxidasa se asocia con un agravamiento del cuadro clínico del paciente diabético.


Introduction: Type 2 diabetes mellitus is characterized by hyperglycemia due to insufficient insulin production by β cells. Myeloperoxidase promotes oxidative stress during inflammation and ceruloplasmin is considered its endogenous inhibitor. Objective: To evaluate the relationship between ceruloplasmin and myeloperoxidase, determined simultaneously in the serum of type 2 diabetic patients. Methods: A total of 362 type 2 diabetic patients and 110 healthy subjects were studied. Serum ceruloplasmin activity was determined by the Siotto KM method and myeloperoxidase by the Kraeisz JE method. Results: 72% of diabetic patients had hyperglycemia and 77% had abdominal obesity. The activities of both enzymes were significantly increased relative to the control group. The correlation coefficient of enzyme activity was low. The ORMO/CP ratio of diabetic patients exceeded that of controls. Ceruloplasmin did not inhibit myeloperoxidase. Conclusions: Myeloperoxidase predominated, therefore, the inhibitory effect of ceruloplasmin was not manifested. The high activity of myeloperoxidase was associated with a worsening of the clinical picture of the diabetic patient.

18.
3 Biotech ; 14(1): 23, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38156038

ABSTRACT

Microalgae have become promising microorganisms for generating high-value commercial products and removing pollutants in aquatic systems. This research evaluated the impact of sunlight intensity on intracellular pigment generation and phosphorus removal from secondary effluents by autoflocculating microalgae consortium BR-UANL-01 in photobioreactor culture. Microalgae were grown in a secondary effluent from a wastewater treatment plant, using a combination of low and high light conditions (photon irradiance; 44 µmol m-2 s-1 and ≈ 1270 µmol m-2 s-1, respectively) and 16:8 h light:dark and 24:0 h light:dark (subdivided into 18:6 LED:sunlight) photoperiods. The autoflocculant rate by consortium BR-UANL-01 was not affected by light intensity and achieved 98% in both treatments. Microalgae produced significantly more lutein, (2.91 mg g-1) under low light conditions. Phosphate removal by microalgae resulted above 85% from the secondary effluent, due to the fact that phosphorus is directly associated with metabolic and replication processes and the highest antioxidant activity was obtained in ABTS•+ assay by the biomass under low light condition (51.71% µmol ET g-1). In conclusion, the results showed that the autoflocculating microalgae consortium BR-UANL-01 is capable of synthesizing intracellular lutein, which presents antioxidant activity, using secondary effluents as a growth medium, without losing its autoflocculating activity and assimilating phosphorus.

19.
Rev. cuba. med. mil ; 52(4)dic. 2023.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1559861

ABSTRACT

Introducción: La pandemia por la COVID-19 trajo consigo cambios en el comportamiento humano y afecciones psíquicas que afectan la salud mental. Objetivo: Estimar la adicción a los teléfonos inteligentes en adolescentes mujeres tras la pandemia por la COVID-19. Métodos: Estudio transversal realizado en noviembre y diciembre del 2022, en una institución educativa pública de Ica, Perú. Participaron 581 adolescentes que respondieron a un cuestionario con variables generales y la Escala de Adicción a los Teléfonos Inteligentes. Se aplicó un análisis estadístico descriptivo y multivariado mediante modelos lineales generalizados de la familia Poisson para evaluar la asociación entre las variables. Resultados: De las participantes, el 21,7 % reveló adicción a los teléfonos inteligentes y el 48,7 % se encuentra en riesgo alto de dependencia. Los conflictos familiares en el hogar (razón de prevalencia ajustada - RPa= 1,41; intervalo de confianza -IC 95 %: 1,00-1,99) y los sentimientos de vergüenza (RPa= 1,44; IC 95 %: 1,01-2,03), se asociaron a mayor adicción a los teléfonos inteligentes. No obstante, el sentimiento de tristeza, ansiedad o depresión y el hecho de sentirse rechazado por la sociedad presentaron asociación, no ajustada. Conclusiones: La adición a los teléfonos inteligentes y el riesgo de padecer este trastorno es alto en las adolescentes; existen variables generales susceptibles de ser modificadas que podrían mermar dicha afección comportamental inducida o potenciada por la pandemia de la COVID-19.


Introduction: The COVID-19 pandemic brought with it changes in human behavior and psychic conditions that affect mental health. Objective: Estimate smartphone addiction in female adolescents after COVID-19 pandemic. Methods: Cross-sectional study, conducted during November to December 2022, in a public educational institution in Ica, Peru. A total of 581 adolescents participated and answered a questionnaire with general variables and the Smartphone Addiction Scale. A descriptive and multivariate statistical analysis was applied using Poisson family generalized linear models to evaluate the association between variables. Results: Of the participants, 21.7% revealed addiction to smartphones and 48.7% were at high risk of dependence on these devices. Family conflicts at home (adjusted prevalence ratio-RPa = 1.41; 95% confidence interval-CI: 1.00-1.99) and feelings of shame (RPa = 1.44; 95% CI: 1.01-2.03), were associated with higher smartphone addiction. However, feelings of sadness, anxiety or depression and feeling rejected by society showed an unadjusted association. Conclusions: Smartphone addiction and risk for this disorder is high in adolescent girls; there are general variables amenable to modification that could diminish such a behavioral condition induced or potentiated by the COVID-19 pandemic.

20.
Article in Spanish | LILACS | ID: biblio-1536557

ABSTRACT

(analítico) Considerando la necesidad de escuchar a niños y niñas migrantes, examinamos desde su mirada las dificultades y vulnerabilidades a las que ellos, ellas y sus familias se enfrentaron durante las cuarentenas, en la pandemia por covid-19 en Chile; durante ellas mantuvieron clases a distancia, en línea o por guías de trabajo. Hicimos entrevistas semiestructuradas con guión temático -utilizando técnicas gráficas- a 37 niños y niñas migrantes de Latinoamérica, y realizamos análisis de contenido. Evidenciamos que las familias migrantes, desde la mirada de los niños y niñas, se han visto expuestas a dificultades y preocupaciones (dada la distancia física entre familiares), vulnerabilidades económicas, falta de redes familiares y dificultades en la organización del trabajo productivo y reproductivo; en cada caso desde los puntos de vista objetivo y subjetivo.


(analytical) After identifying the need to listen to migrant children regarding the vulnerability they and their families faced during the COVID-19 pandemic in Chile, we sought to examine the difficulties and vulnerabilities faced by their families from their point of view. Semistructured interviews with thematic scripts and graphic support were conducted with 37 children whose families had migrated from other countries in Latin America. Content analysis was carried out using the data collected during these interviews. According to these children, it was evident that migrant families faced a number of difficulties and vulnerabilities during the pandemic that included: physical distance between family members; economic vulnerabilities; lack of family support networks; and difficulties with accessing work. These vulnerabilities were evidenced using both objective and subjective points of view.


(analítico) Considerando a necessidade de ouvir a voz das crianças migrantes a respeito das vulnerabilidades enfrentadas por suas famílias durante o período de aulas online durante a pandemia da Covid-19 no Chile, procuramos examinar as dificuldades e vulnerabilidades enfrentadas por suas famílias a partir de seu ponto de vista. Foram realizadas entrevistas semi-estruturadas com roteiros temáticos, utilizando técnicas gráficas, com 37 crianças migrantes latino-americanas, e foi realizada uma análise de conteúdo. Tornou-se evidente que as famílias migrantes, do ponto de vista das crianças, foram expostas a dificuldades e preocupações, dada a distância física entre os membros da família; vulnerabilidades econômicas e falta de redes familiares; e dificuldades na organização do trabalho produtivo e reprodutivo. As vulnerabilidades são evidentes de um ponto de vista objetivo e subjetivo.


Subject(s)
Child
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