Natural hemozoin and β-hematin induce tissue damage and apoptosis in human placental explants.

Unlabelled: Hemozoin (HZ) is a waste product of hemoglobin digestion by and has been implicated in several pathological processes, including inflammation, oxidative stress, endothelial dysfunction, and immune dysregulation. Studying the effects of HZ on the human placenta is essential to understanding the impact of malaria infection during pregnancy. The present study explored the impact of HZ produced by and β-hematin, referred to here as natural HZ (nHZ) and synthetic HZ (sHZ), respectively, on human placental explants exposed .

Quantitative Tc-pyrophosphate myocardial uptake: Changes on transthyretin stabilization therapy.

Background: Quantitative technetium-99m-pyrophosphate cardiac single-photon emission computed tomography (Tc-PYP SPECT/CT) is an emerging method for estimating myocardial burden of transthyretin cardiac amyloidosis (ATTR-CA), but its efficacy in monitoring longitudinal changes remains uncertain. We aimed to investigate longitudinal changes in cardiac ATTR amyloid burden following transthyretin stabilization therapy using visual and quantitative Tc-PYP SPECT/CT and to relate these with changes in cardiac biomarkers and function.

Methods: This prospective longitudinal cohort study investigated changes in Tc-PYP SPECT/CT in 23 participants with ATTR-CA on transthyretin stabilization therapy (median: 2.

Crosstalk between degradation and bioenergetics: how autophagy and endolysosomal processes regulate energy production.

Cells undergo metabolic reprogramming to adapt to changes in nutrient availability, cellular activity, and transitions in cell states. The balance between glycolysis and mitochondrial respiration is crucial for energy production, and metabolic reprogramming stipulates a shift in such balance to optimize both bioenergetic efficiency and anabolic requirements. Failure in switching bioenergetic dependence can lead to maladaptation and pathogenesis.

An expert review of clozapine in Latin American countries: Use, monitoring, and pharmacovigilance.

There is growing interest in clozapine clinical use, monitoring, and research, particularly adverse drug reactions (ADRs) other than agranulocytosis. In this study we focused on clozapine pharmacovigilance. Hence, we contacted clinicians and researchers in Latin America and requested information about local psychiatric services, clozapine availability, clinical use, and ADR monitoring with the VigiBase system.

Effect of the COVID-19 Pandemic on Musculoskeletal Care in the Emergency Room.

Objective: Study the effect of the coronavirus disease (COVID-19) pandemic on emergency room (ER) utilization for musculoskeletal (MSK) complaints.

Methods: Data from ER encounters in a teaching hospital for years 2019 and 2020 were extracted from an electronic database. The ICD-10-CM codes were used to assign the primary diagnosis.

Acute Thalamic Ischemic Stroke in an Older Patient Newly Vaccinated with COVID-19 Vaccine Based on Adenoviral Vectors.

Introduction: Recent reports have shown several cases of cerebrovascular events after vaccination against COVID-19. The effects have been described mainly in women within the first two weeks of receiving the vaccine.

Clinical Case: We describe here the first Colombian case of a cerebrovascular event after vaccination against COVID-19 in a 67-year-old woman with a vascular history.

TSIUNAS: A Videogame for Preventing Gender-Based Violence.

Gender-based violence (GBV) is a public health problem worldwide. Nonetheless, in rural areas and low-income countries, the problem may be more difficult to eradicate because there are stereotypes that reinforce negative attitudes toward women, which increase the severity of the problem. This article presents the development of "Tsiunas," a videogame designed to increase GBV awareness.

Morphological and molecular characterization of Castniidae (Lepidoptera) associated to sugarcane in Colombia.

The giant sugarcane borer, Telchin licus, has been reported as an economically important sugarcane pest in Colombia; however, its taxonomic status has been scarcely investigated and previous reports offer an ambiguous characterization of both the immature and adult stages. The objective of this work is to identify Telchin species affecting sugarcane and alternative hosts in different departments of the country by integrating molecular analysis and conventional morphology. To date, T.

Surveillance of phlebotomine fauna and Didelphis marsupialis (Didelphimorphia: Didelphidae) infection in an area highly endemic for visceral leishmaniasis in Colombia.

Introduction: The study of the interaction between the parasite, the vector and the mammalian hosts, including man, allows to understand the behavior of the leishmaniases.

Objective: To determine the presence of Lutzomyia species and to detect the Leishmania infection in Didelphis marsupialis in an endemic area for visceral leishmaniasis.

Materials And Methods: Phlebotomine fauna and individuals of D.

Primaquine-quinoxaline 1,4-di-N-oxide hybrids with action on the exo-erythrocytic forms of Plasmodium induce their effect by the production of reactive oxygen species.

Background: The challenge in anti-malarial chemotherapy is based on the emergence of resistance to drugs and the search for medicines against all stages of the life cycle of Plasmodium spp. as a therapeutic target. Nowadays, many molecules with anti-malarial activity are reported.

Babesiosis prevalence in malaria-endemic regions of Colombia.

Background & Objectives: : The presence of Babesia spp in humans, bovine cattle and ticks (the transmitting vector) has not been well characterized in Colombia. Babesia infection in humans can be overlooked due to similarity of the disease symptoms with malaria specially in the regions where malaria is endemic. The aim of the present work was to study the frequency of Babesia infection in humans, bovines and ticks in a malaria endemic region of Colombia, and explore the possible relationship of infection with host and the environmental factors.

Identification of (4-(9H-fluoren-9-yl) piperazin-1-yl) methanone derivatives as falcipain 2 inhibitors active against Plasmodium falciparum cultures.

Background: Falcipain 2 (FP-2) is the hemoglobin-degrading cysteine protease of Plasmodium falciparum most extensively targeted to develop novel antimalarials. However, no commercial antimalarial drugs based on FP-2 inhibition are available yet due to the low selectivity of most FP-2 inhibitors against the human cysteine proteases.

Methods: A structure-based virtual screening (SVBS) using Maybridge HitFinder™ compound database was conducted to identify potential FP-2 inhibitors.

Novel antimalarial chloroquine- and primaquine-quinoxaline 1,4-di-N-oxide hybrids: Design, synthesis, Plasmodium life cycle stage profile, and preliminary toxicity studies.

Emergence of drug resistance and targeting all stages of the parasite life cycle are currently the major challenges in antimalarial chemotherapy. Molecular hybridization combining two scaffolds in a single molecule is an innovative strategy for achieving these goals. In this work, a series of novel quinoxaline 1,4-di-N-oxide hybrids containing either chloroquine or primaquine pharmacophores was designed, synthesized and tested against both chloroquine sensitive and multidrug resistant strains of Plasmodium falciparum.

Structure-activity relationship of new antimalarial 1-aryl-3-susbtituted propanol derivatives: Synthesis, preliminary toxicity profiling, parasite life cycle stage studies, target exploration, and targeted delivery.

Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70-73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70-73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (ICs < 0.28 μM), and compounds 55, 56, 64, 70, 71, and 72 showed potent biological activity in chloroquine-sensitive and multidrug-resistant strains (ICs < 0.

Huberine, a New Canthin-6-One Alkaloid from the Bark of Picrolemma huberi.

A new alkaloid, Canthin-6-one, Huberine (), together with three known compounds including 1-Hydroxy-canthin-6-one (), Canthin-6-one () and stigma sterol (), were isolated from the stem bark of . The isolation was achieved by chromatographic techniques and the purification was performed on a C18 column using acetonitrile/water (90:10, /) with 0.1% formic acid as the mobile phase.

Anti-plasmodial effect of plant extracts from Picrolemma huberi and Picramnia latifolia.

Background: Malaria is an infectious disease caused by parasites of the genus Plasmodium, of which Plasmodium vivax and Plasmodium falciparum are the major species that cause the disease in humans. As there are relatively few alternatives for malaria treatment, it is necessary to search for new chemotherapeutic options. Colombia possesses a great diversity of plants, which are potential sources of new compounds of medical interest.

[Mutagenicity, genotoxicity and gene expression of Rad51C, Xiap, P53 and Nrf2 induced by antimalarial extracts of plants collected from the middle Vaupés region, Colombia].

Introduction: Due to Plasmodium resistance to antimalarial drugs, it is important to find new therapeutic alternatives for malaria treatment and control. Based on the knowledge of Colombian indigenous communities, we collected extracts of plants with potential antimalarial effects from the middle Vaupés region.

Objective: To evaluate the mutagenic and genotoxic effects, as well as the gene expression of Rad51C, Xiap, P53 and Nrf2 induced by four ethanolic extracts with antimalarial activity (R001, T002, T015 and T028).

EMX2 activates slow myosin heavy chain 2 gene expression in embryonic muscle fibers.

Avian myogenesis is partly characterized by commitment of distinct myoblast cell lineages to the formation of specific muscle fiber types. Previous studies have identified the transcription factor EMX2 as a regulator of slow myosin heavy chain 2 (MyHC2) gene expression in fast/slow primary muscle fibers. We report here the interaction of EMX2 with the slow MyHC2 transcriptional regulatory region in fast/slow embryonic muscle fibers.

New hydrazine and hydrazide quinoxaline 1,4-di-N-oxide derivatives: In silico ADMET, antiplasmodial and antileishmanial activity.

We report the design (in silico ADMET criteria), synthesis, cytotoxicity studies (HepG-2 cells), and biological evaluation of 15 hydrazine/hydrazide quinoxaline 1,4-di-N-oxide derivatives against the 3D7 chloroquine sensitive strain and FCR-3 multidrug resistant strain of Plasmodium falciparum and Leishmania infantum (axenic amastigotes). Fourteen of derivatives are novel quinoxaline 1,4-di-N-oxide derivatives. Compounds 18 (3D7 IC=1.

Exploring the scope of new arylamino alcohol derivatives: Synthesis, antimalarial evaluation, toxicological studies, and target exploration.

Synthesis of new 1-aryl-3-substituted propanol derivatives followed by structure-activity relationship, in silico drug-likeness, cytotoxicity, genotoxicity, in silico metabolism, in silico pharmacophore modeling, and in vivo studies led to the identification of compounds 22 and 23 with significant in vitro antiplasmodial activity against drug sensitive (D6 IC ≤ 0.19 μM) and multidrug resistant (FCR-3 IC ≤ 0.40 μM and C235 IC ≤ 0.

Antiplasmodial and Cytotoxic Activity of Raw Plant Extracts as Reported by Knowledgeable Indigenous People of the Amazon Region (Vaupés Medio in Colombia).

The in vitro antiplasmodial activity of 122 raw extracts prepared in ethanol and water from 35 medicinal plants reported by the Cubeo indigenous village of the Amazon region (Vaupés Medio in Colombia) was evaluated for efficacy against 3D7 (sensitive to chloroquine) and FCR-3 (resistant to chloroquine) Plasmodium falciparum strains. Five percent of these extracts presented a significant antiplasmodial activity (< 5 µg/mL) and 83 % of them were not cytotoxic. These findings highlight the importance of investigating traditional medicinal plants implemented by these ancestral communities of the Amazon region as well as their potential to become a source of new drugs against malaria.

Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome.

Background: With the exception of the presence of the FIP1L1-PDGFRA fusion gene, little is known about predictors of imatinib response in clinically-defined hypereosinophilic syndrome (HES).

Methods: Subjects with FIP1L1-PDGFRA-myeloid neoplasm (FP; n =12), PDGFRA-negative HES with ≥4 criteria suggestive of a myeloid neoplasm (MHES; n =10), or steroid-refractory PDGFRA-negative HES with <4 myeloid criteria (SR; n = 5) were enrolled in a prospective study of imatinib therapy (NCT00044304: registered at clinicaltrials.gov).

Metabolic syndrome and related variables, insulin resistance, leptin levels, and PPAR-γ2 and leptin gene polymorphisms in a pedigree of subjects with bipolar disorder.

Objective: Evidence points to a high prevalence of metabolic dysfunction in bipolar disorder (BD), but few studies have evaluated the relatives of subjects with BD. We conducted a cross-sectional study in an extended family of patients with BD type I.

Methods: The available relatives of the same family were interviewed (DSM-IV-R) and assessed in fasting conditions for body mass index, constituent variables of the metabolic syndrome (MS), leptin levels, insulin resistance index, and single nucleotide polymorphisms (SNPs) for the leptin receptor and promoter and PPAR-γ2 genes.

In vitro susceptibility of Plasmodium vivax to antimalarials in Colombia.

The in vitro susceptibilities of 30 isolates of Plasmodium vivax to a number of antimalarials (chloroquine [CQ], mefloquine, amodiaquine, quinine, and artesunate [AS]) were evaluated. The isolates came from the region of Urabá in Colombia, in which malaria is endemic, and were evaluated by the schizont maturation test. The 50% inhibitory concentration (IC50) was 0.