Falla en la extubación en el paciente con trauma raquimedular: parálisis diafragmática. Una entidad por considerar

La parálisis diafragmática es una entidad con epidemiologia no constatada, sin embargo, debe considerarse en el paciente con antecedente de trauma raquimedular asociado que presente signos tempranos de dificultad respiratoria, para de esta forma investigar y ofrecer manejos oportunos en esta condición clínica. Se presenta caso de varón de 65 años con debilidad diafragmática crónica por antecedente de herida por arma de fuego a nivel de la columna cervical.

Diaphragmatic paralysis is an entity with an unproven epidemiology. However, it should be considered in patients with a history of associated spinal cord trauma who present early signs of respiratory difficulty, to investigate and offer timely management to this clinical condition. We present the case of a 65-year-old man with chronic diaphragmatic weakness due to a history of gunshot wounds at the level of the cervical spine.

LRP8-mediated selenocysteine uptake is a targetable vulnerability in MYCN-amplified neuroblastoma.

Ferroptosis has emerged as an attractive strategy in cancer therapy. Understanding the operational networks regulating ferroptosis may unravel vulnerabilities that could be harnessed for therapeutic benefit. Using CRISPR-activation screens in ferroptosis hypersensitive cells, we identify the selenoprotein P (SELENOP) receptor, LRP8, as a key determinant protecting MYCN-amplified neuroblastoma cells from ferroptosis. Genetic deletion of LRP8 leads to ferroptosis as a result of an insufficient supply of selenocysteine, which is required for the translation of the antiferroptotic selenoprotein GPX4. This dependency is caused by low expression of alternative selenium uptake pathways such as system Xc- . The identification of LRP8 as a specific vulnerability of MYCN-amplified neuroblastoma cells was confirmed in constitutive and inducible LRP8 knockout orthotopic xenografts. These findings disclose a yet-unaccounted mechanism of selective ferroptosis induction that might be explored as a therapeutic strategy for high-risk neuroblastoma and potentially other MYCN-amplified entities.

Submandibular Ectopic Parathyroid Adenoma: A Case Report.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by hypercalcemia and elevated or abnormally normal parathyroid hormone (PTH) levels, due to excessive secretion of PTH by 1 or more parathyroid glands. In this report, we discuss the diagnostic and therapeutic challenges posed by ectopic parathyroid adenomas, a rare but atypical presentation of PHPT. We present the case of a 36-year-old female with PHPT due to an ectopic parathyroid adenoma located in the submandibular region. The patient presented with bone pain and was initially evaluated with routine imaging studies, which were negative. [18F] F-choline positron emission tomography (PET)/Computed tomography revealed the ectopic adenoma, leading to successful surgical management. Ectopic parathyroid adenomas are rare but can occur in various locations, and functional imaging modalities such as choline PET can aid in their detection. Surgical resection remains the definitive treatment for parathyroid adenomas, with intraoperative PTH monitoring guiding the extent of resection. Proper evaluation and management of PHPT is essential to avoid significant morbidity. Our case adds to the growing body of literature on the importance of considering ectopic locations of parathyroid adenomas in patients with PHPT.

[Chronic care for patients with post-COVID-19 syndrome after discharge from an intensive care unitCuidados prolongados de pacientes com síndrome pós-COVID-19 após internação em unidade de terapia intensiva]. / Cuidados crónicos en pacientes con síndrome pos-COVID-19 tras el egreso de la unidad de cuidados intensivos.

Objective: To describe the clinical features of patients with post-COVID-19 syndrome who have recently been discharged from intensive care units (ICUs) included in a chronic care program in Colombia. Methods: Descriptive case series study of a cohort of patients with post-COVID-19 syndrome who entered the Remeo® chronic care program between July 2020 and May 2021. Clinical features, complications, and treatments are described. Results: Among patients in the program discharged from an ICU, 122 cases of post-COVID-19 syndrome were identified. These patients continued in the program. The mean age was 66.9 years (CI 64-68); 62.29% were men, 88.9% (109) had a tracheostomy, 72.8% (90) had a gastrostomy, and 99% required supplemental oxygen. In the first four months, 9,518 interventions were carried out, including physical therapy (x̄:20.7), occupational therapy (x̄:10.9), respiratory therapy (x̄:41.4), and psychology (x̄:4.8). Conclusions: The chronic care program was an option for patients with post-COVID-19 syndrome recently discharged from an ICU, with a view to minimizing ICU occupation rates and facilitating patients' return to their homes.

Objetivo: Descrever as características clínicas de pacientes com síndrome pós-COVID-19 após internação em unidade de terapia intensiva (UTI), acompanhados em um programa de cuidados prolongados na Colômbia. Métodos: Estudo descritivo de série de casos oriundos de uma coorte de pacientes com síndrome pós-COVID-19 admitidos no programa de cuidados prolongados Remeo® entre julho de 2020 e maio de 2021. Foram descritas as características clínicas desses pacientes, assim como complicações e tratamentos. Resultados: Foram identificados 122 casos de pacientes com síndrome pós-COVID-19 que foram acompanhados no programa após alta da UTI. A média de idade foi 66,9 anos (IC 64­68), 62,29% pertenciam ao sexo masculino, 88,9% (109) haviam sido submetidos a traqueostomia, 72,8% (90) a gastrostomia e 99% precisavam usar oxigênio suplementar. Ao todo, 9.518 intervenções foram realizadas nos 4 meses iniciais de acompanhamento no programa, incluindo fisioterapia (x̄ 20,7), terapia ocupacional (x̄ 10,9), terapia respiratória (x̄ 41,4) e atendimento psicológico (x̄ 4,8). Conclusões: O programa de cuidados prolongados ofereceu uma alternativa aos pacientes com síndrome pós-COVID-19 após internação em UTI e teve o objetivo de reduzir a ocupação das UTIs e facilitar a transição do paciente da UTI para casa.

Cuidados crónicos en pacientes con síndrome pos-COVID-19 tras el egreso de la unidad de cuidados intensivos

[RESUMEN]. Objetivo. Describir las características clínicas de pacientes con síndrome pos-COVID-19 recién egresados de unidades cuidado intensivo (UCI) incluidos en un programa de cuidados crónicos en Colombia. Métodos. Estudio descriptivo de serie de casos procedentes de una cohorte de pacientes con síndrome pos-COVID-19 que ingresaron al programa de cuidados crónicos Remeo® entre julio de 2020 y mayo de 2021. Se describen las características clínicas, las complicaciones y el tratamiento de estos pacientes. Resultados. Se identificaron 122 casos de síndrome pos-COVID-19 dados de alta de la UCI para continuar en el Programa. La media de la edad fue de 66,9 años (IC 64-68); 62,29% fueron hombres, 88,9% (109) tenían traqueostomía, 72,8% (90) gastrostomía, y 99% requerían oxígeno suplementario. Se llevaron a cabo 9 518 intervenciones en los primeros 4 meses, inclusive terapia física (x¯:20,7), terapia ocupacional (x¯:10,9), terapia respiratoria (x¯:41,4) y psicología (x¯:4,8). Conclusiones. El Programa de cuidados crónicos representó una alternativa para pacientes con síndrome pos-COVID-19 recién egresados de las UCI, dirigido a minimizar la ocupación de estas y facilitar el paso del paciente desde la UCI al domicilio.

[ABSTRACT]. Objective. To describe the clinical features of patients with post-COVID-19 syndrome who have recently been discharged from intensive care units (ICUs) included in a chronic care program in Colombia. Methods. Descriptive case series study of a cohort of patients with post-COVID-19 syndrome who entered the Remeo® chronic care program between July 2020 and May 2021. Clinical features, complications, and treatments are described. Results. Among patients in the program discharged from an ICU, 122 cases of post-COVID-19 syndrome were identified. These patients continued in the program. The mean age was 66.9 years (CI 64–68); 62.29% were men, 88.9% (109) had a tracheostomy, 72.8% (90) had a gastrostomy, and 99% required supplemental oxygen. In the first four months, 9,518 interventions were carried out, including physical therapy (x¯:20.7), occupational therapy (x¯:10.9), respiratory therapy (x¯:41.4), and psychology (x¯:4.8). Conclusions. The chronic care program was an option for patients with post-COVID-19 syndrome recently discharged from an ICU, with a view to minimizing ICU occupation rates and facilitating patients' return to their homes.

[RESUMO]. Objetivo. Descrever as características clínicas de pacientes com síndrome pós-COVID-19 após internação em unidade de terapia intensiva (UTI), acompanhados em um programa de cuidados prolongados na Colômbia. Métodos. Estudo descritivo de série de casos oriundos de uma coorte de pacientes com síndrome pós- COVID-19 admitidos no programa de cuidados prolongados Remeo® entre julho de 2020 e maio de 2021. Foram descritas as características clínicas desses pacientes, assim como complicações e tratamentos. Resultados. Foram identificados 122 casos de pacientes com síndrome pós-COVID-19 que foram acompanhados no programa após alta da UTI. A média de idade foi 66,9 anos (IC 64–68), 62,29% pertenciam ao sexo masculino, 88,9% (109) haviam sido submetidos a traqueostomia, 72,8% (90) a gastrostomia e 99% precisavam usar oxigênio suplementar. Ao todo, 9.518 intervenções foram realizadas nos 4 meses iniciais de acompanhamento no programa, incluindo fisioterapia (x¯ 20,7), terapia ocupacional (x¯ 10,9), terapia respiratória (x¯ 41,4) e atendimento psicológico (x¯ 4,8). Conclusões. O programa de cuidados prolongados ofereceu uma alternativa aos pacientes com síndrome pós-COVID-19 após internação em UTI e teve o objetivo de reduzir a ocupação das UTIs e facilitar a transição do paciente da UTI para casa.

MYCN mediates cysteine addiction and sensitizes neuroblastoma to ferroptosis.

Aberrant expression of MYC transcription factor family members predicts poor clinical outcome in many human cancers. Oncogenic MYC profoundly alters metabolism and mediates an antioxidant response to maintain redox balance. Here we show that MYCN induces massive lipid peroxidation on depletion of cysteine, the rate-limiting amino acid for glutathione (GSH) biosynthesis, and sensitizes cells to ferroptosis, an oxidative, non-apoptotic and iron-dependent type of cell death. The high cysteine demand of MYCN-amplified childhood neuroblastoma is met by uptake and transsulfuration. When uptake is limited, cysteine usage for protein synthesis is maintained at the expense of GSH triggering ferroptosis and potentially contributing to spontaneous tumor regression in low-risk neuroblastomas. Pharmacological inhibition of both cystine uptake and transsulfuration combined with GPX4 inactivation resulted in tumor remission in an orthotopic MYCN-amplified neuroblastoma model. These findings provide a proof of concept of combining multiple ferroptosis targets as a promising therapeutic strategy for aggressive MYCN-amplified tumors.

Cuidados crónicos en pacientes con síndrome pos-COVID-19 tras el egreso de la unidad de cuidados intensivos / Chronic care for patients with post-COVID-19 syndrome after discharge from an intensive care unit / Cuidados prolongados de pacientes com síndrome pós-COVID-19 após internação em unidade de terapia intensiva

RESUMEN Objetivo. Describir las características clínicas de pacientes con síndrome pos-COVID-19 recién egresados de unidades cuidado intensivo (UCI) incluidos en un programa de cuidados crónicos en Colombia. Métodos. Estudio descriptivo de serie de casos procedentes de una cohorte de pacientes con síndrome pos-COVID-19 que ingresaron al programa de cuidados crónicos Remeo® entre julio de 2020 y mayo de 2021. Se describen las características clínicas, las complicaciones y el tratamiento de estos pacientes. Resultados. Se identificaron 122 casos de síndrome pos-COVID-19 dados de alta de la UCI para continuar en el Programa. La media de la edad fue de 66,9 años (IC 64-68); 62,29% fueron hombres, 88,9% (109) tenían traqueostomía, 72,8% (90) gastrostomía, y 99% requerían oxígeno suplementario. Se llevaron a cabo 9 518 intervenciones en los primeros 4 meses, inclusive terapia física (x̄:20,7), terapia ocupacional (x̄:10,9), terapia respiratoria (x̄:41,4) y psicología (x̄:4,8). Conclusiones. El Programa de cuidados crónicos representó una alternativa para pacientes con síndrome pos-COVID-19 recién egresados de las UCI, dirigido a minimizar la ocupación de estas y facilitar el paso del paciente desde la UCI al domicilio.

ABSTRACT Objective. To describe the clinical features of patients with post-COVID-19 syndrome who have recently been discharged from intensive care units (ICUs) included in a chronic care program in Colombia. Methods. Descriptive case series study of a cohort of patients with post-COVID-19 syndrome who entered the Remeo® chronic care program between July 2020 and May 2021. Clinical features, complications, and treatments are described. Results. Among patients in the program discharged from an ICU, 122 cases of post-COVID-19 syndrome were identified. These patients continued in the program. The mean age was 66.9 years (CI 64-68); 62.29% were men, 88.9% (109) had a tracheostomy, 72.8% (90) had a gastrostomy, and 99% required supplemental oxygen. In the first four months, 9,518 interventions were carried out, including physical therapy (x̄:20.7), occupational therapy (x̄:10.9), respiratory therapy (x̄:41.4), and psychology (x̄:4.8). Conclusions. The chronic care program was an option for patients with post-COVID-19 syndrome recently discharged from an ICU, with a view to minimizing ICU occupation rates and facilitating patients' return to their homes.

RESUMO Objetivo. Descrever as características clínicas de pacientes com síndrome pós-COVID-19 após internação em unidade de terapia intensiva (UTI), acompanhados em um programa de cuidados prolongados na Colômbia. Métodos. Estudo descritivo de série de casos oriundos de uma coorte de pacientes com síndrome pós-COVID-19 admitidos no programa de cuidados prolongados Remeo® entre julho de 2020 e maio de 2021. Foram descritas as características clínicas desses pacientes, assim como complicações e tratamentos. Resultados. Foram identificados 122 casos de pacientes com síndrome pós-COVID-19 que foram acompanhados no programa após alta da UTI. A média de idade foi 66,9 anos (IC 64-68), 62,29% pertenciam ao sexo masculino, 88,9% (109) haviam sido submetidos a traqueostomia, 72,8% (90) a gastrostomia e 99% precisavam usar oxigênio suplementar. Ao todo, 9.518 intervenções foram realizadas nos 4 meses iniciais de acompanhamento no programa, incluindo fisioterapia (x̄ 20,7), terapia ocupacional (x̄ 10,9), terapia respiratória (x̄ 41,4) e atendimento psicológico (x̄ 4,8). Conclusões. O programa de cuidados prolongados ofereceu uma alternativa aos pacientes com síndrome pós-COVID-19 após internação em UTI e teve o objetivo de reduzir a ocupação das UTIs e facilitar a transição do paciente da UTI para casa.

Ferroptosis: Concepts and Definitions.

Ferroptosis is a newly discovered form of cell death that is rapidly becoming associated to a variety of diseases and explaining their pathological mechanisms. This book addresses new emerging topics in the field of ferroptosis, with special attention to diseases more recently explained through ferroptotic mechanisms, including infectious diseases and neurodegeneration. In this chapter, we will provide the readers with an introduction to the concepts and pathways involved in ferroptosis to further move into a more detailed exposition of the topics advertised in this book. In special, we aim for this book to broaden the perspectives on how ferroptosis is regulated and connected to human diseases and motivate new studies in this emerging field.

Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma.

The migrational propensity of neuroblastoma is affected by cell identity, but the mechanisms behind the divergence remain unknown. Using RNAi and time-lapse imaging, we show that ADRN-type NB cells exhibit RAC1- and kalirin-dependent nucleokinetic (NUC) migration that relies on several integral components of neuronal migration. Inhibition of NUC migration by RAC1 and kalirin-GEF1 inhibitors occurs without hampering cell proliferation and ADRN identity. Using three clinically relevant expression dichotomies, we reveal that most of up-regulated mRNAs in RAC1- and kalirin-GEF1-suppressed ADRN-type NB cells are associated with low-risk characteristics. The computational analysis shows that, in a context of overall gene set poverty, the upregulomes in RAC1- and kalirin-GEF1-suppressed ADRN-type cells are a batch of AU-rich element-containing mRNAs, which suggests a link between NUC migration and mRNA stability. Gene set enrichment analysis-based search for vulnerabilities reveals prospective weak points in RAC1- and kalirin-GEF1-suppressed ADRN-type NB cells, including activities of H3K27- and DNA methyltransferases. Altogether, these data support the introduction of NUC inhibitors into cancer treatment research.

A new species of Procestus Townes (Hymenoptera: Ichneumonidae: Banchinae) from Brazil.

A new species of Procestus Townes, 1970 is described from Brazil. An identification key to all known species is provided. Figures of the holotypes of Procestus nabis Townes, 1970 and P. simplex Townes, 1970, and a paratype of P. pammae Ugalde Gauld, 2002 are included.                Procestus nabis and P. simplex are redescribed.

Proteína moduladora de la actividad del receptor de aril hidrocarburos (AIP): genética, bioquímica e impacto clínico / Aryl hydrocarbon receptor interacting protein (AIP): genetics, biochemistry and clinical impact

El gen AIP (proteína moduladora de la actividad del receptor de aril hidrocarburos) se localiza en la región 11q13.2 y codifica para una proteína de 330 aminoácidos que interactúa con el factor de transcripción AhR (receptor para aril hidrocarburos). Las mutaciones en este gen se han asociado con adenomas pituitarios aislados de tipo familiar (APAF). Se caracterizan por una presentación temprana (alrededor de 20 años), por lo regular producen hormona de crecimiento y/o prolactina, tienen un comportamiento clínico agresivo y poca respuesta a análogos de somatostatina.

The AIP gene (aryl hydrocarbon receptor interacting protein) is located on chromosome 11q13.2 and encodes a 330 amino acid protein which interacts with the aryl hydrocarbon receptor (AHR) transcription factor. Mutations in the AIP gene have been associated with familial isolated pituitary adenomas (FIPA). They characterize by an early-onset (around the age of 20 years old) and for being aggressive, growth hormone and/or prolactin-secreting tumors, with poor response to somatostatin analogues.

Diabetes posterior a tratamiento no quirúrgico de un insulinoma maligno: reporte de caso y revisión literatura / Diabetes after non-surgical treatment of a malignant insulinoma: Case report and literature review

Resumen Los tumores neuroendocrinos pancreáticos (TNEsP) son un grupo poco frecuente de neoplasias, pueden ser funcionales y causan síndromes clínicos diversos, o no funcionales, con síntomas secundarios a invasión a estructuras cercanas o enfermedad metastásica (1). Se presenta el caso de una paciente de 55 años con insulinoma maligno con compromiso metastásico extenso, no candidata a intervención quirúrgica, hipoglucemia de difícil manejo sin respuesta a tratamiento con diazóxido y prednisolona, y que requirió manejo con quimioterapia y embolización de metástasis hepáticas, con posterior mejoría clínica, estabilidad de la enfermedad por imágenes diagnósticas y retiro de medicamentos para manejo de hipoglucemia. En seguimiento presenta síntomas de hiperglucemia con HbA1c en 12%, con lo cual se diagnosticó diabetes mellitus de novo y se inició manejo con insulina.

Abstract Pancreatic neuroendocrine tumors (TNEP) are a rare group of neoplasms, which can secrete peptide hormones causing various clinical syndromes, or be non-secretory, with symptoms secondary to invasion of neighboring or distant structures (1). The case of a 55-year-old patient with malignant insulinoma with extensive metastatic involvement, not operable, with persistent hypoglycemia refractory to treatment with diazoxide and prednisolone, who received management with chemotherapy and embolization of liver metastases, achieving the withdrawal of medications for the management of hypoglycemia and a tumor response of stable disease in the comparison of images during the 12-month follow-up. During the 15th cycle of chemotherapy, he presented symptoms of hyperglycemia with HbA1c in 12%, with which diabetes de novo mellitus was diagnosed and insulin management was initiated.

New species of Grotea Cresson (Hymenoptera: Ichneumonidae: Labeninae) from Brazil and Suriname.

Four new species of Grotea Cresson are described: Grotea goianiense Herrera-Flórez sp. n., G. paulista Herrera-Flórez sp. n. and G. amazonensis Herrera-Flórez sp. n. from Brazil and G. surinamese Herrera-Flórez sp. n. from Suriname. An identification key to Brazilian and Suriname species of this genus is given. New descriptions for G. delicator (Thunberg 1822) and G. perplexa Slobodchikoff 1970 are provided.

Three new species of Grotea Cresson (Hymenoptera: Ichneumonidae: Labeninae) from Colombia.

Three new species of Grotea Cresson 1864 from Colombia are described: Grotea llanera, G. santandereana and G. cundinamarquesa. An identification key to Colombian species of this genus is given.

A new species of Umanella Gauld (Hymenoptera: Ichneumonidae: Pimplinae) from Colombia.

A new species of Umanella Gauld 1991, U. tricoloripes Herrera-Florez, sp. n., is described from two males collected in Colombia. Umanella tricoloripes sp. nov. differs substantially from the other species of the genus in color pattern.

Cell-Cycle Position of Single MYC-Driven Cancer Cells Dictates Their Susceptibility to a Chemotherapeutic Drug.

While many tumors initially respond to chemotherapy, regrowth of surviving cells compromises treatment efficacy in the long term. The cell-biological basis of this regrowth is not understood. Here, we characterize the response of individual, patient-derived neuroblastoma cells driven by the prominent oncogene MYC to the first-line chemotherapy, doxorubicin. Combining live-cell imaging, cell-cycle-resolved transcriptomics, and mathematical modeling, we demonstrate that a cell's treatment response is dictated by its expression level of MYC and its cell-cycle position prior to treatment. All low-MYC cells enter therapy-induced senescence. High-MYC cells, by contrast, disable their cell-cycle checkpoints, forcing renewed proliferation despite treatment-induced DNA damage. After treatment, the viability of high-MYC cells depends on their cell-cycle position during treatment: newborn cells promptly halt in G1 phase, repair DNA damage, and form re-growing clones; all other cells show protracted DNA repair and ultimately die. These findings demonstrate that fast-proliferating tumor cells may resist cytotoxic treatment non-genetically, by arresting within a favorable window of the cell cycle.

A new species of Jomine Graf-Kumagai (Hymenoptera: Ichneumonidae: Campopleginae) from Brazil.

The genus Jomine Graf-Kumagai has two described species known only from Brazil. A new species, J. paulista Herrera-Florez sp. n. is described and its host is given here. The material used in this work was obtained during a survey of the Geometridae larvae and their parasitoids in an understory at São Paulo, Brazil. An identification key to the species of Jomine is provided.

A new species of Sphelodon Townes (Hymenoptera: Ichneumonidae: Banchinae) from Colombia.

The genus Sphelodon Townes has 13 described species, nine species from the Neotropical region, three species from the Nearctic region and one (Sphelodon phoxopteridis) that occurs in both regions. A new species, Sphelodon antioquensis sp. n. is described here. This is the first record of Sphelodon for Colombia. A key to Sphelodon species occurring in the Neotropical Region is provided.

Parálisis periódica hipocalémica: reporte de caso y revisión del tema / Hypokalemic periodic paralysis: A case report and a topic review

Las parálisis periódicas primarias son canalopatías poco frecuentes, de las cuales hacen parte: la parálisis periódica hipocalémica, la parálisis periódica hipercalémica y el síndrome Andersen-Tawil; son caracterizadas por ataques de debilidad muscular generalizada, con recuperación de la fuerza entre los ataques. Presentamos el caso de una mujer de 21 años con el segundo episodio de parálisis y documentación de hipocalemia, sin antecedentes de importancia, sin factores clínicos o paraclínicos que expliquen el trastorno electrolítico, con recuperación posterior de la fuerza al realizar tratamiento de la hipocalemia. Posteriormente se lleva a cabo una revisión del tema.

Primary periodic paralyses are rare channelopathies which include: hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and Andersen-Tawil Syndrome. These entities are characterized by attacks of generalized muscle weakness and recovery of muscle strength between attacks. A case is presented of a 21-year-old woman who presented a second episode of paralysis and documented hypokalemia, with no important antecedents, with no clinical or diagnostic test factors which explain her electrolyte disorder, with recovery of muscle strength after receiving treatment for hypokalemia. A review of the topic was conducted.

Drug search for leishmaniasis: a virtual screening approach by grid computing.

The trypanosomatid protozoa Leishmania is endemic in ~100 countries, with infections causing ~2 million new cases of leishmaniasis annually. Disease symptoms can include severe skin and mucosal ulcers, fever, anemia, splenomegaly, and death. Unfortunately, therapeutics approved to treat leishmaniasis are associated with potentially severe side effects, including death. Furthermore, drug-resistant Leishmania parasites have developed in most endemic countries. To address an urgent need for new, safe and inexpensive anti-leishmanial drugs, we utilized the IBM World Community Grid to complete computer-based drug discovery screens (Drug Search for Leishmaniasis) using unique leishmanial proteins and a database of 600,000 drug-like small molecules. Protein structures from different Leishmania species were selected for molecular dynamics (MD) simulations, and a series of conformational "snapshots" were chosen from each MD trajectory to simulate the protein's flexibility. A Relaxed Complex Scheme methodology was used to screen ~2000 MD conformations against the small molecule database, producing >1 billion protein-ligand structures. For each protein target, a binding spectrum was calculated to identify compounds predicted to bind with highest average affinity to all protein conformations. Significantly, four different Leishmania protein targets were predicted to strongly bind small molecules, with the strongest binding interactions predicted to occur for dihydroorotate dehydrogenase (LmDHODH; PDB:3MJY). A number of predicted tight-binding LmDHODH inhibitors were tested in vitro and potent selective inhibitors of Leishmania panamensis were identified. These promising small molecules are suitable for further development using iterative structure-based optimization and in vitro/in vivo validation assays.