Diagnostic delays prevent most Chagas disease patients from receiving timely therapy during the acute phase when treatment is effective. qPCR-based diagnostic methods provide high sensitivity during this phase but require specialized equipment and complex protocols. More simple and cost-effective tools are urgently needed to optimize early Chagas disease diagnosis in low-income endemic regions.
View Article and Find Full Text PDFUnlabelled: Streptolysin O (SLO) is a virulence determinant of group A (), the agent of streptococcal sore throat and severe invasive infections. SLO is a member of a family of bacterial pore-forming toxins known as cholesterol-dependent cytolysins, which require cell membrane cholesterol for pore formation. While cholesterol is essential for cytolytic activity, accumulating data suggest that cell surface glycans may also participate in the binding of SLO and other cholesterol-dependent cytolysins to host cells.
View Article and Find Full Text PDFMacrophages hold tremendous promise as effectors of cancer immunotherapy, but the best strategies to provoke these cells to attack tumors remain unknown. Here, we evaluated the therapeutic potential of targeting two distinct macrophage immune checkpoints: CD47 and CD24. We found that antibodies targeting these antigens could elicit maximal levels of phagocytosis when combined together in vitro.
View Article and Find Full Text PDFMacrophages are critical effectors of antibody therapies for lymphoma, but the best targets for this purpose remain unknown. Here, we sought to define a comprehensive repertoire of cell surface antigens that can be targeted to stimulate macrophage-mediated destruction of B-cell lymphoma. We developed a high-throughput assay to screen hundreds of antibodies for their ability to provoke macrophages to attack B-cell lymphoma cells.
View Article and Find Full Text PDFMacrophage immune checkpoint inhibitors, such as anti-CD47 antibodies, show promise in clinical trials for solid and hematologic malignancies. However, the best strategies to use these therapies remain unknown, and ongoing studies suggest they may be most effective when used in combination with other anticancer agents. Here, we developed an unbiased, high-throughput screening platform to identify drugs that render lung cancer cells more vulnerable to macrophage attack, and we found that therapeutic synergy exists between genotype-directed therapies and anti-CD47 antibodies.
View Article and Find Full Text PDFDetermining the true availability of resources and understanding the level of training of surgeons involved in the treatment of patients with pelvic fractures and haemorrhagic shock is critical. In the herein study, the availability of technical, technological, and human resources for the care of this injury in Latin America region was analysed, and the preferences of orthopaedic trauma surgeons when performing interventions for the diagnosis and treatment of patients with pelvic trauma and associated haemorrhagic shock was described. A cross sectional web-based survey containing questions on knowledge, attitudes, and practices with respect to imaging resources, emergency pelvic stabilization methods, and interventions used for bleeding control was sent to 948 Latin America orthopaedic trauma surgeons treating pelvic fractures in the emergency department.
View Article and Find Full Text PDFObjective: The aim of this study was to evaluate the Latin American orthopaedic trauma surgeons preference regarding knee positioning and entry portals for IM nailing and identify the reasons of these preferences.
Methods: Using the AO Trauma database, 22.285 surveys were distributed by email to Latin American orthopaedic surgeons.
Postoperative bone infection is a severe complication in the treatment of fractures. The management of this pathology is challenging, but recent advances have been made to achieve standardization that can help diagnosis and decision-making. However, we are unaware of studies validating these models in Latin America.
View Article and Find Full Text PDFDuring in vitro maturation (IVM) cumulus-oocyte complexes (COCs) are exposed to conditions that can trigger oxidative stress, thus, reducing oocyte maturation and viability. Aiming to mitigate these detrimental conditions, the effects of IVM medium supplementation with anethole have been tested. Anethole, also known as trans-anethole (1-methoxy-4 [1-propenyl]-benzene), is a naturally occurring phenylpropanoid with various pharmacological properties, including antioxidant effects.
View Article and Find Full Text PDFThe role of the type, stage and status of cancer in the outcome of COVID-19 remains unclear. Moreover, the characteristic pathological changes of severe COVID-19 reveled by laboratory and radiological findings are similar to those due to the development of cancer itself and antineoplastic therapies. To identify potential predictors of mortality of COVID-19 in cancer patients.
View Article and Find Full Text PDFMacrophage immune checkpoint inhibitors, such as anti-CD47 antibodies, show promise in clinical trials for solid and hematologic malignancies. However, the best strategies to use these therapies remain unknown and ongoing studies suggest they may be most effective when used in combination with other anticancer agents. Here, we developed a novel screening platform to identify drugs that render lung cancer cells more vulnerable to macrophage attack, and we identified therapeutic synergy exists between genotype-directed therapies and anti-CD47 antibodies.
View Article and Find Full Text PDFNicotinamide adenine dinucleotide (NAD+) is an essential co-factor for cellular metabolism and serves as a substrate in enzymatic processes. NAD+ is produced by de novo synthesis or salvage pathways in nearly all bacterial species. Haemophilus influenzae lacks the capacity for de novo synthesis, so it is dependent on import of NAD+ from the external environment or salvage biosynthetic pathways for recycling of NAD+ precursors and breakdown products.
View Article and Find Full Text PDFPurpose: Kaposi's sarcoma (KS) is a multifocal angioproliferative disease. In Peru, the implementation of the highly active antiretroviral treatment (HAART) program was in 2005, the model for treating patients with HIV-positive KS shifted to a potential cure. In this study, we aim to compare clinicopathological characteristics and prognostic factors associated with outcomes in patients with HIV-positive KS.
View Article and Find Full Text PDFThe emergence and continued dominance of a Streptococcus pyogenes (group A Streptococcus, GAS) M1T1 clonal group is temporally correlated with acquisition of genomic sequences that confer high level expression of cotoxins streptolysin O (SLO) and NAD-glycohydrolase (NADase). Experimental infection models have provided evidence that both toxins are important contributors to GAS virulence. SLO is a cholesterol-dependent pore-forming toxin capable of lysing virtually all types of mammalian cells.
View Article and Find Full Text PDFRev Peru Med Exp Salud Publica
July 2021
Listeriosis infection is a severe disease, with high morbidity and mortality in the immunocompromised patient, especially with disseminated and fatal presentations in cancer patients. A descriptive study was developed to describe the clinical and epidemiologic characteristics in oncologic patients with listeriosis in the Instituto Nacional de Enfermedades Neoplásicas between the years 2005-2015. A total of 29 patients were included; 23 (79.
View Article and Find Full Text PDFDiagnosing primary central nervous system lymphoma (PCNSL) frequently requires neurosurgical biopsy due to nonspecific radiologic features and the low yield of cerebrospinal fluid (CSF) studies. We characterized the clinical evaluation of suspected PCNSL (N = 1007 patients) and designed a rapid multiplexed genotyping assay for MYD88, TERT promoter, IDH1/2, H3F3A, and BRAF mutations to facilitate the diagnosis of PCNSL from CSF and detect other neoplasms in the differential diagnosis. Among 159 patients with confirmed PCNSL, the median time to secure a diagnosis of PCNSL was 10 days, with a range of 0 to 617 days.
View Article and Find Full Text PDFBackground: Immune-oncology agents (IOA) represent a turning point in the treatment of several solid tumors (ST). Although their toxicity compares favorably with other treatments, IOA associate immune-related adverse events (IR-AE), among which endocrine-related AE stand out. We retrospectively evaluated the occurrence of endocrine (E) IR-AE in a cohort of patients with several ST treated with IOA.
View Article and Find Full Text PDFGlioblastoma (GB) is the most common primary brain tumour in adults and it is associated with a high mortality rate. According to the stem cell theory, the growth, relapse and treatment response of GB is determined by the stem cell subpopulation present in the tumour. Our aim is to study the prognostic value of stem cell markers (CD44, Nestin, Olig2 and SOX2) in a series of homogeneously treated GBs.
View Article and Find Full Text PDFT-DM1 is an antibody drug conjugate that combines trastuzumab with emtansine via a stable thioether linker. In two phase III clinical trials, EMILIA and TH3RESA, T-DM1 was shown to be effective in HER2-positive metastatic breast cancer patients who had progressed to taxanes and trastuzumab. We have performed a real-world study to complement the findings of the clinical trials.
View Article and Find Full Text PDFThe orphan regulator RocA plays a critical role in the colonization and pathogenesis of the obligate human pathogen group A Despite multiple lines of evidence supporting a role for RocA as an auxiliary regulator of the control of virulence two-component regulatory system CsrRS (or CovRS), the mechanism of action of RocA remains unknown. Using a combination of and techniques, we now find that RocA interacts with CsrS in the streptococcal membrane via its N-terminal region, which contains seven transmembrane domains. This interaction is essential for RocA-mediated regulation of CsrRS function.
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