Control of myeloid-derived suppressor cell dynamics potentiates vaccine protection in multiple mouse models of infection.

To date, there is no licensed vaccine against the protozoan parasite (, the etiological agent of Chagas Disease. has evolved numerous mechanisms to evade and manipulate the host immune system. Among the subversive strategies employed by the parasite, marked increases in CD11b+ Gr-1+ myeloid-derived suppressor cells (MDSCs) in several organs have been described.

Multiple-Point Metamaterial-Inspired Microwave Sensors for Early-Stage Brain Tumor Diagnosis.

Simple, instantaneous, contactless, multiple-point metamaterial-inspired microwave sensors, composed of multi-band, low-profile metamaterial-inspired antennas, were developed to detect and identify meningioma tumors, the most common primary brain tumors. Based on a typical meningioma tumor size of 5-20 mm, a higher operating frequency, where the wavelength is similar or smaller than the tumor target, is crucial. The sensors, designed for the microwave Ku band range (12-18 GHz), where the electromagnetic property values of tumors are available, were implemented in this study.

Simple protocol for measuring CD11b+ GR-1+ (Ly6C+/Ly6G+) myeloid cells from a minimum volume of mouse peripheral blood.

Myeloid-derived suppressor cells (MDSCs) comprise a heterogeneous population of myeloid origin and immature state, whose hallmark is the capacity to suppress T cells and other immune populations. In mice, the first approach to identify MDSCs relies in the measurement of their phenotypical markers: CD11b and GR-1. In addition, two main subtypes of MDSCs have been defined based on the expression of the following markers: CD11b+ Ly6G- Ly6C+ (monocytic-MDSCs, M-MDSCs) and CD11b+ Ly6G+ Ly6C (polymorphonuclear-MDSCs, PMN-MDSCs).

Role of myeloid-derived suppressor cells during Trypanosoma cruzi infection.

Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, is the third largest parasitic disease burden globally. Currently, more than 6 million people are infected, mainly in Latin America, but international migration has turned CD into an emerging health problem in many nonendemic countries. Despite intense research, a vaccine is still not available.

The effects of dendritic cell-based vaccines in the tumor microenvironment: Impact on myeloid-derived suppressor cells.

Dendritic cells (DCs) are a heterogenous population of professional antigen presenting cells whose main role is diminished in a variety of malignancies, including cancer, leading to ineffective immune responses. Those mechanisms are inhibited due to the immunosuppressive conditions found in the tumor microenvironment (TME), where myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature myeloid cells known to play a key role in tumor immunoevasion by inhibiting T-cell responses, are extremely accumulated. In addition, it has been demonstrated that MDSCs not only suppress DC functions, but also their maturation and development within the myeloid linage.

Bedside Echocardiography Diagnosis of Tricuspid Valve Infective Endocarditis in the Emergency Department.

Infective endocarditis (IE) is a rare life-threatening entity that remains difficult to diagnose in the emergency department (ED). Focused cardiac ultrasound (FOCUS) with transthoracic echocardiography (TTE) is an indispensable bedside tool for the emergency physician (EP) to promptly diagnosis and expedite clinical management of IE. This report describes a case in which EP-performed FOCUS led to the early identification of right-sided tricuspid valve IE complicated with septic pulmonary emboli.

Myeloid-derived suppressor cells and vaccination against pathogens.

It is widely accepted that the immune system includes molecular and cellular components that play a role in regulating and suppressing the effector immune response in almost any process in which the immune system is involved. Myeloid-derived suppressor cells (MDSCs) are described as a heterogeneous population of myeloid origin, immature state, with a strong capacity to suppress T cells and other immune populations. Although the initial characterization of these cells was strongly associated with pathological conditions such as cancer and then with chronic and acute infections, extensive evidence supports that MDSCs are also involved in physiological/non-pathological settings, including pregnancy, neonatal period, aging, and vaccination.

Development of low-cost cage-like particles to formulate veterinary vaccines.

Low-cost adjuvants are urgently needed for the development of veterinary vaccines able to trigger strong immune responses. In this work, we describe a method to obtain a low-cost cage-like particles (ISCOMATRIX-like) adjuvant useful to formulate veterinary vaccines candidates. The main components to form the particles are lipids and saponins, which were obtained from egg yolk by ethanolic extraction and by dialyzing a non-refined saponins extract, respectively.

Film Forming Nanogels for Needle-Free Transdermal Vaccination.

Transcutaneous immunization (TCI) provides a valuable alternative approach to conventional vaccination because of the high accessibility and the exceptional immunological characteristics of the skin, but its application is limited by the low permeability of the stratum corneum. Although nanogels (NGs) have proven to enhance skin penetration of macromolecules with minimum damage, their use in TCI remains almost unexplored. In this context, this article evaluates the performance of novel film-forming NGs (FF-NGs) as TCI.

Assessment of a combined treatment with a therapeutic vaccine and benznidazole for the Trypanosoma cruzi chronic infection.

The difficulties encountered in achieving treatments for chronic Chagas disease have promoted the investigation of new therapeutic strategies. In this study, we used two murine models of Trypanosoma cruzi chronic infection to determine the usefulness of applying a therapeutic vaccine alone or followed by benznidazole (Bz) chemotherapy. A vaccine formulation based on an N-terminal fragment of Trans-sialidase (TS) and Immunostimulant Particle Adjuvant (ISPA) - TSNt-ISPA was obtained.

Targeting Myeloid-Derived Suppressor Cells to Enhance a Trans-Sialidase-Based Vaccine Against .

() is a hemoflagellate protozoan parasite that causes Chagas disease, a neglected tropical disease that affects more than 6 million people around the world, mostly in Latin America. Despite intensive research, there is no vaccine available; therefore, new approaches are needed to further improve vaccine efficacy. It is well established that experimental infection induces a marked immunosuppressed state, which includes notably increases of CD11b+ GR-1+ myeloid-derived suppressor cells (MDSCs) in the spleen, liver and heart of infected mice.

Point-of-Care Ultrasound Diagnosis of a Crohn's Disease-Related Intraabdominal Abscess in the Emergency Department.

The emergency department (ED) diagnosis of Crohn's disease (CD)-associated complications is typically established with abdominopelvic computed tomography imaging. Ultrasonography has been suggested as an effective alternative modality for diagnosing several CD complications, including intraabdominal abscesses. We report the identification of a CD-related intraabdominal abscess by emergency physician (EP)-performed point-of-care ultrasound (POCUS).

Bedside Ocular Ultrasound Diagnosis of a Traumatic Lens Dislocation.

Rapid identification of ophthalmologic emergencies can be challenging in the ED, and a missed or delayed diagnosis may have vision-threatening consequences. The application of ocular point-of-care ultrasound (POCUS) by the emergency physician (EP) can facilitate the timely recognition of a myriad of emergent eye conditions. This report describes a case in which EP-performed POCUS established the prompt diagnosis of a traumatic lens dislocation in a patient with chronic vision changes.

Point-of-care ultrasound diagnosis of a pyogenic liver abscess in the emergency department.

Pyogenic liver abscess (PLA) is a rarely encountered condition in the emergency department (ED) that necessitates a timely diagnosis by the emergency physician. An early ED diagnosis is challenging as the presenting symptoms of PLA are often variable and nonspecific. The rapid bedside diagnosis of PLA with point-of-care ultrasound (POCUS) performed by emergency physicians has not been investigated thoroughly.

Emergency physician-performed bedside ultrasound of pyomyositis.

Point-of-care ultrasound (POCUS) is an indispensable tool for emergency physicians in the rapid bedside diagnosis of skin and soft tissue infections. The utility of POCUS for the differentiation of cellulitis and subcutaneous abscess is well established; however, there is a paucity of studies highlighting POCUS as a first-line imaging approach for pyomyositis, an uncommon skeletal muscle infection and/or intramuscular abscess formation requiring emergent diagnosis. This report describes a case in which emergency physician-performed POCUS led to the early detection and timely management of pyomyositis in the emergency department.

Emergency Physician-Performed Bedside Ultrasound of Gastric Volvulus.

Gastric volvulus (GV) is a seldomly encountered life-threatening condition that necessitates rapid diagnosis in the emergency department (ED). The diagnosis of GV is traditionally established with cross-sectional imaging and/or endoscopy with surgical confirmation. The potential role of point-of-care ultrasound (POCUS) as a bedside tool to support the early identification of GV by emergency physicians (EPs) has not been thoroughly investigated.

Emergent Diagnosis of a Flail Mitral Leaflet With Bedside Echocardiography.

Flail mitral leaflet (FML) with associated acute pulmonary edema and acute decompensated heart failure is an emergent condition requiring prompt recognition by the emergency physician (EP). Focused cardiac ultrasound (FOCUS) and lung ultrasound (LUS) have a vital role in the evaluation of FML in the emergency department. This case report describes the identification of a FML with EP-performed bedside echocardiography.

Right Heart Thrombus in Transit Diagnosed With Focused Cardiac Ultrasound in the Emergency Department.

The diagnosis of a right heart thrombus (RHTh) in transit associated with pulmonary embolism (PE) is an uncommon phenomenon with a high mortality rate. Timely recognition of RHTh with focused cardiac ultrasound (FOCUS) in cases of suspected PE is necessary for critical decision making in the emergency department (ED). We present a case of RHTh with submassive PE in which the patient underwent successful catheter-directed thrombolysis.

Point-of-Care Ultrasound Diagnosis of Pneumoperitoneum in the Emergency Department.

Prompt and accurate diagnostic evaluation of the nontraumatic acute abdomen in the emergency department (ED) is crucial to lessen mortality burden. In patients with perforated viscus and pneumoperitoneum, point-of-care ultrasound (POCUS) can assist the emergency physician (EP) in the rapid bedside diagnosis. This report describes a case in which EP-performed POCUS led to the early detection and timely management of an atypical presentation of pneumoperitoneum.

Serial Point-of-care Echocardiography Performed by an Emergency Physician to Guide Thrombolytic Management of Massive Pulmonary Embolism.

Massive pulmonary embolism (PE) is a life-threatening condition with a high mortality burden. The rapid diagnosis of PE can be supported with focused cardiac ultrasound (FOCUS) by identifying signs of right ventricular dysfunction (RVD). This case report describes a patient with hemodynamically unstable massive PE who received systemic thrombolytic therapy.

Vaccines and the regulatory arm of the immune system. An overview from the Trypanosoma cruzi infection model.

The knowledge that the immune system is composed of a regulatory/suppressor arm added a new point of view to better understand the nature of several pathologies including cancer, transplants, infections and autoimmune diseases. The striking discoveries concerning molecules and cells involved in this kind of regulation were followed by the elucidation of equally notable mechanisms used by several pathogens to manipulate the host immune system. Vaccines against pathogens are an invaluable tool developed to help the immune system cope with a potential infection or prevent disease pathology.

Genetic Engineering of Co-producing Antigen and the Mucosal Adjuvant 3' 5'- cyclic di Adenosine Monophosphate (c-di-AMP) as a Design Strategy to Develop a Mucosal Vaccine Prototype.

is a promising candidate for the development of mucosal vaccines. More than 20 years of experimental research supports this immunization approach. In addition, 3' 5'- cyclic di-adenosine monophosphate (c-di-AMP) is a bacterial second messenger that plays a key role in the regulation of diverse physiological functions (potassium and cellular wall homeostasis, among others).

Cyclopentadienones via a tandem -cyclopropylnitrone cyclization-cycloreversion sequence.

Aldonitrones derived from spiro[2.4]hepta-4,6-diene-1-carbaldehyde and its benzo analog undergo a tandem uncatalyzed intramolecular cyclopropane-nitrone cyclization-5,6-dihydro-1,2-oxazine cycloreversion to give cyclopentadienones. Similarly, the NH-nitrone generated in situ from spiro[cyclopropane-1,1'-indene]carbaldehyde oxime leads to benzocyclopentadienone (1-inden-1-one) by the same mechanism.