Current situation of endemic mycosis in the Americas and the Caribbean: Proceedings of the first international meeting on endemic mycoses of the Americas (IMEMA).

BACKGROUND: The Americas are home to biologically and clinically diverse endemic fungi, including Blastomyces, Coccidioides, Emergomyces, Histoplasma, Paracoccidioides and Sporothrix. In endemic areas with high risk of infection, these fungal pathogens represent an important public health problem. OBJECTIVES: This report aims to summarise the main findings of the regional analysis carried out on the status of the endemic mycoses of the Americas, done at the first International Meeting on Endemic Mycoses of the Americas (IMEMA). METHODS: A regional analysis for the Americas was done, the 27 territories were grouped into nine regions. A SWOT analysis was done. RESULTS: All territories reported availability of microscopy. Seventy percent of territories reported antibody testing, 67% of territories reported availability of Histoplasma antigen testing. None of the territories reported the use of (1-3)-ß-d-glucan. Fifty two percent of territories reported the availability of PCR testing in reference centres (mostly for histoplasmosis). Most of the territories reported access to medications such as trimethoprim-sulfamethoxazole, itraconazole, voriconazole and amphotericin B (AMB) deoxycholate. Many countries had limited access to liposomal formulation of AMB and newer azoles, such as posaconazole and isavuconazole. Surveillance of these fungal diseases was minimal. CONCLUSIONS: A consensus emerged among meeting participants, this group concluded that endemic mycoses are neglected diseases, and due to their severity and lack of resources, the improvement of diagnosis, treatment and surveillance is needed.

PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function.

Dendritic cells (DCs) are critical in asthma and many other immune diseases. We previously demonstrated a role for PARP-1 in asthma. Evidence on PARP-1 playing a role in Th2-associated DC function is not clear. In this study, we examined whether PARP-1 is critical for DC differentiation and function using bone marrow progenitors and their migration to the lung in an ovalbumin-based mouse model of asthma. Results show that changes in PARP-1 levels during GM-CSF-induced DC differentiation from bone marrow progenitors were cyclic and appear to be part of an array of changes that included STAT3/STAT5/STAT6/GRAIL/RAD51. Interestingly, PARP-1 gene deletion affected primarily STAT6 and γH2AX. PARP-1 inhibition significantly reduced the migration of DCs to the lungs of ovalbumin-challenged mice, which was associated with a concomitant reduction in lung levels of the adhesion molecule VCAM-1. The requirement of PARP-1 for VCAM-1 expression was confirmed using endothelial and lung smooth muscle cells. PARP-1 expression and activity were also required for VCAM-1 in differentiated DCs. An assessment of CD11b+/CD11c+/MHCIIhigh DCs in spleens and lymph nodes of OVA-sensitized mice revealed that PARP-1 inhibition genetically or by olaparib exerted little to no effect on DC differentiation, percentage of CD80+/CD86+/CD40+-expressing cells, or their capacity to promote proliferation of ovalbumin-primed (OTII) CD4+ T cells. These findings were corroborated using GM-CSF-induced differentiation of DCs from the bone marrow. Surprisingly, the PARP-1-/- DCs exhibited a higher intrinsic capacity to induce OTII CD4+ T cell proliferation in the absence of ovalbumin. Overall, our results show that PARP-1 plays little to no role in DC differentiation and function and that the protective effect of PARP-1 inhibition against asthma is associated with a prevention of DC migration to the lung through a reduction in VCAM-1 expression. Given the current use of PARP inhibitors (e.g., olaparib) in the clinic, the present results may be of interest for the relevant therapies.

B cells interactions in lipid immune responses: implications in atherosclerotic disease.

Atherosclerosis is considered as an inflammatory and chronic disorder with an important immunologic component, which underlies the majority of cardiovascular diseases; condition that belongs to a group of noncommunicable diseases that to date and despite of prevention and treatment approaches, they remain as the main cause of death worldwide, with 17.5 million of deaths every year. The impact of lipids in human health and disease is taking center stage in research, due to lipotoxicity explained by elevated concentration of circulating lipids, in addition to altered adipose tissue metabolism, and aberrant intracellular signaling. Immune response and metabolic regulation are highly integrated systems and the proper function of each one is dependent on the other. B lymphocytes express a variety of receptors that can recognize foreign, endogenous or modified self-antigens, among them oxidized low density lipoproteins, which are the main antigens in atherosclerosis. Mechanisms of B cells to recognize, remove and present lipids are not completely clear. However, it has been reported that B cell can recognize/remove lipids through a range of receptors, such as LDLR, CD1d, FcR and SR, which might have an atheroprotector or proatherogenic role during the course of atherosclerotic disease. Pertinent literature related to these receptors was examined to inform the present conclusions.

Aging and Erectile Dysfunction.

INTRODUCTION: Erectile dysfunction (ED) has been identified as the most common sexual problem that affects mainly men older than 40 years. According to this, there is a strong evidence linking ED with a number of medical conditions and related risk factors that had been described in the literature, yet there is limited information about the specific mechanism involved in the establishment of ED among healthy older men. AIM: The purpose of this study is to review the literature and mainly focus on the basic physiologic and vascular alterations and morphologic changes related to aging and its related risk factors, summarizing the main and the latest findings in basic research of tissue remodeling process involved in ED pathophysiology. METHODS: Data from the pertinent literature were examined to inform our conclusions. MAIN OUTCOME MEASURE: This article defines the morphologic and physiologic mechanisms involved in the process of aging, which play a key role in the development of sexual dysfunction. RESULTS: ED has been considered as a nonlife-threatening condition, but the recognition of its multiple comorbid conditions, the importance of aging process over the male sexual performance among them its relation with vascular and nitric oxide content alteration, as well as penile morphologic changes, and the fact that it is a widespread under-reported disease, have established the need of an early diagnosis and treatment of this common sexual problem within the general male population. CONCLUSION: In this case, morphologic and physiologic mechanisms that are involved in the aging process play a key role in the development of sexual dysfunction in the absence of any other clinical or medical condition.