Clinical and Epidemiological Features of Hospitalized and Ambulatory Patients with Human Monkeypox Infection: A Retrospective Observational Study in Portugal.

Monkeypox, a neglected and re-emergent zoonotic disease caused by monkeypox virus (MPXV) infection, has been endemic in Central and Western Africa for decades. More recently, an outbreak has spread to a global level, occurring in sites with no previous reported cases and being clustered among men who have sex with men, suggesting new modes of transmission. There is an urgent need for research for a better understanding of the genomic evolution and changing epidemiology of the Orthopoxvirus group. Our work aimed to characterize the clinical and epidemiological features of a cohort of patients with MPXV infection in a Portuguese hospital, admitted between 5 May and 26 July 2022. In this retrospective observational study, aggregate data of a case series on the presentation, clinical course, and outcomes of confirmed MPXV infections are reported. The study included 40 men and 1 woman, with a mean age of 37.2 years old; 92.7% identified as men who have sex with men, 90.2% had unprotected sex or sex with multiple or anonymous partners in the previous month, and 39.0% reported to have had sex with an MPXV-confirmed case; 59.5% had previously known human immunodeficiency virus (HIV) infection, all of whom were under antiretroviral therapy, and no patients had acquired immunodeficiency syndrome (AIDS) criteria. About a quarter of patients were observed only a week after symptom onset. All patients had skin or mucosal lesions and the anogenital region was the most frequent lesion site. There were no statistically significant clinical differences between HIV-positive and negative individuals. Four patients were admitted to the inpatient clinic, two of whom had proctitis with difficult-to-manage anal pain. There were no reported deaths. Our findings suggest the sexual route as a relevant mode of transmission of MPXV and confirm the mostly benign presentation of this disease.

Improvement in circulating endothelial progenitor cells pool after cardiac resynchronization therapy: increasing the list of benefits.

BACKGROUND: Recent studies suggest that circulating endothelial progenitor cells (EPCs) may influence the response to cardiac resynchronization therapy (CRT). The aim of this study was to evaluate the effect of CRT on EPC levels and to assess the impact of EPCs on long-term clinical outcomes. POPULATION AND METHODS: Prospective study of 50 patients submitted to CRT. Two populations of circulating EPCs were quantified previously to CRT implantation: CD34+KDR+ and CD133+KDR+ cells. EPC levels were reassessed 6 months after CRT. Endpoints during the long-term follow-up were all-cause mortality, heart transplantation, and hospitalization for heart failure (HF) management. RESULTS: The proportion of non-responders to CRT was 42% and tended to be higher in patients with an ischemic vs non-ischemic etiology (64% vs 35%, p = 0.098). Patients with ischemic cardiomyopathy (ICM) showed significantly lower CD34+KDR+ EPC levels when compared to non-ischemic dilated cardiomyopathy patients (DCM) (0.0010 ± 0.0007 vs 0.0030 ± 0.0024 cells/100 leukocytes, p = 0.032). There were no significant differences in baseline EPC levels between survivors and non-survivors nor between patients who were rehospitalized for HF management during follow-up or not. At 6-month follow-up, circulating EPC levels were significantly higher than baseline levels (0.0024 ± 0.0023 vs 0.0047 ± 0.0041 CD34+KDR+ cells/100 leukocytes, p = 0.010 and 0.0007 ± 0.0004 vs 0.0016 vs 0.0013 CD133+/KDR+ cells/100 leukocytes, p = 0.007). CONCLUSIONS: Patients with ICM showed significantly lower levels of circulating EPCs when compared to their counterparts. CRT seems to improve the pool of endogenously circulating EPCs and reduced baseline EPC levels seem not to influence long-term outcomes after CRT.

Different danger signals differently impact on microglial proliferation through alterations of ATP release and extracellular metabolism.

Microglia rely on their ability to proliferate in the brain parenchyma to sustain brain innate immunity and participate in the reaction to brain damage. We now studied the influence of different danger signals activating microglia, both internal (typified by glutamate, associated with brain damage) and external (using a bacterial lipopolysaccharide, LPS), on the proliferation of microglia cells. We found that LPS (100 ng/mL) increased, whereas glutamate (0.5 mM) decreased proliferation. Notably, LPS decreased whereas glutamate increased the extracellular levels of ATP. In contrast, LPS increased whereas glutamate decreased the extracellular catabolism of ATP into adenosine through ecto-nucleotidases and ecto-5'-nucleotidase. Finally, apyrase (degrades extracellular ATP) abrogated glutamate-induced inhibition of microglia proliferation; conversely, inhibitors of ecto-nucleotidases (ARL67156 or α,ß-methylene ADP) and adenosine deaminase (degrades extracellular adenosine) abrogated the LPS-induced increase of microglia proliferation, which was blocked by a selective A2A receptor antagonist, SCH58261 (50 nM). Overall, these results highlight the importance of the extracellular purinergic metabolism to format microglia proliferation and influence the spatio-temporal profile of neuroinflammation in different conditions of brain damage.

Role of microglia adenosine A(2A) receptors in retinal and brain neurodegenerative diseases.

Neuroinflammation mediated by microglial cells in the brain has been commonly associated with neurodegenerative diseases. Whether this microglia-mediated neuroinflammation is cause or consequence of neurodegeneration is still a matter of controversy. However, it is unequivocal that chronic neuroinflammation plays a role in disease progression and halting that process represents a potential therapeutic strategy. The neuromodulator adenosine emerges as a promising targeting candidate based on its ability to regulate microglial proliferation, chemotaxis, and reactivity through the activation of its G protein coupled A2A receptor (A2AR). This is in striking agreement with the ability of A2AR blockade to control several brain diseases. Retinal degenerative diseases have been also associated with microglia-mediated neuroinflammation, but the role of A2AR has been scarcely explored. This review aims to compare inflammatory features of Parkinson's and Alzheimer's diseases with glaucoma and diabetic retinopathy, discussing the therapeutic potential of A2AR in these degenerative conditions.