Leishmaniasis treatment—a challenge that remains: a review

Leishmaniasis is a disease caused by flagellate protozoan Leishmania spp. and represents an emergent illness with high morbidity and mortality in the tropics and subtropics. Since the discovery of the first drugs for Leishmaniasis treatment (i.e., pentavalent antimonials), until the current days, the search for substances with antileishmanial activity, without toxic effects, and able to overcome the emergence of drug resistant strains still remains as the current goal. This article reports the development of new chemotherapies through the rational design of new drugs, the use of products derived from microorganisms and plants, and treatments related to immunity as new alternatives for the chemotherapy of leishmaniasis.     

Comparative antiviral (HIV) photoactivity of metalized meso- tetraphenylsulfonated porphyrins

We have carried out the study of the photochemical properties of a series of synthetic meso-tetraphenylsulfonated porphyrins (TPPMS4) bonded to several metal ions such as: Cu(II), Zn(II), Pd(II), Mn(II), Fe(III), Ni(II) and Co(II) for the optimization of their clinical applications as antiviral agents against the human immunodeficiency virus (HIV-1) as well as the study of the in vitro antiviral photoinactivation mechanisms with future application in blood sterilization. A selective inhibition has been determined in the viral growth (HIV-1) when this is irradiated in the presence of the complex TPPFeS4 and TPPMnS4 (photosensitizer-mediated Type I reaction) as well as in the 1O2-mediated (Type II reaction) in the presence of TPPPdS4 and TPPZnS4, remaining cellular viability unaltered in each case.     

Frontline treatment for transplant‐eligible multiple myeloma: A 6474 patients network meta‐analysis

Autologous transplantation continues to be the cornerstone of younger and fit multiple myeloma patients. It is known that frontline induction therapy before transplantation can influence post‐transplant results. Therefore, best frontline treatment for transplant‐eligible patients should be based on best available evidence to guide therapy. Furthermore, until now due to data scarcity, it was not possible to thoroughly compare lenalidomide to other regimens in this setting. We performed a systematic review and network (mixed treatment comparison) meta‐analysis of 21 clinical trial publications, enrolling 6474 patients and comparing 11 different treatment frontline setting regimens regarding survival, response, and safety outcomes. OS analysis showed superiority of CRD (cyclophosphamide‐lenalidomide‐dexamethasone) over TD‐based (thalidomide‐dexamethasone, HR = 0.76,0.62‐0.90), VAD‐based (HR = 0.71,0.52‐0.90), and Z‐Dex (idarubicin‐dexamethasone, HR = 0.37,0.17‐0.76) regimens. Concerning PFS, VTD (bortezomib‐thalidomide‐dexametasone) showed superior results when compared with TD‐based (HR = 0.66,0.51‐0.84), VAD‐based (HR = 0.61,0.46‐0.82), Z‐Dex (HR = 0.42,0.22‐0.78), and high dose dexamethasone (Dex, HR = 0.62,0.41‐0.90) regimens. Bortezomib/thalidomide regimens were not superior to lenalidomide, considering these outcomes. Also, concerning complete and overall response, VTD ranked first among other regimens, showing clear superiority over thalidomide‐only containing protocols. Safety outcome evaluated infectious, cardiac, gastrointestinal, neurological, thrombotic, and hematological grade 3 to 4 adverse events. Risk of thrombotic events was higher with TAD (thalidomide‐doxorubicin‐dexamethasone), neurological with PAD (bortezomib‐doxorubicin‐dexamethasone), infectious with Dex, hematological with Z‐Dex, gastrointestinal with VTD, and cardiac with PAD regimens. Our study endorses current recommendations on combined immunomodulatory drugs and proteasome inhibitors frontline regimens (in triplets) in transplant‐eligible multiple myeloma patients, but also formally demonstrates the favorable performance of lenalidomide in overall and progression‐free survival, when compared with bortezomib/thalidomide protocols.     

Stimulation-induced entrainment of hippocampal network activity: Identifying optimal input frequencies

The hippocampus contains rich oscillatory activity, with continuous ebbs and flows of rhythmic currents that constrain its ability to integrate inputs. During associative learning, the hippocampus must integrate inputs from a range of sources carrying information about events and the contexts in which they occur. Under these circumstances, temporal coordination of activity between sender and receiver is likely essential for successful communication. Previously, it has been shown that the coordination of rhythmic activity between the lateral entorhinal cortex (LEC) and the CA1 region of the hippocampus is tightly correlated with the onset of learning in an associative learning task. We aimed to examine whether rhythmic inputs from the LEC in specific frequency ranges were sufficient to enhance the temporal coordination of activity in downstream CA1. In urethane-anesthetized rats, we applied extracellular low-intensity alternating current stimulation across the length of the LEC. Using this method, we aimed to phase-bias ongoing neuronal activity in LEC at a range of different frequencies (from 1.25 to 55 Hz). Rhythmic stimulation of LEC at both 35 and 50 Hz increased the proportion of CA1 neurons significantly entrained to the phase of the applied stimulation current. A subset of stimulation frequencies modified CA1 spiking relationships to the phase of local ongoing CA1 oscillations, with each stimulation frequency exerting a unique influence upon downstream CA1, often in frequency ranges outside the target stimulation frequency. These results suggest there are optimal frequencies for LEC–CA1 communication, and that different profiles of LEC rhythms likely have distinct outcomes upon CA1 processing.     

Do socioeconomic factors impact atopic dermatitis outcome? A single-center study

Background

Race and socioeconomic status are thought to influence the severity of atopic dermatitis (AD), but findings differ between countries and measures used. The role of social determinants of health versus biologic factors in causing these differences is poorly understood.

Objective

We hypothesized that spatially-derived factors correlate with AD severity and patient-reported outcome (PRO) in a pediatric cohort from Chicago, USA.

Methods

Children with AD and caregivers were enrolled from February 2018 to April 2019 in this single-site cross-sectional study. Severity was self- and physician-assessed using validated measures. Patient addresses were geocoded and linked to census tract IDs. Deprivation index (DI) was calculated using variables of the 2018 American Community Survey.

Results

Among 216 children aged 5–17 years old, 111 (51.4%) lived in urban, 104 (48.1%) suburban, and one (0.5%) in rural areas. Race was self-classified as White in 31.0%, Black 24.5%, other or mixed 25.0%, and Asian 19.4%; 24.5% were Hispanic. Median DI was 0.32 (range 0.03–0.72), with higher scores indicating more deprivation. DI correlated with insurance type, family income, ethnicity, race, and parental education, and weakly with selected PRO T-scores. However, no correlations between any AD severity score and DI, race, ethnicity, income, education, or insurance type were found.

Conclusion

The impact of socioeconomic factors on AD severity in our study population was less pronounced than expected. This could be because of regional differences, including access to high-quality care. The role of access as a deciding factor in the impact of socioeconomic status on AD outcome deserves further investigation.