BACKGROUND: Excessive weight and obesity (EwO) are independent factors in the development of heart failure; they lead to a state of myocardiopathy via inflammatory and hormonal mechanisms. If excessively accumulated, epicardial fat favors a proinflammatory state. Ventricular asynchrony is a marker of heart failure progression and has been poorly studied in EwO. The objective was evaluate the relation between epicardial fat, body mass index (BMI) and mechanical synchrony measured by echocardiography, in healthy individuals with EwO. METHODS: We included 55 healthy individuals between the ages of 18 and 35, 17 had a BMI < 25 kg/m2 (30.9%) and 38 had a BMI > 25 kg/m2 (EwO group) (69.09%), anthropometric measurements, transthoracic echocardiogram and synchrony evaluation were obtained. RESULTS: Left atrial volume, telediastolic and telesystolic left ventricular volumes and the baseline volume of the right ventricle were greater in the EwO group (20 mL/m2 vs. 15 mL/m2, p = 0.001; 106 mL vs. 82 mL, p = 0.0149 vs. 32 mL, p = 0.001 and 34 mm vs. 31 mm, p = 0.02, respectively). The Yu index also correlated with epicardial fat, r = 0.53, p < 0.01, whereby the greater the amount of epicardial fat, the greater the dispersion timing of ventricular activation. The systolic synchrony index also correlated with the BMI, p = 0.01. CONCLUSION: Mechanical intraventricular asynchrony is associated to EwO and the amount of epicardial fat; hence, asynchrony may be one more factor leading to heart failure in EwO individuals.
Body Mass Index ; Cardiomyopathies ; Echocardiography ; Heart Failure ; Heart Ventricles ; Obesity* ; Pilot Projects*

OBJECTIVE: The present study sought to analyze the influence of Levetiracetam (LEV) in cognitive performance by identifying the changes produced by LEV in reaction time, in neuropsychological assessment of attention and memory and in absolute theta power in frontal activity. METHODS: Twelve healthy subjects (5 men and 7 women; mean age, 30.08 years, standard deviation, 4.71) were recruited for this study. The neuropsychological tests: Trail Making Test (A and B), Digit Span (direct and indirect numerical orders/working memory); Stroop test (inhibitory control of attention); Tower of London (planning and decision-making) and a quantitative electroencephalography were applied in 2 different days after and before the participants ingested the capsule of placebo or 500 mg LEV. RESULTS: A two-way-ANOVA was implemented to observe the interaction between conditions (placebo or LEV 500 mg) and moments (pre- and post-ingestion of LEV or placebo). The data were analyzed by the SPSS statistical package (p<0.05). For the neuropsychological parameter, the Trail Making Test (A) was the only test that showed significant difference for condition in the task execution time (p=0.026). Regarding the reaction time in the behavioral parameter, an interaction between both factors (p=0.034) was identified through a two-way-ANOVA (condition versus moment). Electrophysiological measures showed a significant interaction for electrodes: F7, F3, and FZ. CONCLUSION: The findings showed that LEV promotes an important cognitive enhancement in the executive functions.
Electrodes ; Electroencephalography ; Executive Function ; Female ; Humans ; Male ; Memory ; Neuropsychological Tests ; Reaction Time ; Stroop Test ; Trail Making Test

PURPOSE: The purpose of this study was to demonstrate the existence of a bimodal survival pattern in metastatic uveal melanoma. Secondary aims were to identify the characteristics and prognostic factors associated with long-term survival and to develop a clinical decision tree. MATERIALS AND METHODS: The medical records of 99 metastatic uveal melanoma patients were retrospectively reviewed. Patients were classified as either short (≤ 12 months) or long-term survivors (> 12 months) based on a graphical interpretation of the survival curve after diagnosis of the first metastatic lesion. Ophthalmic and oncological characteristicswere assessed in both groups. RESULTS: Of the 99 patients, 62 (62.6%) were classified as short-term survivors, and 37 (37.4%) as long-term survivors. The multivariate analysis identified the following predictors of long-term survival: age ≤ 65 years (p=0.012) and unaltered serum lactate dehydrogenase levels (p=0.018); additionally, the size (smaller vs. larger) of the largest liver metastasis showed a trend towards significance (p=0.063). Based on the variables significantly associated with long-term survival, we developed a decision tree to facilitate clinical decision-making. CONCLUSION: The findings of this study demonstrate the existence of a bimodal survival pattern in patients with metastatic uveal melanoma. The presence of certain clinical characteristics at diagnosis of distant disease is associated with long-term survival. A decision tree was developed to facilitate clinical decision-making and to counsel patients about the expected course of disease.
Clinical Decision-Making ; Decision Trees* ; Diagnosis ; Humans ; L-Lactate Dehydrogenase ; Liver ; Medical Records ; Melanoma* ; Multivariate Analysis ; Neoplasm Metastasis ; Retrospective Studies ; Survivors

Background: Photodynamic therapy (PDT) using chloroaluminium phthalocyanine (ClAlPc) and paromomycin sulfate (PM) can be effective against New World Leishmania species involved in cutaneous leishmaniasis (CL). The aim of this study is to assay the skin permeation and the antileishmanial effects of a nanoemulsion (NE) containing both ClAlPc and PM in experimental CL by Leishmania (Viannia) braziliensis.Material and Methods: Cremophor ELP/castor oil-based NEs were prepared by a low-energy method and characterized for their physicochemical parameters. The NEs were used to deliver both ClAlPc and PM to leishmania cells. The in vitro toxicity of NEs were tested in vitro against L. (V.) braziliensis and THP-1 cells. The in vivo toxicity was assessed in non-infected BALB/c mice. Ex-vivo permeation and retention studies using healthy mice skin were also conducted. Finally, the in vivo activity of NE-PM+ClAlPc after PDT was tested in BALB/c mice infected with parasites. Results: NEs are colloidally stable with average droplet diameter of 30 nm, polydispersity index (PDI) below 0.2, and zeta potential near zero. Both promastigotes and intracellular amastigotes treated with NE-PM, NE-ClAlPc and NE-PM+ClAlPc were inhibited at >50%, >95%, >88%, respectively, after PDT with a phototoxic index (PI) >1.2. No skin ClAlPc permeation was observed. In contrast, PM skin permeation was 80-fold higher using PMloaded NE formulation in comparison to aqueous PM solution. Topical treatment with NE formulations showed no signs of local toxicity or genotoxicity. In addition, concentrations of PM between 27.3 - 292.5 μM/25 mg of tissue were detected in different organs. in vivo, the NE-PM+ClAlPc treatment did not reduce skin lesions. Conclusion The Cremophor ELP/castor oil NE formulation increases the permeation of PM through the skin and can be used to co-deliver PM plus ClAlPc for combined PDT protocols.However, the lack of efficacy in the in vivo model evidences that the therapeutical scheme has to be improved.

Background: Photodynamic therapy (PDT) using chloroaluminium phthalocyanine (ClAlPc) and paromomycin sulfate (PM) can be effective against New World Leishmania species involved in cutaneous leishmaniasis (CL). The aim of this study is to assay the skin permeation and the antileishmanial effects of a nanoemulsion (NE) containing both ClAlPc and PM in experimental CL by Leishmania (Viannia) braziliensis.Material and Methods: Cremophor ELP/castor oil-based NEs were prepared by a low-energy method and characterized for their physicochemical parameters. The NEs were used to deliver both ClAlPc and PM to leishmania cells. The in vitro toxicity of NEs were tested in vitro against L. (V.) braziliensis and THP-1 cells. The in vivo toxicity was assessed in non-infected BALB/c mice. Ex-vivo permeation and retention studies using healthy mice skin were also conducted. Finally, the in vivo activity of NE-PM+ClAlPc after PDT was tested in BALB/c mice infected with parasites. Results: NEs are colloidally stable with average droplet diameter of 30 nm, polydispersity index (PDI) below 0.2, and zeta potential near zero. Both promastigotes and intracellular amastigotes treated with NE-PM, NE-ClAlPc and NE-PM+ClAlPc were inhibited at >50%, >95%, >88%, respectively, after PDT with a phototoxic index (PI) >1.2. No skin ClAlPc permeation was observed. In contrast, PM skin permeation was 80-fold higher using PMloaded NE formulation in comparison to aqueous PM solution. Topical treatment with NE formulations showed no signs of local toxicity or genotoxicity. In addition, concentrations of PM between 27.3 - 292.5 μM/25 mg of tissue were detected in different organs. in vivo, the NE-PM+ClAlPc treatment did not reduce skin lesions. Conclusion The Cremophor ELP/castor oil NE formulation increases the permeation of PM through the skin and can be used to co-deliver PM plus ClAlPc for combined PDT protocols.However, the lack of efficacy in the in vivo model evidences that the therapeutical scheme has to be improved.

Obesity is a major worldwide health problem that is related to most chronic diseases, including male infertility. Owing to its wide impact on health, mechanisms underlying obesity-related infertility remain unknown. In this study, we report that mice fed a high-fat diet (HFD) for over 2 months showed reduced fertility rates and increased germ cell apoptosis, seminiferous tubule degeneration, and decreased intratesticular estradiol (E2) and E2-to-testosterone ratio. Interestingly, we also detected a decrease in testicular fatty acid levels, behenic acid (C22:0), and docosahexaenoic acid (DHA, 22:6n-3), which may be related to the production of dysfunctional spermatozoa. Overall, we did not detect any changes in the frequency of seminiferous tubule stages, sperm count, or rate of in vitro capacitation. However, there was an increase in spontaneous and progesterone-induced acrosomal exocytosis (acrosome reaction) in spermatozoa from HFD-fed mice. These data suggest that a decrease in E2 and fatty acid levels influences spermatogenesis and some steps of acrosome biogenesis that will have consequences for fertilization. Thus, our results add new evidence about the adverse effect of obesity in male reproduction and suggest that the acrosomal reaction can also be affected under this condition.

The chronic indeterminate phase of Chagas’ disease is asymptomatic despite positive test results for antibodies specific to Trypanosoma cruzi. CD62P-APC (P-selectin) and PAC-1 FITC (GpIIb/IIIa) may improve diagnosis as biomarkers of platelet activity. Nine asymptomatic seropositive subjects, previously untreated, were selected from a blood bank within a year of Chagas’ disease detection, in addition to a control group of four. All subjects were evaluated by flow cytometry for CD62P, PAC-1 and CD41, and in a complementary study, by Tissue Doppler Echocardiography for isovolumic relaxation times (IVRT) and E/A ratios. The subjects were classified as positive or negative for CD62P and PAC-1 by a cut off obtained from their mean±2SD. For IVRT and E/A ratios, cut offs were obtained from the American Society of Echocardiography and the European Association of Cardiovascular Imaging recommendations. Fisher’s exact test was used for associated findings. Pre-test and post-test probability, sensitivity, specificity, positive and negative predictive values and likelihood ratios were calculated. Abnormalities were expressed as platelet hyperactivity and ventricular dysfunction in CD62P, PAC-1, IVRT and E/A ratios. CD62P appears to have greater sensitivity (0.75) and PAC-1, more accurate specificity (0.75), which may explain thrombotic events in Chagas’ disease. We recommend the use of CD62P and PAC-1 as biomarkers of platelet hyperactivity in patients in the chronic indeterminate phase of Chagas’ disease.

The main protease (M^pro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent M^pro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent M^pro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent M^pro inhibitors with desirable properties have been developed based on available crystal structures of M^pro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^pro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent M^pro inhibitors are also discussed.