An immunoinformatic approach for identification of Trypanosoma cruzi HLA-A2-restricted CD8\u3csup\u3e+\u3c/sup\u3e T cell epitopes

Chagas disease is a major neglected tropical disease caused by persistent chronic infection with the protozoan parasite Trypanosoma cruzi. An estimated 8 million people are infected with T. cruzi, however only 2 drugs are approved for treatment and no vaccines are available. Thus there is an urgent need to develop vaccines and new drugs to prevent and treat Chagas disease. In this work, we identify T cell targets relevant for human infection with T. cruzi. The trans-sialidase (TS) gene family is a large family of homologous genes within the T. cruzi genome encoding over 1,400 members. There are 12 highly conserved TS gene family members which encode enzymatically active TS (functional TS; F-TS), while the remaining TS family genes are less conserved, enzymatically inactive and have been hypothesized to be involved in immune evasion (non-functional TS; NF-TS). We utilized immunoinformatic tools to identify HLA-A2-restricted CD8+ T cell epitopes conserved within F-TS family members and NF-TS gene family members. We also utilized a whole-genome approach to identify T cell epitopes present within genes which have previously been shown to be expressed in life stages relevant for human infection (Non-TS genes). Thirty immunogenic HLA-A2-restricted CD8+ T cell epitopes were identified using IFN-γ ELISPOT assays after vaccination of humanized HLA-A2 transgenic mice with mature dendritic cells pulsed with F-TS, NF-TS, and Non-TS peptide pools. The immunogenic HLA-A2-restricted T cell epitopes identified in this work may serve as potential components of an epitope-based T cell targeted vaccine for Chagas disease

Food insecurity status and its contributing factors in slums’ dwellers of southwest Iran, 2021: a cross-sectional study

Background: One major factor causing food insecurity is believed to be poverty. Approximately 20 million Iranians live in slums with a vulnerable socioeconomic context. The outbreak of COVID-19, on top of the economic sanctions against Iran, has increased this vulnerability and made its inhabitants prone to food insecurity. The current study investigates food insecurity and its associated socioeconomic factors among slum residents of Shiraz, southwest Iran. Methods: Random cluster sampling was used to select the participants in this cross-sectional study. The heads of the households completed the validated Household Food Insecurity Access Scale questionnaire to assess food insecurity. Univariate analysis was utilized to calculate the unadjusted associations between the study variables. Moreover, a multiple logistic regression model was employed to determine the adjusted association of each independent variable with the food insecurity risk. Results: Among the 1227 households, the prevalence of food insecurity was 87.20%, with 53.87% experiencing moderate and 33.33% experiencing severe food insecurity. A significant relationship was observed between socioeconomic status and food insecurity, indicating that people with low socioeconomic status are more prone to food insecurity (P < 0.001). Conclusions: The current study revealed that food insecurity is highly prevalent in slum areas of southwest Iran. The socioeconomic status of households was the most important determinant of food insecurity among them. Noticeably, the coincidence of the COVID-19 pandemic with the economic crisis in Iran has amplified the poverty and food insecurity cycle. Hence, the government should consider equity-based interventions to reduce poverty and its related outcomes on food security. Furthermore, NGOs, charities, and governmental organizations should focus on local community-oriented programs to make basic food baskets available for the most vulnerable households

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

&lt;p&gt;Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.&lt;/p&gt; &lt;p&gt;Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate &#60;60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.&lt;/p&gt; &lt;p&gt;Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.&lt;/p&gt

Efficacy of microneedling plus topical 4 tranexamic acid solution vs 4 hydroquinone in the treatment of melasma: A single-blind randomized clinical trial

Background: There are various treatment modalities for melasma, but none of them are effective on dermal component of melasma. Aims: In this study, we decided to evaluate the efficacy of microneedling plus tranexamic acid in comparison with 4 hydroquinone in the treatment of melasma. Methods: This is a single-blind randomized clinical trial on 70 participants with 14 dropout, and therefore, 60 patients with melasma completed the study. Patients were randomized based on simple randomization in 2 groups of A (microneedling plus topical 4 tranexamic acid, monthly) and B (topical 4 hydroquinone, nightly). Evaluation of mean MASI score, patient and physician assessments was performed at 4th, 8th and12th weeks of the treatment. Statistical analysis was performed by paired t test, chi-square test and Fisher's exact test, respectively. Results: Sixty women (30 patients in each group) were completed the study. Mean MASI score in group A was significantly lower at the end of the treatment (6.84 ± 4.31) than at the baseline (12.89 ± 5.16) (P <.01). Mean MASI score in group B was significantly lower at the end of the treatment (7.16 ± 4.38) than at the baseline (13.56 ± 4.88) (P <.01). There was no statistical difference between 2 groups regarding MASI score, physician and patient assessments during the treatment. Percentage of patient satisfaction was significantly higher than physician satisfaction in both treatment groups (P <.01). Conclusion: In our study, the combination of microneedling with tranexamic acid did not differ from 4 hydroquinone in the treatment of melasma. © 2020 Wiley Periodicals, Inc

Amitriptyline Pharmacokinetics in Experimental Spinal Cord Injury in the Rabbit

Previous studies have demonstrated that pharmacokinetic behavior of several drugs such as paracetamol, theophylline, and aminoglycosides are significantly altered in spinal cord injured patients. No pharmacokinetic study of amitriptyline has been performed in patients and experimental models of spinal cord injury. Pharmacokinetic parameters of amitriptyline in orally treated rabbits subjected to laminectomy and spinal cord injury compared with those underwent laminectomy alone. Among twenty four male rabbits were included in this study, nine of them subjected to spinal cord injury at the 8th thoracic level by knife severance method and six rabbits underwent laminectomy alone (sham group) and nine rabbits treated as control. All received a single oral dose of amitriptyline (20 mg/kg) 24 h after injury. Blood sampling were done at predetermined times to 36 h after drug administration. Amitriptyline concentration in serum samples was determined by high-performance liquid chromatography. Pharmacokinetic parameters including maximum concentration (Cmax), time to reach maximum concentration (Tmax), half life, and the area under the curve to last detectable concentration time point (AUC0-t) were directly determined from the concentration-time curve. Maximum concentration was observed at 6.5 h after administration in sham group with a concentration of 439.6 ng/ml, whereas in SCI group Tmax was at 2.7 h with a concentration of 2763.9 ng/ml. In control group it was 3.3 h and 396 ng/ml, respectively. In SCI group, AUC was 9465.6 ng.h/ml and half life was 6 h and for control group it was 2817.4 ng.h/ml and 6.4 h, respectively. Statistical analysis of data showed that SCI didn't induce significant changes in amitriptyline pharmacokinetic parameters

The co-administration of nicotine/ marijuana and morphine changes pro-inflammatory cytokines in rats

Background: Simultaneous co-consumption of abused substances is common among drug users. This study examined the effects of co-administration of marijuana/ nicotine and morphine on some cytokines in rats. Method: Ninety eight rats were randomly divided into fourteen experimental groups including control (saline 1 ml/kg, i.p.), morphine (1, 3 and 5 mg/kg, i.p.), nicotine (0.5, 2 and 4 mg/kg, i.p.), marijuana (2.5, 5 and 10 mg/kg, i.p.) and the combination groups in which the rats received the combination of either effective or sub-effective doses of nicotine/ marijuana and morphine. Inflammation was induced via formalin injection into the left hind paw of all the control and the treated rats. The serum concentrations of some cytokines (TNF-�, IL-1, and IL-6) were measured by using an enzyme-linked immune-sorbent assay (ELISA) technique. Results: A significant reduction in TNF-�, IL-1, and IL-6 concentration was observed in marijuana, nicotine and morphine treated rats. Also, the co-administration of effective doses of marijuana/ nicotine and morphine caused a significant reduction in cytokines, indicating either an additive or a synergistic effect. Conclusion: The clinical application for the combined use of these substances has not been determined yet and further research is needed to clarify the efficacy, safety and tolerability of these combinations in inflammatory process. © 2020, Kerman University of Medical Sciences. All rights reserved