Blood leukocytes from benznidazole-treated indeterminate chagas disease patients display an overall type-1-modulated cytokine profile upon short-term in vitro stimulation with trypanosoma cruzi antigens

ABSTRACT: BACKGROUND: Benznidazole (Bz)-chemotherapy is recommended to prevent Chagas disease progression, despite its limited efficacy during chronic disease. However, the host mechanisms underlying these benefits still remain to be elucidated. METHODS: In this study, we have used short-term whole blood cultures to describe the cytokine profile of Bz-treated Indeterminate Chagas disease patients-(INDt) as compared to untreated patients-(IND). RESULTS: Our findings showed that IND presented increased levels of IL-10+neutrophils, IL-12+ and IL-10+monocytes and IFN-gamma +NK-cells. Moreover, IND showed slight increase of IL- 4+CD4+T-cells and enhanced levels of IL-10+CD8+T-cells and B-cells. Additional analysis of cytokine Low and High producers also highlighted the presence of High cytokine producers within IND, including IL-10 from CD4+ T-cells and IFN-gamma from CD8+ T-cells, as compared to NI. The Bz-treatment lead to an overall cytokine down-regulation in the innate and adaptive compartments, including low levels of IL-12+ and IL-10+neutrophils and monocytes, IFN-gamma +NK-cells, IL-12+, TNF-alpha +, IFN-gamma + and IL-5+CD4+T-cells and IL-10+B-cells, along with basal levels of cytokine-expressing CD8+T-cells in INDt as compared to IND. The in vitro antigen stimulation shifted the cytokine profile toward a type 1-modulated profile, with increased levels of IL-12+ and IL-10+ monocytes, IFN-gamma + and IL-4+NK-cells along with TNF- alpha + and IFN-gamma +CD8+T-cells. Analysis of Low and High cytokine producers, upon in vitro antigen stimulation, further confirm these data. CONCLUSION: Together, our findings showed that the Bz treatment of Indeterminate Chagas' disease patients shifts the cytokine patterns of peripheral blood monocytes, NK-cells and CD8+ Tcells towards a long-lasting Type-1-modulated profile that could be important to the maintenance of a non-deleterious immunological microenvironment.     

Intraoperative assessment of esophagogastric junction distensibility during per oral endoscopic myotomy (POEM) for esophageal motility disorders

Background

Per oral endoscopic myotomy (POEM) is a novel treatment for esophageal motility disorders such as achalasia. To date, the extent of the myotomy has been determined based on the subjective assessment of the endoscopist. We hypothesized that the real-time measurement of esophagogastric junction (EGJ) distensibility using a novel functional lumen-imaging probe would enable objective evaluation of POEM.

Methods

Patients diagnosed with achalasia disorders electively underwent POEM. Using impedance planimetry with a transorally inserted functional lumen-imaging probe (EndoFLIP^®), cross-sectional areas (CSA) and distensibilities at the EGJ were measured intraoperatively immediately before and after the transoral myotomy (n = 4). All patients completed their 6-month follow-up and two patients had repeat distensibility tests at this time. Four healthy volunteers served as a control group.

Results

POEM was successfully performed in all patients (4/4). Premyotomy measurements (40-ml fill mode) showed a median diameter of 6.5 mm (range = 5.2–7.9 mm) at the narrowest location of the EGJ and was 10.1 mm (7.3–13.2 mm) following POEM. CSA increased from 41.5 mm² (20–49 mm²) to 86 mm² (41–137 mm²) at a similar median intraballoon pressure (40.3 vs. 38.6 mmHg). The increased EGJ distensibility (DI, 1.0 vs. 2.4 mm²/mmHg) was comparable to that of healthy volunteers (2.7 mm²/mmHg).

Conclusion

Functional lumen distensibility measures show that POEM can result in an immediate correction of the nonrelaxing lower esophageal sphincter, which appears similar to that of healthy controls. Intraoperative EGJ profiling may be an important tool to objectively guide the needed extent and completeness of the myotomy during POEM.     

Acute renal failure potentiates brain energy dysfunction elicited by methylmalonic acid

The influence of acute renal failure induced by gentamicin administration on the effects of MMA on mitochondrial respiratory chain complexes, citrate synthase, succinate dehydrogenase and creatine kinase activities in cerebral cortex and kidney of young rats were investigated. Animals received one intraperitoneal injection of saline or gentamicin (70 mg/kg). One hour after, the animals received three consecutive subcutaneous injections of MMA (1.67 μmol/g) or saline (11 h interval between injections) and 60 min after the last injection the animals were killed. Acute MMA administration decreased creatine kinase activity in both tissues and increased complexes I–III activity in cerebral cortex. Creatine kinase activity was also inhibited by gentamicin administration. Simultaneous administration of MMA and gentamicin increased the activities of citrate synthase in cerebral cortex and kidney and complexes II–III in cerebral cortex. The other enzyme activities in cerebral cortex and kidney of animals receiving MMA plus gentamicin did not significantly differ from those observed in animals receiving only MMA. Our present data is line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on the Krebs cycle and respiratory chain in brain and peripheral tissues.     

Interaction of child disability and stressful life events in predicting maternal psychological health. Results of an area-based study of very preterm infants at two years corrected age

This study aimed at exploring the relationship between severe neuromotor and/or sensory disability in very preterm infants assessed at 2 years corrected age and their mothers’ psychological health. Data on 581 Italian singletons born at 22–31 weeks of gestation in five Italian regions and their mothers were analyzed. Maternal psychological distress was measured through the General Health Questionnaire short version (GHQ-12). The prevalence of any maternal distress (GHQ scores ≥ 2) and of clinical distress (scores ≥ 5) were 31.3% and 8.1% respectively. At multivariable analysis, we found a statistically significant association between child's disability and mothers’ GHQ scoring ≥5 (OR 3.45, 95% CI 1.07–11.15). Also lower maternal education appeared to increase the likelihood of psychological distress (OR 1.38, 95% CI 1.14–1.66). The impact of child disability was weaker in women who had experienced additional stressful life events since delivery, pointing to the existence of a “ceiling” effect. Maternal psychological assessment and support should be included in follow-up programs targeting very preterm infants.     

The efficacy of speed of processing training for improving processing speed in individuals with multiple sclerosis: a randomized clinical trial

Journal of Neurology - The current study examines the efficacy of speed of processing training (SOPT) to improve processing speed (PS) in individuals with multiple sclerosis (MS). Outcomes included...     

Extracorporeal Life Support Bridge to Ventricular Assist Device: The Double Bridge Strategy

In patients requiring left ventricular assist device (LVAD) support, it can be difficult to ascertain suitability for long‐term mechanical support with LVAD and eventual transplantation. LVAD implantation in a shocked patient is associated with increased morbidity and mortality. Interest is growing in the utilization of extracorporeal life support (ECLS) as a bridge‐to‐bridge support for these critically unwell patients. Here, we reviewed our experience with ECLS double bridging. We hypothesized that ECLS double bridging would stabilize end‐organ dysfunction and reduce ventricular assist device (VAD) implant perioperative mortality. We conducted a retrospective review of prospectively collected data for 58 consecutive patients implanted with a continuous‐flow LVAD between January 2010 and December 2013 at The Alfred Hospital, Melbourne, Victoria, Australia. Twenty‐three patients required ECLS support pre‐LVAD while 35 patients underwent LVAD implantation without an ECLS bridge. Preoperative morbidity in the ECLS bridge group was reflected by increased postoperative intensive care duration, blood loss, blood product use, and postoperative renal failure, but without negative impact upon survival when compared with the no ECLS group. ECLS stabilization improved end‐organ function pre‐VAD implant with significant improvements in hepatic and renal dysfunction. This series demonstrates that the use of ECLS bridge to VAD stabilizes end‐organ dysfunction and reduces VAD implant perioperative mortality from that traditionally reported in these “crash and burn” patients.     

Factors associated with unintended pregnancy in Brazil: cross-sectional results from the Birth in Brazil National Survey, 2011/2012

Background

Unintended pregnancy, a pregnancy that have been either unwanted or mistimed, is a serious public health issue in Brazil. It is reported for more than half of women who gave birth in the country, but the characteristics of women who conceive unintentionally are rarely documented. The aim of this study is to analyse the prevalence and the association between unintended pregnancy and a set of sociodemographic characteristics, individual-level variables and history of obstetric outcomes.

Methods

Birth in Brazil is a cross-sectional study with countrywide representation that interviewed 23,894 women after birth. The information about intendedness of pregnancy was obtained after birth at the hospital and classified into three categories: intended, mistimed or unwanted. Multinomial regression analysis was used to estimate the associations between intendedness of a pregnancy, and sociodemographic and obstetric variables, calculating odds ratios and 95 % confidence intervals. All significant variables in the bivariate analysis were included in the multinomial multivariate model and the final model retaining variables that remained significant at the 5 % level.

Results

Unintended pregnancy was reported by 55.4 % of postpartum women. The following variables maintained positive and significant statistical associations with mistimed pregnancy: maternal age?<?20 years (OR?=?1.89, 95 % CI: 1.68–2.14); brown (OR?=?1.15, 95 % CI: 1.04–1.27) or yellow skin color (OR?=?1.56, 95 % CI: 1.05–2.32); having no partner (OR?=?2.32, 95 % CI: 1.99–2.71); having no paid job (OR?=?1.15, 95 % CI: 1.04–1.27); alcohol abuse with risk of alcoholism (OR?=?1.25, 95 % CI: 1.04–1.50) and having had three or more births (OR?=?2.01, 95 % CI: 1.63–2.47). The same factors were associated with unwanted pregnancy, though the strength of the associations was generally stronger. Women with three or more births were 14 times more likely to have an unwanted pregnancy, and complication in the previous pregnancies and preterm birth were 40 % and 19 % higher, respectively. Previous neonatal death was a protective factor for both mistimed (OR?=?0.61, 95 % CI: 0.44–0.85) and unwanted pregnancy (OR?=?0.44, 95 % CI: 0.34–0.57).

Conclusions

This study confirms findings from previous research about the influence of socioeconomic and individual risk factors on unintended pregnancy. It takes a new approach to the problem by showing the importance of previous neonatal death, preterm birth and complication during pregnancy as risk factors for unintended pregnancy.