Mechanisms of long-term cognitive dysfunction of sepsis: from blood-borne leukocytes to glial cells.

Several mechanisms are associated with brain dysfunction during sepsis; one of the most important are activation of microglia and astrocytes. Activation of glial cells induces changes in permeability of the blood-brain barrier, secretion of inflammatory cytokines, and these alterations could induce neuronal dysfunction. Furthermore, blood-borne leukocytes can also reach the brain and participate in inflammatory response.

Oxidative Stress in Dilated Cardiomyopathy Caused by MYBPC3 Mutation.

Cardiomyopathies can result from mutations in genes encoding sarcomere proteins including MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C). However, whether oxidative stress is augmented due to contractile dysfunction and cardiomyocyte damage in MYBPC3-mutated cardiomyopathies has not been elucidated. To determine whether oxidative stress markers were elevated in MYBPC3-mutated cardiomyopathies, a previously characterized 3-month-old mouse model of dilated cardiomyopathy (DCM) expressing a homozygous MYBPC3 mutation (cMyBP-C((t/t))) was used, compared to wild-type (WT) mice.

A Systematic Review and Meta-Analysis of Long-Term Outcomes After Septal Reduction Therapy in Patients With Hypertrophic Cardiomyopathy.

Objectives: The aim of this meta-analysis was to compare long-term outcomes after myectomy and alcohol septal ablation (ASA) in patients with hypertrophic cardiomyopathy (HCM).

Background: Surgical myectomy and ASA are both accepted treatment options for medical therapy-resistant obstructive HCM. Previous meta-analyses only evaluated short-term outcomes.

Left ventricular outflow tract gradient is associated with reduced capillary density in hypertrophic cardiomyopathy irrespective of genotype.

Background: Coronary microvascular dysfunction (CMD) is an important feature of hypertrophic cardiomyopathy (HCM), which contributes negatively to symptoms and long-term outcome. Previous in vivo imaging studies in HCM suggest that left ventricular outflow tract (LVOT) gradient and genetic status are important contributors to CMD. CMD may be caused by reduced capillary density.

New parameters available on Sysmex XE-5000 hematology analyzers contribute to differentiating dengue from leptospirosis and enteric fever.

Introduction: Distinguishing dengue virus infection from other febrile thrombocytopenic illnesses such as leptospirosis or enteric fever is important but difficult, due to the unavailability of reliable diagnostic tests. Sysmex XE-5000 hematology analyzers use fluorescence flow cytometry to quantitate new parameters including cells in the atypical lymphocyte area (AL), high-fluorescent lymphocyte counts (HFLC), immature granulocytes (IG), and immature platelets (IPF). This study aimed to investigate whether these parameters can help to discriminate between the diseases.

Effects of primaquine and chloroquine on oxidative stress parameters in rats.

Primaquine and chloroquine are used for the treatment of malaria; evidence from the literature suggests that these drugs may induce oxidative stress. In this study we investigated the effects of primaquine and chloroquine on oxidative damage and DNA damage in brain, liver and kidney of rats after 7, 14 and 21 days of administration. Our results demonstrated that primaquine causes DNA damage in brain after 7, 14 and 21 days, and in liver after 7 and 14 days.

Universal rescaling of flow curves for yield-stress fluids close to jamming.

The experimental flow curves of four different yield-stress fluids with different interparticle interactions are studied near the jamming concentration. By appropriate scaling with the distance to jamming all rheology data can be collapsed onto master curves below and above jamming that meet in the shear-thinning regime and satisfy the Herschel-Bulkley and Cross equations, respectively. In spite of differing interactions in the different systems, master curves characterized by universal scaling exponents are found for the four systems.

Polymorphisms of the UCP2 Gene Are Associated with Glomerular Filtration Rate in Type 2 Diabetic Patients and with Decreased UCP2 Gene Expression in Human Kidney.

Introduction: Uncoupling protein 2 (UCP2) reduces production of reactive oxygen species (ROS) by mitochondria. ROS overproduction is one of the major contributors to the pathogenesis of chronic diabetic complications, such as diabetic kidney disease (DKD). Thus, deleterious polymorphisms in the UCP2 gene are candidate risk factors for DKD.

Decreased plasma levels of the endothelial protective sphingosine-1-phosphate are associated with dengue-induced plasma leakage.

Background: A transient endothelial hyperpermeability is a hallmark of severe dengue infections. Sphingosine-1-phosphate (S1P) maintains vascular integrity and protects against plasma leakage. We related plasma S1P levels to dengue-induced plasma leakage and studied mechanisms that may underlie the decrease in S1P levels in dengue.

Plasma nitric oxide, endothelin-1, arginase and superoxide dismutase in the plasma and placentae from preeclamptic patients.

The aim of this study was to determine parameters of NO metabolism in plasma and placenta of preeclamptic (PE) patients. It was conducted a case-control study at São José Hospital, Brazil. Thirty-three PE and 33 normotensive pregnant were included in the study.

Validation of the 2014 European Society of Cardiology guidelines risk prediction model for the primary prevention of sudden cardiac death in hypertrophic cardiomyopathy.

Background: The recently released 2014 European Society of Cardiology guidelines of hypertrophic cardiomyopathy (HCM) use a new clinical risk prediction model for sudden cardiac death (SCD), based on the HCM Risk-SCD study. Our study is the first external and independent validation of this new risk prediction model.

Methods And Results: The study population consisted of a consecutive cohort of 706 patients with HCM without prior SCD event, from 2 tertiary referral centers.

Normal free interleukin-18 (IL-18) plasma levels in dengue virus infection and the need to measure both total IL-18 and IL-18 binding protein levels.

Activated monocytes/macrophages and T lymphocytes that produce a cytokine storm are assumed to play a pivotal role in the pathogenesis of dengue. Interleukin-18 (IL-18) is a proinflammatory cytokine that is increased during dengue and known to induce gamma interferon (IFN-γ), which is crucial for dengue immune response. No data are available regarding the balance between IL-18 and its natural inhibitor IL-18 binding protein (IL-18BP) and how they interact within the inflammatory reaction of patients with dengue virus infections.

CD40-CD40 Ligand Pathway is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis.

Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response.

Anxious phenotypes plus environmental stressors are related to brain DNA damage and changes in NMDA receptor subunits and glutamate uptake.

This study aimed at investigating the effects of chronic mild stress on DNA damage, NMDA receptor subunits and glutamate transport levels in the brains of rats with an anxious phenotype, which were selected to represent both the high-freezing (CHF) and low-freezing (CLF) lines. The anxious phenotype induced DNA damage in the hippocampus, amygdala and nucleus accumbens (NAc). CHF rats subjected to chronic stress presented a more pronounced DNA damage in the hippocampus and NAc.

Obesity promotes oxidative stress and exacerbates sepsis-induced brain damage.

Sepsis is a severe clinical syndrome in which a system-wide inflammatory response follows initial attempts to eliminate pathogens. It is not novel that in sepsis the brain is one of the first organs affected which causes an increase in morbidity and mortality and its consequences may be exacerbated when associated with a diagnosis of chronic inflammation, such as in obesity. Thus, the aim of the present study is to evaluate the susceptibility to brain damage after sepsis in obese rats.

Defining phenotypes and disease progression in sarcomeric cardiomyopathies: contemporary role of clinical investigations.

Mutations in cardiac sarcomere protein genes are associated with a variety of clinical phenotypes, including hypertrophic (HCM), dilated (DCM), and restrictive (RCM) cardiomyopathy as well as left ventricular non-compaction, with the overlap of morpho-functional manifestations in individual patients and families. Over time, initial phenotypes may undergo profound changes which determine clinical course and disease progression. Although genetic defects causing HCM and DCM have opposite effects at the myofilament level, a number of downstream maladaptive mechanisms, ranging from microvascular dysfunction and ischaemia to myocardial fibrosis and from diastolic dysfunction to abnormal sympathetic activation and arrhythmogenesis, seem to recur in sarcomeric cardiomyopathies, independent of the presenting phenotype.

Long-term benefit of myectomy and anterior mitral leaflet extension in obstructive hypertrophic cardiomyopathy.

Severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HC) may benefit from surgical myectomy. In patients with enlarged mitral leaflets and mitral regurgitation, myectomy can be combined with anterior mitral leaflet extension (AMLE) to stiffen the midsegment of the leaflet. The aim of this study was to evaluate the long-term results of myectomy combined with AMLE in patients with obstructive HC.

Long-term outcomes after medical and invasive treatment in patients with hypertrophic cardiomyopathy.

Objectives: The aim of this study was to determine the long-term outcomes (all-cause mortality and sudden cardiac death [SCD]) after medical therapy, alcohol septal ablation (ASA), and myectomy in patients with hypertrophic cardiomyopathy (HCM).

Background: Therapy-resistant obstructive HCM can be treated both surgically and percutaneously. But there is no consensus on the long-term effects of ASA, especially on SCD.

Compound heterozygous or homozygous truncating MYBPC3 mutations cause lethal cardiomyopathy with features of noncompaction and septal defects.

Familial hypertrophic cardiomyopathy (HCM) is usually caused by autosomal dominant pathogenic mutations in genes encoding sarcomeric or sarcomere-associated cardiac muscle proteins. The disease mainly affects adults, although young children with severe HCM have also been reported. We describe four unrelated neonates with lethal cardiomyopathy, and performed molecular studies to identify the genetic defect.

Resveratrol prevents social deficits in animal model of autism induced by valproic acid.

Autism spectrum disorders (ASD) involve a complex interplay of both genetic and environmental risk factors, such as prenatal exposure to valproic acid (VPA). Considering the neuroprotective, antioxidant and anti-inflammatory effects of resveratrol (RSV), we investigated the influence of prenatal RSV treatment on social behaviors of a rodent model of autism induced by prenatal exposure to VPA. In the three-chambered apparatus test, the VPA group showed a reduced place preference conditioned by conspecific and no preference between exploring a wire-cage or a rat enclosed inside a wire cage, revealing sociability impairments.

Growth of Tetraselmis suecica in a tubular photobioreactor on wastewater from a fish farm.

Wastewater from a fish farm was remediated in a continuously operated tubular photobioreactor in which Tetraselmis suecica was cultured. The N and P removal efficiencies and the productivity of T. suecica growing on the wastewater were determined.

Impact of adverse left ventricular remodeling on sudden cardiac death in patients with hypertrophic cardiomyopathy.

Background: Adverse left ventricular (LV) remodeling predicts heart failure symptoms and overt LV dysfunction in patients with hypertrophic cardiomyopathy (HCM), but its influence on the occurrence of sudden cardiac death (SCD) is unknown. The aim of this study was to investigate the effect of adverse LV remodeling on SCD risk in patients with HCM.

Hypothesis: Adverse LV remodeling increases SCD in HCM patients.

The role of microglia activation in the development of sepsis-induced long-term cognitive impairment.

Oxidative stress and inflammation is likely to be a major step in the development of sepsis-associated encephalopathy (SAE) and long-term cognitive impairment. To date, it is not known whether brain inflammation and oxidative damage are a direct consequence of systemic inflammation or whether these events are driven by brain resident cells, such as microglia. Therefore, the aim of this study is to evaluate the effect of minocycline on behavioral and neuroinflammatory parameters in rats submitted to sepsis.

Faster cross-bridge detachment and increased tension cost in human hypertrophic cardiomyopathy with the R403Q MYH7 mutation.

The first mutation associated with hypertrophic cardiomyopathy (HCM) is the R403Q mutation in the gene encoding β-myosin heavy chain (β-MyHC). R403Q locates in the globular head of myosin (S1), responsible for interaction with actin, and thus motor function of myosin. Increased cross-bridge relaxation kinetics caused by the R403Q mutation might underlie increased energetic cost of tension generation; however, direct evidence is absent.