Francisella tularensis: possible agent in bioterrorism.

Francisella tularensis, the causative agent of tularemia, is a highly infectious gram-negative coccobacillus. Due to its high infectivity it is of major concern to public health officials as a possible biological weapon. Although accidental exposure can occur through arthropod bites, handling infected animals, or breathing in aerosols, cases are usually isolated and contained. In the event of an intentional exposure such as in a bioterrorist attack, inhalation of aerosols can result in devastating consequences with much causality. Although a vaccine is available, sufficient quantities may not be readily accessible in an actual attack. Therefore, it is very important for both medical professionals and public health officials to be prepared to contain and control the situation should it actually occur.     

Sympathetic nervous system activation and heart failure: Current state of evidence and the pathophysiology in the light of novel biomarkers

Heart failure (HF) is a complex clinical syndrome characterized by the activation of at least several neurohumoral pathways that have a common role in maintaining cardiac output and adequate perfusion pressure of target organs and tissues. The sympathetic nervous system (SNS) is upregulated in HF as evident in dysfunctional baroreceptor and chemoreceptor reflexes, circulating and neuronal catecholamine spillover, attenuated parasympathetic response, and augmented sympathetic outflow to the heart, kidneys and skeletal muscles. When these sympathoexcitatory effects on the cardiovascular system are sustained chronically they initiate the vicious circle of HF progression and become associated with cardiomyocyte apoptosis, maladaptive ventricular and vascular remodeling, arrhythmogenesis, and poor prognosis in patients with HF. These detrimental effects of SNS activity on outcomes in HF warrant adequate diagnostic and treatment modalities. Therefore, this review summarizes basic physiological concepts about the interaction of SNS with the cardiovascular system and highlights key pathophysiological mechanisms of SNS derangement in HF. Finally, special emphasis in this review is placed on the integrative and up-to-date overview of diagnostic modalities such as SNS imaging methods and novel laboratory biomarkers that could aid in the assessment of the degree of SNS activation and provide reliable prognostic information among patients with HF.     

Can Fasting Curb the Metabolic Syndrome Epidemic?

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities that includes hypertension, central obesity, insulin resistance, and atherogenic dyslipidemia. Due to the high prevalence (around 1/3 of the world population) economic burden of MetS, there is a need for new dietary, lifestyle, and therapeutic options. Recently, fasting emerged as a dietary method proposed for controlling metabolic risk factors. Intermittent fasting (IF), or time-restricted feeding (TRF), describes an array of feeding patterns in which calorie intake is restricted to a specific time period. Hence, this review aimed to elucidate the latest data on MetS and explore the viability of simple management options, such as IF and TRF. Preclinical studies have shown how IF/TRF exerts beneficial effects on the gut microbiota, glucose and insulin metabolism, weight and visceral fat, and lipid metabolism. However, the results obtained from human studies are somewhat conflicting, as weight loss was achieved in all studies, whereas in some studies, there was no significant effect on insulin resistance, cholesterol/lipid metabolism, or blood pressure. Nevertheless, as only very few human studies were performed, there is a need for more randomized control trials on larger cohorts of patients with MetS to gather higher-yield evidence to clarify whether IF/TRF are suitable dietary patterns for this population.     

Correlation between uterine artery Doppler and the sFlt-1/PlGF ratio in different phenotypes of placental dysfunction

Objective: To explore correlations between the sFlt-1/PlGF ratio and uterine arteries (UtA) Doppler indexes in placental dysfunction-related disorders (PDD).

Methods: We prospectively included women with a singleton pregnancy with preeclampsia (PE) only (n = 22), preeclampsia with fetal growth restriction (FGR) (n = 32), FGR only (n = 12), or normal pregnancy (n = 29).

Results: In PDDs, significantly positive correlations between the sFlt-1/PlGF ratio and the mean UtA pulsatility (mPI-UtA), as well as the resistance index (mRI-UtA) were found (p = 0.015, p = 0.019, respectively), but not in normal pregnancies. PDD with signs of impaired placentation, evidenced by the increased sFlt-1/PlGF ratio and mPI-UtA, was found in 50.0%, and, by the increased sFlt-1/PlGF ratio and mRI-UtA, in 65.2%. PDD without signs of impaired placentation, evidenced by the increased sFlt-1/PlGF ratio but normal mPI-UtA, was found in 24.2%, and, by the increased sFlt-1/PlGF ratio but normal mRI-UtA, in 7.6%. A substantial proportion of women with signs of impaired placentation were diagnosed with FGR with or without PE.

Conclusion: In PDD, the sFlt-1/PlGF ratio and UtA Doppler indexes increase proportionally. Correlations between the sFlt-1/PlGF ratio and UtA Doppler indexes might help to distinguish between PDDs with and without impaired placentation. However, further studies are needed to explore the correlations in different phenotypes of PDD.     

Short-term effects of a new bicarbonate/lactate-buffered and conventional peritoneal dialysis fluid on peritoneal and systemic inflammation in CAPD patients: a randomized controlled study.

OBJECTIVES: This study was designed to compare the local peritoneal and systemic inflammatory effects of a conventional lactate-based (Lac) peritoneal dialysis (PD) solution and a new biocompatible bicarbonate/lactate-based (Bic/Lac) solution having low concentration of glucose degradation products. METHODS: 26 stable, prevalent PD patients were enrolled in this prospective study. They sequentially underwent 3 months of therapy with the Lac solution and 3 months with the Bic/Lac solution in a randomized order. Flow cytometry was used to measure the expression of inflammatory molecules on peritoneal cells in overnight effluent collected at the end of each study period. RESULTS: 21 patients successfully completed the study. Mean fluorescence intensity of human leukocyte antigen (HLA)-DR and CD14 expression by macrophages were not different between Lac and Bic/Lac. The peritoneal appearance rate of cancer antigen 125 (kU/minute) was 68 +/- 37 with Lac and 133 +/- 66 with Bic/Lac (p < 0.001), and of interleukin (IL)-6 (ng/minute), 0.28 +/- 0.2 with Lac and 0.18 +/- 0.16 with Bic/Lac (p = 0.014). HLA-DR macrophage expression and IL-6 peritoneal appearance rates did not correlate. Serum concentrations with Lac and Bic/Lac were, for IL-6, 3.49 +/- 2.28 and 3.72 +/- 2.46 ng/L (p = 0.17), and for high-sensitivity C-reactive protein, 2.31 +/- 2.98 and 2.71 +/- 3.31 mg/L (p = 0.32) respectively. The concentration of effluent macrophages (x10(6)/L) with Lac was 1.6 +/- 1.6 and with Bic/Lac 2.6 +/- 3.3 (p = 0.07). CONCLUSIONS: We conclude that, although there was a significant reduction in peritoneal IL-6 in patients using Bic/Lac solution, systemic levels of inflammatory markers did not differ between the two solutions and no changes were present in macrophage surface activation markers, suggesting perhaps a less important role of peritoneal macrophages in the intraperitoneal chronic inflammatory process. The number of effluent macrophages tended to be higher in patients using the Bic/Lac solution, possibly contributing to improved intraperitoneal defense.     

Immunolocalization of nestin, mesothelin and epithelial membrane antigen (EMA) in developing and adult serous membranes and mesotheliomas

The spatial and temporal distribution of epithelial membrane antigen (EMA), mesothelin and nestin was immunohistochemically analyzed in developing and adult human serous membranes and mesotheliomas in order to detect possible differences in the course of mesenchymal to epithelial transformation, which is associated with differentiation of mesothelial cells during normal development and tumorigenesis. Pleura and pericardium developing from the visceral mesoderm gradually transform into mesothelial cells and connective tissue. EMA appeared in mesothelium of both serous membranes during the early fetal period, whereas during further development, EMA expression was retained only in the pericardial mesothelium. It increased in both pleural mesothelium and connective tissue. Mesothelin appeared first in pericardial submesothelial cells and later in surface mesothelium, while in pleura it was immediately localized in mesothelium. In adult serous membranes, EMA and mesothelin were predominantly expressed in mesothelium. Nestin never appeared in mesothelium, but in connective tissues and myocardial cells and subsequently decreased during development, apart from in the walls of blood vessels. Mesothelial cells in the two serous membranes developed in two separate developmental pathways. We speculate that submesothelial pericardial and mesothelial pleural cells might belong to a population of stem cells. In epithelioid mesotheliomas, 13% of cells expressed nestin, 39% EMA and 7% mesothelin.