Insanity as a Defense to the Civil Fraud Penalty

Most neurological diseases are associated with chronic inflammation initiated by the activation of microglia, which produce cytotoxic and inflammatory factors. Signal transducers and activators of transcription (STATs) are potent regulators of gene expression but contribution of particular STAT to inflammatory gene expression and STAT-dependent transcriptional networks underlying brain inflammation need to be identified. In the present study, we investigated the genomic distribution of Stat binding sites and the role of Stats in the gene expression in lipopolysaccharide (LPS)-activated primary microglial cultures. Integration of chromatin immunoprecipitation-promoter microarray data and transcriptome data revealed novel Stat-target genes including Jmjd3, Ccl5, Ezr, Ifih1, Irf7, Uba7, and Pim1. While knockdown of individual Stat had little effect on the expression of tested genes, knockdown of both Stat1 and Stat3 inhibited the expression of Jmjd3 and inflammatory genes. Transcriptional regulation of Jmjd3 by Stat1 and Stat3 is a novel mechanism crucial for launching inflammatory responses in microglia. The effects of Jmjd3 on inflammatory gene expression were independent of its H3K27me3 demethylase activity. Forced expression of constitutively activated Stat1 and Stat3 induced the expression of Jmjd3, inflammation-related genes, and the production of proinflammatory cytokines as potently as lipopolysacharide. Gene set enrichment and gene function analysis revealed categories linked to the inflammatory response in LPS and Stat1C + Stat3C groups. We defined upstream pathways that activate STATs in response to LPS and demonstrated contribution of Tlr4 and Il-6 and interferon-. signaling. Our findings define novel direct transcriptional targets of Stat1 and Stat3 and highlight their contribution to inflammatory gene expression

The use of bio-electrical impedance analysis (BIA) to guide fluid management, resuscitation and deresuscitation in critically ill patients : a bench-to-bedside review

The impact of a positive fluid balance on morbidity and mortality has been well established. However, little is known about how to monitor fluid status and fluid overload. This narrative review summarises the recent literature and discusses the different parameters related to bio-electrical impedance analysis (BIA) and how they might be used to guide fluid management in critically ill patients. Definitions are listed for the different parameters that can be obtained with BIA; these include among others total body water (TBW), intracellular water (ICW), extracellular water (ECW), ECW/ICW ratio and volume excess (VE). BIA allows calculation of body composition and volumes by means of a current going through the body considered as a cylinder. Reproducible measurements can be obtained with tetrapolar electrodes with two current and two detection electrodes placed on hands and feet. Modern devices also apply multiple frequencies, further improving the accuracy and reproducibility of the results. Some pitfalls and conditions are discussed that need to be taken into account for correct BIA interpretation. Although BIA is a simple, noninvasive, rapid, portable, reproducible, and convenient method of measuring body composition and fluid distribution with fewer physical demands than other techniques, it is still unclear whether it is sufficiently accurate for clinical use in critically ill patients. However, the potential clinical applications are numerous. An overview regarding the use of BIA parameters in critically ill patients is given, based on the available literature. BIA seems a promising tool if performed correctly. It is non-invasive and relatively inexpensive and can be performed at bedside, and it does not expose to ionising radiation. Modern devices have very limited between-observer variations, but BIA parameters are population-specific and one must be aware of clinical situations that may interfere with the measurement such as visible oedema, nutritional status, or fluid and salt administration. BIA can help guide fluid management, resuscitation and de-resuscitation. The latter is especially important in patients not progressing spontaneously from the Ebb to the Flow phase of shock. More research is needed in critically ill patients before widespread use of BIA can be suggested in this patient population.The impact of a positive fluid balance on morbidity and mortality has been well established. However, little is known about how to monitor fluid status and fluid overload. This narrative review summarises the recent literature and discusses the different parameters related to bio-electrical impedance analysis (BIA) and how they might be used to guide fluid management in critically ill patients. Definitions are listed for the different parameters that can be obtained with BIA; these include among others total body water (TBW), intracellular water (ICW), extracellular water (ECW), ECW/ICW ratio and volume excess (VE). BIA allows calculation of body composition and volumes by means of a current going through the body considered as a cylinder. Reproducible measurements can be obtained with tetrapolar electrodes with two current and two detection electrodes placed on hands and feet. Modern devices also apply multiple frequencies, further improving the accuracy and reproducibility of the results. Some pitfalls and conditions are discussed that need to be taken into account for correct BIA interpretation. Although BIA is a simple, noninvasive, rapid, portable, reproducible, and convenient method of measuring body composition and fluid distribution with fewer physical demands than other techniques, it is still unclear whether it is sufficiently accurate for clinical use in critically ill patients. However, the potential clinical applications are numerous. An overview regarding the use of BIA parameters in critically ill patients is given, based on the available literature. BIA seems a promising tool if performed correctly. It is non-invasive and relatively inexpensive and can be performed at bedside, and it does not expose to ionising radiation. Modern devices have very limited between-observer variations, but BIA parameters are population-specific and one must be aware of clinical situations that may interfere with the measurement such as visible oedema, nutritional status, or fluid and salt administration. BIA can help guide fluid management, resuscitation and de-resuscitation. The latter is especially important in patients not progressing spontaneously from the Ebb to the Flow phase of shock. More research is needed in critically ill patients before widespread use of BIA can be suggested in this patient population

Antiferroelectric liquid crystals with induced intermediate polar phases and the effects of doping with carbon nanotubes

By mixing a commercial broad-temperature-range nematic liquid crystal mixture with a single-component antiferroelectric chiral smectic exhibiting two different chiral smectic-C-type phases as only mesophases, we have induced three phases which appear in neither of the two components; the paraelectric SmA* phase and the so-called intermediate phases SmC b and SmC c, antiferroelectric and heli- electric in nature, respectively. The generation of the two latter phases in mixtures where one component is an essentially non-chiral nematic is highly unexpected, since these phases are generally linked to high degree of smectic order and/or strong chiral interactions. It is probably made possible through microphase segregation driven by the incompatibility of the fluorinated tail of the smectic compo- nent with the non-fluorinated constituents of the nematic mixture. We also doped the nematic with single-wall carbon nanotubes (SWCNTs) before adding it to the smectic at the same concentration, allowing us to study the effect of SWCNTs on antiferroelectric liquid crystals. Although the final SWCNT concentration was very small (0.002 wt%) the phase sequence was radically altered, the ordin- ary SmC* phase now being present all the way between SmA* and crystallization, while all other variations of smectic-C-type order were suppressed

Usage of the powder metallurgy method for fabrication of titanium implant alloy

In the paper research of the new implant titanium alloy obtained by powder metallurgy method were presented. The Ti15Mo2,8Nb alloy was fabricated from pure alloying component powders. The structure was observed by scanning electron microscope and analyzed by X-ray diffraction. The effect of grinding time of mixtures as well as the size of titanium powder grain on compatibility, compression strength and yield point of sintered alloys was analysed. It was found that grain size has a significant effect on strength properties of the alloy. However, the prolonging of grinding time caused deterioration of compatibility as well as mechanical properties of sinter

Usage of the powder metallurgy method for fabrication of titanium implant alloy

In the paper research of the new implant titanium alloy obtained by powder metallurgy method were presented. The Ti15Mo2,8Nb alloy was fabricated from pure alloying component powders. The structure was observed by scanning electron microscope and analyzed by X-ray diffraction. The effect of grinding time of mixtures as well as the size of titanium powder grain on compatibility, compression strength and yield point of sintered alloys was analysed. It was found that grain size has a significant effect on strength properties of the alloy. However, the prolonging of grinding time caused deterioration of compatibility as well as mechanical properties of sinter

Outcome of Alcohol Septal Ablation in Mildly Symptomatic Patients With Hypertrophic Obstructive Cardiomyopathy: A Long-Term Follow-Up Study Based on the Euro-Alcohol Septal Ablation Registry

Background The long‐term efficacy and safety of alcohol septal ablation ( ASA ) in patients with highly symptomatic hypertrophic obstructive cardiomyopathy has been demonstrated. The aim of this study was to evaluate the long‐term outcomes of mildly symptomatic patients with hypertrophic obstructive cardiomyopathy treated with ASA . Methods and Results We retrospectively evaluated consecutive patients enrolled in the Euro‐ ASA registry (1427 patients) and identified 161 patients (53±13 years; 27% women) who were mildly symptomatic (New York Heart Association [ NYHA ] class II ) pre‐ ASA . The median (interquartile range) follow‐up was 4.8 (1.7–8.5) years. The clinical outcome was assessed and compared with the age‐ and sex‐matched general population. The 30‐day mortality after ASA was 0.6% and the annual all‐cause mortality rate was 1.7%, which was similar to the age‐ and sex‐matched general population ( P =0.62). A total of 141 (88%) patients had resting left ventricular outflow tract gradient at the last clinical checkup ≤30 mm Hg. Obstruction was reduced from 63±32 to 15±19 mm Hg ( P &lt;0.01), and the mean NYHA class decreased from 2.0±0 to 1.3±0.1 ( P &lt;0.01); 69%, 29%, and 2% of patients were in NYHA class I, II , and III at the last clinical checkup, respectively. Conclusions Mildly symptomatic hypertrophic obstructive cardiomyopathy patients treated with ASA had sustained symptomatic and hemodynamic relief with a low risk of developing severe heart failure. Their survival is comparable to the general population. </jats:sec