Notes

Searching at night: Perfect the light in several predictors of non-response to psychiatric therapy regarding borderline personality condition.
Brain natriuretic peptide (BNP), often used to evaluate degree of heart failure, has been implicated in fluid dysregulation and inflammation in critically-ill patients. Twenty to 30% of patients with aneurysmal subarachnoid hemorrhage (aSAH) will develop some degree of neurogenic stress cardiomyopathy (NSC) and in turn elevation of BNP levels. We sought to explore the association between BNP levels and development of delayed cerebral ischemia (DCI) in patients with aSAH.

We retrospectively evaluated the records of 149 patients admitted to the Neurological Intensive Care Unit between 2006 and 2015 and enrolled in an existing prospectively maintained aSAH database. Demographic data, treatment and outcomes, and BNP levels at admission and throughout the hospital admission were noted.

Of the 149 patients included in the analysis, 79 developed DCI during their hospital course. We found a statistically significant association between DCI and the highest recorded BNP (OR 1.001, 95% CI-1.001-1.002, p=0.002). The ROC curve analysis for DCI based on BNP showed that the highest BNP level during hospital admission (AUC 0.78) was the strongest predictor of DCI compared to the change in BNP over time (AUC 0.776) or the admission BNP (AUC 0.632).

Our study shows that DCI is associated not only with higher baseline BNP values (admission BNP), but also with the highest BNP level attained during the hospital course and the rapidity of change or increase in BNP over time. Prospective studies are needed to evaluate whether routine measurement of BNP may help identify SAH patients at high risk of DCI.
Our study shows that DCI is associated not only with higher baseline BNP values (admission BNP), but also with the highest BNP level attained during the hospital course and the rapidity of change or increase in BNP over time. Prospective studies are needed to evaluate whether routine measurement of BNP may help identify SAH patients at high risk of DCI.Stroke is a major public health problem with an imperative need for a more effective and tolerated therapy. Neuroprotective therapy may be an effective therapeutic intervention for stroke. The morbidity and mortality of stroke-induced secondary brain injury is mainly caused by neuronal apoptosis, which can be executed in a caspase-dependent or apoptosis inducing factor (AIF)-dependent manner. As apoptosis is an energy-dependent process with a relative time delay, abnormal energy metabolism could be a significant and fundamental pathophysiological basis of stroke. To our knowledge, convincible evidences that AMPK inhibition exerts neuroprotection in cerebral ischemia injury via anti-apoptosis remain to be investigated. PIK-75 clinical trial Accordingly, the aims of this study were to investigate the protective effects of AMPK inhibitor BML-275 on cerebral ischemic/reperfusion (I/R) injury and to elucidate the underlying mechanisms. Cerebral ischemia was induced by transient middle cerebral artery occlusion (tMCAO) in male C57BL/6 mice. The therapeutic effects of BML-275 were evaluated by infarct sizes, neurological scores and the proportion of apoptotic neurons after 24 h of reperfusion. The cell apoptosis markers cyt c and AIF were also evaluated. The results showed that intraperitoneally administration of BML-275 alleviate the cerebral infarction, neurological deficit and neuronal apoptosis induced by MCAO. BML-275 simultaneously induces anti-apoptosis and decreases the expression of cyt c and AIF. This study supports the hypothesis that anti-apoptosis is one of potential neuroprotective strategies for the treatment of stroke.Chenodeoxycholic acid (CDCA) is a natural germination inhibitor for C. difficile spores. In our previous study (J. Med. Chem., 2018, 61, 6759-6778), we identified N-phenyl-3α,7α,12α-trihydroxy-5β-cholan-24-amide as an inhibitor of C. difficile strain R20291 with an IC50 of 1.8 μM. Studies of bile salts on spore germination have shown that chenodeoxycholate, ursodeoxycholate and lithocholate are more potent inhibitors of germination compared to cholate. Given this, we created amide analogs of chenodeoxycholic, deoxycholic, lithocholic and ursodeoxycholic acids using amines identified from our previous studies. We found that chenodeoxy- and deoxycholate derivatives were active with potencies equivalent to those for cholanamides. This indicates that only 2 out of the 3 hydroxyl groups are needed for activity and that the alpha stereochemistry at position 7 is required for inhibition of spore germination.In this work, we have developed an approach for the synthesis of sugar amino acid oligomers based on the glucosamine scaffold. We found that the solid-phase approach was unsuccessful for the preparation of sugar amino acid oligomers and the limitation of the liquid-phase approach revolved around the low solubility of larger oligomers. Nevertheless, this strategy allowed the coupling of alkynylated carbohydrate amino acids with podophyllotoxin-bearing an azide functional group yielding novel podophyllotoxin analogues. Due to their low solubility, the antiproliferative study revealed no anticancer activity of these newly synthesized analogues.A rapid, efficient, and sensitive liquid chromatographic assay hyphenated to fluorometric detector (HPLC-FLD) was developed and validated for the determination of doxorubicin (DXR) and prodigiosin (PDG) in rat plasma. The sample pre-treatment involves a protein precipitation with acetonitrile with satisfying extraction efficiency (98% and 85% for DXR and PDG, respectively). The chromatographic separation was accomplished using stationary phase Agilent Zorbax Eclipse plus-C18 analytical column (250 × 4.6 mm, 5 μm) and gradient eluting mobile phase of ammonium acetate (pH = 3), acetonitrile and methanol with programmed fluorescence detection. As the proposed method has been validated, it was subsequently implemented to evaluate DXR and PDG loaded on novel eco-friendly Casein nano drug delivery system after intravenous injection in healthy rats. A comparative pharmacokinetics' study was carried out in rats for DXR in free form, DXR alone entrapped in the nanomicelle and DXR with PDG entrapped in the nano micelle. After testing the differences in pharmacokinetic parameters of the different formulations using ANOVA, the results showed insignificant differences among the tested parameters. This indicates that the presented nanomicelle delivery system has succeeded to incorporate PDG and DXR in a hydrophilic, safe, and potent formulation. This novel nanomicelle has negligible effect on the distribution and elimination of DXR.Both 5-year-old children and adults infer the structure of a sentence as they are hearing it. Prior work, however, has found that children do not always make use of the same information that adults do to guide these inferences. Specifically, when hearing ambiguous sentences like "You can tickle the frog with the feather," children seem to ignore the aspects of the referential context that adults rely on to resolve the ambiguity-e.g., are there two frogs in the scene, one with a feather and one without? Or is there only one frog to be tickled by using a feather? The present study explored two hypotheses about children's failure to use high-level, top-down context cues to infer the structure of these ambiguous sentences First, children may be less likely to use any top-down cue during comprehension. Second, children may only have difficulties with top-down cues that are unreliable predictors of which syntactic structure is being used. Thus, to disentangle these hypotheses, we conducted a visual world study of adults' and children's ambiguity resolution, manipulating a more reliable top-down cue (the plausibility of the interpretation) and pitting it against a robust bottom-up cue (lexical biases). We find that adults' and children's final interpretations are influenced by both sources of information adults, however, give greater weight to the top-down cue, whereas children primarily rely on the bottom-up cue. Thus, children's tendency to make minimal use of top-down information persists even when this information is highly valid and dominates adult comprehension. We propose that children have a systematic propensity to rely on bottom-up processing to a greater degree than adults, which could reflect differences in the architecture of the adult and child language comprehension systems or differences in processing speed.Wastewater treatment plants (WWTPs) receive sewage water from a variety of sources, including livestock farms, hospitals, industries, and households, that contain antimicrobial resistant bacteria (ARB) and antimicrobial resistant genes (ARGs). Current treatment technologies are unable to completely remove ARB and ARGs, which are eventually released into the aquatic environment. This study focused on the core resistome of urban WWTPs that are persistent through wastewater treatment processes. We adopted the Hiseq-based metagenomic sequencing approach to identify the core resistome, their genetic context, and pathogenic potential of core ARGs in the influent (IN) and effluent (EF) samples of 12 urban WWTPs in South Korea. In this study, the abundance of ARGs ranged from 0.32 to 3.5 copies of ARGs per copy of the 16S rRNA gene, where the IN samples were relatively higher than the EF samples, especially for the macrolide-lincosamide-streptogramin (MLS)- and tetracycline- resistant genes. On the other hand, there te environmental dissemination of ARG by WWTPs.Photochemical properties of dissolved organic matter (DOM) vary widely in natural and engineered water systems due to the different dominant compositions. However, seasonal patterns of DOM photochemical properties in urban rivers remain unclear. In this study, two seasons (wet and dry) of water samples were collected from eleven sites throughout the Pearl River (China) to investigate the spatiotemporal variability of DOM optical and photochemical properties. The optical properties of DOM in the Pearl River were characterized by UV-vis and fluorescence spectroscopies, which showed the substantial decrease in absorption coefficient and fluorescence intensity and increase in absorbence ratio (E2/E3) and specific absorption coefficient (SUVA) from the wet to dry season. The photochemical properties in terms of the apparent quantum yields of 3DOM*, 1O2 and ·OH from DOM (Φ3DOM*, Φ1O2 and Φ·OH, DOM) under illumination also displayed a significant decrease from the wet to the dry season. Spearman's rank correlation analysis revealed the strongest relationships between Φ3DOM*, Φ1O2 and Φ·OH, DOM and the relative abundance of microbial humic-like component (C2%) derived from parallel factor analysis (PARAFAC). Partial least squares regression (PLSR) modelling exhibited an excellent prediction strength for steady-state concentrations of 1O2 ([1O2]ss) and ·OH ([·OH]ss) with adjusted R2 values of 0.85 and 0.91, respectively, by using DOC concentration ([DOC]), optical properties, nitrate and nitrite concentrations as the response variables. In addition, the model identified that the Fmax of humic-like component C4 (Fmax-C4) was the most effective predictor amongst the used response variables. This study provides an approach to describe and predict the seasonal patterns of DOM photochemical properties in urbanized rivers, offering a good understanding of the formation mechanism of reactive species from river DOM.
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