Documenting asthma severity: do we get it right?

BACKGROUND: The 1997 National Asthma Education and Prevention Program (NAEPP) recommends a severity classification scheme to optimize the use of anti-inflammatory therapy for persistent asthma. Physician documentation of asthma severity is often used as a quality assurance measure. OBJECTIVE: To test the hypothesis that physician documentation of asthma severity is associated with appropriate use of anti-inflammatory therapy. DESIGN/METHODS: Setting: inner-city academic health center. First, we reviewed a consecutive sample of charts of scheduled pediatric patients. Then, we administered a structured parent survey regarding the child's asthma symptoms and current asthma therapy. We used NAEPP guidelines to classify patients' severity of asthma. The main outcome measure was appropriate use of anti-inflammatory therapy. Appropriate therapy was defined as: (1) mild persistent asthmatics using anti-inflammatory therapy, and (2) moderate-severe persistent asthmatics using inhaled steroids. Chart classification of asthma severity was compared with the NAEPP-applied classification. RESULTS: Of 784 charts, 214 (27%) were asthmatic. Of these, 176 (82%) were surveyed. The mean age was 7.4 years; 61% were males. Severity classification was documented in 77% of charts. Chart documentation differed significantly from survey classification for the same patients: (mild intermittent 54% vs. 40%, mild persistent 21% vs. 14%, moderate persistent 24% vs. 36%, severe persistent 1% vs. 10%; all p < .001). Correctly classified patients were more likely to be on appropriate therapy. CONCLUSIONS: Physicians underestimated the severity classification of asthmatic patients. Incorrect classification was associated with inappropriate asthma therapy. These findings have implications for the institution of asthma quality improvement programs.     

Early indices of warm ischemic damage in autotransplanted canine kidneys preserved by simple hypothermic storage

After measurement of normal renal function, dog kidneys (n = 52) were subjected to 3, 15, or 30 min of normothermic warm ischemia (WI). After 24 hr of preservation by simple hypothermic storage (SHS) in a modified Collins solution, autotransplant was done and renal function was again measured beginning at 1 hr. Compared with preharvest values, kidneys with minimal (3 min) WI had significantly decreased clearances of creatinine (Cr) and para-aminohippuric acid (PAH), PAH extraction, absolute and fractional Na reabsorption, Na excretion, and urinary Na concentration; no change in urine flow rate or K excretion; and significantly increased fractional excretion of Na, K, and H2O. Compared with minimal WI, 30-min WI produced further significant decreases in clearances of Cr, PAH, and PAH extraction; and further increases in fractional excretion of Na, K, and H2O. Urine flow was also decreased by about half and urine Na concentration rose significantly. Several parameters were very significantly correlated with the length of WI, but the most reliable index was the fractional reabsorption of Na. When several functional parameters were used together, kidneys with significant (30 min) WI prior to preservation could be identified with a high degree of statistical reliability.     

Anterior Communicating Artery Aneurysm Following Radiation Therapy for Optic Glioma: Report of a Case and Review of the Literature

A 42-year-old female presented with subarachnoid hemorrhage (SAH), presumably from a radiation-induced anterior communicating artery aneurysm. Six years earlier, she had undergone radiation treatment for an optic glioma that was diagnosed based on imaging criteria. The aneurysm was successfully clipped, and the optic glioma was biopsied to verify the diagnosis histologically. Radiation-induced cerebral aneurysms often manifest with a fatal SAH. These aneurysms typically develop in the field of radiation and are diagnosed a mean of 8.52 years after radiation. Rarely, the aneurysm sac thromboses spontaneously. Clipping or coiling of the aneurysm can be an effective treatment.     

Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network

The metabolic network in the yeast Saccharomyces cerevisiae was reconstructed using currently available genomic, biochemical, and physiological information. The metabolic reactions were compartmentalized between the cytosol and the mitochondria, and transport steps between the compartments and the environment were included. A total of 708 structural open reading frames (ORFs) were accounted for in the reconstructed network, corresponding to 1035 metabolic reactions. Further, 140 reactions were included on the basis of biochemical evidence resulting in a genome-scale reconstructed metabolic network containing 1175 metabolic reactions and 584 metabolites. The number of gene functions included in the reconstructed network corresponds to approximately 16% of all characterized ORFs in S. cerevisiae. Using the reconstructed network, the metabolic capabilities of S. cerevisiae were calculated and compared with Escherichia coli. The reconstructed metabolic network is the first comprehensive network for a eukaryotic organism, and it may be used as the basis for in silico analysis of phenotypic functions.     

Synthetic organic hard capsule colouring agents: in vitro effect on human true and pseudo-cholinesterases

Hard capsules are made of pure gelatin and small quantities of additives, including colouring agents permitted for use in food. In this study, the effects of three colouring agents (sunset yellow, quinoline yellow and erythrosine) on true and pseudo-cholinesterases (ChE) are assessed in erythrocytes and plasma, respectively. Results indicated that the synthetic compounds affected both true and pseudo ChE activity. The concentration of sunset yellow which caused 50% inhibition (IC50) of true ChE was about 64% that of pseudo-ChE; for erythrosine, IC50 was approximately the same for both true and pseudo-ChE; and for quinoline yellow, IC50 for true ChE was 25% of pseudo-ChE, although its effect on both true and pseudo-ChE was greater than seen with the other two dyes. Inhibitions of both true and pseudo-ChE were of mixed type (competitive and non-competitive). The enzyme-inhibitor dissociation constant (Ki) indicated that quinoline yellow was most potent and erythrosine was least potent out of the three compounds. Inhibition of both true and pseudo-ChE by each of the three dyes was abolished by dialysis, indicating that the effects were reversible.     

Iron oxide nanoparticles supported on biogenic silica derived from bamboo leaf ash for rhodamine B photodegradation

This research demonstrates the use of biogenic silica derived from bamboo leaf ash as a support for iron oxide nanoparticles. The preparation includes silica extraction from bamboo leaf ash and iron oxide nanoparticle impregnation into the silica gel under hydrothermal conditions, which is followed by calcination at 400 °C for 2 h. The physicochemical characterization includes X-ray diffraction analysis, gas sorption analysis, scanning electron microscopic analysis and transmission electron microscopic analysis. The light absorption capability and the band gap energy of the materials were determined by diffuse-reflectance UV–visible spectrophotometry. The materials obtained by varying the Fe content to 5 and 10% wt. were evaluated in rhodamine B photocatalytic degradation and photooxidation systems. It was found that the materials have a combined hematite and magnetite nanostructure, with the ratio of 9:10, and the particle sizes range from 10 to 40 nm. With a band gap energy of 2.27 eV, the prepared materials produce the successive photocatalytic degradation of rhodamine B. It was clarified that the formation of composite enhances stability and reusability of photocatalyst as shown by the stable initial rate at wide pH range and reuse for 5 cycles. Degradation mechanism is enhanced by the addition of H₂O₂ as an oxidant, and the investigation of the effect of scavengers shows that the degradation rate not only depends on radical formation but also on other species related to the formation of oxidizing agent.     

Immune checkpoints in targeted-immunotherapy of pancreatic cancer: New hope for clinical development

Immunotherapy has been recently considered as a promising alternative for cancer treatment. Indeed, targeting of immune checkpoint (ICP) strategies have shown significant success in human malignancies. However, despite remarkable success of cancer immunotherapy in pancreatic cancer (PCa), many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far. In this process, immunosuppression in the tumor microenvironment (TME) is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method. In this paper, the latest findings on the ICPs, which mediate immunosuppression in the TME have been reviewed. In addition, different approaches for targeting ICPs in the TME of PCa have been discussed. This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa.KEY WORDS: Immune checkpoint, Pancreatic cancer, Tumor microenvironment, Immunotherapy, Clinical development