Risk-Adjusted Cancer Screening and Prevention (RiskAP): Complementing Screening for Early Disease Detection by a Learning Screening Based on Risk Factors

BackgroundRisk-adjusted cancer screening and prevention is a promising and continuously emerging option for improving cancer prevention. It is driven by increasing knowledge of risk factors and the ability to determine them for individual risk prediction. However, there is a knowledge gap between evidence of increased risk and evidence of the effectiveness and efficiency of clinical preventive interventions based on increased risk. This gap is, in particular, aggravated by the extensive availability of genetic risk factor diagnostics, since the question of appropriate preventive measures immediately arises when an increased risk is identified. However, collecting proof of effective preventive measures, ideally by prospective randomized preventive studies, typically requires very long periods of time, while the knowledge about an increased risk immediately creates a high demand for action.SummaryTherefore, we propose a risk-adjusted prevention concept that is based on the best current evidence making needed and appropriate preventive measures available, and which is constantly evaluated through outcome evaluation, and continuously improved based on these results. We further discuss the structural and procedural requirements as well as legal and socioeconomical aspects relevant for the implementation of this concept.     

九一针疗法背部肌筋膜综合征

背部肌筋膜综合征主要是指因背部肌肉劳损、受凉引起，临床以背痛为主的一组征候群。只要诊断、定位明确，九一针疗法对此具有良好的疗效。     

S-allylcysteine scavenges singlet oxygen and hypochlorous acid and protects LLC-PK(1) cells of potassium dichromate-induced toxicity.

It has been found that S-allylcysteine (SAC), a garlic-derived compound, has in vivo and in vitro antioxidant properties. In addition, it is known that SAC is able to scavenge different reactive oxygen or nitrogen species including superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)), hydroxyl radical (OH()), and peroxynitrite anion (ONOO(-)) although the IC(5O) values for each reactive species has not been calculated and the potential ability of SAC to scavenge singlet oxygen ((1)O(2)) and hypochlorous acid (HOCl) has not been explored. The purposes of this work was (a) to explore the potential ability of SAC to scavenge (1)O(2) and HOCl, (b) to further characterize the O(2)(-), H(2)O(2), OH(), and ONOO(-) scavenging ability of SAC by measuring the IC(50) values using in vitro assays, and (c) to explore the potential ability of SAC to ameliorate the potassium dichromate (K(2)Cr(2)O(7))-induced cytotoxicity in LLC-PK1 cells in which oxidative stress is involved. The scavenging activity was compared against the following reference compounds: N-acetylcysteine for O(2)(-), sodium pyruvate for H(2)O(2), dimethylthiourea for OH(), lipoic acid and glutathione for (1)O(2), lipoic acid for HOCl, and penicillamine for ONOO(-). It was found that SAC was able to scavenge concentration-dependently all the species assayed with the following IC(5O) (mean+/-SEM, mM): O(2)(-) (14.49+/-1.67), H(2)O(2) (68+/-1.92), OH() (0.68+/-0.06), (1)O(2) (1.93+/-0.27), HOCl (2.86+/-0.15), and ONOO(-) (0.80+/-0.05). When the ability of SAC to scavenge these species was compared to those of the reference compounds it was found that the efficacy of SAC (a) to scavenge O(2)(-), H(2)O(2), OH(), and ONOO(-) was lower, (b) to scavenge HOCl was similar, and (c) to scavenge (1)O(2) was higher. In addition, it was found that SAC was able to prevent K(2)Cr(2)O(7)-induced toxicity in LLC-PK1 cells in culture. It was showed for the first time that SAC is able to scavenge (1)O(2) and HOCl and to ameliorate the K(2)Cr(2)O(7)-induced toxicity.     

Role of 5-lipoxygenase pathway in the regulation of RAW 264.7 macrophage proliferation

Arachidonic acid (AA) metabolites control cell proliferation, among other physiologic functions. RAW 264.7 macrophages can metabolise AA through the cyclooxygenase and lipoxygenase (LOX) pathways. We aimed to study the role of AA-metabolites derived from 5-LOX in the control of RAW 264.7 macrophage growth. Our results show that zileuton, a specific 5-LOX inhibitor, and nordihydroguaiaretic acid (NDGA), a non-specific LOX inhibitor, inhibit cell proliferation and [(3)H]-thymidine incorporation in a concentration-dependent fashion. Growth inhibition induced by NDGA can be explained by an apoptotic process, while zileuton does not seem to induce apoptosis. Moreover, these treatments delay the cell cycle, as analysed by flow cytometry. On the other hand, the leukotriene (LT) B(4) receptor antagonist U-75302, the LTD(4) receptor antagonists LY-171883 and MK-571, and the cysteinyl-LT receptor antagonist REV-5901 also inhibit cell proliferation and [(3)H]-thymidine incorporation in a concentration-dependent manner, and delay the RAW 264.7 cell cycle. However, these antagonists did not induce annexin V staining, caspase activation or DNA fragmentation. Furthermore, we demonstrated that exogenous addition of LTB(4) or LTD(4) revert the cell growth inhibition induced by zileuton or the leukotriene receptor antagonists mentioned above. Finally, we observed that LTB(4) and LTD(4), in the absence of growth factors, have pro-proliferative effects on macrophages, and we obtained preliminary evidences that this effect could be through mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. In conclusion, our results show that the interaction between LTB(4) and LTD(4) with its respective receptor is involved in the control of RAW 264.7 macrophage growth.     

HTR1B as a risk profile maker in psychiatric disorders: a review through motivation and memory

Purpose  

Serotonin receptor 1B (HTR1B) is involved in the regulation of the serotonin system, playing different roles in specific areas of the brain. We review the characteristics of the gene coding for HTR1B, its product and the functional role of HTR1B in the neural networks involved in motivation and memory; the central role played by HTR1B in these functions is thoroughly depicted and show HTR1B to be a candidate modulator of the mnemonic and motivationally related symptoms in psychiatric illnesses.     

Percutaneous Absorption of Nicardipine and Ketorolac in Rhesus Monkeys

Vehicle effects on the percutaneous absorption of nicardipine base, nicardipine hydrochloride, ketorolac acid, and ketorolac tromethamine were determined using the rhesus monkey as an in vivo model for human skin penetration. Vehicles investigated included blends of propylene glycol, trimethylene glycol, ethanol, Azone, Tween 20, water, and long-chain fatty acids. Formulations were prepared such that the compound dose, application area, and percentage saturation of the compound in the vehicle were held constant. Variations in absorption of the compounds were therefore attributable to vehicle effects. Each formulation was applied to three monkeys for a period of 24 hr using 10 Hill Top Chambers. Plasma samples were taken at appropriate intervals for 36 to 48 hr. The results indicated that trimethylene glycol and Tween 20 did not enhance absorption of the test compounds despite claims by other investigators. Azone and ethanol provided moderate enhancement of both the rate and the extent of absorption, while long-chain fatty acids in combination with propylene glycol significantly enhanced penetration. In general, higher fluxes were observed with the more lipophilic compounds nicardipine base and ketorolac acid as compared to the hydrochloride and tromethamine salts.     

LTA and FAU-X Iron-Enriched Zeolites: Use for Phosphate Removal from Aqueous Medium

Hydrothermally synthesized Linde type A (LTA) and faujasite X (FAU-X) zeolites are low-cost and environmentally benign inorganic carriers for environmental applications. In this study, (oxy)hydroxides were incorporated onto LTA and FAU-X zeolites to promote the phosphate adsorption. The performance of LTA-Fe and FAU-X-Fe was evaluated through batch adsorption assays. A complete evaluation was performed to recover phosphate from synthetic wastewater. The effect of pH, concentration, equilibrium, and kinetic parameters on phosphate adsorption and its further reuse in sorption–desorption cycles were evaluated. LTA-Fe and FAU-X-Fe are effective for adsorption of phosphate at neutral (e.g., pH 7.0 ± 0.2) and in a broad range of phosphate concentrations. Higher ratios of adsorption capacities were obtained by synthetic zeolites enriched with iron in comparison to their parent forms. The phosphate adsorption occurred through hydrogen bonding and complexation reactions between protonated iron hydroxyl groups and phosphate anions. The phosphate monolayer adsorption was followed by diffusion through the internal pores and 80% of the equilibrium adsorption was reached within 50 min. The LTA-Fe and FAU-X-Fe can be used for phosphate recovery from wastewater treatment plants. The use of LTA-Fe and FAU-X-Fe in a tertiary wastewater treatment stage could allow to reduce the phosphate–phosphorous content, reaching the regulatory levels (equal 1 mg L⁻¹ total phosphorous). The phosphate adsorption using LTA-Fe and FAU-X-Fe does not require pH adjustment, and it is endothermic. The reusability of both iron zeolites is limited, and they can be finally disposed for soil amendment applications.     

Objective assessment of the human visual attentional state

Primary objective

The purpose of this study was to develop an objective way to assess human visual attention using the alpha-band component of the visual-evoked potential (VEP).

Design and methods

Six different attentional conditions were tested: eyes-open, eyes-closed, eyes-closed with backwards number counting, and three rapid-serial visual presentation (RSVP) tasks. Eighteen visually normal, young-adult subjects (ages 21–28 years) were tested binocularly at 1 m for each condition on two separate days. The Diopsys? NOVA-TR system was used to obtain the visual-evoked potential (VEP) and extracted alpha wave and its related power spectrum. Additionally, the Visual Search and Attention Test (VSAT) was administered as a subjective measure of visual attention.

Results

Subjects exhibited significant decreases in power in the alpha band when comparing the eyes-closed with the eyes-open conditions, with power in the eyes-closed condition being, on average, twice as large. The response from the other four conditions did not reflect the differential attentional demands. The ratio of the power in the eyes-closed condition to the eyes-open condition in the lower-alpha frequencies (8–10 Hz) was found to be significantly correlated with the group’s performance on the VSAT, especially the 10-Hz component.

Conclusions

An individual’s ability to attenuate their alpha component during visual processing may be a predictor of their visual attentional state. These findings solidify the role of the VEP alpha subcomponent as an objective electrophysiological correlate of visual attention, which may be useful in the diagnosis and treatment of human visual attention disorders in the future.