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Integration of ligand and structure-based virtual screening for the identification of the first dual targeting agent for heat shock protein 90 (Hsp90) and tubulin
No full textWe describe the discovery of a novel indazole-based scaffold that represents the “first-in-class” dual Hsp90/tubulin binding compound. Individual known ligands for both targets shared similar 3′,4′,5′- trimethoxyphenyl cores, and from this it was hypothesized that application of an integrated ligand and structure-based virtual screening (VS) workflow could yield a single scaffold with dual binding affinity. Following validation of the VS protocol, we successfully identified a novel dual inhibitor, sourced from a commercial screening collection of 160 000 compounds.
Perceived effects of organizational downsizing and staff cuts on the stress experience : the role of resources
No full textIn response to global financial pressures, retail companies have introduced measures to reduce costs by cutting staff allocations to individual outlets. On the basis of interview data from four employees of a large retail organization, this paper employs an ideographic case-study approach to illustrate how the processes linking job characteristics to job-related strain and well-being (e.g. appraisal, action regulation, coping, resource utilization) unfold within four individual workers, as they attempt to manage perceived increases in demands resulting from staff cuts. We highlight the importance that these employees place on their own psychological resources (e.g. self-efficacy) and coping mechanisms (e.g. disengagement) in dealing with these changes, as well as how the perceived availability or absence of job resources (e.g. social support, decision authority, organizational justice) influences their ability to cope with increased demands. We use the insights gained from the case studies to illustrate the value of integrating multiple theoretical perspectives towards achieving a nuanced understanding of the intricacies involved in these experiences and to suggest ways in which the coping capacities of individual employees might be increased.
The effectiveness and safety of ginger for pregnancy-induced nausea and vomiting : a systematic review
No full textConclusion: The best available evidence suggests that ginger is a safe and effective treatment for PNV. However, there remains uncertainty regarding the maximum safe dosage of ginger, appropriate duration of treatment, consequences of over-dosage, and potential drug–herb interactions; all of which are important areas for future research.
A combination of bentonite-supported bimetallic Fe/Pd nanoparticles and biodegradation for the remediation of p-chlorophenol in wastewater
No full textImpact of Fe and Ni/Fe nanoparticles on biodegradation of phenol by the strain Bacillus fusiformis (BFN) at various pH values
No full textChitosan stabilized bimetallic Fe/Ni nanoparticles used to remove mixed contaminants-amoxicillin and Cd (II) from aqueous solutions
No full textHow good is the Neurophysiology of Pain Questionnaire? : a Rasch analysis of psychometric properties
No full textThe Neurophysiology of Pain Questionnaire (NPQ) was devised to assess how an individual conceptualizes the biological mechanisms that underpin his or her pain. Despite its widespread use, its psychometric properties have not been comprehensively interrogated. Rasch analysis was undertaken on NPQ data from a convenience sample of 300 spinal pain patients, and test-retest reliability was assessed in a sample of 45 low back pain patients. The NPQ effectively targeted the ability of the sample and had acceptable internal consistency and test-retest reliability. However, some items functioned erratically for persons of differing abilities or were psychometrically redundant. The NPQ was reanalyzed with 7 questionable items excluded, and superior psychometric properties were observed. These findings suggest that the NPQ could be improved, but future prospective studies including qualitative measures are needed. In summary, the NPQ is a useful tool for assessing a patient's conceptualization of the biological mechanisms that underpin his or her pain and for evaluating the effects of cognitive interventions in clinical practice and research. These findings suggest that it has adequate psychometric properties for use with chronic spinal pain patients.
Comparison of the clinical effectiveness of different off-loading devices for the treatment of neuropathic foot ulcers in patients with diabetes : a systematic review and meta-analysis
No full textEffective off-loading is considered to be an important part of the successful clinical management of diabetic foot ulcers. The aim of this systematic review is to investigate the safety and effectiveness of different off-loading devices for the treatment of diabetic foot ulcers. The medical literature was extensively searched from January 1966 to May 2012. Systematic reviews and controlled studies that compared the use of different off-loading devices formed the evidence base. Studies were critically appraised to determine their risk of methodological bias, and data were extracted. Results were pooled using random effects meta-analysis and tested for heterogeneity. When compared with removable devices, non-removable off-loading devices were found, on average, to be more effective at promoting the healing of diabetic foot ulcers (RRp = 1.43; 95% CI 1.11, 1.84; I2 = 66.9%; p = 0.001; k = 10). Analysis, stratified by type of removable device, did not detect a statistically significant difference between non-removable off-loading devices and removable cast walkers; however, on average non-removable off-loading devices performed better than therapeutic shoes at promoting the healing of diabetic foot ulcers (RRp = 1.68; 95% CI 1.09, 2.58; I2 = 71.5%; p = 0.004; k = 6). The two types of non-removable off-loading devices i.e. total contact casts and instant total contact casts (removable cast walker rendered irremovable by securing with bandage or lace), were found to be equally effective (RRp = 1.06; 95% CI 0.88, 1.27; I2 = 3.3%; p = 0.31; k = 2). In conclusion, non-removable off-loading devices regardless of type, are more likely to result in ulcer healing than removable off-loading devices, presumably because patient compliance with off-loading is facilitated.
Changes in endothelial function and depression scores are associated following long-term dietary intervention : a secondary analysis
No full textConclusions: Over time, impairments in FMD were independently associated with increased depression, independent of diet composition, or changes in weight and insulin resistance. This data supports a mechanistic association between depression and endothelial function, which may influence long-term health.
Evidence for circulatory benefits of resveratrol in humans
No full textImpairments of endothelial function, which can be assessed noninvasively by flow-mediated dilation (FMD) of the brachial artery, contribute to the development of cardiovascular disease. Associations between FMD and cognition suggest a vascular component in the loss of cognitive function. Certain vasoactive nutrients that have been shown to improve FMD may also have the potential to enhance cerebral perfusion and cognition. Preclinical studies show that trans-resveratrol can enhance nitric oxide bioavailability, thereby increasing endothelium-dependent vasodilation. We have now shown that acute administration of resveratrol elicits dose-dependent increases of FMD with greater potency than other vasoactive nutrients and that this benefit is sustained following regular consumption. We describe the potential implications of this vasodilator benefit of resveratrol and its role in enhancing cerebrovascular and cognitive functions.