Comparison of thermochemistry of aspartame (artificial sweetener) and glucose

We have compared the gas phase thermochemical properties of aspartame (artificial sweetener) and α- and β-glucose. These parameters include metal ion affinities with Li⁺-, Na⁺-, K⁺-, Mg⁺²-, Ca⁺²-, Fe⁺²-, Zn⁺²-ions, and chloride ion affinity by using DFT calculations. For example, for aspartame, the affinity values for the above described metal ions are, respectively, 86.5, 63.2, 44.2, 255.4, 178.4, 235.4, and 300.4, and for β-glucose are 65.2, 47.3 32.9, 212.9, 140.2, 190.1, and 250.0 kcal mol⁻¹, respectively. The study shows differences between the intrinsic chemistry of aspartame and glucose.     

Immunoinformatics Approach to Engineer a Potent Poly-epitope Fusion Protein Vaccine Against Coxiella burnetii

International Journal of Peptide Research and Therapeutics - Coxiella burnetii pathogen, which causes Q fever, is one of the most dangerous pathogens transmitted from the livestock to humans. The...     

Enhanced Optical Transmission Through Metallic Holes Array: Role of TE Polarization in SPP Excitation

Optical transmission through double-layer metallic subwavelength holes array is studied under oblique incidence by split-field finite-difference time-domain method. Both TM and TE polarizations are investigated. It is proved that the transmission peaks can also be observed for TE polarization due to the excitation of surface plasmon polaritons (SPP) through diffraction orders. By changing the incident angle, these transmission peaks follow the SPP wavelength shift. The field profiles, even for the field components not present in the incident field, clearly show the SPP excitation. The mechanism of enhanced transmission will be fully discussed.     

Computational Design of Different Epitope-Based Vaccines Against Salmonella typhi

International Journal of Peptide Research and Therapeutics - Salmonella is a gram-negative bacterium belonging to the Enterobacteriaceae family. One of the major known serotypes of this bacterium...     

Combined and Singular Effects of Dietary PrimaLac® and Potassium Diformate (KDF) on Growth Performance and Some Physiological Parameters of Rainbow Trout (Oncorhynchus mykiss)

The present study was conducted to assess the effects of combined and singular dietary administration of PrimaLac® and potassium diformate (KDF) on growth performance, feed utilization, digestive enzymes activity, and some physiological parameters of rainbow trout (Oncorhynchus mykiss) juvenile. Three hundred sixty rainbow trout juveniles (25 ± 1.8 g) were randomly stocked in 300-L tanks (30 fish/tank), and fed three times daily on a basal diet (control), diets incorporated with 12 g kg⁻¹ KDF (FT₁), 1.5 g kg⁻¹ PrimaLac® (FT₂), and combination of 1.5 g kg⁻¹ probiotic and 12 g kg⁻¹ KDF (FT₃) in triplicates, for 8 weeks. At the end of feeding trial, growth performance, body composition, digestive enzymes, liver enzymes, and biochemical parameters were measured. Our results revealed that combined administration of PrimaLac® and KDF (FT₃) exhibited significantly higher weight gain and specific growth rate (SGR) compared to other groups (P < 0.05). Glucose and cortisol levels showed no significant differences between fish fed different test diets (P > 0.05). The highest lipase, protease and amylase activity were observed in group of fish fed FT₃ followed by FT₂ and FT₁. Besides, the diets FT₂ and FT₃ led to significantly lower of ALP, ALT, and AST compared to control group. The present results indicated that combined administration of PrimaLac® and KDF can be considered as a beneficial feed additive and growth promotor for O. mykiss juvenile.

     

Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson's disease

We reported previously that calpain-mediated Cdk5 activation is critical for mitochondrial toxin-induced dopaminergic death. Here, we report a target that mediates this loss. Prx2, an antioxidant enzyme, binds Cdk5/p35. Prx2 is phosphorylated at T89 in neurons treated with MPP+ and/or MPTP in animals in a calpain/Cdk5/p35-dependent manner. This phosphorylation reduces Prx2 peroxidase activity. Consistent with this, p35-/- neurons show reduced oxidative stress upon MPP+ treatment. Expression of Prx2 and Prx2T89A, but not the phosphorylation mimic Prx2T89E, protects cultured and adult neurons following mitochondrial insult. Finally, downregulation of Prx2 increases oxidative stress and sensitivity to MPP+. We propose a mechanistic model by which mitochondrial toxin leads to calpain-mediated Cdk5 activation, reduced Prx2 activity, and decreased capacity to eliminate ROS. Importantly, increased Prx2 phosphorylation also occurs in nigral neurons from postmortem tissue from Parkinson's disease patients when compared to control, suggesting the relevance of this pathway in the human condition.     

Delayed combinatorial treatment with flavopiridol and minocycline provides longer term protection for neuronal soma but not dendrites following global ischemia

We previously reported that delayed administration of the general cyclin-dependent kinase inhibitor flavopiridol following global ischemia provided transient neuroprotection and improved behavioral performance. However, it failed to provide longer term protection. In the present study, we investigate the ability of delayed flavopiridol in combination with delayed minocycline, another neuroprotectant to provide sustained protection following global ischemia. We report that a delayed combinatorial treatment of flavopiridol and minocycline provides synergistic protection both 2 and 10 weeks following ischemia. However, protected neurons in the hippocampal CA1 are synaptically impaired as assessed by electrophysio logical field potential recordings. This is likely because of the presence of degenerated processes in the CA1 even with combinatorial therapy. This indicates that while we have addressed one important pre-clinical parameter by dramatically improving long-term neuronal survival with delayed combinatorial therapy, the issue of synaptic preservation of protected neurons still exists. These results also highlight the important observation that protection does not always lead to proper function.     

No evidence of the effect of the interventions to combat health care fraud and abuse: a systematic review of literature

Background

Despite the importance of health care fraud and the political, legislative and administrative attentions paid to it, combating fraud remains a challenge to the health systems. We aimed to identify, categorize and assess the effectiveness of the interventions to combat health care fraud and abuse.

Methods

The interventions to combat health care fraud can be categorized as the interventions for ‘prevention’ and ‘detection’ of fraud, and ‘response’ to fraud. We conducted sensitive search strategies on Embase, CINAHL, and PsycINFO from 1975 to 2008, and Medline from 1975–2010, and on relevant professional and organizational websites. Articles assessing the effectiveness of any intervention to combat health care fraud were eligible for inclusion in our review. We considered including the interventional studies with or without a concurrent control group. Two authors assessed the studies for inclusion, and appraised the quality of the included studies. As a limited number of studies were found, we analyzed the data using narrative synthesis.

Findings

The searches retrieved 2229 titles, of which 221 full-text studies were assessed. We found no studies using an RCT design. Only four original articles (from the US and Taiwan) were included: two studies within the detection category, one in the response category, one under the detection and response categories, and no studies under the prevention category. The findings suggest that data-mining may improve fraud detection, and legal interventions as well as investment in anti-fraud activities may reduce fraud.

Discussion

Our analysis shows a lack of evidence of effect of the interventions to combat health care fraud. Further studies using robust research methodologies are required in all aspects of dealing with health care fraud and abuse, assessing the effectiveness and cost-effectiveness of methods to prevent, detect, and respond to fraud in health care.     

Guidelines for Guidelines: Are They Up to the Task? A Comparative Assessment of Clinical Practice Guideline Development Handbooks

Objectives

We conducted a comparative review of clinical practice guideline development handbooks. We aimed to identify the main guideline development tasks, assign weights to the importance of each task using expert opinions and identify the handbooks that provided a comprehensive coverage of the tasks.

Methods

We systematically searched and included handbooks published (in English language) by national, international or professional bodies responsible for evidenced-based guideline development. We reviewed the handbooks to identify the main guideline development tasks and scored each handbook for each task from 0 (the handbook did not mention the task) to 2 (the task suitably addressed and explained), and calculated a weighted score for each handbook. The tasks included in over 75% of the handbooks were considered as ‘necessary’ tasks.

Result

Nineteen guideline development handbooks and twenty seven main tasks were identified. The guideline handbooks’ weighted scores ranged from 100 to 220. Four handbooks scored over 80% of the maximum possible score, developed by the National Institute for Health and Clinical Excellence, Swiss Centre for International Health, Scottish Intercollegiate Guidelines Network and World Health Organization. Necessary tasks were: selecting the guideline topic, determining the guideline scope, identifying relevant existing guidelines, involving the consumers, forming guideline development group,, developing clinical questions, systematic search for evidence, selecting relevant evidence, appraising identifies research evidence, making group decision, grading available evidence, creating recommendations, final stakeholder consultation, guideline implementation strategies, updating recommendations and correcting potential errors.

Discussion

Adequate details for evidence based development of guidelines were still lacking from many handbooks. The tasks relevant to ethical issues and piloting were missing in most handbooks. The findings help decision makers in identifying the necessary tasks for guideline development, provide an updated comparative list of guideline development handbooks, and provide a checklist to assess the comprehensiveness of guideline development processes.     

PhosSA: Fast and accurate phosphorylation site assignment algorithm for mass spectrometry data

Phosphorylation site assignment of high throughput tandem mass spectrometry (LC-MS/MS) data is one of the most common and critical aspects of phosphoproteomics. Correctly assigning phosphorylated residues helps us understand their biological significance. The design of common search algorithms (such as Sequest, Mascot etc.) do not incorporate site assignment; therefore additional algorithms are essential to assign phosphorylation sites for mass spectrometry data. The main contribution of this study is the design and implementation of a linear time and space dynamic programming strategy for phosphorylation site assignment referred to as PhosSA. The proposed algorithm uses summation of peak intensities associated with theoretical spectra as an objective function. Quality control of the assigned sites is achieved using a post-processing redundancy criteria that indicates the signal-to-noise ratio properties of the fragmented spectra. The quality assessment of the algorithm was determined using experimentally generated data sets using synthetic peptides for which phosphorylation sites were known. We report that PhosSA was able to achieve a high degree of accuracy and sensitivity with all the experimentally generated mass spectrometry data sets. The implemented algorithm is shown to be extremely fast and scalable with increasing number of spectra (we report up to 0.5 million spectra/hour on a moderate workstation). The algorithm is designed to accept results from both Sequest and Mascot search engines. An executable is freely available at http://helixweb.nih.gov/ESBL/PhosSA/ for academic research purposes.