Some aspects of the antibacterial mode of action of 4,7-phenanthroline-5,6-quinone (Phanquone)

The aim of this project is to study the mechanism(s) by which Phanquone causes damage and consequently death to the bacterial cell. The investigation (and elucidation) of its mode of action may help in the evaluation of this antimicrobial agent, thus broadening or restricting its practical applications

The genetics of asthma and the promise of genomics-guided drug target discovery

Asthma is an inflammatory airway disease that is estimated to affect 339 million people globally. The symptoms of about 5-10% of patients with asthma are not adequately controlled with current therapy, and little success has been achieved in developing drugs that target the underlying mechanisms of asthma rather than suppressing symptoms. Over the past 3 years, well powered genetic studies of asthma have increased the number of independent asthma-associated genetic loci to 128. In this Series paper, we describe the immense progress in asthma genetics over the past 13 years and link asthma genetic variants to possible drug targets. Further studies are needed to establish the functional significance of gene variants associated with asthma in subgroups of patients and to describe the biological networks within which they function. The genomics-guided discovery of plausible drug targets for asthma could pave the way for the repurposing of existing drugs for asthma and the development of new treatments

Exploring phase control in a quantum dot light-emitting diode:

We report phase control in a periodically driven chaotic nanosystem consisting of a quantum dot light-emitting diode. Such a dynamical system is a class C laser, whence the charactering features are intrinsically chaotic. Phase control relies on the addition of small parametric harmonic perturbations with adjustable phase. Phase control is demonstrated by changing both frequency and strength of the controlling perturbations. Our results show that phase control has two crucial effects on a quantum dot light-emitting diode. First, it can enhance the spiking behavior in either regular or chaotic regimes; second, it is able to turn periodic behavior to chaotic behavior with a minimal perturbation when a resonance condition at half of the driving frequency is achieved

Use of evidence to support healthy public policy: a policy effectiveness-feasibility loop

Public policy plays a key role in improving population health and in the control of diseases, including non-communicable diseases. However, an evidence-based approach to formulating healthy public policy has been difficult to implement, partly on account of barriers that hinder integrated work between researchers and policy-makers. This paper describes a “policy effectiveness–feasibility loop” (PEFL) that brings together epidemiological modelling, local situation analysis and option appraisal to foster collaboration between researchers and policy-makers. Epidemiological modelling explores the determinants of trends in disease and the potential health benefits of modifying them. Situation analysis investigates the current conceptualization of policy, the level of policy awareness and commitment among key stakeholders, and what actually happens in practice, thereby helping to identify policy gaps. Option appraisal integrates epidemiological modelling and situation analysis to investigate the feasibility, costs and likely health benefits of various policy options. The authors illustrate how PEFL was used in a project to inform public policy for the prevention of cardiovascular diseases and diabetes in four parts of the eastern Mediterranean. They conclude that PEFL may offer a useful framework for researchers and policy-makers to successfully work together to generate evidence-based policy, and they encourage further evaluation of this approach

Application of the ESMACS Binding Free Energy Protocol to a Multi‐Binding Site Lactate Dehydogenase A Ligand Dataset

Over the past two decades, the use of fragment‐based lead generation has become a common, mature approach to identify tractable starting points in chemical space for the drug discovery process. This approach naturally involves the study of the binding properties of highly heterogeneous ligands. Such datasets challenge computational techniques to provide comparable binding free energy estimates from different binding modes. The performance of a range of statistically robust ensemble‐based binding free energy calculation protocols, called ESMACS (enhanced sampling of molecular dynamics with approximation of continuum solvent), is evaluated. Ligands designed to target two binding pockets in the lactate dehydogenase, a target protein, which vary in size, charge, and binding mode, are studied. When compared to experimental results, excellent statistical rankings are obtained across this highly diverse set of ligands. In addition, three approaches to account for entropic contributions are investigated: 1) normal mode analysis, 2) weighted solvent accessible surface area (WSAS), and 3) variational entropy. Normal mode analysis and WSAS correlate strongly with each other—although the latter is computationally far cheaper—but do not improve rankings. Variational entropy corrects exaggerated discrimination of ligands bound in different pockets but creates three outliers which reduce the quality of the overall ranking

Transitional cell carcinomas of the urinary bladder. A histopathological study

Objective: To determine the histological grading and muscle invasion in Transitional Cell Carcinomas of the Urinary Bladder; and to evaluate whether any correlation exists between tumour grade and muscle invasion. Method: A Retrospective study of all consecutive cases of Transitional Cell Carcinomas of the Urinary Bladder diagnosed at Aga Khan University Hospital between 1st Jan 1997 and 31st Dec 2000. Results: This study included 495 cases of Transitional Cell Carcinoma of the Urinary Bladder. M: F ratio was 4:1. Ages of patients ranged from 30 years to 87 years. Mean age in males was 59.1 years and in females 58.8 years. Forty four percent cases were Grade II, and 29.5% Grade Ill. None of the Grade I lesions were invasive, 10% Grade II tumours, 61 .41% of Grade Ill and all Grade IV tumours were invasive. Conclusion: There is a definite correlation between advancing tumour grade and muscle invasion

Influence of Eysenckian Personality Traits in Choice of Specialization by Young Omani Doctors.

Objectives:The role of personality in occupational specialty choices has been explored in many parts of the world. To our knowledge, there is a dearth of such studies in the Arab/Islamic population and Oman is no exception. This study aimed to explore the relationship between personality traits and specialty choice among residents of Oman Medical Specialty Board (OMSB). Methods: A cross-sectional study was carried out among Omani resident physicians working under OMSB. The Eysenck Personality Questionnaire–Revised was employed to quantify personality subtypes (e.g., psychoticism, extraversion, and neuroticism). Specialties were categorized as surgical, medical, and diagnostics as per standard of North American medical specialties. A total of 255 residents in 17 medical specialties participated in the study (m = 40.4%; f = 59.6%) of 300 eligible subjects giving a response rate of 85.0%. Results: Respondents who had chosen surgical specialties scored significantly higher on the psychoticism subscale than those who had opted for medical and diagnostic specialties. As for individual specialties, orthopedic respondents had statistically significant higher mean scores on psychoticism and neuroticism compared to radiologists and psychiatrists who scored the lowest in the two personality traits, respectively. Conclusions: This study found statistically significant associations between personality traits and choices of specialty by young Omani doctors. We recommend more detailed studies that examine further psychological and cultural variables that are likely to affect the choices of specializations by young Omani professionals in both medical and non-medical fields

Acetylcholinesterase inhibition ameliorates deficits in motivational drive

<p>Abstract</p> <p>Background</p> <p>Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS) protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes.</p> <p>Methods</p> <p>We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes.</p> <p>Results</p> <p>CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens.</p> <p>Conclusions</p> <p>Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.</p

Correlating structure, strain, and morphology of self-assembled InAs quantum dots on GaAs

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98668/1/ApplPhysLett_98_021903.pd