Spatial covariance analysis of FDG-PET and HMPAO-SPECT for the differential diagnosis of dementia with Lewy bodies and Alzheimer's disease.

We investigated diagnostic characteristics of spatial covariance analysis (SCA) of FDG-PET and HMPAO-SPECT scans in the differential diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), in comparison with visual ratings and region of interest (ROI) analysis. Sixty-seven patients (DLB 29, AD 38) had both HMPAO-SPECT and FDG-PET scans. Spatial covariance patterns were used to separate AD and DLB in an initial derivation group (DLB n=15, AD n=19), before being forward applied to an independent group (DLB n=14, AD n=19).

Demonstration of functional rehabilitation treatment effects in children and young people after severe acquired brain injury.

Purpose: To examine relationships between functional outcomes after pediatric acquired brain injury (ABI) and measures of rehabilitation dose.

Methods: An observational study of children receiving residential neurorehabilitation after severe ABI.

Results: Basic total rehabilitation dose shows a paradoxical relationship to global outcome.

Rats in a levered T-maze task show evidence of time-place discriminations in two different measures.

It is difficult for rats to learn to go to an arm of a T-maze to receive food that is dependent on the time of day, unless the amount of food in each daily session is different. In the same task, rats show evidence of time-place discriminations if they are required to press levers in the arms of the T-maze, but learning is only evident when the first lever press is considered, and not the first arm visited. These data suggest that rats struggle to use time as a discriminative stimulus unless the rewards/events differ in some dimension, or unless the goal locations can be visited prior to making a response.

Testing Modeling Assumptions in the West Africa Ebola Outbreak.

The Ebola virus in West Africa has infected almost 30,000 and killed over 11,000 people. Recent models of Ebola Virus Disease (EVD) have often made assumptions about how the disease spreads, such as uniform transmissibility and homogeneous mixing within a population. In this paper, we test whether these assumptions are necessarily correct, and offer simple solutions that may improve disease model accuracy.

The effects of prolonged administration of norepinephrine reuptake inhibitors on long-term potentiation in dentate gyrus, and on tests of spatial and object recognition memory in rats.

Phasic norepinephrine (NE) release events are involved in arousal, novelty detection and in plasticity processes underlying learning and memory in mammalian systems. Although the effects of phasic NE release events on plasticity and memory are prevalently documented, it is less understood what effects chronic NE reuptake inhibition and sustained increases in noradrenergic tone, might have on plasticity and cognitive processes in rodent models of learning and memory. This study investigates the effects of chronic NE reuptake inhibition on hippocampal plasticity and memory in rats.

In a daily time-place learning task, time is only used as a discriminative stimulus if each daily session is associated with a distinct spatial location.

It is difficult for rats to acquire daily time-place (TP) learning tasks. One theory suggests that rats do not use time of day as a stimulus signaling a specific response. In the present study, we tested rats' ability to use time of day as a discriminative stimulus.

The effects of bilateral lesions to the dorsal tegmental nucleus on spatial learning in rats.

The head-direction (HD) signal is believed to originate in the dorsal tegmental nucleus (DTN) and lesions to this structure have been shown to disrupt HD cell firing in other areas along the HD cell circuit. To investigate the role of the DTN in spatial navigation, rats with bilateral, electrolytic (Experiment 1), or neurotoxic (Experiment 2) lesions to the DTN were compared with sham controls on two tasks that differed in difficulty and could be solved using directional heading. Rats were first trained on a direction problem in a water T maze where they learned to travel either east or west from two locations in the experimental room.

Structural trends in ten-vertex endohedral clusters, M@E(10) and the synthesis of a new member of the family, [Fe@Sn10]3-.

The synthesis of a new endohedral ten-vertex Zintl ion cluster, [Fe@Sn10](3-), isoelectronic with [Fe@Ge10](3-), is reported. In an attempt to place this new cluster within the context of the known structural chemistry of the M@E10 family (M = transition metal, E = main group element), we have carried out a detailed electronic structure analysis of the different structural types: viz bicapped square antiprismatic ([Ni@Pb10](2-), [Zn@In10](8-)), tetra-capped trigonal prismatic ([Ni@In10](10-)) and the remarkable pentagonal prismatic [Fe@Ge10](3-) and [Co@Ge10](3-). We establish that the structural trends can be interpreted in terms of a continuum of effective electron counts at the E10 cage, ranging from electron deficient (<4n + 2) in [Ni@In10](10-) to highly electron rich (>4n + 2) in [Fe@Ge10](3-).

What is the role of informal healthcare providers in developing countries? A systematic review.

Informal health care providers (IPs) comprise a significant component of health systems in developing nations. Yet little is known about the most basic characteristics of performance, cost, quality, utilization, and size of this sector. To address this gap we conducted a comprehensive literature review on the informal health care sector in developing countries.

Chitosan microparticles for the controlled delivery of fluoride.

Objectives: To manufacture and characterise chitosan/fluoride microparticles prepared by spray drying and assess their utility as controlled release vehicles for fluoride.

Methods: Microparticles were manufactured from dispersions containing 1.0% and 2.

Formulation and characterization of a captopril ethyl ester drug-in-adhesive-type patch for percutaneous absorption.

Background: The ethyl ester of captopril has been shown to exhibit enhanced permeation across human skin compared to the parent drug. A drug-in-adhesive patch formulation of a captopril ethyl ester was therefore developed for optimum drug release.

Method: A wide range of transdermal patches were prepared using two commercially available bioadhesive polymers.

Metabolism of captopril carboxyl ester derivatives for percutaneous absorption.

Objectives: To determine the metabolism of captopril n-carboxyl derivatives and how this may impact on their use as transdermal prodrugs. The pharmacological activity of the ester derivatives was also characterised in order to compare the angiotensin converting enzyme inhibitory potency of the derivatives compared with the parent drug, captopril.

Methods: The metabolism rates of the ester derivatives were determined in vitro (using porcine liver esterase and porcine ear skin) and in silico (using molecular modelling to investigate the potential to predict metabolism).

Renin-angiotensin-system gene polymorphisms and depression.

Given the abundance of the renin-angiotensin system (RAS) components in the brain, their importance in behavior and cognition, and the data that implicates them in the etiology and treatment of depression, it is possible that those RAS gene polymorphisms associated with increased RAS activity may also be associated with depression. The frequencies of common polymorphisms of genes encoding for components of the RAS, namely angiotensinogen (M235T), angiotensin converting enzyme (ACE) (insertion, I; deletion, D), angiotensin receptor type I (A1166C), and angiotensin receptor type II (C3123A) were determined in DNA extracted from buccal cells from a Lebanese population of 132 depressed patients and their first-degree relative case-controls. The angiotensin receptor type 1 (A1166C) CC genotype was significantly associated with depression (p=0.

A potential anti-implantation and spermicidal strategy: putative derivatives of nonoxynol-9 and anti-inflammatory agents and their spermicidal activity.

Objectives: We report the synthesis of novel ester derivatives of nonoxynol-9, an approved spermicidal agent, using the non-steroidal inflammatory drugs (NSAIDs) ibuprofen and indomethacin. Indomethacin has previously been shown to inhibit the implantation of the fertilised ovum into the uterus wall of pregnant rats. It is proposed that nonoxynol-9, in combination with a non-selective NSAID may exhibit both anti-implantation and spermicidal properties.

An in vitro assessment of bioadhesive zinc/carbomer complexes for antimicrobial therapy within the oral cavity.

The effectiveness of antimicrobial agents in the oral cavity is limited by their retention at the site of action. In this work the antimicrobial cation zinc was complexed with the bioadhesive agent Carbopol 971P, in order to allow an extended antimicrobial effect. Zinc ions were shown to form stable complexes with the polymer, and were not released into distilled water.

Design, synthesis and characterization of captopril prodrugs for enhanced percutaneous absorption.

Most drugs are designed primarily for oral administration, but the activity and stability profiles desirable for this route often make them unsuitable for transdermal delivery. We were therefore interested in designing analogues of captopril, a model drug with poor percutaneous penetration, for which the sustained steady-state blood plasma level associated with transdermal delivery (and which is unattainable orally) would be particularly beneficial. Quantitative structure-permeability relationships (QSPRs) predicted that ester and thiol prodrug derivatives of captopril would have lower maximal transdermal flux (J(m)) than the parent drug, since the increases in permeability coefficient (k(p)) of prodrugs would be outweighed by the reductions in aqueous solubility.

Gastric and thymic assay of acute oral treatment of rats with nitric oxide esters of ibuprofen or indomethacin.

Two common non-steroidal anti-inflammatory drugs (NSAIDs) and their nitric oxide (NO) adducts were evaluated for effects on stomach and thymus. Following 4-h duration (acute) oral dosing of fasted male Wistar rats, 1.33 x 10(-4)mol/kg of ibuprofen caused significant visual irritation score and microscopic thinning, although an ulceration assay proved insensitive.

Synthesis and spermicidal activity of a putative nitric oxide-releasing derivative of nonoxynol-9.

Objectives: We report on the synthesis of a potential nitric oxide releasing derivative of nonoxynol-9 (N9).

Methods: This derivative was synthesised via AgNO3 mediated nitroxylation of a chloride derivative of a N9 which itself was synthesised by thionyl chloride mediated chlorination of N9. In an initial in vitro study the spermicidal efficacy of the nitric oxide derivative and the parent compound (N9) was examined using boar spermatozoa.

A novel anti-oxidant and anti-cancer strategy: a peptoid anti-inflammatory drug conjugate with SOD mimic activity.

Activation of reactive oxygen and nitrogen species (RONS) by redox-active metal ions has been proposed to contribute to oxidative damage in inflamed tissues. Here, we report a dual-function anti-oxidant conjugate comprising an anti-inflammatory agent (5-aminosalicylic acid) and a chelator with potential as a superoxide dismutase mimic. The conjugate ethylenediaminetetraacetic acid bis-(5-aminosalicylic acid methyl ester) [EBAME] chelates Cu(II) ions in a 1:1 ratio, as assessed spectrophotometrically using Job's method.