Role of channel activation in cognitive enhancement mediated by alpha7 nicotinic acetylcholine receptors.

Background And Purpose: Several agonists of the alpha7 nicotinic acetylcholine receptor (nAChR) have been developed for treatment of cognitive deficits. However, agonist efficacy in vivo is difficult to reconcile with rapid alpha7 nAChR desensitization in vitro; and furthermore, the correlation between in vitro receptor efficacy and in vivo behavioural efficacy is not well delineated. The possibility that agonists of this receptor actually function in vivo as inhibitors via desensitization has not been finally resolved.

The ecology and impact of chytridiomycosis: an emerging disease of amphibians.

Emerging infectious diseases are increasingly recognized as key threats to wildlife. Batrachochytrium dendrobatidis (Bd), the causative agent of chytridiomycosis, has been implicated in widespread amphibian declines and is currently the largest infectious disease threat to biodiversity. Here, we review the causes of Bd emergence, its impact on amphibian populations and the ecology of Bd transmission.

Defining ductal anatomy using CT cholangiography in a patient with gallbladder duplication.

Duplication of the gallbladder is a rare congenital abnormality. Pre-operative diagnosis is challenging and, with the almost universal use of laparoscopic cholecystectomy, the scope for missing the second intrahepatic gallbladder is increased. Here we report the use of CT cholangiography to define ductal anatomy successfully in a patient with gallbladder duplication.

Iliotibial band syndrome: an examination of the evidence behind a number of treatment options.

Iliotibial band (ITB) syndrome (ITBS) is a common cause of distal lateral thigh pain in athletes. Treatment often focuses on stretching the ITB and treating local inflammation at the lateral femoral condyle (LFC). We examine the area's anatomical and biomechanical properties.

A genome scan in affected sib-pairs with familial vesicoureteral reflux identifies a locus on chromosome 5.

The basis for vesicoureteral reflux (VUR) is considered to be primarily genetic, with a 30-50% incidence of VUR in first-degree relatives of patients. The search for the causative gene or genes has been elusive, likely because of VUR being genetically heterogeneous with complex inheritance patterns. In this study, a genome-wide analysis of VUR with high-density single nucleotide polymorphisms was conducted with the aim of identifying susceptibility loci for VUR in 98 families with two or more affected children.

Evaluation of alpha7 nicotinic acetylcholine receptor agonists and positive allosteric modulators using the parallel oocyte electrophysiology test station.

Neuronal acetylcholine receptors (nAChRs) of the alpha7 subtype are ligand-gated ion channels that are widely distributed throughout the central nervous system and considered as attractive targets for the treatment of various neuropsychiatric and neurodegenerative diseases. Both agonists and positive allosteric modulators (PAMs) are being developed as means to enhance the function of alpha7 nAChRs. The in vitro characterization of alpha7 ligands, including agonists and PAMs, relies on multiple technologies, but only electrophysiological measurements assess the channel activity directly.

Environmental health risks and vulnerability in post-conflict regions.

The importance of environmental factors during and after conflict has often not received adequate attention, and is of particular importance when assessing those groups most vulnerable to changing conditions. Post-war reconstruction and aid policies must take note of which groups are most susceptible to environmental health risks, and how the conflict itself often created new vulnerabilities through deliberate destruction of the natural and built environments. The environmental security and public health fields have a good deal to offer in understanding these dynamics, and must work more closely together in the future to identify potential vulnerabilities in advance of conflicts and disasters.

Percutaneous transhepatic insertion of self-expanding short metal stents for biliary obstruction before resection of pancreatic or duodenal malignancy proves to be safe and effective.

Background: The British Society of Gastroenterology guidelines for the management of malignant obstructive jaundice state: "If a stent is placed prior to surgery, this should be of the plastic type and it should be placed endoscopically. Self-expanding metal stents should not be inserted in patients who are likely to proceed to resection." In 2003, a small series of complications after endoscopic intervention caused a change in the authors' practice.

Introduction of a day-case laparoscopic cholecystectomy service in the UK: a critical analysis of factors influencing same-day discharge and contact with primary care providers.

Introduction: The objective of this study was to determine the safety and acceptability of the implementation of a day-case laparoscopic cholecystectomy (LC) service in a large UK teaching hospital, and analyse factors influencing contact with primary care providers. Wide-spread introduction of day-case LC in the UK is a major target of healthcare providers. However, few centres have reported their experience.

Stimulation of dopamine release by nicotinic acetylcholine receptor ligands in rat brain slices correlates with the profile of high, but not low, sensitivity alpha4beta2 subunit combination.

alpha4beta2 neuronal nicotinic receptors (nAChRs) can exist in high and low sensitivity states possibly due to distinct stoichiometries during subunit assembly: (alpha4)(2)(beta2)(3) pentamer (high sensitivity, HS) and (alpha4)(3)(beta2)(2) pentamer (low sensitivity, LS). To determine if there is a linkage between HS or LS states and receptor-mediated responses in brain, we profiled several clinically studied alpha4beta2* nAChR agonists for the displacement of radioligand binding to alpha4beta2 [(3)H]-cytisine sites in rat brain membranes, effects on stimulation of [(3)H]-dopamine release from slices of rat prefrontal cortex and striatum, and activation of HS and LS human alpha4beta2 nAChRs expressed in Xenopus laevis oocytes. Binding affinities (pK(i)) and potency (pEC(50)) values for [(3)H]-dopamine release closely correlated with a rank order: varenicline>(-)-nicotine>AZD3480>dianicline congruent with ABT-089.

Selectivity of ABT-089 for alpha4beta2* and alpha6beta2* nicotinic acetylcholine receptors in brain.

Numerous pharmaceutical efforts have targeted neuronal nicotinic receptors (nAChRs) for amelioration of cognitive deficits. While alpha4beta2 and alpha7 are the more prominent nAChR in brain, other heteromeric nAChR can have important impact on agonist pharmacology. ABT-089 is a pioneer nAChR agonist found to enhance cognitive function with an exceptionally low incidence of adverse effects.

Quality counts: new parameters in blood cell counting.

Recently several parameters have been introduced to the complete blood count such as nucleated red blood cells, immature granulocytes; immature reticulocyte fraction, immature platelet fraction and red cell fragments as well as new parameters for detection of functional iron deficiency. Leucocyte positional parameters, which may diagnose specific diseases (e.g.

Discovery of 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744) as a novel positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor.

The discovery of a series of pyrrole-sulfonamides as positive allosteric modulators (PAM) of alpha7 nAChRs is described. Optimization of this series led to the identification of 19 (A-867744), a novel type II PAM with good potency and selectivity. Compound 19 showed acceptable pharmacokinetic profile across species and brain levels sufficient to modulate alpha7 nAChRs.

In vitro pharmacological characterization of a novel allosteric modulator of alpha 7 neuronal acetylcholine receptor, 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744), exhibiting unique pharmacological profile.

Targeting alpha7 neuronal acetylcholine receptors (nAChRs) with selective agonists and positive allosteric modulators (PAMs) is considered a therapeutic approach for managing cognitive deficits in schizophrenia and Alzheimer's disease. In this study, we describe a novel type II alpha7 PAM, 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744), that exhibits a unique pharmacological profile. In oocytes expressing alpha7 nAChRs, A-867744 potentiated acetylcholine (ACh)-evoked currents, with an EC(50) value of approximately 1 microM.

Skin microbes on frogs prevent morbidity and mortality caused by a lethal skin fungus.

Emerging infectious diseases threaten human and wildlife populations. Altered ecological interactions between mutualistic microbes and hosts can result in disease, but an understanding of interactions between host, microbes and disease-causing organisms may lead to management strategies to affect disease outcomes. Many amphibian species in relatively pristine habitats are experiencing dramatic population declines and extinctions due to the skin disease chytridiomycosis, which is caused by the chytrid fungus Batrachochytrium dendrobatidis.

'It looks good on paper': transitions of care between midwives and child and family health nurses in New South Wales.

Background: The way in which women and their babies transition from maternity services to the care of child and family health nurses differs across Australia. The aim of the study was to understand the transition of care from one service to another and how to promote collaboration in the first few weeks after the birth.

Method: A descriptive study was undertaken.

Confronting health disparities: Latin American social medicine in Venezuela.

Objectives: We explored the emergence and effectiveness of Venezuela's Misión Barrio Adentro, "Inside the Neighborhood Mission," a program designed to improve access to health care among underserved residents of the country, hoping to draw lessons to apply to future attempts to address acute health disparities.

Methods: We conducted our study in 3 capital-region neighborhoods, 2 small cities, and 2 rural areas, combining systematic observations with interviews of 221 residents, 41 health professionals, and 28 government officials. We surveyed 177 female and 91 male heads of household.

Systematic review of minimally invasive pancreatic resection.

Background: Pancreatic resection is associated with a significant morbidity. Efforts to reduce hospital stay and enhance recovery have seen the introduction of minimally invasive surgical techniques. This article reviews the current published literature on the safety and efficacy of minimally invasive surgery of the pancreas.

Prognostic molecular markers in cholangiocarcinoma: a systematic review.

The worldwide incidence of cholangiocarcinoma (CC) is steadily rising, with the incidence in United Kingdom (UK) now exceeding 1000 cases per year. It is an aggressive malignancy typified by unresponsiveness to the existing chemotherapy and radiotherapy regimes in the vast majority of cases. Surgery offers the only hope of a cure, though post-operative disease recurrence is common, with 5-year survival rates of less than 25% following resection.

Rehabilitation and Disability Services' Quality Projects: A Comparison against the Australian Council on Healthcare Standards' Clinical Criteria.

The Australian Council on Healthcare Standards (ACHS) Evaluation, Quality and Improvement (EQuIP 4) standards provide a useful clinical and corporate framework for the analysis of quality projects by both health and disability services. Two ACHS EQuIP 4 clinical standards were used to compare quality projects conducted by community-based and on-site rehabilitation and disability services, as generated by a commercial database. Reliable information is a major asset for healthcare organisations, and the use of the ACHS clinical standards to interpret quality project data can overcome a lack of conceptual framework to interpret data.

Spatial dynamics of lyme disease: a review.

Lyme disease (LD), the most frequently reported vector-borne disease in the United States, requires that humans, infected vector ticks, and infected hosts all occur in close spatial proximity. Understanding the spatial dynamics of LD requires an understanding of the spatial determinants of each of these organisms. We review the literature on spatial patterns and environmental correlates of human cases of LD and the vector ticks, Ixodes scapularis in the northeastern and midwestern United States and Ixodes pacificus in the western United States.

Effect of temperature on host response to Batrachochytrium dendrobatidis infection in the mountain yellow-legged frog (Rana muscosa).

The pathogenic chytrid fungus Batrachochytrium dendrobatidis, which causes the disease chytridiomycosis, has been implicated in declines of amphibian populations throughout the world, including declines and extinctions of local populations of mountain yellow-legged frogs, Rana muscosa, in the California Sierra Nevada. Previous studies have shown B. dendrobatidis achieves its maximum growth rate in culture in the temperature range of 17-25 C, and exposure to very high temperatures can clear frogs of B.