In Pursuit of an Allosteric Human Tropomyosin Kinase A (TrkA) Inhibitor for Chronic Pain.

Human β-nerve growth factor (β-NGF) and its associated receptor, human tropomyosin receptor kinase A (TrkA), have been demonstrated to be key factors in the perception of pain. However, efficacious small molecule therapies targeting the intracellularly located TrkA kinase have not been explored thoroughly for pain management. Herein, we report the pharmacological properties of a selective TrkA allosteric inhibitor, .

Serotonin-Modulating Antidepressants and Risk of Bleeding after Trauma.

Serotonin-modulating antidepressants have been associated with increased risk of gastrointestinal bleeding and increased blood loss during elective surgery. This study sought to investigate the effect of preinjury selective-serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) use on transfusion requirements after trauma, and to evaluate whether resumption of SSRI/SNRI after trauma may worsen bleeding risk. This was a retrospective matched-cohort study evaluating patients with solid organ injury.

Efficacy of alvimopan following bowel resection: a comparison of two dosing strategies.

Background: Alvimopan is indicated to accelerate the time to gastrointestinal recovery following partial bowel resection with primary anastomosis. The approved dosing regimen includes an initial dose prior to surgery and 12 mg twice daily after surgery for up to 7 days; however, there are no human studies evaluating the need for the preoperative dose. We report our experience with gastrointestinal recovery when the preoperative dose is omitted.

Evaluating contemporary antibiotics as a risk factor for Clostridium difficile infection in surgical trauma patients.

Background: With most Clostridium difficile infections (CDI) occurring after exposure to antimicrobial treatment, specific antibiotics and duration of exposure were evaluated independently for increased risk of CDI in surgical patients.

Methods: A retrospective, case-control design was used to study surgical inpatients. The case group had a positive Clostridium difficile toxin assay, whereas the control group did not.

Lead Diversification 2: application to P38, gMTP and lead compounds.

Lead Diversification is a new technology platform developed at Pfizer for the functionalization of drug molecules using C-H activation. We describe its application to some drug programs such as P38 and gMTP and the development of some new plate based screens including a fluorination screen.

A high-fidelity simulation mannequin to introduce pharmacy students to advanced cardiovascular life support.

Objective: To design and implement an advanced cardiac life support (ACLS) workshop featuring a human patient simulator (HPS) for third-year pharmacy students.

Design: The ACLS workshop consisted of a pre-session lecture, a calculation exercise, and a 40-minute ACLS session using an HPS. Twenty-four 5-member teams of students were assigned roles on a code team and participated in a ventricular fibrillation/pulseless ventricular tachycardia case.

Efficient Constrained Local Model Fitting for Non-Rigid Face Alignment.

Active appearance models (AAMs) have demonstrated great utility when being employed for non-rigid face alignment/tracking. The "simultaneous" algorithm for fitting an AAM achieves good non-rigid face registration performance, but has poor real time performance (2-3 fps). The "project-out" algorithm for fitting an AAM achieves faster than real time performance (> 200 fps) but suffers from poor generic alignment performance.

Comparing Object Alignment Algorithms with Appearance Variation: Forward-Additive vs Inverse-Composition.

A common problem that affects object alignment algorithms is when they have to deal with objects with unseen intra-class appearance variation. Several variants based on gradient-decent algorithms, such as the Lucas-Kanade (or forward-additive) and inverse-compositional algorithms, have been proposed to deal with this issue by solving for both alignment and appearance simultaneously. In [1], Baker and Matthews showed that without appearance variation, the inverse-compositional (IC) algorithm was theoretically and empirically equivalent to the forward-additive (FA) algorithm, whilst achieving significant improvement in computational efficiency.

Least Squares Congealing for Unsupervised Alignment of Images.

In this paper, we present an approach we refer to as "least squares congealing" which provides a solution to the problem of aligning an ensemble of images in an unsupervised manner. Our approach circumvents many of the limitations existing in the canonical "congealing" algorithm. Specifically, we present an algorithm that:- (i) is able to simultaneously, rather than sequentially, estimate warp parameter updates, (ii) exhibits fast convergence and (iii) requires no pre-defined step size.

BRCA1 and BRCA2 mutation prevalence and clinical characteristics of a population-based series of ovarian cancer cases from Denmark.

Purpose: To evaluate the prevalence of BRCA1 and BRCA2 mutations and associations with clinical correlates of disease in a population-based series of ovarian cancer cases from Denmark.

Methods: DNA sequencing and multiplex ligation-dependent probe amplification analysis were used to analyze the BRCA1 and BRCA2 genes for coding sequence mutations and large genomic rearrangements in 445 confirmed cases of ovarian cancer. We evaluated associations between mutation status and clinical characteristics, including cancer risks for first-degree relatives and clinicopathologic features of tumors.

Effect of etanercept, a tumor necrosis factor-alpha inhibitor, on neuropathic pain in the rat chronic constriction injury model.

Study Design: The effects of a low, local dose of a tumor necrosis factor-alpha (TNF-alpha) inhibitor on neuropathic pain behaviors in a rat chronic constriction injury model were evaluated.

Objective: To investigate whether a peripherally implanted polymer drug depot can deliver a dose of etanercept sufficient to reduce thermal hyperalgesia and mechanical allodynia in a rat model of neuropathic pain.

Summary Of Background Data: TNF-alpha inhibitors reduce pain-associated behavior in experimental models of neuropathic pain.

Contribution of BRCA1 and BRCA2 mutations to inherited ovarian cancer.

A total of 283 epithelial ovarian cancer families from the United Kingdom (UK) and the United States (US) were screened for coding sequence changes and large genomic alterations (rearrangements and deletions) in the BRCA1 and BRCA2 genes. Deleterious BRCA1 mutations were identified in 104 families (37%) and BRCA2 mutations in 25 families (9%). Of the 104 BRCA1 mutations, 12 were large genomic alterations; thus this type of change represented 12% of all BRCA1 mutations.

Screening for the BRCA1-ins6kbEx13 mutation: potential for misdiagnosis. Mutation in brief #964. Online.

Misdiagnosis of a germline mutation associated with an inherited disease syndrome can have serious implications for the clinical management of patients. A false negative diagnosis (mutation missed by genetic screening) limits decision making about intervention strategies within families. More serious is the consequence of a false positive diagnosis (genetic test suggesting a mutation is present when it is not).

Increased gastric-end tidal P(CO2) gap during exercise at high altitude measured by gastric tonometry.

Using automated air gastric tonometry, the hypothesis that gastric perfusion is reduced while exercising at high altitude was explored. This prospective observational study of 5 well acclimatized healthy volunteers was performed during a medical research expedition to Chamlang base camp (5000 m), Hongu valley, Nepal. We used gastric tonometry at rest and during graded submaximal exercise.

Resuscitation from hemorrhagic shock using rectally administered fluids in a wilderness environment.

We report the successful use in a wilderness environment of rectally administered oral rehydation fluid to resuscitate a patient who was in shock. The subject was a 21-year-old Nepali man who had experienced a major upper gastrointestinal hemorrhage.

Barrett's surveillance is worthwhile and detects curable cancers. A prospective cohort study addressing cancer incidence, treatment outcome and survival.

Objectives: To establish whether Barrett's surveillance is worthwhile in terms of incident cancers and whether outcomes are favourable.

Methods: A prospective non-randomized single centre Barrett's surveillance programme commencing 1 January 1992 through 1 April 2001 (112 months). Oesophagectomy recommended for high-grade dysplasia or carcinoma.

Mycobacteria other than Mycobacterium tuberculosis are not present in erythema induratum/nodular vasculitis: a case series and literature review of the clinical and histologic findings.

Erythema induratum (EI)/nodular vasculitis (NV) is characterized by recurrent crops of tender oedematous nodules on the lower legs. A lobular panniculitis with granulomatous inflammation, vasculitis, focal necrosis and septal fibrosis is present. Mycobacterium tuberculosis DNA has been detected in some lesions by means of polymerase chain reaction (PCR).

Economic and demographic factors affecting mangrove loss in the coastal provinces of Thailand, 1979-1996.

The following paper analyzes the economic and demographic factors determining the conversion of mangroves in the coastal provinces of Thailand to commercial shrimp farming. Mangrove conversion therefore is determined by the returns to shrimp farmers, (i.e.