mTOR complex 2 mediates Akt phosphorylation that requires PKCε in adult cardiac muscle cells.

Our earlier work showed that mammalian target of rapamycin (mTOR) is essential to the development of various hypertrophic responses, including cardiomyocyte survival. mTOR forms two independent complexes, mTORC1 and mTORC2, by associating with common and distinct cellular proteins. Both complexes are sensitive to a pharmacological inhibitor, torin1, although only mTORC1 is inhibited by rapamycin.

Systemic oxidative stress, as measured by urinary allantoin and F(2)-isoprostanes, is not increased in Down syndrome.

Purpose: Oxidative stress has been implicated in Down syndrome (DS) pathology. This study compares DS individuals and controls on their urinary levels of allantoin and 2,3-dinor-iPF2α-III; these biomarkers have been previously validated in a clinical model of oxidative stress.

Methods: Urine samples were collected from 48 individuals with DS and 130 controls.

Communicating with people with dementia.

It can be very difficult to communicate with people with dementia. Each case requires its own unique handling. Not every scenario is covered, as many times your own judgment is what will work, best according to the circumstances.

Improving the usefulness of the Multidimensional Pain Inventory.

Background: The Multidimensional Pain Inventory (MPI) is a reliable and valid self-report instrument that measures the impact of pain on an individual's life, quality of social support and general activity. Criticism of the MPI has focused on this instrument's internal structure and the stability of its classification taxonomy.

Objectives: To determine whether empirical summary scales could be developed for the MPI based on a large sample of respondents diagnosed with fibromyalgia syndrome.

AMEE 2010 symposium: medical student education in the twenty-first century - a new Flexnerian era?

As we mark the 100th anniversary of the Flexner report which revolutionized the process of medical education, there is again concern that we face a critical need for change in the process of medical education in order to meet the needs of learners, teachers, and patients. In this symposium, panelists shared perspectives on medical education reform from throughout the world, including The Future of Medical Education in Canada, the role of regulators in contributing to reform, the evolution of accreditation standards, the current state of medical education in Southeast Asia, and the perspectives of a medical student on medical education reform. In the "Audience discussion" section, themes emerged surrounding medical education as a social good, the need for governmental support of medical education, the cost of medical education and the rise of for-profit medical schools, and embracing a broader view of health professional education.

Rapamycin treatment augments both protein ubiquitination and Akt activation in pressure-overloaded rat myocardium.

Ubiquitin-mediated protein degradation is necessary for both increased ventricular mass and survival signaling for compensated hypertrophy in pressure-overloaded (PO) myocardium. Another molecular keystone involved in the hypertrophic growth process is the mammalian target of rapamycin (mTOR), which forms two distinct functional complexes: mTORC1 that activates p70S6 kinase-1 to enhance protein synthesis and mTORC2 that activates Akt to promote cell survival. Independent studies in animal models show that rapamycin treatment that alters mTOR complexes also reduces hypertrophic growth and increases lifespan by an unknown mechanism.

Safety and efficacy of rivastigmine in adolescents with Down syndrome: long-term follow-up.

Following the completion of a 20-week, open-label study of the safety and efficacy of liquid rivastigmine for adolescents with Down syndrome, 5 of the 10 adolescents in the clinical trial continued long-term rivastigmine therapy and 5 did not. After an average period of 38 months, all 10 subjects returned for a follow-up assessment to determine the safety and efficacy of long-term rivastigmine use. Rivastigmine was well tolerated and overall health appeared to be unaffected by long-term rivastigmine use.

Management of autoimmune associated alopecia areata.

Alopecia areata or hair loss occurs in one in 1000 people. If medical reasons for the hair loss are ruled out, opinion and hypothesis point towards autoimmunity and stress as possible causes. Dealing with the gradual or sudden loss of head hair, eyebrows, eyelashes, nasal, ear and body hair poses unique challenges for those it affects.

Introduction of solid foods: do mothers follow recommendations?

Purpose: Infant age at introduction of solid foods was examined, as were maternal characteristics associated with adherence to recommendations.

Methods: In a telephone survey, 2153 mothers living in Ontario were asked questions about the age at which foods were introduced to their infants.

Results: Eighteen percent of respondents introduced infant cereal before age four months, while 5% introduced it at age seven months or later.

Oxidative stress sensitizes bladder cancer cells to TRAIL mediated apoptosis by down-regulating anti-apoptotic proteins.

Purpose: TRAIL, an endogenous protein involved in immunosurveillance and a novel drug in clinical trials, is of particular interest as cancer therapy because it can induce apoptosis in cancer cells but not in normal cells. Since some cancers develop resistance to TRAIL, safe and effective methods of TRAIL sensitization are of clinical interest. We explored how chemotherapy and oxidative stress affect TRAIL sensitivity and expression of proteins in the apoptotic pathway.

Acute medicine teaching in an undergraduate medical curriculum: a blended learning approach.

Background: Acute medical management is an important component of the Modernising Medical Careers (MMC) project which has recently been implemented in the UK. A web-based interactive course in acute medicine has been developed which complements the clinical teaching provided to senior medical students at the University of Glasgow. A study was undertaken to evaluate the teaching and assess the knowledge of acute medicine among final year medical students using an online questionnaire.

Cross-referencing the Scottish Doctor and Tomorrow's Doctors learning outcome frameworks.

Learning outcomes, organised into systems or frameworks which describe and define the output of an educational programme, are being created and used in healthcare education with increasing frequency (Harden 2001, 2002). Medical schools may be required to conform to more than one such outcome framework. For example, both the UK General Medical Council (GMC) and the Scottish Deans' Medical Curriculum Group (SDMCG) have created and published a systematic learning outcome framework for medical graduates.

Role of acid ceramidase in resistance to FasL: therapeutic approaches based on acid ceramidase inhibitors and FasL gene therapy.

Head and neck squamous cell cancers (HNSCC) are particularly aggressive and are resistant to many forms of treatment. Ceramide metabolism has been shown to play an important role in cancer progression and cancer resistance to therapy in many tumor models, including HNSCC. Here, we study the role of the ceramide-metabolizing enzyme acid ceramidase (AC) in therapeutic responses in HNSCC.

Highlights of the European Association of Nuclear Medicine Congress, Athens, Greece, 30 September to 4 October 2006.

The 2006 EANM Congress, held in Athens, Greece, was once again a major event in the nuclear medicine scientific and educational calendar. The scientific programme, which included the second biennial ISRTRD meeting, confirmed the major developments taking place in (1) the diagnostic and prognostic uses of nuclear medicine imaging (both in PET and in single-photon studies), (2) radionuclide therapies, (3) radiochemistry and radiopharmacy, and (4) physics. This paper outlines the major findings in each of these areas.

Combined therapeutic use of AdGFPFasL and small molecule inhibitors of ceramide metabolism in prostate and head and neck cancers: a status report.

As of January 2005, there were 1020 gene therapy clinical trials ongoing worldwide with 675 or 66.2% devoted to cancer gene therapy. The majority are occurring in the US and Europe (http://www.

FasL gene therapy: a new therapeutic modality for head and neck cancer.

In this study, we investigated the in vitro and in vivo efficacy of Fas ligand (FasL) gene therapy for the treatment of head and neck cancer. Three head and neck squamous cell carcinoma (HNSCC) cell lines (SCC-1, SCC-12, and SCC-14a) were treated with the Fas agonist CH-11, a monoclonal antibody to the Fas receptor, or with a replication-incompetent adenovirus (AdGFPFasL) expressing a modified murine Fas ligand gene fused to green fluorescent protein (GFP). A replication-incompetent adenovirus containing the GFP gene alone was used as a control for viral transduction toxicity (AdGFP).

Doxorubicin increases the effectiveness of Apo2L/TRAIL for tumor growth inhibition of prostate cancer xenografts.

Background: Prostate cancer is a significant health problem among American men. Treatment strategies for androgen-independent cancer are currently not available. Tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is a death receptor ligand that can induce apoptosis in a variety of cancer cell lines, including androgen-independent PC3 prostate carcinoma cells.