AMPK Re-Activation Suppresses Hepatic Steatosis but its Downregulation Does Not Promote Fatty Liver Development.

Nonalcoholic fatty liver disease is a highly prevalent component of disorders associated with disrupted energy homeostasis. Although dysregulation of the energy sensor AMP-activated protein kinase (AMPK) is viewed as a pathogenic factor in the development of fatty liver its role has not been directly demonstrated. Unexpectedly, we show here that liver-specific AMPK KO mice display normal hepatic lipid homeostasis and are not prone to fatty liver development, indicating that the decreases in AMPK activity associated with hepatic steatosis may be a consequence, rather than a cause, of changes in hepatic metabolism.

The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver.

LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver.

Prospective clinical audit of two neuromodulatory treatments for fecal incontinence: sacral nerve stimulation (SNS) and percutaneous tibial nerve stimulation (PTNS).

Background And Purpose: Two types of neuromodulation are currently practised for the treatment of fecal incontinence (FI): sacral nerve stimulation (SNS) and percutaneous tibial nerve stimulation (PTNS). This study compares these therapies, as no data exist to prospectively assess their relative efficacy and costs.

Methods: The subjects of this study were two distinct cohorts undergoing SNS (between 2003 and 2008) or PTNS (2008-onwards) for FI.

Symptom distribution and anorectal physiology results in male patients with rectal intussusception and prolapse.

Background: Rectal intussusception and external rectal prolapse are uncommon proctographic findings in men reflecting the lack of studies investigating such patients. The aim of this study was to identify the demographic, clinical, and physiological characteristics of this population with a view to appreciate the mechanism of development of this condition.

Methods: All men, presenting with symptoms of constipation or fecal incontinence, who were diagnosed proctographically with recto-rectal intussusception (RRI)/recto-anal intussusception (RAI) or external rectal prolapse (ERP) between 1994 and 2007 at a tertiary academic colorectal unit were studied.

Electrically stimulated gracilis neosphincter for end-stage fecal incontinence: the long-term outcome.

Background: Electrically stimulated gracilis neosphincter is an established treatment for patients with end-stage fecal incontinence. Few data, however, describe its long-term efficacy.

Objective: This study aimed to assess the long-term functional outcome associated with this procedure.

Outcome of percutaneous tibial nerve stimulation (PTNS) for fecal incontinence: a prospective cohort study.

Objectives: The aim of this study was to assess the long-term efficacy of percutaneous tibial nerve stimulation (PTNS) in fecal incontinence (FI).

Background: There is extensive evidence regarding the efficacy of PTNS in urinary incontinence. Data on the efficacy of PTNS for FI are limited to a few small case series with relatively short-follow up.

Outcome of sacral nerve stimulation for fecal incontinence in patients refractory to percutaneous tibial nerve stimulation.

Background: Percutaneous tibial nerve stimulation and sacral nerve stimulation are both second-line treatments for fecal incontinence, but the comparative efficacy of the 2 therapies is unknown. In our institution, patients with refractory fecal incontinence are generally treated with percutaneous tibial nerve stimulation before being considered for sacral nerve stimulation.

Objective: The aim of this study was to assess the outcome associated with this treatment algorithm in order to guide future management strategies.

Surgery in young adults with inflammatory bowel disease: a narrative account.

Background: Inflammatory Bowel Disease comprises two major intestinal disorders, Crohn's Disease and Ulcerative Colitis. When medical management cannot control the disease, surgery is necessary. Having an operation is a major concern for young people with Inflammatory Bowel Disease.

Assessment of female patients with rectal intussusception and prolapse: is this a progressive spectrum of disease?

Background: Rectal intussusception may be the initial abnormality of a progressive pelvic floor disorder culminating in external prolapse. The evidence, however, is unclear, and the pathophysiological mechanisms underlying this condition are unknown.

Objective: The aim of this study is to identify the relationship between age, symptom duration, anorectal physiology parameters, and type of intussusception/prolapse in order to appreciate the natural history of the condition.

Percutaneous tibial nerve stimulation for fecal incontinence: a video demonstration.

Background: Fecal incontinence is an increasingly common condition with significant negative impact on quality on life and health care resources. It frequently presents a therapeutic challenge to clinicians. Emerging evidence suggests that percutaneous tibial nerve stimulation is an effective treatment for fecal incontinence with the added benefit of being minimally invasive and cost effective.

Targeted inhibition of T-cell factor activity promotes syndecan-2 expression and sensitization to doxorubicin in osteosarcoma cells and bone tumors in mice.

Alterations of Wnt signaling appear to be involved in the pathogenesis of osteosarcoma, presenting mutations of adenomatous polyposis coli (APC) and epigenetic downregulation of Wnt inhibitory factor 1. However, the precise role of Wnt effectors in the bone cancer progression remains unclear. We previously showed that Wnt/β-catenin/T-cell factor (TCF) activation are responsible for the repression of syndecan-2, a key modulator of apoptosis and chemosensitivity in osteosarcoma cells, suggesting a role of Wnt signaling in chemoresistance.

Efficacy of sacral nerve stimulation for the treatment of fecal incontinence.

Background: Sacral nerve stimulation has been shown to be an effective treatment for fecal incontinence and early studies reported success rates of 67% to 100%. However, "success" has been arbitrarily set at a 50% reduction in symptoms, and data are rarely reported with "intention to treat."

Objective: This study aimed to assess the true efficacy of sacral nerve stimulation for fecal incontinence compared with the published literature.

Calpain-6 is an endothelin-1 signaling dependent protective factor in chemoresistant osteosarcoma.

Bone tumors strongly influence normal tissues and stimulate bone cells for the production of cytokines supporting proliferation and abnormal survival in cancer cells. We previously reported that the proteoglycan syndecan-2 controls the activity of various cytokines and growth factors and also modulates apoptosis and response to cytotoxic agents in osteosarcoma cell lines. Here, we show that syndecan-2 has a stronger tumor suppressor activity in vivo.

Percutaneous tibial nerve stimulation for patients with faecal incontinence.

Percutaneous tibial nerve stimulation (PTNS) is a new, non-invasive treatment for faecal incontinence. It is given in an outpatient setting and has few side effects. An increasing number of studies confirm its efficacy.

High Wnt signaling represses the proapoptotic proteoglycan syndecan-2 in osteosarcoma cells.

Osteosarcoma is characterized by frequent relapse and metastatic disease associated with resistance to chemotherapy. We previously showed that syndecan-2 is a mediator of the antioncogenic effect of chemotherapeutic drugs. The purpose of this work was to elucidate molecular mechanisms responsible for the low expression of syndecan-2 in osteosarcoma.

Conservative management of faecal incontinence in adults.

While faecal incontinence is a common problem, many people may be embarrassed to admit having the condition. An understanding of the various factors that contribute to faecal incontinence can increase nurses' awareness of potential continence problems. Nurses can assess patients for faecal incontinence, provide valuable information and implement a range of management strategies to support patients and improve their quality of life.

Percutaneous tibial nerve stimulation for the treatment of urge fecal incontinence.

Purpose: Percutaneous tibial nerve stimulation has been shown to be an effective treatment in patients with urinary disorders, but its benefit in fecal incontinence is uncertain. This study aimed to assess the efficacy of percutaneous tibial nerve stimulation in the treatment of urge fecal incontinence.

Methods: This prospective study, conducted over a 14-month period, assessed 31 patients with urge fecal incontinence treated with percutaneous tibial nerve stimulation.

Helping to adjust: an holistic approach to stoma care.

The aim of this Learning Unit is to increase your knowledge about the psychological implications of stoma formation and to increase your understanding of the process of psychological adaptation, in order that you can offer more sensitive care.