An Isolated Neurofibromal Polyp of the Colon

Solitary neurofibromal colonic polyps are a rare entity, particularly outside the setting of neurofibromatosis type 1. The clinical significance of such lesions has not yet been established. Though typically benign tumors, neurofibromas have been reported to undergo malignant transformation, with an increased risk of malignancy when associated with neurofibromatosis. In this case report, we present the rare case of a man found to have an isolated colonic neurofibroma without any personal/family history or clinical features of neurofibromatosis. A 59-year-old man with a history of dyslipidemia and degenerative joint disease presented for a routine screening colonoscopy. The colonoscopy revealed no abnormalities except a 3 mm transverse colon polyp and another 4 mm polyp in the descending colon. Biopsy results showed the descending colonic polyp to be a tubular adenoma; however, multiple levels of the 3 mm transverse colon polyp revealed interlacing bundles of spindle cells extending into the lamina propria with comma-shaped nuclei consistent with findings seen in neurofibroma. Isolated colonic neurofibromas are rare and understudied. While they are usually benign, they may undergo malignant transformation, especially when associated with neurofibromatosis. Thus, patients presenting with isolated neurofibromas should be followed for development of neurofibromatosis and malignancies

Caenorhabditis elegans behavioral genetics: where are the knobs?

Thousands of behavioral mutants of Caenorhabditis elegans have been studied. I suggest a set of criteria by which some genes important in the evolution of behavior might be recognized, and identify neuropeptide signaling pathways as candidates

Are Child and Adolescent Responses to Placebo Higher in Major Depression than in Anxiety Disorders? A Systematic Review of Placebo-Controlled Trials

BACKGROUND: In a previous report, we hypothesized that responses to placebo were high in child and adolescent depression because of specific psychopathological factors associated with youth major depression. The purpose of this study was to compare the placebo response rates in pharmacological trials for major depressive disorder (MDD), obsessive compulsive disorder (OCD) and other anxiety disorders (AD-non-OCD). METHODOLOGY AND PRINCIPAL FINDINGS: We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalized disorders, restricting our review to double-blind studies including a placebo arm. Placebo response rates were pooled and compared according to diagnosis (MDD vs. OCD vs. AD-non-OCD), age (adolescent vs. child), and date of publication. From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication (mainly non-tricyclic antidepressants) involving youth with MDD, 7 pertaining to youth with OCD, and 10 pertaining to youth with other anxiety disorders (N = 2533 patients in placebo arms). As hypothesized, the placebo response rate was significantly higher in studies on MDD, than in those examining OCD and AD-non-OCD (49.6% [range: 17-90%] vs. 31% [range: 4-41%] vs. 39.6% [range: 9-53], respectively, ANOVA F = 7.1, p = 0.002). Children showed a higher stable placebo response within all three diagnoses than adolescents, though this difference was not significant. Finally, no significant effects were found with respect to the year of publication. CONCLUSION: MDD in children and adolescents appears to be more responsive to placebo than other internalized conditions, which highlights differential psychopathology

Involvement of Dopamine Receptors in Binge Methamphetamine-Induced Activation of Endoplasmic Reticulum and Mitochondrial Stress Pathways

Single large doses of methamphetamine (METH) cause endoplasmic reticulum (ER) stress and mitochondrial dysfunctions in rodent striata. The dopamine D1 receptor appears to be involved in these METH-mediated stresses. The purpose of this study was to investigate if dopamine D1 and D2 receptors are involved in ER and mitochondrial stresses caused by single-day METH binges in the rat striatum. Male Sprague-Dawley rats received 4 injections of 10 mg/kg of METH alone or in combination with a putative D1 or D2 receptor antagonist, SCH23390 or raclopride, respectively, given 30 min prior to each METH injection. Rats were euthanized at various timepoints afterwards. Striatal tissues were used in quantitative RT-PCR and western blot analyses. We found that binge METH injections caused increased expression of the pro-survival genes, BiP/GRP-78 and P58IPK, in a SCH23390-sensitive manner. METH also caused up-regulation of ER-stress genes, Atf2, Atf3, Atf4, CHOP/Gadd153 and Gadd34. The expression of heat shock proteins (HSPs) was increased after METH injections. SCH23390 completely blocked induction in all analyzed ER stress-related proteins that included ATF3, ATF4, CHOP/Gadd153, HSPs and caspase-12. The dopamine D2-like antagonist, raclopride, exerted small to moderate inhibitory influence on some METH-induced changes in ER stress proteins. Importantly, METH caused decreases in the mitochondrial anti-apoptotic protein, Bcl-2, but increases in the pro-apoptotic proteins, Bax, Bad and cytochrome c, in a SCH23390-sensitive fashion. In contrast, raclopride provided only small inhibition of METH-induced changes in mitochondrial proteins. These findings indicate that METH-induced activation of striatal ER and mitochondrial stress pathways might be more related to activation of SCH23390-sensitive receptors

ICAR: endoscopic skull‐base surgery

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MITF (microphthalmia-associated transcription factor)

Review on MITF (microphthalmia-associated transcription factor), with data on DNA, on the protein encoded, and where the gene is implicated

Partnership for fragility bone fracture care provision and prevention program (P4Bones): study protocol for a secondary fracture prevention pragmatic controlled trial.

ABSTRACT: BACKGROUND: Fractures associated with bone fragility in older adults signal the potential for secondary fracture. Fragility fractures often precipitate further decline in health and loss of mobility, with high associated costs for patients, families, society and the healthcare system. Promptly initiating a coordinated, comprehensive pharmacological bone health and falls prevention program post-fracture may improve osteoporosis treatment compliance; and reduce rates of falls and secondary fractures, and associated morbidity, mortality and costs.Methods/design: This pragmatic, controlled trial at 11 hospital sites in eight regions in Quebec, Canada, will recruit community-dwelling patients over age 50 who have sustained a fragility fracture to an intervention coordinated program or to standard care, according to the site. Site study coordinators will identify and recruit 1,596 participants for each study arm. Coordinators at intervention sites will facilitate continuity of care for bone health, and arrange fall prevention programs including physical exercise. The intervention teams include medical bone specialists, primary care physicians, pharmacists, nurses, rehabilitation clinicians, and community program organizers.The primary outcome of this study is the incidence of secondary fragility fractures within an 18-month follow-up period. Secondary outcomes include initiation and compliance with bone health medication; time to first fall and number of clinically significant falls; fall-related hospitalization and mortality; physical activity; quality of life; fragility fracture-related costs; admission to a long term care facility; participants' perceptions of care integration, expectations and satisfaction with the program; and participants' compliance with the fall prevention program. Finally, professionals at intervention sites will participate in focus groups to identify barriers and facilitating factors for the integrated fragility fracture prevention program.This integrated program will facilitate knowledge translation and dissemination via the following: involvement of various collaborators during the development and set-up of the integrated program; distribution of pamphlets about osteoporosis and fall prevention strategies to primary care physicians in the intervention group and patients in the control group; participation in evaluation activities; and eventual dissemination of study results.Study/trial registration: Clinical Trial.Gov NCT01745068Study ID number: CIHR grant # 267395