Survival,surveillance, and genetics in patients with Peutz–Jeghers syndrome: A nationwide study

Peutz–Jeghers syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome causing increased morbidity and mortality due to complications of polyposis and the development of cancer. STK11 is the only gene known to be associated with PJS, although in 10%–15% of patients fulfilling the diagnostic criteria no pathogenic variant (PV) is identified. The primary aim of this study was to identify the genetic etiology in all known PJS patients in Denmark and to estimate the risk of cancer, effect of surveillance and overall survival. We identified 56 patients (2–83 years old) with PJS. The detection rate of PVs was 96%, including three cases of mosaicism (6%). In two patients a variant was not detected. At the age of 40 years, the probabilities of cancer and death were 21% and 16%, respectively; at the age of 70 years these probabilities were 71% and 69%. Most cases of cancer (92%) were identified between the scheduled examinations in the surveillance program. These observations emphasize that PJS should be regarded as a general cancer predisposition syndrome, where improvement of clinical care is needed.     

The trunk neural crest and its early glial derivatives: a study of survival responses, developmental schedules and autocrine mechanisms

Regulation of survival during gliogenesis from the trunk neural crest is poorly understood. Using adapted survival assays, we directly compared crest cells and the crest-derived precursor populations that generate satellite cells and Schwann cells. A range of factors that supports Schwann cells and glial precursors does not rescue crest, with the major exception of neuregulin-1 that rescues crest cells provided they contact the extracellular matrix. Autocrine survival appears earlier in developing satellite cells than Schwann cells. Satellite cells also show early expression of S100beta, BFABP and fibronectin and early survival responses to IGF-1, NT-3 and PDGF-BB that in developing Schwann cells are not seen until the precursor/Schwann cell transition. These experiments define novel differences between crest cells and early glia and show that entry to the glial lineage is an important point for regulation of survival responses. They show that survival mechanisms among PNS glia differ early in development and that satellite cell development runs ahead of schedule compared to Schwann cells in several significant features.     

Safety and efficacy of 5% imiquimod cream for the treatment of skin dysplasia in high-risk renal transplant recipients: randomized, double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the safety and efficacy of 5% imiquimod cream for cutaneous dysplasia in high-risk renal transplant recipients. DESIGN: A randomized, blinded, placebo-controlled study comparing treated with control skin. SETTING: A specialist organ transplant dermatology clinic. PATIENTS: Twenty-one high-risk patients with skin cancer with comparable areas of clinically atypical skin on dorsal hands or forearms. INTERVENTIONS: Imiquimod or placebo (randomly assigned) applied 3 times a week for 16 weeks to 1 dorsal hand or forearm, with 8 months of follow-up. At week 16, biopsy samples were collected from pre-assigned sites in the treatment and control areas and were examined for dysplasia. MAIN OUTCOME MEASURES: The proportion of patients showing reduced numbers of viral and keratotic lesions and reduced histological severity of dysplasia in the treatment vs control areas at week 16, serum creatinine levels, and tumors developing in the study sites. RESULTS: Fourteen patients receiving imiquimod and 6 receiving placebo completed the study. Seven patients using imiquimod (1 taking placebo) had reduced skin atypia, 7 using imiquimod (none taking placebo) had reduced viral warts, and 5 using imiquimod (1 taking placebo) showed less dysplasia histologically. In 1 year, fewer squamous skin tumors arose in imiquimod-treated skin than in control areas. Renal function was not adversely affected. CONCLUSIONS: Topical 5% imiquimod cream seems to be safe on skin areas up to 60 cm2 in renal transplant recipients. It may be effective in reducing cutaneous dysplasia and the frequency of squamous tumors developing in high-risk patients. Larger studies are required to confirm these results.     

Episodic Future Thinking in Autism Spectrum Disorder and 22q11.2 Deletion Syndrome: Association with Anticipatory Pleasure and Social Functioning

Journal of Autism and Developmental Disorders - Episodic future thinking (EFT) has been suggested to underlie anticipatory pleasure (AP), itself known to play a crucial role in social functioning...     

Developments in acupuncture research: big-picture perspectives from the leading edge

On November 8-9, 2007, the Society for Acupuncture Research (SAR) hosted an international conference to mark the tenth anniversary of the landmark NIH [National Institutes of Health] Consensus Development Conference on Acupuncture. More than 300 acupuncture researchers, practitioners, students, funding agency personnel, and health policy analysts from 20 countries attended the SAR meeting held at the University of Maryland School of Medicine, Baltimore, MD. This paper summarizes important invited lectures in the area of how the field has developed in the past decade, along with a focus on appropriate strategies for advancing the field. Specific topics include: the impact of the 1997 NIH Acupuncture Consensus Conference on acupuncture research; whole-system strategies for developing the evidence without distorting the medicine; use of qualitative research methods to explore acupuncture as a complex intervention; use of qualitative research approaches to explore some "missing" topics in acupuncture research; and the impact of acupuncture research on clinical practice. A concluding section focuses on future directions in acupuncture research.     

Maternal heart rate variability and fetal behavior in hypertensive and normotensive pregnancies

The relation between maternal heart rate variability (HRV) and fetal behavior was examined in hypertensive and normotensive pregnant women. A total of 40 mother-fetal pairs (n = 20 normotensive mothers; n = 20 hypertensive mothers) at 33-41 weeks' gestation were observed using a standardized procedure lasting approximately 50 min. It included the following measurements: maternal beat-by-beat arterial blood pressure and HRV; spontaneous fetal heart rate (HR), body and breathing movements; and an estimate of amniotic fluid volume. The women in the hypertensive group had higher average body mass index (BMI) (33.7 vs. 28.8 kg/m2) than the normotensive group. In the normotensive group, there was no association between maternal HRV and fetal gestational age, HR, body or breathing movements. In the hypertensive group, maternal HRV measures of low-frequency, high-frequency, and total power were associated with fetal gestational age; also, there was an association between maternal autonomic modulation of HR and fetal spontaneous HR. These findings suggest that the maternal autonomic system influences fetal cardiac function in pregnancies complicated by hypertension.