The mechanism of Hsp90-induced oligomerizaton of Tau.

Aggregation of the microtubule-associated protein Tau is a hallmark of Alzheimer's disease with Tau oligomers suspected as the most toxic agent. Tau is a client of the molecular chaperone Hsp90, although it is unclear whether and how the chaperone massages the structure of intrinsically disordered Tau. Using electron paramagnetic resonance, we extract structural information from the very broad conformational ensemble of Tau: Tau in solution is highly dynamic and polymorphic, although "paper clip"-shaped by long-range contacts. Interaction with Hsp90 promotes an open Tau conformation, which we identify as the molecular basis for the formation of small Tau oligomers by exposure of the aggregation-prone repeat domain to other Tau molecules. At the same time, formation of Tau fibrils is inhibited. We therefore provide the nanometer-scale zoom into chaperoning an amyloid client, highlighting formation of oligomers as the consequence of this biologically relevant interaction.

Screening for malnutrition in patients with gastro-entero-pancreatic neuroendocrine tumours: a cross-sectional study.

OBJECTIVES: To investigate whether screening for malnutrition using the validated malnutrition universal screening tool (MUST) identifies specific characteristics of patients at risk, in patients with gastro-entero-pancreatic neuroendocrine tumours (GEP-NET). DESIGN: Cross-sectional study. SETTING: University Hospitals Coventry & Warwickshire NHS Trust; European Neuroendocrine Tumour Society Centre of Excellence. PARTICIPANTS: Patients with confirmed GEP-NET (n=161) of varying primary tumour sites, functioning status, grading, staging and treatment modalities. MAIN OUTCOME MEASURE: To identify disease and treatment-related characteristics of patients with GEP-NET who score using MUST, and should be directed to detailed nutritional assessment. RESULTS: MUST score was positive (≥1) in 14% of outpatients with GEP-NET. MUST-positive patients had lower faecal elastase concentrations compared to MUST-negative patients (244±37 vs 383±20 µg/g stool; p=0.018), and were more likely to be on treatment with long-acting somatostatin analogues (65 vs 38%, p=0.021). MUST-positive patients were also more likely to have rectal or unknown primary NET, whereas, frequencies of other GEP-NET including pancreatic NET were comparable between MUST-positive and MUST-negative patients. CONCLUSIONS: Given the frequency of patients identified at malnutrition risk using MUST in our relatively large and diverse GEP-NET cohort and the clinical implications of detecting malnutrition early, we recommend routine use of malnutrition screening in all patients with GEP-NET, and particularly in patients who are treated with long-acting somatostatin analogues.

Autoimmune progesterone dermatitis: a diagnosis easily missed.

Autoimmune progesterone dermatitis (AIPD) is a rare, poorly characterized dermatosis, with about 60 previously reported cases. It typically undergoes cyclical flares relating to the menstrual cycle, especially the luteal phase, when levels of progesterone are at their highest. We report the case of a 34-year-old woman with an 8-year history of a profoundly pruritic eruption, associated with her menstrual cycle, in whom the diagnosis had proved elusive. Buserelin nasal spray resulted in complete clearance. AIPD is a diagnosis to consider in intractable eruptions in women, particularly if there is cyclical variation.

Drug-induced subacute cutaneous lupus erythematosus associated with omeprazole.

Subacute cutaneous lupus erythematosus (SCLE) is characterized by annular scaly erythematous plaques in a photosensitive distribution, and the presence of anti-Ro (SSA) and/or anti-La (SSB) antibodies. Most cases of SCLE are idiopathic, but occasional cases may be drug-induced or associated with a hereditary deficiency of complement components. We report two cases of drug-induced SCLE precipitated by the proton pump inhibitor, omeprazole. Drug-induced disease should be considered in all atypical or extensive cases of SCLE, especially in elderly patients.

Factors predicting use of mental health and social services by children 6-16 years old: findings from the Ontario Child Health Study.

Correlates of mental health and social service utilization are examined based on Ontario Child Health Study data. Findings indicate that psychiatric disorder as a predictor of service use may be confounded by school performance and parental use of services, thus calling into question the extent to which program planning should be based on prevalence rates of child psychiatric disorder. Children from low-income families tend to make greater use of available services, suggesting that programs need to be tailored more specifically to their needs.