Convergent total synthesis of (±) myricanol, a cyclic natural diarylheptanoid.

Myricanol 1, a constituent of Myrica species, has been reported to lower the levels of the microtubule-associated protein tau (MAPT), whose accumulation plays an important role in some neurodegenerative diseases, such as Alzheimer's disease (AD). Herein we described a new synthetic route to prepare myricanol in 9 steps and 4.9% overall yield starting from commercially available 2,3-dimethoxyphenol and methyl 3-(4-benzyloxyphenyl)propanoate. The key steps are a cross-metathesis to obtain a linear diarylheptanoid intermediate and a Suzuki-Miyaura domino reaction to generate the challenging macrocycle.

Subthalamic deep brain stimulation influences complex emotional musical experience in Parkinson's disease.

Subthalamic deep brain stimulation (STN DBS) is an effective treatment for reducing the motor symptoms of patients with Parkinson's disease (PD), but several side effects have been reported, concerning the processing of emotions. Music has been shown to evoke powerful emotional experiences - not only basic emotions, but also complex, so-called aesthetic experiences. The goal of the present study was therefore to investigate how STN DBS influences the experience of both basic and more complex musical emotions in patients with PD. In a three-group between-participants design, we compared healthy controls (HC), patients receiving STN DBS (PD-DBS), and patients who were candidates for STN DBS and receiving medication only (PD-MO) on their assessments of subjectively experienced musical emotions. Results showed that in general, the experience of musical emotions differed only marginally between the PD-MO, PD-DBS, and HC groups. Nonetheless, we were able to discern subtle but distinct effects of PD and STN DBS in the emotional responses. Happy music, for instance, seemed to induce a heightened experience of negative emotions (tension) in PD-MO patients. STN DBS appeared to normalize this particular effect, but increased nostalgic feelings - a rather complex affective experience - in response to the same emotional stimuli. This should not be taken as indicating a bias for nostalgia in the PD-DBS subgroup, as these patients found music inducing melancholy to be less nostalgic and more joyful than HC did. In conclusion, our study showed that music elicits slightly altered emotional experiences in patients with and without STN DBS. In particular, STN DBS seems to induce less distinct emotional responses, blurring the boundaries between complex musical emotions.

Clinical improvements following bilateral anterior capsulotomy in treatment-resistant depression.

BACKGROUND: The purpose of this study was to evaluate a programme of lesion surgery carried out on patients with treatment-resistant depression (TRD). METHOD: This was a retrospective study looking at clinical and psychometric data from 45 patients with TRD who had undergone bilateral stereotactic anterior capsulotomy surgery over a period of 15 years, with the approval of the Mental Health Act Commission (37 with unipolar depression and eight with bipolar disorder). The Beck Depression Inventory (BDI) before and after surgery was used as the primary outcome measure. The Montgomery-Asberg Depression Rating Scale was administered and cognitive aspects of executive and memory functions were also examined. We carried out a paired-samples t test on the outcome measures to determine any statistically significant change in the group as a consequence of surgery. RESULTS: Patients improved on the clinical measure of depression after surgery by -21.20 points on the BDI with a 52% change. There were no significant cognitive changes post-surgery. Six patients were followed up in 2013 by phone interview and reported a generally positive experience. No major surgical complications occurred. CONCLUSIONS: With the limitations of an uncontrolled, observational study, our data suggest that capsulotomy can be an effective treatment for otherwise TRD. Performance on neuropsychological tests did not deteriorate.

The accuracy of breast volume measurement methods: A systematic review.

Breast volume is a key metric in breast surgery and there are a number of different methods which measure it. However, a lack of knowledge regarding a method's accuracy and comparability has made it difficult to establish a clinical standard. We have performed a systematic review of the literature to examine the various techniques for measurement of breast volume and to assess their accuracy and usefulness in clinical practice. Each of the fifteen studies we identified had more than ten live participants and assessed volume measurement accuracy using a gold-standard based on the volume, or mass, of a mastectomy specimen. Many of the studies from this review report large (>200 ml) uncertainty in breast volume and many fail to assess measurement accuracy using appropriate statistical tools. Of the methods assessed, MRI scanning consistently demonstrated the highest accuracy with three studies reporting errors lower than 10% for small (250 ml), medium (500 ml) and large (1000 ml) breasts. However, as a high-cost, non-routine assessment other methods may be more appropriate.

Recent trends in the incidence of anxiety and prescription of anxiolytics and hypnotics in children and young people: An e-cohort study.

BACKGROUND: Little is known regarding the recognition of anxiety in children and young people (CYP) in primary care. This study examined trends in the presentation, recognition and recording of anxiety and of anxiolytic and hypnotic prescriptions for CYP in primary care. METHOD: A population-based retrospective electronic cohort of individuals aged 6-18 years between 2003 and 2011 within the Secure Anonymised Information Linkage (SAIL) Databank primary care database was created. Incidence rates were calculated using person years at risk (PYAR) as a denominator accounting for deprivation, age and gender. RESULTS: We identified a cohort of 311,343 registered individuals providing a total of 1,546,489 person years of follow up. The incidence of anxiety symptoms more than tripled over the study period (Incidence Rate Ratio (IRR)=3.55, 95% CI 2.65-4.77) whilst that of diagnosis has remained stable. Anxiolytic/hypnotic prescriptions for the cohort as a whole did not change significantly over time; however there was a significant increase in anxiolytic prescriptions for the 15-18 year age group (IRR 1.62, 95% CI 1.30-2.02). LIMITATIONS: There was a lack of reliable information regarding other interventions available or received at a primary, secondary or tertiary level such as psychological treatments. CONCLUSIONS: There appears to be a preference over time for the recording of general symptoms over diagnosis for anxiety in CYP. The increase in anxiolytic prescriptions for 15-18 year olds is discrepant with current prescribing guidelines. Specific guidance is required for the assessment and management of CYP presenting with anxiety to primary care, particularly older adolescents.

Development and assessment of a Microsoft Kinect based system for imaging the breast in three dimensions.

Three-dimensional surface imaging technologies have been used in the planning and evaluation of breast reconstructive and cosmetic surgery. The aim of this study was to develop a 3D surface imaging system based on the Microsoft Kinect and assess the accuracy and repeatability with which the system could image the breast. A system comprising two Kinects, calibrated to provide a complete 3D image of the mannequin was developed. Digital measurements of Euclidean and surface distances between landmarks showed acceptable agreement with manual measurements. The mean differences for Euclidean and surface distances were 1.9mm and 2.2mm, respectively. The system also demonstrated good intra- and inter-rater reliability (ICCs>0.999). The Kinect-based 3D surface imaging system offers a low-cost, readily accessible alternative to more expensive, commercially available systems, which have had limited clinical use.

Unusual C-6 Lithiation of 2-Chloropyridine-Mediated by BuLi-Me(2)N(CH(2))(2)OLi. New Access to 6-Functional-2-chloropyridines and Chloro-bis-heterocycles.

The reaction of 2-chloropyridine with alkylithium generally results in nucleophilic addition leading to the loss of chlorine atom while exclusive directed ortho metalation is obtained using LDA. Herein it is shown that the BuLi-Me(2)N(CH(2))(2)OLi (BuLi-LiDMAE) superbase promotes an unprecedented regioselective C-6 lithiation. The method was successfully applied to the preparation of potentially useful chlorinated pyridinic and bis-heterocyclic synthons.