Design and feasibility testing of a novel group intervention for young women who binge drink in groups

BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18–35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics

Background: Lipids have critical functions in cellular energy storage, structure and signaling. Many individual lipid molecules have been associated with the evolution of prostate cancer; however, none of them has been approved to be used as a biomarker. The aim of this study is to identify lipid molecules from hundreds plasma apparent lipid species as biomarkers for diagnosis of prostate cancer. Methodology/Principal Findings: Using lipidomics, lipid profiling of 390 individual apparent lipid species was performed on 141 plasma samples from 105 patients with prostate cancer and 36 male controls. High throughput data generated from lipidomics were analyzed using bioinformatic and statistical methods. From 390 apparent lipid species, 35 species were demonstrated to have potential in differentiation of prostate cancer. Within the 35 species, 12 were identified as individual plasma lipid biomarkers for diagnosis of prostate cancer with a sensitivity above 80%, specificity above 50% and accuracy above 80%. Using top 15 of 35 potential biomarkers together increased predictive power dramatically in diagnosis of prostate cancer with a sensitivity of 93.6%, specificity of 90.1% and accuracy of 97.3%. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) demonstrated that patient and control populations were visually separated by identified lipid biomarkers. RandomForest and 10-fold cross validation analyses demonstrated that the identified lipid biomarkers were able to predict unknown populations accurately, and this was not influenced by patient's age and race. Three out of 13 lipid classes, phosphatidylethanolamine (PE), ether-linked phosphatidylethanolamine (ePE) and ether-linked phosphatidylcholine (ePC) could be considered as biomarkers in diagnosis of prostate cancer. Conclusions/Significance: Using lipidomics and bioinformatic and statistical methods, we have identified a few out of hundreds plasma apparent lipid molecular species as biomarkers for diagnosis of prostate cancer with a high sensitivity, specificity and accuracy

Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; <4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

Bronchial artery embolization for management of massive cryptogenic hemoptysis: a case series

<p>Abstract</p> <p>Introduction</p> <p>Hemoptysis constitutes a common and urgent medical problem. Swift and effective management is of crucial importance, especially in severe, life-threatening cases. In cases of idiopathic hemoptysis, in which no underlying pulmonary pathology can be identified, treatment is challenging. We report our experience with bronchial artery embolization in the treatment of massive idiopathic hemoptysis.</p> <p>Cases presentation</p> <p>We report three consecutive cases of acute severe idiopathic hemoptysis. Our patients (two men aged 51 and 56 years and one woman aged 46 years), were of Caucasian ethnicity. We discuss the results and management of the patients, and review the literature. All three patients were treated safely and successfully with transcatheter embolization of the bronchial arteries using tris-acryl gelatin microspheres. Hemoptysis was controlled. All cases were followed up for 12 months, and there was no recurrence of bleeding.</p> <p>Conclusion</p> <p>Bronchial artery embolization is an effective tool for the evaluation and treatment of massive idiopathic hemoptysis.</p

Psychologists’ dilemmas in career counselling practice

In this study, we explored main dilemmas psychologists face in career counselling in two main professional settings: employment and education. Participants included 24 experienced Portuguese psychologists, working in employment (n = 14) and educational (n = 10) settings. We used consensual qualitative research to conduct and analyse semi-structured interviews. Results revealed dilemmas’ in five domains: neutrality, assessment, dual loyalty, role boundaries, and confidentiality, with the typical dilemma in the domain of neutrality. Differences between groups were found in the domains of dual loyalty and role boundaries.Dans cette étude, nous avons exploré les principaux dilemmes rencontrés par les psychologues dans le conseil en orientation dans deux milieux professionnels centraux: le placement et l’éducation. Parmi les participants figuraient 24 psychologues portugais expérimentés travaillant dans des contextes de placement (n = 14) et d’éducation (n = 10). Nous avons utilisé la recherche qualitative consensuelle pour mener et analyser les entretiens semi-structurés. Les re´sultats ont révé lé des dilemmes dans cinq domaines: la neutralité, l’évaluation, la double loyauté, les limites du rôle, et la confidentialité, avec le dilemme typique dans le domaine de la neutralité. Les différences entre les groupes ont été identifiees dans les domaines de la double loyauté et les limites du rôle.In dieser Studie untersuchten wir die hauptsä chlichen Dilemmata, mit denen Psychologen in der Berufsberatung in zwei wesentlichen professionellen Einrichtungen konfrontiert sind: Beruf und Bildung. Zu den Teilnehmern geho ¨rten 24 erfahrene portugiesische Psychologen, die in Einrichtungen von Beruf (n = 14) und Bildung (n = 10) arbeiteten. Wir verwendeten einvernehmliche qualitative Forschung um semi-strukturierte Interviews durchzufu¨hren und zu analysieren. Die Ergebnisse zeigten Dilemmata in fünf Bereichen: Neutralität, Beurteilung, doppelte Loyalität, Rollengrenzen und Vertraulichkeit, mit dem typischen Dilemma in der Domäne der Neutralität. Unterschiede zwischen den Gruppen wurden in den Bereichen der doppelten Loyalität und Rollengrenzen gefunden

Characterization of long and stable de novo single alpha-helix domains provides novel insight into their stability

Naturally-occurring single α-helices (SAHs), are rich in Arg (R), Glu (E) and Lys (K) residues, and stabilized by multiple salt bridges. Understanding how salt bridges promote their stability is challenging as SAHs are long and their sequences highly variable. Thus, we designed and tested simple de novo 98-residue polypeptides containing 7-residue repeats (AEEEXXX, where X is K or R) expected to promote salt-bridge formation between Glu and Lys/Arg. Lys-rich sequences (EK3 (AEEEKKK) and EK2R1 (AEEEKRK)) both form SAHs, of which EK2R1 is more helical and thermo-stable suggesting Arg increases stability. Substituting Lys with Arg (or vice versa) in the naturally-occurring myosin-6 SAH similarly increased (or decreased) its stability. However, Arg-rich de novo sequences (ER3 (AEEERRR) and EK1R2 (AEEEKRR)) aggregated. Combining a PDB analysis with molecular modelling provides a rational explanation, demonstrating that Glu and Arg form salt bridges more commonly, utilize a wider range of rotamer conformations, and are more dynamic than Glu–Lys. This promiscuous nature of Arg helps explain the increased propensity of de novo Arg-rich SAHs to aggregate. Importantly, the specific K:R ratio is likely to be important in determining helical stability in de-novo and naturally-occurring polypeptides, giving new insight into how single α-helices are stabilized

Neuroanatomical Abnormalities in Violent Individuals with and without a Diagnosis of Schizophrenia

Several structural brain abnormalities have been associated with aggression in patients with schizophrenia. However, little is known about shared and distinct abnormalities underlying aggression in these subjects and non-psychotic violent individuals. We applied a region-of interest volumetric analysis of the amygdala, hippocampus, and thalamus bilaterally, as well as whole brain and ventricular volumes to investigate violent (n = 37) and non-violent chronic patients (n = 26) with schizophrenia, non-psychotic violent (n = 24) as well as healthy control subjects (n = 24). Shared and distinct volumetric abnormalities were probed by analysis of variance with the factors violence (non-violent versus violent) and diagnosis (non-psychotic versus psychotic), adjusted for substance abuse, age, academic achievement and negative psychotic symptoms. Patients showed elevated vCSF volume, smaller left hippocampus and smaller left thalamus volumes. This was particularly the case for non-violent individuals diagnosed with schizophrenia. Furthermore, patients had reduction in right thalamus size. With regard to left amygdala, we found an interaction between violence and diagnosis. More specifically, we report a double dissociation with smaller amygdala size linked to violence in non-psychotic individuals, while for psychotic patients smaller size was linked to non-violence. Importantly, the double dissociation appeared to be mostly driven by substance abuse. Overall, we found widespread morphometric abnormalities in subcortical regions in schizophrenia. No evidence for shared volumetric abnormalities in individuals with a history of violence was found. Finally, left amygdala abnormalities in non-psychotic violent individuals were largely accounted for by substance abuse. This might be an indication that the association between amygdala reduction and violence is mediated by substance abuse. Our results indicate the importance of structural abnormalities in aggressive individuals

Searching the protein structure database for ligand-binding site similarities using CPASS v.2

<p>Abstract</p> <p>Background</p> <p>A recent analysis of protein sequences deposited in the NCBI RefSeq database indicates that ~8.5 million protein sequences are encoded in prokaryotic and eukaryotic genomes, where ~30% are explicitly annotated as "hypothetical" or "uncharacterized" protein. Our Comparison of Protein Active-Site Structures (CPASS v.2) database and software compares the sequence and structural characteristics of experimentally determined ligand binding sites to infer a functional relationship in the absence of global sequence or structure similarity. CPASS is an important component of our Functional Annotation Screening Technology by NMR (FAST-NMR) protocol and has been successfully applied to aid the annotation of a number of proteins of unknown function.</p> <p>Findings</p> <p>We report a major upgrade to our CPASS software and database that significantly improves its broad utility. CPASS v.2 is designed with a layered architecture to increase flexibility and portability that also enables job distribution over the Open Science Grid (OSG) to increase speed. Similarly, the CPASS interface was enhanced to provide more user flexibility in submitting a CPASS query. CPASS v.2 now allows for both automatic and manual definition of ligand-binding sites and permits pair-wise, one versus all, one versus list, or list versus list comparisons. Solvent accessible surface area, ligand root-mean square difference, and Cβ distances have been incorporated into the CPASS similarity function to improve the quality of the results. The CPASS database has also been updated.</p> <p>Conclusions</p> <p>CPASS v.2 is more than an order of magnitude faster than the original implementation, and allows for multiple simultaneous job submissions. Similarly, the CPASS database of ligand-defined binding sites has increased in size by ~ 38%, dramatically increasing the likelihood of a positive search result. The modification to the CPASS similarity function is effective in reducing CPASS similarity scores for false positives by ~30%, while leaving true positives unaffected. Importantly, receiver operating characteristics (ROC) curves demonstrate the high correlation between CPASS similarity scores and an accurate functional assignment. As indicated by distribution curves, scores ≥ 30% infer a functional similarity. Software URL: <url>http://cpass.unl.edu</url>.</p

Prediction of Glioblastoma Multiform Response to Bevacizumab Treatment Using Multi-Parametric MRI

Glioblastoma multiform (GBM) is a highly malignant brain tumor. Bevacizumab is a recent therapy for stopping tumor growth and even shrinking tumor through inhibition of vascular development (angiogenesis). This paper presents a non-invasive approach based on image analysis of multi-parametric magnetic resonance images (MRI) to predict response of GBM to this treatment. The resulting prediction system has potential to be used by physicians to optimize treatment plans of the GBM patients. The proposed method applies signal decomposition and histogram analysis methods to extract statistical features from Gd-enhanced regions of tumor that quantify its microstructural characteristics. MRI studies of 12 patients at multiple time points before and up to four months after treatment are used in this work. Changes in the Gd-enhancement as well as necrosis and edema after treatment are used to evaluate the response. Leave-one-out cross validation method is applied to evaluate prediction quality of the models. Predictive models developed in this work have large regression coefficients (maximum R2 = 0.95) indicating their capability to predict response to therapy

The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines

<p>Abstract</p> <p>Background</p> <p>Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37) were gamma-irradiated (200 Gy), approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate ³H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV)-irradiation as a possible adjunct to, or replacement for gamma-irradiation.</p> <p>Methods</p> <p>Melanoma cells were gamma- and/or UV-irradiated. ³H-thymidine uptake was used to assess proliferation of the treated and untreated cells. Caspase-3 activity and DNA fragmentation were measured as indicators of apoptosis. Immunohistochemistry and Western blot analysis was used to assess antigen expression.</p> <p>Results</p> <p>UV-irradiation, either alone or in combination with gamma-irradiation, proved to be extremely effective in controlling the proliferation of melanoma cells. In contrast to gamma-irradiation, UV-irradiation was also capable of inducing significant levels of apoptosis. UV-irradiation, but not gamma-irradiation, was associated with the loss of tyrosinase expression. Neither form of radiation affected the expression of gp100, MART-1/MelanA, or S100.</p> <p>Conclusion</p> <p>These results indicate that UV-irradiation may increase the safety of autologous melanoma vaccines, although it may do so at the expense of altering the antigenic profile of the irradiated tumor cells.</p