Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer???s disease

The absence of effective therapeutics against Alzheimer???s disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-?? (A??), metal-A??, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets??? reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs.ope

Body Acupuncture for Nicotine Withdrawal Symptoms: A Randomized Placebo-controlled Trial

This study evaluated whether improvements in nicotine withdrawal symptoms (NWS), depression and anxiety are greater for body acupuncture than for sham acupuncture. Smoking volunteers from the public were randomized to receive six sessions of either real or sham acupuncture for 2 weeks. The primary outcome measure was NWS measured by the Minnesota Nicotine Withdrawal Score, and the secondary measures were scores on the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Eighty volunteers were randomized into real acupuncture (n = 38) and sham acupuncture (n = 42) groups, of which 46 subjects (22 and 24 in the real and sham acupuncture groups, respectively) completed the treatment and the 2-week follow-up. An intention-to-treat analysis revealed that the NWS did not differ significantly between the real and sham acupuncture groups immediately after the treatment (12.2 ± 9.7 and 12.8 ± 7.7, respectively; mean ± SD) and at the 2-week follow-up (11.7 ± 10.2 and 12.6 ± 7.8). Both groups also showed similar improvements in BDI and BAI scores. These results indicate that the real acupuncture treatment tested in this trial was no more effective than sham acupuncture at reducing NWS, depression and anxiety for smoking cessation

Effects of Elsholtzia splendens and Cirsium japonicum on premenstrual syndrome

Premenstrual syndrome is a common chronic disorder in most women of reproductive age. The main symptoms are depression, anxiety, tension, feeling out of control, and mastalgia. In premenstrual syndrome, the effects of aromatic edible Elsholtzia splendens and Cirsium japonicum were investigated for over 3 months in 30 women participants in their twenties. In the Elsholtzia splendens capsule treated group, scores of depression and anxiety were significantly lower than those in the Cirsium japonicum capsule treated group. Moreover, instability of the premenstrual assessment form was significantly decreased in the Elsholtzia splendens capsule treated group. Our results suggest that Elsholtzia splendens could be an effective plant material in relieving symptoms of premenstrual syndrome

Quantification of Cell Signaling Networks Using Kinase Activity Chemosensors

The ability to directly determine endogenous kinase activity in tissue homogenates provides valuable insights into signaling aberrations that underlie disease phenotypes. When activity data is collected across a panel of kinases, a unique “signaling fingerprint” is generated that allows for discrimination between diseased and normal tissue. Here we describe the use of peptide-based kinase activity sensors to fingerprint the signaling changes associated with disease states. This approach leverages the phosphorylation-sensitive sulfonamido-oxine (Sox) fluorophore to provide a direct readout of kinase enzymatic activity in unfractionated tissue homogenates from animal models or clinical samples. To demonstrate the application of this technology, we focus on a rat model of nonalcoholic fatty liver disease (NAFLD). Sox-based activity probes allow for the rapid and straightforward analysis of changes in kinase enzymatic activity associated with disease states, providing leads for further investigation using traditional biochemical approaches

Patients' knowledge and perception on optic neuritis management before and after an information session

<p>Abstract</p> <p>Background</p> <p>Patients' understanding of their condition affect the choice of treatment. The aim of this study is to evaluate patients' understanding and treatment preferences before and after an information session on the treatment of acute optic neuritis.</p> <p>Methods</p> <p>Participants were asked to complete a questionnaire consisting of 14 questions before and after an information session presented by a neuro-ophthalmologist. The information session highlighted the treatment options and the treatment effects based on the Optic Neuritis Treatment Trial in plain patient language. The information session stressed the finding that high dose intravenous steroid therapy accelerated visual recovery but does not change final vision and that treatment with oral prednisone alone resulted in a higher incidence of recurrent optic neuritis.</p> <p>Results</p> <p>Before the information session, 23 (85%) participants knew that there was treatment available for ON and this increased to 27 (100%) after the information session. There were no significantly change in patients knowledge of symptoms of ON and purpose of treatment before and after the information session. Before the information session, 4 (14%) respondents reported they would like to be treated by oral steroid alone in the event of an optic neuritis and 5 (19%) did not respond. After the education session, only 1 patient (4%) indicated they would undergo treatment with oral steroid alone but 25 (92%) indicated they would undergo treatment with intravenous steroid treatment, alone or in combination with oral treatment. Results indicated that there were significant differences in the numbers of participants selecting that they would undergo treatment with a steroid injection (n = 22, p = 0.016).</p> <p>Conclusions</p> <p>In this study, patients have shown good understanding of the symptoms and signs of optic neuritis. The finding that significant increases in the likelihood of patients engaging in best practice can be achieved with an information session is very important. This suggests that patient knowledge of available treatments and outcomes can play an important role in implementing and adopting guideline recommendations.</p

Australian Sphingidae – DNA Barcodes Challenge Current Species Boundaries and Distributions

© 2014 Rougerie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

The Nigerian Twin and Sibling Registry:An update

Here we provide an update of the 2013 report on the Nigerian Twin and Sibling Registry (NTSR). The major aim of the NTSR is to understand genetic and environmental influences and their interplay in psychological and mental health development in Nigerian children and adolescents. Africans have the highest twin birth rates among all human populations, and Nigeria is the most populous country in Africa. Due to its combination of large population and high twin birth rates, Nigeria has one of the largest twin populations in the world. In this article, we provide current updates on the NTSR samples recruited, recruitment procedures, zygosity assessment and findings emerging from the NTSR

Inter-hemispheric EEG coherence analysis in Parkinson's disease : Assessing brain activity during emotion processing

Parkinson’s disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3–AF4, F7–F8, F3–F4, FC5–FC6, T7–T8, P7–P8, and O1–O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities

Neural Correlate of Filtering of Irrelevant Information from Visual Working Memory

In a dynamic environment stimulus task relevancy could be altered through time and it is not always possible to dissociate relevant and irrelevant objects from the very first moment they come to our sight. In such conditions, subjects need to retain maximum possible information in their WM until it is clear which items should be eliminated from WM to free attention and memory resources. Here, we examined the neural basis of irrelevant information filtering from WM by recording human ERP during a visual change detection task in which the stimulus irrelevancy was revealed in a later stage of the task forcing the subjects to keep all of the information in WM until test object set was presented. Assessing subjects' behaviour we found that subjects' RT was highly correlated with the number of irrelevant objects and not the relevant one, pointing to the notion that filtering, and not selection, process was used to handle the distracting effect of irrelevant objects. In addition we found that frontal N150 and parietal N200 peak latencies increased systematically as the amount of irrelevancy load increased. Interestingly, the peak latency of parietal N200, and not frontal N150, better correlated with subjects' RT. The difference between frontal N150 and parietal N200 peak latencies varied with the amount of irrelevancy load suggesting that functional connectivity between modules underlying fronto-parietal potentials vary concomitant with the irrelevancy load. These findings suggest the existence of two neural modules, responsible for irrelevant objects elimination, whose activity latency and functional connectivity depend on the number of irrelevant object