The early detection of major depression in elderly individuals who are at risk of developing the disease is of prime importance when it comes to the prevention of geriatric depression. We used resting-state functional magnetic resonance imaging (fMRI) to examine changes in regional homogeneity (ReHo) of spontaneous activity in late-life subthreshold depression (StD), and we evaluated the sensitivity/specificity performance of these changes. Nineteen elderly individuals with StD and 18 elderly controls underwent a resting-state fMRI scan. The ReHo approach was employed to examine whether StD was related to alterations in resting-state neural activity, in the form of abnormal regional synchronization. Receiver operating characteristic curve analysis and the Fisher stepwise discriminant analysis were used to evaluate the sensitivity/specificity characteristics of the ReHo index in discriminating between the StD subjects and normal controls. The results demonstrated that, compared to controls, StD subjects display lower ReHo in the right orbitofrontal cortex (OFC), left dorsolateral prefrontal cortex (DLPFC), left postcentral gyrus (PCG), and left middle frontal and inferior temporal gyri, as well as higher ReHo in the bilateral insula and right DLPFC. The left PCG and the right DLPFC, OFC, and posterior insula, together reported a predictive accuracy of 91.9%. These results suggest that the regional activity coherence was changed in the resting brain of StD subjects, and that these alterations may serve as potential markers for the early detection of StD in late-life depression.
The M‐superfamily of conotoxins has a typical Cys framework (‐CC‐C‐C‐CC‐), and is one of the eight major superfamilies found in the venom of the cone snail. Depending on the number of residues located in the last Cys loop (between Cys4 and Cys5), the M‐superfamily family can be divided into four branches, namely M‐1, ‐2, ‐3 and ‐4. Recently, two M‐1 branch conotoxins (mr3e and tx3a) have been reported to possess a new disulfide bond arrangement between Cys1 and Cys5, Cys2 and Cys4, and Cys3 and Cys6, which is different from those seen in the M‐2 and M‐4 branches. Here we report the 3D structure of mr3e determined by 2D 1H NMR in aqueous solution. Twenty converged structures of this peptide were obtained on the basis of 190 distance constraints obtained from NOE connectivities, as well as six ϕ dihedral angle, three hydrogen bond, and three disulfide bond constraints. The rmsd values about the averaged coordinates of the backbone atoms were 0.43 ± 0.19 Å. Although mr3e has the same Cys arrangement as M‐2 and M‐4 conotoxins, it adopts a distinctive backbone conformation with the overall molecule resembling a ‘flying bird’. Thus, different disulfide linkages may be employed by conotoxins with the same Cys framework to result in a more diversified backbone scaffold.
BackgroundDysmenorrhea is a common menstrual complaint among adolescent girls and women of reproductive age. The treatment of dysmenorrhea is typically selected from multidisciplinary options, including complementary and alternative medicine such as acupuncture and moxibustion. However, there are few published randomized controlled trials concerning moxibustion treatment for dysmenorrhea. This trial aims to investigate the efficacy and safety of moxibustion for primary dysmenorrhea, and to identify the optimal time of moxibustion treatment for primary dysmenorrhea.Methods/DesignThis protocol is for a randomized controlled trial in which the assessor and statistician will be blinded. A total of 222 eligible patients with dysmenorrhea will be randomly assigned to three groups in a 1:1:1 ratio as treatment group A (treated before menstruation onset), treatment group B (treated at the onset of menstruation), or control group C (waiting list group). The participants assigned to the treatment groups will receive suspended moxibustion treatment at Sanyinjiao (SP6) and Guanyuan (CV4), while the waiting list group will not receive moxibustion treatment until the completion of the study. The trial period will consist of three baseline menstrual cycles, three menstrual cycles of treatment, and three menstrual cycles in the follow-up period. The primary outcome will be measured by changes in the Cox Menstrual Symptom Scale and the secondary outcomes will be measured using the Visual Analogue Scale, Cox Retrospective Symptom Scale, diary entries, the Self-rating Depression Scale, and the Self-rating Anxiety Scale. The safety of moxibustion will be assessed at every visit.DiscussionThis trial aims to assess the effectiveness and safety of moxibustion for primary dysmenorrhea, as well as to determine whether the optimal time of treatment for primary dysmenorrhea in clinical practice is before or after the onset of menstrual pain.Trial registrationChinese Clinical Trial Register: ChiCTR-TRC-14004627, registered on 9 May 2014.
As an integral part of traditional Chinese medicine (TCM), acupuncture is a convenient and effective therapy with fewer adverse effects. Recently, researches on meridian essence have become core issues of modern TCM. Numerous experiments have demonstrated the objective existence of meridians by different technologies since 1950s, such as biophysics, biochemistry, and molecular biology. In this paper, we review biophysical studies on electric, acoustic, thermal, optical, magnetic, isotopic, and myoelectric aspects of meridians and acupoints. These studies suggest that meridians/acupoints have biophysical characteristics which are different from nonacupuncture points. Owing to the limitations of previous studies, future research using high-throughput technologies such as omics and multicenter randomized controlled trials should be performed to explore the acupuncture's mechanisms of action and demonstration of efficacy.
Major depression disorder (MDD) is closely associated with functional and structural changes in the hippocampus (HC). Neuroimaging studies have demonstrated abnormal functional connectivity (FC) of the HC in patients with MDD, but it remains unknown whether this abnormal hippocampal FC pattern occurs in individuals with subthreshold depression (StD) who are at high risk of MDD. Resting-state functional magnetic resonance imaging data were collected from 19 elderly individuals with StD and 18 normal controls. Whole brain voxel-wise FC analyses were conducted to investigate the hippocampal FC pattern by selecting the HC as the region of interest, and correlation analyses were performed to explore the association of altered FC of the HC with self-reported depressive symptoms. The results showed that elderly individuals with StD had substantially decreased FC of the HC to the prefrontal and cuneus cortices compared with healthy normal controls. Moreover, the strength of HC-cuneus connectivity was correlated with self-reported depressive symptoms in elderly individuals with StD. These findings suggest that dysfunctional integration within the HC and cortical regions may occur at an early stage of depression.
In the present work, density functional theory (DFT) has been used to investigate CO binding to the hexacoordinated heme in neuroglobin (Ngb) protein. Structural relaxation of the selected model system in the protein environment has been fully included by the alternative quantum and molecular mechanical optimizations. The polarized continuum model (PCM) was used to simulate interaction between the model system and the protein environment. The CO binding could take place in a concerted way and a barrier of 17.9 kcal mol(-1) was predicted on the concerted singlet pathway, which is not favorable in energy. The adiabatically sequential pathway requires an energy of 14.5 kcal mol(-1) for formation of the singlet intermediate. There exist two nonadiabatic sequential pathways for the CO binding, which involves the triplet and quintet states of intermediate. Both the singlet/triplet and singlet/quintet intersections play an important role in nonadiabatic sequential processes, which enhance the probability that the processes occur. The nonadiabatic processes that involve the triplet and quintet states of intermediate are the most probable pathways for the CO binding to the hexacoordinated heme in Ngb to form the product complex.
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