Are Preoperative Kattan and Stephenson Nomograms Predicting Biochemical Recurrence after Radical Prostatectomy Applicable in the Chinese Population?

Purpose. Kattan and Stephenson nomograms are based on the outcomes of patients with prostate cancer recruited in the USA, but their applicability to Chinese patients is yet to be validated. We aim at studying the predictive accuracy of these nomograms in the Chinese population. Patients and Methods. A total of 408 patients who underwent laparoscopic or open radical resection of prostate from 1995 to 2009 were recruited. The preoperative clinical parameters of these patients were collected, and they were followed up regularly with PSA monitored. Biochemical recurrence was defined as two or more consecutive PSA levels >0.4 ng/mL after radical resection of prostate or secondary cancer treatment. Results. The overall observed 5-year and 10-year biochemical recurrence-free survival rates were 68.3% and 59.8%, which was similar to the predicted values by the Kattan and Stephenson nomograms, respectively. The results of our study achieved a good concordance with both nomograms (Kattan: 5-years, 0.64; Stephenson: 5-years, 0.62, 10-years, 0.71). Conclusions. The incidence of prostate cancer in Hong Kong is increasing together with the patients’ awareness of this disease. Despite the fact that Kattan nomograms were derived from the western population, it has been validated in our study to be useful in Chinese patients as well

Distinct but overlapping roles of LRRTM1 and LRRTM2 in developing and mature hippocampal circuits

LRRTMs are postsynaptic cell adhesion proteins that have region-restricted expression in the brain. To determine their role in the molecular organization of synapses in vivo, we studied synapse development and plasticity in hippocampal neuronal circuits in mice lacking both Lrrtm1 and Lrrtm2. We found that LRRTM1 and LRRTM2 regulate the density and morphological integrity of excitatory synapses on CA1 pyramidal neurons in the developing brain but are not essential for these roles in the mature circuit. Further, they are required for long-term-potentiation in the CA3-CA1 pathway and the dentate gyrus, and for enduring fear memory in both the developing and mature brain. Our data show that LRRTM1 and LRRTM2 regulate synapse development and function in a cell-type and developmental-stage-specific manner, and thereby contribute to the fine-tuning of hippocampal circuit connectivity and plasticity

Cag rnas induce dna damage and apoptosis by silencing nudt16 expression in polyglutamine degeneration

DNA damage plays a central role in the cellular pathogenesis of polyglutamine (polyQ) diseases, including Huntington's disease (HD). In this study, we showed that the expression of untranslatable expanded CAG RNA per se induced the cellular DNA damage response pathway. By means of RNA sequencing (RNA-seq), we found that expression of the Nudix hydrolase 16 (NUDT16) gene was down-regulated in mutant CAG RNA-expressing cells. The loss of NUDT16 function results in a misincorporation of damaging nucleotides into DNAs and leads to DNA damage. We showed that small CAG (sCAG) RNAs, species generated from expanded CAG transcripts, hybridize with CUG-containing NUDT16 mRNA and form a CAG-CUG RNA heteroduplex, resulting in gene silencing of NUDT16 and leading to the DNA damage and cellular apoptosis. These results were further validated using expanded CAG RNAexpressing mouse primary neurons and in vivo R6/2 HD transgenic mice. Moreover, we identified a bisamidinium compound, DB213, that interacts specifically with the major groove of the CAG RNA homoduplex and disfavors the CAG-CUG heteroduplex formation. This action subsequently mitigated RNA-induced silencing complex (RISC)-dependent NUDT16 silencing in both in vitro cell and in vivo mouse disease models. After DB213 treatment, DNA damage, apoptosis, and locomotor defects were rescued in HD mice. This work establishes NUDT16 deficiency by CAG repeat RNAs as a pathogenic mechanism of polyQ diseases and as a potential therapeutic direction for HD and other polyQ diseases

Tai-Chi for Residential Patients with Schizophrenia on Movement Coordination, Negative Symptoms, and Functioning: A Pilot Randomized Controlled Trial

Objective. Patients with schizophrenia residing at institutions often suffer from negative symptoms, motor, and functional impairments more severe than their noninstitutionalized counterparts. Tai-chi emphasizes body relaxation, alertness, and movement coordination with benefits to balance, focus, and stress relief. This pilot study explored the efficacy of Tai-chi on movement coordination, negative symptoms, and functioning disabilities towards schizophrenia. Methods. A randomized waitlist control design was adopted, where participants were randomized to receive either the 6-week Tai-chi program and standard residential care or only the latter. 30 Chinese patients with schizophrenia were recruited from a rehabilitation residency. All were assessed on movement coordination, negative symptoms, and functional disabilities at baseline, following intervention and 6 weeks after intervention. Results. Tai-chi buffered from deteriorations in movement coordination and interpersonal functioning, the latter with sustained effectiveness 6 weeks after the class was ended. Controls showed marked deteriorations in those areas. The Tai-chi group also experienced fewer disruptions to life activities at the 6-week maintenance. There was no significant improvement in negative symptoms after Tai-chi. Conclusions. This study demonstrated encouraging benefits of Tai-chi in preventing deteriorations in movement coordination and interpersonal functioning for residential patients with schizophrenia. The ease of implementation facilitates promotion at institutional psychiatric services

Elastic theory for the vortex-lattice melting in iron-based high-Tc superconductors

The vortex-lattice melting transitions in two typical iron-based high-Tc superconductor $Ba(Fe_{1-x}Co_{x})_{2}As_{2}$ (122-type) and$Nd(O_{1-x}F_{x})FeAs$ (1111-type) for magnetic fields both parallel and perpendicular to the anisotropy axis are studied within the elastic theory. Using the parameters from experiments, the vortex-lattice melting lines in the H-T diagram are located systematically by various groups of Lindemann numbers. It is observed that the theoretical result for the vortex melting on $Ba(Fe_{1-x}Co_{x})_{2}As_{2}$ for parallel fields agrees well the recent experimental data. The future experimental results for the vortex melting can be compared with the present theoretical prediction by tuning reasonable Lindemann numbers.Comment: 10 pages, 5 figure

Probing the Reactivity of the Ce=O Multiple Bond in a Cerium(IV) Oxo Complex

The reactivity of the cerium­(IV) oxo complex [(L_OEt)₂Ce^IV(O)­(H₂O)]·MeC­(O)­NH₂ (<b>1</b>; L_OEt^– = [CoCp­{P­(O)­(OEt)₂}₃]⁻, where Cp = η⁵-C₅H₅) toward electrophiles and Brønsted acids has been investigated. The treatment of <b>1</b> with acetic anhydride afforded the diacetate complex [Ce^IV(L_OEt)₂(O₂CMe)₂] (<b>2</b>). The reaction of <b>1</b> with B­(C₆F₅)₃ yielded [Ce^IV(L_OEt)₂(Me₂CONH₂)₂]­[B­(C₆F₅)₃(OH)]₂ (<b>3</b>), in which the [B­(C₆F₅)₃(OH)]⁻ anions are H-bonded to the O-bound acetamide ligands. The treatment of <b>1</b> with HCl and HNO₃ afforded [Ce^IV(L_OEt)₂Cl₂] and [Ce^IV(L_OEt)₂(NO₃)₂], respectively. Protonation of <b>1</b> with triflic acid (HOTf) gave the diaqua complex [Ce^IV(L_OEt)₂(H₂O)₂]­(OTf)₂ (<b>4</b>), in which the triflate anions are H-bonded to the two aqua ligands. The treatment of <b>1</b> with phenol afforded the phenoxide complex [Ce^IV(L_OEt)₂(OPh)₂] (<b>5</b>). The oxo-bridged bimetallic complex [(L_OEt)₂(Me₂CONH₂)­Ce^IV(O)­NaL_OEt] (<b>6</b>) with the Ce–O_oxo and Na–O_oxo distances of 1.953(4) and 2.341(4) Å, respectively, was obtained from the reaction of <b>1</b> with [NaL_OEt]. Density functional theory calculations showed that the model complex [(L_OMe)₂Ce^IV(Me₂CONH₂)­(O)­NaL_OMe] (<b>6A</b>; L_OMe^– = [CoCp­{P­(O)­(OMe)₂}₃]⁻) contains a polarized CeO multiple bond. The energy for dissociation of the {NaL_OMe} fragment from <b>6A</b> in acetonitrile was calculated to be +33.7 kcal/mol, which is higher than that for dissociation of the H-bonded acetamide from [(L_OMe)₂Ce^IV(O)­(H₂O)]·MeC­(O)­NH₂ (<b>1A</b>) (calculated to be +17.4 kcal/mol). In hexanes containing trace water, complex <b>1</b> decomposed readily to a mixture of a tetranuclear cerium­(IV) oxo cluster, [Ce^IV₄(L_OEt)₄(μ₄-O)­(μ₂-O)₄(μ₂-OH)₂] (<b>7</b>), and a cerium­(III) complex, [Ce^III(L_OEt)₂(H₂O)₂]­[L_OEt] [<b>8</b>(L_OEt)], whereas the cerium/sodium oxo complex <b>6</b> is stable under the same conditions. The crystal structures of <b>3</b>, <b>4</b>·H₂O, <b>6</b>, and <b>8</b>(L_OEt) have been determined

Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study

Objectives To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling

Skewed Distribution of Circulating Activated Natural Killer T (NKT) Cells in Patients with Common Variable Immunodeficiency Disorders (CVID)

Common variable immunodeficiency disorder (CVID) is the commonest cause of primary antibody failure in adults and children, and characterized clinically by recurrent bacterial infections and autoimmune manifestations. Several innate immune defects have been described in CVID, but no study has yet investigated the frequency, phenotype or function of the key regulatory cell population, natural killer T (NKT) cells. We measured the frequencies and subsets of NKT cells in patients with CVID and compared these to healthy controls. Our results show a skewing of NKT cell subsets, with CD4+ NKT cells at higher frequencies, and CD8+ NKT cells at lower frequencies. However, these cells were highly activated and expression CD161. The NKT cells had a higher expression of CCR5 and concomitantly expression of CCR5+CD69+CXCR6 suggesting a compensation of the remaining population of NKT cells for rapid effector action