Association of treatment satisfaction and psychopathological sub-syndromes among involuntary patients with psychotic disorders

Publisher's version: http://www.springerlink.com/content/rx24036274667t10

Tear proteomic analysis of Sjogren syndrome patients with dry eye syndrome by two-dimensional-nano-liquid chromatography coupled with tandem mass spectrometry

We examined the tear film proteome of patients with Sjögren's syndrome (SS) and dry eye syndrome (group A), patients with dry eye symptoms (group B) and normal volunteers (group C). Tear samples were pooled from 8 subjects from each group and were subjected to two-dimensional-nano-liquid chromatography coupled with tandem mass spectrometry (2D-nano-LC-MS/MS). The tear breakup time for group A was significantly reduced compared with group B and C (P < 0.001). Group A (Schirmer I test, 2.13 +/- 2.38 mm/5 min) had markedly lower tear volume than group B (5.94 +/- 4.75 mm/5 min) and C (14.44 +/- 6.57 mm/5 min) (P < 0.001). Group A had significantly higher normalized tear protein content (1.8291 +/- 0.2241 mu g/mm) than group B (1.0839 +/- 0.1120 mu g/mm) (P = 0.001) and C (0.2028 +/- 0.0177 mu g/mm) (P = 0.001). The 2D-nano-LC-MS/MS analysis identified a total of 435 proteins, including 182 (54.8%),247 (74.4%) and 278 (83.7%) in group A, B, and C, respectively, with 56 (16.7%) proteins including defensin alpha 1, clusterin and lactotransferrin unique to group A. In conclusion, dry eye syndrome in SS patients is associated with an altered proteomic profile with dysregulated expression of proteins involved in a variety of important cellular process including inflammation, immunity, and oxidative stress

Accuracy of Transperineal Targeted Prostate Biopsies, Visual Estimation and Image Fusion in Men Needing Repeat Biopsy in the PICTURE Trial

PURPOSE: To evaluate detection of clinically significant prostate cancer (csPCa) using MRI-targeted biopsies, and compare visual-estimation to image-fusion targeting, in patients requiring repeat prostate biopsies. MATERIALS AND METHODS: Prospective, ethics-committee approved, registered PICTURE trial enrolling 249 consecutive patients (11th/January/2012-29th/January/2014). Men underwent an mpMRI and were blinded to its results. All underwent transperineal template prostate mapping (TTPM) biopsies. In 200 with a lesion, this was preceded by visual-estimation and image-fusion targeted biopsies. For the primary endpoint, csPCa was defined as Gleason >/=4+3 and/or any grade of cancer length >/=6mm. Other definitions of csPCa were also evaluated. RESULTS: Mean (SD) age was 62.6 (7) years, median (IQR) PSA 7.17ng/ml (5.25, 10.09), mean primary lesion size 0.37cc (SD1.52), with mean 4.3 (SD2.3) targeted cores per lesion (visual-estimation and image-fusion combined) and mean 48.7 (SD12.3) TTPM-biopsy cores. TTPM-biopsies detected 97 (48.5%) cases of csPCa and 85 (42.5%) insignificant cancers. Overall, mpMRI-targeted biopsies detected 81 (40.5%) csPCa and 63 (31.5%) insignificant cancers. Eighteen (9%) with csPCa on MRI-targeted biopsies were benign or clinically insignificant on TTPM-biopsy. Thirty-four (17%) had csPCa detected on TTPM-biopsy but not on MRI-targeted biopsies; approximately half of these were present in non-targeted areas. csPCa was found with visual-estimation and image-fusion in 53/169 (31.3%) and 48/169 (28.4%) (McNemar's test, p=0.5322). Visual-estimation missed 23 (13.6%) csPCa detected by image-fusion; image-fusion missed 18 (10.8%) csPCa that visual-estimation detected. CONCLUSIONS: MRI-targeted biopsies are accurate at detection of csPCa and reducing over-diagnosis of insignificant cancers. To maximise detection both visual-estimation and image-fusion targeted biopsies are required

Self-assembly of Microcapsules via Colloidal Bond Hybridization and Anisotropy

Particles with directional interactions are promising building blocks for new functional materials and may serve as models for biological structures. Mutually attractive nanoparticles that are deformable due to flexible surface groups, for example, may spontaneously order themselves into strings, sheets and large vesicles. Furthermore, anisotropic colloids with attractive patches can self-assemble into open lattices and colloidal equivalents of molecules and micelles. However, model systems that combine mutual attraction, anisotropy, and deformability have---to the best of our knowledge---not been realized. Here, we synthesize colloidal particles that combine these three characteristics and obtain self-assembled microcapsules. We propose that mutual attraction and deformability induce directional interactions via colloidal bond hybridization. Our particles contain both mutually attractive and repulsive surface groups that are flexible. Analogous to the simplest chemical bond, where two isotropic orbitals hybridize into the molecular orbital of H2, these flexible groups redistribute upon binding. Via colloidal bond hybridization, isotropic spheres self-assemble into planar monolayers, while anisotropic snowman-like particles self-assemble into hollow monolayer microcapsules. A modest change of the building blocks thus results in a significant leap in the complexity of the self-assembled structures. In other words, these relatively simple building blocks self-assemble into dramatically more complex structures than similar particles that are isotropic or non-deformable

Single Molecule Analysis of Replicated DNA Reveals the Usage of Multiple KSHV Genome Regions for Latent Replication

Kaposi's sarcoma associated herpesvirus (KSHV), an etiologic agent of Kaposi's sarcoma, Body Cavity Based Lymphoma and Multicentric Castleman's Disease, establishes lifelong latency in infected cells. The KSHV genome tethers to the host chromosome with the help of a latency associated nuclear antigen (LANA). Additionally, LANA supports replication of the latent origins within the terminal repeats by recruiting cellular factors. Our previous studies identified and characterized another latent origin, which supported the replication of plasmids ex-vivo without LANA expression in trans. Therefore identification of an additional origin site prompted us to analyze the entire KSHV genome for replication initiation sites using single molecule analysis of replicated DNA (SMARD). Our results showed that replication of DNA can initiate throughout the KSHV genome and the usage of these regions is not conserved in two different KSHV strains investigated. SMARD also showed that the utilization of multiple replication initiation sites occurs across large regions of the genome rather than a specified sequence. The replication origin of the terminal repeats showed only a slight preference for their usage indicating that LANA dependent origin at the terminal repeats (TR) plays only a limited role in genome duplication. Furthermore, we performed chromatin immunoprecipitation for ORC2 and MCM3, which are part of the pre-replication initiation complex to determine the genomic sites where these proteins accumulate, to provide further characterization of potential replication initiation sites on the KSHV genome. The ChIP data confirmed accumulation of these pre-RC proteins at multiple genomic sites in a cell cycle dependent manner. Our data also show that both the frequency and the sites of replication initiation vary within the two KSHV genomes studied here, suggesting that initiation of replication is likely to be affected by the genomic context rather than the DNA sequences

Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice

Several vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies

Transmission Pattern of Drug-Resistant Tuberculosis and Its Implication for Tuberculosis Control in Eastern Rural China

OBJECTIVE: Transmission patterns of drug-resistant Mycobacterium tuberculosis (MTB) may be influenced by differences in socio-demographics, local tuberculosis (TB) endemicity and efficaciousness of TB control programs. This study aimed to investigate the impact of DOTS on the transmission of drug-resistant TB in eastern rural China. METHODS: We conducted a cross-sectional study of all patients diagnosed with drug-resistant TB over a one-year period in two rural Chinese counties with varying lengths of DOTS implementation. Counties included Deqing, with over 11 years' DOTS implementation and Guanyun, where DOTS was introduced 1 year prior to start of this study. We combined demographic, clinical and epidemiologic information with IS6110-based restricted fragment length polymorphism (RFLP) and Spoligotyping analysis of MTB isolates. In addition, we conducted DNA sequencing of resistance determining regions to first-line anti-tuberculosis agents. RESULTS: Of the 223 drug-resistant isolates, 73(32.7%) isolates were identified with clustered IS6110RFLP patterns. The clustering proportion among total drug-resistant TB was higher in Guanyun than Deqing (26/101.vs.47/122; p,0.04), but not significantly different among the 53 multidrug-resistant isolates (10/18.vs.24/35; p,0.35). Patients with cavitary had increased risk of clustering in both counties. In Guanyun, patients with positive smear test or previous treatment history had a higher clustering proportion. Beijing genotype and isolates resistant to isoniazid and/or rifampicin were more likely to be clustered. Of the 73 patients with clustered drug-resistant isolates, 71.2% lived in the same or neighboring villages. Epidemiological link (household and social contact) was confirmed in 12.3% of the clustered isolates. CONCLUSION: Transmission of drug-resistant TB in eastern rural China is characterized by small clusters and limited geographic spread. Our observations highlight the need for supplementing DOTS with additional strategies, including active case finding at the village level, effective treatment for patients with cavities and drug susceptibility testing for patients at increased risk for drug-resistance

Structure of hadron resonances with a nearby zero of the amplitude

We discuss the relation between the analytic structure of the scattering amplitude and the origin of an eigenstate represented by a pole of the amplitude.If the eigenstate is not dynamically generated by the interaction in the channel of interest, the residue of the pole vanishes in the zero coupling limit. Based on the topological nature of the phase of the scattering amplitude, we show that the pole must encounter with the Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the dynamical component of the eigenstate is small if a CDD zero exists near the eigenstate pole. We show that the line shape of the resonance is distorted from the Breit-Wigner form as an observable consequence of the nearby CDD zero. Finally, studying the positions of poles and CDD zeros of the KbarN-piSigma amplitude, we discuss the origin of the eigenstates in the Lambda(1405) region.Comment: 7 pages, 3 figures, v2: published versio

Lack of association between genetic polymorphisms within DUSP12 - ATF6 locus and glucose metabolism related traits in a Chinese population

<p>Abstract</p> <p>Background</p> <p>Genome-wide linkage studies in multiple ethnic populations found chromosome 1q21-q25 was the strongest and most replicable linkage signal in the human chromosome. Studies in Pima Indian, Caucasians and African Americans identified several SNPs in <it>DUSP12 </it>and <it>ATF6</it>, located in chromosome 1q21-q23, were associated with type 2 diabetes.</p> <p>Methods</p> <p>We selected 19 single nucleotide polymorphisms (SNPs) that could tag 98% of the SNPs with minor allele frequencies over 0.1 within <it>DUSP12-ATF6 </it>region. These SNPs were genotyped in a total of 3,700 Chinese Han subjects comprising 1,892 type 2 diabetes patients and 1,808 controls with normal glucose regulation.</p> <p>Results</p> <p>None of the SNPs and haplotypes showed significant association to type 2 diabetes in our samples. No association between the SNPs and quantitative traits was observed either.</p> <p>Conclusions</p> <p>Our data suggests common SNPs within <it>DUSP12</it>-<it>ATF6 </it>locus may not play a major role in glucose metabolism in the Chinese.</p