Background

Evidence suggests that minority populations have lower levels of attendance and retention in mental health care than non-Latino whites. Patient activation and empowerment interventions may be effective in increasing minority patients’ attendance and retention.

Objectives

This study developed and evaluated a patient self-reported activation and empowerment strategy in mental health care.

Research Design

The Right Question Project–Mental Health (RQP-MH) trainings consisted of 3 individual sessions using a pre/post test comparison group design with patients from 2 community mental health clinics. The RQP-MH intervention taught participants to identify questions that would help them consider their role, process and reasons behind a decision; and empowerment strategies to better manage their care.

Subjects

A total of 231 participated, completing at least the pretest interview (n = 141 intervention site, 90 comparison site).

Measures

Four main outcomes were linked to the intervention: changes in self-reported patient activation; changes in self-reported patient empowerment; treatment attendance; and retention in treatment.

Results

Findings show that intervention participants were over twice as likely to be retained in treatment and over 3 times more likely than comparison participants to have scheduled at least 1 visit during the 6-month follow-up period. Similarly, intervention participants demonstrated 29% more attendance to scheduled visits than comparison patients. There was no evidence of an effect on self-reported patient empowerment, only on self-reported patient activation.

Conclusions

Results demonstrate the intervention’s potential to increase self-reported patient activation, retention, and attendance in mental health care for minority populations. By facilitating patient-provider communication, the RQP-MH intervention may help minorities effectively participate in mental health care.

The long-range interactions, required to the accurate predictions of tertiary structures of β-sheet-containing proteins, are still difficult to simulate. To remedy this problem and to facilitate β-sheet structure predictions, many efforts have been made by computational methods. However, known efforts on β-sheets mainly focus on interresidue contacts or amino acid partners. In this study, to go one step further, we studied β-sheets on the strand level, in which a statistical analysis was made on the terminal extensions of paired β-strands. In most cases, the two paired β-strands have different lengths, and terminal extensions exist. The terminal extensions are the extended part of the paired strands besides the common paired part. However, we found that the best pairing required a terminal alignment, and β-strands tend to pair to make bigger common parts. As a result, 96.97%  of β-strand pairs have a ratio of 25% of the paired common part to the whole length. Also 94.26% and 95.98%  of β-strand pairs have a ratio of 40% of the paired common part to the length of the two β-strands, respectively. Interstrand register predictions by searching interacting β-strands from several alternative offsets should comply with this rule to reduce the computational searching space to improve the performances of algorithms.

Some of the main concerns with in vivo application of naked small interfering RNA are rapid degradation and urinary excretion resulting in a short plasma half-life. In this study we investigated how conjugation of polyethylene glycol (PEG) with variable chain length affects siRNA pharmacokinetics and biodistribution.

The PEG chains were conjugated to chemically stabilized siRNA at the 5' terminal end of the passenger strand using click chemistry. The siRNA conjugate remained functionally active and showed significantly prolonged circulation in the blood stream after intravenous injection. siRNA conjugated with 20kDa PEG (PEG20k-siRNA) was most persistent, approximately 50% PEG20k-siRNA remained 1h post-injection, while the uncoupled siRNA was rapidly removed >90% at 15min. In vivo fluorescent imaging of the living animal showed increased concentration of siRNA in peripheral tissue and delayed urine excretion when coupled to PEG 20k. Biodistribution studies by northern blotting revealed equal distribution of conjugated siRNA in liver, kidney, spleen and lung without significant degradation 24 h post-injection. Our study demonstrates that PEG conjugated siRNA can be applied as a delivery system to improve siRNA bioavailability in vivo and may potentially increase the efficiency of siRNA in therapeutic applications.

The AgI atom in the title centrosymmetric dinuclear compound, [Ag2(C11H10N3O)2(C11H11N3O)2]·2H2O, shows a T-shaped coordination arising from bonding to the N atom of a neutral 2-[(pyrimidin-2-yl)amino­meth­yl]phenol ligand, the N atom of the 2-[(pyrimidin-2-yl)amino­meth­yl]phenolate anion [N—Ag—N = 171.8 (1)°] and the terminal O atom of the other anion [Ag—O = 2.606 (3) Å]. A pair of 2-[(pyrimidin-2-yl)amino­meth­yl]phenolate anions link the two AgI atoms to form the dinuclear compound. In the crystal, adjacent dinuclear mol­ecules are linked to the lattice water mol­ecules, generating an O—H⋯O- and N—H⋯O-connected three-dimensional network. In the crystal, the hy­droxy H atom is disordered over two positions in a 1:1 ratio; one half-occupancy H atom is connected to one hy­droxy group, whereas the other half-occupancy H atom is connected to another hy­droxy group.

The title coordination polymer, {[Ag2(C6H5N2O)(C6H6N2O)2]NO3}n, features a deprotonated N-(pyridin-4-yl­methyl­idene)hy­droxy­laminate anion and two neutral N-(pyridin-4-yl­methyl­idene)hydroxyl­amine mol­ecules in the asymmetric unit. The anion connects three AgI atoms through its O and two N-donor atoms. One neutral ligand functions in a monodentate mode; the other functions in a bridging mode, binding though its two N atoms. The coordination geometry of the two independent metal atoms is T-shaped; the manner of bridging gives rise to a layer motif parallel to (100). In the crystal, the nitrate ion is disordered over two positions in a 1:1 ratio, and is sandwiched between adjacent layers. O—H⋯O hydrogen bonding is present between nitrate ions and layers, and also between adjacent layers.

In the mononuclear title compound, [Ag(NO3)(C6H6N2O)2], the AgI atom is located on a twofold rotation axis and the nitrate-chelated AgI atom is further coordinated by two aromatic N atoms of hydroxyl­amine ligands in a distorted tetra­hedral geometry. In the crystal, the nitrate ion has 2 symmetry with the N atom and one O atom located on the twofold rotation axis, and is linked to hy­droxy groups of the hydroxyl­amine ligands by O—H⋯O hydrogen bonds, generating a chain running along the b axis.

The AgI atom in the title compound, [Ag(C11H11N3O)3]NO3, shows a T-shaped coordination arising from bonding to the N atom of three N-heterocycles; the geometry is distorted towards square pyramidal owing to two weak Ag⋯Onitrate inter­actions [Ag⋯O = 2.691 (5) and 3.073 (5) Å]. The cation and anion are linked by O—H⋯N and N—H⋯O hydrogen bonds, generating a three-dimensional network.

In the centrosymmetric dinuclear title AgI compound, [Ag2(C6H6N2O)4](NO3)2, the aromatic amine-coordinated AgI atom is further bridged by two hydroxyl­amine mol­ecules that use aromatic and oxime N atoms for bridging, and it exists in a distorted trigonal-planar geometry. In the crystal, the nitrate anions link to the dinuclear compound mol­ecules via O—H⋯O hydrogen bonds, generating a chain running along the a-axis direction.

The AgI atom in the polycationic salt, {[Ag(C11H11N3O)]NO3}n, shows a linear coordination [N—Ag—N = 175.0 (2)°]; the polymeric nature arises from bridging by the pyrazine portion of the ligand, resulting in chains extending parallel to [100]. The NO3 − counter-ions surround the polymeric chain and inter­act only weakly with it [Ag⋯O = 2.701 (4) and 2.810 (5) Å]. Adjacent chains are linked into a three-dimensional network by O—H⋯O and N—H⋯O hydrogen bonds.

Induction of the suppressor of cytokine signalling 3 (SOCS-3) gene is vital to the normal control of inflammatory signalling. In order to understand these processes we investigated the role of the proto-oncogene component of the AP-1 transcription factor complex, c-Jun, in the regulation of SOCS-3 gene induction. We found that cyclic AMP stimulation of HUVECs promoted phosphorylation and activation of JNK MAP kinase and its substrate c-Jun. The JNK responsive element of the human SOCS-3 promoter mapped to a putative AP-1 site within 1000 bp of the transcription start site. The PKC inhibitors, GF-109203X, Gö-6983 and Ro-317549, were all found to inhibit AP-1 transcriptional activity, transcriptional activation of this minimal SOCS-3 promoter and SOCS-3 gene induction in HUVECs. Interestingly, Ro-317549 treatment was also found to promote PKC-dependent activation of ERK and JNK MAP kinases and promote JNK-dependent hyper-phosphorylation of c-Jun, whereas GF-109203X and Gö-6983 had little effect. Despite this, all three PKC inhibitors were found to be effective inhibitors of c-Jun DNA-binding activity. The JNK-dependent hyper-phosphorylation of c-Jun in response to Ro-317549 treatment of HUVECs does therefore not interfere with its ability to inhibit c-Jun activity and acts as an effective inhibitor of c-Jun-dependent SOCS-3 gene induction.

Highlights

► Ro-317549 triggers hyper-phosphorylation of c-Jun in HUVECs. ► Elevations in intracellular cyclic AMP also induce JNK-dependent, c-Jun activation. ► c-Jun is required for the full transcriptional activation of the human SOCS-3 gene. ► Ro-317549, GF-109203X and Gö 6983 inhibit c-Jun and SOCS-3 gene induction.

The two aromatic rings of the title compound, C11H11N3O, are nearly perpendicular to one another, with a dihedral angle between their planes of 80.52 (18)°. In the crystal, the amino N atom is a hydrogen-bond donor to the pyrazine N1 atom of an inversion-related mol­ecule and the hy­droxy O atom is a hydrogen-bond donor to the pyrazine N4 atom of another mol­ecule. The two hydrogen bonds lead to the formation of a helical chain that runs along the b axis.

The planes of the aromatic rings of the title compound, C12H12N2O, are twisted by 50.33 (15)°. The phenol O atom is a hydrogen-bond donor to the pyridine N atom, resulting in the formation of an eight-membered ring in the mol­ecule. The amino N atom is a hydrogen-bond donor to the phenol O atom of an adjacent mol­ecule; this hydrogen bond leads to the formation of a helical chain that runs along the a axis.

The planes of the aromatic rings in the cation of the title salt, C12H13N2O+·NO3 −, are twisted along the –CH2—NH– single bond by 75.3 (1)°. In the crystal, the phenol O, amine N and pyridinium N atoms are hydrogen-bond donors to the O atoms of the nitrate counter-ions. These hydrogen bonds lead to the formation of a layer in the crystal.

In the crystal structure of the title co-crystal, C11H12N3O+·ClO4 −·C11H11N3O, the perchlorate ion is disordered about a twofold rotation axis with the Cl atom located on the twofold rotation axis; the 2-[(2-hy­droxy­benz­yl)amino]­pyrazinium cation and the neutral 2-[(pyrazin-2-yl­amino)­meth­yl]phenol mol­ecule are disordered about the rotation axis in a 1:1 ratio. These two are connected by a pyrazine–pyrazine N1—H⋯N4 hydrogen bond. The cation, whose two aromatic rings are twisted along the –CH2—NH– bond by 76.8 (1)°, is a hydrogen-bond donor to the perchlorate ion through the N atom of this link.

Clostridium botulinum neurotoxins are used to treat a variety of neuro-muscular disorders, as well as in cosmetology. The increased demand requires efficient methods for the production and purification of these toxins. In this study, a new purification process was developed for purifying type B neurotoxin. The kinetics of C.botulinum strain growth and neurotoxin production were determined for maximum yield of toxin. The neurotoxin was purified by polyethylene glycol (PEG) precipitation and chromatography. Based on design of full factorial experiment, 20% (w/v) PEG-6000, 4°C, pH 5.0 and 0.3 M NaCl were optimal conditions to obtain a high recovery rate of 87% for the type B neurotoxin complex, as indicated by a purification factor of 61.5 fold. Furthermore, residual bacterial cells, impurity proteins and some nucleic acids were removed by PEG precipitation. The following purification of neurotoxin was accomplished by two chromatography techniques using Sephacryl™ S-100 and phenyl HP columns. The neurotoxin was recovered with an overall yield of 21.5% and the purification factor increased to 216.7 fold. In addition, a mouse bioassay determined the purified neurotoxin complex possessed a specific toxicity (LD50) of 4.095 ng/kg.

Background

Identification of phosphorylation sites by computational methods is becoming increasingly important because it reduces labor-intensive and costly experiments and can improve our understanding of the common properties and underlying mechanisms of protein phosphorylation.

Methods

A multitask learning framework for learning four kinase families simultaneously, instead of studying each kinase family of phosphorylation sites separately, is presented in the study. The framework includes two multitask classification methods: the Multi-Task Least Squares Support Vector Machines (MTLS-SVMs) and the Multi-Task Feature Selection (MT-Feat3).

Results

Using the multitask learning framework, we successfully identify 18 common features shared by four kinase families of phosphorylation sites. The reliability of selected features is demonstrated by the consistent performance in two multi-task learning methods.

Conclusions

The selected features can be used to build efficient multitask classifiers with good performance, suggesting they are important to protein phosphorylation across 4 kinase families.

Consonants, unlike vowels, are thought to be speech specific and therefore no interactions would be expected between consonants and pitch, a basic element for musical tones. The present study used an electrophysiological approach to investigate whether, contrary to this view, there is integrative processing of consonants and pitch by measuring additivity of changes in the mismatch negativity (MMN) of evoked potentials. The MMN is elicited by discriminable variations occurring in a sequence of repetitive, homogeneous sounds. In the experiment, event-related potentials (ERPs) were recorded while participants heard frequently sung consonant-vowel syllables and rare stimuli deviating in either consonant identity only, pitch only, or in both dimensions. Every type of deviation elicited a reliable MMN. As expected, the two single-deviant MMNs had similar amplitudes, but that of the double-deviant MMN was also not significantly different from them. This absence of additivity in the double-deviant MMN suggests that consonant and pitch variations are processed, at least at a pre-attentive level, in an integrated rather than independent way. Domain-specificity of consonants may depend on higher-level processes in the hierarchy of speech perception.

Cell penetrating peptides (CPPs) have tremendous potential for use in gene and drug delivery applications. The selection of new CPPs with desired capabilities from randomized peptide libraries is challenging, since the CPP phenotype is a complex selection target. Here we report the discovery of an unusual new CPP from a randomized peptide library using a functional selection system based on plasmid display (PD). After four rounds of screening of a 14-mer peptide library over PC12 cells, several peptides were identified and tested for their ability to deliver the green fluorescent protein (GFP). One peptide (SG3) exhibited a cell penetrating phenotype, however unlike other well-known CPPs such as TAT or Penetratin, the newly identified peptide was not highly cationic. The PD protocol necessitated the addition of a cationic lipid (Lipofectamine2000), and in the presence of this compound, the SG3 peptide significantly outperformed the well-known TAT CPP in the delivery of GFP to PC12 cells and primary astrocytes. When the SG3 peptide was fused to the pro-apoptotic BH3 peptide from the Bak protein, significant cell death was induced in cultured primary astrocytes, indicating relevant, intracellular delivery of a functional cargo. The PD platform is a useful method for identifying functional new CPPs from randomized libraries with unique delivery capabilities.

Small RNAs (sRNA), including microRNAs (miRNA) and small interfering RNAs (siRNA), are produced abundantly in plants and animals and function in regulating gene expression or in defense against virus or viroid infection. Analysis of siRNA profiles upon virus infection in plant may allow for virus identification, strain differentiation, and de novo assembly of virus genomes. In the present study, four suspected virus-infected tomato samples collected in the U.S. and Mexico were used for sRNA library construction and deep sequencing. Each library generated between 5–7 million sRNA reads, of which more than 90% were from the tomato genome. Upon in-silico subtraction of the tomato sRNAs, the remaining highly enriched, virus-like siRNA pools were assembled with or without reference virus or viroid genomes. A complete genome was assembled for Potato spindle tuber viroid (PSTVd) using siRNA alone. In addition, a near complete virus genome (98%) also was assembled for Pepino mosaic virus (PepMV). A common mixed infection of two strains of PepMV (EU and US1), which shared 82% of genome nucleotide sequence identity, also could be differentially assembled into their respective genomes. Using de novo assembly, a novel potyvirus with less than 60% overall genome nucleotide sequence identity to other known viruses was discovered and its full genome sequence obtained. Taken together, these data suggest that the sRNA deep sequencing technology will likely become an efficient and powerful generic tool for virus identification in plants and animals.

In the title compound, [Cu2(C2H4NO2)2(C10H6O6S2)(H2O)6], the naphthalene­disulfonate group lies on a center of inversion and bridges two glycinate-chelated CuII atoms. The CuII atom exists in a CuNO4 square-pyramidal geometry that is distorted towards an octa­hedron owing to a long Cu—Osulfonate bond [2.636 (2) Å]. In the crystal, extensive N—H⋯O and O—H⋯O hydrogen bonds link adjacent mol­ecules into a three-dimensional network

Each of the ions in the title salt, [Ag(C6H6N2O)2]ClO4, is completed by the application of crystallographic twofold symmetry. The AgI atom is coordinated by two pyridine N atoms in an almost linear fashion [N—Ag—N = 170.0 (2)°], with the T-shaped coordination geometry being completed by a weakly associated perchlorate-O atom. Supra­molecular zigzag chains along [100] mediated by O—H⋯N hydrogen bonds [as parts of R 2 2(6) loops] feature in the crystal packing. The perchlorate O atoms are disordered over two sets of sites in a statistical ratio.

The two independent CdII atoms in the polymeric title compound, [Cd(C10H8N2)(H2O)4](C7H4O6S)·H2O, lie on twofold rotation axes, and each is coordinated by four water mol­ecules and the N atoms of two 4,4′-bipyridine mol­ecules in an octa­hedral geometry. Bridging gives rise to chains along [101] and [-101]. The 4-hy­droxy-3-sulfonato­benzoate dianions are not connected to the CdII atoms, but form hydrogen bonds to the coordinated water mol­ecules as well as the lattice water mol­ecule, generating a three-dimensional network.

The 1,10-phenanthroline-chelated CoII atom in the polymeric title compound, {[Co(C7H4O6S)(C12H8N2)(H2O)2]·1.5H2O}n, is connected to the sulfonate O atom of one 4-hy­droxy-3-sulfonato­benzoate dianion and to the carboxyl­ate O atom of another dianion. It is also coordinated by two water mol­ecules in a trans-CoN2O4 octa­hedral environment. The dianion links adjacent metal atoms into a chain running along [110]. The chains are linked by O—H⋯O hydrogen bonds into a three-dimensional network.