Cognitive and behavioral predictors of light therapy use

Objective: Although light therapy is effective in the treatment of seasonal affective disorder (SAD) and other mood disorders, only 53-79% of individuals with SAD meet remission criteria after light therapy. Perhaps more importantly, only 12-41% of individuals with SAD continue to use the treatment even after a previous winter of successful treatment. Method: Participants completed surveys regarding (1) social, cognitive, and behavioral variables used to evaluate treatment adherence for other health-related issues, expectations and credibility of light therapy, (2) a depression symptoms scale, and (3) self-reported light therapy use. Results: Individuals age 18 or older responded (n = 40), all reporting having been diagnosed with a mood disorder for which light therapy is indicated. Social support and self-efficacy scores were predictive of light therapy use (p's<.05). Conclusion: The findings suggest that testing social support and self-efficacy in a diagnosed patient population may identify factors related to the decision to use light therapy. Treatments that impact social support and self-efficacy may improve treatment response to light therapy in SAD. © 2012 Roecklein et al

Early stage transplantation of bone marrow cells markedly ameliorates copper metabolism and restores liver function in a mouse model of Wilson disease

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated that normal bone marrow (BM) cells transplantation can correct liver injury in a mouse model of Wilson disease (WD). However, it still remains unknown when BM cells transplantation should be administered. The aim of this study was to investigate the potential impact of normal BM cells transplantation at different stages of WD to correct liver injury in toxic milk (tx) mice.</p> <p>Methods</p> <p>Recipient tx mice were sublethally irradiated (5 Gy) prior to transplantation. The congenic wild-type (DL) BM cells labeled with CM-DiI were transplanted via caudal vein injection into tx mice at the early (2 months of age) or late stage (5 months of age) of WD. The same volume of saline or tx BM cells were injected as controls. The DL donor cell population, copper concentration, serum ceruloplasmin oxidase activity and aspartate aminotransferase (AST) levels in the various groups were evaluated at 1, 4, 8 and 12 weeks post-transplant, respectively.</p> <p>Results</p> <p>The DL BM cells population was observed from 1 to 12 weeks and peaked by the 4^thweek in the recipient liver after transplantation. DL BM cells transplantation during the early stage significantly corrected copper accumulation, AST across the observed time points and serum ceruloplasmin oxidase activity through 8 to 12 weeks in tx mice compared with those treated with saline or tx BM cells (all <it>P </it>< 0.05). In contrast, BM cells transplantation during the late stage only corrected AST levels from 4 to 12 weeks post-transplant and copper accumulation at 12 weeks post-transplant (all <it>P </it>< 0.05). No significant difference was found between the saline and tx BM cells transplantation groups across the observed time points (<it>P </it>> 0.05).</p> <p>Conclusions</p> <p>Early stage transplantation of normal BM cells is better than late stage transplantation in correcting liver function and copper metabolism in a mouse model of WD.</p

L-Glutamine therapy reduces endothelial adhesion of sickle red blood cells to human umbilical vein endothelial cells

BACKGROUND: We have previously demonstrated that therapy with orally administered L-glutamine improves nicotinamide adenosine dinucleotide (NAD) redox potential of sickle red blood cells (RBC). On further analysis of L-glutamine therapy for sickle cell anemia patients, the effect of L-glutamine on adhesion of sickle RBC to human umbilical vein endothelial cells (HUVEC) was examined. METHODS: The first part of the experiment was conducted with the blood samples of the 5 adult sickle cell anemia patients who had been on L-glutamine therapy for at least 4 weeks on a dosage of 30 grams per day compared to those of patient control group. In the second part of the experiment 6 patients with sickle cell anemia were studied longitudinally. Five of these patients were treated with oral L-glutamine 30 grams daily and one was observed without treatment as the control. t-test and paired t-test were used for determination of statistical significance in cross-sectional and longitudinal studies respectively. RESULTS: In the first study, the mean adhesion to endothelial cells with the autologous plasma incubated cells were 0.97 ± 0.45 for the treated group and 1.91 ± 0.53 for the nontreated group (p < 0.02). Similarly with lipopolysaccharide (LPS) incubated cells the mean adhesion to endothelial cells were 1.39 ± 0.33 for the treated group and 2.80 ± 0.47 for the untreated group (p < 0.001). With the longitudinal experiment, mean decrease in the adhesion to endothelial cells was 1.13 ± 0.21 (p < 0.001) for the 5 treated patients whereas the control patient had slight increase in the adhesion to endothelial cells. CONCLUSION: In these studies, oral L-glutamine administration consistently resulted in improvement of sickle RBC adhesion to HUVEC. These data suggest positive physiological effects of L-glutamine in sickle cell disease

Identifying Modules of Coexpressed Transcript Units and Their Organization of Saccharopolyspora erythraea from Time Series Gene Expression Profiles

BACKGROUND: The Saccharopolyspora erythraea genome sequence was released in 2007. In order to look at the gene regulations at whole transcriptome level, an expression microarray was specifically designed on the S. erythraea strain NRRL 2338 genome sequence. Based on these data, we set out to investigate the potential transcriptional regulatory networks and their organization. METHODOLOGY/PRINCIPAL FINDINGS: In view of the hierarchical structure of bacterial transcriptional regulation, we constructed a hierarchical coexpression network at whole transcriptome level. A total of 27 modules were identified from 1255 differentially expressed transcript units (TUs) across time course, which were further classified in to four groups. Functional enrichment analysis indicated the biological significance of our hierarchical network. It was indicated that primary metabolism is activated in the first rapid growth phase (phase A), and secondary metabolism is induced when the growth is slowed down (phase B). Among the 27 modules, two are highly correlated to erythromycin production. One contains all genes in the erythromycin-biosynthetic (ery) gene cluster and the other seems to be associated with erythromycin production by sharing common intermediate metabolites. Non-concomitant correlation between production and expression regulation was observed. Especially, by calculating the partial correlation coefficients and building the network based on Gaussian graphical model, intrinsic associations between modules were found, and the association between those two erythromycin production-correlated modules was included as expected. CONCLUSIONS: This work created a hierarchical model clustering transcriptome data into coordinated modules, and modules into groups across the time course, giving insight into the concerted transcriptional regulations especially the regulation corresponding to erythromycin production of S. erythraea. This strategy may be extendable to studies on other prokaryotic microorganisms

An agonist sensitive, quick and simple cell-based signaling assay for determination of ligands mimicking prostaglandin E2 or E1 activity through subtype EP1 receptor: Suitable for high throughput screening

<p>Abstract</p> <p>Background</p> <p>Conventionally the active ingredients in herbal extracts are separated into individual components, by fractionation, desalting, and followed by high-performance liquid chromatography (HPLC). In this study we have tried to directly screen water-soluble fractions of herbs with potential active ingredients before purification or extraction. We propose that the herbal extracts mimicking prostaglandin E₁(PGE₁) and E₂(PGE₂) can be identified in the water-soluble non-purified fraction. PGE₁is a potent anti-inflammatory molecule used for treating peripheral vascular diseases while PGE₂is an inflammatory molecule.</p> <p>Methods</p> <p>We used cell-based assays (CytoFluor multi-well plate reader and fluorescence microscopy) in which a calcium signal was generated by the recombinant EP₁receptor stably expressed in HEK293 cells (human embryonic kidney). PGE₁and PGE₂were tested for their ability to generate a calcium signal. Ninety-six water soluble fractions of Treasures of the east (single Chinese herb dietary supplements) were screened.</p> <p>Results</p> <p>After screening, the top ten stimulators were identified. The identified herbs were then desalted and the calcium fluorescent signal reconfirmed using fluorescence microscopy. Among these top ten agonists identified, seven stimulated the calcium signaling (1-40 μM concentration) using fluorescence microscopy.</p> <p>Conclusions</p> <p>Fluorescence microscopy and multi-well plate readers can be used as a target specific method for screening water soluble fractions with active ingredients at a very early stage, before purification. Our future work consists of purifying and separating the active ingredients and repeating fluorescence microscopy. Under ordinary circumstances we would have to purify the compounds first and then test all the extracts from 96 herbs. Conventionally, for screening natural product libraries, the procedure followed is the automated separation of all constituents into individual components using fractionation and high performance liquid chromatography. We, however, demonstrated that the active ingredients of the herbal extracts can be tested before purification using an agonist sensitive, quick and simple cell-based signaling assay for ligands mimicking the agonists, PGE₁and PGE₂.</p

Shared cognition in childhood anxiety: interpretation bias in preschool children and their parents

Although interpretation bias has been associated with the development and/or maintenance of childhood anxiety, its origins remain unclear. The present study is the first to examine intergenerational transmission of this bias from parents to their preschool-aged children via the verbal information pathway. A community sample of fifty parent–child pairs was recruited. Parents completed measures of their own trait anxiety and interpretation bias, their child’s anxiety symptoms, and a written story-stem measure, to capture the way parents tell their children stories. Interpretation bias was assessed in preschool-aged children (aged between 2 years 7 months and 5 years 8 months) using an extended story-stem paradigm. Young children’s interpretation bias was not significantly associated with their own anxiety symptoms. Neither was there evidence for a significant association between parent and child interpretation bias. However, parents who reported they would tell their child one or more threatening story endings in the written story-stem task had significantly higher anxiety than those who did not include any threatening story endings. In turn, children whose parents did not include any threatening endings in their written stories had significantly lower threat interpretations on the child story-stem paradigm, compared to those with parents who included at least one threatening story ending. The results suggest that parental verbal information could play a role in the development of interpretation bias in young children

Characterization of human Sec16B: indications of specialized, non-redundant functions

The endoplasmic reticulum (ER) represents the entry point into the secretory pathway and from here newly synthesized proteins and lipids are delivered to the Golgi. The selective cargo export from the ER is mediated by COPII-assembly at specific sites of the ER, the so-called transitional ER (tER). The peripheral membrane protein Sec16, first identified in yeast, localizes to transitional ER and plays a key role in organization of these sites. Sec16 defines the tER and is thought to act as a scaffold for the COPII coat assembly. In humans two isoforms of Sec16 are present, the larger Sec16A and the smaller Sec16B. Nevertheless, the functional differences between the two isoforms are ill-defined. Here we describe characterization of the localization and dynamics of Sec16B relative to Sec16A, provide evidence that Sec16B is likely a minor or perhaps specialized form of Sec16, and that it is not functionally redundant with Sec16A

The Role of Maternal Depression on Treatment Outcome for Children with Externalizing Behavior Problems

Studies have shown that, on average, Parent Management Training combined with cognitive-behavioral therapy decreases children’s externalizing behavior, but some children do not improve through treatment. The current study aimed to examine the role of maternal depression in understanding this variability in treatment outcome. Children with externalizing behavioral problems and their parents were recruited from combined Parent Management Training and Cognitive-Behavioral programs in “real-world” clinical settings. At pre- and post treatment, maternal depression and children’s externalizing behavior were assessed. Results showed that treatment was less effective for children of depressed mothers compared to non-depressed mothers and that improvements in maternal depression were associated with improvements in children’s externalizing behavior. These findings suggest that treatment programs for children with externalizing problems may be able to improve outcomes if maternal depression is a target of intervention

Predictors of Multidrug- and Extensively Drug-Resistant Tuberculosis in a High HIV Prevalence Community

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIV-prevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control. METHODS: We performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drug-resistant TB. Controls were selected in a 1:1:1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors. RESULTS: We enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4-414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1-13.3] and 6.1 [CI 1.8-21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3-52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0-27.6). DISCUSSION: In this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric second-line TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB