Distress levels in patients undergoing chemotherapy in Brazil

Objective: The objective of this study was to measure distress at three points during the course of chemotherapy: beginning, middle, and the last day of therapy in a private cancer center in Brazil. Methods: One hundred patients were assessed at three points during chemotherapy using the Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS). The data were analyzed with the support of SPSS 15.0 software. Results: At the beginning of chemotherapy, patients mean scores were distress (82%), anxiety (78%) and depression (55%). In the middle of treatment, the percentages of distress, anxiety and depression decreased to 36.4, 25 and 25.3%, respectively. On the last day, the levels were 18.2% for distress and 14.3% for both anxiety and depression. Conclusion: Distress is highest in these patients at the beginning of chemotherapy, suggesting that evaluation of patients for psychosocial needs is important. Screening with a simple rapid instrument such as the DT is feasible and useful. Copyright © 2010 John Wiley & Sons, Ltd.     

The Estimated Annual Cost of ADHD to the US Education System

The purpose of this study was to examine and monetize the educational outcomes of students with ADHD. Data were examined from the Pittsburgh ADHD Longitudinal Study, a follow-up study of children diagnosed with ADHD in childhood and recontacted for follow-up in adolescence and young adulthood. A comprehensive educational history was obtained for all participants from Kindergarten through 12th grade. Annual economic impact was derived from costs incurred through special education placement, grade retention, and disciplinary incidents. Results indicated that, as compared to students without ADHD, students with ADHD incurred a higher annual cost to the US Education system. Specifically, a student with ADHD incurred an average annual incremental cost to society of 5,007, as compared with5,007, as compared with 318 for students in the comparison group. These results suggest that prevention and intervention strategies are greatly needed to offset the large financial impact of educating youth with ADHD.     

Export of RNA silencing from C. elegans tissues does not require the RNA channel SID-1

Double-stranded RNA (dsRNA) triggers RNA interference (RNAi) to silence genes of matching sequence. In some animals this experimentally induced silencing is transported between cells, and studies in the nematode Caenorhabditis elegans have shown that the dsRNA channel SID-1 is required for the import of such transported silencing signals. Gene silencing can also be triggered by endogenously expressed RNAi triggers, but it is unknown whether such silencing is transported between cells. Here, we show that, in C. elegans, SID-1 is required for efficient silencing of multicopy transgenes, indicating that mobile silencing signals contribute to transgene silencing. Further, most tissues can transport silencing initiated by the tissue-specific transgenic expression of RNAi triggers to other tissues, consistent with expressed RNAi triggers generating mobile silencing signals. Whereas the import of silencing signals requires SID-1, we found that mobile silencing signals generated by transgene-expressed RNAi triggers are exported to other tissues through a SID-1-independent mechanism. Furthermore, when RNAi triggers are expressed in ingested Escherichia coli, silencing signals can be transported to internal tissues from the gut lumen across gut cells that lack SID-1. Thus, C. elegans can transport endogenous and exogenous RNA silencing signals between many different tissues via at least 2 SID-1 independent export pathways.     

Myeloma cells exhibit an increase in proteasome activity and an enhanced response to proteasome inhibition in the bone marrow microenvironment in vivo

The proteasome inhibitor bortezomib has a striking clinical benefit in patients with multiple myeloma. It is unknown whether the bone marrow microenvironment directly contributes to the dramatic response of myeloma cells to proteasome inhibition in vivo. We have used the well‐characterized 5TGM1 murine model of myeloma to investigate myeloma growth within bone and response to the proteasome inhibitor bortezomib in vivo. Myeloma cells freshly isolated from the bone marrow of myeloma‐bearing mice were found to have an increase in proteasome activity and an enhanced response to in vitro proteasome inhibition, as compared with pre‐inoculation myeloma cells. Treatment of myeloma‐bearing mice with bortezomib resulted in a greater reduction in tumor burden when the myeloma cells were located within the bone marrow when compared with extra‐osseous sites. Our results demonstrate that myeloma cells exhibit an increase in proteasome activity and an enhanced response to bortezomib treatment when located within the bone marrow microenvironment in vivo. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.     

Glioma Cell Migration on Three-dimensional Nanofiber Scaffolds Is Regulated by Substrate Topography and Abolished by Inhibition of STAT3 Signaling

A hallmark of malignant gliomas is their ability to disperse through neural tissue, leading to long-term failure of all known therapies. Identifying new antimigratory targets could reduce glioma recurrence and improve therapeutic efficacy, but screens based on conventional migration assays are hampered by the limited ability of these assays to reproduce native cell motility. Here, we have analyzed the motility, gene expression, and sensitivity to migration inhibitors of glioma cells cultured on scaffolds formed by submicron-sized fibers (nanofibers) mimicking the neural topography. Glioma cells cultured on aligned nanofiber scaffolds reproduced the elongated morphology of cells migrating in white matter tissue and were highly sensitive to myosin II inhibition but only moderately affected by stress fiber disruption. In contrast, the same cells displayed a flat morphology and opposite sensitivity to myosin II and actin inhibition when cultured on conventional tissue culture polystyrene. Gene expression analysis indicated a correlation between migration on aligned nanofibers and increased STAT3 signaling, a known driver of glioma progression. Accordingly, cell migration out of glioblastoma-derived neurospheres and tumor explants was reduced by STAT3 inhibitors at subtoxic concentrations. Remarkably, these inhibitors were ineffective when tested at the same concentrations in a conventional two-dimensional migration assay. We conclude that migration of glioma cells is regulated by topographical cues that affect cell adhesion and gene expression. Cell migration analysis using nanofiber scaffolds could be used to reproduce native mechanisms of migration and to identify antimigratory strategies not disclosed by other in vitro models.     

Rhythms of Consciousness: Binocular Rivalry Reveals Large-Scale Oscillatory Network Dynamics Mediating Visual Perception

Consciousness has been proposed to emerge from functionally integrated large-scale ensembles of gamma-synchronous neural populations that form and dissolve at a frequency in the theta band. We propose that discrete moments of perceptual experience are implemented by transient gamma-band synchronization of relevant cortical regions, and that disintegration and reintegration of these assemblies is time-locked to ongoing theta oscillations. In support of this hypothesis we provide evidence that (1) perceptual switching during binocular rivalry is time-locked to gamma-band synchronizations which recur at a theta rate, indicating that the onset of new conscious percepts coincides with the emergence of a new gamma-synchronous assembly that is locked to an ongoing theta rhythm; (2) localization of the generators of these gamma rhythms reveals recurrent prefrontal and parietal sources; (3) theta modulation of gamma-band synchronization is observed between and within the activated brain regions. These results suggest that ongoing theta-modulated-gamma mechanisms periodically reintegrate a large-scale prefrontal-parietal network critical for perceptual experience. Moreover, activation and network inclusion of inferior temporal cortex and motor cortex uniquely occurs on the cycle immediately preceding responses signaling perceptual switching. This suggests that the essential prefrontal-parietal oscillatory network is expanded to include additional cortical regions relevant to tasks and perceptions furnishing consciousness at that moment, in this case image processing and response initiation, and that these activations occur within a time frame consistent with the notion that conscious processes directly affect behaviour.     

Screening HIV-infected patients for non-AIDS-defining malignancies

The use of antiretroviral therapy has reduced mortality and shifted the spectrum of malignancies affecting people living with HIV/AIDS (PLWH). We review guidelines and evidence for screening PLWH for non-AIDS-defining malignancies as compared with the general population. Cervical cancer screening clearly differs for HIV-seropositive women, with two Pap tests 6 months apart in the first year and then annually if normal. The role of cervical human papillomavirus screening has not yet been defined in HIV-seropositive women. Anal cancer screening consists of an annual digital rectal examination, and some (but not all) guidelines also recommend annual anal Pap tests. Screening for breast and colorectal cancer should follow standard, age-appropriate screening recommendations that apply to the general population. Screening HIV-infected men for prostate cancer, as with the general population, lacks a clear benefit. Despite increasing rates of hepatocellular carcinoma and lung cancers among PLWH, there is insufficient evidence to support routine screening.     

An Evaluation of a Direct Instructions Flashcard System on the Acquisition and Generalization of Numerals, Shapes, and Colors for Preschool-Aged Students with Developmental Delays

The purpose of this study was to evaluate the effectiveness of the DI Flashcard system for teaching preliminary mathematic skills to three preschool students. The participants attended a self-contained special education preschool. All three participants’ eligibility category was “developmentally delayed”. A concurrent multiple baseline design across three sets (colors, shapes, and numerals) was use to evaluate the effectiveness of the DI flashcard system. The results indicated that all three participants showed an increase in their performance when DI flashcards were in effect. However, the amount of improvement varied for each participant. The importance of employing evidence-based procedures to teach skills to preschool students with developmental delays was outlined.     

Imaging abnormal skin sensations: a novel functional MRI study

BackgroundA subgroup of patients present to dermatological services with unexplained skin sensations, usually ascribing them to infestation; however, no medical cause can be found. This condition is referred to as delusional infestation, a rare and difficult to treat disorder with considerable impact on psychosocial functioning. The neurobiological mechanisms underlying this condition are unclear. We undertook the first functional MRI (fMRI) study in this group of patients.MethodsFive patients presenting with medically unexplained skin sensations were recruited from the specialist psychodermatology service at The Royal London Hospital, UK (mean age 52·8 years, four women, one man). Five healthy controls were matched for age and gender. Whole brain fMRI data were acquired with a 1·5 T scanner. In an event-related design, participants were randomly shown six classes of images: insects on skin, insects on leaf, other objects on skin, other objects on leaf, neutral images, and disgusting and fearful images. Functional images were analysed with statistical parametric mapping, version 8. A full factorial model was used to analyse the results with two factors—group and stimulus type.FindingsResults are reported at the significance threshold p<0·001 (whole brain analysis xyz co-ordinates, z score, k voxel number). Across the two groups the main effect of insect versus non-insect images was to activate occipital lobe (?52, ?70, 6, z 4·04, k 92). In this contrast, patients showed greater activity in the right parahippocampus than did controls (22, ?32, ?4, z 3·35, k 2). The main effect of presentation of skin rather than leaf was to activate inferior parietal lobule (44, ?40, 30, z 4·07, k 21), with patients showing increased activity in this area. Across all conditions patients showed greater activity in the right parahippocampus (26, ?4, ?32, z 3·77, k 21). Patients showed greater activity in bilateral temporal lobes when viewing disgusting or fearful images than when viewing neutral images.InterpretationWe have shown for the first time that brain activity differs between patients with abnormal skin sensations and controls when viewing pictures. This activity is in regions of brain supporting emotional awareness.FundingUK Medical Research Council.