Association Between Pretreatment Sleep Disturbance and Radiation Therapy-Induced Pain in 573 Women With Breast Cancer

ContextPain can be a debilitating side effect of radiation therapy (RT). Data from the general population have shown that sleep disturbance can influence pain incidence and severity; however, less is known about this relationship in patients with breast cancer receiving RT.ObjectivesThis secondary analysis examined the association of pretreatment moderate/severe levels of sleep disturbance with subsequent RT-induced pain after adjusting for pre-RT pain.MethodsWe report on 573 female patients with breast cancer undergoing RT from a previously completed Phase II clinical trial for radiation dermatitis. Sleep disturbance, total pain, and pain subdomains—sensory pain, affective pain, and perceived pain intensity were assessed at pre-RT and post-RT. At pre-RT, patients were dichotomized into two groups: those with moderate/severe sleep disturbance (N = 85) vs. those with no/mild sleep disturbance (control; N = 488).ResultsAt pre-RT, women with moderate/severe sleep disturbance were younger, less likely to be married, more likely to have had mastectomy and chemotherapy, and more likely to have depression/anxiety disorder and fatigue than the control group (all Ps < 0.05). Generalized estimating equations model, after controlling for pre-RT pain and other covariates (e.g., trial treatment condition and covariates that were significantly correlated with post-RT pain), showed that women with moderate/severe sleep disturbance at pre-RT vs. control group had significantly higher mean post-RT total pain as well as sensory, affective, and perceived pain (effect size = 0.62, 0.60, 0.69, and 0.52, respectively; all Ps < 0.05).ConclusionThese findings suggest that moderate/severe disturbed sleep before RT is associated with increased pain from pre-to-post-RT in patients with breast cancer.     

Cognitive Therapy in the Treatment and Prevention of Depression: A Fifty-Year Retrospective with an Evolutionary Coda

In the 50 years since it was first introduced, cognitive therapy has been shown to be as efficacious as antidepressant medications (on average) in the acute treatment of nonpsychotic depression, although some patients will do better on one than on the other. Moreover, patients treated to remission with cognitive therapy are less than half as likely to relapse following treatment termination as patients treated to remission with medications. However, a recent study suggests that adding medications interferes with any such enduring effect and medications themselves may have an iatrogenic effect that suppresses symptoms at the expense of prolonging the underlying episode. Neural imaging suggests that cognitive therapy works from the “top down” to facilitate cortical regulation of affect processes whereas medications work from the “bottom up” to dampen the stress response. Adaptationist theory suggests that depression is an evolved adaptation that served to keep our ancestors ruminating about complex social problems until they arrived at a solution; if true then any intervention that facilitates problem solving is likely preferable to one that merely anesthetizes distress.

     

Selection and evaluation of single domain antibodies toward MS2 phage and coat protein

MS2 phage (MS2 Ø) is a coli phage, non-pathogenic to eukaryotic cells, which has been used as a simulant for viral biothreats, such as those causing smallpox and hemorrhagic fever. MS2 Ø consists of an icosahedral capsid, 28 nm in diameter, and a single stranded RNA genome; the viral capsid is composed of 180 copies of coat protein (CP). In this study, we isolated anti-MS2 Ø single domain antibodies (sdAbs) for the sensitive detection of the MS2 Ø. To achieve this, a first immune sdAb library was prepared from llamas immunized with purified coat protein and a second from animals immunized with MS2 Ø. By panning the two libraries against CP, MS2 Ø, or alternating between the two targets, anti-MS2 Ø and anti-CP sdAbs were selected, sequenced, and characterized for their binding affinity. Both direct binding assays and capture sandwich assays were performed on the MAGPIX platform. One of the best anti-MS2 Ø sdAb, Lib2CP12H, could detect MS2 Ø concentrations as low as 1.45 ng/mL (～5.0E+6 pfu/mL), providing equivalent detection to conventional antibodies. This sdAb is thermally stable with a melting temperature around 60 °C and recovered 80% of its secondary structure after heat denaturation.     

DOES VISUAL SUBORDINATE-LEVEL CATEGORISATION ENGAGE THE FUNCTIONALLY DEFINED FUSIFORM FACE AREA?

Functional magnetic resonance imaging was used to compare brain activation associated with basic-level (e.g. bird) and subordinate-level (e.g. eagle) processing for both visual and semantic judgements. We localised the putative face area for 11 subjects, who also performed visual matching judgements for pictures and aurally presented words. The middle fusiform and occipital gyri were recruited for subordinate minus basic visual judgements, reflecting additional perceptual processing. When the face area was localised individually for each subject, analyses in the middle fusiform gyri revealed that subordinate-level processing activated the individuals face area. We propose that what is unique about the way faces engage this region is the focal spatial distribution of the activation rather than the recruitment of the face per se. Eight subjects also performed semantic judgements on aurally presented basic- and subordinate-level words. The parahippocampal gyri were more activated for subordinate-level than basic-level semantic judgements. Finally, the left posterior inferior temporal gyrus was activated for subordinate-level judgements, both visual and semantic, as well as during passive viewing of faces.     

Warm Partner Contact Is Related to Lower Cardiovascular Reactivity

Abstract

The authors investigated the relationship between brief warm social and physical contact among cohabitating couples and blood pressure (BP) reactivity to stress in a sample of healthy adults (66 African American, 117 Caucasian; 74 women, 109 men). Prior to stress, the warm contact group underwent a 10-minute period of handholding while viewing a romantic video, followed by a 20-second hug with their partner, while the no contact group rested quietly for 10 minutes and 20 seconds. In response to a public speaking task, individuals receiving prestress partner contact demonstrated lower systolic BP, diastolic BP, and heart rate increases compared with the no contact group. The effects of warm contact were comparable for men and women and were greater for African Americans compared with Caucasians. These findings suggest that affectionate relationships with a supportive partner may contribute to lower reactivity to stressful life events and may partially mediate the benefit of marital support on better cardiovascular health.     

Interstitial high-dose-rate brachytherapy in the treatment of keloids: Moving toward a volumetric approach

PurposeBrachytherapy (BT) after surgical resection of keloids reduces the risk of local recurrence, but standardization of dose/technique is lacking. Typical keloid BT treatment utilizes a single-channel source prescribed to 5-mm depth. We investigated the dosimetry of a volume-based target definition for interstitial high-dose-rate BT treatment of keloids.Methods and MaterialsWe retrospectively identified consecutive 14 patients who had a total of 20 keloids treated with interstitial high-dose-rate BT for keloids at our institution between 2004 and 2014. Keloids were treated with a single 8 Gy fraction prescribed to 5 mm beneath the scar within 36 h of surgery. Retrospectively, a 3-mm skin high-risk clinical target volume (HR-CTV) was contoured under the scar for volume-based dose calculations.ResultsMean (SD) HR-CTV was 3.91 cm³ (3.1) and mean (SD) HR-CTV dose was 11.3 Gy (3.6). Mean D₉₀ (SD) was 62.9% (25.8) and mean V₁₀₀ (SD) was 56.5% (26.4). The mean V₁₅₀ (SD), V₂₀₀ (SD), and V₃₀₀ (SD) were as follows: 37.6% (19.9), 25.1% (14.4), and 11.3% (6.5), respectively. No local failures were reported at 9 months median followup. There were no Grade 2 or higher late toxicities.ConclusionsUsing a volume-based target definition, a wide range of target coverage was observed. This is likely a consequence of the curvature of the skin and the challenges of keeping the catheter equidistant from the skin across the target. Additional data are needed to define the potential clinical impact on outcomes/toxicities of dosimetric correlates with single-catheter BT keloid treatment.     

Deep Artificial Neural Networks Reveal a Distributed Cortical Network Encoding Propositional Sentence-Level Meaning

Understanding how and where in the brain sentence-level meaning is constructed from words presents a major scientific challenge. Recent advances have begun to explain brain activation elicited by sentences using vector models of word meaning derived from patterns of word co-occurrence in text corpora. These studies have helped map out semantic representation across a distributed brain network spanning temporal, parietal, and frontal cortex. However, it remains unclear whether activation patterns within regions reflect unified representations of sentence-level meaning, as opposed to superpositions of context-independent component words. This is because models have typically represented sentences as “bags-of-words” that neglect sentence-level structure. To address this issue, we interrogated fMRI activation elicited as 240 sentences were read by 14 participants (9 female, 5 male), using sentences encoded by a recurrent deep artificial neural-network trained on a sentence inference task (InferSent). Recurrent connections and nonlinear filters enable InferSent to transform sequences of word vectors into unified “propositional” sentence representations suitable for evaluating intersentence entailment relations. Using voxelwise encoding modeling, we demonstrate that InferSent predicts elements of fMRI activation that cannot be predicted by bag-of-words models and sentence models using grammatical rules to assemble word vectors. This effect occurs throughout a distributed network, which suggests that propositional sentence-level meaning is represented within and across multiple cortical regions rather than at any single site. In follow-up analyses, we place results in the context of other deep network approaches (ELMo and BERT) and estimate the degree of unpredicted neural signal using an “experiential” semantic model and cross-participant encoding.SIGNIFICANCE STATEMENT A modern-day scientific challenge is to understand how the human brain transforms word sequences into representations of sentence meaning. A recent approach, emerging from advances in functional neuroimaging, big data, and machine learning, is to computationally model meaning, and use models to predict brain activity. Such models have helped map a cortical semantic information-processing network. However, how unified sentence-level information, as opposed to word-level units, is represented throughout this network remains unclear. This is because models have typically represented sentences as unordered “bags-of-words.” Using a deep artificial neural network that recurrently and nonlinearly combines word representations into unified propositional sentence representations, we provide evidence that sentence-level information is encoded throughout a cortical network, rather than in a single region.     

Progression of sleep disturbances in Parkinson’s disease: a 5-year longitudinal study

Journal of Neurology - Sleep disorders can occur in early Parkinson’s disease (PD). However, the relationship between different sleep disturbances and their longitudinal evolution has not...