Cognitive compensatory processes of older, clinically fit patients with hematologic malignancies undergoing chemotherapy: A longitudinal cohort study

peer reviewedObjective: Despite the well-known negative impacts of cancer and anticancer therapies on cognitive performance, little is known about the cognitive compensatory processes of older patients with cancer. This study was designed to investigate the cognitive compensatory processes of older, clinically fit patients with hematologic malignancies undergoing chemotherapy. Methods: We assessed 89 consecutive patients (age ≥ 65 y) without severe cognitive impairment and 89 age-, sex-, and education level-matched healthy controls. Cognitive compensatory processes were investigated by (1) comparing cognitive performance of patients and healthy controls in novel (first exposure to cognitive tasks) and non-novel (second exposure to the same cognitive tasks) contexts, and (2) assessing psychological factors that may facilitate or inhibit cognitive performance, such as motivation, psychological distress, and perceived cognitive performance. We assessed cognitive performance with the Trail-Making, Digit Span and FCSR-IR tests, psychological distress with the Hospital Anxiety and Depression Scale, and perceived cognitive performance with the FACT-Cog questionnaire. Results: In novel and non-novel contexts, average cognitive performances of healthy controls were higher than those of patients and were associated with motivation. Cognitive performance of patients was not associated with investigated psychological factors in the novel context but was associated with motivation and psychological distress in the non-novel context. Conclusions: Older, clinically fit patients with hematologic malignancies undergoing chemotherapy demonstrated lower cognitive compensatory processes compared to healthy controls. Reducing distress and increasing motivation may improve cognitive compensatory processes of patients in non-novel contexts. Copyright © 2017 John Wiley & Sons, Ltd

Direct measurements of the effects of salt and surfactant on interaction forces between colloidal particles at water-oil interfaces

The forces between colloidal particles at a decane-water interface, in the presence of low concentrations of a monovalent salt (NaCl) and of the surfactant sodium dodecylsulfate (SDS) in the aqueous subphase, have been studied using laser tweezers. In the absence of electrolyte and surfactant, particle interactions exhibit a long-range repulsion, yet the variation of the interaction for different particle pairs is found to be considerable. Averaging over several particle pairs was hence found to be necessary to obtain reliable assessment of the effects of salt and surfactant. It has previously been suggested that the repulsion is consistent with electrostatic interactions between a small number of dissociated charges in the oil phase, leading to a decay with distance to the power -4 and an absence of any effect of electrolyte concentration. However, the present work demonstrates that increasing the electrolyte concentration does yield, on average, a reduction of the magnitude of the interaction force with electrolyte concentration. This implies that charges on the water side also contribute significantly to the electrostatic interactions. An increase in the concentration of SDS leads to a similar decrease of the interaction force. Moreover the repulsion at fixed SDS concentrations decreases over longer times. Finally, measurements of three-body interactions provide insight into the anisotropic nature of the interactions. The unique time-dependent and anisotropic interactions between particles at the oil-water interface allow tailoring of the aggregation kinetics and structure of the suspension structure.Comment: Submitted to Langmui

Perceived control, locus of control and preparatory information: effects on the perception of an acute pain stimulus

This study investigated the effects of differences in a pre-procedure briefing (providing or withholding preparatory information and explicit control) on the perception of the second of two identical acute pain stimuli. 61 healthy participants were allocated to one of three conditions: Information + Control (I+C), Information - No Control (I-NC) or No information - No Control (NINC). Baseline measures of Pressure Pain Threshold (PPT) and pain rating using Visual Analogue Scales (VAS) were taken, as was a measure of general internal/external Locus of Control (LOC). Participants were read the briefing and subjected to a second pain stimulus of identical intensity to their baseline measures. Participants rated the second stimulus using the VASs, and compared it to the first using comparison scales. Results show that differences in a pre-procedure briefing significantly altered participants' perception of the pain stimulus. Participants in the I-NC group rated the second stimulus more painful than the first, and participants in the NI-NC group rated the second stimulus as less painful than the first. There is also suggestive evidence that these differences may relate to individual LOC style. We recommend encouragement of patient participation to engender at least the perception of control in clinical situations involving acutely painful procedures

Somatostatin receptor in human hepatocellular carcinomas: Biological, patient and tumor characteristics

Background/Aim: The evidence on the efficacy of somatostatin analogues in the treatment of hepatocellular carcinoma (HCC) in humans is conflicting. A variety of human tumors demonstrate somatostatin receptors. All subtypes bind human somatostatin with high affinity, while somatostatin analogues bind with high affinity to somatostatin receptor subtype 2 (sst2). We investigated the sst2 expression in HCC and examined whether HCCs expressing sst2 are a distinct subgroup. Patients and Methods: Forty-five human HCCs were tested for sst2 expression and biological alterations. The proliferative capacity was determined with Ki67 immunostaining and the DNA ploidy status was measured by fluorescent in situ hybridization with a chromosome 1-specific repetitive DNA probe. Expression of tumor suppressor genes (p16, p53 and Rb1) was measured by immunohistochemistry. Results: sst2 expression was detected in 30 tumors (67%). No correlation existed between sst2 expression and the immunoprofiles of the tumor suppressor genes, aneuploidy, proliferation, age, gender, α-fetoprotein levels, tumor size, tumor grade and underlying liver disease. Conclusion: In 67% of the patients with HCC, sst2 could be detected in the tumor. No clinical, pathological or biological characteristics were specific for sst2-positive tumors. Copyrigh

Is it possible to improve the breaking bad news skills of residents when a relative is present? A randomised study.

peer reviewe

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Altered Cigarette Smoke-Induced Lung Inflammation Due to Ablation of Grx1

Glutaredoxins (Grx) are redox enzymes that remove glutathione bound to protein thiols, know as S-glutathionylation (PSSG). PSSG is a reservoir of GSH and can affect the function of proteins. It inhibits the NF-κB pathway and LPS aspiration in Grx1 KO mice with decreased inflammatory cytokine levels. In this study we investigated whether absence of Grx1 similarly repressed cigarette smoke-induced inflammation in an exposure model in mice. Cigarette smoke exposure for four weeks decreased lung PSSG levels, but increased PSSG in lavaged cells and lavage fluid (BALF). Grx1 KO mice had increased levels of PSSG in lung tissue, BALF and BAL cells in response to smoke compared to wt mice. Importantly, levels of multiple inflammatory mediators in the BALF were decreased in Grx1 KO animals following cigarette smoke exposure compared to wt mice, as were levels of neutrophils, dendritic cells and lymphocytes. On the other hand, macrophage numbers were higher in Grx1 KO mice in response to smoke. Although cigarette smoke in vivo caused inverse effects in inflammatory and resident cells with respect to PSSG, primary macrophages and epithelial cells cultured from Grx1 KO mice both produced less KC compared to cells isolated from WT mice after smoke extract exposure. In this manuscript, we provide evidence that Grx1 has an important role in regulating cigarette smoke-induced lung inflammation which seems to diverge from its effects on total PSSG. Secondly, these data expose the differential effect of cigarette smoke on PSSG in inflammatory versus resident lung cells

Differences in gene expression and cytokine production by crystalline vs. amorphous silica in human lung epithelial cells

<p>Abstract</p> <p>Background</p> <p>Exposure to respirable crystalline silica particles, as opposed to amorphous silica, is associated with lung inflammation, pulmonary fibrosis (silicosis), and potentially with lung cancer. We used Affymetrix/GeneSifter microarray analysis to determine whether gene expression profiles differed in a human bronchial epithelial cell line (BEAS 2B) exposed to cristobalite vs. amorphous silica particles at non-toxic and equal surface areas (75 and 150 × 10⁶μm²/cm²). Bio-Plex analysis was also used to determine profiles of secreted cytokines and chemokines in response to both particles. Finally, primary human bronchial epithelial cells (NHBE) were used to comparatively assess silica particle-induced alterations in gene expression.</p> <p>Results</p> <p>Microarray analysis at 24 hours in BEAS 2B revealed 333 and 631 significant alterations in gene expression induced by cristobalite at low (75) and high (150 × 10⁶μm²/cm²) amounts, respectively (p < 0.05/cut off ≥ 2.0-fold change). Exposure to amorphous silica micro-particles at high amounts (150 × 10⁶μm²/cm²) induced 108 significant gene changes. Bio-Plex analysis of 27 human cytokines and chemokines revealed 9 secreted mediators (p < 0.05) induced by crystalline silica, but none were induced by amorphous silica. QRT-PCR revealed that cristobalite selectively up-regulated stress-related genes and cytokines (<it>FOS, ATF3, IL6 </it>and <it>IL8</it>) early and over time (2, 4, 8, and 24 h). Patterns of gene expression in NHBE cells were similar overall to BEAS 2B cells. At 75 × 10⁶μm²/cm², there were 339 significant alterations in gene expression induced by cristobalite and 42 by amorphous silica. Comparison of genes in response to cristobalite (75 × 10⁶μm²/cm²) revealed 60 common, significant gene alterations in NHBE and BEAS 2B cells.</p> <p>Conclusions</p> <p>Cristobalite silica, as compared to synthetic amorphous silica particles at equal surface area concentrations, had comparable effects on the viability of human bronchial epithelial cells. However, effects on gene expression, as well as secretion of cytokines and chemokines, drastically differed, as the crystalline silica induced more intense responses. Our studies indicate that toxicological testing of particulates by surveying viability and/or metabolic activity is insufficient to predict their pathogenicity. Moreover, they show that acute responses of the lung epithelium, including up-regulation of genes linked to inflammation, oxidative stress, and proliferation, as well as secretion of inflammatory and proliferative mediators, can be indicative of pathologic potential using either immortalized lines (BEAS 2B) or primary cells (NHBE). Assessment of the degree and magnitude of these responses <it>in vitro </it>are suggested as predictive in determining the pathogenicity of potentially harmful particulates.</p