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

Transfer of Communication Skills to the Workplace during Clinical Rounds : Impact of a Program for Residents

peer reviewe

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

Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease

peer reviewedOBJECTIVES: The use of monoclonal anti-tumor necrosis factor (TNF) antibodies (infliximab, Remicade) is a new therapeutic approach for severe refractory luminal or fistulizing, Crohn's disease (CD). However, up to 30% of patients do not respond to this treatment. So far, no parameters predictive of response to anti-TNT have been identified. Our aim was to determine whether serological markers ASCA (anti-Saccharomyces cerevisiae antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibodies) could identify Crohn's patients likely to benefit from anti-TNF therapy. METHODS: Serum samples of 279 CID patients were analyzed for ASCA and pANCA before anti-TNF therapy. A blinded physician determined clinical response at week 4 (refractory luminal CD) or week 10 (fistulizing CD) after the first infusion of infliximab (5 mg/kg). RESULTS: Overall, there was no relationship between ASCA or pANCA and response to therapy. However, lower response rates were observed for patients with refractory intestinal disease carrying the pANCA+/ASCA- combination, although this lacked significance (p = 0.067). CONCLUSIONS: In this cohort of infliximab-treated patients, neither ASCA nor pANCA could predict response to treatment. However, the combination pANCA+/ASCA- might warrant further investigation for its value in predicting nonresponse in patients with refractory luminal disease

The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013 The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration

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

ERS International Congress 2023: highlights from the Basic and Translational Sciences Assembly.

Early career members of Assembly 3 (Basic and Translational Sciences) of the European Respiratory Society (ERS) summarise the key messages discussed during six selected sessions that took place at the ERS International Congress 2023 in Milan, Italy. Aligned with the theme of the congress, the first session covered is "Micro- and macro-environments and respiratory health", which is followed by a summary of the "Scientific year in review" session. Next, recent advances in experimental methodologies and new technologies are discussed from the "Tissue modelling and remodelling" session and a summary provided of the translational science session, "What did you always want to know about omics analyses for clinical practice?", which was organised as part of the ERS Translational Science initiative's aims. The "Lost in translation: new insights into cell-to-cell crosstalk in lung disease" session highlighted how next-generation sequencing can be integrated with laboratory methods, and a final summary of studies is presented from the "From the transcriptome landscape to innovative preclinical models in lung diseases" session, which links the transcriptome landscape with innovative preclinical models. The wide range of topics covered in the selected sessions and the high quality of the research discussed demonstrate the strength of the basic and translational science being presented at the international respiratory conference organised by the ERS

Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas

Reactive oxygen species (ROS) increase ligation of Fas (CD95), a receptor important for regulation of programmed cell death. Glutathionylation of reactive cysteines represents an oxidative modification that can be reversed by glutaredoxins (Grxs). The goal of this study was to determine whether Fas is redox regulated under physiological conditions. In this study, we demonstrate that stimulation with Fas ligand (FasL) induces S-glutathionylation of Fas at cysteine 294 independently of nicotinamide adenine dinucleotide phosphate reduced oxidase–induced ROS. Instead, Fas is S-glutathionylated after caspase-dependent degradation of Grx1, increasing subsequent caspase activation and apoptosis. Conversely, overexpression of Grx1 attenuates S-glutathionylation of Fas and partially protects against FasL-induced apoptosis. Redox-mediated Fas modification promotes its aggregation and recruitment into lipid rafts and enhances binding of FasL. As a result, death-inducing signaling complex formation is also increased, and subsequent activation of caspase-8 and -3 is augmented. These results define a novel redox-based mechanism to propagate Fas-dependent apoptosis

The therapeutic effect of the neuropeptide hormone somatostatin on Schistosoma mansoni caused liver fibrosis

BACKGROUND: The neuropeptide somatostatin is one of the major regulatory peptides in the central nervous system and the digestive tract. Our recent work has delineated an association between fibrosis and low levels of endogenous somatostatin plasma levels in Schistosoma mansoni infected subjects. Based on these results this paper explores the therapeutic potential of somatostatin in a mouse model of hepatic fibrosis associated with S. mansoni infections. METHODS: Groups of outbred Swiss mice were infected with 100 S. mansoni cercariae, infection maintained till weeks 10 or 14, and then somatostatin therapy delivered in two regimens – Either a one or a two-day treatment. All animals were sacrificed one week after therapy and controlled for liver, spleen and total body weight. Circulating somatostatin levels in mice plasma were measured at the time of sacrifice by means of a radio-immuno assay. GraphPad Prism(® )was used for statistical calculations. RESULTS: Somatostatin administration showed little toxicity, probably due to its short half-life. Total liver and spleen weights of S. mansoni infected animals increased over time, with no changes observed due to somatostatin therapy. Total body weights were decreased after infection but were not affected by somatostatin therapy. Snap frozen liver sections were stained with haematoxylin-eosin or Masson's trichrome to study parasite count, hepatocyte status, granuloma size and cellularity. After somatostatin treatment mean egg counts per liver section (43.76 ± 3.56) were significantly reduced as compared to the egg counts in untreated mice after 10 weeks of infection (56.01 ± 3.34) (P = 0.03). Similar significant reduction in parasite egg counts were also observed after somatostatin treatment at 14 weeks of infection (56.62 ± 3.02) as compared to untreated animals (69.82 ± 2.77)(P = 0.006). Fibrosis was assessed from the spectrophotometric determination of tissue hydroxyproline. Infection with S. mansoni caused increased hydroxyproline levels (9.37 ± 0.63 μmol at wk10; 9.65 ± 0.96 μmol at wk14) as compared to uninfected animals (1.06 ± 0.10 μmol). This significant increase in collagen content (P = 0.01; 0.007 respectively) marks the fibrosis observed at these time points. Treatment with somatostatin resulted in a significant decrease in hydroxyproline levels both at wk10 (4.76 ± 0.58 μmol) and at wk14 (5.8 ± 1.13 μmol) (P = 0.01; 0.03 respectively). Endogenous somatostatin levels were increased at wk10 (297 ± 37.24 pg/ml) and wk14 (206 ± 13.30 pg/ml) of infection as compared to uninfected mice (119 ± 11.99 pg/ml) (P = 0.01; 0.008 respectively). Circulating somatostatin levels in infected animals were not significantly affected by somatostatin treatment. Hepatocyte status remained unaltered and granulomas were not remarkably changed in size or cellularity. CONCLUSION: Our experiments reveal an antifibrotic effect of somatostatin in schistosomiasis. We have previously shown that the somatostatin receptors SSTR2 and SSTR3 are present on the parasite egg and worms. We therefore hypothesize that somatostatin reduces either the number of parasite eggs or the secretion of fibrosis inducing-mediators. Our data suggest somatostatin may have therapeutic potential in S. mansoni mediated liver pathology