Oral Lubrication Matters: Effects on Satiety

As overeating, overweight and obesity remain public health concerns, it is crucial to design satiety-enhancing foods that suppress appetite and lower snack intake. Existing research identifies oro-sensory targets to promote satiation and satiety within the “satiety cascade” yet it remains unclear as to whether it is ‘chewing’ or ‘oral lubrication’ that might amplify satiation signals.Here we have combined techniques from experimental psychology, food material science and mechanical engineering to measure the role of chewing and lubrication using novel, model foods as preloads on subjective appetite and intake of a salty snack. Three mint flavoured hydrogels were engineered to vary in their texture (fracture stress) and lubrication (inverse of friction coefficient) properties, and a control group received a mint tea. Results showed that snack intake was suppressed by 32% after eating the low chewing/high lubricating preload as compared to the high chewing/low lubricating preload (p<0.05). No other significant effects were found for snack intake. Hunger ratings decreased from t1 to t3 (p<0.05), however differences between conditions were subtle and not significant. Thus, this proof-of-concept study demonstrates that manipulating oral lubrication is a promising new construct to reduce snack intake that merits future research in the oro-sensory satiety domain

Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo) Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer

Purpose Trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprising the cytotoxic agent DM1, a stable linker, and trastuzumab, has demonstrated substantial activity in human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer, raising interest in evaluating the feasibility and cardiac safety of T-DM1 in early-stage breast cancer (EBC). Patients and Methods Patients (N = 153) with HER2-positive EBC and prechemotherapy left ventricular ejection fraction (LVEF) \u3e= 55% received (neo) adjuvant doxorubicin plus cyclophosphamide or fluorouracil plus epirubicin plus cyclophosphamide followed by T-DM1 for four cycles. Patients could then receive three to four cycles of optional docetaxel with or without trastuzumab. T-DM1 was then resumed with optional radiotherapy (sequential or concurrent) for 1 year (planned) of HER2-directed therapy. The coprimary end points were rate of prespecified cardiac events and safety. Results Median follow-up was 24.6 months. No prespecified cardiac events or symptomatic congestive heart failures were reported. Four patients (2.7%) had asymptomatic LVEF declines (\u3e= 10 percentage points from baseline to LVEF\u3c 50%), leading to T-DM1 discontinuation in one patient. Of 148 patients who received \u3e= one cycle of T-DM1, 82.4% completed the planned 1-year duration of HER2-directed therapy. During T-DM1 treatment, 38.5% and 2.7% of patients experienced grade 3 and 4 adverse events, respectively. Approximately 95% of patients receiving T-DM1 plus radiotherapy completed \u3e= 95% of the planned radiation dose with dela

Surface adsorption and lubrication properties of plant and dairy proteins: A comparative study

The aim of this work was to compare the surface adsorption and lubrication properties of plant and dairy proteins. Whey protein isolate (WPI) and pea protein isolate (PPI) were chosen as model animal and plant proteins, respectively, and various protein concentrations (0.1–100 mg/mL) were studied with/without heat treatment (90 °C/60 min). Quartz crystal microbalance with dissipation monitoring (QCM-D) experiments were performed on hydrophilic (gold) and hydrophobic polydimethylsiloxane (PDMS) sensors, with or without a mucin coating, latter was used to mimic the oral surface. Soft tribology using PDMS tribopairs in addition to wettability measurements, physicochemical characterization (size, charge, solubility) and gel electrophoresis were performed. Soluble fractions of PPI adsorbed to significantly larger extent on PDMS surfaces, forming more viscous films as compared to WPI regardless of heat treatment. Introducing a mucin coating on a PDMS surface led to a decrease in binding of the subsequent dietary protein layers, with PPI still adsorbing to a larger extent than WPI. Such large hydrated mass of PPI resulted in superior lubrication performance at lower protein concentration (≤10 mg/mL) as compared to WPI. However, at 100 mg/mL, WPI was a better lubricant than PPI, with the former showing the onset of elastohydrodynamic lubrication. Enhanced lubricity upon heat treatment was attributed to the increase in apparent viscosity. Fundamental insights from this study reveal that pea protein at higher concentrations demonstrates inferior lubricity than whey protein and could result in unpleasant mouthfeel, and thus may inform future replacement strategies when designing sustainable food products

Braided racks, Hurwitz actions and Nichols algebras with many cubic relations

We classify Nichols algebras of irreducible Yetter-Drinfeld modules over groups such that the underlying rack is braided and the homogeneous component of degree three of the Nichols algebra satisfies a given inequality. This assumption turns out to be equivalent to a factorization assumption on the Hilbert series. Besides the known Nichols algebras we obtain a new example. Our method is based on a combinatorial invariant of the Hurwitz orbits with respect to the action of the braid group on three strands.Comment: v2: 35 pages, 6 tables, 14 figure

Physics at a Neutrino Factory

In response to the growing interest in building a Neutrino Factory to produce high intensity beams of electron- and muon-neutrinos and antineutrinos, in October 1999 the Fermilab Directorate initiated two six-month studies. The first study, organized by N. Holtkamp and D. Finley, was to investigate the technical feasibility of an intense neutrino source based on a muon storage ring. This design study has produced a report in which the basic conclusion is that a Neutrino Factory is technically feasible, although it requires an aggressive R&D program. The second study, which is the subject of this report, was to explore the physics potential of a Neutrino Factory as a function of the muon beam energy and intensity, and for oscillation physics, the potential as a function of baseline.Comment: 133 pages, 64 figures. Report to the Fermilab Directorate. Available from http://www.fnal.gov/projects/muon_collider/ This version fixes some printing problem

Stability of individual LPS-induced ex vivo cytokine release in a whole blood assay over a five-year interval

Objective: In epidemiological and clinical studies, whole blood assay (WBA) has been used as a measure to characterize inter-individual differences in the cytokine response of individuals exposed to inflammatory agents, such as endotoxins. Several short-time repeatability studies have shown stable cytokine levels in individuals over periods of days, weeks or months, but little is known about the long-term stability of cytokine reactivity. Methods: We studied cytokine response levels in LPS-stimulated whole blood in a cohort of 193 farmers and agricultural industry workers at two time points with a five-year interval. Results: IL-10 and IL-1 beta responses measured with a five-year time interval showed a weak positive correlation (r = 0.22 and 0.27, respectively), whereas no correlation was observed for TNF alpha (r = 0.06). Cytokine reactivity measured repeatedly at the same time point showed high correlations (IL-10 r = 0.80, IL-1 beta r = 0.53 and TNF alpha r = 0.74), suggesting that the observed weak correlations over time are reflective of actual variations in cytokine reactivity over time. Conclusions: Repeatability of ex vivo cytokine reactivity showed to be differential for the measured cytokines, being more stable for IL-10 and IL-1 beta than for TNF alpha. However, in general, repeatability of ex vivo cytokine reactivity was weak, reflecting that cytokine reactivity can mostly be explained by (short term) intra-individual (immunological) or time varying environmental factors and less by genetic or other time-invariant factors. Therefore, WBA should be regarded as a viable tool to study relationships with current health status and exposure, and only partially as a predictor for a future response

Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer

BACKGROUND: Circulating tumour cells (CTCs) offer a non-invasive approach to obtain and characterise metastatic tumour cells, but their usefulness has been limited by low CTC yields from conventional isolation methods. METHODS: To improve CTC yields and facilitate their molecular characterisation we compared the Food and Drug Administration-approved CellSearch Epithelial Kit (CEK) to a simplified CTC capture method, CellSearch Profile Kit (CPK), on paired blood samples from patients with metastatic breast (n=75) and lung (n=71) cancer. Molecular markers including Human Epidermal growth factor Receptor 2 (HER2) were evaluated on CTCs by fluorescence in situ hybridisation (FISH) and compared to patients' primary and metastatic cancer. RESULTS: The median cell count from patients with breast cancer using the CPK was 117 vs 4 for CEK (P<0.0001). Lung cancer samples were similar; CPK: 145 cells vs CEK:4 cells (P<0.0001). Recovered CTCs were relatively pure (60-70%) and were evaluable by FISH and immunofluorescence. A total of 10 of 30 (33%) breast cancer patients with HER2-negative primary and metastatic tissue had HER2-amplified CTCs. CONCLUSION: The CPK method provides a high yield of relatively pure CTCs, facilitating their molecular characterisation. Circulating tumour cells obtained using CPK technology demonstrate that significant discordance exists between HER2 amplification of a patient's CTCs and that of the primary and metastatic tumour

Prorenin anno 2008

For many years, prorenin has been considered to be nothing more than the inactive precursor of renin. Yet, its elevated levels in diabetic subjects with microvascular complications and its extrarenal production at various sites in the body suggest otherwise. This review discusses the origin, regulation, and enzymatic activity of prorenin, its role during renin inhibition, and the angiotensin-dependent and angiotensin-independent consequences of its binding to the recently discovered (pro)renin receptor. The review ends with the concept that prorenin rather than renin determines tissue angiotensin generation

Trastuzumab-DM1 causes tumour growth inhibition by mitotic catastrophe in trastuzumab-resistant breast cancer cells in vivo

Introduction Trastuzumab is widely used for the treatment of HER2-positive breast cancer. Despite encouraging clinical results, a significant fraction of patients are, or become, refractory to the drug. To overcome this, trastuzumab-DM1 (T-DM1), a newer, more potent drug has been introduced. We tested the efficacy and mechanisms of action of T-DM1 in nine HER2-positive breast cancer cell lines in vitro and in vivo. The nine cell lines studied included UACC-893, MDA-453 and JIMT-1, which are resistant to both trastuzumab and lapatinib. Methods AlamarBlue cell-proliferation assay was used to determine the growth response of breast cancer cell lines to trastuzumab and T-DM1 in vitro. Trastuzumab- and T-DM1-mediated antibody-dependent cellular cytotoxicity (ADCC) was analysed by measuring the lactate dehydrogenase released from the cancer cells as a result of ADCC activity of peripheral blood mononuclear cells. Severe Combined Immunodeficient (SCID) mice were inoculated with trastuzumab-resistant JIMT-1 cells to investigate the tumour inhibitory effect of T-DM1 in vivo. The xenograft samples were investigated using histology and immunohistochemistry. Results T-DM1 was strongly growth inhibitory on all investigated HER2-positive breast cancer cell lines in vitro. T-DM1 also evoked antibody-dependent cellular cytotoxicity (ADCC) similar to that of trastuzumab. Outgrowth of JIMT-1 xenograft tumours in SCID mice was significantly inhibited by T-DM1. Histologically, the cellular response to T-DM1 consisted of apoptosis and mitotic catastrophe, the latter evidenced by an increased number of cells with aberrant mitotic figures and giant multinucleated cells. Conclusions Our results suggest mitotic catastrophe as a previously undescribed mechanism of action of T-DM1. T-DM1 was found effective even on breast cancer cell lines with moderate HER2 expression levels and cross-resistance to trastuzumab and lapatinib (MDA-453 and JIMT-1).BioMed Central Open acces