Incidence, clinical features, and outcomes of special types in breast cancer in a single institution population.

The low incidence of special types of breast cancer hinders adequate clinical research efforts. As such, collecting sufficient data to develop well-established therapy strategies are difficult. The aim of our study was to obtain more data on these special types in order to better understand the different characteristics and optimize therapy strategies. A single-institution retrospective cohort study from January 2007 until September 2015. One hundred and five patients remained after excluding the patients with invasive ductal and lobular carcinoma. The percentage of these so called special types in this population was 4%. Tubular carcinoma, cribriform carcinoma, carcinoma with medullary features, carcinoma with apocrine differentiation, secretory carcinoma, mucinous carcinoma, and invasive papillary carcinoma had a good or excellent prognosis, while invasive micropapillary carcinoma, adenoid cystic carcinoma, metaplastic carcinoma, and carcinoma with neuroendocrine features had a worse prognosis. Special types of breast cancer form a heterogeneous group. Submitting them all to the same treatment modality may lead to both over- and under-treatment. We need to combine our data to optimize treatment strategies for the different special types.

International round-robin experiment for angle-resolved light scattering measurement.

An international round-robin experiment has been conducted to test procedures and methods for the measurement of angle-resolved light scattering. ASTM E2387-05 has been used as the main guide, while the experience gained should also contribute to the new ISO standard of angle-resolved scattering currently under development (ISO/WD 19986:2016). Seven laboratories from Europe and the United States measured the angle-resolved scattering from Al/SiO2-coated substrates, transparent substrates, volume diffusors, quasi-volume diffusors, white calibration standards, and grating samples at laser wavelengths in the UV, VIS, and NIR spectra. Results were sent to Fraunhofer IOF, which coordinated the experiments and analyzed the data, while ESA-ESTEC, as the project donor, defined conditions and parameters. Depending mainly on the sample type, overall good to reasonable agreements were observed, with largest deviations at scattering angles very close to the specular beam. Volume diffusor characterization unexpectedly turned out to be challenging. Not all participants provided measurement uncertainty ranges according to the Guide to the Expression of Uncertainty in Measurement; often, a single general scatterometer-related measurement uncertainty value was stated. Although relative instrument measurement uncertainties close to 1% are sometimes claimed, the comparison results did not support these claims for specular scattering samples as mirrors, substrates, or gratings.

Weight loss-induced cellular stress in subcutaneous adipose tissue and the risk for weight regain in overweight and obese adults.

BACKGROUND/OBJECTIVE: Weight loss is often followed by weight regain after the dietary intervention (DI). Cellular stress is increased in adipose tissue of obese individuals. However, the relation between cellular stress and weight regain is unclear. Previously, we observed increased adipose tissue cellular stress of participants regaining weight compared with participants maintaining weight loss. In the current study, we further investigated the relation between weight regain and changes in the expression of stress-related genes and stress protein levels to determine possible predictors of weight regain. PARTICIPANTS/METHODS: In this randomized controlled trial, sixty-one healthy overweight/obese participants followed a DI of either a 5-week very-low-calorie diet (500 kcal per day) or a 12-week low-calorie diet (1250 kcal per day; WL period) with a subsequent 4-week weight stable diet (WS period), and a 9-month follow-up. The WL and WS period taken together was named the DI. Abdominal subcutaneous adipose tissue biopsies were collected in 53 participants for microarray and liquid chromatography-mass spectrometry analysis. RNA and protein levels for a broad set of stress-related genes were correlated to the weight regain percentage. RESULTS: Different gene sets correlated to weight regain percentage during WS and DI. Bioinformatics clustering suggests that during the WS phase-defined genes for actin filament dynamics, glucose handling and nutrient sensing are related to weight regain. HIF-1 (hypoxia-inducible factor-1) is indicated as an important regulator. With regard to DI, clustering of correlated genes indicate that LGALS1, ENO1 and ATF2 are important nodes for conferring risk for weight regain. CONCLUSIONS: Our present findings indicate that the risk for weight regain is related to expression changes of distinct sets of stress-related genes during the first 4 weeks after returning to energy balance, and during the DI. Further research is required to investigate the mechanistic significance of these findings and find targets for preventing weight regain.

Adipose tissue gene expression is differentially regulated with different rates of weight loss in overweight and obese humans.

BACKGROUND/OBJECTIVES: Moderate weight loss (WL) can ameliorate adverse health effects associated with obesity, reflected by an improved adipose tissue (AT) gene expression profile. However, the effect of rate of WL on the AT transcriptome is unknown. We investigated the global AT gene expression profile before and after two different rates of WL that resulted in similar total WL, and after a subsequent weight stabilization period. SUBJECTS/METHODS: In this randomized controlled trial, 25 male and 28 female individuals (body mass index (BMI): 28-35 kg m-2) followed either a low-calorie diet (LCD; 1250 kcal day-1) for 12 weeks or a very-low-calorie diet (VLCD; 500 kcal day-1) for 5 weeks (WL period) and a subsequent weight stable (WS) period of 4 weeks. The WL period and WS period together is termed dietary intervention (DI) period. Abdominal subcutaneous AT biopsies were collected for microarray analysis and gene expression changes were calculated for all three periods in the LCD group, VLCD group and between diets (ΔVLCD-ΔLCD). RESULTS: WL was similar between groups during the WL period (LCD: -8.1±0.5 kg, VLCD: -8.9±0.4 kg, difference P=0.25). Overall, more genes were significantly regulated and changes in gene expression appeared more pronounced in the VLCD group compared with the LCD group. Gene sets related to mitochondrial function, adipogenesis and immunity/inflammation were more strongly upregulated on a VLCD compared with a LCD during the DI period (positive ΔVLCD-ΔLCD). Neuronal and olfactory-related gene sets were decreased during the WL period and DI period in the VLCD group. CONCLUSIONS: The rate of WL (LCD vs VLCD), with similar total WL, strongly regulates AT gene expression. Increased mitochondrial function, angiogenesis and adipogenesis on a VLCD compared with a LCD reflect potential beneficial diet-induced changes in AT, whereas differential neuronal and olfactory regulation suggest functions of these genes beyond the current paradigm.

Diet-induced weight loss decreases adipose tissue oxygen tension with parallel changes in adipose tissue phenotype and insulin sensitivity in overweight humans.

BACKGROUND/OBJECTIVES: Although adipose tissue (AT) hypoxia is present in rodent models of obesity, evidence for this in humans is limited. Here, we investigated the effects of diet-induced weight loss (WL) on abdominal subcutaneous AT oxygen tension (pO2), AT blood flow (ATBF), AT capillary density, AT morphology and transcriptome, systemic inflammatory markers and insulin sensitivity in humans. SUBJECTS/METHODS: Fifteen overweight and obese individuals underwent a dietary intervention (DI), consisting of a 5-week very-low-calorie diet (VLCD, 500 kcal day-1; WL), and a subsequent 4-week weight stable diet (WS). Body composition, AT pO2 (optochemical monitoring), ATBF (133Xe washout), and whole-body insulin sensitivity were determined, and AT biopsies were collected at baseline, end of WL (week 5) and end of WS (week 9). RESULTS: Body weight, body fat percentage and adipocyte size decreased significantly during the DI period. The DI markedly decreased AT pO2 and improved insulin sensitivity, but did not alter ATBF. Finally, the DI increased AT gene expression of pathways related to mitochondrial biogenesis and non-mitochondrial oxygen consumption. CONCLUSIONS: VLCD-induced WL markedly decreases abdominal subcutaneous AT pO2, which is paralleled by a reduction in adipocyte size, increased AT gene expression of mitochondrial biogenesis markers and non-mitochondrial oxygen consumption pathways, and improved whole-body insulin sensitivity in humans.

Changes in substance P and NK1 receptor immunohistochemistry following human spinal cord injury.

STUDY DESIGN: An immunohistological assessment of substance P (SP), its NK1 receptor and claudin-5 in human spinal cord injury (SCI) tissue. OBJECTIVE: To determine whether SP and NK1 receptor immunoreactivity are altered following human traumatic SCI. SETTING: Australia. SUMMARY OF BACKGROUND DATA: SP has been implicated in the development of neurogenic inflammation and subsequent edema development following both traumatic brain injury and ischemic stroke. In these conditions, inhibition of its NK1 receptor has been shown to be neuroprotective as reflected in a reduction of edema and improved functional outcome. However, the role of SP following human SCI has not yet been assessed. METHODS: Archived human SCI tissue was grouped according to survival times: control (no injury; n=5); immediate (death within an hour of the incident; n=6); 2-5 h (n=3); 3 days (n=5); 1 week (n=3); and 3-4 weeks (n=6). Sections were assessed for SP, its NK1 receptor and claudin-5 using immunohistochemical techniques. RESULTS: Following SCI, dorsal horn SP immunoreactivity demonstrated a profound decrease compared with control tissue, indicating the loss of SP with SCI. A marked increase in perivascular NK1 staining was demonstrated after SCI compared with control levels. No obvious change in claudin-5 immunoreactivity was present immediately following injury, however, by 1 week post-SCI, decreased levels were noted. CONCLUSION: This study demonstrates that severe acute traumatic human SCI results in decreased SP and an immediate increase in NK1 receptor immunoreactivity, suggesting that there is a neurogenic inflammatory component following human SCI.

Domain formation in membranes with quenched protein obstacles: lateral heterogeneity and the connection to universality classes.

We show that lateral fluidity in membranes containing quenched protein obstacles belongs to the universality class of the two-dimensional random-field Ising model. The main feature of this class is the absence of a phase transition: there is no critical point and macroscopic domain formation does not occur. Instead there is only one phase. This phase is highly heterogeneous with a structure consisting of microdomains. The presence of quenched protein obstacles thus provides a mechanism to stabilize lipid rafts in equilibrium. Crucial for two-dimensional random-field Ising universality is that the obstacles are randomly distributed and have a preferred affinity to one of the lipid species. When these conditions are not met standard Ising or diluted Ising universality applies. In these cases a critical point does exist which then marks the onset toward macroscopic demixing.

Friction on incommensurate substrates: Role of anharmonicity and defects.

We present molecular dynamics simulations of one- and two-dimensional bead-spring models sliding on incommensurate substrates after an initial kick, in the case where the coupling to the underlying substrate is weak, i.e., energy can dissipate only into the internal degrees of freedom of the sliding object, but not into the substrate below. We investigate how sliding friction is affected by structural defects and interaction anharmonicity. In their absence, we confirm earlier findings, namely, that at special resonance sliding velocities, friction is maximal. When sliding off-resonance, partially thermalized states are possible, whereby only a small number of vibrational modes becomes excited, but whose kinetic energies are already Maxwell-Boltzmann distributed. Anharmonicity and defects typically destroy partial thermalization and instead lead to full thermalization, implying much higher friction. For sliders with periodic boundaries, thermalization begins with vibrational modes whose spatial modulation is compatible with the incommensurate lattice. For a disk-shaped slider, modes corresponding to modulations compatible with the slider radius are initially the most dominant. By tuning the mechanical properties of the slider's edge, this effect can be controlled, resulting in significant changes in the sliding distance covered.

Nematics with quenched disorder: violation of self-averaging.

We consider the isotropic-to-nematic transition in liquid crystals confined to aerogel hosts, and assume that the aerogel acts as a random field. We generally find that self-averaging is violated. For a bulk transition that is weakly first order, the violation of self-averaging is so severe that even the correlation length becomes non-self-averaging: no phase transition remains in this case. For a bulk transition that is more strongly first order, the violation of self-averaging is milder, and a phase transition is observed.

Attitudes of Dutch intensive care unit clinicians towards oxygen therapy.

BACKGROUND: Over the last decade, there has been an increasing awareness for the potential harm of the administration of too much oxygen. We aimed to describe self-reported attitudes towards oxygen therapy by clinicians from a large representative sample of intensive care units (ICUs) in the Netherlands. METHODS: In April 2019, 36 ICUs in the Netherlands were approached and asked to send out a questionnaire (59 questions) to their nursing and medical staff (ICU clinicians) eliciting self-reported behaviour and attitudes towards oxygen therapy in general and in specific ICU case scenarios. RESULTS: In total, 1361 ICU clinicians (71% nurses, 24% physicians) from 28 ICUs returned the questionnaire. Of responding ICU clinicians, 64% considered oxygen-induced lung injury to be a major concern. The majority of respondents considered a partial pressure of oxygen (PaO2) of 6-10 kPa (45-75 mmHg) and an arterial saturation (SaO2) of 85-90% as acceptable for 15 minutes, and a PaO2 7-10 kPa (53-75 mmHg) and SaO2 90-95% as acceptable for 24-48 hours in an acute respiratory distress syndrome (ARDS) patient. In most case scenarios, respondents reported not to change the fraction of inspired oxygen (FiO2) if SaO2 was 90-95% or PaO2 was 12 kPa (90 mmHg). CONCLUSION: A representative sample of ICU clinicians from the Netherlands were concerned about oxygen-induced lung injury, and reported that they preferred PaO2 and SaO2 targets in the lower physiological range and would adjust ventilation settings accordingly.

The role of excitatory amino acids and NMDA receptors in traumatic brain injury.

Brain injury induced by fluid percussion in rats caused a marked elevation in extracellular glutamate and aspartate adjacent to the trauma site. This increase in excitatory amino acids was related to the severity of the injury and was associated with a reduction in cellular bioenergetic state and intracellular free magnesium. Treatment with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist dextrophan or the competitive antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid limited the resultant neurological dysfunction; dextrorphan treatment also improved the bioenergetic state after trauma and increased the intracellular free magnesium. Thus, excitatory amino acids contribute to delayed tissue damage after brain trauma; NMDA antagonists may be of benefit in treating acute head injury.

Guidelines' risk assessment recommendations for venous thromboembolism prophylaxis: A comparison and implementability appraisal.

INTRODUCTION: Venous thromboembolism (VTE) prophylaxis guidelines for non-surgical patients recommend VTE- and bleeding risk assessment to guide prophylactic strategies. These recommendations differ between guidelines and implementation is suboptimal. Assessing a guideline's implementability characteristics helps predicting the ease of implementation and reveals barriers. OBJECTIVES: We aimed to compare guidelines' risk assessment recommendations and critically appraise the implementability characteristics. MATERIAL AND METHODS: Two guidelines, one from the American College of Chest Physicians and one from the National Institute for Health and Care Excellence were selected for comparison. Risk assessment methods and subsequent prophylactic recommendations were compared. Eight experts then appraised the guideline recommendations on intrinsic implementability characteristics using the GuideLine Implementability Appraisal (GLIA) instrument. GLIA identifies barriers and facilitators for guideline implementation in nine dimensions. RESULTS: Eleven out of 20 individual VTE-risk factors and 2 out of 19 individual bleeding-risk factors used, were present in both guidelines. Additionally, a high VTE- or bleeding risk was defined differently between the two guidelines. The GLIA appraisal identified implementation barriers within all recommendations analyzed. On content level, barriers were identified in recommendations addressing bleeding risk assessment, mechanical prophylaxis and critical care patients. On implementability level, barriers were identified in decidability, flexibility, effect on process of care and computability dimensions. CONCLUSION: Depending on the guideline used, VTE-prophylaxis will most likely be provided to different non-surgical patient populations, primarily due to discordance in bleeding risk assessment. Revising the recommendations, taking into account the most apparent implementation barriers, should be considered. However, insufficient evidence to support the recommendations currently complicates this.

Correlations suggest low magnesium may lead to higher rates of type 2 diabetes in Indigenous Australians.

INTRODUCTION: Diabetes accounts for a significant part of the morbidity and mortality experienced by Australian Aboriginal and Torres Strait Islander populations. Research over the past two decades has provided evidence of a clinical correlation between diabetes and low magnesium intake. Hypomagnesaemia is the most common electrolyte abnormality in diabetic outpatients and may be linked to the development of both macrovascular and microvascular diabetic complications. A diabetes risk reduction of 33%-34% has been found among those with diets highest in magnesium. OBJECTIVE: This study examines the case for magnesium as a potential contributor to diabetes in Australia, especially among Aboriginal and Torres Strait Islander peoples. Specifically explored are associations between diabetes and the magnesium content of drinking water and diet, as well as climatic and socioeconomic factors that may impact on magnesium status including temperature, rainfall, education, employment and income. METHODS: Queensland age-standardized death rates due to diabetes were correlated with the magnesium content of drinking water, maximum average temperature, rainfall, unemployment rate, proportion of population with post-school qualification, weekly income, and the percentage population identified as Indigenous. Multiple-pass 24-hour recalls from a convenience sample of 100 Indigenous patients at a regional centre were also analyzed to estimate dietary magnesium intake. The Indigenous nutrient intake was then compared with the Australian National Nutrition Survey estimates. RESULTS: Diabetes related mortality was significantly correlated to the percentage of the population identified as Indigenous (r = 0.675), to water magnesium levels (r = -.414), and to average maximum daily temperature (r = 0.579). The average daily magnesium intake in an Indigenous cohort from a regional centre was 248 mg (men: 267 mg +/- 17; women: 245 mg +/- 6 mg), significantly less than intakes observed in the 1995 National Nutrition Survey (p<.001). CONCLUSIONS: Although not representative of all Indigenous people, this study identified low dietary magnesium intake among an Indigenous cohort from a regional centre. We also found a significant correlation between the magnesium content of municipal water supplies and age-standardized deaths due to diabetes. We hypothesise that low magnesium dietary intake, compounded by inadequate magnesium replenishment in drinking water, may increase the risk of hypomagnesaemia in the Indigenous population of Queensland. The associations identified in this study support the hypothesis that magnesium may be a potential contributor to diabetes in Australia, especially among Indigenous people, and confirm the need for further research.

Coexistence diameter in two-dimensional colloid-polymer mixtures.

We demonstrate that the law of the rectilinear coexistence diameter in two-dimensional mixtures of nonspherical colloids and nonadsorbing polymers is violated. Upon approach to the critical point, the diameter shows logarithmic singular behavior governed by a term t ln t, with t the relative distance from the critical point. No sign of a term t2beta could be detected, with beta the critical exponent of the order parameter, indicating a very weak or absent Yang-Yang anomaly. Our analysis thus reveals that nonspherical particle shape alone is not sufficient for the formation of a pronounced Yang-Yang anomaly in the critical behavior of fluids.

Critical behavior of a colloid-polymer mixture confined between walls.

We investigate the influence of confinement on phase separation in colloid-polymer mixtures. To describe the particle interactions, the colloid-polymer model of Asakura and Oosawa [J. Chem. Phys. 22, 1255 (1954)] is used. Grand canonical Monte Carlo simulations are then applied to this model confined between two parallel hard walls, separated by a distance D = 5 colloid diameters. We focus on the critical regime of the phase separation and look for signs of crossover from three-dimensional (3D) Ising to two-dimensional (2D) Ising universality. To extract the critical behavior, finite size scaling techniques are used, including the recently proposed algorithm of Kim et al [Phys. Rev. Lett. 91, 065701 (2003)]. Our results point to "effective" critical exponents that differ profoundly from 3D Ising values, and that are already very close to 2D Ising values. In particular, we observe that the critical exponent of the order parameter in the confined system is smaller than in 3D bulk, yielding a "flatter" binodal. Our results also show an increase in the critical colloid packing fraction in the confined system with respect to the bulk. The latter seems consistent with theoretical expectations, although subtleties due to singularities in the critical behavior of the coexistence diameter cannot be ruled out.

Critical behavior in colloid-polymer mixtures: theory and simulation.

We extensively investigated the critical behavior of mixtures of colloids and polymers via the two-component Asakura-Oosawa model and its reduction to a one-component colloidal fluid using accurate theoretical and simulation techniques. In particular the theoretical approach, hierarchical reference theory [A. Parola and L. Reatto, Adv. Phys. 44, 211 (1995)], incorporates realistically the effects of long-range fluctuations on phase separation giving exponents which differ strongly from their mean-field values, and are in good agreement with those of the three-dimensional Ising model. Computer simulations combined with finite-size scaling analysis confirm the Ising universality and the accuracy of the theory, although some discrepancy in the location of the critical point between one-component and full-mixture description remains. To assess the limit of the pair-interaction description, we compare one-component and two-component results.

Phase diagram and structure of colloid-polymer mixtures confined between walls.

The influence of confinement, due to flat parallel structureless walls, on phase separation in colloid-polymer mixtures, is investigated by means of grand-canonical Monte Carlo simulations. Ultrathin films, with thicknesses between D=3-10 colloid diameters, are studied. The Asakura-Oosawa model [J. Chem. Phys. 22, 1255 (1954)] is used to describe the particle interactions. To simulate efficiently, a "cluster move" [J. Chem. Phys. 121, 3253 (2004)] is used in conjunction with successive umbrella sampling [J. Chem. Phys. 120, 10925 (2004)]. These techniques, when combined with finite size scaling, enable an accurate determination of the unmixing binodal. Our results show that the critical behavior of the confined mixture is described by "effective" critical exponents, which gradually develop from values near those of the two-dimensional Ising model, to those of the three-dimensional Ising model, as D increases. The scaling predictions of and Fisher and Nakanishi [J. Chem. Phys. 75, 5875 (1981)] for the shift of the critical point are compatible with our simulation results. Surprisingly, however, the colloid packing fraction at criticality approaches its bulk (D-->infinity) value nonmonotonically, as D is increased. Far from the critical point, our results are compatible with the simple Kelvin equation, implying a shift of order 1/D in the coexistence colloid chemical potential. We also present density profiles and pair distribution functions for a number of state points on the binodal, and the influence of the colloid-wall interaction is studied.

The temporal profile of edema formation differs between male and female rats following diffuse traumatic brain injury.

Although female hormones are known to influence edema formation following traumatic brain injury (TBI), no studies have actually compared the temporal profile of edema formation in both male and female rats following diffuse TBI. In this study, male, female, and female ovariectomized rats were injured using the 2 m impact acceleration model of diffuse TBI. The temporal profile of brain water content was assessed over 1 week post-trauma. Male animals demonstrated increased (p < 0.05) edema at 5 hours, 24 hours, 3 days, 4 days, and 5 days after TBI with a peak at 5 hours post-injury. This time point was associated with increased blood-brain barrier (BBB) permeability. In contrast, intact females showed increased levels of edema (p < 0.05) at 5 hours, 24 hours, 3 days, and 4 days post-TBI, with a peak at 24 hours. No BBB opening was present in intact females at 5 hours. Female animals demonstrated more edema than male animals at 24 hours, but less at 5 hours, 3 days, and 5 days. Ovariectomy produced an edema profile that was similar to that observed in males. The temporal profile of edema formation after TBI seems to depend on endogenous hormone levels, a difference which may have an influence on clinical management.

Magnesium restores altered aquaporin-4 immunoreactivity following traumatic brain injury to a pre-injury state.

Magnesium reduces edema following traumatic brain injury (TBI), although the associated mechanisms are unknown. Recent studies suggest that edema formation after TBI may be related to alterations in aquaporin-4 (AQP4) channels. In this study, we characterize the effects of magnesium administration on AQP4 immunoreactivity following TBI. Male Sprague-Dawley rats were injured by impact-acceleration diffuse TBI and a subgroup was administered 30 mg/kg magnesium sulphate 30 minutes after injury. Animals were fixed by perfusion 5 hours later, which corresponded to the time of maximum edema formation according to previous studies. One half of the brain was cut using a Vibratome and the other half blocked in paraffin wax. Wax and Vibratome sections were immunostained for detection of AQP4 by light and electron microscopy, respectively. In untreated animals, AQP4 immunoreactivity was increased in the subependymal inner glia limitans and the subpial outer glia limitans, and decreased in perivascular astrocytic processes in the cerebrum and brain stem. In contrast, animals treated with magnesium sulphate had AQP4 profiles similar to normal and sham control animals. We conclude that magnesium decreases brain edema formation after TBI, possibly by restoring the polarized state of astrocytes and by down-regulation of AQP4 channels in astrocytes.