Is it safe to operate selected low-risk endometrial cancer patients in secondary hospitals?

INTRODUCTION: The aim of this study was to assess the accuracy of a preoperative screening algorithm in identifying low-risk endometrial cancer (EC) patients to ensure optimal care. METHODS: A total of 277 patients with primary EC confirmed through biopsy underwent magnetic resonance imaging (MRI). Patients with risk factors for advanced high-risk EC, such as non-endometrioid histology, high-grade differentiation status, deep myometrial invasion, or spread beyond the uterine corpus, were systematically excluded. The remaining preoperatively screened patients with stage IA low-grade endometrioid EC (EEC) (n = 93) underwent surgery in a tertiary hospital. The accuracy of the preoperative diagnosis was evaluated by comparing the findings with the postoperative histopathological results. Disease-free survival (DFS) and overall survival (OS) were analyzed using 8-year follow-up data. RESULTS: Postoperative histopathological analysis revealed that all patients had grade 1-2 EEC localized to the corpus uteri. Only three patients had deep myometrial invasion (stage IB), but they remained disease-free after 6-9 years of follow-up. The median follow-up time for all patients was 8.7 years. The DFS was 7.6 years, and the OS was 8.6 years. Two patients with stage IA grade 1 EEC experienced relapse and, despite treatment, died of EC. No other EC-related deaths occurred. CONCLUSIONS: The screening algorithm accurately identified low-risk EC patients without compromising survival. Therefore, the algorithm appears to be feasible for selecting patients for surgery in secondary hospitals.

Different Methods to Detect Stress in Knowledge Workers: A Pilot Study for Long-term Monitoring.

Stress is a common part of working life, but knowledge is lacking on how to identify it early and with little effort on the part of the employee. We investigated whether simple stress reports and computer usage data could be useful tools for long-term assessment of stress in real life. 38 experts responded to a baseline questionnaire on need for recovery (NFR) and psychological distress (General Health Questionnaire, GHQ12). Their computer usage for work was recorded for 5 months, during which they filled in a 4-month simple diary and a 2-week detailed diary on, for example, stress and productivity. Salivary cortisol and heart rate variability were collected on 3 consecutive days. Generalized estimating equations models were used for the analyses. High NFR and GHQ12 predicted self-reported stress during work, and a decrease in (some) mouse usage features, but not keyboard usage features, over the following months. Some mouse usage features were associated with stress and productivity. The results provide some support for the usefulness of simple stress questions and mouse usage features in assessing long-term stress in real life.

Positive affect state is a good predictor of movement and stress: combining data from ESM/EMA, mobile HRV measurements and trait questionnaires.

Personality describes the average behaviour and responses of individuals across situations; but personality traits are often poor predictors of behaviour in specific situations. This is known as the "personality paradox". We evaluated the interrelations between various trait and state variables in participants' everyday lives. As state measures, we used 1) experience sampling methodology (ESM/EMA) to measure perceived affect, stress, and presence of social company; and 2) heart rate variability and 3) real-time movement (accelerometer data) to indicate physiological stress and physical movement. These data were linked with self-report measures of personality and personality-like traits. Trait variables predicted affect states and multiple associations were found: traits neuroticism and rumination decreased positive affect state and increased negative affect state. Positive affect state, in turn, was the strongest predictor of observed movement. Positive affect was also associated with heart rate and heart rate variability (HRV). Negative affect, in turn, was not associated with neither movement, HR or HRV. The study provides evidence on the influence of personality-like traits and social context to affect states, and, in turn, their influence to movement and stress variables.

Influence of Personality and Differences in Stress Processing Among Finnish Students on Interest to Use a Mobile Stress Management App: Survey Study.

BACKGROUND: Excessive stress has a negative impact on many aspects of life for both individuals and societies, from studying and working to health and well-being. Each individual has their unique level of stress-proneness, and positive or negative outcomes of stress may be affected by it. Technology-aided interventions have potential efficacy in the self-management of stress. However, current Web-based or mobile stress management solutions may not reach the individuals that would need them the most, that is, stress-sensitive people. OBJECTIVE: The aim of this study was to examine how personality is associated with stress among Finnish university students and their interest to use apps that help in managing stress. METHODS: We used 2 structured online questionnaires (combined, n=1001) that were advertised in the University of Helsinki's mailing lists. The first questionnaire (n=635) was used to investigate intercorrelations between the Big Five personality variables (neuroticism, extraversion, openness, agreeableness, and conscientiousness) and other stress-related background variables. The second questionnaire (n=366) was used to study intercorrelations between the above-mentioned study variables and interest in using stress management apps. RESULTS: The quantitative findings of the first questionnaire showed that higher levels of extraversion, agreeableness, and conscientiousness were associated with lower self-reported stress. Neuroticism, in turn, was found to be strongly associated with rumination, anxiety, and depression. The findings of the second questionnaire indicated that individuals characterized by the Big Five personality traits of neuroticism and agreeableness were particularly interested to use stress management apps (r=.27, P<.001 and r=.11, P=.032, respectively). Moreover, the binary logistic regression analysis revealed that when a person's neuroticism is one SD above average (ie, it is higher than among 84% of people), the person has roughly 2 times higher odds of being interested in using a stress management app. Respectively, when a person's agreeableness is one SD above average, the person has almost 1.4 times higher odds of being interested in using a stress management app. CONCLUSIONS: Our results indicated that personality traits may have an influence on the adoption interest of stress management apps. Individuals with high neuroticism are, according to our results, adaptive in the sense that they are interested in using stress management apps that may benefit them. On the contrary, low agreeableness may lead to lower interest to use the mobile stress management apps. The practical implication is that future mobile stress interventions should meaningfully be adjusted to improve user engagement and support health even among less-motivated users, for instance, to successfully engage individuals with low agreeableness.

P13, the EMBL macromolecular crystallography beamline at the low-emittance PETRA III ring for high- and low-energy phasing with variable beam focusing.

The macromolecular crystallography P13 beamline is part of the European Molecular Biology Laboratory Integrated Facility for Structural Biology at PETRA III (DESY, Hamburg, Germany) and has been in user operation since mid-2013. P13 is tunable across the energy range from 4 to 17.5 keV to support crystallographic data acquisition exploiting a wide range of elemental absorption edges for experimental phase determination. An adaptive Kirkpatrick-Baez focusing system provides an X-ray beam with a high photon flux and tunable focus size to adapt to diverse experimental situations. Data collections at energies as low as 4 keV (λ = 3.1 Å) are possible due to a beamline design minimizing background and maximizing photon flux particularly at low energy (up to 1011 photons s-1 at 4 keV), a custom calibration of the PILATUS 6M-F detector for use at low energies, and the availability of a helium path. At high energies, the high photon flux (5.4 × 1011 photons s-1 at 17.5 keV) combined with a large area detector mounted on a 2θ arm allows data collection to sub-atomic resolution (0.55 Å). A peak flux of about 8.0 × 1012 photons s-1 is reached at 11 keV. Automated sample mounting is available by means of the robotic sample changer `MARVIN' with a dewar capacity of 160 samples. In close proximity to the beamline, laboratories have been set up for sample preparation and characterization; a laboratory specifically equipped for on-site heavy atom derivatization with a library of more than 150 compounds is available to beamline users.

Parental Resources, Sibship Size, and Educational Performance in 20 Countries: Evidence for the Compensation Model.

We study whether having several siblings decreases the level of educational performance of adolescents and whether this phenomenon can be compensated by other factors such as the economic or cultural resources of the parents. Based on this compensation model, parental resources should be associated with children's educational attainments more strongly in families with a higher rather than a lower number of children. We analyzed the Program for International Student Assessment (PISA) data from 20 Western countries and found that better family wealth, an increased level of parental education, and a higher parental occupational status were associated with increased educational attainments more strongly among 15-year-old children who have siblings than among children without siblings. The same effect was not found in the case of family cultural possessions. Although parental resources may matter more in larger families than in smaller families, some types of resources are more important than others regarding compensation.

Urolithins display both antioxidant and pro-oxidant activities depending on assay system and conditions.

The biological effects of polyphenolic ellagitannins are mediated by their intestinal metabolites, urolithins. This study investigated redox properties of urolithins A and B using ORAC assay, three cell-based assays, copper-initiated pro-oxidant activity (CIPA) assay, and cyclic voltammetry. Urolithins were strong antioxidants in the ORAC assay, but mostly pro-oxidants in cell-based assays, although urolithin A was an antioxidant in cell culture medium. Parent compound ellagic acid was a strong extracellular antioxidant, but showed no response in the intracellular assay. The CIPA assay confirmed the pro-oxidant activity of ellagitannin metabolites. In the cell proliferation assay, urolithins but not ellagic acid decreased growth and metabolism of HepG2 liver cells. In cyclic voltammetry, the oxidation of urolithin A was partly reversible, but that of urolithin B was irreversible. These results illustrate how strongly measured redox properties depend on the employed assay system and conditions and emphasize the importance of studying pro-oxidant and antioxidant activities in parallel.

Vitamin C inhibits staphylococcus aureus growth and enhances the inhibitory effect of quercetin on growth of Escherichia coli in vitro.

Quercetin is a natural flavonoid possessing a number of health beneficial effects. Its bioactivity is restricted by low solubility and sensitivity to oxidative degradation, factors that are often ignored in laboratory studies. We studied the antimicrobial effects of quercetin on Staphylococcus aureus, Escherichia coli and Lactobacillus plantarum at concentrations at which it is soluble and investigated how the antioxidant vitamin C modulates these activities. S. aureus was the most sensitive of the studied bacteria. After 12 hours of culturing, 90 µM quercetin decreased the growth of S. aureus to 75 % of the value for a control culture. 1 mM vitamin C combined with 90 µM quercetin diminished the growth of S. aureus drastically to 3 % of that of the control culture supplemented with vitamin C only. Interestingly, vitamin C by itself inhibited the growth of S. aureus as well, and 5 mM vitamin C inhibited growth completely. The growth inhibition of E. coli was slightly but significantly better in the presence of both quercetin and vitamin C than in the presence of quercetin alone. Probiotic L. plantarum was resistant to quercetin in the presence and absence of vitamin C. Enhancement of quercetin's antimicrobial activity by vitamin C is partly explained by the stabilizing effect of vitamin C on quercetin. Even though the acidity of vitamin C contributes to the inhibition of S. aureus growth, neutralized vitamin C also inhibits the growth efficiently even without quercetin. Our results suggest that vitamin C affects the metabolism of S. aureus and that these changes are likely to result in the observed growth inhibition. Although vitamin C itself is a powerful antioxidant, its aerobic metabolism increases oxidative stress on bacterial cells. Vitamin C may therefore be a safe and natural alternative for restricting the growth of S. aureus when non-toxicity is required.

Amphiphilic nanotubes in the crystal structure of a biosurfactant protein hydrophobin HFBII.

Atomic scale experimental data by X-ray crystallography have been collected on an amphiphilic protein nanotube, consisting of a biosurfactant protein Trichoderma reesei hydrophobin HFBII.

Crystal structures of Trichoderma reesei ß-galactosidase reveal conformational changes in the active site.

We have determined the crystal structure of Trichoderma reesei (Hypocrea jecorina) ß-galactosidase (Tr-ß-gal) at a 1.2Å resolution and its complex structures with galactose, IPTG and PETG at 1.5, 1.75 and 1.4Å resolutions, respectively. Tr-ß-gal is a potential enzyme for lactose hydrolysis in the dairy industry and belongs to family 35 of the glycoside hydrolases (GH-35). The high resolution crystal structures of this six-domain enzyme revealed interesting features about the structure of Tr-ß-gal. We discovered conformational changes in the two loop regions in the active site, implicating a conformational selection-mechanism for the enzyme. In addition, the Glu200, an acid/base catalyst showed two different conformations which undoubtedly affect the pK(a) value of this residue and the catalytic mechanism. The electron density showed extensive glycosylation, suggesting a structure stabilizing role for glycans. The longest glycan showed an electron density that extends to the eighth monosaccharide unit in the extended chain. The Tr-ß-gal structure also showed a well-ordered structure for a unique octaserine motif on the surface loop of the fifth domain.

Crystallization and preliminary diffraction analysis of a beta-galactosidase from Trichoderma reesei.

An extracellular beta-galactosidase from Trichoderma reesei was crystallized from sodium cacodylate buffer using polyethylene glycol (PEG) as a precipant. Crystals grown by homogenous streak-seeding belonged to space group P1, with unit-cell parameters a = 67.3, b = 69.1, c = 81.5 A, alpha = 109.1, beta = 97.3, gamma = 114.5 degrees . The crystals diffracted to 1.8 A resolution using a rotating-anode generator and to 1.2 A resolution using a synchrotron source. On the basis of the Matthews coefficient (V(M) = 3.16 A(3) Da(-1)), one molecule is estimated to be present in the asymmetric unit. The aim of the determination of the crystal structure is to increase the understanding of this industrially significant enzyme.

The effect of age on attentional modulation in Dichotic listening.

The right-ear advantage (REA) in Dichotic listening (DL) reflects stimulus-driven bottom-up asymmetry in speech processing. The REA can be modified by top-down attentional control. We investigated attentional control in DL task as a function of age. A total of 186 participants between the ages of 5 and 79 years were tested. The youngest children demonstrated a REA that was not modified by attention, suggesting that bottom-up functional asymmetry was present. The 10-11-year-olds began to show ability to voluntarily modify DL, but only young adults were fully capable of doing so. In 59-79-year-olds, this top-down attentional control was lost again.

The contribution of polystyrene nanospheres towards the crystallization of proteins.

BACKGROUND: Protein crystallization is a slow process of trial and error and limits the amount of solved protein structures. Search of a universal heterogeneous nucleant is an effort to facilitate crystallizability of proteins. METHODOLOGY: The effect of polystyrene nanospheres on protein crystallization were tested with three commercial proteins: lysozyme, xylanase, xylose isomerase, and with five research target proteins: hydrophobins HFBI and HFBII, laccase, sarcosine dimethylglycine N-methyltransferase (SDMT), and anti-testosterone Fab fragment 5F2. The use of nanospheres both in screening and as an additive for known crystallization conditions was studied. In screening, the addition of an aqueous solution of nanosphere to the crystallization drop had a significant positive effect on crystallization success in comparison to the control screen. As an additive in hydrophobin crystallization, the nanospheres altered the crystal packing, most likely due to the amphiphilic nature of hydrophobins. In the case of laccase, nanospheres could be used as an alternative for streak-seeding, which insofar had remained the only technique to produce high-diffracting crystals. With methyltransferase SDMT the nanospheres, used also as an additive, produced fewer, larger crystals in less time. Nanospheres, combined with the streak-seeding method, produced single 5F2 Fab crystals in shorter equilibration times. CONCLUSIONS: All in all, the use of nanospheres in protein crystallization proved to be beneficial, both when screening new crystallization conditions to promote nucleation and when used as an additive to produce better quality crystals, faster. The polystyrene nanospheres are easy to use, commercially available and close to being inert, as even with amphiphilic proteins only the crystal packing is altered and the nanospheres do not interfere with the structure and function of the protein.

Characterization and crystallization of a recombinant IgE Fab fragment in complex with the bovine beta-lactoglobulin allergen.

A D1 Fab fragment containing the allergen-binding variable domains of the IgE antibody was characterized by ESI FT-ICR mass spectrometry and crystallized with bovine beta-lactoglobulin (BLG) using the hanging-drop vapour-diffusion method at 293 K. X-ray data suitable for structure determination were collected to 2.8 A resolution using synchrotron radiation. The crystal belonged to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 67.0, b = 100.6, c = 168.1 A. The three-dimensional structure of the D1 Fab fragment-BLG complex will provide the first insight into IgE antibody-allergen interactions at the molecular level.

Molecular interactions between a recombinant IgE antibody and the beta-lactoglobulin allergen.

Allergies are caused by the immune reaction to commonly harmless proteins, allergens. This reaction is typified by immunoglobulin E (IgE) antibodies. We report the crystal structure of an IgE Fab fragment in complex with beta-lactoglobulin (BLG), one of the major allergens of bovine milk. The solved structure shows how two IgE/Fab molecules bind the dimeric BLG. The epitope of BLG consists of six different short fragments of the polypeptide chain, which are located especially in the beta strands, covering a flat area on the allergen surface. All six CDR (complementary-determining region) loops of the IgE Fab participate in the binding of BLG. The light chain CDR loops are responsible for the binding of the flat beta sheet region of BLG. The IgE epitope is different from common IgG epitopes that are normally located in the exposed loop regions of antigens and observed also in the two recently determined allergen-IgG complexes.

Crystal structures of hydrophobin HFBII in the presence of detergent implicate the formation of fibrils and monolayer films.

Hydrophobins are small, amphiphilic proteins secreted by filamentous fungi. Their functionality arises from a patch of hydrophobic residues on the protein surface. Spontaneous self-assembly of hydrophobins leads to the formation of an amphiphilic layer that remarkably reduces the surface tension of water. We have determined by x-ray diffraction two new crystal structures of Trichoderma reesei hydrophobin HFBII in the presence of a detergent. The monoclinic crystal structure (2.2A resolution, R = 22, R(free) = 28) is composed of layers of hydrophobin molecules where the hydrophobic surface areas of the molecules are aligned within the layer. Viewed perpendicular to the aligned hydrophobic surface areas, the molecules in the layer pack together to form six-membered rings, thus leaving small pores in the layer. Similar packing has been observed in the atomic force microscopy images of the self-assembled layers of class II hydrophobin, indicating that the crystal structure resembles that of natural hydrophobin film. The orthorhombic crystal structure (1.0 A resolution, R = 13, R(free) = 15) is composed of fiber-like arrays of protein molecules. Rodlet structures have been observed on amphiphilic layers formed by class I hydrophobins; fibrils of class II hydrophobins appear by vigorous shaking. We propose that the structure of the fibrils and/or rodlets is similar to that observed in the crystal structure.