An international update of the EORTC questionnaire for assessing quality of life in breast cancer patients: EORTC QLQ-BR45.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23 was one of the first disease-specific questionnaires developed in 1996 to assess quality of life (QoL) in patients with breast cancer (BC). However, since 1996 major changes in BC treatment have occurred, requiring an update of the EORTC BC module. This study presents the results of the phase I-III update of the QLQ-BR23 questionnaire. PATIENTS AND METHODS: The update of the EORTC QLQ-BR23 module followed standard EORTC guidelines. A systematic literature review revealed 83 potential relevant QoL issues during phases I and II. After shortening the issues list and following interviews with patients and health care providers, 15 relevant issues were transformed into 27 items. The preliminary module was pretested in an international, multicentre phase III study to identify and solve potential problems with wording comprehensibility and acceptability of the items. Descriptive statistics are provided. Analyses were qualitative and quantitative. We provide a psychometric structure of the items. RESULTS: The phase I and II results indicated the need to supplement the original QLQ-BR23 with additional items related to newer therapeutic options. The phase III study recruited a total of 250 patients (from 12 countries). The final updated phase III module contains a total of 45 items: 23 items from the QLQ-BR23 and 22 new items. The new items contain two multi-item scales: a target symptom scale and a satisfaction scale. The target symptom scale can be divided into three subscales: endocrine therapy, endocrine sexual and skin/mucosa scale. CONCLUSION: Our work has led to the development of a new EORTC QLQ-BR45 module that provides a more accurate and comprehensive assessment of the impact of new and scalable treatments on patients' QoL. The final version of the EORTC QLQ-BR45 is currently available for use in clinical practice. The final phase IV study is underway to confirm psychometric properties of the module.

Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus.

BACKGROUND: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. METHODS: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. DISCUSSION: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

Filtering Statistics on Networks.

Compression, filtering, and cryptography, as well as the sampling of complex systems, can be seen as processing information. A large initial configuration or input space is nontrivially mapped to a smaller set of output or final states. We explored the statistics of filtering of simple patterns on a number of deterministic and random graphs as a tractable example of such information processing in complex systems. In this problem, multiple inputs map to the same output, and the statistics of filtering is represented by the distribution of this degeneracy. For a few simple filter patterns on a ring, we obtained an exact solution of the problem and numerically described more difficult filter setups. For each of the filter patterns and networks, we found three key numbers that essentially describe the statistics of filtering and compared them for different networks. Our results for networks with diverse architectures are essentially determined by two factors: whether the graphs structure is deterministic or random and the vertex degree. We find that filtering in random graphs produces much richer statistics than in deterministic graphs, reflecting the greater complexity of such graphs. Increasing the graph's degree reduces this statistical richness, while being at its maximum at the smallest degree not equal to two. A filter pattern with a strong dependence on the neighbourhood of a node is much more sensitive to these effects.

Vertebrate SLRP family evolution and the subfunctionalization of osteoglycin gene duplicates in teleost fish.

BACKGROUND: Osteoglycin (OGN, a.k.a. mimecan) belongs to cluster III of the small leucine-rich proteoglycans (SLRP) of the extracellular matrix (ECM). In vertebrates OGN is a characteristic ECM protein of bone. In the present study we explore the evolution of SLRP III and OGN in teleosts that have a skeleton adapted to an aquatic environment. RESULTS: The SLRP gene family has been conserved since the separation of chondrichthyes and osteichthyes. Few gene duplicates of the SLRP III family exist even in the teleosts that experienced a specific whole genome duplication. One exception is ogn for which duplicate copies were identified in fish genomes. The ogn promoter sequence and in vitro mesenchymal stem cell (MSC) cultures suggest the duplicate ogn genes acquired divergent functions. In gilthead sea bream (Sparus aurata) ogn1 was up-regulated during osteoblast and myocyte differentiation in vitro, while ogn2 was severely down-regulated during bone-derived MSCs differentiation into adipocytes in vitro. CONCLUSIONS: Overall, the phylogenetic analysis indicates that the SLRP III family in vertebrates has been under conservative evolutionary pressure. The retention of the ogn gene duplicates in teleosts was linked with the acquisition of different functions. The acquisition by OGN of functions other than that of a bone ECM protein occurred early in the vertebrate lineage.

Finding the Optimal Nets for Self-Folding Kirigami.

Three-dimensional shells can be synthesized from the spontaneous self-folding of two-dimensional templates of interconnected panels, called nets. However, some nets are more likely to self-fold into the desired shell under random movements. The optimal nets are the ones that maximize the number of vertex connections, i.e., vertices that have only two of its faces cut away from each other in the net. Previous methods for finding such nets are based on random search, and thus, they do not guarantee the optimal solution. Here, we propose a deterministic procedure. We map the connectivity of the shell into a shell graph, where the nodes and links of the graph represent the vertices and edges of the shell, respectively. Identifying the nets that maximize the number of vertex connections corresponds to finding the set of maximum leaf spanning trees of the shell graph. This method allows us not only to design the self-assembly of much larger shell structures but also to apply additional design criteria, as a complete catalog of the maximum leaf spanning trees is obtained.

Great tit response to decreasing industrial heavy metal emissions.

This study evaluated the effects of environmental pollution on decreasing great tit (Parus major) breeding parameters in an industrial area in the west coast of Portugal. Several great tit breeding parameters were monitored in the industrial area, as well as in a rural area not affected by industrial emissions. Low levels of air pollution in both industrial and rural areas were confirmed by assessing trace element concentrations in pine needles. Concentrations of Cd and Hg in pine needles from the industrial area (Cd = 0.05 ppm; Hg = 0.005 ppm) were significantly lower than those found in needles collected from the reference area (Cd = 0.07 ppm; Hg = 0.007 ppm). Additionally, the breeding success of great tits increased in the industrial area in comparison to the reference area (0.93 ± 0.08 and 0.62 ± 0.22, respectively). The changes on great tit breeding parameters were probably related with changes in the breeding density of other competitive species, together with a decreasing frass-fall biomass. Further long-term ecological studies in industrial areas are necessary to understand the changing breeding performance and strategies used by great tits in response to pollution shifts in the environment.

Assessing heavy metal pollution using Great Tits (Parus major): feathers and excrements from nestlings and adults.

Passerine species have been increasingly used as bioindicators of metal bioaccumulation especially by taking benefit of non-invasive procedures, such as collecting feathers and excrements. In 2009, metal (As, Cd, Cu, Hg, Ni, Pb, Se and Zn) concentrations were determined in feathers and excrements of nestling and adult female great tits (Parus major) in industrial (a paper mill) and rural sites in maritime pine forests on the west coast of Portugal. The aim of this study was to compare the levels of metals between the areas but also between sampling methods (feather vs. excrement) and age classes (nestling vs. adult). Although excrements and feathers of nestling great tits showed different concentrations, similar patterns of accumulation were detected in both study areas. There was a significantly higher concentration of mercury in the industrial area and significantly higher concentrations of arsenic in the rural area in both sample types. Metal levels in adult females had quite different results when compared to nestlings, and only nickel presented significantly higher levels near the paper mill. Since metal levels showed a consistent pattern in feathers and excrements of nestling great tits, we conclude that both represent good and non-invasive methods for the evaluation of these elements in polluted areas.

Epidemiological and clinicopathological findings in 15 fatal outbreaks of salmonellosis in dairy calves and virulence genes in the causative Salmonella enterica Typhimurium and Dublin strains.

Salmonella enterica is a major food-borne pathogen that affects cattle-rearing systems worldwide. Little information is available on the epidemiology and pathology of salmonellosis and the virulence genes (VGs) carried by Salmonella in spontaneous outbreaks in cattle. We describe epidemiological findings in 15 fatal outbreaks of salmonellosis in Uruguayan dairy farms and the age, clinical signs, and pathology in 20 affected calves. We also describe the serotypes and frequencies of 17 VGs in the causative Salmonella strains and explore their associations with epidemiological, clinical, and pathological findings. Salmonella Typhimurium and Dublin were identified in 11/15 and 4/15 outbreaks, respectively. The most frequent reason for consultation was digestive disease (8 outbreaks caused by S. Typhimurium), followed by sudden death (4 outbreaks, 3 caused by S. Dublin). Morbidity, mortality, and lethality ranged 4.8-100%, 3.8-78.9%, and 10-100%, without significant differences between serotypes. Diarrhea, the most common clinical sign (14 cases), was associated with the Typhimurium serotype (OR = 26.95), especially in ≤ 30-day-old calves with fibrinous enteritis as the main autopsy finding. The Dublin serotype affected ≥ 50-day-old calves and was associated with fibrinosuppurative splenitis (p = 0.01) and tubulointerstitial nephritis (OR = 48.95). The chances of the Dublin serotype increased significantly with age. There was low variability of VG across serotypes. The pefA gene was associated with the Typhimurium serotype (OR = 21.95), macroscopic enteritis (p = 0.03), and microscopic fibrinosuppurative splenitis (p = 0.04). Understanding the epidemiology, pathology, and virulence of S. enterica at the farm level is key to delineating prevention and control strategies to mitigate its impact on animal and human health.

Molecular and cellular changes in skin and muscle during metamorphosis of Atlantic halibut (Hippoglossus hippoglossus) are accompanied by changes in deiodinases expression.

Flatfish metamorphosis is the most dramatic post-natal developmental event in teleosts. Thyroid hormones (TH), thyroxine (T4) and 3,3'-5'-triiodothyronine (T3) are the necessary and sufficient factors that induce and regulate flatfish metamorphosis. Most of the cellular and molecular action of TH is directed through the binding of T3 to thyroid nuclear receptors bound to promoters with consequent changes in the expression of target genes. The conversion of T4 to T3 and nuclear availability of T3 depends on the expression and activity of a family of 3 selenocysteine deiodinases that activate T4 into T3 or degrade T4 and T3. We have investigated the role of deiodinases in skin and muscle metamorphic changes in halibut. We show that, both at the whole body level and at the cellular level in muscle and skin of the Atlantic halibut (Hippoglossus hippoglossus) during metamorphosis, the coordination between activating (D2) and deactivating (D3) deiodinases expression is strongly correlated with the developmental TH-driven changes. The expression pattern of D2 and D3 in cells of both skin and muscle indicate that TH are necessary for the maintenance of larval metamorphic development and juvenile cell types in these tissues. No break in symmetry occurs in the expression of deiodinases and in metamorphic developmental changes occurring both in trunk skin and muscle. The findings that two of the major tissues in both larvae and juveniles maintain their symmetry throughout metamorphosis suggest that the asymmetric changes occurring during flatfish metamorphosis are restricted to the eye and head region.

Trace elements in faeces of great tit nestlings in relation to breeding performance in coastal areas in central Portugal.

This long-term study (2003-2010) compared the breeding parameters of great tits living in a paper-and-pulp-industry area to those of great tits living in a rural area on the west coast of Portugal. We also measured the abundance of caterpillar biomass, an important food source and determinant of breeding success for tits. In 2009, we further analysed trace metal [arsenic (As), calcium (Ca), cadmium, copper, mercury (Hg), nickel, lead, selenium, and zinc] as well as Ca concentrations in excrement of 15-day-old great tit nestlings. Generally, for most trace metals, fecal concentrations were similar at both sites. Nonetheless, greater Hg levels and lower As levels were detected in the industrial area. Great tits laid more eggs and produced more fledglings in the industrial area than in the rural area. Caterpillar biomass was also greater in the industrial area, which likely explains the better breeding success. Our results suggest that there are no direct effects of emissions on the studied species.

Hidden transition in multiplex networks.

Weak multiplex percolation generalizes percolation to multi-layer networks, represented as networks with a common set of nodes linked by multiple types (colors) of edges. We report a novel discontinuous phase transition in this problem. This anomalous transition occurs in networks of three or more layers without unconnected nodes, [Formula: see text]. Above a critical value of a control parameter, the removal of a tiny fraction [Formula: see text] of nodes or edges triggers a failure cascade which ends either with the total collapse of the network, or a return to stability with the system essentially intact. The discontinuity is not accompanied by any singularity of the giant component, in contrast to the discontinuous hybrid transition which usually appears in such problems. The control parameter is the fraction of nodes in each layer with a single connection, [Formula: see text]. We obtain asymptotic expressions for the collapse time and relaxation time, above and below the critical point [Formula: see text], respectively. In the limit [Formula: see text] the total collapse for [Formula: see text] takes a time [Formula: see text], while there is an exponential relaxation below [Formula: see text] with a relaxation time [Formula: see text].

Subcutaneous injection of an immunologically tolerated protein up to 5 days before skin injuries improves wound healing.

Oral tolerance blocks the development of specific immune responses to proteins ingested by the oral route. One of the first registries of oral tolerance showed that guinea pigs fed corn became refractory to hypersensitivity to corn proteins. Mice fed with chow containing corn are tolerant to zein, and parenteral injection of zein plus adjuvant blocks immunization to unrelated proteins injected concomitantly and reduces unspecific inflammation. Extensive and prolonged inflammatory infiltrate in the wound bed is one of the causes of pathological wound healing. Previous research shows that intraperitoneal injection of zein concomitant with skin injuries reduces the inflammatory infiltrate in the wound bed and improves wound healing. Herein, we tested if one subcutaneous injection of zein before skin injury improves wound healing. We also investigated how long the effects triggered by zein could improve skin wound healing. Mice fed zein received two excisional wounds on the interscapular skin under anesthesia. Zein plus Al(OH)3 was injected at the tail base at 10 min, or 3, 5, or 7 days before skin injuries. Wound healing was analyzed at days 7 and 40 after injury. Our results showed that a zein injection up to 5 days before skin injury reduced the inflammatory infiltrate, increased the number of T-cells in the wound bed, and improved the pattern of collagen deposition in the neodermis. These findings could promote the development of new strategies for the treatment and prevention of pathological healing using proteins normally found in the common diet.

The role of mitochondrial DNA damage in the citotoxicity of reactive oxygen species.

Mitochondria contain their own genome, a small circular molecule of around 16.5 kbases. The mitochondrial DNA (mtDNA) encodes for only 13 polypeptides, but its integrity is essential for mitochondrial function, as all 13 proteins are regulatory subunits of the oxidative phosphorylation complexes. Nonetheless, the mtDNA is physically associated with the inner mitochondrial membrane, where the majority of the cellular reactive oxygen species are generated. In fact, the mitochondrial DNA accumulates high levels of oxidized lesions, which have been associated with several pathological and degenerative processes. The cellular responses to nuclear DNA damage have been extensively studied, but so far little is known about the functional outcome and cellular responses to mtDNA damage. In this review we will discuss the mechanisms that lead to damage accumulation and the in vitro models we are establishing to dissect the cellular responses to oxidative damage in the mtDNA and to sort out the differential cellular consequences of accumulation of damage in each cellular genome, the nuclear and the mitochondrial genome.

The use of passerine feathers to evaluate heavy metal pollution in Central Portugal.

In 2003, two sampling strategies were applied in order to evaluate metal contamination in passerine bird feathers. One strategy included the use of nest boxes and nestling great tits in a forest habitat (MU). The other strategy focused on the use of mist nets to capture adult blackbirds, robins and blackcaps in a fragmented non-forested habitat (EST). There was a significantly higher concentration of mercury in great tits (1.09 ± 0.40) sampled in MU and also in robins (3.44 ± 0.91) and blackcaps (1.62 ± 1.99) sampled in EST, in comparison to the reference site (0.66 ± 0.68; 2.04 ± 1.12; 0.32 ± 0.43; respectively). Concerning interspecific differences, robins accumulated significantly more metals than blackbirds or blackcaps.

Approximating nonbacktracking centrality and localization phenomena in large networks.

Message-passing theories have proved to be invaluable tools in studying percolation, nonrecurrent epidemics, and similar dynamical processes on real-world networks. At the heart of the message-passing method is the nonbacktracking matrix, whose largest eigenvalue, the corresponding eigenvector, and the closely related nonbacktracking centrality play a central role in determining how the given dynamical model behaves. Here we propose a degree-class-based method to approximate these quantities using a smaller matrix related to the joint degree-degree distribution of neighboring nodes. Our findings suggest that in most networks, degree-degree correlations beyond nearest neighbor are actually not strong, and our first-order description already results in accurate estimates, particularly when message-passing itself is a good approximation to the original model in question, that is, when the number of short cycles in the network is sufficiently low. We show that localization of the nonbacktracking centrality is also captured well by our scheme, particularly in large networks. Our method provides an alternative to working with the full nonbacktracking matrix in very large networks where this may not be possible due to memory limitations.

Explosive percolation transition is actually continuous.

Recently a discontinuous percolation transition was reported in a new "explosive percolation" problem for irreversible systems [D. Achlioptas, R. M. D'Souza, and J. Spencer, Science 323, 1453 (2009)] in striking contrast to ordinary percolation. We consider a representative model which shows that the explosive percolation transition is actually a continuous, second order phase transition though with a uniquely small critical exponent of the percolation cluster size. We describe the unusual scaling properties of this transition and find its critical exponents and dimensions.

Choosing among alternative histories of a tree.

The structure of an evolving network contains information about its past. Extracting this information efficiently, however, is, in general, a difficult challenge. We formulate a fast and efficient method to estimate the most likely history of growing trees, based on exact results on root finding. We show that our linear-time algorithm produces the exact stepwise most probable history in a broad class of tree growth models. Our formulation is able to treat very large trees and therefore allows us to make reliable numerical observations regarding the possibility of root inference and history reconstruction in growing trees. We obtain the general formula 〈lnN〉≅NlnN-cN for the size dependence of the mean logarithmic number of possible histories of a given tree, a quantity that largely determines the reconstructability of tree histories. We also reveal an uncertainty principle: a relationship between the inferability of the root and that of the complete history, indicating that there is a tradeoff between the two tasks; the root and the complete history cannot both be inferred with high accuracy at the same time.

Exotic critical behavior of weak multiplex percolation.

We describe the critical behavior of weak multiplex percolation, a generalization of percolation to multiplex or interdependent networks. A node can determine its active or inactive status simply by referencing neighboring nodes. This is not the case for the more commonly studied generalization of percolation to multiplex networks, the mutually connected clusters, which requires an interconnecting path within each layer between any two vertices in the giant mutually connected component. We study the emergence of a giant connected component of active nodes under the weak percolation rule, finding several nontypical phenomena. In two layers, the giant component emerges with a continuous phase transition, but with quadratic growth above the critical threshold. In three or more layers, a discontinuous hybrid transition occurs, similar to that found in the giant mutually connected component. In networks with asymptotically powerlaw degree distributions, defined by the decay exponent γ, the discontinuity vanishes but at γ=1.5 in three layers, more generally at γ=1+1/(M-1) in M layers.

Prevalence of entanglements of seabirds in marine debris in the central Portuguese coast.

Plastic pollution and the subsequent entanglement of marine animals is a global and increasing problem. In this study we present an analysis of the seabirds recorded as entangled by a rehabilitation centre and an associated marine animal stranding network, along the central coast of Portugal, between 2008 and 2018. Results show a high annual rate of entangled seabirds (average 6.9%) compared to other studies and fisheries related materials are a relevant cause of seabird entanglement (82%) compared to other debris. When comparing age classes, juveniles were more vulnerable to entanglement than other age classes in the species studied. Regarding the rehabilitation of entangled seabirds, the release rate was higher in non-fishing material entanglement cases. In conclusion, this study highlights the impact of fisheries related material on marine fauna and the need for reinforcement of the existing legislation for protecting seabirds and the implementation of mitigation measures associated with fishing activities.