National and regional breast cancer incidence and mortality trends in Mexico 2001–2011: Analysis of a population-based database

IntroductionBreast cancer is the most common malignancy in Mexican women since 2006. However, due to a lack of cancer registries, data is scarce. We sought to describe breast cancer trends in Mexico using population-based data from a national database and to analyze geographical and age-related differences in incidence and mortality rates.MethodsAll incident breast cancer cases reported to the National Epidemiological Surveillance System and all breast cancer deaths registered by the National Institute of Statistics and Geography in Mexico from 2001 to 2011 were included. Incidence and mortality rates were calculated for each age group and for 3 geographic regions of the country. Joinpoint regression analysis was performed to examine trends in BC incidence and mortality. We estimated annual percentage change (APC) using weighted least squares log-linear regression.ResultsWe found an increase in the reported national incidence, with an APC of 5.9% (95% CI 4.1–7.7, p < 0.05). Women aged 60–65 had the highest increase in incidence (APC 7.89%; 95% CI 5.5 −10.3, p < 0.05). Reported incidence rates were significantly increased in the Center and in the South of the country, while in the North they remained stable. Mortality rates also showed a significant increase, with an APC of 0.4% (95% CI 0.1–0.7, p < 0.05). Women 85 and older had the highest increase in mortality (APC 2.99%, 95% CI 1.9–4.1; p < 0.05).ConclusionsThe reporting of breast cancer cases in Mexico had a continuous increase, which could reflect population aging, increased availability of screening, an improvement in the number of clinical facilities and better reporting of cases. Although an improvement in the detection of cases is the most likely explanation for our findings, our results point towards an epidemiological transition in Mexico and should help in guiding national policy in developing countries.     

AraPPISite: a database of fine-grained protein–protein interaction site annotations for Arabidopsis thaliana

Knowledge about protein interaction sites provides detailed information of protein–protein interactions (PPIs). To date, nearly 20,000 of PPIs from Arabidopsis thaliana have been identified. Nevertheless, the interaction site information has been largely missed by previously published PPI databases. Here, AraPPISite, a database that presents fine-grained interaction details for A. thaliana PPIs is established. First, the experimentally determined 3D structures of 27 A. thaliana PPIs are collected from the Protein Data Bank database and the predicted 3D structures of 3023 A. thaliana PPIs are modeled by using two well-established template-based docking methods. For each experimental/predicted complex structure, AraPPISite not only provides an interactive user interface for browsing interaction sites, but also lists detailed evolutionary and physicochemical properties of these sites. Second, AraPPISite assigns domain–domain interactions or domain–motif interactions to 4286 PPIs whose 3D structures cannot be modeled. In this case, users can easily query protein interaction regions at the sequence level. AraPPISite is a free and user-friendly database, which does not require user registration or any configuration on local machines. We anticipate AraPPISite can serve as a helpful database resource for the users with less experience in structural biology or protein bioinformatics to probe the details of PPIs, and thus accelerate the studies of plant genetics and functional genomics. AraPPISite is available at http://systbio.cau.edu.cn/arappisite/index.html.     

Trends in hospital admissions for adverse drug reactions in England: analysis of national hospital episode statistics 1998–2005

Background  

Adverse drug reactions (ADRs) are a frequent cause of mortality and morbidity to patients worldwide, with great associated costs to the healthcare providers including the NHS in England. We examined trends in hospital admissions associated with adverse drug reaction in English hospitals and the accuracy of national reporting.     

Localization of receptors for calcitonin-gene-related peptide to intraganglionic laminar endings of the mouse esophagus: peripheral interaction between vagal and spinal afferents?

The calcitonin-gene-related peptide (CGRP) receptor is a heterodimer of calcitonin-receptor-like receptor (CLR) and receptor-activity-modifying protein 1 (RAMP1). Despite the importance of CGRP in regulating gastrointestinal functions, nothing is known about the distribution and function of CLR/RAMP1 in the esophagus, where up to 90 % of spinal afferent neurons contain CGRP. We detected CLR/RAMP1 in the mouse esophagus using immunofluorescence and confocal laser scanning microscopy and examined their relationship with neuronal elements of the myenteric plexus. Immunoreactivity for CLR and RAMP1 colocalized with VGLUT2-positive intraganglionic laminar endings (IGLEs), which were contacted by CGRP-positive varicose axons presumably of spinal afferent origin, typically at sites of CRL/RAMP1 immunoreactivity. This provides an anatomical basis for interaction between spinal afferent fibers and IGLEs. Immunoreactive CLR and RAMP1 also colocalized in myenteric neurons. Thus, CGRP-containing spinal afferents may interact with both vagal IGLEs and myenteric neurons in the mouse esophagus, possibly modulating motility reflexes and inflammatory hypersensitivity.     

Sensitivity analysis of the Poisson Nernst–Planck equations: a finite element approximation for the sensitive analysis of an electrodiffusion model

Biological structures exhibiting electric potential fluctuations such as neuron and neural structures with complex geometries are modelled using an electrodiffusion or Poisson Nernst–Planck system of equations. These structures typically depend upon several parameters displaying a large degree of variation or that cannot be precisely inferred experimentally. It is crucial to understand how the mathematical model (and resulting simulations) depend on specific values of these parameters. Here we develop a rigorous approach based on the sensitivity equation for the electrodiffusion model. To illustrate the proposed methodology, we investigate the sensitivity of the electrical response of a node of Ranvier with respect to ionic diffusion coefficients and the membrane dielectric permittivity.

     

Interactions between different predator–prey states: a method for the derivation of the functional and numerical response

Journal of Mathematical Biology - In this paper we introduce a formal method for the derivation of a predator’s functional response from a system of fast state transitions of the prey or...     

PRICE (PRotein Interface Conservation and Energetics): a server for the analysis of protein–protein interfaces

Residues in a protein–protein interface that are important for forming and stabilizing the interaction can usually be identified by looking at patterns of evolutionary conservation in groups of homologous proteins and also by the computational identification of binding hotspots. The PRICE (PRotein Interface Conservation and Energetics) server takes the coordinates of a protein–protein complex, dissects the interface into core and rim regions, and calculates (1) the degree of conservation (measured as the sequence entropy), as well as (2) the change in free energy of binding (∆∆G, due to alanine scanning mutagenesis) of interface residues. Results are displayed as color-coded plots and also made available for download. This enables the computational identification of binding hot spots, based on which further experiments can be designed. The method will aid in protein functional prediction by correct assignment of hot regions involved in binding. Consideration of sequence entropies for residues with large ∆∆G values may provide an indication of the biological relevance of the interface. Finally, the results obtained on a test set of alanine mutants has been compared to those obtained using other servers/methods. The PRICE server is a web application available at .     

A retrospective analysis of health care utilization for patients with mitochondrial disease in the United States: 2008–2015

Background

Oral cholic acid (CA) replacement has been shown to be an effective therapy in children with primary bile acid synthesis defects, which are rare and severe genetic liver diseases. To date there has been no report of the effects of this therapy in children reaching adulthood. The aim of the study was to evaluate the long-term effectiveness and safety of CA therapy.

Methods

Fifteen patients with either 3β-hydroxy-Δ⁵-C₂₇-steroid oxidoreductase (3β-HSD) (n = 13) or Δ⁴–3-oxosteroid 5β-reductase (Δ⁴–3-oxo-R) (n = 2) deficiency confirmed by mass spectrometry and gene sequencing received oral CA and were followed prospectively.

Results

The median age at last follow-up and the median time of follow-up with treatment were 24.3 years (range: 15.3–37.2) and 21.4 years (range: 14.6–24.1), respectively. At last evaluation, physical examination findings and blood laboratory test results were normal in all patients. Liver sonograms were normal in most patients. Mean daily CA dose was 6.9 mg/kg of body weight. Mass spectrometry analysis of urine showed that excretion of the atypical metabolites remained low or traces in amount with CA therapy. Liver fibrosis scored in liver biopsies or assessed by elastography in 14 patients, after 10 to 24 years with CA therapy, showed a marked improvement with disappearance of cirrhosis (median score < F1; range: F0-F2). CA was well tolerated in all patients, including five women having 10 uneventful pregnancies during treatment.

Conclusions

Oral CA therapy is a safe and effective long-term treatment of 3β-HSD and Δ⁴–3-oxo-R deficiencies and allows affected children to reach adulthood in good health condition without the need for a liver transplantation.

     

Transfer function analysis of heart rate variability correlated with gastric myoelectrical activity using a liquid nutritional meal compared to water: are they different?

We aimed to investigate difference in the effects of water and a liquid nutritional meal on the parasympathetic and gastric myoelectrical activities. The study was a repeated-measures design in which each subject was presented with 500 ml of water and a liquid nutritional meal (Ensure) on two separate and random sessions. The electrogastrography (EGG) and electrocardiogram were simultaneously recorded in 16 healthy subjects. There were no significant changes in the EGG-3 cycle per minute (cpm) power, any HRV variable, or the transfer function magnitude after Ensure intake. Water ingestion resulted in a significant increase in both the EGG-3 cpm power and the transfer magnitude compared to Ensure intake (P < 0.05). The effects of water and Ensure on the parasympathetic and gastric electric activities are different, in which the latter is less likely to provoke an autonomic response after gastric stimulation.     

Barriers and Bridges to Prevention and Control of Dengue: The Need for a Social–Ecological Approach

This article critically examines how programs for the prevention and control of dengue fever have been conducted in the absence of an integrated approach, and considers the social and ecological factors influencing their effectiveness. Despite recognition of dengue fever as the most important arboviral disease affecting humans, and in spite of a greater emphasis on community-based control approaches, the burden placed on the communities, countries, and regions affected by this disease continues to rise. In considering historical experience in the Americas and the Asia-Pacific region, as well as the global forces that are exerting new pressures, the important elements of successful control programs are identified as community ownership, partnership with government, leadership, scalability, and control of immature mosquitoes. The key barriers to the exchange of knowledge and the transdisciplinary cooperation necessary for sustainable dengue control are rooted in differences in values among policy-makers, citizens, and scientists and are repeatedly expressed in technical, economic, cultural, geographic, and political dimensions. Through consideration of case studies in Cuba, Guatemala, Singapore, Thailand, Indonesia, and Vietnam, the limitations of control approaches that fail to take into account the complexities of ecological and social systems are presented. Bridges to effective control are identified as the basis for adaptability, both of control programs to the mosquito vector’s changing behavior and of education programs to public, regional and local particularities, as well as transdisciplinarity, community empowerment, the ability to scale local experiences up to the macro-level, and the capacity to learn from experience to achieve sustainability.     

A contact model to simulate human–artifact interaction based on force optimization: implementation and application to the analysis of a training machine

Musculoskeletal multibody models are increasingly used to analyze and optimize physical interactions between humans and technical artifacts. Since interaction is conveyed by contact between the human body and the artifact, a computationally robust modeling approach for frictional contact forces is a crucial aspect. In this contribution, we propose a parametric contact model and formulate an associated force optimization problem to simultaneously estimate unknown muscle and contact forces in an inverse dynamic manner from a prescribed motion trajectory. Unlike existing work, we consider both the static and the kinetic regime of Coulomb’s friction law. The approach is applied to the analysis of a leg extension training machine with the objective to reduce the stress on the tibiofemoral joint. The uncertainty of the simulation results due to a tunable parameter of the contact model is of particular interest.     

Genetic analysis of a divergent selection for resistance to Rous sarcomas in chickens?. This article is dedicated to the memory of Pierrick Thoraval (1960–2000).

Selection for disease resistance related traits is a tool of choice for evidencing and exploring genetic variability and studying underlying resistance mechanisms. In this framework, chickens originating from a base population, homozygote for the B¹⁹ major histocompatibility complex (MHC) were divergently selected for either progression or regression of tumors induced at 4 weeks of age by a SR-D strain of Rous sarcoma virus (RSV). The first generation of selection was based on a progeny test and subsequent selections were performed on full-sibs. Data of 18 generations including a total of 2010 birds measured were analyzed for the tumor profile index (TPI), a synthetic criterion of resistance derived from recording the volume of the tumors and mortality. Response to selection and heritability of TPI were estimated using a restricted maximum likelihood method with an animal model. Significant progress was shown in both directions: the lines differing significantly for TPI and mortality becoming null in the "regressor" line. Heritability of TPI was estimated as 0.49 ± 0.05 and 0.53 ± 0.06 within the progressor and regressor lines respectively, and 0.46 ± 0.03 when estimated over lines. Preliminary results showed within the progressor line a possible association between one Rfp-Y type and the growth of tumors.     

Dynamic analysis of competition and complementarity for light and N use to understand the yield and the protein content of a durum wheat–winter pea intercrop

In a previous paper [Bedoussac L, Justes E (2009) Plant Soil, doi: 10.1007/s11104-009-0082-2], we showed that intercropping of durum wheat and winter pea increased the yield and protein concentration of durum wheat when early N availability was less than 120 kg N ha^?1. The aim of the present work was to understand these results by analysing intercrop species dynamics for growth, light and N acquisition. A 2-year field experiment was carried out in southwest France with different fertilizer-N levels in order to compare wheat (Triticum turgidum L.) and pea (Pisum sativum L.) grown as sole crops and as an intercrop in a row substitutive design. The advantages of intercropping in low N conditions were due mainly to: (1) better light use (up to 10%), thanks to species dynamic complementarity for leaf area index and height; (2) growth complementarity over time (higher growth rate of wheat until pea flowering and then of pea until wheat flowering); and (3) dynamic complementary N acquisition associated with better wheat N status throughout growth. Disadvantages, underlining poorer complementarity within the intercrop stand, were observed with ample available N in early growth. This induced higher cereal growth during winter, which led to increase interspecies competition by reducing pea light absorption and, consequently, its biomass production.     

New methods to analyse auxin-induced growth II: The swelling reaction of protoplasts – a model system for the analysis of auxin signal transduction?

A method for monitoring the time course of auxin-induced volume changesby protoplasts at a high temporal resolution was developed for Zeamays coleoptile protoplasts. Auxins, like indole-3-acetic acid(IAA), induce a rapid change in volume. Immediately after addition ofthis auxin, a transient shrinkage was observed, followed by a long-termswelling response. This reaction occurred in the same time window as thetypical auxin growth response of intact coleoptiles. Active auxins, like1-naphthalene acetic acid (1-NAA) and 4-chloroindole-3-acetic acid(4-Cl-IAA), caused similar volume changes, whereas the inactive analogue2-naphthalene acetic acid (2-NAA) had no effect. The phytotoxinfusicoccin (FC) induced a rapid swelling response. We conclude that thissingle cell system is very adequate to analyse mechanisms of auxinsignal transduction.