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Linear infrastructure networks, including railways, are undergoing rapid development in order to connect distant urban areas. Particularly, High-Speed Railways are increasingly seen as a viable alternative to domestic flights in many countries. However, this development of linear infrastructures is known to affect the surrounding faunal communities due to the changes in the landscape and operation of said linear infrastructures. Both positive and negative effects of linear infrastructures on adjacent faunal communities have been reported. In this study, we determined the influence of the High-Speed Railway infrastructure on the bird community that surrounds it. Birds were surveyed by using both linear transect and direct counting methods, both in the area directly adjacent to the railway infrastructure and 500m away from it in a period of two years of surveys. A total of 16114 individuals belonging to 71 species were recorded. The presence of the High-Speed Railway caused species-specific changes in the bird communities that surround it, causing the attraction of some species and the rejection of others. Furthermore, we show that the presence of the infrastructure altered the natural species turnover as the landscape changes by attracting the same bird species regardless of changes in the landscape, and filtering out others. We propose that further work in mitigation and development plans should focus on species-specific measures to assess the risk bird communities are exposed to.

A methodological proposal of a scale for human perception assessment of acoustic environment (acoustic comfort) in urban public spaces is presented: Acoustic Comfort Assessment Scale (ACAS 12). This paper shows the process of constructing this scale and its psychometric properties and validation. The approach is based on the soundscape conceptualisation collected in ISO 12913-1:2014 (Acoustics-Soundscape: Definition and conceptual framework). The proposed scale is a 5-point semantic differential scale made up of twelve pairs of bipolar adjectives, grouped around five theoretical dimensions. It is based on previous versions of 2-point and 3-point scales. The ACAS-12 scale is the result of several empirical studies carried out by the authors on environmental and acoustic comfort assessment, beginning in 2011 in some cities of the Basque Country (Spain). Selected urban open places cover a wide variability of acoustic and non-acoustic characteristics, as well as the type of participants (real users) and activities carried out in these places. The original language of this scale is Spanish. The back-translation technique has been applied to create the English version. The results highlight the good psychometric properties of the ACAS 12 scale (Cronbach's alpha 0.91 and composite reliability 0.90) and indicate that the best factorial solution is that of a single factor composed of the 12 pairs of adjectives that would explain approximately 50% of the ACAS-12 variance (44% of extracted variance by Raykov's method or 56% by the MAP test). The absolute and incremental fit indices were above the minimum reference value of 0.90 and the residual-based indices showed values close to suitability (SRMR = 0.057; RMSEA = 0.042). This result supports the consideration of the ACAS-12 scale as a general measure of acoustic comfort.

Background Latent autoimmune diabetes in adults (LADA) is a type of diabetes mellitus showing overlapping characteristics between type 1 Diabetes Mellitus and type 2 Diabetes Mellitus (T2DM), and autoimmunity against insulin-producing pancreatic cells. For its diagnosis, at least one type of anti-pancreatic islet antibody (GADAb is the most common) is required. Many authors recommend performing this measure in all newly diagnosed patients with DM, but it is not possible in Primary Health Care (PHC) due to its high cost. Currently, a relevant proportion of patients diagnosed as T2DM could be LADA. Confusing LADA with T2DM has clinical and safety implications, given its different therapeutic approach. The main objective of the study is to develop and validate a clinical score for identifying adult patients with DM at high risk of LADA in PHC. Methods This is an observational, descriptive, cross-sectional study carried out in Primary Care Health Centers with a centralized laboratory. All people over 30 years of age diagnosed with diabetes within a minimum of 6 months and a maximum of 4 years before the start of the study will be recruited. Individuals will be recruited by consecutive sampling. The study variables will be obtained through clinical interviews, physical examinations, and electronic medical records. The following variables will be recorded: those related to Diabetes Mellitus, sociodemographic, anthropometric, lifestyle habits, laboratory parameters, presence of comorbidities, additional treatments, personal or family autoimmune disorders, self-perceived health status, Fourlanos criteria, and LADA diagnosis (as main variable) according to current criteria. Discussion The study will provide an effective method for identifying patients at increased risk of LADA and, therefore, candidates for antibody testing. However, a slight participation bias is to be expected. Differences between participants and non-participants will be studied to quantify this potential bias.

Background Several chronic conditions have been identified as risk factors for severe COVID-19 infection, yet the implications of multimorbidity need to be explored. The objective of this study was to establish multimorbidity clusters from a cohort of COVID-19 patients and assess their relationship with infection severity/mortality. Methods The MRisk-COVID Big Data study included 14 286 COVID-19 patients of the first wave in a Spanish region. The cohort was stratified by age and sex. Multimorbid individuals were subjected to a fuzzy c-means cluster analysis in order to identify multimorbidity clusters within each stratum. Bivariate analyses were performed to assess the relationship between severity/mortality and age, sex, and multimorbidity clusters. Results Severe infection was reported in 9.5% (95% CI: 9.0–9.9) of the patients, and death occurred in 3.9% (95% CI: 3.6–4.2). We identified multimorbidity clusters related to severity/mortality in most age groups from 21 to 65 years. In males, the cluster with highest percentage of severity/mortality was Heart-liver-gastrointestinal (81–90 years, 34.1% severity, 29.5% mortality). In females, the clusters with the highest percentage of severity/mortality were Diabetes-cardiovascular (81–95 years, 22.5% severity) and Psychogeriatric (81–95 years, 16.0% mortality). Conclusion This study characterized several multimorbidity clusters in COVID-19 patients based on sex and age, some of which were found to be associated with higher rates of infection severity/mortality, particularly in younger individuals. Further research is encouraged to ascertain the role of specific multimorbidity patterns on infection prognosis and identify the most vulnerable morbidity profiles in the community. Trial registration NCT04981249. Registered 4 August 2021 (retrospectively registered).

Recent research has focused on the monitoring of global-scale online data for improved detection of epidemics, mood patterns, movements in the stock market political revolutions, box-office revenues, consumer behaviour and many other important phenomena. However, privacy considerations and the sheer scale of data available online are quickly making global monitoring infeasible, and existing methods do not take full advantage of local network structure to identify key nodes for monitoring. Here, we develop a model of the contagious spread of information in a global-scale, publicly-articulated social network and show that a simple method can yield not just early detection, but advance warning of contagious outbreaks. In this method, we randomly choose a small fraction of nodes in the network and then we randomly choose a friend of each node to include in a group for local monitoring. Using six months of data from most of the full Twittersphere, we show that this friend group is more central in the network and it helps us to detect viral outbreaks of the use of novel hashtags about 7 days earlier than we could with an equal-sized randomly chosen group. Moreover, the method actually works better than expected due to network structure alone because highly central actors are both more active and exhibit increased diversity in the information they transmit to others. These results suggest that local monitoring is not just more efficient, but also more effective, and it may be applied to monitor contagious processes in global-scale networks.

BackgroundThe outbreak of the COVID-19 epidemic lead to high levels of morbidity and mortality around the globe. Consequences of this outbreak and possible associated infection are an increase in mental health disorders and an increased likelihood of internalizing problems, particularly depression. However, to date few studies have tested this hypothesis while taking into account individuals' preexisting mental health difficulties.MethodsWe used longitudinal data collected among 729 persons in the context of the French TEMPO cohort between March and June 2020 (7 waves of data collection). COVID-19-like symptoms as well as anxiety/depression (assessed by the Adult Self Report), were reported at each wave of data collection. To study the relationship between COVID-19-like symptoms and anxiety/depression, we used generalized estimation equation (GEE) models controlled for socio-demographic and health-related characteristics, including anxiety/depression prior to 2020.ResultsOverall, 27.2% of study participants reported anxiety/depression during lockdown. 17.1% of participants reported COVID-19-like symptoms during the course of follow-up, 7.3% after the beginning of lockdown, with an average number of 2.7 symptoms, and 3.6% reported respiratory distress. In multivariate analyses, nearly all the considered indicators of COVID-19-like symptoms were associated with higher odds of symptoms of anxiety/depression (symptoms Yes/No: OR = 1.66, 95% CI = 1.08-2.55; symptoms after the beginning of lockdown: OR = 1.91, 95% CI = 1.03-3.52; number of symptoms: OR for each additional symptom = 1.19, 95% CI = 1.02-1.39. This relationship exists after taking into account prior symptoms of anxiety/depression, which are associated with a 5-fold increased likelihood of psychological distress. And this impact is stronger among men than women.ConclusionsOur study shows higher risk of anxiety/depression among persons who experienced COVID-19-like symptoms, even after accounting for prior mental health difficulties. COVID-19 infection could have both a direct and indirect impact on the occurrence of psychological difficulties, and this association should be studied in greater detail.

Streptococcus pneumoniae infections are one of the major causes of morbility and mortality worldwide. Although vaccination and antibiotherapy constitute fundamental and complementary strategies against pneumococcal infections, they present some limitations including the increase in non-vaccine serotypes and the emergence of multidrug-resistances, respectively. Ribosomally-synthesized antimicrobial peptides (i.e. bacteriocins) produced by Lactic Acid Bacteria (LAB) may represent an alternative or complementary strategy to antibiotics for the control of pneumococal infections. We tested the antimicrobial activity of 37 bacteriocinogenic LAB, isolated from food and other sources, against clinical S. pneumoniae strains. Streptococcus infantarius subsp. infantarius LP90, isolated from Venezuelan water-buffalo milk, was selected because of its broad and strong anti-pneumococcal spectrum. The in vitro safety assessment of S. infantarius LP90 revealed that it may be considered avirulent. The analysis of a 19,539-bp cluster showed the presence of 29 putative open reading frames (ORFs), including the genes encoding 8 new class II-bacteriocins, as well as the proteins involved in their secretion, immunity and regulation. Transcriptional analyses evidenced that the induction factor (IF) structural gene, the bacteriocin/IF transporter genes, the bacteriocin structural genes and most of the bacteriocin immunity genes were transcribed. MALDI-TOF analyses of peptides purified using different multichromatographic procedures revealed that the dairy strain S. infantarius LP90 produces at least 6 bacteriocins, including infantaricin A1, a novel anti-pneumococcal two-peptide bacteriocin.

Venezuela is going through the worst economical, political and social crisis in its modern history. Basic products like food or medicine are scarce and hyperinflation is combined with economic depression. This situation is creating an unprecedented refugee and migrant crisis in the region. Governments and international agencies have not been able to consistently leverage reliable information using traditional methods. Therefore, to organize and deploy any kind of humanitarian response, it is crucial to evaluate new methodologies to measure the number and location of Venezuelan refugees and migrants across Latin America. In this paper, we propose to use Facebook's advertising platform as an additional data source for monitoring the ongoing crisis. We estimate and validate national and sub-national numbers of refugees and migrants and break-down their socio-economic profiles to further understand the complexity of the phenomenon. Although limitations exist, we believe that the presented methodology can be of value for real-time assessment of refugee and migrant crises world-wide.

[This corrects the article DOI: 10.1371/journal.pone.0229175.].

BACKGROUND:Human breast milk (BM) fortification is required to feed preterm newborns with less than 32 weeks of gestation. However, addition of fortifiers increases osmolarity and osmolarity values higher than 450 mOsm/kg may be related to gastrointestinal pathology. Hence, fortifier selection and dosage are key to achieve optimal feeding. OBJECTIVES:To compare the effect on osmolality of adding different fortifications, including recently developed formulations, to BM and to study evolution of osmolarity over time in supplemented BM. METHODS:Frozen mature BM from 10 healthy mothers of premature newborns was fortified with each of the following human milk fortifiers (HMF): AlmirónFortifier®, NANFM85®, or PreNANFM85®. In addition, fortified BMs were modified with one of the following nutritional supplements (NS): Duocal MCT®, Nutricia® AminoAcids Mix, or Maxijul®. Osmolality of BM alone, fortified and/or supplemented was measured at 1 and 22 hours after their preparation. All samples were kept at 4°C throughout the study. RESULTS:Osmolality of BM alone was close to 300 mOsm/kg and did not change over 22 hours. When equicaloric amounts of HMF AlmirónFortifier®, NANFM85®, and PreNANFM85® were added to BM, osmolality increased roughly to 480 mOsm/kg with the first two fortifiers and only to 433±6 mOsm/kg with the third one. Upon addition of any of four different NSs to BM modified with AlmirónFortifier® and NANFM85®, osmolality reached values greater than 520 mOsm/kg, while osmolality of PreNANFM85® with two out of the four NSs remained below 490 mOsm/kg. NSs supplementing carbohydrates and hydrolysed proteins resulted into a higher increase of BM osmolarity. Osmolality increased significantly with time and, after 22h, only BM modified with PreNANFM85® remained below 450 mOsm/kg. CONCLUSIONS:Upon addition of the HMFs tested, BM osmolality increases significantly and keeps raising over time. All HMFs but the recently developed PreNAN FM85® at 4% exceed the AAP recommended threshold for osmolarity of 450 mOsm/kg. Addition of NSs to PreNAN FM85® at 4% significantly increases osmolality above 450 mOsm/Kg. Thus, using PreNAN FM85® at 5% may be preferable to adding nutritional supplements since nutritional recommendations by the ESPGHAN are reached with a lower increase in osmolality.

Modern day investigation in fields of archaeology and palaeontology can be greatly characterised by an exponential growth of integrated new technologies, nevertheless, while these advances are of great significance to multiple lines of research, their evaluation and update over time is equally as important. Here we present an application of inter and intra-observer analysis in taphonomy based geometric morphometrics, employing robust non-parametric statistical analyses for the study of experimental carnivore tooth pit morphologies. To fully understand the influence of measurement errors in the collection of this data, our statistical assessment was performed on fully superimposed, partially superimposed and raw landmark coordinates collected from 3D surface scanning. Experimental samples used to assess these errors includes wolf and dog tooth pits used in modern day ecological livestock predation analysis. Results obtained from this study highlight the importance of landmark type in the assessment of error, emphasising the value of semi-landmark models over the use of ambiguous Type III landmarks. In addition to this, data also reveals the importance of observer experience for the collection of data alongside an interesting increase in error when working with fully superimposed landmarks due to the "Pinocchio Effect". Through this study we are able to redefine the geometric morphometric models used for tooth pit morphological analyses. This final hybrid Type II fixed landmark and semi-landmark model presents a significant reduction in human induced error, generating a more metrically reliable and replicable method that can be used for data pooling in future inter-institutional research. These results can be considered a fundamental step forward for carnivore inspired studies, having an impact on archaeological, palaeontological, modern-day ecological research as well as applications in other forensic sciences.

To what extent can online social networks predict who is at risk of an infection? Many infections are transmitted through physical encounter between humans, but collecting detailed information about it can be expensive, might invade privacy, or might not even be possible. In this paper, we ask whether online social networks help predict and contain epidemic risk. Using a dataset from a popular online review service which includes over 100 thousand users and spans 4 years of activity, we build a time-varying network that is a proxy of physical encounter between its users (the encounter network) and a static network based on their reported online friendship (the friendship With computer simulations, we compare stochastic infection processes on the two networks, considering infections on the encounter network as the benchmark. First, we show that the friendship network is useful to identify the individuals at risk of infection, despite providing lower accuracy than the ideal case in which the encounters are known. This limited prediction accuracy is not only due to the static nature of the friendship network because a static version of the encounter network provides more accurate prediction of risk than the friendship network. Then, we show that periodical monitoring of the infection spreading on the encounter network allows to correct the infection predicted by a process spreading on the friendly staff ndship network, and achieves high prediction accuracy. Finally, we show that the friendship network contains valuable information to effectively contain epidemic outbreaks even when a limited budget is available for immunization. In particular, a strategy that immunizes random friends of random individuals achieves the same performance as knowing individuals' encounters at a small additional cost, even if the infection spreads on the encounter network.

Paralogues pairs are more frequently observed in eels (Anguilla sp.) than in other teleosts. The paralogues often show low phylogenetic distances; however, they have been assigned to the third round of whole genome duplication (WGD), shared by all teleosts (3R), due to their conserved synteny. The apparent contradiction of low phylogenetic difference and 3R conserved synteny led us to study the duplicated gene complement of the freshwater eels. With this aim, we assembled de novo transcriptomes of two highly relevant freshwater eel species: The European (Anguilla anguilla) and the Japanese eel (Anguilla japonica). The duplicated gene complement was analysed in these transcriptomes, and in the genomes and transcriptomes of other Actinopterygii species. The study included an assessment of neutral genetic divergence (4dTv), synteny, and the phylogenetic origins and relationships of the duplicated gene complements. The analyses indicated a high accumulation of duplications (1217 paralogue pairs) among freshwater eel genes, which may have originated in a WGD event after the Elopomorpha lineage diverged from the remaining teleosts, and thus not at the 3R. However, very similar results were observed in the basal Osteoglossomorpha and Clupeocephala branches, indicating that the specific genomic regions of these paralogues may still have been under tetrasomic inheritance at the split of the teleost lineages. Therefore, two potential hypotheses may explain the results: i) The freshwater eel lineage experienced an additional WGD to 3R, and ii) Some duplicated genomic regions experienced lineage specific rediploidization after 3R in the ancestor to freshwater eels. The supporting/opposing evidence for both hypotheses is discussed.

Background: Latent autoimmune diabetes in adults (LADA) is a type of diabetes mellitus showing overlapping characteristics between type 1 Diabetes Mellitus and type 2 Diabetes Mellitus (T2DM), and autoimmunity against insulin-producing pancreatic cells. For its diagnosis, at least one type of anti-pancreatic islet antibody (GADAb is the most common) is required. Many authors recommend performing this measure in all newly diagnosed patients with DM, but it is not possible in Primary Health Care (PHC) due to its high cost. Currently, a relevant proportion of patients diagnosed as T2DM could be LADA. Confusing LADA with T2DM has clinical and safety implications, given its different therapeutic approach. The main objective of the study is to develop and validate a clinical score for identifying adult patients with DM at high risk of LADA in PHC. Methods: This is an observational, descriptive, cross-sectional study carried out in Primary Care Health Centers with a centralized laboratory. All people over 30 years of age diagnosed with diabetes within a minimum of 6 months and a maximum of 4 years before the start of the study will be recruited. Individuals will be recruited by consecutive sampling. The study variables will be obtained through clinical interviews, physical examinations, and electronic medical records. The following variables will be recorded: those related to Diabetes Mellitus, sociodemographic, anthropometric, lifestyle habits, laboratory parameters, presence of comorbidities, additional treatments, personal or family autoimmune disorders, self-perceived health status, Fourlanos criteria, and LADA diagnosis (as main variable) according to current criteria. Discussion: The study will provide an effective method for identifying patients at increased risk of LADA and, therefore, candidates for antibody testing. However, a slight participation bias is to be expected. Differences between participants and non-participants will be studied to quantify this potential bias. [ABSTRACT FROM AUTHOR]

There is increasing interest in the search for accurate, repeatable and widely applicable clinical biomarkers for the early detection of cardiometabolic alterations and oxidative status. Viscosity is a promising tool in that sense, although most studies have used simple viscosimeters, providing limited information, and have not considered oxidative status. The aim of this study was to assess whether viscosity determinations were associated with cardiometabolic and oxidative status in subjects at a primary stage of cardiometabolic risk. A pilot study (n = 20) was conducted in subjects with abdominal obesity, determining urine and plasma viscosity with a rotational rheometer at different shear rates (10000-1000 s-1 in plasma and 1000-50 s-1 in urine). Simple regression showed that urine viscosity was significantly (p< 0.05) associated with markers of oxidative status, and plasma viscosity with blood glucose. Categorical Principal Component Analysis plots showed that urine viscosity measurements at different shear rates clustered in three groups (low, intermediate and high shear rates) were selectively associated with uric acid, polyphenols and antioxidant capacity respectively. Plasma viscosity did not seem to be a relevant clinical marker in subjects with abdominal obesity. Therefore, urine viscosity could potentially serve as a complimentary marker in the evaluation of oxidative status.

[This corrects the article DOI: 10.1371/journal.pone.0132546.].

The assignation of lineages in Mycobacterium tuberculosis (MTB) provides valuable information for evolutionary and phylogeographic studies and makes for more accurate knowledge of the distribution of this pathogen worldwide. Differences in virulence have also been found for certain lineages. MTB isolates were initially assigned to lineages based on data obtained from genotyping techniques, such as spoligotyping or MIRU-VNTR analysis, some of which are more suitable for molecular epidemiology studies. However, since these methods are subject to a certain degree of homoplasy, other criteria have been chosen to assign lineages. These are based on targeting robust and specific SNPs for each lineage. Here, we propose two newly designed multiplex targeting methods-both of which are single-tube tests-to optimize the assignation of the six main lineages in MTB. The first method is based on ASO-PCR and offers an inexpensive and easy-to-implement assay for laboratories with limited resources. The other, which is based on SNaPshot, enables more refined standardized assignation of lineages for laboratories with better resources. Both methods performed well when assigning lineages from cultured isolates from a control panel, a test panel, and a problem panel from an unrelated population, Mexico, which included isolates in which standard genotyping was not able to classify lineages. Both tests were also able to assign lineages from stored isolates, without the need for subculture or purification of DNA, and even directly from clinical specimens with a medium-high bacilli burden. Our assays could broaden the contexts where information on lineages can be acquired, thus enabling us to quickly update data from retrospective collections and to merge data with those obtained at the time of diagnosis of a new TB case.

To describe the prevalence of Peripheral Artery Disease (PAD) in a random population sample and to evaluate its relationship with Mediterranean diet and with other potential cardiovascular risk factors such as serum uric acid and pulse pressure in individuals ranged 45 to 74 years.Cross-sectional analysis of 1568 subjects (mean age 6.5 years, 43% males), randomly selected from the population. A fasting blood sample was obtained to determine glucose, lipids, and HbA1C levels. An oral glucose tolerance test was performed in non-diabetic subjects. PAD was evaluated by ankle-brachial index and/or having a prior diagnosis.PAD prevalence was 3.81% (95% CI, 2.97-4.87) for all participants. In men, PAD prevalence was significantly higher than in women [5.17% (95% CI, 3.74-7.11) vs. 2.78% (95% CI, 1.89-4.07); p = 0.014]. Serum uric acid in the upper quartile was associated with the highest odds ratio (OR) of PAD (for uric acid > 6.1 mg/dl, OR = 4.31; 95% CI, 1.49-12.44). The remaining variables more strongly associated with PAD were: Heart rate >90 bpm (OR = 4.16; 95%CI, 1.62-10.65), pulse pressure in the upper quartile (≥ 54 mmHg) (OR = 3.82; 95%CI, 1.50-9.71), adherence to Mediterranean diet (OR = 2.73; 95% CI, 1.48-5.04), and former smoker status (OR = 2.04; 95%CI, 1.00-4.16).Our results show the existence of a low prevalence of peripheral artery disease in a population aged 45-74 years. Serum uric acid, pulse pressure and heart rate >90 bpm were strongly associated with peripheral artery disease. The direct association between Mediterranean diet and peripheral artery disease that we have found should be evaluated through a follow-up study under clinical practice conditions.

SCOPE:Olive-tree polyphenols have demonstrated potential for the management of obesity-related pathologies. We aimed to explore the capacity of Olive-tree leaves extract to modulate triglyceride accumulation and AMP-activated protein kinase activity (AMPK) on a hypertrophic adipocyte model. METHODS:Intracellular triglycerides and AMPK activity were measured on the hypertrophic 3T3-L1 adipocyte model by AdipoRed and immunofluorescence microscopy, respectively. Reverse phase high performance liquid chromatography coupled to time-of-flight mass detection with electrospray ionization (RP-HPLC-ESI-TOF/MS) was used for the fractionation of the extract and the identification of the compounds. In-silico molecular docking of the AMPK alpha-2, beta and gamma subunits with the identified compounds was performed. RESULTS:Olive-tree leaves extract decreased the intracellular lipid accumulation through AMPK-dependent mechanisms in hypertrophic adipocytes. Secoiridoids, cinnamic acids, phenylethanoids and phenylpropanoids, flavonoids and lignans were the candidates predicted to account for this effect. Molecular docking revealed that some compounds may be AMPK-gamma modulators. The modulatory effects of compounds over the alpha and beta AMPK subunits appear to be less probable. CONCLUSIONS:Olive-tree leaves polyphenols modulate AMPK activity, which may become a therapeutic aid in the management of obesity-associated disturbances. The natural occurrence of these compounds may have important nutritional implications for the design of functional ingredients.

To evaluate the performance of the Finnish Diabetes Risk Score (FINDRISC) and a simplified FINDRISC score (MADRISC) in screening for undiagnosed type 2 diabetes mellitus (UT2DM) and dysglycaemia.A population-based, cross-sectional, descriptive study was carried out with participants with UT2DM, ranged between 45-74 years and lived in two districts in the north of metropolitan Madrid (Spain). The FINDRISC and MADRISC scores were evaluated using the area under the receiver operating characteristic curve method (ROC-AUC). Four different gold standards were used for UT2DM and any dysglycaemia, as follows: fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), HbA1c, and OGTT or HbA1c. Dysglycaemia and UT2DM were defined according to American Diabetes Association criteria.The study population comprised 1,426 participants (832 females and 594 males) with a mean age of 62 years (SD = 6.1). When HbA1c or OGTT criteria were used, the prevalence of UT2DM was 7.4% (10.4% in men and 5.2% in women; p

Strong evidence suggests that lipid metabolism (LM) has an essential role in tumor growth to support special energetic and structural requirements of tumor cells. Recently, overexpression of LM-related genes, apolipoproteins related to metabolic syndrome, and ACSL/SCD network involved in fatty acid activation have been proposed as prognostic markers of colon cancer (CC). Furthermore, activation of this latter lipid network has been recently demonstrated to confer invasive and stem cell properties to tumor cells promoting tumor aggressiveness and patient relapse. With the aim of elucidating whether any genetic variation within these genes could influence basal expression levels and consequent susceptibility to relapse, we genotype, in 284 CC patients, 57 polymorphisms located in the 7 genes of these lipid networks previously associated with worse clinical outcome of CC patients (ABCA1, ACSL1, AGPAT1, APOA2, APOC1, APOC2 and SCD), some of them related to CC aggressiveness. After adjusting with clinical confounding factors and multiple comparisons, an association between genotype and disease-free survival (DFS) was shown for rs8086 in 3'-UTR of ACSL1 gene (HR 3.08; 95% CI 1.69-5.63; adjusted p = 0.046). Furthermore, the risk T/T genotype had significantly higher ACSL1 gene expression levels than patients carrying C/T or C/C genotype (means = 5.34; 3.73; 2.37 respectively; p-value (ANOVA) = 0.019), suggesting a functional role of this variant. Thus, we have identified a "risk genotype" of ACSL1 gene that confers constitutive high levels of the enzyme, which is involved in the activation of fatty acids through conversion to acyl-CoA and has been recently related to increased invasiveness of tumor cells. These results suggest that rs8086 of ACSL1 could be a promising prognostic marker in CC patients, reinforcing the relevance of LM in the progression of CC.

Antithrombin is a crucial anticoagulant serpin whose even moderate deficiency significantly increases the risk of thrombosis. Most cases with antithrombin deficiency carried genetic defects affecting exons or flanking regions of SERPINC1.We aimed to identify regulatory mutations inSERPINC1 through sequencing the promoter, intron 1 and 2 of this gene in 23 patients with antithrombin deficiency but without known genetic defects. Three cases with moderate antithrombin deficiency (63-78%) carried potential regulatory mutations. One located 200 bp before the initiation ATG and two in intron 1. These mutations disrupted two out of five potential vitamin D receptor elements (VDRE) identified in SERPINC1 with different software. One genetic defect, c.42-1060_-1057dupTTGA, was a new low prevalent polymorphism (MAF: 0.01) with functional consequences on plasma antithrombin levels. The relevance of the vitamin D pathway on the regulation of SERPINC1 was confirmed in a cell model. Incubation of HepG2 with paricalcitol, a vitamin D analog, increased dose-dependently the levels of SERPINC1transcripts and antithrombin released to the conditioned medium. This study shows further evidence of the transcriptional regulation of SERPINC1 by vitamin D and first describes the functional and pathological relevance of mutations affecting VDRE of this gene. Our study opens new perspectives in the search of new genetic defects involved in antithrombin deficiency and the risk of thrombosis as well as in the design of new antithrombotic treatments.

[This corrects the article DOI: 10.1371/journal.pone.0152159.].

Modern day investigation in fields of archaeology and palaeontology can be greatly characterised by an exponential growth of integrated new technologies, nevertheless, while these advances are of great significance to multiple lines of research, their evaluation and update over time is equally as important. Here we present an application of inter and intra-observer analysis in taphonomy based geometric morphometrics, employing robust non-parametric statistical analyses for the study of experimental carnivore tooth pit morphologies. To fully understand the influence of measurement errors in the collection of this data, our statistical assessment was performed on fully superimposed, partially superimposed and raw landmark coordinates collected from 3D surface scanning. Experimental samples used to assess these errors includes wolf and dog tooth pits used in modern day ecological livestock predation analysis. Results obtained from this study highlight the importance of landmark type in the assessment of error, emphasising the value of semi-landmark models over the use of ambiguous Type III landmarks. In addition to this, data also reveals the importance of observer experience for the collection of data alongside an interesting increase in error when working with fully superimposed landmarks due to the "Pinocchio Effect". Through this study we are able to redefine the geometric morphometric models used for tooth pit morphological analyses. This final hybrid Type II fixed landmark and semi-landmark model presents a significant reduction in human induced error, generating a more metrically reliable and replicable method that can be used for data pooling in future inter-institutional research. These results can be considered a fundamental step forward for carnivore inspired studies, having an impact on archaeological, palaeontological, modern-day ecological research as well as applications in other forensic sciences. [ABSTRACT FROM AUTHOR]

midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP). We sought to confirm whether MR-proADM added to Pneumonia Severity Index (PSI) improves the potential prognostic value of PSI alone, and tested to what extent this combination could be useful in predicting poor outcome of patients with CAP in an Emergency Department (ED).Consecutive patients diagnosed with CAP were enrolled in this prospective, single-centre, observational study. We analyzed the ability of MR-proADM added to PSI to predict poor outcome using receiver operating characteristic (ROC) curves, logistic regression and risk reclassification and comparing it with the ability of PSI alone. The primary outcome was "poor outcome", defined as the incidence of an adverse event (ICU admission, hospital readmission, or mortality at 30 days after CAP diagnosis).226 patients were included; 33 patients (14.6%) reached primary outcome. To predict primary outcome the highest area under curve (AUC) was found for PSI (0.74 [0.64-0.85]), which was not significantly higher than for MR-proADM (AUC 0.72 [0.63-0.81, p > 0.05]). The combination of PSI and MR-proADM failed to improve the predictive potential of PSI alone (AUC 0.75 [0.65-0.85, p=0.56]). Ten patients were appropriately reclassified when the combined PSI and MR-proADM model was used as compared with the model of PSI alone. Net reclassification improvement (NRI) index was statistically significant (7.69%, p = 0.03) with an improvement percentage of 3.03% (p = 0.32) for adverse event, and 4.66% (P = 0.02) for no adverse event.MR-proADM in combination with PSI may be helpful in individual risk stratification for short-term poor outcome of CAP patients, allowing a better reclassification of patients compared with PSI alone.

Recent widespread adoption of electronic and pervasive technologies has enabled the study of human behavior at an unprecedented level, uncovering universal patterns underlying human activity, mobility, and interpersonal communication. In the present work, we investigate whether deviations from these universal patterns may reveal information about the socio-economical status of geographical regions. We quantify the extent to which deviations in diurnal rhythm, mobility patterns, and communication styles across regions relate to their unemployment incidence. For this we examine a country-scale publicly articulated social media dataset, where we quantify individual behavioral features from over 19 million geo-located messages distributed among more than 340 different Spanish economic regions, inferred by computing communities of cohesive mobility fluxes. We find that regions exhibiting more diverse mobility fluxes, earlier diurnal rhythms, and more correct grammatical styles display lower unemployment rates. As a result, we provide a simple model able to produce accurate, easily interpretable reconstruction of regional unemployment incidence from their social-media digital fingerprints alone. Our results show that cost-effective economical indicators can be built based on publicly-available social media datasets.

This study compares the health-related quality of life of Spanish-born and Latin American-born individuals settled in Spain. Socio-demographic and psychosocial factors associated with health-related quality of life are analyzed.A cross-sectional Primary Health Care multi center-based study of Latin American-born (n = 691) and Spanish-born (n = 903) outpatients from 15 Primary Health Care Centers (Madrid, Spain). The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) was used to assess health-related quality of life. Socio-demographic, psychosocial, and specific migration data were also collected.Compared to Spanish-born participants, Latin American-born participants reported higher health-related quality of life in the physical functioning and vitality dimensions. Across the entire sample, Latin American-born participants, younger participants, men and those with high social support reported significantly higher levels of physical health. Men with higher social support and a higher income reported significantly higher mental health. When stratified by gender, data show that for men physical health was only positively associated with younger age. For women, in addition to age, social support and marital status were significantly related. Both men and women with higher social support and income had significantly better mental health. Finally, for immigrants, the physical and mental health components of health-related quality of life were not found to be significantly associated with any of the pre-migration factors or conditions of migration. Only the variable "exposure to political violence" was significantly associated with the mental health component (p = 0.014).The key factors to understanding HRQoL among Latin American-born immigrants settled in Spain are age, sex and social support. Therefore, strategies to maintain optimal health outcomes in these immigrant communities should include public policies on social inclusion in the host society and focus on improving social support networks in order to foster and maintain the health and HRQoL of this group.

The phylogeny of Kinorhyncha was analyzed using morphology and the molecular loci 18S rRNA and 28S rRNA. The different datasets were analyzed separately and in combination, using maximum likelihood and Bayesian Inference. Bayesian inference of molecular sequence data in combination with morphology supported the division of Kinorhyncha into two major clades: Cyclorhagida comb. nov. and Allomalorhagida nom. nov. The latter clade represents a new kinorhynch class, and accommodates Dracoderes, Franciscideres, a yet undescribed genus which is closely related with Franciscideres, and the traditional homalorhagid genera. Homalorhagid monophyly was not supported by any analyses with molecular sequence data included. Analysis of the combined molecular and morphological data furthermore supported a cyclorhagid clade which included all traditional cyclorhagid taxa, except Dracoderes that no longer should be considered a cyclorhagid genus. Accordingly, Cyclorhagida is divided into three main lineages: Echinoderidae, Campyloderidae, and a large clade, 'Kentrorhagata', which except for species of Campyloderes, includes all species with a midterminal spine present in adult individuals. Maximum likelihood analysis of the combined datasets produced a rather unresolved tree that was not regarded in the following discussion. Results of the analyses with only molecular sequence data included were incongruent at different points. However, common for all analyses was the support of several major clades, i.e., Campyloderidae, Kentrorhagata, Echinoderidae, Dracoderidae, Pycnophyidae, and a clade with Paracentrophyes + New Genus and Franciscideres (in those analyses where the latter was included). All molecular analyses including 18S rRNA sequence data furthermore supported monophyly of Allomalorhagida. Cyclorhagid monophyly was only supported in analyses of combined 18S rRNA and 28S rRNA (both ML and BI), and only in a restricted dataset where taxa with incomplete information from 28S rRNA had been omitted. Analysis of the morphological data produced results that were similar with those from the combined molecular and morphological analysis. E.g., the morphological data also supported exclusion of Dracoderes from Cyclorhagida. The main differences between the morphological analysis and analyses based on the combined datasets include: 1) Homalorhagida appears as monophyletic in the morphological tree only, 2) the morphological analyses position Franciscideres and the new genus within Cyclorhagida near Zelinkaderidae and Cateriidae, whereas analyses including molecular data place the two genera inside Allomalorhagida, and 3) species of Campyloderes appear in a basal trichotomy within Kentrorhagata in the morphological tree, whereas analysis of the combined datasets places species of Campyloderes as a sister clade to Echinoderidae and Kentrorhagata.

INTRODUCTION:Osteoarthritis (OA) is characterized by altered homeostasis of joint cartilage and bone, whose functional properties rely on chondrocytes and osteoblasts, belonging to mesenchymal stem cells (MSCs). WNT signaling acts as a hub integrating and crosstalking with other signaling pathways leading to the regulation of MSC functions. The aim of this study was to evaluate the existence of a differential signaling between Healthy and OA-MSCs during osteogenesis. METHODS:MSCs of seven OA patients and six healthy controls were isolated, characterised and expanded. During in vitro osteogenesis, cells were recovered at days 1, 10 and 21. RNA and protein content was obtained. Expression of WNT pathway genes was evaluated using RT-qPCR. Functional studies were also performed to study the MSC osteogenic commitment and functional and post-traslational status of β-catenin and several receptor tyrosine kinases. RESULTS:Several genes were downregulated in OA-MSCs during osteogenesis in vitro. These included soluble Wnts, inhibitors, receptors, co-receptors, several kinases and transcription factors. Basal levels of β-catenin were higher in OA-MSCs, but calcium deposition and expression of osteogenic genes was similar between Healthy and OA-MSCs. Interestingly an increased phosphorylation of p44/42 MAPK (ERK1/2) signaling node was present in OA-MSCs. CONCLUSION:Our results point to the existence in OA-MSCs of alterations in expression of Wnt pathway components during in vitro osteogenesis that are partially compensated by post-translational mechanisms modulating the function of other pathways. We also point the relevance of other signaling pathways in OA pathophysiology suggesting their role in the maintenance of joint homeostasis through modulation of MSC osteogenic potential.

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.

Recent research has focused on the monitoring of global-scale online data for improved detection of epidemics, mood patterns, movements in the stock market political revolutions, box-office revenues, consumer behaviour and many other important phenomena. However, privacy considerations and the sheer scale of data available online are quickly making global monitoring infeasible, and existing methods do not take full advantage of local network structure to identify key nodes for monitoring. Here, we develop a model of the contagious spread of information in a global-scale, publicly-articulated social network and show that a simple method can yield not just early detection, but advance warning of contagious outbreaks. In this method, we randomly choose a small fraction of nodes in the network and then we randomly choose a friend of each node to include in a group for local monitoring. Using six months of data from most of the full Twittersphere, we show that this friend group is more central in the network and it helps us to detect viral outbreaks of the use of novel hashtags about 7 days earlier than we could with an equal-sized randomly chosen group. Moreover, the method actually works better than expected due to network structure alone because highly central actors are both more active and exhibit increased diversity in the information they transmit to others. These results suggest that local monitoring is not just more efficient, but also more effective, and it may be applied to monitor contagious processes in global-scale networks.

The pervasive use of new mobile devices has allowed a better characterization in space and time of human concentrations and mobility in general. Besides its theoretical interest, describing mobility is of great importance for a number of practical applications ranging from the forecast of disease spreading to the design of new spaces in urban environments. While classical data sources, such as surveys or census, have a limited level of geographical resolution (e.g., districts, municipalities, counties are typically used) or are restricted to generic workdays or weekends, the data coming from mobile devices can be precisely located both in time and space. Most previous works have used a single data source to study human mobility patterns. Here we perform instead a cross-check analysis by comparing results obtained with data collected from three different sources: Twitter, census, and cell phones. The analysis is focused on the urban areas of Barcelona and Madrid, for which data of the three types is available. We assess the correlation between the datasets on different aspects: the spatial distribution of people concentration, the temporal evolution of people density, and the mobility patterns of individuals. Our results show that the three data sources are providing comparable information. Even though the representativeness of Twitter geolocated data is lower than that of mobile phone and census data, the correlations between the population density profiles and mobility patterns detected by the three datasets are close to one in a grid with cells of 2×2 and 1×1 square kilometers. This level of correlation supports the feasibility of interchanging the three data sources at the spatio-temporal scales considered.

The formation and budding of endoplasmic reticulum ER-derived vesicles depends on the COPII coat protein complex that was first identified in yeast Saccharomyces cerevisiae. The ER-associated Sec12 and the Sar1 GTPase initiate the COPII coat formation by recruiting the Sec23-Sec24 heterodimer following the subsequent recruitment of the Sec13-Sec31 heterotetramer. In yeast, there is usually one gene encoding each COPII protein and these proteins are essential for yeast viability, whereas the plant genome encodes multiple isoforms of all COPII subunits. Here, we used a systematic yeast complementation assay to assess the functionality of Arabidopsis thaliana COPII proteins. In this study, the different plant COPII subunits were expressed in their corresponding temperature-sensitive yeast mutant strain to complement their thermosensitivity and secretion phenotypes. Secretion was assessed using two different yeast cargos: the soluble α-factor pheromone and the membranous v-SNARE (vesicle-soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor) Snc1 involved in the fusion of the secretory vesicles with the plasma membrane. This complementation study allowed the identification of functional A. thaliana COPII proteins for the Sec12, Sar1, Sec24 and Sec13 subunits that could represent an active COPII complex in plant cells. Moreover, we found that AtSec12 and AtSec23 were co-immunoprecipitated with AtSar1 in total cell extract of 15 day-old seedlings of A. thaliana. This demonstrates that AtSar1, AtSec12 and AtSec23 can form a protein complex that might represent an active COPII complex in plant cells.

In patients with type 2 diabetes, the prevalence of hypertension is higher than in non-diabetic subjects. Despite the high cardiovascular risk involving hypertension in these patients, its prevalence and control are not well known. The aims of this study were: to estimate the hypertension prevalence, awareness, treatment and control in Spanish adults with type 2 diabetes attended in Primary Care; and to analyse its time trend from 2003 to 2009. A serial cross-sectional study from 2003 to 2009 was performed in 21 Primary Care Centres in Madrid. The study population comprised all patients with diagnosed type 2 diabetes in their computerised medical history. Overall annual prevalence during the period 2003-2009 was calculated from and according to sex and age groups. Linear trend tests, regression lines and coefficients of determination were used. In 2003 89.78% (CI 87.92-91.64) of patients with type 2 diabetes suffered hypertension and 94.76% (CI: 92.85-96.67) in 2009. This percentage was greater for women and for patients over 65 years old. 30% of patients suffered previously undiagnosed hypertension in 2003 and 23.1% in 2009. 97% of diagnosed patients received pharmacological treatment and 28.79% reached the blood pressure objective in 2009. The average number of antihypertensive drugs taken was 2.72 in 2003 and 3.27 in 2009. Only 5.2% of patients with type 2 diabetes show blood pressure levels below 130/80 mmHg. Although significant improvements have been achieved in the diagnosis and control of hypertension in people with type 2 diabetes, these continue to remain far from optimum.

Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk.We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998-2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression analysis to assess multiple SNPs simultaneously.Based on classical analyses, SNPs in BAK1 (1), IGF1R (5), P53AIP1 (1), PMAIP1 (2), SERINPB5 (3), TP63 (3), and TP73 (1) showed significant associations at p-value≤0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value≥0.8). LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95%CI 1.05-1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation.We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies.

Liver growth factor (LGF) is a hepatic mitogen purified some years ago that promotes proliferation of different cell types and the regeneration of damaged tissues, including brain tissue. Considering the possibility that LGF could be used as a therapeutic agent in Parkinson's disease, we analyzed its potential neuroregenerative and/or neuroprotective activity when peripherally administered to unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. For these studies, rats subjected to nigrostriatal lesions were treated intraperitoneally twice a week with LGF (5 microg/rat) for 3 weeks. Animals were sacrificed 4 weeks after the last LGF treatment. The results show that LGF stimulates sprouting of tyrosine hydroxylase-positive terminals and increases tyrosine hydroxylase and dopamine transporter expression, as well as dopamine levels in the denervated striatum of 6-OHDA-lesioned rats. In this structure, LGF activates microglia and raises tumor necrosis factor-alpha protein levels, which have been reported to have a role in neuroregeneration and neuroprotection. Besides, LGF stimulates the phosphorylation of MAPK/ERK1/2 and CREB, and regulates the expression of proteins which are critical for cell survival such as Bcl2 and Akt. Because LGF partially protects dopamine neurons from 6-OHDA neurotoxicity in the substantia nigra, and reduces motor deficits in these animals, we propose LGF as a novel factor that may be useful in the treatment of Parkinson's disease.

BackgroundBrachypodium distachyon s. l. has been widely investigated across the world as a model plant for temperate cereals and biofuel grasses. However, this annual plant shows three cytotypes that have been recently recognized as three independent species, the diploids B. distachyon (2n = 10) and B. stacei (2n = 20) and their derived allotetraploid B. hybridum (2n = 30).Methodology/principal findingsWe propose a DNA barcoding approach that consists of a rapid, accurate and automatable species identification method using the standard DNA sequences of complementary plastid (trnLF) and nuclear (ITS, GI) loci. The highly homogenous but largely divergent B. distachyon and B. stacei diploids could be easily distinguished (100% identification success) using direct trnLF (2.4%), ITS (5.5%) or GI (3.8%) sequence divergence. By contrast, B. hybridum could only be unambiguously identified through the use of combined trnLF+ITS sequences (90% of identification success) or by cloned GI sequences (96.7%) that showed 5.4% (ITS) and 4% (GI) rate divergence between the two parental sequences found in the allopolyploid.Conclusion/significanceOur data provide an unbiased and effective barcode to differentiate these three closely-related species from one another. This procedure overcomes the taxonomic uncertainty generated from methods based on morphology or flow cytometry identifications that have resulted in some misclassifications of the model plant and its allies. Our study also demonstrates that the allotetraploid B. hybridum has resulted from bi-directional crosses of B. distachyon and B. stacei plants acting either as maternal or paternal parents.

CRB3 (Crumbs homologue 3), a member of the CRB protein family (homologous to the Drosophila Crumbs), is expressed in different epithelium-derived cell types in mammals, where it seems to be involved in regulating the establishment and stability of tight junctions and in ciliogenesis. This protein has been also detected in the retina, but little is known about its localization and function in this tissue. Our goal here was to perform an in-depth study of the presence of CRB3 protein in the mouse retina and to analyze its expression during photoreceptor ciliogenesis and the establishment of the plexiform retinal layers. Double immunofluorescence experiments for CRB3 and well-known markers for the different retinal cell types were performed to study the localization of the CRB3 protein. According to our results, CRB3 is present from postnatal day 0 (P0) until adulthood in the mouse retina. It is localized in the inner segments (IS) of photoreceptor cells, especially concentrated in the area where the connecting cilium is located, in their synaptic terminals in the outer plexiform layer (OPL), and in sub-populations of amacrine and bipolar cells in the inner plexiform layer (IPL).

Cross-reactivity of plant foods is an important phenomenon in allergy, with geographical variations with respect to the number and prevalence of the allergens involved in this process, whose complexity requires detailed studies. We have addressed the role of thaumatin-like proteins (TLPs) in cross-reactivity between fruit and pollen allergies. A representative panel of 16 purified TLPs was printed onto an allergen microarray. The proteins selected belonged to the sources most frequently associated with peach allergy in representative regions of Spain. Sera from two groups of well characterized patients, one with allergy to Rosaceae fruit (FAG) and another against pollens but tolerant to food-plant allergens (PAG), were obtained from seven geographical areas with different environmental pollen profiles. Cross-reactivity between members of this family was demonstrated by inhibition assays. Only 6 out of 16 purified TLPs showed noticeable allergenic activity in the studied populations. Pru p 2.0201, the peach TLP (41%), chestnut TLP (24%) and plane pollen TLP (22%) proved to be allergens of probable relevance to fruit allergy, being mainly associated with pollen sensitization, and strongly linked to specific geographical areas such as Barcelona, Bilbao, the Canary Islands and Madrid. The patients exhibited >50% positive response to Pru p 2.0201 and to chestnut TLP in these specific areas. Therefore, their recognition patterns were associated with the geographical area, suggesting a role for pollen in the sensitization of these allergens. Finally, the co-sensitizations of patients considering pairs of TLP allergens were analyzed by using the co-sensitization graph associated with an allergen microarray immunoassay. Our data indicate that TLPs are significant allergens in plant food allergy and should be considered when diagnosing and treating pollen-food allergy.

The study of cross-reactivity in allergy is key to both understanding. the allergic response of many patients and providing them with a rational treatment In the present study, protein microarrays and a co-sensitization graph approach were used in conjunction with an allergen microarray immunoassay. This enabled us to include a wide number of proteins and a large number of patients, and to study sensitization profiles among members of the LTP family. Fourteen LTPs from the most frequent plant food-induced allergies in the geographical area studied were printed into a microarray specifically designed for this research. 212 patients with fruit allergy and 117 food-tolerant pollen allergic subjects were recruited from seven regions of Spain with different pollen profiles, and their sera were tested with allergen microarray. This approach has proven itself to be a good tool to study cross-reactivity between members of LTP family, and could become a useful strategy to analyze other families of allergens.

Implementation of a standardized language in Nursing Care Plans (SNCP) allows for increased efficiency in nursing data management. However, the potential relationship with patientś health outcomes remains uncertain. The aim of this study was to evaluate the effectiveness of SNCP implementation, based on North American Nursing Diagnosis Association (NANDA) and Nursing Interventions Classification (NIC), in the improvement of metabolic, weight, and blood pressure control of Type 2 Diabetes Mellitus (T2DM) patients.A two-year prospective follow-up study, in routine clinical practice conditions. 31 primary health care centers (Spain) participated with 24,124 T2DM outpatients. Data was collected from Computerized Clinical Records; SNCP were identified using NANDA and NIC taxonomies. Descriptive and ANCOVA analyses were conducted.18,320 patients were identified in the Usual Nursing Care (UNC) group and 5,168 in the SNCP group. At the two-year follow-up, the SNCP group improved all parameters except LDL cholesterol and diastolic blood pressure. We analyzed data adjustming by the baseline value for these variables and variables with statistically significant differences between groups at baseline visit. Results indicated a lowering of all parameters except HbA1c, but a statistically significant reduction was only observed with diastolic blood pressure results. However, the adjusted reduction of diastolic blood pressure is of little clinical relevance. Greater differences of control values for diastolic blood pressure, HbA1c, LDL-cholesterol and Body Mass Index were found in the SNCP group, but only reached statistical significance for HbA1c. A greater proportion of patients with baseline HbA1c ≥7 decreased to

Gene regulatory networks have been conserved during evolution. The Drosophila wing and the vertebrate hindbrain share the gene network involved in the establishment of the boundary between dorsal and ventral compartments in the wing and adjacent rhombomeres in the hindbrain. A positive feedback-loop between boundary and non-boundary cells and mediated by the activities of Notch and Wingless/Wnt-1 leads to the establishment of a Notch dependent organizer at the boundary. By means of a Systems Biology approach that combines mathematical modeling and both in silico and in vivo experiments in the Drosophila wing primordium, we modeled and tested this regulatory network and present evidence that a novel property, namely refractoriness to the Wingless signaling molecule, is required in boundary cells for the formation of a stable dorsal-ventral boundary. This new property has been validated in vivo, promotes mutually exclusive domains of Notch and Wingless activities and confers stability to the dorsal-ventral boundary. A robustness analysis of the regulatory network complements our results and ensures its biological plausibility.