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Actinomycosis is a chronic suppurative granulomatous inflammation caused by Actinomyces species. Abdominal actinomycosis is a rare condition, with very low incidence in childhood, and usually associated to trauma or perforation of hollow viscera. We are presenting a case of a ten-year-old boy with omental actinomycosis mimic and appendiceal infection, without a history of trauma or perforation, suggesting a hemmatogen spread. The complete resection of the affected tissue may warrant a cure in spite of a short antibiotic curse.

Purpose: SBRT-Spanish Group-05 (ClinicalTrials.gov.Identifier: NCT02192788) is a collaborative (SBRT-SG, Grupo de Investigación Clínica en Oncología Radioterápica, and Sociedad Española de Oncología Radioterápica) prospective multicenter phase II trial testing stereotactic body radiation therapy (SBRT) and androgen deprivation therapy (ADT) in patients with oligorecurrent prostate cancer., Methods and Materials: Two cohorts of patients with prostate cancer in an oligorecurrent stage (hormone-sensitive in the principal cohort and castration-resistant in the exploratory cohort) were assigned to receive ADT and SBRT for at least 24 months from the time of the enrollment. Concomitant treatment with chemotherapy, abiraterone, or enzalutamide was not allowed. Oncologic outcomes were assessed in both cohorts. Toxicity was prospectively analyzed., Results: From 2014 to 2019, 81 patients with a total of 126 lesions from 14 centers met the inclusion criteria, 14 of whom were castration-resistant. With a median follow-up of 40 months (12-58 months), 3-year local recurrence-free survival was 92.5% (95% CI, 79.9%-96.3%) and 85.7% (95% CI, 48.2%-95.6%) in the principal and exploratory cohorts, respectively. In the principal cohort, biochemical relapse-free survival and metastasis progression-free survival at 1, 2, and 3 years were 91% (95% CI, 81%-95.8%), 73.7% (95% CI, 61.1%-82.8%), 50.6% (95% CI, 36.2%-63.3%), and 92% (95% CI, 83%-97%), 81% (95% CI, 70%-89%), and 67% (95% CI, 53%-77%), respectively. In the exploratory cohort, metastasis progression-free survival at 1, 2, and 3 years was 64% (95% CI, 34%-83%), 43% (95% CI, 18%-66%), and 26% (95% CI, 7%-51%), respectively. None of the patients developed grade III or higher toxicity or symptoms related to local progression, and only 2 (2.4%) patients developed grade II toxicity., Conclusions: The combination of SBRT and ADT is safe and shows favorable clinical outcomes in patients with hormone-sensitive and castration-resistant prostate cancer. Validation studies are needed in patients with castration-resistant prostate cancer., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

The field of transplantation would benefit from the integration of advanced precision medicine techniques. Although predictive tests for lung transplantation require a well-defined clinical end-point, there exists no consensus regarding which outcomes are optimal end-points for these purposes. While many possible candidate end-points exist, we propose that time-to-extubation is an optimal end-point for prognostic tests because of its: clinical relevance; objectiveness; stability over time; and association with healthcare expenditure. Herein, we describe the rationale for this selection and present the limitations of alternative outcomes for this purpose. Using a 72-hour cut-off, time to extubation correlated well with Primary Graft Dysfunction Grade 3, intensive care unit and hospital length of stay, and a greater than 2-fold increase in healthcare cost ratios. Given that time-to-extubation is an objective measure that is readily measured by all lung transplant centers, this metric represents a preferred primary end-point for prognostic tests developed for lung transplantation., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Stroke is becoming increasingly prevalent among the non-elderly adults (<65 years of age) in the United States. Using the National Health Interview Survey database from 2012 to 2018, we examined the association of traditional risk factors, sociodemographic, cardiovascular risk factor (CRF) profile, family income, and educational attainment in young (18-44 years) and middle-aged (45-64 years) adults. CRF profiles were defined by the number of traditional risk factors with "Poor" (≥4 risk factors), "Average," or "Optimal" (0-1). The study included 168,862 non-elderly adults (55% in young adults). Overall prevalence of stroke was 1.83% among the non-elderly (0.64% and 3.31% in young- and middle-aged adults, respectively). Adults with low family income, lesser education, and who were Non-Hispanic Blacks were more likely to have stroke. Those with poor CRF profiles exhibited a 3-4 times higher odds of stroke compared to those with optimal CRF profiles. Lower income status coupled with a poor CRF profile augmented the prevalence of stroke in non-elderly adults. This national survey of non-elderly US adults showed a correlation between lower income and education, both factors of SES, and stroke. When viewed together, there was an increasing stroke burden in the non-elderly with worsening CRF profile, income status, and educational attainment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Low-income, rural frontline communities of California's Central Valley experience environmental and socioeconomic injustice, water insecurity, extremely poor air quality, and lack of fundamental infrastructure (sewage, green areas, health services), which makes them less resilient. Many communities depend financially on agriculture, while water scarcity and associated policy may trigger farmland retirement further hindering socioeconomic opportunities. Here we propose a multi-benefit framework to repurpose cropland in buffers inside and around (400-m and 1600-m buffers) 154 rural disadvantaged communities of the Central Valley to promote socioeconomic opportunities, environmental benefits, and business diversification. We estimate the potential for (1) reductions in water and pesticide use, nitrogen leaching, and nitrogen gas emissions, (2) managed aquifer recharge, and (3) economic and employment impacts associated with clean industries and solar energy. Retiring cropland within 1600-m buffers can result in reductions in water use of 2.18 km 3 /year, nitrate leaching into local aquifers of 105,500 t/year, greenhouse gas emissions of 2,232,000 t CO 2 -equivalent/year, and 5388 t pesticides/year, with accompanying losses in agricultural revenue of US$4213 million/year and employment of 25,682 positions. Buffer repurposing investments of US$27 million/year per community for ten years show potential to generate US$101 million/year per community (total US$15,578 million/year) for 30 years and 407 new jobs/year (total 62,697 jobs/year) paying 67 % more than prior farmworker jobs. In the San Joaquin Valley (southern Central Valley), where groundwater overdraft averages 2.3 km 3 /year, potential water use reduction is 1.8 km 3 /year. We have identified 99 communities with surficial soils adequate for aquifer recharge and canals/rivers within 1600 m. This demonstrates the potential of managed aquifer recharge in buffered zones to substantially reduce overdraft. The buffers framework shows that well-planned land repurposing near disadvantaged communities can create multiple benefits for farmers and industry stakeholders, while improving quality of life in disadvantaged communities and producing positive externalities for society., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The burden of total coronary plaque, plaque subtypes, and high-risk plaque features was unknown in asymptomatic individuals from the general U.S. primary prevention population., Objectives: In a large, asymptomatic U.S. cohort evaluated using coronary computed tomography angiography (CCTA), we aimed to assess the burden of total coronary plaque, plaque subtypes, and high-risk plaque features; the interplay between CCTA findings and coronary artery calcium (CAC) scores; and identify independent predictors of coronary plaque., Methods: Cross-sectional analysis in the MiHeart (Miami Heart Study), a cohort of 2,359 asymptomatic individuals from the Greater Miami Area (mean age 53 years, 50% women, 47% Hispanic/Latino, 43% non-Hispanic White). We estimated the burden of CAC (=0, >0 to <100, ≥100), CCTA-based plaque features (any plaque, stenosis ≥50%, ≥70%, high-risk features), and their interplay., Results: Overall, 58% participants had CAC = 0, 28% CAC >0 to <100, and 13% CAC ≥100. A total of 49% participants had plaque on the CCTA, including 16% among those with CAC = 0. Overall, 6% participants had coronary stenosis ≥50% (12% among those with coronary plaque), 1.8% had stenosis ≥70% (3.7% among those with plaque), and 7% had at least 1 coronary plaque with ≥1 high-risk feature (13.8% among those with plaque). Only 0.8% participants with CAC = 0 had stenosis ≥50%, 0.1% stenosis ≥70%, and 2.3% plaque with high-risk features. In logistic regression models, independent predictors of coronary plaque and high-risk plaque were older age, male sex, tobacco use, diabetes, overweight, and obesity. Male sex, overweight, and obesity were independent predictors of plaque if CAC = 0., Conclusions: The Miami Heart Study confirms substantial prevalence of coronary plaque in asymptomatic individuals. Overall, 49% of participants had coronary plaque, 6% had stenosis ≥50%, and 7% had plaques with at least 1 high-risk feature. These proportions were 16%, 0.8%, and 2.3%, respectively, among those with CAC = 0. Longitudinal follow-up will shed further light on the prognostic implications of these findings in asymptomatic individuals., Competing Interests: Funding Support and Author Disclosures The Miami Heart Study was funded by Baptist Health South Florida. Dr Nasir is on the advisory board of Amgen, Novartis, Novo Nordisk; his research is partly supported by the Jerold B. Katz Academy of Translational Research; and he is a member of the Steering Committee of the PAK-SEHAT Study, which is partially funded by an unrestricted research grant from Getz Pharma. Dr Cainzos-Achirica is also member of the Steering Committee of the PAK-SEHAT Study. Dr Blankstein has received research support from Amgen Inc and Novartis Inc; and he is a consultant to Caristo Diagnostics, Silence Therapeutics, and Roivant Sciences Inc. Dr Shapiro is on the advisory boards of Amgen, Novartis, and Novo Nordisk. Dr Cury is consultant to GE Healthcare, Covera Health, and Cleerly. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

COVID-19 has led to an unprecedented health and economic crisis worldwide. Many governments of the world have accelerated an adoption of public policies to address this crisis; however, a trade-off between the economy and public health exists. Previous studies in this area have mainly focused on the impact of COVID-19 on human life and the environment. This work adds to the literature by analyzing how individual environmental concern can affect citizens' preferences for public policies that deal with COVID-19. A data set of 26,131 participants from 26 countries was used to test the research model. Results indicate that environmental concern is positively associated with a preference for long-term oriented altruistic policies, and it shapes the relationship between economic and health problems at the country level on our dependent variable. Specifically, as the level of environmental concern increases, the negative effect of COVID-19's economic problems on the preference for long-term altruistic policies is diminished. In turn, in the case of health problems, the impact on the preference for long-term altruistic policies increases as environmental concern increases. Also, both individual-level and country-level characteristics affect citizens' preferences for policies related to the COVID-19 pandemic., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Ex vivo lung perfusion (EVLP) has being increasingly used for the pretransplant assessment of extended-criteria donor lungs. Mathematical models to predict lung acceptance during EVLP have not been reported so far. Thus, we hypothesized that predictors of lung acceptance could be identified and used to develop a mathematical model describing the clinical decision-making process used in our institution. Donor lungs characteristics and EVLP physiologic parameters included in our EVLP registry were examined (derivation cohort). Multivariable logistic regression analysis was performed to identify predictors independently associated with lung acceptance. A mathematical model (EX vivo lung PerfusIon pREdiction [EXPIRE] model) for each hour of EVLP was developed and validated using a new cohort (validation cohort). Two hundred eighty donor lungs were assessed with EVLP. Of these, 186 (66%) were accepted for transplantation. ΔPO 2 and static compliance/total lung capacity were identified as independent predictors of lung acceptance and their respective cut-off values were determined. The EXPIRE model showed a low discriminative power at the first hour of EVLP assessment (AUC: 0.69 [95% CI: 0.62-0.77]), which progressively improved up to the fourth hour (AUC: 0.87 [95% CI: 0.83-0.92]). In a validation cohort, the EXPIRE model demonstrated good discriminative power, peaking at the fourth hour (AUC: 0.85 [95% CI: 0.76-0.94]). The EXPIRE model may help to standardize lung assessment in centers using the Toronto EVLP technique and improve overall transplant rates., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: The objective of this study was to describe the prevalence of patients with forgone/delayed care for heart failure (HF) and examine the associated demographic characteristics, health care utilization, and costs., Background: HF is a leading cause of morbidity and mortality, with health care expenditures projected to increase 3-fold from 2012 to 2030. The proportion of HF patients with forgone/delayed medical care and the association with health care expenditures and utilization remain unknown., Methods: Data on patients with HF were obtained from the Medical Expenditure Panel Survey to assess expenditures and health care utilization in the United States from 2004 to 2015. Patients with HF who reported forgone/delayed care, any missed or delayed medical treatment, were compared with those without care lapses., Results: Overall, 16% of patients with HF reported forgone/delayed care, including 10% among the elderly (aged ≥65 years) and 27% among the nonelderly (aged <65 years). Patients with HF who reported forgone/delayed care had annual health care expenses $8,027 (95% CI: $1,181-$14,872) higher than those who did not. Among the elderly, those reporting forgone/delayed care had more emergency department visits (43% vs 58%; P < 0.05), and had higher annual inpatient costs (+$7,548; 95% CI: $1,109-$13,988) and total health care costs (+$10,581; 95% CI: $1,754-$19,409). Sixty percent of nonelderly and 46% of elderly patients with HF reported deferring care due to financial barriers., Conclusions: Nearly 1 in 6 patients with HF in the United States reported forgone/delayed medical care, with one-half attributing it to financial reasons, and this was associated with higher overall health care spending., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Groundwater is a common pool resource that supports agriculture, human communities, and the environment. Public participation in common pool natural resources management can be affected by media representation of stakeholders and perceptions of identity as a stakeholder. Newspaper media has an outsized influence on framing subject matter, expertise, organizations, and who should participate. Media shapes individual, local, and regional perspectives around resource management and defines potential solutions to natural resources management. This study analyzes media coverage about California's new Sustainable Groundwater Management Act (SGMA) to understand impacts on public participation in common pool natural resources management and to identify represented stakeholders and solutions involved in groundwater sustainability. A total of 365 newspaper articles were collected from California newspapers in three readership locations. We also searched for representation of SGMA in Spanish-language publications. Article characteristics were analyzed through qualitative content analysis and quantitative nonparametric analysis. Results indicate bias for featuring agricultural industry, politician, and water managers' voices. Solutions for managing water resources were focused on new supply, demand reduction and infrastructure investment, though novel solutions were also presented. Most newspaper articles included few stakeholders and solutions, illustrating isolated, short narratives about a common pool resource. The trends and gaps in representation in California media coverage may contribute to the public's low levels of engagement in groundwater planning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

During aging, lifestyle-related factors shape the brain's response to insults and modulate the progression of neurodegenerative pathologies such as Alzheimer's disease (AD). This is the case for chronic hyperglycemia associated with type 2 diabetes, which reduces the brain's ability to handle the neurodegenerative burden associated with AD. However, the mechanisms behind the effects of chronic hyperglycemia in the context of AD are not fully understood. Here, we show that newly generated neurons in the hippocampal dentate gyrus of triple transgenic AD (3xTg-AD) mice present increased dendritic arborization and a number of synaptic puncta, which may constitute a compensatory mechanism allowing the animals to cope with a lower neurogenesis rate. Contrariwise, chronic hyperglycemia decreases the complexity and differentiation of 3xTg-AD newborn neurons and reduces the levels of β-catenin, a key intrinsic modulator of neuronal maturation. Moreover, synaptic facilitation is depressed in hyperglycemic 3xTg-AD mice, accompanying the defective hippocampal-dependent memory. Our data suggest that hyperglycemia evokes cellular and functional alterations that accelerate the onset of AD-related symptoms, namely memory impairment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aims: Socioeconomic status (SES) has been linked to worse cardiovascular risk factor (CRF) profiles and higher rates of cardiovascular disease (CVD), with an especially high burden of disease for low-income groups. We aimed to describe the trends in prevalence of CRFs among US adults by SES from 2002 to 2013., Methods: Data from the Medical Expenditure Panel Survey was analyzed. CRFs (obesity, diabetes, hypertension, physical inactivity, smoking and hypercholesterolemia), were ascertained by ICD-9-CM and/or self-report., Results: The proportion of individuals with obesity, diabetes and hypertension increased overall, with low-income groups representing a higher prevalence for each CRF. Of note, physical inactivity had the highest prevalence increase, with the "lowest-income" group observing a relative percent increase of 71.1%., Conclusions: Disparities in CRF burden continue to increase, across SES groups. Strategies to potentially eliminate the persistent health disparities gap may include a shift to greater coverage for prevention, and efforts to engage in healthy lifestyle behaviors., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Interlocked molecular architectures are well known in supramolecular chemistry and are widely used for various applications like sensors, molecular machines and logic gates. The use of DNA for constructing these interlocked structures has increased significantly within the current decade. Because of Watson-Crick base pairing rules, DNA is an excellent material for the self-assembly of well-defined interlocked nanoarchitectures. These DNA nanostructures exhibit sufficient stability, good solubility in aqueous media, biocompatibility, and can be easily combined with other biomolecules in bio-hybrid nano-assemblies. Therefore, the study of novel DNA-based interlocked systems is of interest for nanotechnology, synthetic biology, supramolecular chemistry, biotechnology, and for sensing purposes. Here we summarize recent developments and applications of interlocked supramolecular architectures made of DNA. Examples illustrating that these systems can be precisely controlled by switching on and off the molecular motion of its mechanically trapped components are discussed. Introducing different triggers into such systems creates molecular assemblies capable of performing logic gate operations and/or catalytic activity control. Interlocked DNA-based nanostructures thus represent promising frameworks for building increasingly complex and dynamic nanomachines with highly controllable functionality., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Excessive bleeding is a major concern in scar debridement and grafting procedures. TT-173 is a new topical hemostatic agent based on recombinant human tissue factor that has shown promising results in patients who underwent tooth extraction. EHTIC study sought to evaluate the efficacy and safety of TT-173 to reduce the bleeding in donor sites of skin grafting procedures., Methods: EHTIC study was a phase II, randomized, parallel, double blind, placebo controlled trial. Patients received TT-173 (n=38) or placebo (n=33) sprayed over donor site after graft harvest. Time to hemostasis and incidence of adverse events were recorded. Systemic absorption of the product and its immunogenicity were also measured during the follow up of the subjects., Results: Treatment with TT-173 significantly reduced the bleeding time from 7 to 3min (Log-Rank p<0.0001). Moreover, bleeding stopped within the 10min of evaluation period in all the patients that received TT-173. In contrast, 24.24% of patients from placebo group required additional measures to arrest hemorrhage (Fisher p=0.0013). Product related adverse events, systemic absorption into blood stream, interferences with the healing of the donor site or immunogenic reaction against TT-173 were not observed., Conclusion: The new hemostatic agent TT-173 has proven efficacious and safe to reduce the bleeding from donor site. This study paves the way for further investigation of the product as topical hemostatic treatment in plastic surgery and other surgical indications., (Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.)

Background and Aims: Given the prevalence and economic burden of diabetes mellitus (DM), we studied the impact of a favorable cardiovascular risk factor (CRF) profile on healthcare expenditures and resource utilization among individuals without cardiovascular disease (CVD), by DM status., Methods: 25,317 participants were categorized into 3 mutually-exclusive strata: "Poor", "Average" and "Optimal" CRF profiles (≥4, 2-3, 0-1 CRF, respectively). Two-part econometric models were utilized to study cost data., Results: Mean age was 45 (48% male), with 54% having optimal, 39% average, and 7% poor CRF profiles. Individuals with DM were more likely to have poor CRF profile vs. those without DM (OR 7.7, 95% CI 6.4, 9.2). Individuals with DM/poor CRF profile had a mean annual expenditure of $9,006, compared to $6,461 among those with DM/optimal CRF profile (p < 0.001)., Conclusions: A favorable CRF profile is associated with significantly lower healthcare expenditures and utilization in CVD-free individuals across DM status, suggesting that these individuals require aggressive individualized prescriptions targeting lifestyle modifications and therapeutic treatments., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The necrotrophic fungus Botrytis cinerea is a very damaging phytopathogen of wide host range and environmental persistence. It is difficult to control because of its genetic versatility, expressed in the many phenotypical differences among isolates. The genomes of the B. cinerea B05.10 and T4 strains have been recently sequenced, becoming a model system for necrotrophic pathogens, and thus opening new alternatives for functional genomics analysis. In this work, the mycelium and secreted proteome of six wild-type strains with different host range, and grown in liquid minimal medium, have been analyzed by using complementary gel-based (1-DE and 2-DE) and gel-free/label-free (nUPLC-MS(E)) approaches. We found differences in the protein profiles among strains belonging to both the mycelium and the secretome. A total of 47 and 51 variable proteins were identified in the mycelium and the secretome, respectively. Some of them, such as malate dehydrogenase or peptidyl-prolyl cis-trans isomerase from the mycelium, and endopolygalacturonase, aspartic protease or cerato-platanin protein from the secretome have been reported as virulence factors, which are involved in host-tissue invasion, pathogenicity or fungal development., Biological Significance: The necrotrophic fungus Botrytis cinerea is an important phytopathogen of wide host range and environmental persistence, causing substantial economic losses worldwide. In this work, the mycelium and secreted proteome of six B. cinerea wild-type strains with different host range have been analyzed by using complementary gel-based and gel-free/label-free approaches. Fungal genetic versatility was confirmed at the proteome level for both mycelium proteome and secreted proteins. A high number of hypothetical proteins with conserved domains related to toxin compounds or to unknown functions were identified, having qualitative differences among strains. The identification of hypothetical proteins suggests that the B. cinerea strains differ mostly in processes involved in adaptation to a particular environment or a growth condition, rather than in essential metabolic reactions. Proteomics can help in the identification of variable proteins related to the infection and colonization of host plant tissues, as well as of virulence and aggressiveness factors among different B. cinerea wild-type strains. This article is part of a Special Issue entitled: Trends in Microbial Proteomics., (© 2013. Published by Elsevier B.V. All rights reserved.)

A series of β-(1,3)-d-glucans have been synthesized incorporating structural variations specifically on the reducing end of the oligomers. Both O- and C-glucosides derived from di- and trisaccharides have been obtained in good overall yields and with complete selectivity. Whereas the O-glycosides were obtained via a classical Koenigs-Knorr glycosylation, the corresponding C-glycosides were obtained through allylation of the anomeric carbon and further cross-metathesis reaction. Finally, the compounds were evaluated against two glycosidases and two endo-glucanases and no inhibitory activity was observed., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Neuropeptide Y (NPY) has been implicated in the modulation of important features of neuronal physiology, including calcium homeostasis, neurotransmitter release and excitability. Moreover, NPY has been involved as an important modulator of hippocampal and thalamic circuits, receiving particular attention as an endogenous antiepileptic peptide and as a potential master regulator of feeding behavior. NPY not only inhibits excessive glutamate release (decreasing circuitry hyperexcitability) but also protects neurons from excitotoxic cell death. Furthermore, NPY has been involved in the modulation of the dynamics of dentate gyrus and subventricular zone neural stem cell niches. In both regions, NPY is part of the chemical resource of the neurogenic niche and acts through NPY Y1 receptors to promote neuronal differentiation. Interestingly, NPY is also considered a neuroimmune messenger. In this review, we highlight recent evidences concerning paracrine/autocrine actions of NPY involved in neuroprotection, neurogenesis and neuroinflammation. In summary, the three faces of NPY, discussed in the present review, may contribute to better understand the dynamics and cell fate decision in the brain parenchyma and in restricted areas of neurogenic niches, in health and disease., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

This paper presents an analysis of Holm oak pollen proteome, together with an evaluation of the potentiality that a proteomic approach may have in the provenance variability assessment. Proteins were extracted from pollen of four Holm oak provenances, and they were analyzed by gel-based (1- and 2-DE in combination with MALDI-TOF/TOF) and gel-free (nLC-LTQ Orbitrap MS) approaches. A comparison of 1- and 2-DE protein profiles of the four provenances revealed significant differences, both qualitative and quantitative, in abundance (18 bands and 16 spots, respectively). Multivariate statistical analysis carried out on bands and spots clearly showed distinct associations between provenances, which highlight their geographical origins. A total of 100 spots selected from the 402 spots observed on 2-DE gels were identified by MALDI-TOF/TOF. Moreover, a complementary gel-free shotgun approach was performed by nLC-LTQ Orbitrap MS. The identified proteins were classified according to biological processes, and most proteins in both approaches were related to metabolism and defense/stress processes. The nLC-LTQ Orbitrap MS analysis allowed us the identification of proteins belonging to the cell wall and division, transport and translation categories. Besides providing the first reference map of Holm oak pollen, our results confirm previous studies based on morphological observations and acorn proteomic analysis. Moreover, our data support the valuable use of proteomic techniques as phylogenetic tool in plant studies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs)., Methods: We performed a case-control association study of common nsSNPs in Galician (northwest Spain) samples using the Affymetrix GeneChip Human 20k cSNP Kit, followed by a replication study of the more promising results. After quality control procedures, the discovery sample consisted of 5100 nsSNPs at minor allele frequency >5% analyzed in 476 schizophrenia patients and 447 control subjects. The replication sample consisted of 4069 cases and 15,128 control subjects of European origin. We also performed multilocus analysis, using aggregated scores of nsSNPs at liberal significance thresholds and cross-validation procedures., Results: The 5 independent nsSNPs with false discovery rate q ≤ .25, as well as 13 additional nsSNPs at p < .01 and located in functional candidate genes, were genotyped in the replication samples. One SNP, rs13107325, located at the metal ions transporter gene SLC39A8, reached significance in the combined sample after Bonferroni correction (trend test, p = 2.7 × 10(-6), allelic odds ratio = 1.32). This SNP presents minor allele frequency of 5% to 10% in many European populations but is rare outside Europe. We also confirmed the polygenic component of susceptibility., Conclusions: Taking into account that another metal ions transporter gene, SLC39A3, is associated to bipolar disorder, our findings reveal a role for brain metal homeostasis in psychosis., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Studies of variability in Holm oak (Quercus ilex subsp. ballota [Desf.] Samp.), the dominant tree species in the typical Mediterranean forest, have been carried out by using electrophoresis-based proteomic analysis of acorns. Ten populations distributed throughout the Andalusia region have been surveyed. Acorns were sampled from individual trees and proteins extracted from seed flour by using the TCA-acetone precipitation protocol. Extracts were subjected to SDS-PAGE and 2-DE for protein separation, gel images captured, spot or bands quantified, and subjected to statistical analysis (ANOVA, SOM and clustering). Variable bands or spots among populations were subjected to MALDI-TOF/TOF and LC-MS/MS for identification. The protein yield of the used protocol varied among populations, and it was in the 2.92-5.92 mg/g dry weight range. A total of 23 bands were resolved by SDS-PAGE in the 3-35 kDa Mr range, with 8 and 12, out of the total, showing respectively qualitative and quantitative statistically significant differences among populations. Data allowed grouping populations, with groups being correlated according to geographical location and climate conditions, to northern and southern, as well as the discrimination of both mesic and xeric groups. Acorn flour extracts from the most distant populations were analyzed by 2-DE, and 56 differential spots were proposed as markers of variability. Identified proteins were classified into two principal categories; storage and stress/defense protein. Besides providing the first reference map of mature acorn seeds, the use of SDS-PAGE and proteomics in characterizing natural biodiversity in forest trees will be discussed., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Alzheimer's disease (AD) is characterized by progressive memory decline and neuropsychiatric symptoms. Despite common emotional symptoms in AD such as anxiety and fear are associated with a more rapid cognitive decline, the pathological mechanisms involved in these behavioral changes remain largely elusive. In this study, we examined the pathological mechanisms of emotional behavior in well-established AD transgenic mice expressing human mutant beta-amyloid (Abeta) precursor protein (APP(Ind) and APP(Sw,Ind)) and tau (3xTg-AD)., Methods: We evaluated unconditioned and conditioned fear-induced freezing behavior and spatial memory in APP(Ind), APP(Sw,Ind), and 3xTg-AD transgenic mice. The Abeta and tau pathologies and signaling pathways involved in emotional processing were studied by immunohistochemistry and immunoblotting analyses., Results: The APP(Ind)/APP(Sw,Ind) and 3xTg-AD transgenic mice displayed at early ages enhanced innate and conditioned fear symptoms and spatial memory deficits coinciding with enhanced accumulation of Abeta in gamma-aminobutyric acid (GABA)ergic and glutamatergic neurons, respectively, of the basolateral amygdala (BLA). Similarly, the number of neurons with intraneuronal Abeta40 and Abeta42 was significantly increased in the BLA of human AD brains. Fear responses might reflect an influence of anxiety, because the anxiolytic compounds valproate, diazepam, and buspirone reduced efficiently unconditioned and conditioned fear responses in APP transgenic mice. In addition, phosphorylation of extracellular signal-regulated kinase (ERK)1/2, which is critical for acquisition and consolidation of fear conditioning, was increased in the amygdala of APP transgenic mice after cued conditioning., Conclusions: We propose a deleterious role of intraneuronal Abeta on amygdala-dependent emotional responses by affecting the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway., (Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

This review is the continuation of three previously published articles [Jorrin JV, Maldonado AM, Castillejo MA. Plant proteome analysis: a 2006 update. Proteomics 2007; 7: 2947-2962; Rossignol M, Peltier JB, Mock HP, Matros A, Maldonado AM, Jorrin JV. Plant proteome analysis: a 2004-2006 update. Proteomics 2006; 6: 5529-5548; Canovas FM, Dumas-Gaudot E, Recorbet G, Jorrin J, Mock HP, Rossignol M. Plant proteome analysis. Proteomics 2004; 4: 285-298] and aims to update the contribution of Proteomics to plant research between 2007 and September 2008 by reviewing most of the papers, which number approximately 250, that appeared in the Plant Proteomics field during that period. Most of the papers published deal with the proteome of Arabidopsis thaliana and rice (Oryza sativa), and focus on profiling organs, tissues, cells or subcellular proteomes, and studying developmental processes and responses to biotic and abiotic stresses using a differential expression strategy. Although the platform based on 2-DE is still the most commonly used, the use of gel-free and second-generation Quantitative Proteomic techniques has increased. Proteomic data are beginning to be validated using complementary -omics or classical biochemical or cellular biology techniques. In addition, appropriate experimental design and statistical analysis are being carried out in accordance with the required Minimal Information about a Proteomic Experiment (MIAPE) standards. As a result, the coverage of the plant cell proteome and the plant biology knowledge is increasing. Compared to human and yeast systems, however, plant biology research has yet to exploit fully the potential of proteomics, in particular its applications to PTMs and Interactomics.

Multivalency plays a pivotal role in biological recognition, particularly at protein-protein and protein-carbohydrate interaction sites. Scaffolds of diverse structure, flexibility, and valency are gaining increasing biomedical importance in the development of artificial multivalent ligands for these interfaces. Relevant examples range from small C(4) symmetric calix[4]arenes and porphyrin ligands, which may achieve nanomolar affinity for protein surfaces of pharmaceutical interest, to large-sized dendrimers that provide promising adherence-inhibition for toxins and other relevant lectins. In addition, highly flexible supramolecular platforms like rotaxanes and polymers have been proposed as challenging alternatives to more rigid designs. Finally, nanoparticles are being exploited for this aim as they present important advantages from the biological and synthetic points of view.

This study was designed to evaluate the safety and tolerability of oxaliplatin combined with weekly boluses of 5-fluorouracil (5-FU) and low doses of leucovorin (LV) and to determine objective response, progression-free survival, and overall survival of patients with previously untreated advanced colorectal cancer. Seventy-nine patients enrolled in an observational, multicenter, prospective, open-label phase II study received intravenous (I.V.) infusions of oxaliplatin 85 mg/m2 over the course of 2 hours on days 1 and 14 and LV 20 mg/m2 over the course of 2 hours and 5-FU 500 mg/m2 as a bolus on days 1, 7, and 14 every 4 weeks until disease progression or unacceptable toxicity occurred. Seventy-nine patients were evaluable for safety, and data from 70 patients were used for efficacy analysis. The objective response rate was 51.4%. Complete responses occurred in 7 patients (10%), and partial responses occurred in 29 patients (41.4%). Disease control, defined as response or stable disease, was obtained in 56 of 70 patients (80%). The median duration of response was 8.34 weeks (range, 7.3-11.5 weeks). The median time to progression was 7.13 months (range, 6.28-7.72 months), and median overall survival time was 15 months (range, 12.32-18.37 months). Acute dose-limiting toxicities were grade 3/4 diarrhea and neutropenia, which occurred in 10.5% and 3.9% of patients, respectively. Among the 70 patients who experienced neurosensory toxicity, it was estimated that only 1.3% had grade 3 symptoms. Preliminary data showed that the regimen is at least as active as other regimens combining oxaliplatin and infusional schedules of 5-FU and might be more convenient for patients because it avoids the need for I.V. catheter implantation.

We report four cases of burn injuries inflicted by hot coolant after the explosion of the heating unit in four motor-vehicles of the same make and version, in similar circumstances while the patients were driving their cars. Burns of this type can cause considerable morbidity with an accompanying high risk of a traffic accident.

The annual rhythmic variations of the serum concentrations of follitropin, lutropin, sex-hormone-binding globulin and testosterone, the ratio between the serum concentrations of testosterone and sex-hormone-binding globulin, and the salivary concentration of testosterone were investigated in a group of 20 apparently healthy men. Venous blood and salivary specimens were collected at 1-month intervals during 12 months. The annual rhythms were studied by using a periodic function resulting from the sum of three cosine functions with periods of 365, 182.5 and 121.66 days. For the salivary concentration of testosterone and for the ratio between the serum concentrations of testosterone and sex-hormone-binding globulin, only the cosine function with a period of 365 days was significant, and for the serum concentration of lutropin, only the cosine function with a period of 121.66 days was significant. Serum concentrations of follitropin, sex-hormone-binding globulin and testosterone were significantly affected by 365 and 121.66 rhythmic components. The salivary concentration of testosterone and the serum concentration of follitropin are the quantities with the greatest annual rhythmic variation of those studied.

The entrapment of cisplatin into biodegradable colloidal systems (polyalkylcyanoacrylates) was studied. Nanoparticles were characterized in terms of relevant parameters for organ distribution in vivo, such as particle diameter and particle size distribution, determined by correlation photon spectroscopy and transmission electron microscopy. Association efficiency was also evaluated by Plasma Emission Spectrophotometry. The ability of surfactants (sodium lauryl sulphate and poloxamer 188), and dextrans of various molecular weights, to improve the binding of the drug to polyalkylcyanoacrylates was also studied. The dextran content in nanoparticles, as determined by polarimetry, increases with the molecular weight of the polysaccharide. The highest value of association efficiency of cisplatin to nanoparticles was obtained in the presence of dextran 70 with sodium lauryl sulphate (0.08%) as stabiliser.

Acute colonic pseudo-obstruction as a syndrome was first described by Ogilvie in 1948 (Br. Med J. 2, 671). It is characterized by colonic dilatation with no mechanical cause which affects critically ill patients. As a result of this complication the prognosis worsens. Initially there are few clinical symptoms, but subsequently colonic obstruction develops which, if not treated, can cause perforation of the caecum resulting in a high mortality rate. The treatment includes decompression via rectal and nasogastric probes, colonoscopy and caecostomy.

Fungal infections are assuming a more prominent role in the sepsis of patients with burns. Torula glabrata (Candida glabrata) is a fungus increasingly found in immunosuppressed patients. This report describes a seriously burned patient who developed a torula infection in the lungs.