Bullying According to Gender, and Immigration Background in Spanish Students.

BACKGROUND: Boys are more frequent aggressors than girls, but there are no conclusive findings on gender differences in victimization. There is a relationship between immigration background and bullying, but differences between generations are still debated. Therefore, the objectives of this study were: 1) to analyze victimization according to gender and immigration background (first and second generation); 2) to compare the attitudes of students against bullying based on these variables. METHOD: A multivariate analysis of covariance (MANCOVA) was carried out, considering gender and immigration background as independent variables, and types of offline bullying (physical, verbal and relational) as dependent variables. The sample was made up of 6,335 Spanish students (50.1% girls; 49.9% boys; average age: 15.83, DT: 0.29). RESULTS: Statistically significant differences were detected in types of bullying (considered together) and in attitudes against bullying according to gender and immigration background (p <.001). CONCLUSIONS: Being a first-generation immigrant stands out as the main risk factor. Findings are discussed as to the need to address cultural victimization in schools.

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism.

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.

Redirected Stress Responses in a Genome-Minimized 'midiBacillus' Strain with Enhanced Capacity for Protein Secretion.

Genome engineering offers the possibility to create completely novel cell factories with enhanced properties for biotechnological applications. In recent years, genome minimization was extensively explored in the Gram-positive bacterial cell factory Bacillus subtilis, where up to 42% of the genome encoding dispensable functions was removed. Such studies showed that some strains with minimized genomes gained beneficial features, especially for secretory protein production. However, strains with the most minimal genomes displayed growth defects. This focused our attention on strains with less extensive genomic deletions that display close-to-wild-type growth properties while retaining the acquired beneficial traits in secretory protein production. A strain of this category is B. subtilis IIG-Bs27-47-24, here referred to as midiBacillus, which lacks 30.95% of the parental genome. To date, it was unknown how the altered genomic configuration of midiBacillus impacts cell physiology in general, and protein secretion in particular. The present study bridges this knowledge gap through comparative quantitative proteome analyses with focus on protein secretion. Interestingly, the results show that the secretion stress responses of midiBacillus, as elicited by high-level expression of the immunodominant staphylococcal antigen A, are completely different from secretion stress responses that occur in the parental strain 168. We further show that midiBacillus has an increased capacity for translation and that a variety of critical Sec secretion machinery components is present at elevated levels. Altogether, our observations demonstrate that high-level protein secretion has different consequences for wild-type and genome-engineered Bacillus strains, dictated by the altered genomic and proteomic configurations. IMPORTANCE Our present study showcases a genome-minimized nonpathogenic bacterium, the so-called midiBacillus, as a chassis for the development of future industrial strains that serve in the production of high-value difficult-to-produce proteins. In particular, we explain how midiBacillus, which lacks about one-third of the original genome, effectively secretes a protein of the major human pathogen Staphylococcus aureus that cannot be produced by the parental Bacillus subtilis strain. This is important, because the secreted S. aureus protein is exemplary for a range of targets that can be implemented in future antistaphylococcal immunotherapies. Accordingly, we anticipate that midiBacillus chassis will contribute to the development of vaccines that protect both humans and livestock against diseases caused by S. aureus, a bacterial pathogen that is increasingly difficult to fight with antibiotics, because it has accumulated resistances to essentially all antibiotics that are currently in clinical practice.

COVID-19 Lockdown: Key Factors in Citizens' Stress.

Background: Confinement due to COVID-19 can have a short- and long-term impact on mental health (increased levels of stress and anxiety and emotional upheaval) and on people's quality of life. Knowing what factors are behind the stress can benefit the development of strategies and resources for future situations of a similar nature. The purpose of this study is to examine the incidence of a series of sociodemographic factors, confinement conditions, and work situation on the stress reported by confined citizens. Method: The sample is made up of 2008 citizens (19.9% men), the Perceived Stress Scale of 14 items (PSS-14) was used to assess the stress level of the population, as well as a sociodemographic questionnaire and different questions aimed at obtain information about the characteristics of the confinement and the employment situation. Data were collected using exponential snowball-type non-probability sampling. Results: The results suggest that sociodemographic factors such as age, gender, and income level could be good predictors of confinement stress. Post-confinement work expectancy along with pre-confinement working conditions can be key to protecting the well-being of confined populations. Limitations: This is a transversal study that forces us to be cautious with causal interpretations. The questionnaire was administered online, which means it excluded a good proportion of the population. Conclusion: The perception of stress being higher in women than men, with the lowest stress in older people and those with higher reported incomes. Stress levels increase as populations spend more weeks in confinement and the pre-confinement work situation seems key to protecting the well-being of the population. A lower stress is observed among stable couples without children confined in residential or suburban areas. Low income or economic instability is associated with a higher rate of stress and anxiety. The results can contribute to prioritizing actions and aid by contributing to the formation of teams and the design of tools for work in the current pandemic situation.

A Conserved Class II Type Thioester Domain-Containing Adhesin Is Required for Efficient Conjugation in Bacillus subtilis.

Conjugation, the process by which a DNA element is transferred from a donor to a recipient cell, is the main horizontal gene transfer route responsible for the spread of antibiotic resistance and virulence genes. Contact between a donor and a recipient cell is a prerequisite for conjugation, because conjugative DNA is transferred into the recipient via a channel connecting the two cells. Conjugative elements encode proteins dedicated to facilitating the recognition and attachment to recipient cells, also known as mating pair formation. A subgroup of the conjugative elements is able to mediate efficient conjugation during planktonic growth, and mechanisms facilitating mating pair formation will be particularly important in these cases. Conjugative elements of Gram-negative bacteria encode conjugative pili, also known as sex pili, some of which are retractile. Far less is known about mechanisms that promote mating pair formation in Gram-positive bacteria. The conjugative plasmid pLS20 of the Gram-positive bacterium Bacillus subtilis allows efficient conjugation in liquid medium. Here, we report the identification of an adhesin gene in the pLS20 conjugation operon. The N-terminal region of the adhesin contains a class II type thioester domain (TED) that is essential for efficient conjugation, particularly in liquid medium. We show that TED-containing adhesins are widely conserved in Gram-positive bacteria, including pathogens where they often play crucial roles in pathogenesis. Our study is the first to demonstrate the involvement of a class II type TED-containing adhesin in conjugation.IMPORTANCE Bacterial resistance to antibiotics has become a serious health care problem. The spread of antibiotic resistance genes between bacteria of the same or different species is often mediated by a process named conjugation, where a donor cell transfers DNA to a recipient cell through a connecting channel. The first step in conjugation is recognition and attachment of the donor to a recipient cell. Little is known about this first step, particularly in Gram-positive bacteria. Here, we show that the conjugative plasmid pLS20 of Bacillus subtilis encodes an adhesin protein that is essential for effective conjugation. This adhesin protein has a structural organization similar to adhesins produced by other Gram-positive bacteria, including major pathogens, where the adhesins serve in attachment to host tissues during colonization and infection. Our findings may thus also open novel avenues to design drugs that inhibit the spread of antibiotic resistance by blocking the first recipient-attachment step in conjugation.

Functional association of the stress-responsive LiaH protein and the minimal TatAyCy protein translocase in Bacillus subtilis.

The bacterial twin-arginine (Tat) pathway serves in the exclusive secretion of folded proteins with bound cofactors. While Tat pathways in Gram-negative bacteria and chloroplast thylakoids consist of conserved TatA, TatB and TatC subunits, the Tat pathways of Bacillus species and many other Gram-positive bacteria stand out for their minimalist nature with the core translocase being composed of essential TatA and TatC subunits only. Here we addressed the question whether the minimal TatAyCy translocase of Bacillus subtilis recruits additional cellular components that modulate its activity. To this end, TatAyCy was purified by affinity- and size exclusion chromatography, and interacting co-purified proteins were identified by mass spectrometry. This uncovered the cell envelope stress responsive LiaH protein as an accessory subunit of the TatAyCy complex. Importantly, our functional studies show that Tat expression is tightly trailed by LiaH induction, and that LiaH itself determines the capacity and quality of TatAyCy-dependent protein translocation. In contrast, LiaH has no role in high-level protein secretion via the general secretion (Sec) pathway. Altogether, our observations show that protein translocation by the minimal Tat translocase TatAyCy is tightly intertwined with an adequate bacterial response to cell envelope stress. This is consistent with a critical need to maintain cellular homeostasis, especially when the membrane is widely opened to permit passage of large fully-folded proteins via Tat.

Membrane Modulation of Super-Secreting "midiBacillus" Expressing the Major Staphylococcus aureus Antigen - A Mass-Spectrometry-Based Absolute Quantification Approach.

Bacillus subtilis has been extensively used as a microbial cell factory for industrial enzymes due to its excellent capacities for protein secretion and large-scale fermentation. This bacterium is also an attractive host for biopharmaceutical production. However, the secretion potential of this organism is not fully utilized yet, mostly due to a limited understanding of critical rearrangements in the membrane proteome upon high-level protein secretion. Recently, it was shown that bottlenecks in heterologous protein secretion can be resolved by genome minimization. Here, we present for the first time absolute membrane protein concentrations of a genome-reduced B. subtilis strain ("midiBacillus") expressing the immunodominant Staphylococcus aureus antigen A (IsaA). We quantitatively characterize the membrane proteome adaptation of midiBacillus during production stress on the level of molecules per cell for more than 400 membrane proteins, including determination of protein concentrations for ∼61% of the predicted transporters. We demonstrate that ∼30% of proteins with unknown functions display a significant increase in abundance, confirming the crucial role of membrane proteins in vital biological processes. In addition, our results show an increase of proteins dedicated to translational processes in response to IsaA induction. For the first time reported, we provide accumulation rates of a heterologous protein, demonstrating that midiBacillus secretes 2.41 molecules of IsaA per minute. Despite the successful secretion of this protein, it was found that there is still some IsaA accumulation occurring in the cytosol and membrane fraction, leading to a severe secretion stress response, and a clear adjustment of the cell's array of transporters. This quantitative dataset offers unprecedented insights into bioproduction stress responses in a synthetic microbial cell.

Publisher Correction: In vitro imaging of bacteria using 18F-fluorodeoxyglucose micro positron emission tomography.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

FGFR4 increases EGFR oncogenic signaling in lung adenocarcinoma, and their combined inhibition is highly effective.

OBJECTIVES: Lung adenocarcinoma accounts for approximately half of lung cancer cases. Twenty to 50% of tumors of this type harbor mutations affecting epidermal growth factor receptor (EGFR) expression or activity, which can be therapeutically targeted. EGFR inhibitors in this context exhibit high efficacy and are currently used in the clinical setting. However, not all adenocarcinomas harboring EGFR mutations respond to therapy, so predictive biomarkers of therapeutic outcomes, as well as novel therapies sensitizing these tumors to EGFR inhibition, are needed. MATERIALS AND METHODS: We performed in vitro gene overexpression/silencing and tumorigenic surrogate assays, as well as in vitro and in vivo combination treatments with Fibroblast Growth Factor Receptor (FGFR)/EGFR inhibitors. At the clinical level, we determined FGFR4 expression levels in tumors from patients treated with EGFR inhibitors and correlated these with treatment response. RESULTS: We describe a cooperative interaction between EGFR and FGFR4, which results in their reciprocal activation with pro-oncogenic consequences in vitro and in vivo. This cooperation is independent of EGFR activating mutations and increases resistance to different EGFR inhibitors. At the therapeutic level, we provide evidence of the synergistic effects of the combination of EGFR and FGFR inhibitors in high FGFR4-expressing, EGFR-activated tumors in vitro and in vivo. Correlated with these results, we found that patients treated with EGFR inhibitors relapse earlier when their tumors exhibit high FGFR4 expression. CONCLUSIONS: We propose a novel predictive biomarker for EGFR-targeted therapy, and a highly efficacious combinatory therapeutic strategy to treat EGFR-dependent; this may may extend the use of appropriate inhibitors beyond EGFR-mutated adenocarcinoma patients.

Effects of Adding Interferential Therapy Electro-Massage to Usual Care after Surgery in Subacromial Pain Syndrome: A Randomized Clinical Trial.

Subacromial pain syndrome (SAPS) is a prevalent condition that results in loss of function. Surgery is indicated when pain and functional limitations persist after conservative measures, with scarce evidence about the most-appropriate post-operative approach. Interferential therapy (IFT), as a supplement to other interventions, has shown to relieve musculoskeletal pain. The study aim was to investigate the effects of adding IFT electro-massage to usual care after surgery in adults with SAPS. A randomized, single-blinded, controlled trial was carried out. Fifty-six adults with SAPS, who underwent acromioplasty in the previous 12 weeks, were equally distributed into an IFT electro-massage group or a control group. All participants underwent a two-week intervention (three times per week). The control group received usual care (thermotherapy, therapeutic exercise, manual therapy, and ultrasound). For participants in the IFT electro-massage group, a 15-min IFT electro-massage was added to usual care in every session. Shoulder pain intensity was assessed with a 100-mm visual analogue scale. Secondary measures included upper limb functionality (Constant-Murley score), and pain-free passive range of movement. A blinded evaluator collected outcomes at baseline and after the last treatment session. The ANOVA revealed a significant group effect, for those who received IFT electro-massage, for improvements in pain intensity, upper limb function, and shoulder flexion, abduction, internal and external rotation (all, p < 0.01). There were no between-group differences for shoulder extension (p = 0.531) and adduction (p = 0.340). Adding IFT electro-massage to usual care, including manual therapy and exercises, revealed greater positive effects on pain, upper limb function, and mobility in adults with SAPS after acromioplasty.

FGFR1 Cooperates with EGFR in Lung Cancer Oncogenesis, and Their Combined Inhibition Shows Improved Efficacy.

INTRODUCTION: There is substantial evidence for the oncogenic effects of fibroblast growth factor receptor 1 (FGFR1) in many types of cancer, including lung cancer, but the role of this receptor has not been addressed specifically in lung adenocarcinoma. METHODS: We performed FGFR1 and EGFR overexpression and co-overexpression assays in adenocarcinoma and in inmortalized lung cell lines, and we also carried out surrogate and interaction assays. We performed monotherapy and combination EGFR/FGFR inhibitor sensitivity assays in vitro and in vivo in cell line- and patient-derived xenografts. We determined FGFR1 mRNA expression in a cohort of patients with anti-EGFR therapy-treated adenocarcinoma. RESULTS: We have reported a cooperative interaction between FGFR1 and EGFR in this context, resulting in increased EGFR activation and oncogenic signaling. We have provided in vitro and in vivo evidence indicating that FGFR1 expression increases tumorigenicity in cells with high EGFR activation in EGFR-mutated and EGFR wild-type models. At the clinical level, we have shown that high FGFR1 expression levels predict higher resistance to erlotinib or gefitinib in a cohort of patients with tyrosine kinase inhibitor-treated EGFR-mutated and EGFR wild-type lung adenocarcinoma. Dual EGFR and FGFR inhibition in FGFR1-overexpressing, EGFR-activated models shows synergistic effects on tumor growth in vitro and in cell line- and patient-derived xenografts, suggesting that patients with tumors bearing these characteristics may benefit from combined EGFR/FGFR inhibition. CONCLUSION: These results support the extended the use of EGFR inhibitors beyond monotherapy in the EGFR-mutated adenocarcinoma setting in combination with FGFR inhibitors for selected patients with increased FGFR1 overexpression and EGFR activation.

Less Is More: Toward a Genome-Reduced Bacillus Cell Factory for "Difficult Proteins".

The availability of complete genome sequences and the definition of essential gene sets were fundamental in the start of the genome engineering era. In a recent study, redundant and unnecessary genes were systematically deleted from the Gram-positive bacterium Bacillus subtilis, an industrial production host of high-value secreted proteins. This culminated in strain PG10, which lacks about 36% of the genome, thus representing the most minimal Bacillus chassis currently available. Here, we show that this "mini Bacillus" strain has synthetic traits that are favorable for producing "difficult-to-produce proteins". As exemplified with different staphylococcal antigens, PG10 overcomes several bottlenecks in protein production related to the secretion process and instability of the secreted product. These findings show for the first time that massive genome reduction can substantially improve secretory protein production by a bacterial expression host, and underpin the high potential of genome-engineered strains as future cell factories.

MAP17 predicts sensitivity to platinum-based therapy, EGFR inhibitors and the proteasome inhibitor bortezomib in lung adenocarcinoma.

BACKGROUND: The high incidence and mortality of lung tumours is a major health problem. Therefore, the identification both of biomarkers predicting efficacy for therapies in use and of novel efficacious therapeutic agents is crucial to increase patient survival. MAP17 (PDZK1IP1) is a small membrane-bound protein whose upregulation is reported as a common feature in tumours from diverse histological origins. Furthermore, MAP17 is correlated with tumour progression. METHODS: We assessed the expression of MAP17 in preclinical models, including cell lines and patient-derived xenografts (PDXs), assessing its correlation with sensitivity to different standard-of-care drugs in lung adenocarcinoma, as well as novel drugs. At the clinical level, we subsequently correlated MAP17 expression in human tumours with patient response to these therapies. RESULTS: We show that MAP17 expression is induced during lung tumourigenesis, particularly in lung adenocarcinomas, and provide in vitro and in vivo evidence that MAP17 levels predict sensitivity to therapies currently under clinical use in adenocarcinoma tumours, including cisplatin, carboplatin and EGFR inhibitors. In addition, we show that MAP17 expression predicts proteasome inhibitor efficacy in this context and that bortezomib, an FDA-approved drug, may be a novel therapeutic approach for MAP17-overexpressing lung adenocarcinomas. CONCLUSIONS: Our results indicate a potential prognostic role for MAP17 in lung tumours, with particular relevance in lung adenocarcinomas, and highlight the predictive pot0065ntial of this membrane-associated protein for platinum-based therapy and EGFR inhibitor efficacy. Furthermore, we propose bortezomib treatment as a novel and efficacious therapy for lung adenocarcinomas exhibiting high MAP17 expression.

Histology-dependent prognostic role of pERK and p53 protein levels in early-stage non-small cell lung cancer.

Lung tumors represent a major health problem. In early stage NSCLC tumors, surgical resection is the preferred treatment, but 30-55% of patients will relapse within 5 years after surgery. Thus, the identification of prognostic biomarkers in early stage NSCLC patients, especially those which are therapeutically addressable, is crucial to enhance survival of these patients. We determined the immunohistochemistry expression of key proteins involved in tumorigenesis and oncogenic signaling, p53, EGFR, pAKT and pERK, and correlated their expression level to clinicopathological characteristics and patient outcome. We found EGFR expression is higher in the squamous cell carcinomas than in adenocarcinomas (p=0.043), and that nuclear p53 staining correlated with lower differentiated squamous tumors (p=0.034). Regarding the prognostic potential of the expression of these proteins, high pERK levels proved to be an independent prognostic factor for overall (p<0.001) and progression-free survival (p<0.001) in adenocarcinoma patients, but not in those from the squamous histology, and high p53 nuclear levels were identified as independent prognostic factor for progression-free survival (p=0.031) only in squamous cell carcinoma patients. We propose a role as early prognostic biomarkers for pERK protein levels in adenocarcinoma, and for nuclear p53 levels in squamous cell lung carcinoma. The determination of these potential biomarkers in the adequate histologic context may predict the outcome of early stage NSCLC patients, and may offer a therapeutic opportunity to enhance survival of these patients.

Evaluation of the Analgesic Effect of Combination Therapy on Chronic Plantar Pain Through the Myofascial Trigger Points Approach.

BACKGROUND: Closely related pathologic disorders sometimes manifest with the same symptoms, making for a complex differential diagnosis. This is the situation in plantar fasciitis (PF) and myofascial pain syndrome (MPS) with myofascial trigger points (MTPs) in the sole of the foot. This research assessed the analgesic effect on plantar pain of combination therapy with interferential current stimulation therapy (ICST), treating MTPs in the great toe adductor muscle and the short flexor muscles of the toes in patients whose diagnosis was compatible with PF or MPS. METHODS: This study included 22 feet of 17 patients with a diagnosis compatible with PF or MPS with MTP. Participants received combination therapy with ICST for 15 sessions, and the decrease in pain was measured with an algometer and the visual analog scale. Both measurements were taken before and after every fifth session. The pressure pain threshold (PPT) results obtained with the Student t test and the pain intensity perception (PIP) results obtained with the Wilcoxon signed rank test were analyzed by comparing the measurements taken before the treatment and after the fifth, tenth, and 15th sessions. RESULTS: The decrease in PIP was significant after the fifth, tenth, and 15th sessions ( P < .001). The increase in PPT was also significant after the fifth ( P = .010), tenth ( P = .023), and 15th ( P = .001) sessions ( P < .05). CONCLUSIONS: The suggested combination therapy of ultrasound with ICST is clinically significant for reducing plantar pain after 15 treatment sessions, with a 6.5-point reduction in mean PIP and a 4.6-point increase in PPT.

Inequalities in the risk of disability due to traffic injuries in the Spanish adult population, 2009-2010.

BACKGROUND: Although traffic injuries (TIs) are an important cause of disability the related factors are little known. We aimed to estimate the differences in risk of TI-related disability according to individual characteristics that might generate health inequalities. METHODS: Cross-sectional study using a representative Spanish population sample drawn from the European Health Interview Survey 2009/2010. We calculated traffic crashes in the preceding year which resulted in injuries. Disability was measured using the Global Activity Limitation Indicator and four indicators of limitations (sensory, physical functional, self-care and domestic activities). Principal socio-demographic and behavioural/lifestyle variables were studied. We used multivariate logistic regression to estimate the risk (ORs) of TI-related disability in the sample as whole and disability-related factors in persons who had experienced TIs. RESULTS: Persons with TIs had a higher risk of global disability (OR = 1.61; 95%CI:1.17-2.20), physical functional limitations (OR = 1.96; 95%CI:1.33-2.89) and self-care limitations (OR = 1.73; 95%CI:0.98-3.05). Among persons with TIs, GALI-related risk was higher in women (OR = 3.06, p = 0.002) and persons aged over 30 years (OR31-45years = 6.81, p < 0.001; OR46-64years = 5.96, p = 0.011; OR>64years = 4.54, p = 0.047). Lower risk was observed among persons with a higher educational level (OR = 0.22, p = 0.003). The risk of disability among persons with TIs who consumed illegal drugs was OR = 3.9 (p = 0.023). CONCLUSIONS: Traffic injuries in the preceding year are associated with higher risk of disability, which is unevenly distributed. Individual (women and persons over 30 years), socio-economic (lower educational level) and behavioural (illegal drug use) factors are involved. Actions aimed at changing the unequal risk among vulnerable subgroups and providing health, social and protective services should be implemented.

Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer.

DNA methylation is important for gene expression and genome stability, and its disruption is thought to play a key role in the initiation and progression of cancer and other diseases. The DLK1-DIO3 cluster has been shown to be imprinted in humans, and some of its components are relevant to diverse pathological processes. The purpose of this study was to assess the methylation patterns of the DLK1-DIO3 cluster in patients with lung cancer to study its relevance in the pathogenesis of this disease. We found a characteristic methylation pattern of this cluster in smoking associated lung cancer, as compared to normal lung tissue. This methylation profile is not patent however in lung cancer of never smokers nor in lung tissue of COPD patients. We found 3 deregulated protein-coding genes at this locus: one was hypermethylated (DIO3) and two were hypomethylated (DLK1 and RTL1). Statistically significant differences were also detected in two different families of SNORDs, two miRNA clusters and four lncRNAs (MEG3, MEG8, MEG9 and LINC00524). These findings were validated using data from the cancer genome atlas (TCGA) database. We have then showed an inverse correlation between DNA methylation and expression levels in 5 randomly selected genes. Several targets of miRNAs included in the DLK1-DIO3 cluster have been experimentally verified as tumor suppressors. All of these results suggest that the dysmethylation of the imprinted DLK1-DIO3 cluster could have a relevant role in the pathogenesis of lung cancer in current and former smokers and may be used for diagnostic and/or therapeutic purposes.

[Effectiveness of a home hospitalization program for patients with urinary tract infection after discharge from an emergency department]. / Efectividad de las unidades de hospitalización a domicilio para el tratamiento de las infecciones del tracto urinario atendidas en urgencias.

OBJECTIVES: To compare outcomes of urinary tract infections (UTIs) in patients referred to a home hospitalization program or admitted to a conventional ward after initial management in the emergency department. MATERIAL AND METHODS: Prospective, quasi-experimental study of patients with UTIs attended in 3 hospital emergency departments in the public health system of the Basque Country, Spain, between January 2012 and June 2013. Patients were assigned to 2 groups according to site of treatment (home or hospital ward) after discharge from the emergency department. We collected sociodemographic data, history of kidney or urologic symptoms, concomitant diseases, risk for complicated UTI, presentation on admission to the emergency department, diagnostic findings, and prescribed treatments. The main outcome was poor clinical course (local complications during hospital or home care, recurrence, or readmission related to UTI. Multivariate logistic modeling was used to analyze factors related to poor clinical course. Home hospitalization was the main independent variable of interest. RESULTS: Patients referred to home hospitalization were more often women (70.6% vs 57.1% men, P=.04). Fewer cases of prior admission were recorded in the group treated at home (2.4% vs 9.5% of hospitalized patients, P=.03). Likewise, fewer home-hospitalization patients had risk factors for complicated UTI (58.7% vs 83.3% in the hospitalized group, P<.001). The only significant difference in complications between the 2 groups was a lower rate of acute confusional state in patients assigned to home hospitalization (0.8% vs 8.3% in hospitalized patients, P=.007). The frequency of poor clinical course was similar in home-hospitalized and ward-admitted patients. CONCLUSION: The clinical course of UTI is similar whether patients are hospitalized after emergency department management or discharged to a home hospitalization program.

OBJETIVO: Comparar la evolución de las infecciones del tracto urinario superior (ITUS) atendidas en urgencias que se derivan y tratan en hospitalización a domicilio (HAD) frente a las que ingresan en hospitalización convencional (HC). METODO: Estudio prospectivo, cuasiexperimental de pacientes con ITUS atendidos en tres hospitales de Osakidetza-Sistema Vasco de Salud (SVS) entre enero de 2012 y junio de 2013. Los pacientes se dividieron en 2 grupos según destino (ingresados en HAD en HC). Se recogieron datos sociodemográficos, antecedentes nefrourológicos, comorbilidades, factores de riesgo de infección complicada, forma de presentación en urgencias, pruebas diagnósticas realizadas y tratamientos prescritos. La variable de resultado principal fue la mala evolución (complicaciones locales durante el ingreso, recurrencia de la infección o reingreso relacionado con la infección). Se realizó un modelo multivariable de regresión logística para analizar la mala evolución, que incluyó el ingreso en HAD como la variable independiente principal. RESULTADOS: Los pacientes derivados a HAD incluyen una mayor proporción de mujeres (70,6% frente a 57,1%, p = 0,04), con menos ingresos previos (2,4% frente a 9,5%, p = 0,03) y menos criterios de presentar ITUS complicadas (58,7% frente a 83,3%, p < 0,001), en relación a los ingresados en HC. No hubo diferencias en complicaciones entre los dos grupos, excepto en la frecuencia de síndrome confusional que fue inferior en el grupo HAD (8,3% frente a 0,8%, p = 0,007). No se encontraron diferencias en las variables de mala evolución entre los que ingresaron en HC y en HAD. CONCLUSIONES: No hay diferencias en la evolución de los pacientes con ITUS ingresados en HAD comparados con los ingresados en HC.

In vitro imaging of bacteria using 18F-fluorodeoxyglucose micro positron emission tomography.

Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (18F-FDG) can be applied to detect infection and inflammation. However, it was so far not known to what extent bacterial pathogens may contribute to the PET signal. Therefore, we investigated whether clinical isolates of frequently encountered bacterial pathogens take up 18F-FDG in vitro, and whether FDG inhibits bacterial growth as previously shown for 2-deoxy-glucose. 22 isolates of Gram-positive and Gram-negative bacterial pathogens implicated in fever and inflammation were incubated with 18F-FDG and uptake of 18F-FDG was assessed by gamma-counting and µPET imaging. Possible growth inhibition by FDG was assayed with Staphylococcus aureus and the Gram-positive model bacterium Bacillus subtilis. The results show that all tested isolates accumulated 18F-FDG actively. Further, 18F-FDG uptake was hampered in B. subtilis pts mutants impaired in glucose uptake. FDG inhibited growth of S. aureus and B. subtilis only to minor extents, and this effect was abrogated by pts mutations in B. subtilis. These observations imply that bacteria may contribute to the signals observed in FDG-PET infection imaging in vivo. Active bacterial FDG uptake is corroborated by the fact that the B. subtilis phosphotransferase system is needed for 18F-FDG uptake, while pts mutations protect against growth inhibition by FDG.