Trends in socioeconomic inequalities in preventable mortality in urban areas of 33 Spanish cities, 1996-2007 (MEDEA project).

Abstract Background: Preventable mortality is a good indicator of possible problems to be investigated in the primary prevention chain, making it also a useful tool with which to evaluate health policies particularly public health policies. This study describes inequalities in preventable avoidable mortality in relation to socioeconomic status in small urban areas of thirty three Spanish cities, and analyses their evolution over the course of the periods 1996–2001 and 2002–2007. Methods: We analysed census tracts and all deaths occurring in the population residing in these cities from 1996 to 2007 were taken into account. The causes included in the study were lung cancer, cirrhosis, AIDS/HIV, motor vehicle traffic accidents injuries, suicide and homicide. The census tracts were classified into three groups, according their socioeconomic level. To analyse inequalities in mortality risks between the highest and lowest socioeconomic levels and over different periods, for each city and separating by sex, Poisson regression were used. Results: Preventable avoidable mortality made a significant contribution to general mortality (around 7.5%, higher among men), having decreased over time in men (12.7 in 1996–2001 and 10.9 in 2002–2007), though not so clearly among women (3.3% in 1996–2001 and 2.9% in 2002–2007). It has been observed in men that the risks of death are higher in areas of greater deprivation, and that these excesses have not modified over time. The result in women is different and differences in mortality risks by socioeconomic level could not be established in many cities. Conclusions: Preventable mortality decreased between the 1996–2001 and 2002–2007 periods, more markedly in men than in women. There were socioeconomic inequalities in mortality in most cities analysed, associating a higher risk of death with higher levels of deprivation. Inequalities have remained over the two periods analysed. This study makes it possible to identify those areas where excess preventable mortality was associated with more deprived zones. It is in these deprived zones where actions to reduce and monitor health inequalities should be put into place. Primary healthcare may play an important role in this process. Keywords: Preventable avoidable mortality, Causes of death, Inequalities in health, Small area analysis

The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism.

Oleoylethanolamide (OEA) is an agonist of the peroxisome proliferator-activated receptor α (PPARα) and has been described to exhibit neuroprotective properties when administered locally in animal models of several neurological disorder models, including stroke and Parkinson's disease. However, there is little information regarding the effectiveness of systemic administration of OEA on Parkinson's disease. In the present study, OEA-mediated neuroprotection has been tested on in vivo and in vitro models of 6-hydroxydopamine (6-OH-DA)-induced degeneration. The in vivo model was based on the intrastriatal infusion of the neurotoxin 6-OH-DA, which generates Parkinsonian symptoms. Rats were treated 2 h before and after the 6-OH-DA treatment with systemic OEA (0.5, 1, and 5 mg/kg). The Parkinsonian symptoms were evaluated at 1 and 4 wk after the development of lesions. The functional status of the nigrostriatal system was studied through tyrosine-hydroxylase (TH) and hemeoxygenase-1 (HO-1, oxidation marker) immunostaining as well as by monitoring the synaptophysin content. In vitro cell cultures were also treated with OEA and 6-OH-DA. As expected, our results revealed 6-OH-DA induced neurotoxicity and behavioural deficits; however, these alterations were less severe in the animals treated with the highest dose of OEA (5 mg/kg). 6-OH-DA administration significantly reduced the striatal TH-immunoreactivity (ir) density, synaptophysin expression, and the number of nigral TH-ir neurons. Moreover, 6-OH-DA enhanced striatal HO-1 content, which was blocked by OEA (5 mg/kg). In vitro, 0.5 and 1 μM of OEA exerted significant neuroprotection on cultured nigral neurons. These effects were abolished after blocking PPARα with the selective antagonist GW6471. In conclusion, systemic OEA protects the nigrostriatal circuit from 6-OH-DA-induced neurotoxicity through a PPARα-dependent mechanism.

The administration of atomoxetine during alcohol deprivation induces a time-limited increase in alcohol consumption after relapse.

The administration of selective serotonin reuptake inhibitors (SSRIs) typically used as antidepressants increases alcohol consumption after an alcohol deprivation period in rats. However, the appearance of this effect after the treatment with selective noradrenaline reuptake inhibitors (SNRIs) has not been studied. In the present work we examined the effects of a 15-d treatment with the SNRI atomoxetine (1, 3 and 10 mg/kg, i.p.) in male rats trained to drink alcohol solutions in a 4-bottle choice test. The treatment with atomoxetine (10 mg/kg, i.p.) during an alcohol deprivation period increased alcohol consumption after relapse. This effect only lasted one week, disappearing thereafter. Treatment with atomoxetine did not cause a behavioral sensitized response to a challenge dose of amphetamine (1.5 mg/kg, i.p.), indicating the absence of a supersensitive dopaminergic transmission. This effect is markedly different from that of SSRI antidepressants that produced both long-lasting increases in alcohol consumption and behavioral sensitization. Clinical implications are discussed.

Perifollicular erythema as a trichoscopy sign of progression in frontal fibrosing alopecia.

INTRODUCTION Frontal fibrosing alopecia (FFA) in an entity characterized by the recession of the frontotemporal hairline (FTHL) with alopecic scarring change. In recent years there are numerous articles discussing the usefulness of dermoscopy for the clinical diagnosis of different types of scarring alopecia. MATERIALS AND METHODS We value 79 patients diagnosed with FFA, evaluating some trichoscopical findings described as typical for FFA: Absence of follicular opening, follicular hyperkeratosis, follicular plugs and erythema. RESULTS In a population of 79 women, 100% showed no follicular opening, 72.1% follicular hyperkeratosis, 66.3% perifollicular erythema and 44.8% follicular plugs. Thus, 100% of patients had at least one of the dermoscopic elements described as suggestive of FFA, 53% two of them, 45% three and 27%, all those elements. Perifollicular erythema was present in 95% of cases in which the disease was active. CONCLUSIONS We consider that the presence of perifollicular erythema will be a direct marker of FFA activity.

Role of Sam68 in post-transcriptional gene regulation.

The STAR family of proteins links signaling pathways to various aspects of post-transcriptional regulation and processing of RNAs. Sam68 belongs to this class of heteronuclear ribonucleoprotein particle K (hnRNP K) homology (KH) single domain-containing family of RNA-binding proteins that also contains some domains predicted to bind critical components in signal transduction pathways. In response to phosphorylation and other post-transcriptional modifications, Sam68 has been shown to have the ability to link signal transduction pathways to downstream effects regulating RNA metabolism, including transcription, alternative splicing or RNA transport. In addition to its function as a docking protein in some signaling pathways, this prototypic STAR protein has been identified to have a nuclear localization and to take part in the formation of both nuclear and cytosolic multi-molecular complexes such as Sam68 nuclear bodies and stress granules. Coupling with other proteins and RNA targets, Sam68 may play a role in the regulation of differential expression and mRNA processing and translation according to internal and external signals, thus mediating important physiological functions, such as cell death, proliferation or cell differentiation.

Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach.

Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning to understand that under the intense pathological and clinical variability of these tumors there underlies strong genetic and biological heterogeneity. Thus, with the increasing available information of inter-tumor and intra-tumor heterogeneity, the classical pathological approach is being displaced in favor of novel molecular classifications. In the present article, we summarize the most relevant proposals of molecular classifications obtained from the analysis of colorectal tumors using powerful high throughput techniques and devices. We also discuss the role that cancer systems biology may play in the integration and interpretation of the high amount of data generated and the challenges to be addressed in the future development of precision oncology. In addition, we review the current state of implementation of these novel tools in the pathological laboratory and in clinical practice.

Osteoarticular Expression of Musashi-1 in an Experimental Model of Arthritis.

Background. Collagen-induced arthritis (CIA), a murine experimental disease model induced by immunization with type II collagen (CII), is used to evaluate novel therapeutic strategies for rheumatoid arthritis. Adult stem cell marker Musashi-1 (Msi1) plays an important role in regulating the maintenance and differentiation of stem/precursor cells. The objectives of this investigation were to perform a morphological study of the experimental CIA model, evaluate the effect of TNFα-blocker (etanercept) treatment, and determine the immunohistochemical expression of Msi1 protein. Methods. CIA was induced in 50 male DBA1/J mice for analyses of tissue and serum cytokine; clinical and morphological lesions in limbs; and immunohistochemical expression of Msi1. Results. Clinically, TNFα-blocker treatment attenuated CIA on day 32 after immunization (P < 0.001). Msi1 protein expression was significantly higher in joints damaged by CIA than in those with no lesions (P < 0.0001) and was related to the severity of the lesions (Spearman's rho = 0.775, P = 0.0001). Conclusions. Treatment with etanercept attenuates osteoarticular lesions in the murine CIA model. Osteoarticular expression of Msi1 protein is increased in joints with CIA-induced lesion and absent in nonlesioned joints, suggesting that this protein is expressed when the lesion is produced in order to favor tissue repair.

TRAF1/C5 but not PTPRC variants are potential predictors of rheumatoid arthritis response to anti-tumor necrosis factor therapy.

BACKGROUND The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response. METHODS We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. RESULTS No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. CONCLUSION This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response.

Enhanced antitumor activity of doxorubicin in breast cancer through the use of poly(butylcyanoacrylate) nanoparticles.

The use of doxorubicin (DOX), one of the most effective antitumor molecules in the treatment of metastatic breast cancer, is limited by its low tumor selectivity and its severe side effects. Colloidal carriers based on biodegradable poly(butylcyanoacrylate) nanoparticles (PBCA NPs) may enhance DOX antitumor activity against breast cancer cells, thus allowing a reduction of the effective dose required for antitumor activity and consequently the level of associated toxicity. DOX loading onto PBCA NPs was investigated in this work via both drug entrapment and surface adsorption. Cytotoxicity assays with DOX-loaded NPs were performed in vitro using breast tumor cell lines (MCF-7 human and E0771 mouse cancer cells), and in vivo evaluating antitumor activity in immunocompetent C57BL/6 mice. The entrapment method yielded greater drug loading values and a controlled drug release profile. Neither in vitro nor in vivo cytotoxicity was observed for blank NPs. The 50% inhibitory concentration (IC50) of DOX-loaded PBCA NPs was significantly lower for MCF-7 and E0771 cancer cells (4 and 15 times, respectively) compared with free DOX. Furthermore, DOX-loaded PBCA NPs produced a tumor growth inhibition that was 40% greater than that observed with free DOX, thus reducing DOX toxicity during treatment. These results suggest that DOX-loaded PBCA NPs have great potential for improving the efficacy of DOX therapy against advanced breast cancers.

The influence of individual, social and physical environment factors on physical activity in the adult population in Andalusia, Spain.

A person's physical and social environment is considered as an influencing factor in terms of rates of engagement in physical activity. This study analyses the influence of socio-demographic, physical and social environmental factors on physical activity reported in the adult population in Andalusia. This is a cross-sectional study using data collected in the Andalusia Health Survey in 1999 and 2003. In addition to the influence of the individual's characteristics, if there are no green spaces in the neighbourhood it is less likely that men and women will take exercise (OR = 1.26; 95% CI = 1.13, 1.41). Likewise, a higher local illiteracy rate also has a negative influence on exercise habits in men (OR = 1.39; 95% CI = 1.21, 1.59) and in women (OR = 1.22; 95% CI = 1.07, 1.40). Physical activity is influenced by individuals' characteristics as well as by their social and physical environment, the most disadvantaged groups are less likely to engage in physical activity.

Prognosis Relevance of Serum Cytokines in Pancreatic Cancer.

The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

Proadrenomedullin: An effective prognostic biomarker in septic patients

Background: Measurement of biomarkers is a potential approach to early prediction of mortality in septic patients. The purpose of this study was to asses the prognostic value of proadrenomedullin (pADM) in adult patients with sepsis with a single measurement in the first 24 hours after the onset of severe sepsis or septic shock. Conclusions: The protein pADM is an important prognostic biomarker of survival when measured on admission of septic patients to the ICU.

C-reactive protein, procalcitonin, lactate and score apache II in septic patients' prognosis.

Background: APACHE-II IS a score, based on several clinical and analytical measurements within 24 hours of admission in Intensive Care Unit (ICU). C-Reactive Protein (CRP), Lactate and recently Procalcitonin (PCT), also are biomarkers for the assessment of septic patients. The aim of this study was to find out if CRP, lactate and PCT during the first 24 hours from severe sepsis or septic shock onset, improved prediction of the APACHE II in terms of prognosis. Conclusions: CRP improves the prediction of patients with sepsis used in conjunction with the APACHE II score in severe sepsis and, lactate along with the CRP are the best precictors of survival in the cases of septic shock. The PCT did not show any predictive value.

Detection of possible variant forms of hemoglobin in HbA1c measurements by chromatography liquid ion exchange high resolution (HPLC)

Background: The glycosylated hemoglobin (HbA1c) is used to help monitor the degree of a diabetic’s hyperglycemia. Security and accuracy of the methods used in its detection are affected by variants forms of Hb or elevations in levels of Fetal Hb (HbF). These interference are the result of a change in the haemoglobin total net charge of the variant due of a substitution of one amino acid in the remaining amino terminal of the beta chain. International Standardization for HbA1c values (NGSP) not include interference assessment as part of the certification program. Therefore, the effect of each variant or the lifting of the HbF on HbA1c result should be examined in each sample depending on the detected variant and the method used for the detection of the same. The objectives were: to describe the possible variants of Hb and their interference in HbA1c measurement by our method, after the implementation of a computer program for their detection. To identify some variants detected by chromatography liquid ion exchange high resolution (HPLC) with DNA molecular sequencing.

Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer.

There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40-60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice.