Exosomes in head and neck cancer. Updating and revisiting

Exosomes have gone from being considered simple containers of intracellular waste substances to be considered important carriers of cellular signals. Its broad capacity to promote tumour growth, both in situ and metastatic, has greatly intensified scientific research on them. In the same way and depending on its content, its tumour suppressive properties have opened a window of light and hope in the fight against cancer. In the present review we try to gather in a simple and understandable way the most relevant knowledge to date on the role of exosomes in oral squamous cell carcinoma, helping to understand their process of formation, release and activity on the tumour microenvironment

A prospective study of the clinical outcomes and prognosis associated with comorbid COPD in the atrial fibrillation population

Background: Patients with COPD are at higher risk of presenting with atrial fibrillation (AF). Information about clinical outcomes and optimal medical treatment of AF in the setting of COPD remains missing. We aimed to describe the prevalence of COPD in a sizeable cohort of real-world AF patients belonging to the same healthcare area and to examine the relationship between comorbid COPD and AF prognosis. Methods: Prospective analysis performed in a specific healthcare area. Data were obtained from several sources within the "data warehouse of the Galician Healthcare Service" using multiple analytical tools. Statistical analyses were completed using SPSS 19 and STATA 14.0. Results: A total of 7,990 (2.08%) patients with AF were registered throughout 2013 in our healthcare area (n=348,985). Mean age was 76.83+/-10.51 years and 937 (11.7%) presented with COPD. COPD patients had a higher mean CHA2DS2-VASc (4.21 vs 3.46; P=0.02) and received less beta-blocker and more digoxin therapy than those without COPD. During a mean follow-up of 707+/-103 days, 1,361 patients (17%) died. All-cause mortality was close to two fold higher in the COPD group (28.3% vs 15.5%; P<0.001). Independent predictive factors for all-cause mortality were age, heart failure, diabetes, previous thromboembolic event, dementia, COPD, and oral anticoagulation (OA). There were nonsignificant differences in thromboembolic events (1.7% vs 1.5%; P=0.7), but the rate of hemorrhagic events was significantly higher in the COPD group (3.3% vs 1.9%; P=0.004). Age, valvular AF, OA, and COPD were independent predictive factors for hemorrhagic events. In COPD patients, age, heart failure, vasculopathy, lack of OA, and lack of beta-blocker use were independent predictive factors for all-cause mortality. Conclusion: AF patients with COPD have a higher incidence of adverse events with significantly increased rates of all-cause mortality and hemorrhagic events than AF patients without COPD. However, comorbid COPD was not associated with differences in cardiovascular death or stroke rate. OA and beta-blocker treatment presented a risk reduction in mortality while digoxin use exerted a neutral effect

Probing highly obscured, self-absorbed galaxy nuclei with vibrationally excited HCN

We present high resolution (0."4) IRAM PdBI and ALMA mm and submm observations of the (ultra) luminous infrared galaxies ((U)LIRGs) IRAS17208-0014, Arp220, IC860 and Zw049.057 that reveal intense line emission from vibrationally excited ($\nu_2$=1) J=3-2 and 4-3 HCN. The emission is emerging from buried, compact (r<17-70 pc) nuclei that have very high implied mid-infrared surface brightness $>$$5\times 10^{13}$ L$_{\odot}$ kpc$^{-2}$. These nuclei are likely powered by accreting supermassive black holes (SMBHs) and/or hot (>200 K) extreme starbursts. Vibrational, $\nu_2$=1, lines of HCN are excited by intense 14 micron mid-infrared emission and are excellent probes of the dynamics, masses, and physical conditions of (U)LIRG nuclei when H$_2$ column densities exceed $10^{24}$ cm$^{-2}$. It is clear that these lines open up a new interesting avenue to gain access to the most obscured AGNs and starbursts. Vibrationally excited HCN acts as a proxy for the absorbed mid-infrared emission from the embedded nuclei, which allows for reconstruction of the intrinsic, hotter dust SED. In contrast, we show strong evidence that the ground vibrational state ($\nu$=0), J=3-2 and 4-3 rotational lines of HCN and HCO$^+$ fail to probe the highly enshrouded, compact nuclear regions owing to strong self- and continuum absorption. The HCN and HCO$^+$ line profiles are double-peaked because of the absorption and show evidence of non-circular motions - possibly in the form of in- or outflows. Detections of vibrationally excited HCN in external galaxies are so far limited to ULIRGs and early-type spiral LIRGs, and we discuss possible causes for this. We tentatively suggest that the peak of vibrationally excited HCN emission is connected to a rapid stage of nuclear growth, before the phase of strong feedback.Comment: 13 pages, 7 figures, accepted for publication in Astronomy and Astrophysic

Correlation of RECIST, Computed Tomography Morphological Response, and Pathological Regression in Hepatic Metastasis Secondary to Colorectal Cancer: The AVAMET Study.

Background: The prospective phase IV AVAMET study was undertaken to correlate response evaluation criteria in solid tumors (RECIST)-defined response rates with computed tomography-based morphological criteria (CTMC) and pathological response after liver resection of colorectal cancer metastases. Methods: Eligible patients were aged >/=18 years, with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and histologically-confirmed colon or rectal adenocarcinoma with measurable liver metastases. Preoperative treatment was bevacizumab (7.5 mg on day 1) + XELOX (oxaliplatin 130 mg/m(2), capecitabine 1000 mg/m(2) bid on days 1-14 q3w). After three cycles, response was evaluated by a multidisciplinary team. Patients who were progression-free and metastasectomy candidates received one cycle of XELOX before undergoing surgery 3-5 weeks later, followed by four cycles of bevacizumab + XELOX. Results: A total of 83 patients entered the study; 68 were eligible for RECIST, 67 for CTMC, and 51 for pathological response evaluation. Of these patients, 49% had a complete or partial RECIST response, 91% had an optimal or incomplete CTMC response, and 81% had a complete or major pathological response. CTMC response predicted 37 of 41 pathological responses versus 23 of 41 responses predicted using RECIST (p = 0.008). Kappa coefficients indicated a lack of correlation between the results of RECIST and morphological responses and between morphological and pathological response rates. Conclusion: CTMC may represent a better marker of pathological response to bevacizumab + XELOX than RECIST in patients with potentially-resectable CRC liver metastases

Geology and rural landscapes in central Spain (Guadalajara, Castilla—La Mancha)

Methods commonly used in regional geological analysis were employed to study the visual landscapes of the Sigüenza–Molina de Aragón area (Spain). Landscape data were compiled to produce a landscape map and a photograph catalogue. Lithological composition, tectonic structure and recent erosive processes are the main factors controlling the visual landscapes. Territorial properties, such as colours and agricultural capacities, are controlled by these geological characteristics. The landscape map and the photographic catalogue is the main contribution of this paper. The first level of landscape classification distinguishes zones with dominance of either flat, concave or convex areas. Other parts of the territory are, however, composed of concave and convex combinations that originate hybrid orographic structures. In a second level of classification, several subdivisions for each of these types are established

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

INTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Increased urinary markers of kidney damage in the institutionalized frail elderly due to recurrent urinary tract infections.

Objective: To characterize the impact on kidney injury of recurrent urinary tract infections (RUTI) in the frail elderly. Methods: Prospective observational study in 200 frail elderly subjects for 1 year. Groups: GA (n = 100): subjects without RUTI, GB (n = 100): subjects with RUTI. Variables: age, concomitant diseases, glomerular filtration rate (GFR), urine neutrophil gelatinase-associated lipocalin (NGAL) at the beginning (NGAL-1) and end (NGAL-2) of the study, urine N-acetyl glucosaminidase (NAG) at the beginning (NAG-1) and the end (NAG-2) of the study, urine transforming growth factor-beta 1 (TGFbeta-1). Descriptive statistics, Mann-Whitney test, Chi-squared test, Fisher's exact test, and multivariate analysis were used. Results: Mean age was 84.33 (65-99) years old, with no difference between GA and GB. Mean NGAL-1 was 1.29 ng/ml (0.04-8). There was lower in GA than in GB. Mean NGAL-2 was 1.41 ng/ml (0.02-9.22). NGAL-2 was lower in GA than in GB. Mean NAG-1 was 0.38 UU.II/ml (0.01-2.63. NAG-1 in GA was lower than in GB. Mean NAG-2 was 0.44 UU.II/ml (0-3.41). NAG-2 was lower in GA compared with GB. Mean TGFbeta-1 was 23.43 pg/ml (0.02-103.76). TGFbeta-1 was lower in GA than GB. There were no differences in the presence of secondary diagnoses between GA and GB. NAG-2 and NGAL-1 were the most determining factors of renal function; in GA it was NGAL-2, followed by NAG-1; in GB it was NGAL-1, followed by NAG-2. Conclusion: Frail elderly with RUTI have higher urinary levels of renal injury markers, specifically NGAL, NAG, and TGFbeta-1, chronically in periods between urinary tract infection (UTI). Urinary markers of renal injury, specifically NGAL, NAG, and TGFbeta-1, identify early deterioration of renal function, compared with serum creatinine, or albuminuria, in frail elderly with recurrent urinary infections

Employment generation by small firms in Spain

Despite the relevance in terms of policy, we still know little in Spain about where and by whom jobs are created, and how that is affecting the size distribution of firms. The main innovation of this paper is to use a rich database that overcomes the problems encountered by other firm-level studies to shed some light on the employment generation of small firms in Spain. We find that small firms contribute to employment disproportionately across all sectors of the economy although the difference between their employment and job creation share is largest in the manufacturing sector. The job creators in that sector are both new and established firms whereas only new small firms outperform their larger counterparts in the service sector. The large annual job creation of the small firm size class is shifting the firm size distribution towards the very small production units, although not uniformly across industries of different technology intensit