Studying the complex expression dependences between sets of coexpressed genes

Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to studge the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between the skeletons of these sets, where this skeleton represents the coexpressed genes with a well-defined nonlinear expression relationship with the skeleton of the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from the skeleton of the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiment

Expansion of serotype coverage in the universal pediatric vaccination calendar: Short-term effects on age- and serotype-dependent incidence of invasive pneumococcal clinical presentations in Madrid, Spain

In Madrid, Spain, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the pediatric universal vaccination calendar in June 2010. A prospective clinical surveillance that included all children hospitalized with culture- and/or PCR-confirmed invasive pneumococcal disease (IPD) was performed in all Madrid hospitals. The incidence rates (IRs) (defined as the number of cases/100,000 inhabitants aged<15 years) in the PCV7 (May 2007 to April 2010) versus PCV13 (May 2011 to April 2012) periods were compared. There were 499 cases in the PCV7 period and 79 cases in the PCV13 period. Globally, the IR significantly decreased from 17.09 (PCV7 period) to 7.70 (PCV13 period), with significant decreases (PCV7 versus PCV13 periods) in all age groups for bacteremic pneumonia (5.51 versus 1.56), parapneumonic pneumococcal empyema (PPE) (5.72 versus 3.12), and meningitis (2.16 versus 0.97). In the PCV13 period, significant reductions (the IR in the PCV7 period versus the IR in the PCV13 period) were found in IPDs caused by PCV13 serotypes (13.49 versus 4.38), and specifically by serotypes 1 (globally [4.79 versus 2.53], for bacteremic pneumonia [2.23 versus 0.97], and for PPE [2.26 versus 1.17]), serotype 5 (globally [1.88 versus 0.00], for bacteremic pneumonia [0.89 versus 0.00], and for PPE [0.55 versus 0.00]), and serotype 19A (globally [3.77 versus 0.49], for bacteremic pneumonia [0.72 versus 0.00], for PPE [0.89 versus 0.00], and for meningitis [0.62 versus 0.00]). IPDs caused by non- PCV13 serotypes did not increase (IR, 3.60 in the PCV7 period versus 3.31 in the PCV13 period), regardless of age or presentation. No IPDs caused by the PCV13 serotypes were found in children who received 3 doses of PCV13. The number of hospitalization days and sanitary costs were significantly lower in the PCV13 period. The switch from PCV7 to PCV13 in the universal pediatric vaccination calendar provided sanitary and economical benefits without a replacement by non-PCV13 serotypesThis work was supported in part by an unrestricted grant from Pfizer S.L.U., Madrid, Spain. J.P. and J.R.-C. have received travel fees from Pfizer for attending and/or speaking at symposiums and congresses. C.M. is an employee of Pfizer S.L.U., Madrid, Spain

Comparison Between two Surgical Techniques for Increasing Vocal Pitch by Endoscopic Shortening of the Vocal Folds

Objective: To compare two surgical techniques, the Wendler glottoplasty (GP) and its modification, the vocal fold shortening, and retrodisplacement of the anterior commissure (VFSRAC) associated with laser assisted voice adjustment (LAVA) cordotomy, used to feminize the voice of transgender women by increasing the fundamental frequency (F0). Methods: A retrospective study of 22 trans-women (20-62 years-old) was carried out. 12 of them were treated with GP and 10 with the VFSRAC+LAVA technique. They were evaluated before surgery and 6 months after surgery and the postoperative speech therapy. Laryngostroboscopy examination, F0 measurements, Transgender Woman Voice Questionnaire (TWVQ) assessment and the perceptual assessment using a visual analog scale (PA-VAS) were obtained from all patients. Results: Laryngostroboscopic findings showed normal vocal folds before surgery and a shortening of the vocal folds, due to the anterior glottic synechia, after surgery. Significant increases of F0 were found in both groups but they were higher in the VFSRAC+LAVA group (47.75Hz in GP group vs 69.70Hz in VFSRAC+LAVA group). TWVQ scores showed a significant decrease in both groups although the difference was greater in the VFSRAC+LAVA group. Similarly, PA-VAS scores lowered significantly in both groups but VFSRAC+LAVA group presented the biggest decreases. Conclusion: Both surgical techniques produce the shortening of the vocal folds through an endoscopic approach and result in voices with higher vocal pitch. Of the two techniques presented, the VFSRAC+LAVA produces better results although when compared with previous studies it seems that the LAVA technique may not significantly contribute to the postoperative results. So, the VFSRAC technique followed by postoperative speech therapy could be recommended for trans-women who wish to feminize their voice.Depto. de Inmunología, Oftalmología y ORLUnidad Docente de Inmunología, Oftalmología y ORLFac. de MedicinaFac. de Óptica y OptometríaTRUEinpres

Relationship between serotypes, age, and clinical presentation of invasive pneumococcal disease in Madrid, Spain, after introduction of the 7-valent pneumococcal conjugate vaccine into the vaccination calendar

To assess invasive pneumococcal disease (IPD) clinical presentations and relationships with age and serotype in hospitalized children (<15 years) after PCV7 implementation in Madrid, Spain, a prospective 2-year (May 2007 to April 2009) laboratory-confirmed (culture and/or PCR) IPD surveillance study was performed (22 hospitals). All isolates (for serotyping) and culture-negative pleural/cerebrospinal fluids were sent to the reference laboratory for pneumolysin (ply) and autolysin (lyt) gene PCR analysis. A total of 330 IPDs were identified: 263 (79.7%) confirmed by culture and 67 (20.3%) confirmed by PCR. IPD distribution by age (months) was as follows: 23.6% (<12), 15.8% (12 to 23), 15.5% (24 to 35), 22.4% (36 to 59), and 22.7% (>59). Distribution by clinical presentation was as follows: 34.5% bacteremic pneumonia, 30.3% pediatric parapneumonic empyema (PPE), 13.6% meningitis, 13.3% primary bacteremia, and 8.2% others. Meningitis and primary bacteremia were the most frequent IPDs in children <12 months old, and bacteremic pneumonia and PPE were most frequent in those >36 months old. Frequencies of IPD-associated serotypes were as follows: 1, 26.1%; 19A, 18.8%; 5, 15.5%; 7F, 8.5%; 3, 3.9%; nontypeable/ other 30 serotypes, 27.3%. Serotype 1 was linked to respiratory-associated IPD (38.6% in bacteremic pneumonia and 38.0% in PPE) and children of >36 months (51.4% for 36 to 59 months and 40.0% for >59 months), while serotype 19A was linked to nonrespiratory IPDs (31.1% in meningitis, 27.3% in primary bacteremia, and 51.9% in others) and children of <24 months (35.9% for children of <12 months and 36.5% for those 12 to 23 months old), with high nonsusceptibility rates for penicillin, cefotaxime, and erythromycin. After PCV7 implementation, non-PCV7 serotypes caused 95.5% of IPDs. The new 13-valent conjugate vaccine would provide 79.1% coverage of serotypes responsible for IPDs in this series

Análisis económico y prospectiva del sector de la moda en Sevilla

El trabajo se estructura en cinco capítulos, en los que se va aproximando progresivamente el contexto geográfico del trabajo, desde el ámbito internacional hasta la situación del sector en la provincia. De este modo, en el primer capítulo se ofrece una visión del entorno internacional en el que se localiza el sector de la Moda, amenazado por la liberalización internacional y la competitividad en costes de mercado asiático. En el segundo, descendemos a nivel nacional para analizar la estructura y características del sector textil en las fases de producción y comercializaron. Complementamos este capítulo con las experiencias regionales de Galicia, Cataluña, País Vasco y, por supuesto, Andalucía, cuyo análisis y recomendaciones se recogen enel tercer capítulo. En el capítulo cuarto se cuantifica, a través de la metodología de impacto económico, el valor añadido generado en la provincia de Sevilla por la Industria de la Moda, desagregando estos impactos por sectores, entre los que destacan el de los Sastres Artesanos y el de la Moda Novias. Mención aparte, en este mismo capítulo, merece el estudio de la Moda Flamenca y su aportación a la economía provincial. Finalmente, en el capítulo quinto se recogen las conclusiones del estudio previo, reflejando la potencialidad del sector de la Moda, junto con sus debilidades, y se ofrecen, para el debate, una batería de posibles estrategias para su futuro

Hallux Limitus Influence on Plantar Pressure Variations during the Gait Cycle: A Case-Control Study

´[Abstract] Background: Hallux limitus is a common foot disorder whose incidence has increased in the school-age population. Hallux limitus is characterized by musculoskeletal alteration that involves the metatarsophalangeal joint causing structural disorders in different anatomical areas of the locomotor system, affecting gait patterns. The aim of this study was to analyze dynamic plantar pressures in a school-aged population both with functional hallux and without. Methods: A full sample of 100 subjects (50 male and 50 female) 7 to 12 years old was included. The subjects were identified in two groups: the case group (50 subjects characterized as having hallux limitus, 22 male and 28 female) and control group (50 subjects characterized as not having hallux limitus, 28 male and 22 female). Measurements were obtained while subjects walked barefoot in a relaxed manner along a baropodometric platform. The hallux limitus test was realized in a seated position to sort subjects out into an established study group. The variables checked in the research were the surface area supported by each lower limb, the maximum peak pressure of each lower limb, the maximum mean pressure of each lower limb, the body weight on the hallux of each foot, the body weight on the first metatarsal head of each foot, the body weight at the second metatarsal head of each foot, the body weight at the third and fourth metatarsal head of each foot, the body weight at the head of the fifth metatarsal of each foot, the body weight at the midfoot of each foot, and the body weight at the heel of each foot. Results: Non-significant results were obtained in the variable of pressure peaks between both study groups; the highest pressures were found in the hallux with a p-value of 0.127 and in the first metatarsal head with a p-value 0.354 in subjects with hallux limitus. A non-significant result with a p-value of 0.156 was obtained at the second metatarsal head in healthy subjects. However, significant results were observed for third and fourth metatarsal head pressure in healthy subjects with a p-value of 0.031 and regarding rearfoot pressure in subjects with functional hallux limitus with a p-value of 0.023. Conclusions: School-age subjects with hallux limitus during gait exhibit more average peak plantar pressure in the heel and less peak average plantar pressure in the third and fourth metatarsal head as compared to healthy children aged between 7 and 12 years old

ECAMulticapa: Effectiveness of double-layered compression therapy for healing venous ulcers in primary care: a Study Protocol

Background: Chronic venous insufficiency, in its final stage can cause venous ulcers. Venous ulcers have a prevalence of 0.5 % to 0.8 % in the general population, and increases starting at 60 years of age. This condition often causes increased dependency in affected individuals, as well as a perceived reduced quality of life and family overload. Local Treating chronic venous ulcers has 2 components: topically healing the ulcer and controlling the venous insufficiency. There is evidence that compressive therapy favours the healing process of venous ulcers. The studies we have found suggest that the use of multilayer bandage systems is more effective than the use of bandages with a single component, these are mostly using in Spain. Multilayer compression bandages with 2 layers are equally effective in the healing process of chronic venous ulcers as 4-layer bandages and are better tolerated and preferenced by patients. More studies are needed to specifically compare the 2-layer bandages systems in the settings where these patients are usually treated. Method/design: Randomised, controlled, parallel, multicentre clinical trial, with 12 weeks of follow-up and blind evaluation of the response variable. The objective is to assess the efficacy of multilayer compression bandages (2 layers) compared with crepe bandages, based on the incidence of healed venous ulcers in individuals treated in primary care nursing consultations, at 12 weeks of follow-up. The study will include 216 individuals (108 per branch) with venous ulcers treated in primary care nursing consultations. The primary endpoint is complete healing at 12 weeks of follow-up. The secondary endpoints are the degree of healing (Resvech.2), quality of life (CCVUQ-e), adverse reactions related to the healing process. Prognosis and demographic variables are also recorder. Effectiveness analysis using Kaplan-Meier curves, a log-rank test and a Cox regression analysis. The analysis was performed by intention to treat. Discussion: The study results can contribute to improving the care and quality of life of patients with venous ulcers, decreasing healing times and healthcare expenditure and contributing to the consistent treatment of these lesions. Trial registration: This study has been recorded in the Clinical Trials.gov site with the code NCT02364921. 17 February 2015.This study was funded by PN of I + D + I 2013–2016 and the ISCIII – Subdirección General de Evaluación y Fomento de la Investigación and FEDER funds (PI13/01975). Ministerio de Economia y Competitividad

Retinal Molecular Changes Are Associated with Neuroinflammation and Loss of RGCs in an Experimental Model of Glaucoma

Signaling mediated by cytokines and chemokines is involved in glaucoma-associated neuroinflammation and in the damage of retinal ganglion cells (RGCs). Using multiplexed immunoassay and immunohistochemical techniques in a glaucoma mouse model at different time points after ocular hypertension (OHT), we analyzed (i) the expression of pro-inflammatory cytokines, anti-inflammatory cytokines, BDNF, VEGF, and fractalkine; and (ii) the number of Brn3a+ RGCs. In OHT eyes, there was an upregulation of (i) IFN-γ at days 3, 5, and 15; (ii) IL-4 at days 1, 3, 5, and 7 and IL-10 at days 3 and 5 (coinciding with downregulation of IL1-β at days 1, 5, and 7); (iii) IL-6 at days 1, 3, and 5; (iv) fractalkine and VEGF at day 1; and (v) BDNF at days 1, 3, 7, and 15. In contralateral eyes, there were (i) an upregulation of IL-1β at days 1 and 3 and a downregulation at day 7, coinciding with the downregulation of IL4 at days 3 and 5 and the upregulation at day 7; (ii) an upregulation of IL-6 at days 1, 5, and 7 and a downregulation at 15 days; (iii) an upregulation of IL-10 at days 3 and 7; and (iv) an upregulation of IL-17 at day 15. In OHT eyes, there was a reduction in the Brn3a+ RGCs number at days 3, 5, 7, and 15. OHT changes cytokine levels in both OHT and contralateral eyes at different time points after OHT induction, confirming the immune system involvement in glaucomatous neurodegeneration

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio