Transanal Hemorrhoidal Dearterialization With Mucopexy Versus Vessel-Sealing Device Hemorrhoidectomy for Grade III to IV Hemorrhoids: Long-term Outcomes From the THDLIGA Randomized Controlled Trial.

BACKGROUND: Both transanal hemorrhoidal dearterialization and vessel-sealing device hemorrhoidectomy are safe for grade III to IV hemorrhoid treatment. Whether one of them is superior regarding long-term results remains unclear. OBJECTIVE: To compare long-term results after transanal hemorrhoidal dearterialization and vessel-sealing device hemorrhoidectomy. DESIGN: Multicenter randomized controlled trial. SETTINGS: This study was conducted at 6 centers. PATIENTS: Patients ≥18 years of age with grade III to IV hemorrhoids were included in the study. INTERVENTIONS: Patients were randomly assigned to transanal hemorrhoidal dearterialization (n = 39) or vessel-sealing device hemorrhoidectomy (n = 41). MAIN OUTCOME MEASURES: The primary outcome was hemorrhoid symptom recurrence assessed by a specific questionnaire 2 years postoperatively. Secondary outcomes included long-term complications, reoperations, fecal continence, and patient satisfaction and quality of life. RESULTS: Five of the 80 patients included in the study were lost to follow-up. Thirty-six patients randomly assigned to transanal hemorrhoidal dearterialization and 39 patients randomly assigned to vessel-sealing device hemorrhoidectomy were included in the long-term analysis. The differences between mean baseline and mean 2-year score in the 2 groups were similar (-11.0, SD 3.8 vs -12.5, SD 3.6; p = 0.080). Three patients in the transanal hemorrhoidal dearterialization group underwent supplementary procedures for hemorrhoid symptoms, compared with none in the vessel-sealing device hemorrhoidectomy group ( p = 0.106). Four patients in the vessel-sealing hemorrhoidectomy group and none in the transanal hemorrhoidal dearterialization group experienced chronic opened wound ( p = 0.116). LIMITATIONS: Lack of stratification for hemorrhoid grade and power calculation based on the main outcome trial but not on the end point of this long-term study. CONCLUSIONS: Transanal hemorrhoidal dearterialization with mucopexy is associated with hemorrhoid symptom recurrence similar to vessel-sealing device hemorrhoidectomy at 2 years. See Video Abstract at http://links.lww.com/DCR/B933 . REGISTRATION: Clinicaltrials.gov ; ID: NCT02654249. DESARTERIALIZACIN HEMORROIDAL TRANSANAL CON MUCOPEXIA VERSUS HEMORROIDECTOMA CON DISPOSITIVO DE SELLADO DE VASOS PARA HEMORROIDES DE GRADO IIIIV RESULTADOS A LARGO PLAZO DEL ENSAYO CLNICO ALEATORIZADO THDLIGARCT: ANTECEDENTES:Tanto la desarterialización hemorroidal transanal como la hemorroidectomía con dispositivo de sellado de vasos son seguras y bien toleradas para el tratamiento de las hemorroides de grado III-IV. La primera se asocia con una necesidad más breve de analgesia posoperatoria que la hemorroidectomía con dispositivo de sellado de vasos. No está claro si uno de ellos es superior con respecto a los resultados a largo plazo.OBJETIVO:El objetivo fue comparar los resultados a largo plazo después de la desarterialización hemorroidal transanal y la hemorroidectomía con dispositivo de sellado de vasos.DISEÑO:Se realizó un ensayo clínico aleatorizado multicéntrico.AJUSTE:Este estudio se realizó en 6 centros.PACIENTES:Se incluyeron en el estudio pacientes de ≥18 años con hemorroides de grado III-IV.INTERVENCIONES:Los pacientes fueron asignados al azar a desarterialización hemorroidal transanal (n = 39) o hemorroidectomía con dispositivo de sellado de vasos (n = 41).PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la recurrencia de los síntomas de hemorroides evaluada mediante un cuestionario específico 2 años después de la operación. Los resultados secundarios incluyeron complicaciones a largo plazo, reoperaciones, continencia fecal, satisfacción del paciente y calidad de vida.RESULTADOS:Cinco de los 80 pacientes incluidos en el estudio se perdieron durante el seguimiento. En el análisis a largo plazo se incluyeron 36 pacientes aleatorizados a desarterialización hemorroidal transanal y 39 aleatorizados a hemorroidectomía con dispositivo de sellado de vasos. Las diferencias entre la puntuación inicial media y la puntuación media a los 2 años en los dos grupos fueron similares (-11,0, DE 3,8 frente a -12,5, DE 3,6; p = 0,080). Tres pacientes en el grupo de desarterialización hemorroidal transanal se sometieron a procedimientos complementarios por síntomas de hemorroides, en comparación con ninguno en el grupo de hemorroidectomía con dispositivo de sellado de vasos (p = 0,106). Cuatro pacientes en el grupo de hemorroidectomía con sellado de vasos y ninguno en el grupo de desarterialización hemorroidal transanal experimentaron herida abierta crónica (p = 0,116). No se encontraron diferencias en cuanto a continencia fecal (p = 0,657), satisfacción del paciente (p = 0,483) y calidad de vida.LIMITACIONES:No hay estratificación para el grado de hemorroides ni el cálculo del poder basado en el resultado principal del ensayo, pero no en el criterio de valoración de este estudio a largo plazo.CONCLUSIONES:La desarterialización hemorroidal transanal con mucopexia se asocia con una recurrencia de síntomas de hemorroides similar a la hemorroidectomía con dispositivo de sellado de vasos a los dos años. See Video Abstract at http://links.lww.com/DCR/B933 . (Traducción- Dr. Francisco M. Abarca-Rendon )REGISTRO DE PRUEBA:Clinicaltrials.gov (NCT02654249).

Telomere Length as a New Risk Marker of Early-Onset Colorectal Cancer.

Early-onset colorectal cancer (EOCRC; age younger than 50 years) incidence has been steadily increasing in recent decades worldwide. The need for new biomarkers for EOCRC prevention strategies is undeniable. In this study, we aimed to explore whether an aging factor, such as telomere length (TL), could be a useful tool in EOCRC screening. The absolute leukocyte TL from 87 microsatellite stable EOCRC patients and 109 healthy controls (HC) with the same range of age, was quantified by Real Time Quantitative PCR (RT-qPCR). Then, leukocyte whole-exome sequencing (WES) was performed to study the status of the genes involved in TL maintenance (hTERT, TERC, DKC1, TERF1, TERF2, TERF2IP, TINF2, ACD, and POT1) in 70 sporadic EOCRC cases from the original cohort. We observed that TL was significantly shorter in EOCRC patients than in healthy individuals (EOCRC mean: 122 kb vs. HC mean: 296 kb; p < 0.001), suggesting that telomeric shortening could be associated with EOCRC susceptibility. In addition, we found a significant association between several SNPs of hTERT (rs79662648), POT1 (rs76436625, rs10263573, rs3815221, rs7794637, rs7784168, rs4383910, and rs7782354), TERF2 (rs251796 and rs344152214), and TERF2IP (rs7205764) genes and the risk of developing EOCRC. We consider that the measurement of germline TL and the status analysis of telomere maintenance related genes polymorphisms at early ages could be non-invasive methods that could facilitate the early identification of individuals at risk of developing EOCRC.

Metabolomics analysis of type 2 diabetes remission identifies 12 metabolites with predictive capacity: a CORDIOPREV clinical trial study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is one of the most widely spread diseases, affecting around 90% of the patients with diabetes. Metabolomics has proven useful in diabetes research discovering new biomarkers to assist in therapeutical studies and elucidating pathways of interest. However, this technique has not yet been applied to a cohort of patients that have remitted from T2DM. METHODS: All patients with a newly diagnosed T2DM at baseline (n = 190) were included. An untargeted metabolomics approach was employed to identify metabolic differences between individuals who remitted (RE), and those who did not (non-RE) from T2DM, during a 5-year study of dietary intervention. The biostatistical pipeline consisted of an orthogonal projection on the latent structure discriminant analysis (O-PLS DA), a generalized linear model (GLM), a receiver operating characteristic (ROC), a DeLong test, a Cox regression, and pathway analyses. RESULTS: The model identified a significant increase in 12 metabolites in the non-RE group compared to the RE group. Cox proportional hazard models, calculated using these 12 metabolites, showed that patients in the high-score tercile had significantly (p-value < 0.001) higher remission probabilities (Hazard Ratio, HR, high versus low = 2.70) than those in the lowest tercile. The predictive power of these metabolites was further studied using GLMs and ROCs. The area under the curve (AUC) of the clinical variables alone is 0.61, but this increases up to 0.72 if the 12 metabolites are considered. A DeLong test shows that this difference is statistically significant (p-value = 0.01). CONCLUSIONS: Our study identified 12 endogenous metabolites with the potential to predict T2DM remission following a dietary intervention. These metabolites, combined with clinical variables, can be used to provide, in clinical practice, a more precise therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00924937.

Familial component of early-onset colorectal cancer: opportunity for prevention.

BACKGROUND: Individuals with a non-syndromic family history of colorectal cancer are known to have an increased risk. There is an opportunity to prevent early-onset colorectal cancer (age less than 50 years) (EOCRC) in this population. The aim was to explore the proportion of EOCRC that is preventable due to family history of colorectal cancer. METHODS: This was a retrospective multicentre European study of patients with non-hereditary EOCRC. The impact of the European Society of Gastrointestinal Endoscopy (ESGE), U.S. Multi-Society Task Force (USMSTF), and National Comprehensive Cancer Network (NCCN) guidelines on prevention and early diagnosis was compared. Colorectal cancer was defined as potentially preventable if surveillance colonoscopy would have been performed at least 5 years before the age of diagnosis of colorectal cancer, and diagnosed early if colonoscopy was undertaken between 1 and 4 years before the diagnosis. RESULTS: Some 903 patients with EOCRC were included. Criteria for familial colorectal cancer risk in ESGE, USMSTF, and NCCN guidelines were met in 6.3, 9.4, and 30.4 per cent of patients respectively. Based on ESGE, USMSTF, and NCCN guidelines, colorectal cancer could potentially have been prevented in 41, 55, and 30.3 per cent of patients, and diagnosed earlier in 11, 14, and 21.1 per cent respectively. In ESGE guidelines, if surveillance had started 10 years before the youngest relative, there would be a significant increase in prevention (41 versus 55 per cent; P = 0.010). CONCLUSION: ESGE, USMSTF, and NCCN criteria for familial colorectal cancer were met in 6.3, 9.4, and 30.4 per cent of patients with EOCRC respectively. In these patients, early detection and/or prevention could be achieved in 52, 70, and 51.4 per cent respectively. Early and accurate identification of familial colorectal cancer risk and increase in the uptake of early colonoscopy are key to decreasing familial EOCRC.

The Applicability of Shear Wave Elastography to Assess Myotendinous Stiffness of Lower Limbs during an Incremental Isometric Strength Test.

The aim of the study was to describe the applicability of shear wave elastography to assess muscular and tendinous stiffness of the lower limbs during an incremental isometric strength test and to differentiate the stiffness evolution between superficial and deep muscle regions. Dominant rectus femoris and patellar tendons of 30 physically active people (28.3 ± 9.2 years, 173.2 ± 7.7 cm, 76.2 ± 12.6 kg) were measured in different isometric strength conditions (relaxed muscle, and at 10%, 20%, 30%, 40%, 50% and 60% of maximal voluntary contraction (MVC)). The percentage of success was >85% at all muscle contraction intensities for rectus femoris muscles but only in a relaxed condition for patellar tendons. Rectus femoris stiffness significantly increased compared to the relaxed condition from 30% to 60% MVC (p ≤ 0.011) in superficial muscle regions, and from 10% to 60% MVC (p ≤ 0.002) in deep muscle regions. Deep muscle regions showed higher stiffness values than superficial muscle regions at 30% MVC (51.46 ± 38.17 vs. 31.83 ± 17.05 kPa; p = 0.019), 40% MVC (75.21 ± 42.27 vs. 51.25 ± 28.90 kPa; p = 0.018), 50% MCV (85.34 ± 45.05 vs. 61.16 ± 37.03 kPa; p = 0.034) and 60% MVC (109.29 ± 40.04 vs. 76.67 ± 36.07 kPa; p = 0.002). Rectus femoris stiffness increased during the incremental isometric contraction test, and inter-region differences were found at 30% MVC.

Effects of Eccentric Single-Leg Decline Squat Training Performed With Different Execution Times on Maximal Strength and Muscle Contraction Properties of the Knee Extensor Muscles.

ABSTRACT: Abián-Vicén, J, Martínez, F, Jiménez, F, and Abián, P. Effects of eccentric single-leg decline squat training performed with different execution times on maximal strength and muscle contraction properties of the knee extensor muscles. J Strength Cond Res 36(11): 3040-3047, 2022-The eccentric phase of the single-leg decline squat (SLDS e ) has been described as a method to maximally load the knee extensor and has been used as an easy and effective rehabilitation exercise for patellar tendinopathy. The purpose of this study was to examine the impact of 6-week SLDS e training with 2 technical execution times on changes related to strength and muscle contractile properties. Thirty-six healthy volunteers were randomly divided into 3 groups: a control group (CG, n = 13, no training), a slow training group ( n = 11, SLDS e in 6 seconds), and a fast training group ( n = 12, SLDS e in 3 seconds). Subjects completed a 6-week SLDS e training program (80% of eccentric one repetation maximum [1RM]) 3 days a week. Pre, post, and 6-week follow-up of maximal dynamic and isometric strength and muscle contractile properties were assessed. After 6 weeks, training maximal loads showed a significant increase ( p < 0.05) in 1RM of the SLDS e (∼92-95%), the concentric peak torque at 180°·s -1 (∼38%) and 60°·s -1 (∼25%), and the extension isometric peak torque (∼12%), with no differences between both experimental groups. Moreover, a decrease ( p < 0.05) was found in the contraction time of the vastus medialis (VM) and the response time of the 3 analyzed quadriceps muscles. After the 6-week detraining period, there was a decrease in strength in all tests and in both experimental groups (1RM = 28-37%, isometric and isokinetic tests = 7-17%) and all contractile properties returned to baseline, except for the response time of the vastus lateralis in the fast training group and the contraction time of the VM in the STG. In conclusion, the SLDS e training protocol produced significant increases in muscle strength, showing important neuromuscular changes regardless of the technical execution time. It was also found that the training reduced the response and contraction time of the knee extensor musculature.

Fungal and Bacterial Biodeterioration of Outdoor Canvas Paintings: The Case of the Cloisters of Quito, Ecuador.

The historic center of Quito, Ecuador, was one of the first World Cultural Heritage Sites declared by UNESCO in 1978. There are numerous religious buildings built during the Spanish colonial period reflecting the cultural heritage in this area. Between them, the cloisters of San Francisco, Santo Domingo, and Santa Clara should be highlighted. The specific problems of conservation of the outdoor canvas paintings are not well known at the moment. The objective of this paper is to achieve a conservation study of the canvas paintings exhibited in these three cloisters of the historic center of Quito in order to identify the microbial agents and the main bioclimatic parameters of deterioration. For this, a study of the state of conservation of five canvas paintings has been carried out, as well as a sampling and identification of the main microorganisms present on the obverse and reverse of the works, employing diverse techniques, traditional and biomolecular ones. An analysis of climatic conditions has also been achieved in the cloister of San Francisco. The results of the study indicate that the exhibition conditions in the cloisters are really problematic for the conservation of paintings. Important biodeteriorating agents have been isolated, including fungi and bacteria species belonging, among others, to the genera Bacillus, Penicillium, Alternaria, Mucor, and Aspergillus. We have also researched its relationship with the deterioration state of the artworks and the exhibition conditions in each case, proposing guidelines for the proper conservation of this important World Cultural Heritage.

Subcutaneous Allergen-Specific Immunotherapy Is Safe in Pediatric Patients with Allergic Rhinitis.

INTRODUCTION: Subcutaneous allergen-specific immunotherapy (SCIT) is one of the main cornerstones in the treatment of allergic rhinitis in pediatric patients. It has demonstrated symptoms and quality of life improvement, but it is not exempt from adverse reactions (ADVrs). Nevertheless, there are a few reports that have evaluated their safety. Our objective was to evaluate the ADVr to SCIT in pediatric patients. METHODS: We reviewed 786 clinical records with SCIT from 2005 to 2018, comparing the clinical characteristics of patients with ADVrs with SCIT versus a group of a similar number of patients who completed SCIT (control group, CG). The analysis of ADVrs was according to the World Allergy Organization (WAO) 2010 grading system by frequency analysis, survival curve, and log rank. RESULTS: Of 786 patients, 106 (13.4%) presented ADVrs, and the patients with ADVr had sensitivity and immunotherapy with at least 2 allergens versus CG p < 0.001, containing a combination of standardized and nonstandardized allergens (p = 0.003). The ADVrs were in the buildup phase (p < 0.001). The survival curve showed that 50% had some reaction at 12 weeks of SCIT. The most frequent ADVr was grade 1 in 73/106 patients (68.8%) and grade 2 in 33/106 (31.1%). The log-rank analysis between the grades of the WAO grading system showed a statistically significant difference (p = 0.02). CONCLUSIONS: The SCIT is safe in pediatric patients. The ADVrs are infrequent, grade 1 being the most reported; however, at >12 weeks, the risk of ADVrs that involve 2 organs systems increases.

Objective Assessment of Regional Stiffness in Vastus Lateralis with Different Measurement Methods: A Reliability Study.

The objective of this study was to evaluate the reliability of four methods of assessing vastus lateralis (VL) stiffness, and to describe the influence of structural characteristics on them. The stiffness of the dominant lower-limb's VL was evaluated in 53 healthy participants (28.4 ± 9.1 years) with shear wave elastography (SWE), strain elastography (SE), myotonometry and tensiomyography (TMG). The SWE, SE and myotonometry were performed at 50%, and TMG was assessed at 30%, of the length from the upper pole of the patella to the greater trochanter. The thickness of the VL, adipose tissue and superficial connective tissue was also measured with ultrasound. Three repeated measurements were acquired to assess reliability, using intraclass correlation coefficients (ICC). Pearson's correlation coefficients were calculated to determine the relationships between methodologic assessments and between structural characteristics and stiffness assessments of the VL. Myotonometry (ICC = 0.93; 95%-CI = 0.89,0.96) and TMG (ICC = 0.89; 95%-CI = 0.82,0.94) showed excellent inter-day reliability whereas with SWE (ICC = 0.62; 95%-CI = 0.41,0.77) and SE (ICC = 0.71; 95%-CI = 0.57,0.81) reliability was moderate. Significant correlations were found between myotonometry and VL thickness (r = 0.361; p = 0.008), adipose tissue thickness (r = -0.459; p = 0.001) and superficial connective tissue thickness (r = 0.340; p = 0.013). Myotonometry and TMG showed the best reliability values, although myotonometry stiffness values were influenced by the structural variables of the supra-adjacent tissue.

How will climate change impact fossorial lizard species? Two examples in the Baja California Peninsula.

Global climate change and the associated erosion of habitat suitability are pervasive threats to biodiversity. It is critical to identify specific stressors to assess a species vulnerability to extinction, especially in species with distinctive natural histories. Here, we present a combination of field, laboratory, and modeling approaches to evaluate the potential consequences of climate change on two endemic, fossorial lizards species (Anniella geronimensis and Bipes biporus) from Baja California, Mexico. We also include soil type in our models to refine the suitable areas using our mechanistic models. Results suggest that both species are at high risk of extinction by global climate change based on the thermal habitat suitability. The forecast for species persistence is most grave under the RCP8.5 scenario. On the one hand, suitable habitat for A. geronimensis diminishes at its southern distribution, but potential suitable expands towards the north. On the other hand, the suitable habitat for B. biporus will contract significantly with a concomitant reduction in its potential distribution. Because both species have low mobility and are restricted to low elevation, the potential for elevational and latitudinal dispersal to mitigate extinction risk along the Baja California Peninsula is unlikely. In addition each species has specialized thermal requirements (i.e., stenothermic) and soil type preferences to which they are adapted. Our ecophysiological models in combination with the type of soil are fundamental in developing conservation strategies.

Influence of Badminton Practice on Age-Related Changes in Patellar and Achilles Tendons.

Regular sport practice could prevent age-related changes in tendinous tissues. The purpose of the study was to investigate the effect of regular badminton practice on patellar and Achilles tendon mechanical properties in senior competitive badminton players (>35 years old) and to compare the results with physically active people matched by age. One hundred ninety-two badminton players and 193 physically active people were divided by age into four groups, between 35 and 44 (U45), between 45 and 54 (U55), between 55 and 64 (U65), and over 65 (O65) years old. A LogiqS8 transducer in elastography mode and a MyotonPRO myotonometer were used to assess patellar and Achilles mechanical properties. Achilles tendon stiffness was higher in the control group than the badminton players for the U45, U55, and O65 age groups (p < .01). Also, the elastography index was higher in the control group than the badminton players for the U45, U55, U65, and O65 age groups (p < .05). In conclusion, regular badminton practice could prevent the decline in mechanical properties of the patellar and Achilles tendons.

Short-term Outcomes of Transanal Hemorrhoidal Dearterialization With Mucopexy Versus Vessel-Sealing Device Hemorrhoidectomy for Grade III to IV Hemorrhoids: A Prospective Randomized Multicenter Trial.

BACKGROUND: Transanal hemorrhoidal dearterialization with mucopexy and vessel-sealing device hemorrhoidectomy seem to reduce postoperative pain compared with classic excisional hemorrhoidectomy, but whether one of them is superior remains unclear. OBJECTIVE: We compared transanal hemorrhoidal dearterialization with mucopexy and vessel-sealing device hemorrhoidectomy. DESIGN: This was a multicenter, randomized controlled trial. SETTING: The study was conducted at 6 Spanish centers. PATIENTS: Patients aged ≥18 years with grade III to IV hemorrhoids were included. INTERVENTIONS: Patients were randomly assigned to transanal hemorrhoidal dearterialization with mucopexy (n = 39) or vessel-sealing device hemorrhoidectomy (n = 41). MAIN OUTCOME MEASURES: Primary outcome was the mean postoperative number of days in which patients needed nonsteroidal anti-inflammatory drugs. Secondary outcomes were postoperative pain, 30-day morbidity, patient satisfaction, Vaizey score, hemorrhoid symptoms score, return to work, and quality of life. RESULTS: More patients were still taking analgesia in the vessel-sealing device hemorrhoidectomy group during the second postoperative week compared with the transanal hemorrhoidal dearterialization with mucopexy group (87.8% vs 53.8%; p = 0.002). For the transanal hemorrhoidal dearterialization with mucopexy group, analgesia consumption continued until day 10.1 (mean; SD = 7.22 d), whereas in the vessel-sealing device hemorrhoidectomy group it continued until day 15.2 (mean; SD = 8.70 d; p = 0.006). The mean daily average pain was similar during the first (p = 0.900) and second postoperative weeks (p = 0.265). Mean operative time was higher for the transanal hemorrhoidal dearterialization with mucopexy group versus the vessel-sealing device hemorrhoidectomy group (45 min; range, 40-60 vs 20 min; range, 15-41 min; p < 0.001). Postoperative complications rate, use of laxatives, patient satisfaction, Vaizey score, hemorrhoids symptoms score, return to work, and quality of life at 1 month after surgery were similar between groups. LIMITATIONS: The main limitation of this study was that the 2 groups did not contain equal numbers of grade III and IV hemorrhoids. CONCLUSIONS: Transanal hemorrhoidal dearterialization with mucopexy is associated with a shorter need for postoperative analgesia compared with vessel-sealing device hemorrhoidectomy. See Video Abstract at http://links.lww.com/DCR/A915. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02654249.

Multi-Objective Evolutionary Rule-Based Classification with Categorical Data.

The ease of interpretation of a classification model is essential for the task of validating it. Sometimes it is required to clearly explain the classification process of a model's predictions. Models which are inherently easier to interpret can be effortlessly related to the context of the problem, and their predictions can be, if necessary, ethically and legally evaluated. In this paper, we propose a novel method to generate rule-based classifiers from categorical data that can be readily interpreted. Classifiers are generated using a multi-objective optimization approach focusing on two main objectives: maximizing the performance of the learned classifier and minimizing its number of rules. The multi-objective evolutionary algorithms ENORA and NSGA-II have been adapted to optimize the performance of the classifier based on three different machine learning metrics: accuracy, area under the ROC curve, and root mean square error. We have extensively compared the generated classifiers using our proposed method with classifiers generated using classical methods such as PART, JRip, OneR and ZeroR. The experiments have been conducted in full training mode, in 10-fold cross-validation mode, and in train/test splitting mode. To make results reproducible, we have used the well-known and publicly available datasets Breast Cancer, Monk's Problem 2, Tic-Tac-Toe-Endgame, Car, kr-vs-kp and Nursery. After performing an exhaustive statistical test on our results, we conclude that the proposed method is able to generate highly accurate and easy to interpret classification models.

Interleukin 16 and CCL17/thymus and activation-regulated chemokine in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Interleukin (IL) 16 and thymus and activation-regulated cytokine (TARC) are chemoattractant cytokines for eosinophils and TH2 cells. Differential levels of these components in aspirin-exacerbated respiratory disease (AERD) and allergic rhinitis with asthma (ARwA) may be related to a different inflammatory response in both asthma phenotypes. OBJECTIVE: To assess the nasal lavage immunoreactivity of IL-16 and TARC cytokines. METHODS: We used multienzyme-linked immunosorbent assays to detect IL-5, IL-13, IL-16, IL-33, I-309/CCL1, TARC/CCL17, monocyte-derived chemokine/CCL22, periostin, and eosinophil cationic protein levels in nasal lavages from patients with AERD and patients with ARwA. RESULTS: The IL-13, IL-16, TARC, and periostin levels were significantly higher in patients with AERD compared with those of patients with ARwA. Correlation analysis of mediator levels in AERD revealed a possible role of IL-16 and TARC in eosinophil recruitment and activation. CONCLUSION: IL-16, TARC, and periostin distinguish between patients with AERD and those with ARwA. These mediators, taken together rather than individually, may comprise good specific nasal markers in patients with AERD. The effects of IL-16 and TARC on TH1, TH2, and T-regulatory cell functions in AERD cannot be disregarded.

Physiopathology and genetics in aspirin-exacerbated respiratory disease.

INTRODUCTION: Aspirin-exacerbated respiratory disease (AERD) is a clinical entity characterized by hypersensitivity to aspirin leading to asthma and chronic rhinosinusitis with nasosinusal polyposis. The pathophysiology of the disease involves disruption at the level of arachidonic acid metabolism. Therefore, genetic association studies have been focused on the genes coding this pathway. As other mechanisms involved in the genesis of the disease were elucidated, the corresponding genes were also explored. AIM: To describe the association reported in the literature between gene polymorphisms involved in the pathophysiology or therapeutic processes of AERD. RESULTS: There is a genetic association between polymorphisms of genes involved in the synthesis of proteins related to arachidonic acid metabolism (LTC4S, ALOX5), antigen presentation (HLA), inflammation (IL5, IL17), and aspirin metabolism (CYP2C19). CONCLUSIONS: Genetic association research in AERD has evaluated studies of SNPs in metabolic pathways related to arachidonic acid. Recently, whole genome analysis strategies have allowed the detection of new genetic variants that were previously not considered. Furthermore, these studies have identified SNPs that are associated with inflammatory processes, which could serve as diagnostic markers or predictors of the therapeutic response.

A novel molecular mechanism involved in multiple myeloma development revealed by targeting MafB to haematopoietic progenitors.

Understanding the cellular origin of cancer can help to improve disease prevention and therapeutics. Human plasma cell neoplasias are thought to develop from either differentiated B cells or plasma cells. However, when the expression of Maf oncogenes (associated to human plasma cell neoplasias) is targeted to mouse B cells, the resulting animals fail to reproduce the human disease. Here, to explore early cellular changes that might take place in the development of plasma cell neoplasias, we engineered transgenic mice to express MafB in haematopoietic stem/progenitor cells (HS/PCs). Unexpectedly, we show that plasma cell neoplasias arise in the MafB-transgenic mice. Beyond their clinical resemblance to human disease, these neoplasias highly express genes that are known to be upregulated in human multiple myeloma. Moreover, gene expression profiling revealed that MafB-expressing HS/PCs were more similar to B cells and tumour plasma cells than to any other subset, including wild-type HS/PCs. Consistent with this, genome-scale DNA methylation profiling revealed that MafB imposes an epigenetic program in HS/PCs, and that this program is preserved in mature B cells of MafB-transgenic mice, demonstrating a novel molecular mechanism involved in tumour initiation. Our findings suggest that, mechanistically, the haematopoietic progenitor population can be the target for transformation in MafB-associated plasma cell neoplasias.

Influence of endurance running on calcaneal bone stiffness in male and female runners.

PURPOSE: The aim of this investigation was to determine the influence of endurance running on calcaneus bone stiffness in male and female runners. METHODS: A total of 122 marathoners (longer distance runners, men = 101; women = 21) and 81 half-marathon and 10-km runners (shorter distance runners; men = 48; women = 33), competing in an international running event, underwent an ultrasonographic assessment of the right and left calcaneus. Calcaneus bone stiffness was estimated using the measurements of the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Seventy-five age-matched sedentary people served as the control group. RESULTS: Male and female longer distance runners and shorter distance runners presented higher values than sedentary counterparts in SOS (P < 0.05), and calcaneus stiffness (P < 0.05). Although there were no significant differences between longer distance and shorter distance runners in the ultrasonographic variables, longer distance runners presented greater effects size in SOS (1.00 vs. 0.93 males; 1.10 vs. 0.77 females), BUA (0.62 vs. 0.25 males; 0.89 vs. 0.20 females) and calcaneus stiffness (0.88 vs. 0.66 males; 1.20 vs. 0.60 females) than shorter distance endurance runners. CONCLUSION: Calcaneus bone stiffness was higher in all endurance runners compared to a sedentary control population. The volume of ground reaction forces which occur during endurance running might induce the adaptation of the calcaneus bone.

A 3-Arm Randomized Trial for Achilles Tendinopathy: Eccentric Training, Eccentric Training Plus a Dietary Supplement Containing Mucopolysaccharides, or Passive Stretching Plus a Dietary Supplement Containing Mucopolysaccharides.

BACKGROUND: Tendinopathy is an overuse tendon injury that occurs in loaded tendons and results in pain and functional impairment. Although many treatments for painful tendons are described, the scientific evidence for most of the conservative and surgical treatments is not always conclusive. OBJECTIVES: This study was designed to evaluate the efficacy of 3 different interventions in patients with Achilles tendinopathy. The interventions include the combination of 2 physical therapy programs (eccentric training [EC] or passive stretching [PS]) with a supplement containing mucopolisaccharides. The efficacy of the interventions was evaluated depending on the stage of the disease. METHODS: Fifty-nine patients were randomly assigned to 1 of 3 treatment groups, and classified according to the disease stage: reactive versus degenerative tendinopathy. Treatment groups were EC; EC + a dietary supplement containing mucopolisaccharides, type I collagen, and vitamin C (MCVC); and a passive stretching program + MCVC. Patients were evaluated at baseline, 6 weeks, and 12 weeks with the Victorian Institute of Sports Assessment-Achilles questionnaire for function, a visual analog scale for pain, and ultrasound characterization for the evolution of tendon structure. RESULTS: A significant improvement in Victorian Institute of Sports Assessment-Achilles questionnaire score, pain at rest, and pain during activity were detected in all 3 treatment groups at 6 and 12 weeks' follow-up when compared with baseline. In patients with reactive tendinopathy, the reduction in pain at rest was greater in the groups who took the supplemental MCVC than in the EC alone group (P < 0.05). CONCLUSIONS: MCVC seems to be therapeutically useful for management of tendinopathies, providing some additional benefit to physical therapy. This is especially evident in early stages of the disease, when the tendon does not present severe matrix and vascular changes. CLINICALTRIALSGOV IDENTIFIER: NCT01691716.