Eficacia de los métodos de manipulación atloidea en las alteraciones temporomandibulares.

Objetivos: Evaluar los cambios en la respuesta dolorosa a la estimulación mecánica, movilidad cervical, apertura vertical de la boca y fuerza prensil en sujetos con dolor en la región cervical alta y/o temporomandibular, tras un tratamiento combinado de inhibición suboccipital y deslizamiento neuromuscular, con o sin empleo de manipulación occipito-atloidea. Material y Métodos: Estudio experimental, longitudinal, prospectivo, aleatorizado y doble ciego. Se incluyeron un total de 64 sujetos (81.5 % mujeres), edad media de 40.86 ± 13.16 años, que fueron distribuidos aleatoriamente en grupo control (n=29) y grupo intervención (n=35). En el grupo control se combinó una maniobra de inhibición suboccipital con trazos neuromusculares en la musculatura masetera. A este protocolo se le añadió una manipulación occipito-atloidea en los sujetos del grupo intervención. Como herramienta de medición se evalúo el umbral de dolor a la presión (UDP) en las ramas nerviosas trigeminales y en las zonas de localización de bandas tensas de los músculos suboccipital, masetero y temporal (algometría). Asimismo, se midió la movilidad cervical con un inclinómetro digital, la máxima apertura oral (MAO) con un pie de rey, y la fuerza de prensión mediante un dinamómetro hidráulico. Las mediciones se hicieron de forma previa e inmediatamente después de la intervención. Resultados: Para el UDP, la comparativa entre grupos observó diferencias estadísticamente significativas sólo para el musculo suboccipital en el lado no dominante (P = 0.003) y el nervio infraorbital en el lado dominante (P = 0.016). No obstante, si se encontró significancia estadística en parámetros de movilidad cervical, (rotación cervical a ambos lados y extensión, P 0.05). Conclusión: La manipulación cervical alta combinada con maniobras de inhibición a nivel suboccipital y maseterogenera un mayor impacto en la mejora de la movilidad cervical que el uso del mismo protocolo sin manipulación espinal (ME) en sujetos con dolor cervical y/o temporomandibular. Por el contrario, la inclusión de ME no añade cambio alguno en la mecanosensibilidad local y a distancia, la fuerza de agarre y la movilidad de apertura bucal.Aims: to assess the changes in painful response to mechanical stimulation, cervical mobility, vertical mouth opening and prehensile strength in individuals with pain in the high cervical and/or temporomandibular region, after a combined treatment of suboccipital inhibition and neuromuscular glide, with or without atlanto-occipital joint manipulation. Equipment and methods: an experimental, longitudinal, prospective, randomised and double-blinded study. A total of 64 individuals were included in the study (81.5 % women), with an average age of 40.86 ± 13.16 years old, who were randomly distributed within a control group (n=35) and an intervention group (n=29). In the control group, a suboccipital inhibition manoeuvre was combined with a neuromuscular technique on the masseter. An atlanto-occipital manipulation was added to this protocol in individuals of the intervention group. As a measurement tool, pressure pain threshold (PPT) was assessed on trigeminal nerve branches and on areas where tight bands of suboccipital, masseter and temporal muscles were located (algometry). Likewise, cervical mobility was measured with a digital inclinometer, maximal mouth opening (MMO) with a vernier caliper, and prehensile strength with a hydraulic dynamometer. Measurements were made before the intervention and immediately afterwards. Results: In relation to the PPT, the comparison between groups showed statistically significant differences only in the non-dominant side of the suboccipital muscle (Pressure = 0.003) and in the dominant side of the infraorbital nerve (Pressure = 0.016). Nonetheless, a statistically significant difference was found in the cervical mobility parameters (cervical rotation and extension to both sides, Pressure 0.05). Conclusion: High cervical manipulation combined with suboccipital and masseter inhibition manoeuvres generates a greater impact in the cervical mobility improvement than using the same protocol without spinal manipulation in individuals with cervical and/or temporomandibular pain. On the other side, the inclusion of spinal manipulation does not add any change in the local and distant mechanosensitivity, grip strength and mouth opening mobility

Local and Widespread Pressure Pain Hyperalgesia Is Not Side Specific in Females with Unilateral Neck Pain that Can Be Reproduced during Passive Neck Rotation

Current evidence for widespread hyperalgesia in non-specific neck pain (NSNP) is unclear. It is currently recommended to group NSNP patients according to pain-provoking movements. The aim of this study was to investigate local and widespread pain sensitivity in females with unilateral NSNP that is reproducible during passive neck rotation compared with matched controls, and to compare the side specific effect of pain location on pressure pain sensitivity among females with unilateral NSNP. Thirty-six females with unilateral NSNP evoked during passive ipsilateral (n = 20) or contralateral (n = 16) rotation toward the painful side were compared with 20 controls. Participants reported their pain intensity at rest and during passive neck rotation and completed the Neck Disability Index. Pressure pain thresholds (PPTs) were assessed bilaterally over the anterior scalene; the sternocleidomastoid; the levator scapulae; lateral to the spinous process of C6; the median, ulnar, and radial nerves; and the tibialis anterior. The ANOVA revealed lower PPTs in females with unilateral NSNP compared with the controls (all at p < 0.001), but no differences were found between the sides, nor was there any Groupside interaction. Among females with NSNP, those with higher pain intensity during ipsilateral rotation toward the painful side showed lower PPTs over the anterior scalene, median nerve, ulnar nerve, and tibialis anterior (all, p < 0.05) than females with higher pain intensity during contralateral rotation toward the painful side. These findings demonstrated bilateral local and widespread pressure pain hyperalgesia in females with unilateral NSNP that was reproducible during passive neck rotation compared with controls. There was no side specific effect of pain location on PPTs among females with unilateral NSNP.Ministerio de Educación, Cultura y Deporte (CAS 16/00046

Visualizing Classification Results: Confusion Star and Confusion Gear

Recent developments in machine learning applications are deeply concerned with the poor interpretability of most of these techniques. To gain some insights in the process of designing data-based models it is common to graphically represent the algorithm's results, either in their final or intermediate stage. Specially challenging is the task of plotting multiclass classification results as they involve categorical variables (classes) rather than numeric results. Using the well-known MNIST dataset and a simple neural network as an example, this paper reviews the existing techniques to visualize classification results, from those centered on a particular instance or set of instances, to those representing an overall performance metric. As classification results are commonly summarized in the form of a confusion matrix, special attention is paid to its graphical representation. From this analysis, a new visualization tool is derived, which is presented in two forms: confusion star and confusion gear. The confusion star is centered on the classification errors, while the confusion gear focuses on the classification hits. The proposed visualization tools are also evaluated when facing: (i) balanced and imbalanced classifiers issues; (ii) the problem of representing errors with different orders of magnitude. By using shapes instead of colors to represent the value of each matrix cell, the new tools significantly improve the readability of the confusion matrices. Furthermore, we show how the area enclosed by the confusion stars and gears are directly related to standard classification metrics. The new graphic tools can be also usefully employed to visualize the performances of a sequence of classifiers

Using the Social-Local-Mobile App for Smoking Cessation in the SmokeFreeBrain Project: Protocol for a Randomized Controlled Trial

Background: Smoking is considered the main cause of preventable illness and early deaths worldwide. The treatment usually prescribed to people who wish to quit smoking is a multidisciplinary intervention, combining both psychological advice and pharmacological therapy, since the application of both strategies significantly increases the chance of success in a quit attempt. Objective: We present a study protocol of a 12-month randomized open-label parallel-group trial whose primary objective is to analyze the efficacy and efficiency of usual psychopharmacological therapy plus the Social-Local-Mobile app (intervention group) applied to the smoking cessation process compared with usual psychopharmacological therapy alone (control group). Methods: The target population consists of adult smokers (both male and female) attending the Smoking Cessation Unit at Virgen del Rocío University Hospital, Seville, Spain. Social-Local-Mobile is an innovative intervention based on mobile technologies and their capacity to trigger behavioral changes. The app is a complement to pharmacological therapies to quit smoking by providing personalized motivational messages, physical activity monitoring, lifestyle advice, and distractions (minigames) to help overcome cravings. Usual pharmacological therapy consists of bupropion (Zyntabac 150 mg) or varenicline (Champix 0.5 mg or 1 mg). The main outcomes will be (1) the smoking abstinence rate at 1 year measured by means of exhaled carbon monoxide and urinary cotinine tests, and (2) the result of the cost-effectiveness analysis, which will be expressed in terms of an incremental cost-effectiveness ratio. Secondary outcome measures will be (1) analysis of the safety of pharmacological therapy, (2) analysis of the health-related quality of life of patients, and (3) monitoring of healthy lifestyle and physical exercise habits. Results: Of 548 patients identified using the hospital’s electronic records system, we excluded 308 patients: 188 declined to participate and 120 did not meet the inclusion criteria. A total of 240 patients were enrolled: the control group (n=120) will receive usual psychopharmacological therapy, while the intervention group (n=120) will receive usual psychopharmacological therapy plus the So-Lo-Mo app. The project was approved for funding in June 2015. Enrollment started in October 2016 and was completed in October 2017. Data gathering was completed in November 2018, and data analysis is under way. The first results are expected to be submitted for publication in early 2019. Conclusions: Social networks and mobile technologies influence our daily lives and, therefore, may influence our smoking habits as well. As part of the SmokeFreeBrain H2020 European Commission project, this study aims at elucidating the potential role of these technologies when used as an extra aid to quit smoking

Persistence of wild rabbit (Oryctolagus cuniculus) latrines and its implication for monitoring programs

Counting latrines is a standard method to estimate European wild rabbits (Oryctolagus cuniculus) abundance. This method plays an important role in endangered predators’ conservation programs in the Iberian Peninsula, especially in potential reintroduction areas for the Iberian lynx (Lynx pardinus). However, since the last half-century, rabbit populations have declined dramatically within their native range, mainly due to the effect of two viral diseases, which have caused even local extinctions of natural populations. Hence, we raise the question regarding how reliable the method of counting latrines may be in ensuring the abundance of rabbit populations after an event of sudden decline or even local extinction. To answer this question, we carry out a simple experiment where we set ten lines with rabbit latrines with two different sizes each (small and large) and simulated low- and high-abundant rabbit population scenarios on five latrine lines each, respectively

Evaluation of four ELISA assays to diagnose Mycobacterium tuberculosis complex infection in pigs

Resumen del trabajo presentado al 8th European Symposium of Porcine Health Management and 24th International Pig Veterinary Society Congress, celebrados en Dublin (Irlanda) del 7 al 10 de junio de 2016.[Introduction]: In countries in which bovine tuberculosis (bTB) is still prevalent or is re-emerging the contact among different animal species in extensive systems may contribute to the circulation of Mycobacterium bovis and other members of the Mycobacterium tuberculosis complex (MTC) and the spread of this disease. Thus, free-range pigs may be infected by MTC, developing subclinical infections, which are not detected until meat inspection procedures at slaughterhouse. Serodiagnosis has been recently proposed as a reliable screening tool for detecting infected herds. In this study four ELISA assays using different M. bovis peptides/proteins (MPB70+MPB83, INGENASA; treated bovine purified protein derivative, t-bPPD; bPPD1; and bPPD2 VACUNEK) as coating antigens were evaluated to diagnose MTC infection in pigs. [Materials and Methods]: Submandibular lymph nodes (SLN) and blood samples from 129 free-range pigs raised on Southern Spain farms with a history of condemnation due to tuberculosis-like lesions were sampled at slaughterhouse. SLN were tested by gross examination, histopathology, bacteriological culture and qPCR. Ninety-seven out of these animals were classified as bTB positive cases (compatible lesions and MTC detection by means of culture and qPCR) or bTB negative cases (absence of compatible lesions and negative MTC detection) and used as reference method. When necessary different cut-off values were evaluated. [Results]: All assays had a very good concordance between them (k ≥ 0.82). The MPB70+MPB83 based ELISA had the best sensitivity (Se) (78%, CI95 67.4%>88.5%) and a good concordance with the reference method (k=0.69). The t-bPPD and the bPPD1 in-house assays presented a slightly reduced Se (71.2%, CI95 59.6%>82.7%; and 66.1%, CI95 54%>78.2%; respectively) and a moderate concordance with the reference method (k=0.57 and 0.52, respectively). When the bPPD2 based ELISA was evaluated, similar Se to the previous ones was obtained using a cut-off of 0.35 (Se: 66.1%, CI95 54%>78.2%; k=0.52). Conclusion` +: These results suggest that despite the fact that MPB70+MPB83 ELISA presented the best results all four evaluated ELISA assays could be used as a screening tool to conduct TB surveillance in pigs at a population level. In addition, a cut-off of 0.35 is recommended for bPPD2 ELISA in order to obtain better diagnostic values.This study was financially supported by the Council of Economy, Science, Innovation and Employment of the Andalusian Government (AGR-2685-2012) and by the European Project WILDTBVAC (FP7-KBBE-613799).Peer Reviewe

Biological Evaluation of New Thienopyridinium and Thienopyrimidinium Derivatives as Human Choline Kinase Inhibitors

Due to its role in lipid biosynthesis, choline kinase α1 (CKα1) is an interesting target for the development of new antitumor agents. In this work, we present a series of 41 compounds designed based on the well-known and successful strategy of introducing thienopyridine and pyrimidine as bioisosteres of other heterocycles in active antitumor compounds. Notwithstanding the fact that some of these compounds do not show significant enzymatic inhibition, others, in contrast, feature substantially improved enzymatic and antiproliferative inhibition values. This is also confirmed by docking analysis, whereby compounds with longer linkers and thienopyrimidine cationic head have been identified as the most compelling. Among the best compounds is Ff-35, which inhibits the growth of different tumor cells at submicromolar concentrations. Moreover, Ff-35 is more potent in inhibiting CKα1 than other previous biscationic derivatives. Treatment of A549, Hela, and MDA-MB-231 cells with Ff-35 results in their arrest at the G1 phase of the cell cycle. Furthermore, the compound induces cellular apoptosis in a concentration-dependent manner. Altogether, these findings indicate that Ff-35 is a promising new chemotherapeutic agent with encouraging preclinical potential

Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer

Recent data suggested that plasma Ghrelin O-Acyl Transferase enzyme (GOAT) levels could represent a new diagnostic biomarker for prostate cancer (PCa). In this study, we aimed to explore the diagnostic and prognostic/aggressiveness capacity of GOAT in urine, as well as to interrogate its putative pathophysiological role in PCa. We analysed urine/plasma levels of GOAT in a cohort of 993 patients. In vitro (i.e., cell-proliferation) and in vivo (tumor-growth in a xenograft-model) approaches were performed in response to the modulation of GOAT expression/activity in PCa cells. Our results demonstrate that plasma and urine GOAT levels were significantly elevated in PCa patients compared to controls. Remarkably, GOAT significantly outperformed PSA in the diagnosis of PCa and significant PCa in patients with PSA levels ranging from 3 to 10 ng/mL (the so-called PSA grey-zone). Additionally, urine GOAT levels were associated to clinical (e.g., Gleason-score, PSA levels) and molecular (e.g., CDK2/CDK6/CDKN2A expression) aggressiveness parameters. Indeed, GOAT overexpression increased, while its silencing/blockade decreased cell-proliferation in PCa cells. Moreover, xenograft tumors derived from GOAT-overexpressing PCa (DU145) cells were significantly higher than those derived from the mock-overexpressing cells. Altogether, our results demonstrate that GOAT could be used as a diagnostic and aggressiveness marker in urine and a therapeutic target in PCa

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London