Monitoring the decreasing trend of testicular cancer mortality in Spain during 2005-2019 through a Bayesian approach

Purpose : To assess time trends of testicular cancer (TC) mortality in Spain for period 1985-2019 for age groups 15-74 years old through a Bayesian age-period-cohort (APC) analysis. Methods: A Bayesian age-drift model has been fitted to describe trends. Projections for 2005-2019 have been calculated by means of an autoregressive APC model. Prior precision for these parameters has been selected through evaluation of an adaptive precision parameter and 95% credible intervals (95% CRI) have been obtained for each model parameter. Results: A decrease of -2.41% (95% CRI: -3.65%; -1.13%) per year has been found for TC mortality rates in age groups 15-74 during 1985-2004, whereas mortality showed a lower annual decrease when data was restricted to age groups 15-54 (-1.18%; 95% CRI: -2.60%; -0.31%). During 2005-2019 is expected a decrease of TC mortality of 2.30% per year for men younger than 35, whereas a leveling off for TC mortality rates is expected for men older than 35. Conclusions: A Bayesian approach should be recommended to describe and project time trends for those diseases with low number of cases. Through this model it has been assessed that management of TC and advances in therapy led to decreasing trend of TC mortality during the period 1985-2004, whereas a leveling off for these trends can be considered during 2005-2019 among men older than 35.

Monitoring the decreasing trend of testicular cancer mortality in Spain during 2005-2019 through a Bayesian approach

Purpose : To assess time trends of testicular cancer (TC) mortality in Spain for period 1985-2019 for age groups 15-74 years old through a Bayesian age-period-cohort (APC) analysis. Methods: A Bayesian age-drift model has been fitted to describe trends. Projections for 2005-2019 have been calculated by means of an autoregressive APC model. Prior precision for these parameters has been selected through evaluation of an adaptive precision parameter and 95% credible intervals (95% CRI) have been obtained for each model parameter. Results: A decrease of -2.41% (95% CRI: -3.65%; -1.13%) per year has been found for TC mortality rates in age groups 15-74 during 1985-2004, whereas mortality showed a lower annual decrease when data was restricted to age groups 15-54 (-1.18%; 95% CRI: -2.60%; -0.31%). During 2005-2019 is expected a decrease of TC mortality of 2.30% per year for men younger than 35, whereas a leveling off for TC mortality rates is expected for men older than 35. Conclusions: A Bayesian approach should be recommended to describe and project time trends for those diseases with low number of cases. Through this model it has been assessed that management of TC and advances in therapy led to decreasing trend of TC mortality during the period 1985-2004, whereas a leveling off for these trends can be considered during 2005-2019 among men older than 35.

Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas

Multiple osteochondromas is an autosomal dominant skeletal disorder characterized by the formation of multiple cartilage-capped tumours. Two causal genes have been identified, EXT1 and EXT2, which account for 65% and 30% of cases, respectively. We have undertaken a mutation analysis of the EXT1 and EXT2 genes in 39 unrelated Spanish patients, most of them with moderate phenotype, and looked for genotype-phenotype correlations. We found the mutant allele in 37 patients, 29 in EXT1 and 8 in EXT2. Five of the EXT1 mutations were deletions identified by MLPA. Two cases of mosaicism were documented. We detected a lower number of exostoses in patients with missense mutation versus other kinds of mutations. In conclusion, we found a mutation in EXT1 or in EXT2 in 95% of the Spanish patients. Eighteen of the mutations were novel.

Etude des niveaux de concentration d'hydrocarbures aromatiques polycycliques (HAPs) dans la poussière de bois et des marqueurs biologiques d'effets génotoxiques chez les travailleurs du bois

L'exposition aux poussières de bois est associé à un risque accru d'adénocarcinomes des fosses nasales et des sinus paranasaux (SNC, 'Sinonasal cancer') chez les travailleurs du bois. Les poussières de bois sont ainsi reconnues comme cancérogènes avérés pour l'homme par le Centre international de Recherche sur le Cancer (CIRC). Toutefois, l'agent causal spécifique et le mécanisme sous-jacent relatifs au cancer lié aux poussières de bois demeurent inconnus. Une possible explication est une co-exposition aux poussières de bois et aux Hydrocarbures Aromatiques Polycycliques (HAP), ces derniers étant potentiellement cancérogènes. Dans les faits, les travailleurs du bois sont non seulement exposés aux poussières de bois naturel, mais également à celles générées lors d'opérations effectuées à l'aide de machines (ponceuses, scies électriques, etc.) sur des finitions de bois (bois traités) ou sur des bois composites, tels que le mélaminé et les panneaux de fibres à densité moyenne (MDF, 'Medium Density Fiberboard'). Des HAP peuvent en effet être générés par la chaleur produite par l'utilisation de ces machines sur la surface du bois. Les principaux objectifs de cette thèse sont les suivants: (1) quantifier HAP qui sont présents dans les poussières générées lors de diverses opérations courantes effectuées sur différents bois (2) quantifier l'exposition individuelle aux poussières de bois et aux HAP chez les travailleurs, et (3) évaluer les effets génotoxiques (dommages au niveau de l'ADN et des chromosomes) due à l'exposition aux poussières de bois et aux HAP. Cette thèse est composée par une étude en laboratoire (objectif 1) et par une étude de terrain (objectifs 2 et 3). Pour l'étude en laboratoire, nous avons collecté des poussières de différents type de bois (sapin, MDF, hêtre, sipo, chêne, bois mélaminé) générées au cours de différentes opérations (comme le ponçage et le sciage), et ceci dans une chambre expérimentale et dans des conditions contrôlées. Ensuite, pour l'étude de terrain, nous avons suivi, dans le cadre de leur activité professionnelle, 31 travailleurs de sexe masculin (travailleurs du bois et ébenistes) exposés aux poussières de bois pendant deux jours de travail consécutifs. Nous avons également recruté, comme groupe de contrôle, 19 travailleurs non exposés. Pour effectuer une biosurveillance, nous avons collecté des échantillons de sang et des échantillons de cellules nasales et buccales pour chacun des participants. Ces derniers ont également rempli un questionnaire comprenant des données démographiques, ainsi que sur leur style de vie et sur leur exposition professionnelle. Pour les travailleurs du bois, un échantillonnage individuel de poussière a été effectué sur chaque sujet à l'aide d'une cassette fermée, puis nous avons évalué leur exposition à la poussière de bois et aux HAP, respectivement par mesure gravimétrique et par Chromatographie en phase gazeuse combinée à la spectrométrie de masse. L'évaluation des dommages induits à l'ADN et aux chromosomes (génotoxicité) a été, elle, effectuée à l'aide du test des micronoyaux (MN) sur les cellules nasales et buccales et à l'aide du test des comètes sur les échantillons de sang. Nos résultats montrent dans la poussière de la totalité des 6 types de bois étudiés la présence de HAP (dont certains sont cancérogènes). Des différences notoires dans les concentrations ont été néanmoins constatées en fonction du matériau étudié : les concentrations allant de 0,24 ppm pour la poussière de MDF à 7.95 ppm pour le mélaminé. Nos résultats montrent également que les travailleurs ont été exposés individuellement à de faibles concentrations de HAP (de 37,5 à 119,8 ng m-3) durant les opérations de travail du bois, alors que les concentrations de poussières inhalables étaient relativement élevés (moyenne géométrique de 2,8 mg m-3). En ce qui concerne la génotoxicité, les travailleurs exposés à la poussière de bois présentent une fréquence significativement plus élevée en MN dans les cellules nasales et buccales que les travailleurs du groupe témoin : un odds ratio de 3.1 a été obtenu pour les cellules nasales (IC 95% : de 1.8 à 5.1) et un odds ratio de 1,8 pour les cellules buccales (IC 95% : de 1.3 à 2.4). En outre, le test des comètes a montré que les travailleurs qui ont déclaré être exposés aux poussières de MDF et/ou de mélaminé avaient des dommages à l'ADN significativement plus élevés que les deux travailleurs exposés à la poussière de bois naturel (sapin, épicéa, hêtre, chêne) et que les travailleurs du groupe témoin (p <.01). Enfin, la fréquence des MN dans les cellules nasales et buccales augmentent avec les années d'exposition aux poussières de bois. Par contre, il n'y a pas de relation dose-réponse concernant la génotoxicité due à l'exposition journalière à la poussière et aux HAP. Cette étude montre qu'une exposition aux HAP eu bien lieu lors des opérations de travail du bois. Les travailleurs exposés aux poussières de bois, et donc aux HAP, courent un risque plus élevé (génotoxicité) par rapport au groupe témoin. Étant donné que certains des HAP détectés sont reconnus potentiellement cancérogènes, il est envisageable que les HAP générés au cours du travail sur les matériaux de bois sont un des agents responsables de la génotoxicité de la poussière de bois et du risque élevé de SNC observé chez les travailleurs du secteur. Etant donné la corrélation entre augmentation de la fréquence des MN, le test des micronoyaux dans les cellules nasales et buccales constitue sans conteste un futur outil pour la biosurveillance et pour la détection précoce du risque de SNC chez les travailleurs. - Exposures to wood dust have been associated with an elevated risk of adenocarcinomas of the Dasal cavity and the paranasal sinuses (sinonasal cancer or SNC) among wood workers. Wood dust is recognized as a human carcinogen by the International Agency for Research on Cancer. However, the specific cancer causative agent(s) and the mechanism(s) behind wood dust related carcinogenesis remains unknown. One possible explanation is a co-exposure to wood dust and polycyclic aromatic hydrocarbons (PAH), the latter being carcinogenic. In addition, wood workers are not only exposed to natural wood but also to wood finishes and composite woods such as wood melamine and medium density fiber (MDF) boards during the manipulation with power tools. The heat produced by the use of power tools can cause the generation of PAH from wood materials. The main objectives of the present thesis are to: (1) quantify possible PAH concentrations in wood dust generated during various common woodworking operations using different wood materials; (2) quantify personal wood dust concentrations and PAH exposures among wood workers; and (3) assess genotoxic effects (i.e., DNA and chromosomal damage) of wood dust and PAH exposure in wood workers. This thesis is composed by a laboratory study (objective 1) and a field study (objectives 2 and 3). In the laboratory study we collected wood dust from different wood materials (fir, MDF, beech, mahagany, oak, and wood melamine) generated during different wood operations (e.g., sanding and sawing) in an experimental chamber under controlled conditions. In the following field study, we monitored 31 male wood workers (furniture and construction workers) exposed to wood dust during their professional activity for two consecutive work shifts. Additionally, we recruited 19 non exposed workers as a control group. We collected from each participant blood samples, and nasal and buccal cell samples. They answered a questionnaire including demographic and life-style data and occupational exposure (current and past). Personal wood dust samples were collected using a closed-face cassette. We used gravimetrie analysis to determine the personal wood dust concentrations and capillary gas chromatography - mass spectrometry analysis to determine PAH concentrations. Genotoxicity was assessed with the micronucleus (MN) assay for nasal and buccal cells and with the comet assay for blood samples. Our results show that PAH (some of them carcinogenic) were present in dust from all six wood materials tested, yet at different concentrations depending on the material. The highest concentration was found in dust from wood melamine (7.95 ppm) and the lowest in MDF (0.24 ppm). Our results also show that workers were individually exposed to low concentrations of PAHs (37.5-119.8 ng m"3) during wood working operations, whereas the concentrations of inhalable dust were relatively high (geometric mean 2.8 mg m"3). Concerning the genotoxicity, wood workers had a significantly higher MN frequency in nasal and buccal cells than the workers in the control group (odds ratio for nasal cells 3.1 (95%CI 1.8-5.1) and buccal cells 1.8 (95%CI 1.3-2.4)). Furthermore, the comet assay showed that workers who reported to be exposed to dust from wooden boards (MDF and wood melamine) had significantly higher DNA damage than both the workers exposed to natural woods (fir, spruce, beech, oak) and the workers in the control group (p < 0.01). Finally, MN frequency in nasal and buccal cells increased with increasing years of exposure to wood dust. However, there was no genotoxic dose-response relationship with the per present day wood dust and PAH exposure. This study shows that PAH exposure occurred during wood working operations. Workers exposed to wood dust, and thus to PAH, had a higher risk for genotoxicity compared to the control group. Since some of the detected PAH are potentially carcinogenic, PAH generated from operations on wood materials may be one of the causative agents for the observed increased genotoxicity in wood workers. Since increased genotoxicity is manifested in an increased MN frequency, the MN assay in nasal and buccal cells may become a relevant biomonitoring tool in the future for early detection of SNC risk.

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD'

Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas

Multiple osteochondromas is an autosomal dominant skeletal disorder characterized by the formation of multiple cartilage-capped tumours. Two causal genes have been identified, EXT1 and EXT2, which account for 65% and 30% of cases, respectively. We have undertaken a mutation analysis of the EXT1 and EXT2 genes in 39 unrelated Spanish patients, most of them with moderate phenotype, and looked for genotype-phenotype correlations. We found the mutant allele in 37 patients, 29 in EXT1 and 8 in EXT2. Five of the EXT1 mutations were deletions identified by MLPA. Two cases of mosaicism were documented. We detected a lower number of exostoses in patients with missense mutation versus other kinds of mutations. In conclusion, we found a mutation in EXT1 or in EXT2 in 95% of the Spanish patients. Eighteen of the mutations were novel.

Sensorimotor Plasticity after Music-Supported Therapy in Chronic Stroke Patients Revealed by Transcranial Magnetic Stimulation

BACKGROUND: Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention. METHODS AND RESULTS: In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance. CONCLUSION: Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.

Prognostic value of cortically induced motor evoked activity by TMS in chronic stroke: caveats from a very revealing single clinical case

Background: We report the case of a chronic stroke patient (62 months after injury) showing total absence of motor activity evoked by transcranial magnetic stimulation (TMS) of spared regions of the left motor cortex, but near-to-complete recovery of motor abilities in the affected hand. Case presentation: Multimodal investigations included detailed TMS based motor mapping, motor evoked potentials (MEP), and Cortical Silent period (CSP) as well as functional magnetic resonance imaging (fMRI) of motor activity, MRI based lesion analysis and Diffusion Tensor Imaging (DTI) Tractography of corticospinal tract (CST). Anatomical analysis revealed a left hemisphere subinsular lesion interrupting the descending left CST at the level of the internal capsule. The absence of MEPs after intense TMS pulses to the ipsilesional M1, and the reversible suppression of ongoing electromyographic (EMG) activity (indexed by CSP) demonstrate a weak modulation of subcortical systems by the ipsilesional left frontal cortex, but an inability to induce efficient descending volleys from those cortical locations to right hand and forearm muscles. Functional MRI recordings under grasping and finger tapping patterns involving the affected hand showed slight signs of subcortical recruitment, as compared to the unaffected hand and hemisphere, as well as the expected cortical activations. Conclusions: The potential sources of motor voluntary activity for the affected hand in absence of MEPs are discussed. We conclude that multimodal analysis may contribute to a more accurate prognosis of stroke patients.

Pronóstico y tratamiento de la boca seca. Revisión sistemática

No existen protocolos claramente establecidos para el tratamiento de la boca seca. El objetivo de este trabajo es realizar una revisión sistemática de la literatura médica de los últimos 10 años. Hemos utilizado las palabras: «dry mouth», «prognosis», «treatment» y «dentistry». En una primera búsqueda hemos encontrado 1.450 entradas. Con la restricción «clinical trials OR randomized controlled trial OR systemic reviews» se han reducido a 522, de las que 145 eran metaanálisis y revisiones sistemáticas. Se han eliminado las que no eran pertinentes al tema y han quedado reducidas a 53. Posteriormente se descartaron 24 (8 no pertinentes, 7 revisiones y 9 opiniones personales). De los 29 artículos analizados, 15 son ensayos clínicos controlados, 2 ensayos no controlados, 4 estudios observacionales, 2 revisiones sistemáticas y 5 revisiones. Los enfermos mejor estudiados son los pacientes con síndrome de Sjögren y los pacientes irradiados. El tratamiento se centra en el etiológico, preventivo, sintomático, de estimulación salival local y sistémicos. Podemos concluir que el tratamiento debe ser individualizado, pudiéndose aplicar sustitutos salivales y diferentes técnicas de estimulación mecánica. There are no clearly established protocols for the treatment of dry mouth. The aim of this paper is a systematic review of the literature of the past 10 years using the words «dry mouth», «prognosis», «treatment» and «dentistry». The initial search found 1,450 entries and within the restriction «clinical trials OR randomized controlled trial OR systemic reviews» it has been reduced to 522, which 145 were meta-analysis and systematic reviews. Papers not relevant to the issue were removed reducing the entries to 53. Twenty-four were dismissed (8 irrelevant, 7 reviews without adequate information and 9 personal opinions). Of the 29 items tested, 15 were controlled trials, 2 uncontrolled trials, 4 observational studies, 2 systematic reviews and 5 non systematic reviews. The most studied patients were Sjögren's syndrome and the irradiated patients. Treatments are focused on the etiology, prevention, symptomatic, local salivary stimulation and systemic treatments. It can be concluded that treatment must be individualized, salivary substitutes and mechanical stimulation techniques can be applied.

Síndrome de boca ardiente: claves diagnósticas y terapéuticas

El síndrome de boca ardiente (SBA) se conoce también como boca escaldada, ardor bucal, glosodinia, glosopirosis, estomatodinia, estomatopirosis o disestesia oral. Se caracteriza por dolor o sensación de ardor, escozor o picazón, a veces aspereza, sobre todo en la lengua, paladar duro y labio inferior, en ausencia de datos clínicos o de laboratorio que justifiquen estos síntomas. Puede acompañarse de disgeusia (trastornos del gusto) y de xerostomía (boca seca), constituyendo la tríada clásica. Su etiología, poco precisa, es multifactorial. La evolución del cuadro tiende a ser crónica, alternando períodos de exacerbación y mejoría durante meses o años. Es más frecuente en mujeres perimenopáusicas o posmenopáusicas. Los episodios de SBA aparecen de forma espontánea y presentan un abanico variable en la gravedad de los síntomas. Mientras algunos pacientes refieren malestar leve o moderado, otros manifiestan dolor insoportable. Los síntomas suelen ser menos intensos...

Boca seca y boca ardiente

La saliva es esencial para mantener la salud oral. El 99% de su composición es agua. El desencadenante más común de boca seca es la toma de medicamentos, generalmente acompañada de escasa ingesta de líquidos. Entre sus complicaciones cabe destacar xerostomía, disgeusia y ardor bucal, entre otras. Estos síntomas son tríada frecuente del síndrome de boca ardiente (SBA). Su etiología es imprecisa y multifactorial, sin datos clínicos o de laboratorio específicos. En su patogenia intervienen factores locales, sistémicos y psicológicos. Es común la asociación de hábitos parafuncionales evidentes, dentarios y linguales, con repercusión en tejidos duros (desgaste, ATM) y blandos (lesiones facticias, irritación de papilas linguales). Afecta más a mujeres en edad perimenopáusica, en proporción hasta 7:1 respecto a los hombres. A menudo se asocian ansiedad o depresión. En este trabajo se propone la parafunción deglutoria como parte integrante del síndrome.

Síndrome de boca ardiente: claves diagnósticas y terapéuticas

El síndrome de boca ardiente (SBA) se conoce también como boca escaldada, ardor bucal, glosodinia, glosopirosis, estomatodinia, estomatopirosis o disestesia oral. Se caracteriza por dolor o sensación de ardor, escozor o picazón, a veces aspereza, sobre todo en la lengua, paladar duro y labio inferior, en ausencia de datos clínicos o de laboratorio que justifiquen estos síntomas. Puede acompañarse de disgeusia (trastornos del gusto) y de xerostomía (boca seca), constituyendo la tríada clásica. Su etiología, poco precisa, es multifactorial. La evolución del cuadro tiende a ser crónica, alternando períodos de exacerbación y mejoría durante meses o años. Es más frecuente en mujeres perimenopáusicas o posmenopáusicas. Los episodios de SBA aparecen de forma espontánea y presentan un abanico variable en la gravedad de los síntomas. Mientras algunos pacientes refieren malestar leve o moderado, otros manifiestan dolor insoportable. Los síntomas suelen ser menos intensos...

Disparities in work, risk and health between immigrants and native-born Spaniards

We analyse the impact of working and contractual conditions, particularly exposure to job risks, on the probability of acquiring a permanent disability, controlling for other personal and firm characteristics. We postulate a model in which this impact is mediated by the choice of occupation, with a level of risk associated with it. We assume this choice is endogenous, and that it depends on preferences and opportunities in the labour market, both of which may differ between immigrants and natives. To test this hypothesis we apply a bivariate probit model to data for 2006 from the Continuous Sample of Working Lives provided by the Spanish Social Security system, containing records for over a million workers. We find that risk exposure increases the probability of permanent disability arising from any cause - by almost 5%.

Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study.

Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician"s brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy.