Sex-specific impact of inflammation on traditional cardiovascular risk factors and atherosclerosis in axial spondyloarthritis. A multicentre study of 913 patients.

INTRODUCTION: The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in this regard are yet to be assessed. METHODS: Study including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment. RESULTS: After a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (ß coefficient: -1.2 (95% CI: -0.3 to -0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (ß coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high-very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis. CONCLUSION: Inflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.

Topographic modification of the extracellular matrix precedes the onset of bladder cancer.

Background: Non-muscle invasive bladder cancer (NMIBC) patients are affected by a high risk of recurrence. The topography of collagen fibers represents a hallmark of the neoplastic extracellular microenvironment. Objective: Assess the topographic change associated with different stages of bladder cancer (from neoplastic lesions to bona fide tumor) and whether those changes favour the development of NMIBC. Design Setting and Participants: Seventy-one clinical samples of urothelial carcinoma at different stages were used. Topographic changes preceding tumor onset and progression were evaluated in the rat bladder cancer model induced by nitrosamine (BBN), a bladder-specific carcinogen. The preclinical model of actinic cystitis was also used in combination with BBN. Validated hematoxylin-eosin sections were used to assess the topography of collagen fibrils associated with pre-tumoral steps, NMIBC, and MIBC. Findings: Linearization of collagen fibers was higher in Cis and Ta vs. dysplastic urothelium, further increased in T1 and greatest in T2 tumors. In the BBN preclinical model, an increase in the linearization of collagen fibers was established since the beginning of inflammation, such as the onset of atypia of a non-univocal nature and dysplasia, and further increased in the presence of the tumor. Linearization of collagen fibers in the model of actinic cystitis was associated with earlier onset of BBN-induced tumor. Conclusions: The topographic modification of the extracellular microenvironment occurs during the inflammatory processes preceding and favoring the onset of bladder cancer. The topographic reconfiguration of the stroma could represent a marker for identifying and treating the non-neoplastic tissue susceptible to tumor recurrence.

Long-Term Survival of Subcutaneous Biosimilar Tumor Necrosis Factor Inhibitors Compared to Originators: Results From a Multicenter Prospective Registry.

OBJECTIVE: To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. METHODS: Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. RESULTS: A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. CONCLUSION: No significant differences were found between treatments in long-term survival due to inefficacy or AEs.

Childhood-Onset Non-Infectious Uveitis in the "Biologic Era". Results From Spanish Multicenter Multidisciplinary Real-World Clinical Settings.

OBJECTIVE: To characterize and describe clinical experience with childhood-onset non-infectious uveitis. STUDY DESIGN: A multicenter retrospective multidisciplinary national web-based registry of 507 patients from 21 hospitals was analyzed. Cases were grouped as immune disease-associated (IMDu), idiopathic (IDIu) or ophthalmologically distinct. Characteristics of juvenile idiopathic arthritis-associated (non-HLA-B27-related) uveitis (JIAu), IDIu, and pars planitis (PP) were compared. RESULTS: IMDu (62.3%) and JIAu (51.9%) predominated in young females; and IDIu (22.7%) and PP (13.6%) in older children, without sex imbalance. Ocular complications occurred in 45.3% of cases (posterior synechiae [28%], cataracts [16%], band keratopathy [14%], ocular hypertension [11%] and cystoid macular edema [10%]) and were associated with synthetic (86%) and biologic (65%) disease-modifying antirheumatic drug (DMARD) use. Subgroups were significantly associated (p < 0.05) with different characteristics. JIAu was typically anterior (98%), insidious (75%), in ANA-positive (69%), young females (82%) with fewer complications (31%), better visual outcomes, and later use of uveitis-effective biologics. In contrast, IDIu was characteristically anterior (87%) or panuveitic (12.1%), with acute onset (60%) and more complications at onset (59%: synechiae [31%] and cataracts [9.6%]) and less DMARD use, while PP is intermediate, and was mostly bilateral (72.5%), persistent (86.5%) and chronic (86.8%), with more complications (70%; mainly posterior segment and cataracts at last visit), impaired visual acuity at onset, and greater systemic (81.2%), subtenon (29.1%) and intravitreal (10.1%) steroid use. CONCLUSION: Prognosis of childhood uveitis has improved in the "biologic era," particularly in JIAu. Early referral and DMARD therapy may reduce steroid use and improve outcomes, especially in PP and IDIu.

Osteoporosis in psoriatic arthritis: Risk factors, insufficiency fractures and its association with the disease activity.

OBJECTIVE: The prevalence of osteoporosis (OP) and insufficiency fractures in psoriatic arthritis (PsA) remains controversial. The aim of this study was to describe the prevalence of OP and insufficiency fractures in a representative cohort of patients with PsA, and to analyse its association with general risk factors and characteristics of the psoriatic disease in our geographical area. METHODS: Multi-centric, descriptive study of patients with PsA. We recorded clinical characteristics, as well as protective and risk factors for OP and insufficiency fractures. Hip and lumbar densitometry and lateral X-ray of the spine were evaluated. Descriptive statistics for OP and risk factors were calculated. The patients with OP were compared to those without by univariate analyses, and results were adjusted by age and sex. The association of OP and fractures with clinical characteristics was analysed by logistic regression. RESULTS: 166 patients (50 men; 116 women) were included. OP was present in 26.5%, and it was more frequent in women and patients above 50 years old. Insufficiency fractures occurred in 5.4% of the total sample. In the logistic regression, OP was associated with age over 50 [OR 3.7; 95% CI (1.2-11.6); p=.02]. No association with clinical parameters was found. The most frequent risk factors among patients with OP were vitamin D insufficiency, sedentary behaviour, low calcium intake, and active smoking. In the logistic regression, OP was associated with early menopause [OR 11.7; 95% CI (1.29-106.0); p=.029] and sedentary behaviour [OR 2.3; 95% CI (1.0-5.2); p=.049]. CONCLUSIONS: In patients with PsA, OP is more frequent in women and patients over 50 years old. A sedentary lifestyle and early menopause may add extra risk for OP. Type, duration disease, and treatments are not associated with OP or insufficiency fractures.

Progressive alteration of murine bladder elasticity in actinic cystitis detected by Brillouin microscopy.

Bladder mechanical properties are critical for organ function and tissue homeostasis. Therefore, alterations of tissue mechanics are linked to disease onset and progression. This study aims to characterize the tissue elasticity of the murine bladder wall considering its different anatomical components, both in healthy conditions and in actinic cystitis, a state characterized by tissue fibrosis. Here, we exploit Brillouin microscopy, an emerging technique in the mechanobiology field that allows mapping tissue mechanics at the microscale, in non-contact mode and free of labeling. We show that Brillouin imaging of bladder tissues is able to recognize the different anatomical components of the bladder wall, confirmed by histopathological analysis, showing different tissue mechanical properties of the physiological bladder, as well as a significant alteration in the presence of tissue fibrosis. Our results point out the potential use of Brillouin imaging on clinically relevant samples as a complementary technique to histopathological analysis, deciphering complex mechanical alteration of each tissue layer of an organ that strongly relies on mechanical properties to perform its function.

Elaboración de dimensiones e indicadores para la toma de decisiones en la preparación táctica del judo

El desarrollo del deporte contemporáneo posee características que ejercen gran influencia en la organización de la preparación y del entrenamiento de los atletas. Este trabajo está relacionado con los resultados de la investigación que se realiza sobre la toma de decisiones en la preparación táctica del judo, para lo que se hace necesario la evaluación de los deportistas en las diferentes circunstancias en las que se encuentren dentro del combate; por lo que tiene como objetivo elaborar dimensiones e indicadores para la evaluación de la toma de decisiones desde la preparación táctica en los atletas de judo categoría juvenil de la Eide "Osmani Arenado", de Pinar del Río. La necesidad de que los judocas presenten niveles adecuados en la toma de decisiones en cada competencia a la que se enfrentan eleva las posibilidades de alcanzar resultados deportivos superiores; hecho que estimula la búsqueda, por parte de los entrenadores, de formas novedosas del proceso de preparación que se diferencien de las tradicionales. En la investigación, se utilizaron métodos teóricos como el análisis-síntesis y el sistémico-estructural-funcional; empíricos, la revisión de documentos, la observación científica, la entrevista y la consulta a especialistas; además de la estadística descriptiva. Como resultado, se determinaron los indicadores por cada dimensión establecida con sus correspondientes criterios de medida que permitieron el otorgamiento de una evaluación integral del proceso de toma de decisiones en los atletas de judo.

O desenvolvimento do esporte contemporâneo tem características que exercem grande influência na organização da preparação e do treinamento dos atletas. Este trabalho está relacionado aos resultados da pesquisa realizada sobre a tomada de decisão na preparação tática do judô, para a qual é necessário avaliar os atletas nas diferentes circunstâncias em que se encontram no combate; assim, tem como objetivo desenvolver dimensões e indicadores para a avaliação da tomada de decisão a partir da preparação tática em atletas de judô da categoria juvenil da Eide "Osmani Arenado", Pinar del Río. A necessidade de os judocas apresentarem níveis adequados de tomada de decisão em cada competição que enfrentam aumenta as possibilidades de alcançar resultados esportivos superiores, fato que estimula a busca, por parte dos treinadores, de novas formas do processo de preparação que se diferenciem das tradicionais. A pesquisa utilizou métodos teóricos, como análise-síntese e sistêmico-estrutural-funcional; empíricos, revisão de documentos, observação científica, entrevista e consulta a especialistas; bem como estatísticas descritivas. Como resultado, foram determinados indicadores para cada dimensão estabelecida com seus critérios de medição correspondentes que permitiram a concessão de uma avaliação integral do processo de tomada de decisão em atletas de judô.

The development of contemporary sport has characteristics that have a great influence on the organization of the preparation and training of athletes. This work is related to the results of the research that is carried out on decision-making in the tactical preparation of judo, for which it is necessary to evaluate the athletes in the different circumstances in which they are in combat; therefore, its objective is to elaborate dimensions and indicators for the evaluation of decision-making from the tactical preparation in the youth category judo athletes of "Ormany Arenado" Sport Initiation School (Eide in Spanish) from Pinar del Río. The need for judo athletes to present adequate levels in decision-making in each competition they face increases the possibilities of achieving superior sporting results; fact that stimulates the search, on the part of the coaches, of novel forms of the preparation process that differ from the traditional ones. In the research, theoretical methods such as analysis-synthesis and systemic-structural-functional, as well as empirical ones like document review, scientific observation, interview and consultation with specialists were used; in addition to descriptive statistics. As a result, the indicators were determined for each established dimension with their corresponding measurement criteria that allowed the granting of a comprehensive evaluation of the decision-making process in judo athletes.

Sex differences in cardiovascular and disease-related features in axial spondyloarthritis. A multicenter study of 912 patients.

OBJECTIVES: To determine the potential impact of sex-specific disease-related characteristics on cardiovascular (CV) disease in axial spondyloarthritis (axSpA). METHODS: Cross-sectional study of the Spanish AtheSpAin cohort to study CV disease in axSpA. Data on carotid ultrasound and CV disease and disease-related features were collected. RESULTS: 611 men and 301 women were recruited. Classic CV risk factors were significantly less prevalent in women, who also showed a lower frequency of carotid plaques (p = 0.001), lower carotid intima-media thickness (IMT) values ​​(p<0.001) and CV events (p = 0.008). However, after adjustment for classic CV risk factors, only the differences with respect to carotid IMT remained statistically significant. Women showed higher ESR at diagnosis (p = 0.038), and more active disease (ASDAS, p = 0.012, and BASDAI, p<0.001). They had shorter disease duration (p<0.001), lower prevalence of psoriasis (p = 0.008), less structural damage (mSASSS, p<0.001), and less mobility limitation (BASMI, p = 0.033). To establish whether these findings could lead to sex differences in CV disease burden, we compared the prevalence of carotid plaques in men and women with the same level of CV risk stratified according to the Systematic Coronary Risk Evaluation (SCORE). Men included in the low-moderate CV risk SCORE category had more carotid plaques (p = 0.050), along with longer disease duration (p = 0.004), higher mSASSS (p = 0.001) and psoriasis (p = 0.023). In contrast, in the high-very high-risk SCORE category, carotid plaques were observed more frequently in women (p = 0.028), who were characterized as having worse BASFI (p = 0.011), BASDAI (p<0.001) and ASDAS (p = 0.027). CONCLUSION: Disease-related features may influence the expression of atherosclerosis in patients with axSpA. This may be especially applicable to women at high CV risk, characterized by greater disease severity and more severe subclinical atherosclerosis than men, suggesting a stronger interaction between disease activity and atherosclerosis in women with axSpA.

Micro-mechanical fingerprints of the rat bladder change in actinic cystitis and tumor presence.

Tissue mechanics determines tissue homeostasis, disease development and progression. Bladder strongly relies on its mechanical properties to perform its physiological function, but these are poorly unveiled under normal and pathological conditions. Here we characterize the mechanical fingerprints at the micro-scale level of the three tissue layers which compose the healthy bladder wall, and identify modifications associated with the onset and progression of pathological conditions (i.e., actinic cystitis and bladder cancer). We use two indentation-based instruments (an Atomic Force Microscope and a nanoindenter) and compare the micromechanical maps with a comprehensive histological analysis. We find that the healthy bladder wall is a mechanically inhomogeneous tissue, with a gradient of increasing stiffness from the urothelium to the lamina propria, which gradually decreases when reaching the muscle outer layer. Stiffening in fibrotic tissues correlate with increased deposition of dense extracellular matrix in the lamina propria. An increase in tissue compliance is observed before the onset and invasion of the tumor. By providing high resolution micromechanical investigation of each tissue layer of the bladder, we depict the intrinsic mechanical heterogeneity of the layers of a healthy bladder as compared with the mechanical properties alterations associated with either actinic cystitis or bladder tumor.

PepSeq: a fully in vitro platform for highly multiplexed serology using customizable DNA-barcoded peptide libraries.

PepSeq is an in vitro platform for building and conducting highly multiplexed proteomic assays against customizable targets by using DNA-barcoded peptides. Starting with a pool of DNA oligonucleotides encoding peptides of interest, this protocol outlines a fully in vitro and massively parallel procedure for synthesizing the encoded peptides and covalently linking each to a corresponding cDNA tag. The resulting libraries of peptide/DNA conjugates can be used for highly multiplexed assays that leverage high-throughput sequencing to profile the binding or enzymatic specificities of proteins of interest. Here, we describe the implementation of PepSeq for fast and cost-effective epitope-level analysis of antibody reactivity across hundreds of thousands of peptides from <1 µl of serum or plasma input. This protocol includes the design of the DNA oligonucleotide library, synthesis of DNA-barcoded peptide constructs, binding of constructs to sample, preparation for sequencing and data analysis. Implemented in this way, PepSeq can be used for a number of applications, including fine-scale mapping of antibody epitopes and determining a subject's pathogen exposure history. The protocol is divided into two main sections: (i) design and synthesis of DNA-barcoded peptide libraries and (ii) use of libraries for highly multiplexed serology. Once oligonucleotide templates are in hand, library synthesis takes 1-2 weeks and can provide enough material for hundreds to thousands of assays. Serological assays can be conducted in 96-well plates and generate sequencing data within a further ~4 d. A suite of software tools, including the PepSIRF package, are made available to facilitate the design of PepSeq libraries and analysis of assay data.

Cardiovascular and disease-related features associated with extra-articular manifestations in axial spondyloarthritis. A multicenter study of 888 patients.

OBJECTIVES: To determine the potential impact of extra-articular manifestations (EAMs) on disease characteristics and cardiovascular (CV) risk in patients with axial spondylarthritis (axSpA). METHODS: This is a cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Data on the history of CV events, subclinical carotid atherosclerosis, and disease-related features, including EAMs, were collected. RESULTS: 888 axSpA patients were recruited. Concomitant acute anterior uveitis (AAU), psoriasis (PSO), and inflammatory bowel disease (IBD) were present in 177 (19.9%), 96 (10.8%), and 57 (6.4%) patients, respectively. When compared with axSpA patients without EAMs, a significant increase in past CV events was observed in patients with PSO (9% versus 4%, p = 0.048) and in those with at least one EAM (7% versus 4%, p = 0.032) or with more than one EAM (11% versus 4%, p = 0.022). The frequency of carotid plaques and the values of cIMT were higher in patients with EAMs than in those without EAMs, although only the univariable analysis for carotid plaques in patients with PSO (39% versus 30%, p = 0.038) and for cIMT in patients with AAU (665 ± 156 µm versus 637 ± 139 µm, p = 0.042) and those with at least one EAM (661 ± 155 µm versus 637 ± 139 µm, p = 0.024) showed significant results. In addition, patients with PSO or IBD were found to have specific disease-related features, such as higher ESR at diagnosis, and more frequent use of glucocorticoids and TNF inhibitors than those without EAMs. Also, PSO patients had more commonly peripheral involvement and those with AAU more severe radiographic damage than those without EAMs. The frequency of HLA B27 was higher in patients with AAU and lower in those with PSO or IBD compared to those without EAMs. CONCLUSION: Patients with axSpA and EAMs, in addition to displaying their own disease-related features, are likely to have an increased CV risk that appears proportional to the number of EAMs and could be related to proatherogenic factors other than traditional CV risk factors, such as the inflammatory load and the use of glucocorticoids.

Irisin as a Novel Biomarker of Subclinical Atherosclerosis, Cardiovascular Risk and Severe Disease in Axial Spondyloarthritis.

Introduction: Patients with axial spondyloarthritis (axSpA) have a high disease burden mainly due to the rheumatic disease itself, and also exhibit accelerated atherosclerosis, that leads to a higher incidence of cardiovascular (CV) disease. Accordingly, the identification of biomarkers of CV risk and inflammation in axSpA patients is clinically relevant. In this sense, given the beneficial functions exerted by the adipomyokine irisin in processes related to CV disease and inflammation, our aim was to assess, for the first time, the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis, CV risk and disease severity in axSpA patients. Methods: A large cohort of 725 Spanish patients with axSpA was included. Subclinical atherosclerosis (presence of plaques and abnormal carotid intima-media thickness values) was evaluated by carotid ultrasound. Four irisin polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A, and rs1570569 G/T) were genotyped by TaqMan probes. Additionally, serum irisin levels were determined by ELISA. Results: Low irisin levels were linked to the presence of plaques (p=0.002) and atherogenic index values ≥4 (p=0.01). Serum irisin were positively correlated with C-peptide levels (p<0.001) and negatively correlated with visual analogue scale and Bath Ankylosing Spondylitis Metrology Index (p<0.05 in all the cases). Moreover, lower irisin levels were observed in patients with sacroiliitis and in those with a negative HLA-B27 status (p<0.001 and p=0.006, respectively), as well as in those treated with non-steroidal anti-inflammatory drugs and conventional disease-modifying antirheumatic drugs (p<0.001 and p=0.002, respectively). Interestingly, the TT genotype and the T allele of rs16835198 were less frequent in axSpA patients with ASDAS >2.1 (Odds Ratio (OR): 0.48 [0.28-0.83] and OR: 0.73 [0.57-0.92], respectively, p=0.01 in both cases). Additionally, the frequency of rs1570569 T allele was higher in these patients (OR: 1.46 [1.08-1.97], p=0.01). Furthermore, the GGGT haplotype was more frequent in patients with ASDAS values >2.1 (OR: 1.73 [1.13-2.66], p=0.01). Conclusions: Our results indicate that low serum irisin levels could be indicators of the presence of subclinical atherosclerosis, high CV risk and more severe disease in axSpA patients. In addition, irisin may also constitute a genetic biomarker of disease activity in axSpA.

Factors associated with atherosclerosis in radiographic and non-radiographic axial spondyloarthritis. A multicenter study on 838 patients.

OBJECTIVES: To identify disease-related factors associated with subclinical atherosclerosis and cardiovascular (CV) events in a large series of patients with axial spondyloarthritis (axSpA) and to identify possible differences in the effect of the potential pro-atherogenic factors between ankylosing spondylitis (AS) non-radiographic axSpA (nr-axSpA). METHODS: This is a cross-sectional observational study of the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Subclinical atherosclerosis determined by carotid ultrasound included assessment of carotid intima-media thickness (cIMT) and plaque detection. RESULTS: 639 AS and 167 nr-axSpA patients were recruited. CV risk factors (CRF) and several disease-related factors showed a statistically significant association with subclinical atherosclerosis in the crude analysis. After adjustment for age, sex, and smoking (model 1), associations remained statistically significant for spinal mobility, inflammatory bowel disease, use of prednisone, and Disease-modifying antirheumatic drugs (DMARD) when assessing carotid plaques and for acute phase reactants (APR) at diagnosis, use of prednisone, DMARD, and TNF-inhibitors when measuring cIMT. In model 2, which also included classic CRF as confounding factors to identify axSpA features with a potential independent pro-atherogenic effect, the functional status was the only variable significantly associated with plaques and the use of prednisone and APR at diagnosis with cIMT. No association differences were found between both subtypes of patients. Besides, APR at diagnosis were also associated with subsequent development of CV events that had occurred in 33 patients. CONCLUSION: Apart from CRF, atherosclerotic disease in AxSpA is associated with disease-related factors such as inflammatory response and disease severity, with no differences between AS and nr-axSpA.

Assessment of Co-Formulants in Marketed Plant Protection Products by LC-Q-Orbitrap-MS: Application of a Hybrid Data Treatment Strategy Combining Suspect Screening and Unknown Analysis.

The aim of this study was the determination of co-formulants in 15 different chlorantraniliprole- and difenoconazole-based plant protection products (PPPs) belonging to different formulations. Samples were analyzed by ultrahigh-performance liquid chromatography coupled to Q-Orbitrap high-resolution mass accuracy spectrometry (UHPLC-Q-Orbitrap-MS), operating in full-scan MS and data-dependent acquisition (ddMS2) modes. A total of 78 co-formulants were tentatively identified by a combination of suspect screening and unknown analysis. Nine of them were later confirmed by analytical standards. Finally, the analytical method was successfully validated and co-formulants were quantified. Linear alkyl ethoxylates (LAS) were the most common type of co-formulant, followed by sodium alkylbenzene sulfonates. Moreover, sodium dodecyl benzene sulfonate had the highest concentration of any co-formulant (up to 32.33 g/L). In all, an innovative identification of co-formulants in a large number of PPPs is presented, which will give room for future studies delving into the composition of PPPs or determining these co-formulants in environmental or agricultural samples.

Medicine, Religion, and the Humanitarian Ethos: Walter B. Cannon, Unitarianism, and the Care of Spanish Republican Refugees in France.

Biographies of Walter B. Cannon (1871-1945) usually present two sides of his life: one, where he was an outstanding man of science in the United States during the so-called "Golden Age of Medicine," and the other, where he was a leading humanitarian activist engaged in myriad causes, notably in the defense of Spanish democracy during the Civil War (1936-1939). However, these biographies fail to take into account that the apparent link between these two sides of his life was his religious conviction. This study summarizes the aims and accomplishments of the American Medical Bureau to Aid the Spanish Democracy (AMBASD) of which Cannon was chair between 1937 and 1939. Then, it examines Cannon's inspirational role on the international relief work with Spanish Republican refugees in France, through the case of the Varsovie Hospital of Toulouse that between 1945 and 1949 was jointly managed by the Unitarian Service Committee (USC) and the Joint Anti-Fascist Refugee Committee (JAFRC), and renamed Varsovie Hospital/Walter B. Cannon Memorial in recognition of the Spanish Republicans' debt for his extraordinary contribution during the Spanish Civil War and beyond. Finally, the article investigates the Unitarian roots of Cannon's humanitarian ethos by exploring the historical relations of this religious movement with science and with many major actors at Harvard University as well as the links of Cannon's relatives to Unitarianism. The analysis reveals Unitarianism's influence on Cannon's views about science, democracy, and liberty, as well as on his remarkable involvement in the medical solidarity movement with the Second Spanish Republic and other similar commitments. In sum, it shows how important is to branch out in our studies of medical and scientific practice to include practitioners' broader social and religious communities in order to understand their motivations, achievements, and behavior.

Alternativa metodológica para mejorar el pensamiento táctico al Tashi Waza en los atletas de judo de Pinar del Río

La etapa contemporánea de desarrollo del deporte posee ciertas características que ejercen una gran influencia en la organización de la preparación y del entrenamiento de los deportistas, determinando para el entrenador nuevas tareas y exigencias más complejas. El presente trabajo tuvo como objetivo diseñar una alternativa metodológica para el mejoramiento del pensamiento táctico al Tashi Waza en los atletas de judo, categoría 15-16 años, de la Eide de Pinar del Río. Para entrar en materia, se esbozaron las características más importantes de la estrategia y la táctica del judo, así como los principios esenciales que las sustentan. Además, se puntualizó la conveniencia de utilizar formas auxiliares en la preparación técnica-táctica y formación del judoka. El estudio continúo con un ligero análisis aplicado al judo como una variable relevante en el desarrollo del pensamiento táctico. Se hizo hincapié en los diferentes tipos de táctica en el combate de judo, así como en los procesos psicomotores en cada una de las fases del combate, todo esto teniendo en cuenta las particularidades de los atletas en estas edades. Los métodos científicos de carácter empírico utilizados fueron la observación y la entrevista, teóricos como el histórico lógico y el análisis síntesis, los cuales le ofrecieron mayor rigor a la investigación. La idea de indagar sobre el pensamiento táctico del judo surgió desde hace unos años, ante la interrogante de enseñar a los atletas a darle solución por sí mismos, a los innumerables problemas que se les presentan en el combate.

A fase contemporânea do desenvolvimento do esporte tem certas características que influenciam muito a organização da preparação e treinamento dos atletas, determinando novas tarefas e exigências mais complexas para o treinador. O objetivo do presente trabalho era projetar uma alternativa metodológica para a melhoria do pensamento tático no Tashi Waza em atletas de judô, categoria 15-16 anos, do Eide de Pinar del Río. Foram apresentadas as características mais importantes da estratégia e das táticas de judô, bem como os princípios essenciais que as sustentam. Além disso, foi apontada a conveniência de utilizar formulários auxiliares na preparação e no treinamento técnico-táctico do judô. O estudo continuou com uma análise leve aplicada ao judô como uma variável relevante no desenvolvimento do pensamento tático. Foi dada ênfase aos diferentes tipos de táticas no combate ao judô, bem como aos processos psicomotores em cada uma das fases do combate, tudo isso levando em conta as particularidades dos atletas desta época. Os métodos científicos empíricos utilizados foram a observação e entrevista, e métodos teóricos como a análise e síntese histórico-lógica, que ofereceram mais rigor à pesquisa. A idéia de investigar o pensamento tático no judô surgiu há alguns anos, em resposta à questão de ensinar os atletas a encontrar suas próprias soluções para os inúmeros problemas que surgem no combate.

The contemporary stage of sport development has certain characteristics that exert a great influence on the organization of the preparation and training of athletes, determining for the coach new tasks and more complex demands. The present work had as objective to design a methodological alternative for the improvement of tactical thinking to Tashi Waza in judo athletes, category 15-16 years old, of the Initial Sport School (Eide in Spanish) of Pinar del Rio. To get into the subject, the most important characteristics of judo strategy and tactics were outlined, as well as the essential principles that support them. In addition, the convenience of using auxiliary forms in the technical-tactical preparation and training of the judo athletes was pointed out. The study continued with a light analysis applied to judo as a relevant variable in the development of tactical thinking. Emphasis was placed on the different types of tactics in judo combat, as well as on the psychomotor processes in each of the phases of combat, all this taking into account the particularities of athletes at these ages. The empirical scientific methods used were observation and interview, and the theoretical ones were historical-logical and synthesis analysis, which offered greater rigor to the research. The idea of investigating the tactical thinking in judo arose a few years ago, in response to the question of teaching athletes to solve by themselves the innumerable problems that arise in combat.

Human papilloma virus screening: evaluation of testing and surveillance in rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus.

BACKGROUND AND OBJECTIVES: Immunosuppression is a known risk factor for cervical cancer. Women with rheumatic conditions are immunosuppressed due to the disease and the treatments. One of the main risk factors for this neoplasm is the lack of adherence to early detection programmes for human papillomavirus. The objectives of this study were to evaluate the adherence to the screening programme of patients in the Rheumatology Clinic, as well as to evaluate the prevalence of cervical lesions and their association with the different disease characteristics and the treatments received. METHODS: A descriptive retrospective study. The electronic medical history of patients actively being followed up in a tertiary hospital with rheumatoid arthritis (RA), psoriatic arthritis (PSA) and systemic lupus erythematosus (SLE) were reviewed. RESULTS: Finally, 307 patients were included. No data were found for screening programme attendance in up to 42.4% of the patients (39.6% in RA, 43.8% in PSA and 46% in SLE). Among the patients who attended the screening programme at least once (57.6%), the prevalence of cervical dysplasia was 5.1%. No cases of neoplasia were found. In the simple logistic regression analysis, there was no association between attending the screening programme and any variable. The study also showed no association between the variables collected and the presence of infection and dysplasia. CONCLUSION: These results are influenced by the absence of screening data in a significant percentage of patients and by the low prevalence of dysplasia found in this series of patients with rheumatic diseases.

Use of benzodiazepines and antidepressants in patients who attend a Rheumatology clinic / Prevalencia de consumo de benzodiacepinas y antidepresivos en los pacientes que acuden por primera vez a la consulta de reumatología

ABSTRACT Introduction: During the last decades, benzodiazepines (BZD) and antidepressants (ADP) have been among the most prescribed therapies in all developed countries. They have side effects, and BZD carry a risk of abuse and dependence disorders. The purpose of this study was to evaluate the prevalence of BZD and ADP among patients who attend a Rheumatology clinic, as well as the indication for these drugs. Methods: The study included patients who were referred for the first time to the Rheumatology clinic. Demographical data, reason for referral, and final diagnosis were recorded. The indication for ADP and/or BZD was recorded, as well as the duration of treatment. Sample size was estimated for a 0.05% alpha risk. Univariate and multivariate analyses were performed in order to study the relationships with the demographical or clinical characteristics. Results: A total of 350 patients were included (women 77.1%, men 22.9%). Most of them (73.4%) had been referred for musculoskeletal pain. More than a third (36.6%) of patients were on BZD and/or ADP. The most frequent reasons for their prescription were anxiety, depression, and insomnia. The final diagnosis in the clinic was a non-inflammatory condition in 82%, and an inflammatory one in 18%. In the univariate analyses, the use of BZD/ADP was associated with female gender (p<.001), unemployment (p<.001) and non-inflammatory final diagnosis (p < .001). In the multivariate analyses, the use of BZD and/or ADP was associated with female sex (p = .002 [OR 3.4, 95% CI; 1.6-7.4]), and a non-inflammatory final diagnosis, specifically fibromyalgia (p = .007 [OR 16.1, 95% CI; 2.2-120.7]). Conclusion: Use of BZD and ADP is high and associated with non-inflammatory disease.

RESUMEN Introducción: Durante las últimas décadas, las benzodiacepinas (BZD) y los antidepresivos (ADP) han estado entre las terapias más prescritas en todos los países desarrollados. Estos fármacos tienen efectos secundarios y las BZD pueden ocasionar abuso y problemas de dependencia. El objetivo de este estudio fue evaluar la prevalencia de consumo de BZD y ADP entre los pacientes que acuden a una consulta de reumatología por primera vez, así como la indicación para ellos. Métodos: Se incluyeron pacientes remitidos por primera vez a la consulta de reumatología. Se registraron los datos demográficos, el motivo de la derivación y el diagnóstico final. Con respecto al tratamiento con ADP y/o BZD, se registraron su duración y la indicación de la prescripción. El tamaño de la muestra se estimó para un riesgo alfa de 0,05%. Se realizaron análisis univariantes y multivariantes para estudiar las asociaciones con características demográficas o clínicas. Resultados: Se incluyeron 350 pacientes (mujeres 77,1%, hombres 22,9%). La mayoría de ellos habían sido remitidos por dolor musculoesquelético (73,4%). Más de un tercio (36,6%) de los pacientes estaban en tratamiento con BZD y/o ADP. Las causas más frecuentes para su prescripción fueron ansiedad, depresión e insomnio. El diagnóstico final fue patología no inflamatoria en el 82% de los casos e inflamatoria en el 18% de estos. En el análisis univariante, el uso de BZD y/o ADP se asoció con el sexo femenino (p< 0,001), el desempleo (p< 0,001) y el diagnóstico de patología no inflamatoria (p< 0,001). En el análisis multivariante, el uso de BZD y/o ADP se asoció con el sexo femenino (p=0,002 [OR 3,4; IC 95% 1,6-7,4]) y el diagnóstico de patología no inflamatoria, específicamente con la fibromyalgia (p = 0,007 [OR 16,1; IC 95% 2,2-120,7]). Conclusión: El consumo de BZD y ADP es frecuente y está asociado con patología no inflamatoria.