Surgical and Radiology Trainees' Proficiency in Reading Mammograms: the Importance of Education for Cancer Localisation.

Medical imaging with mammography plays a very important role in screening and diagnosis of breast cancer, Australia's most common female cancer. The visualisation of cancers on mammograms often forms a diagnosis and guidance for radiologists and breast surgeons, and education platforms that provide real cases in a simulated testing environment have been shown to improve observer performance for radiologists. This study reports on the performance of surgical and radiology trainees in locating breast cancers. An enriched test set of 20 mammography cases (6 cancer and 14 cancer free) was created, and 18 surgical trainees and 32 radiology trainees reviewed the cases via the Breast Screen Reader Assessment Strategy (BREAST) platform and marked any lesions identifiable. Further analysis of performance with high- and low-density cases was undertaken, and standard metrics including sensitivity and specificity. Radiology trainees performed significantly better than surgical trainees in terms of specificity (0.72 vs. 0.35; P < 0.01). No significant differences were observed between the surgical and radiology trainees in sensitivity or lesion sensitivity. Mixed results were obtained with participants regarding breast density, with higher density cases generally having lower performance. The higher specificity of the radiology trainees compared to the surgical trainees likely represents less exposure to negative mammography cases. The use of high-fidelity simulated self-test environments like BREAST is able to benchmark, understand and build strategies for improving cancer education in a safe environment, including identifying challenging scenarios like breast density for enhanced training.

Chronic nasal dysfunction: A clinical case illustrating the concept in practice.

INTRODUCTION: We illustrate the diagnostic method for chronic nasal dysfunction by an observation in which the clinical history was compared to preoperative responses on the DyNaChron self-administered questionnaire, with ENT interpretation of the sinonasal CT scan preceding and guiding nasal endoscopy. CASE REPORT: The initial suspicion of rhinitis medicamentosa was transformed by the radiological and endoscopic findings of chronic respiratory rhinitis signs. Prick tests showing sensitivity to dust mites then suggested an allergic origin of the mucosal inflammation, which affected neither the olfactory nose nor the paranasal sinuses. A septal deviation hampering visualization of the right ethmoidal reliefs completed the clinical picture. Inferior turbinate hypertrophy secondary to allergic inflammation could have been aggravated by prolonged daily use of nasal vasoconstrictors. Failure of medical treatment combining nasal lavage, topical corticosteroids and an attempt at weaning led to effective medical and surgical management combining septoplasty, bilateral inferior turbinoplasty, continuation of topical corticosteroids and initiation of allergen immunotherapy. In addition to complete relief of nasal obstruction and abandonment of nasal vasoconstrictors, improved sense of smell completed the restoration of nasal comfort. DISCUSSION: It is helpful to conceive the nose as being anatomically and pathophysiologically a triple organ and to evaluate therapy in terms of improvement in each symptom.

Improving the design and conduct of aquatic toxicity studies with oils based on 20 years of CROSERF experience.

Laboratory toxicity testing is a key tool used in oil spill science, spill effects assessment, and mitigation strategy decisions to minimize environmental impacts. A major consideration in oil toxicity testing is how to replicate real-world spill conditions, oil types, weathering states, receptor organisms, and modifying environmental factors under laboratory conditions. Oils and petroleum-derived products are comprised of thousands of compounds with different physicochemical and toxicological properties, and this leads to challenges in conducting and interpreting oil toxicity studies. Experimental methods used to mix oils with aqueous test media have been shown to influence the aqueous-phase hydrocarbon composition and concentrations, hydrocarbon phase distribution (i.e., dissolved phase versus in oil droplets), and the stability of oil:water solutions which, in turn, influence the bioavailability and toxicity of the oil containing media. Studies have shown that differences in experimental methods can lead to divergent test results. Therefore, it is imperative to standardize the methods used to prepare oil:water solutions in order to improve the realism and comparability of laboratory tests. The CROSERF methodology, originally published in 2005, was developed as a standardized method to prepare oil:water solutions for testing and evaluating dispersants and dispersed oil. However, it was found equally applicable for use in testing oil-derived petroleum substances. The goals of the current effort were to: (1) build upon two decades of experience to update existing CROSERF guidance for conducting aquatic toxicity tests and (2) to improve the design of laboratory toxicity studies for use in hazard evaluation and development of quantitative effects models that can then be applied in spill assessment. Key experimental design considerations discussed include species selection (standard vs field collected), test substance (single compound vs whole oil), exposure regime (static vs flow-through) and duration, exposure metrics, toxicity endpoints, and quality assurance and control.

Índice trabecular óseo y niveles de 25-hidroxivitamina D en las complicaciones microvasculares de la diabetes mellitus tipo 2 / Trabecular bone score and 25-hydroxyvitamin D levels in microvascular complications of type 2 diabetes mellitus

Antecedentes y objetivo:La enfermedad microvascular (EMV) diabética ha sido asociada con una fragilidad ósea incrementada. El objetivo fue analizar la relación entre la EMV y la microestructura trabecular -evaluada mediante el índice trabecular óseo (trabecular bone score, TBS)- en pacientes diabéticos tipo 2 (DM2). Adicionalmente, conocer la relación entre la vitamina D y la EMV.Pacientes y métodos:Diseño transversal analítico, que incluyó varones > 50 años y mujeres postmenopáusicas con DM2, participantes en una cohorte poblacional. Se clasificó como EMV+ la presencia de nefropatía, neuropatía y/o retinopatía. Fueron analizadas variables clínicas, de laboratorio, el TBS, la 25-hidroxivitamina D [25(OH)D] y la densidad mineral ósea (DMO). Se realizaron análisis bivariable y multivariable.Resultados:Fueron evaluados 361 pacientes (51,1% mujeres), de 63,8 (9) años. De ellos, 92 tenían EMV, con un peor control metabólico, mayor duración de la DM2, menor TBS (1,235 [0,1] vs. 1,287 [0,1]; p=0,003) y menores niveles de 25(OH)D (18,3 [7] vs. 21,6 [8] ng/mL; p=0,0001). No hubo diferencias entre EMV+ y EMV- en la DMO ni en los marcadores P1NP y β-CTX. Tras ajustar por confusores, incluyendo HbA1c y duración de la DM2, el TBS en EMV+ fue 1,252 (IC 95% 1,230-1,274) vs. 1,281 (IC 95% 1,267-1,295) en EMV- (p=0,034). La EMV se asoció a un nivel de 25(OH)D < 20 ng/mL con una OR ajustada=1,88 (IC 95% 1,06-3,31; p=0,028).Conclusiones:Los pacientes con EMV presentaron un TBS significativamente menor, tras ajustar por confusores. El análisis multivariable mostró asimismo una asociación significativa entre un nivel bajo de 25(OH)D y la EMV prevalente. (AU)

Background and objective:Diabetic microvascular disease (MVD) has been associated with increased bone fragility. The objective was to analyse the relationship between MVD and trabecular microstructure -assessed by the trabecular bone score (TBS)- in type 2 diabetic (T2D) patients. A second aim was to know the relationship between vitamin D and MVD.Patients and methods:Cross-sectional study, which included men >50 years and postmenopausal women participating in a population-based cohort, diagnosed with T2D. The presence of nephropathy, neuropathy and/or retinopathy was classified as MVD+. Clinical and laboratory variables, TBS, 25(OH)D and BMD by DXA, were evaluated. Bivariate and multivariate analysis were performed.Results:We evaluated 361 patients (51.1% women), 63.8 (9) years old. Of them, 92 were MVD+ and presented poorer metabolic control, longer duration of T2D, lower TBS [1.235 (.1) vs. 1.287 (.1); p=.007] and lower levels of 25(OH)D [18.3 (7) vs. 21.6 (8) ng/ml; p=.0001). There were no differences between MVD+ and MVD- with regard to BMD or P1NP and β-CTX markers. After adjusting for confounders, including HbA1c and duration of T2D, the TBS value in MVD+ was 1.252 (95% CI 1.230-1.274) vs. 1.281 (95% CI 1.267-1.295) in MVD- (p=.034). MVD was associated with a 25(OH)D level <20 ng ml with an adjusted OR of 1.88 (95% CI 1.06-3.31; p=.028).Conclusions:The MVD+ patients presented a significantly lower TBS, after adjusting for confounders. Furthermore, multivariable analysis showed a significant relationship between a low 25(OH)D level and a prevalent MVD. (AU)

Chronic respiratory rhinitis: Toward endoscopic diagnosis of nasal allergy? An observational study.

OBJECTIVE: The study objective was to assess the functional, endoscopic and tomodensitometric semiology of a cohort of patients with chronic respiratory rhinitis (CRR). The concept of CRR is based on the anatomical, pathophysiological and semiological individualization of the respiratory nose within the sinonasal organ, in which three noses are distinguished by the parallel study of evolution and development in the "evo-devo" theory of the origins of the nose, anterior base of the skull and middle third of the face. MATERIAL AND METHOD: A single-center retrospective study included a cohort of 28 patients (16 men and 12 women, aged 19 to 69years) with CRR. The main objective was to describe symptoms clinically, endoscopically and on CT. The secondary objective was to compare clinical symptomatology and CT data between CRR and a control group of 31 patients with nasal polyposis (NP). The endoscopic semiology of CRR was analyzed consensually on video recordings using a pre-established grid. The DyNaChron self-administered questionnaire was used to compare symptom intensity and deterioration in quality of life. Olfaction was compared using the Sniffin' Sticks test. CT opacities were compared between CRR and NP on Lund-Mackay sinus score and a specific ethmoid opacities score. RESULTS: In CRR, endoscopy found a constant association of inflammatory or edematous signs in the inferior or middle turbinates with signs of hypersecretion. Ethmoid opacities in CRR were discrete and significantly smaller than in NP (P<0.0001), and were mainly located in the medial compartment in contact with the olfactory cleft (P<0.0001). Allergological assessment was positive in 17 of the 28 cases of CRR. Chronic nasal dysfunction was similar in CRR and NP, but olfactory impairment was significantly lower in CRR (P<0.0001). CONCLUSION: The CRR entity clinically resembles atopic central compartment disease. In both entities, endoscopy reveals inflammatory lesions restricted to the nasal cavities without significant ethmoid opacity on CT, an observation which seems to contradict the pathophysiological united airway concept.

Systematic training in master swimmer athletes increases serum insulin growth factor-1 and decreases myostatin and irisin levels.

During ageing, anabolic status is essential to prevent the decrease in quantity and quality of skeletal muscle mass (SMM). Exercise modulates endocrine markers of muscle status. We studied the differences of endocrine markers for muscle status in 62 non-sarcopenic Mexican swimmer adults aged 30-70 y/o, allocated into two groups: the systematic training (ST) group including master athletes with a physical activity level (PAL) >1.6, and the non-systematic training group (NST) composed by subjects with a PAL <1.5. Body composition, diet, biochemical and endocrine markers were analyzed. The ST group showed lower myostatin (MSTN) and irisin (IRI) levels, two strong regulators of SMM. The insulin growth factor-1 (IGF-1) was higher in the ST. This is consistent with most of the evidence in young athletes and resistance training programs, where IGF-1 and IRI seem to play a crucial role in maintaining anabolic status in master athletes.

Trabecular bone score and 25-hydroxyvitamin D levels in microvascular complications of type 2 diabetes mellitus. / Índice trabecular óseo y niveles de 25-hidroxivitamina D en las complicaciones microvasculares de la diabetes mellitus tipo 2.

BACKGROUND AND OBJECTIVE: Diabetic microvascular disease (MVD) has been associated with increased bone fragility. The objective was to analyse the relationship between MVD and trabecular microstructure -assessed by the trabecular bone score (TBS)- in type 2 diabetic (T2D) patients. A second aim was to know the relationship between vitamin D and MVD. PATIENTS AND METHODS: Cross-sectional study, which included men >50 years and postmenopausal women participating in a population-based cohort, diagnosed with T2D. The presence of nephropathy, neuropathy and/or retinopathy was classified as MVD+. Clinical and laboratory variables, TBS, 25(OH)D and BMD by DXA, were evaluated. Bivariate and multivariate analysis were performed. RESULTS: We evaluated 361 patients (51.1% women), 63.8 (9) years old. Of them, 92 were MVD+ and presented poorer metabolic control, longer duration of T2D, lower TBS [1.235 (.1) vs. 1.287 (.1); p=.007] and lower levels of 25(OH)D [18.3 (7) vs. 21.6 (8) ng/ml; p=.0001). There were no differences between MVD+ and MVD- with regard to BMD or P1NP and ß-CTX markers. After adjusting for confounders, including HbA1c and duration of T2D, the TBS value in MVD+ was 1.252 (95% CI 1.230-1.274) vs. 1.281 (95% CI 1.267-1.295) in MVD- (p=.034). MVD was associated with a 25(OH)D level <20 ng ml with an adjusted OR of 1.88 (95% CI 1.06-3.31; p=.028). CONCLUSIONS: The MVD+ patients presented a significantly lower TBS, after adjusting for confounders. Furthermore, multivariable analysis showed a significant relationship between a low 25(OH)D level and a prevalent MVD.

Comparisons of PNEC derivation logic flows under example regulatory schemes and implications for ecoTTC.

Derivation of Predicted No Effect Concentrations (PNECs) for aquatic systems is the primary deterministic form of hazard extrapolation used in environmental risk assessment. Depending on the data availability, different regulatory jurisdictions apply application factors (AFs) to the most sensitive measured endpoint to derive the PNEC for a chemical. To assess differences in estimated PNEC values, two PNEC determination methodologies were applied to a curated public database using the EnviroTox Platform (www.EnviroToxdatabase.org). PNECs were derived for 3647 compounds using derivation procedures based on example US EPA and a modified European Union chemical registration procedure to allow for comparisons. Ranked probability distributions of PNEC values were developed and 5th percentile values were calculated for the entire dataset and scenarios where full acute or full chronic data sets were available. The lowest PNEC values indicated categorization based on chemical attributes and modes of action would lead to improved extrapolations. Full acute or chronic datasets gave measurably higher 5th percentile PNEC values. Algae were under-represented in available ecotoxicity data but drove PNECs disproportionately. Including algal inhibition studies will be important in understanding chemical hazards. The PNEC derivation logic flows are embedded in the EnviroTox Platform providing transparent and consistent PNEC derivations and PNEC distribution calculations.

Multiplexed Signal Ion Emission Reactive Release Amplification (SIERRA) Assay for the Culture-Free Detection of Gram-Negative and Gram-Positive Bacteria and Antimicrobial Resistance Genes.

The global prevalence of antibiotic-resistant bacteria has increased the risk of dangerous infections, requiring rapid diagnosis and treatment. The standard method for diagnosis of bacterial infections remains dependent on slow culture-based methods, carried out in central laboratories, not easily extensible to rapid identification of organisms, and thus not optimal for timely treatments at the point-of-care (POC). Here, we demonstrate rapid detection of bacteria by combining electrochemical immunoassays (EC-IA) for pathogen identification with confirmatory quantitative mass spectral immunoassays (MS-IA) based on signal ion emission reactive release amplification (SIERRA) nanoparticles with unique mass labels. This diagnostic method uses compatible reagents for all involved assays and standard fluidics for automatic sample preparation at POC. EC-IA, based on alkaline phosphatase-conjugated pathogen-specific antibodies, quantified down to 104 bacteria per sample when testing Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa lysates. EC-IA quantitation was also obtained for wound samples. The MS-IA using nanoparticles against S. aureus, E. coli, Klebsiella pneumoniae, and P. aeruginosa allowed selective quantitation of ∼105 bacteria per sample. This method preserves bacterial cells allowing extraction and amplification of 16S ribosomal RNA genes and antibiotic resistance genes, as was demonstrated through identification and quantitation of two strains of E. coli, resistant and nonresistant due to ß-lactamase cefotaximase genes. Finally, the combined immunoassays were compared against culture using remnant deidentified patient urine samples. The sensitivities for these immunoassays were 83, 95, and 92% for the prediction of S. aureus, P. aeruginosa, and E. coli or K. pneumoniae positive culture, respectively, while specificities were 85, 92, and 97%. The diagnostic platform presented here with fluidics and combined immunoassays allows for pathogen isolation within 5 min and identification in as little as 15 min to 1 h, to help guide the decision for additional testing, optimally only on positive samples, such as multiplexed or resistance gene assays (6 h).

Toxicity of sediment oiled with diluted bitumens to freshwater and estuarine amphipods.

To address knowledge gaps and the lack of benchmarks on the toxicity of dilbit oiled sediments, weathered Cold Lake Blend (CLB) and Western Canadian Select (WCS) were assessed in 10-day sediment tests with the amphipods Hyalella azteca and Leptocheirus plumulosus. Lowest observed effect concentrations (LOECs) and 20% effect levels (EC20s) were determined for wet weight sediment concentrations of TPH and total PAHs normalized to 1% organic carbon. LOECs and EC20s for TPH ranged from 216 to 1165 mg/kg sediment in H. azteca, and from 64 to 75 mg/kg sediment in L. plumulosus. Dilbit LOECs and EC20s for total PAHs ranged from 2.9 to 11.8 mg/kg sediment in H. azteca, and from 0.75 to 0.87 mg/kg in L. plumulosus. Comparison of toxicity-based benchmarks derived from the current study to sediment concentrations from past spills indicate that dilbit spills in aquatic habitats may pose substantial risks to freshwater and estuarine benthic organisms.

Radiologic assessment of abdominal aortic calcifications, atherosclerotic burden levels and statistical bias affecting the reliability.

INTRODUCTION: AAC-8 and AAC-24 are two widely used scales to evaluate abdominal aortic calcification (AAC) on X-ray images. Levels of ≥3 (AAC-8) and ≥5 points (AAC-24) are of high relevance since they are associated with greater risk of cardiovascular events. Given that it is unknown, our aim was to determine the reliability of both scales at those levels of atherosclerotic burden. METHODS: The sample (93 subjects, 67.3 ± 9.7 years, BMI 28.8 ± 3.8, 57.6% smokers, 64.1% with hypertension) was classified according to quartiles of calcification. Six clinicians evaluated AAC independently with both scales on lateral lumbar spine X-ray images. We analyzed inter-rater agreement with the intraclass correlation coefficient (ICC) and the Bland-Altman scatterplots. RESULTS: We assessed 15 pairs of raters. Scores in both scales were significantly correlated with cardiovascular risk (r = 0.31 and r = 0.32; p < 0.005). Agreement was very high in the first quartile and moderate in the rest (p < 0.05). At cut-off points, ICC = 0.70 (95%CI, 0.54-0.86) and ICC = 0.68 (95%CI, 0.60-0.85) with AAC-8 and AAC-24. With the Bland-Altman method, mean of the differences ranged between 0 and 0.4 (AAC-8), and between 0.2 and 1 (AAC-24), while 95% limits of agreement showed values between 2.9 and 4.4 (AAC-8), and between 6 and 11.2 (AAC-24). Analyzing entire scales, ICC = 0.97 (95%CI, 0.97-0.98) and ICC = 0.98 (95%CI, 0.97-0.98) for AAC-8 and AAC-24, respectively. CONCLUSION: Both scales presented only moderate reliability at levels of atherosclerotic burden. Analyzing quartiles with ICC and the Bland-Altman plot showed concordant results. High global ICC values traditionally reported with both scales are likely biased. IMPLICATIONS FOR PRACTICE: AAC predicts subsequent vascular morbidity and mortality and should implicate evaluation of cardiovascular risk. Optimal visualisation of AAC and its correct assessment are mandatory in order to maximize patient care.

Trabecular bone score and bone turnover markers in men with DISH: Data from the Camargo Cohort study.

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) has been associated with an increased risk of vertebral fracture. To date, no studies have investigated the relationship between DISH and bone microstructure assessed by the trabecular bone score (TBS). METHODS: Cross-sectional study, nested in a prospective population-based cohort. All men (968) aged≥50 years were included. Clinical covariates, DISH, TBS, serum bone turnover markers and bone mineral density (BMD) were analyzed. RESULTS: Mean age of participants was 65 ± 9 years. 207 (21.6%) had DISH. DISH subjects were older, had higher body mass index (BMI) and abdominal perimeter, lower glomerular filtration rate (GFR), and higher prevalence of metabolic syndrome (MetS) than non-DISH (NDISH) subjects. Bone mineral density at the lumbar spine (LS-BMD) was significantly higher in the DISH group. TBS values were 1.317 [1.303-1.331] for DISH and 1.334 [1.327-1.341] for NDISH subjects, after adjusting by age, BMI, abdominal perimeter, arterial hypertension, diabetes mellitus, MetS, GFR, serum alkaline phosphatase (ALP), LS and femoral neck BMD (p = 0.03). Serum ALP levels were higher in DISH subjects, showing an inverse correlation with TBS that remained significant after adjusting by age and BMI. CONCLUSIONS: TBS values were significantly lower in men with DISH irrespective of age, BMI and BMD, suggesting that the presence of DISH might be related to a worse trabecular microstructure.

Elevated pCO2 and Hypoxia Alter the Acid-Base Homeostasis of Developing Sheepshead Minnows, Cyprinodon variegatus.

Low dissolved oxygen and increased acidification are two environmental variables that concomitantly change in an estuarine environment, both of which are exacerbated by nutrient pollution and subsequent eutrophication. To better understand how estuarine residents compensate for daily fluctuations in these environmental variables, the interactive effects of acidification and hypoxia were assessed in developing sheepshead minnows (Cyprinodon variegatus) using a 2 by 2 factorial design over a 42-day exposure. Embryos were exposed to either acidic (partial pressure of CO2, pCO2, ~2000 µatm), hypoxic (reduced dissolved oxygen, ~2 mg l-1), or combined acidic and hypoxic conditions and monitored for development, hatch rate, and survival. Changes in oxygen consumption, anaerobic metabolism, oxidative stress, and acid-base balance were evaluated at three life stages (embryo, larval, and juvenile fish) to discern if and how fish compensate for these stressors during development. The combination of acidification and hypoxia delayed hatching in embryos and significantly decreased oxygen consumption (p<0.001) in all three life-stages. Neither acidification, hypoxia, nor the combination of the stressors impacted the anaerobic metabolism or oxidative stress of juvenile fish, but acid-base equilibrium was disrupted by all three treatments in larval fish. Elevated carbonic anhydrase activity was observed in the multi-stress treatment in embryos and larval fish, but not in juvenile fish. These results show that developing sheepshead minnows can re-establish cellular homeostasis in compensating to acidified and hypoxic waters.

Application of Interspecies Correlation Estimation (ICE) models and QSAR in estimating species sensitivity to pesticides.

Ecological risk assessment is challenged by the need to assess hazard to the diverse communities of organisms inhabiting aquatic and terrestrial systems. Computational approaches, such as Quantitative Structure Activity Relationships (QSAR) and Interspecies Correlation Estimation (ICE) models, are useful tools that provide estimates of acute toxicity where data are lacking or limited for ecological risk assessments (ERA). This review describes the technical basis of ICE models for use in pesticide ERA that may be used in conjunction with QSAR model estimates or surrogate species toxicity data and demonstrates the potential for improving hazard assessment. Validation and uncertainty analysis of ICE model predictions are summarized and used as guidance for selecting ICE models and evaluating toxicity predictions. A user-friendly web-based ICE modelling platform (Web-ICE) is described and demonstrated through case studies. Case studies include the development of Species Sensitivity Distributions generated from QSAR and ICE estimates, comparative sensitivity for a pesticide and its degradate, and application of ICE-estimated toxicity values for listed species assessments.

Calidad de vida relacionada con la salud (CVRS) en la hipertensión arterial: un análisis diferenciado por género sobre población de cantabria / Health-related quality of life in hypertension: a gender-differentiated analysis in population of Cantabria

OBJETIVO: La hipertensión arterial (HTA), por su elevada prevalencia y morbimortalidad, es un importante problema de Salud Pública. Se asocia a una peor calidad de vida relacionada con la salud (CVRS). El objetivo de este trabajo fue conocer la CVRS de la población hipertensa en un análisis diferenciado por género. MÉTODOS: Se realizó un estudio transversal. Participaron cinco cupos de Medicina de Familia. Se evaluó la CVRS (mediante el cuestionario EuroQol-5D), cuatro variables relacionadas con la HTA (grado de control, duración de la enfermedad, uso de fármacos antihipertensivos y lesión de órgano diana -LOD-), variables sociodemográficas, de estilo de vida y clínicas. Se realizó análisis bivariado y se elaboraron dos modelos multivariados, con el índice EuroQol-5D (iEQ) como variable dependiente. RESULTADOS: Fueron analizadas 198 mujeres (55,7%) y 157 varones. Las mujeres, significativamente, tenían menor nivel educativo, pasaban más tiempo solas, consumían más psicofármacos, su iEQ fue menor (0,887 [0,2] frente a 0,914 [0,1]; p = 0,0001) y puntuaron peor en cuidado personal, actividades cotidianas, dolor/malestar y ansiedad/depresión. En las mujeres, tras ajustar por confusores, ninguna variable relacionada con la HTA presentó una asociación significativa con el iEQ, y la capacidad funcional fue la variable más importante (beta=0,35; p = 0,0001). En los varones, la LOD (beta=0,18) y la duración de la HTA (beta=0,16) se asociaron significativamente con el iEQ, siendo el consumo de psicofármacos la variable más relevante del modelo de regresión (beta=0,42; p = 0,005). CONCLUSIONES: Se observan notables diferencias en la CVRS de las mujeres y los varones con HTA. Detectar dichas diferencias permite conocer los perfiles más frágiles de nuestros pacientes

OBJECTIVE: Hypertension is a major public health problem due to its high prevalence and morbi-mortality. It is associated with a worse health-related quality of life (HRQOL). The aim has been to know the HRQOL of the hypertensive population in a gender-differentiated analysis. METHODS: Cross-sectional study. Hypertensive patients attended in Primary Care were enrolled in the study. We evaluated HRQOL (using the EuroQol-5D questionnaire), four covariates related to hypertension (degree of control, duration of disease, use of antihypertensive drugs and target organ damage -TOD-), and sociodemographic, lifestyle and clinical variables. Bivariate analysis was performed and two multivariate models were developed, with the EuroQol-5D index (iEQ) as the dependent variable. RESULTS: We analyzed 198 women (55.7%) and 157 men. Significantly, females had a lower educational level, spent more time alone, consumed more psychotropic medication, their iEQ was lower [0.887 (0.2) vs. 0.914 (0.1); p = 0.0001] and scored worse in self-care, usual activities, pain / discomfort and anxiety / depression. In women, no variable related to hypertension presented a significant association with the iEQ after adjusting for confounders, and functional capacity was the most important covariate (Beta=0.35; p = 0.0001). In males, TOD (Beta=0.18) and duration of the disease (Beta=0.16) were significantly associated with the iEQ, with the consumption of psychotropic medication being the most relevant covariate in the regression model (Beta=0.42; p = 0.005). CONCLUSIONS: Notable differences in HRQOL of women and men with hypertension have been noted. Detecting these differences allows us to know the frailest states of our patients

New Frontiers: ARID3a in SLE.

Systemic lupus erythematosus (SLE) is a devastating and heterogeneous autoimmune disease that affects multiple organs, and for which the underlying causes are unknown. The majority of SLE patients produce autoantibodies, have increased levels of type-I inflammatory cytokines, and can develop glomerulonephritis. Recent studies indicate an unexpected but strong association between increased disease activity in SLE patients and the expression of the DNA-binding protein ARID3a (A + T rich interaction domain protein 3a) in a number of peripheral blood cell types. ARID3a expression was first associated with autoantibody production in B cells; however, more recent findings also indicate associations with expression of the inflammatory cytokine interferon alpha in SLE plasmacytoid dendritic cells and low-density neutrophils. In addition, ARID3a is expressed in hematopoietic stem cells and some adult kidney progenitor cells. SLE cells expressing enhanced ARID3a levels show differential gene expression patterns compared with homologous healthy control cells, identifying new pathways potentially regulated by ARID3a. The associations of ARID3a expression with increased disease severity in SLE, suggest that it, or its downstream targets, may provide new therapeutic targets for SLE.

Enumeration of Rare Cells in Whole Blood by Signal Ion Emission Reactive Release Amplification with Same-Sample RNA Analysis.

Herein is presented a platform capable of detecting less than 30 cells from a whole blood sample by size-exclusion filtration, microfluidic sample handling, and mass spectrometric detection through signal ion emission reactive release amplification (SIERRA). This represents an approximate 10-fold improvement in detection limits from previous work. Detection by SIERRA is accomplished through the use of novel nanoparticle reagents coupled with custom fluidic fixtures for precise sample transfer. Sample processing is performed in standardized 96-well microtiter plates with commonly available laboratory instrumentation to facilitate assay automation. The detection system is easily amenable to multiplex detection, and compatibility with PCR-based gene assays is demonstrated.

Aged human skin accumulates mast cells with altered functionality that localize to macrophages and vasoactive intestinal peptide-positive nerve fibres.

BACKGROUND: Skin health declines with age and this is partially attributed to immunosenescence. Mast cells (MCs) are innate immune cells that coordinate tissue immune responses integral to skin homeostasis and disease. OBJECTIVES: To understand how MCs contribute to human skin ageing, we investigated how intrinsic ageing impacts MC phenotype and MC relationships with other immune cells and skin structures. METHODS: In photoprotected skin biopsies from young (≤ 30 years) and aged (≥ 75 years) individuals, immunostaining and spatial morphometry were performed to identify changes in MC phenotype, number, distribution and interaction with the vasculature and nerve fibres. Quantitative polymerase chain reaction was used to measure changes in gene expression related to immune cell activity and neuropeptide signalling. RESULTS: Skin MCs, macrophages and CD8+ T cells increased in number in intrinsically aged vs. young skin by 40%, 44% and 90%, respectively (P < 0·05), while CD4+ T cells and neutrophils were unchanged. In aged skin, MCs were more numerous in the papillary dermis and showed a reduced incidence of degranulation (50% lower than in young, P < 0·01), a conserved tryptase-chymase phenotype and coexpression of granzyme B. In aged skin, MCs increased their association with macrophages (~ 48% vs. ~27%, P < 0·05) and nerve fibres (~29% vs. 16%, P < 0·001), while reducing their interactions with blood vessels (~34% vs. 45%, P < 0·001). Additionally, we observed modulation of gene expression of vasoactive intestinal peptide (VIP; increased) and substance P (decreased) with age; this was associated with an increased frequency of VIP+ nerve fibres (around three times higher in aged skin, P < 0·05), which were strongly associated with MCs (~19% in aged vs. 8% in young, P < 0·05). CONCLUSIONS: In photoprotected skin we observed an accumulation of MCs with increasing age. These MCs have both altered functionality and distribution within the skin, which supports a role for these cells in altered tissue homeostasis during ageing.

ARID3a gene profiles are strongly associated with human interferon alpha production.

Type I interferons (IFN) causes inflammatory responses to pathogens, and can be elevated in autoimmune diseases such as systemic lupus erythematosus (SLE). We previously reported unexpected associations of increased numbers of B lymphocytes expressing the DNA-binding protein ARID3a with both IFN alpha (IFNα) expression and increased disease activity in SLE. Here, we determined that IFNα producing low density neutrophils (LDNs) and plasmacytoid dendritic cells (pDCs) from SLE patients exhibit strong associations between ARID3a protein expression and IFNα production. Moreover, SLE disease activity indices correlate most strongly with percentages of ARID3a+ LDNs, but were also associated, less significantly, with IFNα expression in LDNs and pDCs. Hierarchical clustering and transcriptome analyses of LDNs and pDCs revealed SLE patients with low ARID3a expression cluster with healthy controls and identified gene profiles associated with increased proportions of ARID3a- and IFNα-expressing cells of each type. These data identify ARID3a as a potential transcription regulator of IFNα-related inflammatory responses and other pathways important for SLE disease activity.