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Previous studies have found inconsistent associations between heavy metals and metalloids (cadmium, lead, mercury, and arsenic), and reproductive outcomes. The biofluid concentrations of ten non-essential trace elements (Hg, Pb, As, Ba, Sr, Rb, Cs, Sn, Ni, and Co) were evaluated in 51 Spanish women undergoing ICSI, PGT-A, and SET/FET. Nine out of ten non-essential elements were detectable in follicular fluid, whole blood, and urine collected the day of vaginal oocyte retrieval (VOR) and the day of embryo transfer and then analyzed by ICP-MS or Tricell DMA-80 for mercury. Elevated mercury and strontium concentrations in follicular fluid were associated with poor ovarian response and preimplantation outcomes. Worst preimplantation outcomes were also identified in women with elevated whole-blood strontium or mercury, urinary arsenic, barium, and tin the day of VOR. High concentrations of urinary rubidium on VOR day were linked with enhanced fertilization and blastocyst development. Excessive titanium in whole blood was associated with lower odds of implantation, clinical pregnancy, and achieving a live birth in a given IVF cycle. Excessive urinary arsenic on the day of embryo transfer was associated with lower odds of live birth. Although these preliminary results need to be confirmed in larger populations, distinguishing organic and inorganic element forms, our findings show that some non-essential elements have a detrimental impact on human IVF outcomes.

BackgroundMobile phone–based SMS text message reminders have the potential to improve colorectal cancer screening participation rates. ObjectiveThis study assessed the effectiveness and acceptability of adding targeted SMS text message reminders to the standard procedure for those who picked up but did not return their screening kit at the pharmacy within 14 days in a colorectal cancer screening program in Catalonia, Spain. MethodsWe performed a randomized control trial among individuals who picked up a fecal immunochemical test (FIT) kit for colorectal cancer screening at the pharmacy but did not return it within 14 days. The intervention group (n=4563) received an SMS text message reminder on the 14th day of kit pick up and the control group (n=4806) received no reminder. A 30-day reminder letter was sent to both groups if necessary. The main primary outcome was the FIT completion rate within 30, 60, and 126 days from FIT kit pick up (intention-to-treat analysis). A telephone survey assessed the acceptability and appropriateness of the intervention. The cost-effectiveness of adding an SMS text message reminder to FIT completion was also performed. ResultsThe intervention group had higher FIT completion rates than the control group at 30 (64.2% vs 53.7%; P

Background: The 300IR house dust mite (HDM) sublingual immunotherapy (SLIT) tablet is approved for treatment of HDM-induced allergic rhinitis (AR). To provide a comprehensive review of the 300IR HDM-SLIT tablet safety profile based on randomized controlled trial (RCT) pooled data and post-marketing (PM) pharmacovigilance data. Methods: Subjects (5–65 years) with confirmed HDM-AR with or without controlled asthma were treated with 300IR or placebo in 8 RCTs. Reported treatment-emergent adverse events (TEAEs) were pooled and analyzed descriptively in subsets of adults/adolescents and children. Adverse reactions (ADRs) collected from spontaneous reporting and PM studies through a pharmacovigilance system since the first marketing authorization were also analyzed. Results: Across RCTs, 1853 subjects were treated with the 300IR HDM-SLIT tablet and 1846 with placebo. In both subsets of adults/adolescents and children whichever their asthma status, treatment-related TEAEs of higher incidence in active groups vs placebo were mostly consistent with mild or moderate local application-site reactions. They were mainly reported on the first days of treatment and decreased over time. 4 severe laryngopharyngeal reactions (2 requiring adrenaline/epinephrine) and 1 moderate eczema considered serious rapidly resolved with medications; no anaphylaxis was reported. In PM settings, ADRs reported in more than 235,000 patients were in line with RCT findings. Severe systemic reactions occurred rarely; 12 anaphylactic reactions resolved safely (5 with adrenaline). No new safety signal was raised. Conclusion: Safety data from RCTs and more than 7 years of real-life experience confirmed the favorable safety profile of 300IR HDM-SLIT tablet in patients across different regions, regardless of age and asthma status. Clinical trial registrations: NCT00674700; Retrospectively registered 06 May 2008.NCT01199133; Retrospectively registered 09 September 2010.NCT01527188; Retrospectively registered 01 February 2012.NCT02443805; Registered 29 April 2015/EudraCT 2014-004223-46; Registered 16 September 2015.jRCT2080221872/JapicCTI-121917; Registered 01 August 2012.jRCT2080222929/JapicCTI-15298; Registered 04 August 2015.

Abstract Background Women with adenomyosis are characterized by having defective decidualization, impaired endometrial receptivity and/or embryo-maternal communication, and implantation failure. However, the molecular mechanisms underlying adenomyosis-related infertility remain unknown, mainly because of the restricted accessibility and the difficult preservation of endometrial tissue in vitro. We have recently shown that adenomyosis patient-derived endometrial organoids, maintain disease-specific features while differentiated into mid-secretory and gestational endometrial phase, overcoming these research barriers and providing a robust platform to study adenomyosis pathogenesis and the associated molecular dysregulation related to implantation and pregnancy disorders. For this reason, we aim to characterize the dysregulated mechanisms in the mid-secretory and gestational endometrium of patients with adenomyosis by RNA-sequencing. Methods Endometrial organoids were derived from endometrial biopsies collected in the proliferative phase of women with adenomyosis (ADENO) or healthy oocyte donors (CONTROL) (n = 15/group) and differentiated into mid-secretory (-SECorg) and gestational (-GESTorg) phases in vitro. Following RNA-sequencing, the significantly differentially expressed genes (DEGs) (FDR

Mapping-out baseline physiological muscle parameters with their metabolic blueprint across multiple archetype equine breeds, will contribute to better understanding their functionality, even across species.Aims: 1) to map out and compare the baseline fiber type composition, fiber type and mean fiber cross-sectional area (fCSA, mfCSA) and metabolic blueprint of three muscles in 3 different breeds 2) to study possible associations between differences in histomorphological parameters and baseline metabolism.Methods: Muscle biopsies [m. pectoralis (PM), m. vastus lateralis (VL) and m. semitendinosus (ST)] were harvested of 7 untrained Friesians, 12 Standardbred and 4 Warmblood mares. Untargeted metabolomics was performed on the VL and PM of Friesian and Warmblood horses and the VL of Standardbreds using UHPLC/MS/MS and GC/MS. Breed effect on fiber type percentage and fCSA and mfCSA was tested with Kruskal-Wallis. Breeds were compared with Wilcoxon rank-sum test, with Bonferroni correction. Spearman correlation explored the association between the metabolic blueprint and morphometric parameters.Results: The ST was least and the VL most discriminative across breeds. In Standardbreds, a significantly higher proportion of type IIA fibers was represented in PM and VL. Friesians showed a significantly higher representation of type IIX fibers in the PM. No significant differences in fCSA were present across breeds. A significantly larger mfCSA was seen in the VL of Standardbreds. Lipid and nucleotide super pathways were significantly more upregulated in Friesians, with increased activity of short and medium-chain acylcarnitines together with increased abundance of long chain and polyunsaturated fatty acids. Standardbreds showed highly active xenobiotic pathways and high activity of long and very long chain acylcarnitines. Amino acid metabolism was similar across breeds, with branched and aromatic amino acid sub-pathways being highly active in Friesians. Carbohydrate, amino acid and nucleotide super pathways and carnitine metabolism showed higher activity in Warmbloods compared to Standardbreds.Conclusion: Results show important metabolic differences between equine breeds for lipid, amino acid, nucleotide and carbohydrate metabolism and in that order. Mapping the metabolic profile together with morphometric parameters provides trainers, owners and researchers with crucial information to develop future strategies with respect to customized training and dietary regimens to reach full potential in optimal welfare.

This study aimed to determine whether a text message is as good as a postal letter as an invitation method for previous screenees in a breast cancer screening program, considering a non-inferiority margin of -2 percent points on participation rate. A non-inferiority randomized control trial was conducted. Women in the intervention group (n = 5,362) were invited by text message, and women in the control group (n = 5,482) were invited by letter, which is the standard invitation procedure of the program. In both groups, the invitation included a fixed appointment for mammography and a text message reminder 96 hours before the appointment. The primary outcome was screening participation rate (completing mammography within 12 weeks of invitation). Secondary outcomes included mammography attendance to initial or rescheduled appointments and cancellation rate. The intention-to-treat analysis showed a participation rate of 87.3% and 86.6% in the control and intervention groups, respectively. The difference in participation rate was -0.7 percentage points (95% confidence interval [CI], -1.8 to ∞), indicating non-inferiority of text messages compared to letter invitations. The per-protocol analysis showed similar results. Attendance at the initial appointment was higher in women who received the text message invitation compared to those in the control group (P

Background: House dust mite (HDM)-induced allergic rhinitis (AR) is a major cause of allergic respiratory disease. The efficacy and safety of the 300 IR HDM sublingual immunotherapy (SLIT) tablet in patients with moderate-to-severe HDM-AR was confirmed in a large, international, phase 3 randomized controlled trials (RCTs). Here, we analyzed the results in the European population. Methods: Data from 91 European centers that participated in the international, double-blind, RCT (EudraCT 2014-004223-46, NCT02443805) with the 300 IR HDM SLIT tablet versus placebo over 12 months were analyzed post hoc. The treatment effect in European adults and adolescents was notably assessed through the European Academy of Allergy and Clinical Immunology (EAACI)-recommended combined symptom and medication score (CSMS0-6, pre-defined endpoint) and the total combined rhinitis score (TCRS0-24, post hoc endpoint, also balanced) during the primary evaluation period (4 weeks at the end of treatment period) using analysis of covariance (ANCOVA). Results: There were 818 patients who comprised the modified full analysis set in Europe. Over the primary period, the differences in CSMS0-6 and TCRS0-24 between the 300 IR and placebo groups were statistically significant (p

Essential trace elements are micronutrients whose deficiency has been associated with altered fertility and/or adverse pregnancy outcomes, while surplus may be toxic. The concentrations of eight essential trace elements were measured using inductively coupled mass spectrometry (ICP-MS) and assessed with respect to clinical in vitro fertilization (IVF) outcomes in a population of 51 women undergoing IVF with intracytoplasmic sperm injection (ICSI), pre-implantation genetic screening for aneuploidy (PGT-A), and single frozen euploid embryo transfer (SET/FET). Specifically, copper (Cu), zinc (Zn), molybdenum, selenium, lithium, iron, chromium, and manganese were quantified in follicular fluid and whole blood collected the day of vaginal oocyte retrieval (VOR) and in urine collected the day of VOR and embryo transfer. We found that the whole blood Cu/Zn ratio was significantly associated with superior responses to ovarian stimulation. Conversely, the whole blood zinc and selenium concentrations were significantly associated with poor ovarian response outcomes. Higher levels of whole blood zinc and selenium, urinary selenium, lithium, and iron had significant negative associations with embryologic outcomes following IVF. Regarding clinical IVF outcomes, higher urinary molybdenum concentrations the day of VOR were associated with significantly lower odds of implantation and live birth, while higher urinary Cu/Mo ratios on the day of VOR were associated with significantly higher odds of implantation, clinical pregnancy, and live birth. Our results suggest that essential trace element levels may directly influence the IVF outcomes of Spanish patients, with selenium and molybdenum exerting negative effects and copper-related ratios exerting positive effects. Additional studies are warranted to confirm these relationships in other human populations.

Introduction: Measuring soluble interleukin-2 receptor (sIL-2R) might be useful for diagnosis and monitoring of immune-mediated diseases. The study investigated factors associated with serum sIL-2R concentrations in adults. Methods: Serum sIL-2R concentrations were measured in 1499 randomly selected individuals (44.6% male, median age 52 years, range 18–91 years). Lifestyle factors (alcohol consumption, smoking, and physical activity) were assessed by questionnaire. Body mass index and data defining metabolic syndrome were measured in all participants. Atopy was defined by skin tests to aeroallergens. Results: Serum sIL-2R concentrations displayed wide variation (2.5–97.5 percentile range, 209–950 U/mL). A total of 230 (15.3%) individuals showed values higher than the standard reference range (158–623 U/mL). After adjusting for covariates, sIL-2R concentrations increased with age, particularly after 65 years. Serum sIL-2R concentrations were higher in males than in females, were higher in smokers than in never smokers, and were higher in atopic than in non-atopic individuals. Serum sIL-2R concentrations were positively associated with metabolic syndrome, particularly with abdominal obesity, and with a history of ischemic heart disease. Light alcohol drinkers showed lower sIL-2R concentrations than abstainers. Conclusion: Aging, sex, lifestyle factors, atopy, metabolic abnormalities, and ischemic heart disease might influence serum sIL-2R concentrations in adults.

Important changes in glucose transporter (GLUT) expression should be expected if the glucose influx plays a pivotal role in fuelling or connecting metabolic pathways that are upregulated in response to exercise. The aim was to assess GLUT4, 8, and 12 dynamics in response to training and acute exercise.Methods: Sixteen untrained Standardbred mares (3-4 year) performed an incremental SET at the start and end of 8 weeks harness training. M. pectoralis (PM) and M. vastus lateralis (VL) muscle biopsies were taken before and after each SET, allowing for comparing rest and acute samples in untrained (UT) and trained (T) condition using Western Blot for GLUT quantification and Image Pro v.10 for Blot analysis. Data were normalized against GAPDH. Basal GLUT-levels of PM versus VL were analysed with the Wilcoxon matched-pairs signed rank test. The effect of acute exercise or training was assessed using the Friedman test with a post hoc Dunn’s.Results: Basal GLUT4 and GLUT12 protein expression were significantly higher in the VL compared to the PM (PGLUT4 = 0.031 and PGLUT12 = 0.002). Training had no effect on basal GLUT4 expression, neither in the VL (p > 0.9999), nor the PM (p > 0.9999). However, acute exercise in trained condition significantly decreased GLUT4 expression in the VL (p = 0.0148). Neither training nor acute exercise significantly changed total GLUT8 protein expression. Training significantly decreased total GLUT12 protein expression in rest biopsies, only visible in the VL (p = 0.0359). This decrease was even more prominent in the VL after acute exercise in trained condition (PVL = 0.0025).Conclusion: The important changes seen in GLUT12 expression downregulation, both in response to training and acute exercise in the horse, the downregulation of GLUT4 expression after acute exercise in trained condition and the lack of differential shifts in GLUT8 expression in any of the studied conditions, questions the importance of glucose as substrate to fuel training and exercise in healthy horses. These findings encourage to further explore alternative fuels for their involvement in equine muscular energetics.

Background: There is no description of the drivers of prescription for allergen immunotherapy (AIT) for respiratory allergic diseases. Methods: A prospective, multicentre, observational, non-interventional real-life study was performed in France and Spain for 20 months. Data were gathered using 2 different questionnaires, anonymously collected in an online platform. No names of AIT products were recorded. Multivariate analysis and unsupervised cluster analysis were performed. Results: One hundred and three physicians (50.5% from Spain and 49.5% from France) reported 1735 patients (433 in France and 1302 in Spain), 47.9% males, 64.8% adults with a mean age 26.2 years old. They suffered from allergic rhinitis (99%), allergic conjunctivitis (70.4%), allergic asthma (51.8%), atopic dermatitis (13.9%), and food allergy (9.9%). A clustering analysis based on 13 predefined relevant variables for AIT-prescription identified 5 different clusters, each of them including information regarding doctor's profile and patient demographics, baseline disease characteristics, and main AIT indication: 1) Looking at the future: focusing on asthma prevention (n = 355), 2) Efficacy after discontinuation of AIT (n = 293), 3) Fighting severe allergic disease (n = 322), 4) Looking at the present, facing current symptoms (n = 265) and 5) Doctor's own clinical experience (n = 500). Each one of these clusters have specific patients' and doctors' characteristics, representing distinctive AIT prescription drivers. Conclusion: Using data-driven analysis, we identified for the first time some reasons and patterns of AIT prescriptions in real-life clinical settings. There is no uniform indication for prescribing AIT, which varies amongst patients and doctors with multiple but specific drivers, taking into account several relevant parameters.

Objectives Anxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms.Methods This is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6±16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score ≥8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen’s kappa. Two multivariable logistic regressions were built.Results According to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression.Conclusion At least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies.

(1) Aim: To describe, in a general adult population, the serum N-glycome in relation to age in men and women, and investigate the association of N-glycome patterns with age-related comorbidity; (2) Methods: The serum N-glycome was studied by hydrophilic interaction chromatography with ultra-performance liquid chromatography in 1516 randomly selected adults (55.3% women; age range 18–91 years). Covariates included lifestyle factors, metabolic disorders, inflammatory markers, and an index of comorbidity. Principal component analysis was used to define clusters of individuals based on the 46 glycan peaks obtained in chromatograms; (3) Results: The serum N-glycome changed with ageing, with significant differences between men and women, both in individual N-glycan peaks and in groups defined by common features (branching, galactosylation, sialylation, fucosylation, and oligomannose). Through K-means clustering algorithm, the individuals were grouped into a cluster characterized by abundance of simpler N-glycans and a cluster characterized by abundance of higher-order N-glycans. The individuals of the first cluster were older, showed higher concentrations of glucose and glycation markers, higher levels of some inflammatory markers, lower glomerular filtration rate, and greater comorbidity index; (4) Conclusions: The serum N-glycome changes with ageing with sex dimorphism. The N-glycome could be, in line with the inflammaging hypothesis, a marker of unhealthy aging.

(1) Background: Dipeptidyl Peptidases IV (DPPIVs), present in many organisms, are minor components in the venoms of Hymenoptera, where they have been identified as cross-reactive allergenic molecules. Considering that the structure of homologous DPPIVs is well characterized, we aimed to explain which regions have higher similarity among these proteins and present a comparison among them, including a new Vespa velutina DPPIV sequence. Moreover, two cases of sensitization to DPPIVs in wasp- and honeybee-sensitized patients are presented. (2) Methods: Proteomic analyses have been performed on the venom of the Asian hornet Vespa velutina to demonstrate the sequence of its DPPIV (allergen named Vesp v 3, with sequence accession number P0DRB8, and with the proteomic data available via ProteomeXchange with the identifier PXD046030). A comparison performed through their alignments and analysis of the three-dimensional structure showed a region with higher similarity among Hymenoptera DPPIVs. Additionally, ImmunoCAP™ determinations (including specific inhibition experiments), as well as IgE immunoblotting, are performed to demonstrate the allergenicity of Api m 5 and Ves v 3. (3) Results and Conclusions: The data presented demonstrate that the similarities among Hymenoptera DPPIVs are most likely localized at the C-terminal region of these enzymes. In addition, a higher similarity of the Vespa/Vespula DPPIVs is shown. The clinical cases analyzed demonstrated the allergenicity of Api m 5 and Ves v 3 in the sera of the allergic patients, as well as the presence of this minor component in the preparations used in venom immunotherapy.

Abstract Background Previous studies have demonstrated the feasibility of using an asthma app to support medication management and adherence but failed to compare with other measures currently used in clinical practice. However, in a clinical setting, any additional adherence measurement must be evaluated in the context of both the patient and physician perspectives so that it can also help improve the process of shared decision making. Thus, we aimed to compare different measures of adherence to asthma control inhalers in clinical practice, namely through an app, patient self‐report and physician assessment. Methods This study is a secondary analysis of three prospective multicentre observational studies with patients (≥13 years old) with persistent asthma recruited from 61 primary and secondary care centres in Portugal. Patients were invited to use the InspirerMundi app and register their inhaled medication. Adherence was measured by the app as the number of doses taken divided by the number of doses scheduled each day and two time points were considered for analysis: 1‐week and 1‐month. At baseline, patients and physicians independently assessed adherence to asthma control inhalers during the previous week using a Visual Analogue Scale (VAS 0–100). Results A total of 193 patients (72% female; median [P25–P75] age 28 [19–41] years old) were included in the analysis. Adherence measured by the app was lower (1 week: 31 [0–71]%; 1 month: 18 [0–48]%) than patient self‐report (80 [60–95]) and physician assessment (82 [51–94]) (p 0.05). There was a moderate correlation between patient self‐report and physician assessment (ρ = 0.596, p

Background: Allergen immunotherapy (AIT) is today the only etiological therapy for respiratory allergic diseases, including allergic rhinitis, allergic conjunctivitis, and allergic asthma. Even though interest in real-world data has recently increased, publications mainly focus on short-term and long-term efficacy and safety of AIT. Indeed, information is still lacking regarding the “key parameters” or “drivers of prescription” used by doctors to prescribe AIT or by the patients to accept AIT as treatment for their respiratory allergic disease. Examining these factors is therefore the main goal of the CHOICE-Global Survey: “Criteria Used by Health Professionals on the Selection of Allergen Immunotherapy in Real Clinical Practice: An international academic electronic survey”. Methods: We present the methodology of the CHOICE-Global Survey, an academic, prospective, multicenter, observational, transversal, web-based e-survey, conducted in real-life clinical settings designed to collect data from 31 countries representing 9 global different socio-economic and demographic regions. In the present document, we describe the survey, how it was conceived and developed, how data are stored and analyzed, and the different steps that will provide this information to the allergy community. Conclusions: The CHOICE-Global Survey will be able to provide, from an academic point of view, information on the drivers of prescription of AIT in real-life practice and improve understanding regarding the key parameters considered by doctors and patients for such therapy.

Objective To analyse women’s stated preferences for establishing the relative importance of each attribute of shared decision-making (SDM) and their willingness to pay (WTP) for more participatory care in breast cancer screening programmes (BCSP).Design A discrete choice experiment was designed with 12 questions (choice tasks). It included three attributes: ‘How the information is obtained’, regarding benefits and harms; whether there is a ‘Dialogue for scheduled mammography’ between the healthcare professional and the woman; and, ‘Who makes the decision’, regarding participation in BCSP. Data were obtained using a survey that included 12 choice tasks, 1 question on WTP and 7 socioeconomic-related questions. The analysis was performed using conditional mixed-effect logit regression and stratification according to WTP.Setting Data collection related to BCSP was conducted between June and November 2021 in Catalonia, Spain.Participants Sixty-five women aged between 50 and 60.Main outcome measures Women’s perceived utility of each attribute, trade-off on these attributes and WTP for SDM in BCSP.Result The only significant attribute was ‘Who makes the decision’. The decision made alone (coefficient=2.879; 95% CI=2.297 to 3.461) and the decision made together with a healthcare professional (2.375; 95% CI=1.573 to 3.177) were the options preferred by women. The former contributes 21% more utility than the latter. Moreover, 52.3% of the women stated a WTP of €10 or more for SDM. Women’s preferences regarding attributes did not influence their WTP.Conclusions The participant women refused a current paternalistic model and preferred either SDM or informed decision-making in BCSP.

Health risks caused by stings from Vespa velutina nigrithorax (VV), also known as the yellow-legged Asian hornet, have become a public concern, but little is known about its venom composition. This study presents the proteome profile of the VV’s venom sac (VS) based on Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS). The study also performed proteomic quantitative analysis and examined the biological pathways and molecular functions of the proteins in the VS of VV gynes (i.e., future queens [SQ]) and workers [SW]. The total protein content per VS was significantly higher in the SW than in the SQ (274 ± 54 µg/sac vs. 175 ± 22 µg/sac; p = 0.02). We quantified a total of 228 proteins in the VS, belonging to 7 different classes: Insecta (n = 191); Amphibia and Reptilia (n = 20); Bacilli, γ-Proteobacteria and Pisoniviricetes (n = 12); and Arachnida (n = 5). Among the 228 identified proteins, 66 showed significant differential expression between SQ and SW. The potential allergens hyaluronidase A, venom antigen 5 and phospholipase A1 were significantly downregulated in the SQ venom.

Introduction: We aimed to assess differences in breast cancer risk across benign breast disease diagnosed at prevalent or incident screens. Materials and methods: We conducted a retrospective cohort study with data from 629,087 women participating in a long-standing population-based breast cancer screening program in Spain. Each benign breast disease was classified as non-proliferative, proliferative without atypia, or proliferative with atypia, and whether it was diagnosed in a prevalent or incident screen. We used partly conditional Cox hazard regression to estimate the adjusted hazard ratios of the risk of breast cancer. Results: Compared with women without benign breast disease, the risk of breast cancer was significantly higher (p-value = 0.005) in women with benign breast disease diagnosed in an incident screen (aHR, 2.67; 95%CI: 2.24–3.19) than in those with benign breast disease diagnosed in a prevalent screen (aHR, 1.87; 95%CI: 1.57–2.24). The highest risk was found in women with a proliferative benign breast disease with atypia (aHR, 4.35; 95%CI: 2.09–9.08, and 3.35; 95%CI: 1.51–7.40 for those diagnosed at incident and prevalent screens, respectively), while the lowest was found in women with non-proliferative benign breast disease (aHR, 2.39; 95%CI: 1.95–2.93, and 1.63; 95%CI: 1.32–2.02 for those diagnosed at incident and prevalent screens, respectively). Conclusion: Our study showed that the risk of breast cancer conferred by a benign breast disease differed according to type of screen (prevalent or incident). To our knowledge, this is the first study to analyse the impact of the screening type on benign breast disease prognosis.

Abstract Background House dust mite (HDM) allergens constitute the most frequent cause of persistent allergic rhinitis and asthma. The symptoms vary throughout the year but typically peak in spring, autumn and (to a lesser extent) mid-winter. Methods We performed a 13-month, observational, multicentre survey of adult patients with a self-reported history of moderate-to-severe, poorly controlled, physician-diagnosed HDM respiratory allergy in three European countries (France, Italy and Spain). After screening and inclusion, 28 detailed, fortnightly telephone interviews were used to gather extensive data on the participants’ symptom prevalence and intensity, medical consultations, disease burden and medication use from late May 2012 to early July 2013. This report focuses on the disease burden. Results Of the 22,995 screened participants, 313 met the inclusion criteria and completed the post-inclusion questionnaire (n = 114 in Italy, 92 in France and 107 in Spain). The median time since the first symptoms of HDM allergy was ≥ 13 years in each country. A relevant minority of the participants suffered from symptoms of HDM allergy every day or almost every day of the year (14% in Italy, 46% in France and 37% in Spain). According to the fortnightly telephone interviews, the most frequently impacted disease burden variables were sleep, daytime tiredness and irritability, with the highest values in spring 2012, autumn 2012 and spring 2013 (mirroring symptom intensities). Professional activities were more affected than social activities. The burden data were heterogeneous: around a quarter of participants were strongly or very strongly affected but most of the remaining participants were only rarely bothered or not bothered. Conclusions In a 13-month, fortnightly survey of patients in France, Italy and Spain with a self-reported history of moderate-to-severe, poorly controlled, HDM-induced allergic rhinitis and asthma, we found that a relevant minority of participants regularly reported a severe or very severe impact of their allergy on tiredness, sleep and professional activities (including time off work). The disease burden peaked in autumn and late spring.

There is a great need for objective external training load prescription and performance capacity evaluation in equestrian disciplines. Therefore, reliable standardised exercise tests (SETs) are needed. Classic SETs require maximum intensities with associated risks to deduce training loads from pre-described cut-off values. The lactate minimum speed (LMS) test could be a valuable alternative. Our aim was to compare new performance parameters of a modified LMS-test with those of an incremental SET, to assess the effect of training on LMS-test parameters and curve-shape, and to identify the optimal mathematical approach for LMS-curve parameters. Six untrained standardbred mares (3–4 years) performed a SET and LMS-test at the start and end of the 8-week harness training. The SET-protocol contains 5 increments (4 km/h; 3 min/step). The LMS-test started with a 3-min trot at 36–40 km/h [until blood lactate (BL) > 5 mmol/L] followed by 8 incremental steps (2 km/h; 3 min/step). The maximum lactate steady state estimation (MLSS) entailed >10 km run at the LMS and 110% LMS. The GPS, heartrate (Polar®), and blood lactate (BL) were monitored and plotted. Curve-parameters (R core team, 3.6.0) were (SET) VLa1.5/2/4 and (LMS-test) area under the curve (AUC>/ 0.80), Bland-Altman method, and ordinary least products (OLP) regression analyses were determined for test-correlation and concordance. Training induced a significant increase in VLa1.5/2/4. The width of the AW increased significantly while the AUCLMS and LMS decreased post-training (flattening U-curve). The LMS BL steady-state is reached earlier and maintained longer after training. BLmax was significantly lower for LMS vs. SET. The 40° angular method is the optimal approach. The correlation between LMS and VMLSS was significantly better compared to the SET. The VLa4 is unreliable for equine aerobic capacity assessment. The LMS-test allows more reliable individual performance capacity assessment at lower speed and BL compared to SETs. The LMS-test protocol can be further adapted, especially post-training; however, inducing modest hyperlactatemia prior to the incremental LMS-stages and omitting inclusion of a per-test recovery contributes to its robustness. This LMS-test is a promising tool for the development of tailored training programmes based on the AW, respecting animal welfare.

Training-induced follow-up of multiple muscle plasticity parameters in postural stability vs. locomotion muscles provides an integrative physiological view on shifts in the muscular metabolic machinery. It can be expected that not all muscle plasticity parameters show the same expression time profile across muscles. This knowledge is important to underpin results of metabolomic studies. Twelve non-competing Standardbred mares were subjected to standardized harness training. Muscle biopsies were taken on a non-training day before and after 8 weeks. Shifts in muscle fiber type composition and muscle fiber cross-sectional area (CSA) were compared in the m. pectoralis, the m. vastus lateralis, and the m. semitendinosus. In the m. vastus lateralis, which showed most pronounced training-induced plasticity, two additional muscle plasticity parameters (capillarization and mitochondrial density) were assessed. In the m. semitendinosus, additionally the mean minimum Feret's diameter was assessed. There was a significant difference in baseline profiles. The m. semitendinosus contained less type I and more type IIX fibers compatible with the most pronounced anaerobic profile. Though no baseline fiber type-specific and overall mean CSA differences could be detected, there was a clear post-training decrease in fiber type specific CSA, most pronounced for the m. vastus lateralis, and this was accompanied by a clear increase in capillary supply. No shifts in mitochondrial density were detected. The m. semitendinosus showed a decrease in fiber type specific CSA of type IIAX fibers and a decrease of type I fiber Feret's diameter as well as mean minimum Feret's diameter. The training-induced increased capillary supply in conjunction with a significant decrease in muscle fiber CSA suggests that the muscular machinery models itself toward an optimal smaller individual muscle fiber structure to receive and process fuels that can be swiftly delivered by the circulatory system. These results are interesting in view of the recently identified important fuel candidates such as branched-chain amino acids, aromatic amino acids, and gut microbiome-related xenobiotics, which need a rapid gut–muscle gateway to reach these fibers and are less challenging for the mitochondrial system. More research is needed with that respect. Results also show important differences between muscle groups with respect to baseline and training-specific modulation.

Establishing proper policies regarding the recognition and prevention of equine heat stress becomes increasingly important, especially in the face of global warming. To assist this, a detailed view of the variability of equine thermoregulation during field exercise and recovery is essential. 13 endurance horses and 12 trotter horses were equipped with continuous monitoring devices [gastrointestinal (GI) pill, heartrate (HR) monitor, and global positioning system] and monitored under cool weather conditions during four endurance rides over a total of 80 km (40 km loops) and intense trotter track-based exercise over 1,540 m. Recordings included GI temperature (Tc), speed, HR and pre- and post-exercise blood values. A temperature time profile curve of Tc was constructed, and a net area under the curve was calculated using the trapezoidal method. Metabolic heat production and oxygen cost of transport were also calculated in endurance horses. Maximum Tc was compared using an independent samples t-test. Endurance horses (mean speed 14.1 ± 1.7 km h–1) reached mean maximum Tc (39.0 ± 0.4°C; 2 × 40 km in 8 horses) during exercise at 75% of completion of Tc exercise and Tc returned to baseline within 60 min into recovery. However, the mean Tc was still 38.8 ± 0.4°C at a HR of 60 bpm which currently governs “fit to continue” competition decisions. Trotters (40.0 ± 2.9 km h–1) reached a comparable mean max Tc (38.8 ± 0.5°C; 12 horses) always during recovery. In 30% of trotters, Tc was still >39°C at the end of recovery (40 ± 32 min). The study shows that horses are individuals and thermoregulation monitoring should reflect this, no matter what type of exercise is performed. Caution is advised when using HR cut-off values to monitor thermal welfare in horses since we have demonstrated how Tc can peak quite some time after finishing exercise. These findings have implications for training and management of performance horses to safeguard equine welfare and to maximize performance.

Background: Although respiratory allergies to house dust mites (HDMs) can often be controlled with symptomatic medications, some patients do not achieve satisfactory disease control. Objective: To assess fortnightly fluctuations (notably worsening and/or exacerbations) in disease parameters among patients taking only symptomatic medications for HDM allergy. Methods: In a 13-month, observational, multicenter survey of adults with a self-reported history of poorly controlled, moderate-to-severe, physician-diagnosed HDM respiratory allergy in France, Italy, and Spain, fortnightly telephone interviews were used to gather information on medication use, symptoms, the disease burden, and medical consultations from late May 2012 to early July 2013. Results: A total of 313 patients completed the study (n = 114 in Italy, 92 in France, and 107 in Spain). Although most participants reported improvements in symptoms, a substantial minority (ranging from 12% to 44% per fortnightly telephone interview in 2012 and from 16% to 37% in 2013) complained of worsening. A few study participants did not improve at any time in the study: 4% overall, and 2%, 2%, and 7% in Italy, France and Spain, respectively. A change in the weather and/or contact with other allergens were the most frequent self-reported reasons for worsening, although the answer “I don't know” was also prominent. Conclusion: In a 13-month survey of patients with HDM allergy in Italy, France, and Spain, the participants’ symptom status fluctuated significantly — illustrating the complexity of this condition. Although most participants reported improvements, the “never-improver” profile warrants further investigation. More prominence could be given to symptom control and a low exacerbation risk as treatment goals in allergic rhinitis.

Aleurone, a layer of the bran fraction, is deemed to be responsible for the positive health effects associated with the consumption of whole-grain products. Studies on rodents, pigs, and humans report beneficial effects of aleurone in five main areas: the reduction of oxidative stress, immunomodulatory effects, modulation of energy management, digestive health, and the storage of vitamins and minerals. Our study is the first aleurone supplementation study performed in horses. The aim of this study was to investigate the effect of an increase in the dose levels of aleurone on the postprandial glucose-insulin metabolism and the gut microbiome in untrained healthy horses. Seven adult Standardbred horses were supplemented with four different dose levels of aleurone (50, 100, 200, and 400 g/day for 1 week) by using a Latin square model with a 1-week wash out in between doses. On day 7 of each supplementation week, postprandial blood glucose-insulin was measured and fecal samples were collected. 16S ribosomal RNA (rRNA) gene sequencing was performed and QIIME2 software was used for microbiome analysis. Microbial community function was assessed by using the predictive metagenome analysis tool Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) and using the Metacyc database of metabolic pathways. The relative abundancies of a pathway were analyzed by using analysis of composition of microbiomes (ANCOM) in R. There was a significant dose-dependent increase in the postprandial time to peak of glucose (p = 0.030), a significant delay in the time to peak of insulin (p = 0.025), and a significant decrease in both the insulin peak level (p = 0.049) and insulin area under the curve (AUC) (p = 0.019) with increasing dose levels of aleurone, with a consideration of 200 g being the lowest significant dose. Alpha diversity and beta diversity of the fecal microbiome showed no significant changes. Aleurone significantly decreased the relative abundance of the genera Roseburia, Shuttleworthia, Anaerostipes, Faecalibacter, and Succinovibrionaceae. The most pronounced changes in the relative abundance at phyla level were seen in Firmicutes and Verrucomicrobia (downregulation) and Bacteroidetes and Spirochaetes (upregulation). The PICRUSt analysis shows that aleurone induces a downregulation of the degradation of L-glutamate and taurine and an upregulation of the three consecutive pathways of the phospholipid membrane synthesis of the Archaea domain. The results of this study suggest a multimodal effect of aleurone on glucose-insulin metabolism, which is most likely to be caused by its effect on feed texture and subsequent digestive processing; and a synergistic effect of individual aleurone components on the glucose-insulin metabolism and microbiome composition and function.

BackgroundShort message service (SMS) based interventions are widely used in healthcare and have shown promising results to improve cancer screening programs. However, more research is still needed to implement SMS in the screening process. We present a study protocol to assess the impact on health and economics of three targeted SMS-based interventions in population-based cancer screening programs.Methods/designThe M-TICs study is a randomized controlled trial with a formal process evaluation. Participants aged 50-69 years identified as eligible from the colorectal cancer (CRC) and breast cancer (BC) screening program of the Catalan Institute of Oncology (Catalonia, Spain) will be randomly assigned to receive standard invitation procedure (control group) or SMS-based intervention to promote participation. Two interventions will be conducted in the CRC screening program: 1) Screening invitation reminder: Those who do not participate in the CRC screening within 6 weeks of invite will receive a reminder (SMS or letter); 2) Reminder to complete and return fecal immunochemical test (FIT) kit: SMS reminder versus no intervention to individuals who have picked up a FIT kit at the pharmacy and they have not returned it after 14 days. The third intervention will be performed in the BC screening program. Women who had been screened previously will receive an SMS invitation or a letter invitation to participate in the screening. As a primary objective we will assess the impact on participation for each intervention. The secondary objectives will be to analyze the cost-effectiveness of the interventions and to assess participants' perceptions.Expected resultsThe results from this randomized controlled trial will provide important empirical evidence for the use of mobile phone technology as a tool for improving population-based cancer screening programs. These results may influence the cancer screening invitation procedure in future routine practice.Trial registrationRegistry: NCT04343950 (04/09/2020); clinicaltrials.gov.

IntroductionThe effectiveness of colorectal cancer (CRC) screening programs is directly related to participation and the number of interval CRCs. The objective was to analyse specific-mortality in a cohort of individuals invited to a CRC screening program according to type of CRC diagnosis (screen-detected cancers, interval cancers, and cancers among the non-uptake group).Material and methodsRetrospective cohort that included invitees aged 50-69 years of a CRC screening program (target population of 85,000 people) in Catalonia (Spain) from 2000-2015 with mortality follow-up until 2020. A screen-detected CRC was a cancer diagnosed after a positive faecal occult blood test (guaiac or immunochemical); an interval cancer was a cancer diagnosed after a negative test result and before the next invitation to the program (≤24 months); a non-uptake cancer was a cancer in subjects who declined screening.ResultsA total of 624 people were diagnosed with CRC (n = 265 screen-detected, n = 103 interval cancers, n = 256 non-uptake). In the multivariate analysis, we observed a 74% increase in mortality rate in the group with interval CRC compared to screen-detected CRC adjusted for age, sex, location and stage (HR: 1.74%, 95% CI:1.08-2.82, P = 0.02). These differences were found even when we restricted for advanced-cancers participants. In the stratified analysis for type of faecal occult blood test, a lower mortality rate was only observed among FIT screen-detected CRCs.ConclusionCRC screening with the FIT was associated with a significant reduction in CRC mortality.

Epidemiology of Hymenopteran-related deaths in Europe, based on official registers from WHO Mortality Database (Cause Code of Death: X23), are presented. Over a 23-year period (1994–2016), a total of 1691 fatalities were recorded, mostly occurring in Western (42.8%) and Eastern (31.9%) Europe. The victims tended to concentrate in: Germany (n = 327; 1998–2015), France (n = 211; 2000–2014) and Romania (n = 149; 1999–2016). The majority of deaths occurred in males (78.1%) between 25–64 years (66.7%), and in an “unspecified place” (44.2%). The highest X23MR (mortality rate) were recorded in countries from Eastern Europe (0.35) followed by Western (0.28), Northern (0.23) and Southern Europe (0.2). The countries with the highest and lowest mean X23MR were Estonia (0.61), Austria (0.6) and Slovenia (0.55); and Ireland (0.05), United Kingdom (0.06) and the Netherlands (0.06), respectively. The X23 gender ratio (X23GR; male/female) of mortality varied from a minimum of 1.4 for Norway to a maximum of 20 for Slovenia. Country-by-country data show that the incidence of insect-sting mortality is low and more epidemiological data at the regional level is needed to improve our understanding of this incidence. With the expansion of non-native Hymenopteran species across Europe, allergists should be aware that their community’s exposures are continually changing

Wasp allergy with a diagnostic profile of double sensitizations to vespid venom is a frequent clinical problem in areas where different genera of wasps are present. Identification of the insect responsible for serious reactions poses a diagnostic challenge as the only effective treatment to date is immunotherapy based on the specific venom. In southern Europe, the double sensitization to Vespula and Polistes venoms is highly frequent. It has been shown that the major allergenic proteins (Phospholipase A1 and Antigen 5) share sequences across the different genera and species, which would be the cause of cross-reactivity. Additionally, the minor allergens (Dipeptidyl-peptidases, Vitellogenins) have been found to share partial sequence identity. Furthermore, venom contains other homologous proteins whose allergenic nature still remains to be clarified. The traditional diagnostic tools available are insufficient to discriminate between allergy to Vespula and Polistes in a high number of cases. IgE inhibition is the technique that best identifies the cross-reactivity. When a double sensitization has indeed been shown to exist or great uncertainty surrounds the primary sensitization, therapy with two venoms is advisable to guarantee the safety of the patient. In this case, a strategy involving alternate administration that combines effectiveness with efficiency is possible.

The yellow-legged Asian hornet (Vespa velutina Lepeletier 1836 (Hymenoptera: Vespidae)) is naturally distributed in China, Southeast Asia, and India; however, recently it has been detected outside of its native area, confirmed as being established in South Korea, Europe, and Japan. Health risks and deaths caused by the invasive Vespa velutina stings have become a public health concern, being the most common cause of anaphylaxis due to hymenopterans in some European regions. This in turn has led to increased demand from medical practitioners and researchers for Vespa velutina venom for diagnostic and therapeutic purposes. In this study, a straightforward, quick, and inexpensive method for obtaining Vespa velutina venom by electric stimulation is described. The venom extracts were analyzed by nuclear magnetic resonance spectroscopy (1H-NMR). The availability of Vespa velutina venom will lead to improved diagnostic and therapeutic methods, mainly by venom immunotherapy (VIT), in patients allergic to this invasive species.

Abstract Background The decision to participate or not in breast cancer screening is complex due to the trade-off between the expected benefit of breast cancer mortality reduction and the major harm of overdiagnosis. It seems ethically necessary to inform women so that they can actively participate in decision-making and make an informed choice based on their values and preferences. The objective of this study is to assess the effects of receiving information about the benefits and harms of screening on decision-making, in women approaching the age of invitation to mammography screening. Methods A two-stage, randomized controlled trial (RCT). In the first stage, 40 Basic Health Areas (BHAs) will be selected and randomized to intervention or control. In the second stage, women within each BHA will be randomly selected (n = 400). Four breast cancer screening programs (BCSPs) of the Spanish public health system, three in Catalonia and one in the Canary Islands will participate in the study. Women in the intervention arm will receive a leaflet with detailed information on the benefits and harms of screening using mammography. Women in the control arm will receive a standard leaflet that does not mention harms and recommends accepting the invitation to participate in the biennial examinations of the BCSP. The primary outcome is informed choice, a dichotomous variable that combines knowledge, attitudes, and intentions. Secondary outcomes include decisional conflict; confidence in the decision made; anxiety about screening participation; worry about breast cancer; anticipated regret; time perspective; perceived importance of benefits/harms of screening; perceived risk of breast cancer; and leaflet acceptability. Primary and secondary outcomes are assessed 2–3 weeks after the intervention. Discussion This is the first RCT that assesses the effect of informing about the benefits and harms of breast cancer screening in Spain in women facing the decision to be screened using mammography. It aims to assess the impact of information on several decisional outcomes and to contribute to paving the road towards shared decision-making in breast cancer screening in our country. Trial registration ClinicalTrials.gov registry, ID: NCT03046004 . Retrospectively registered on 4 February 2017. Trial name: InforMa study.

Resumen Los feminismos islámicos nacieron en los años noventa del siglo XX y desde entonces han sido objeto de severas críticas por parte de quienes consideran que no es posible luchar por los derechos de las mujeres desde las propias creencias. Frente a sus opositores, académicas y activistas abogan por la hermenéutica coránica como herramienta para desvelar las potencialidades que el texto sagrado ofrece para la igualdad. Su discurso es, además, un ataque directo a las concepciones más tradicionales del feminismo occidental y sus representaciones a menudo estereotipadas de las musulmanas. Abstract Islamic feminisms were born in the 90’s and since then they have been subject to criticism by those who believe that it is not possible to fight for women's rights in the framework of a religion. However, the scholars and activists of the Islamic feminisms advocate for the Koranic hermeneutics as a tool to unveil the potential that the sacred text offers for equality. Their discourse is also a direct attack to the most traditional conceptions of Western feminism and its often-stereotyped representations of Muslim women.

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics.

BACKGROUND:In Spain, women invited to breast screening are not usually informed about potential harms of screening. The objective of the InforMa study is to assess the effect of receiving information about the benefits and harms of breast screening on informed choice and other decision-making outcomes, in women approaching the age of invitation to mammography screening. METHODS:Two-stage randomised controlled trial. In the first stage, 40 elementary territorial units of the public healthcare system were selected and randomised to intervention or control. In the second stage, women aged 49-50 years were randomly selected. The target sample size was 400 women. Women in the intervention arm received a decision aid (DA) with detailed information on the benefits and harms of screening. Women in the control arm received a standard leaflet that did not mention harms and recommended accepting the invitation to participate in the Breast Cancer Screening Program (BCSP). The primary outcome was informed choice, defined as adequate knowledge and intentions consistent with attitudes. Secondary outcomes included decisional conflict, worry about breast cancer, time perspective, opinions about the DA or the leaflet, and participation in the BCSP. RESULTS:In the intervention group, 23.2% of 203 women made an informed choice compared to only 0.5% of 197 women in the control group (p < 0.001). Attitudes and intentions were similar in both study groups with a high frequency of women intending to be screened, 82.8% vs 82.2% (p = 0.893). Decisional conflict was significantly lower in the intervention group. No differences were observed in confidence in the decision, anxiety, and participation in BCSP. CONCLUSIONS:Women in Spain lack knowledge on the benefits and harms of breast screening. Providing quantitative information on benefits and harms has produced a considerable increase in knowledge and informed choice, with a high acceptance of the informative materials. TRIAL REGISTRATION:Trial identifier NCT03046004 at ClinicalTrials.gov registry. Registered on February 4 2017. Trial name: InforMa study.

Access arrangements are pre-exam arrangements that aim to remove any barriers that might prevent students with specific needs from accessing the assessment and demonstrating their knowledge and skills. Access arrangements are not intended to change the assessment demand or reduce its validity. Using a survey questionnaire, the present study reports on the views of 258 centres in eight countries around the world regarding teachers' and students' perceptions of access arrangements. The questionnaire included a mixture of closed and open-ended questions covering the following themes: awareness and provision of access arrangements; resources to provide access arrangements; views on access arrangements (including their usefulness, fairness, and perceived effectiveness of use); and overall views on access and inclusion.

In England, GCSE (General Certificate of Secondary Education) qualifications offered to students aged 14-16 were recently reformed. For mathematics specifically, the new GCSE aimed to be more demanding, provide greater challenge for the most able students, and support progression to post-16 mathematics. However, there have been concerns that the new GCSE could deter students from further education in the subject and, to date, there has been little research on its impact on participation in and learning of mathematics post-16. This research compared progression to and performance in post-16 mathematics pre- and post-GCSE reform and found that, contrary to fears about reduced uptake, progression generally increased following the reform. In particular, the increase was higher among those who achieved top grades in their mathematics GCSE than for students with just a pass. Performance in post-16 mathematics was, in contrast to teacher expectations, lower post-reform.

In England, some secondary-level qualifications comprise non-exam assessments which need to undergo moderation before grading. Currently, moderation is conducted at centre (school) level. This raises challenges for maintaining the standard across centres. Recent technological advances enable novel moderation methods that are no longer bound by centre. This study used simulation to investigate the feasibility of using comparative judgement (CJ) for moderating non-exam assessments. Our study explored the effects of CJ design parameters on the CJ estimates of script quality and how to assign moderator marks after the CJ procedure. The findings showed that certain design parameters had substantial effects on reliability and suggested minimum values for CJ protocols. The method used for assigning moderator marks maintained the rank order of scripts within centres and calibrated the centres to a common standard. Using CJ for moderation could transform current assessment practices, taking advantage of technological developments and ensuring reliability and fairness.

Fundamento: La educación médica en el siglo XXI exige de un estudiante capaz de captar las conexiones entre las diferentes asignaturas para dar solución a determinada problemática y puedan integrar aquello que se les enseñó aisladamente en las asignaturas. Objetivo: Describir procedimientos generales de las asignaturas de Anatomía Patológica, Microbiología y Genética para elaborar tareas integradoras que contribuyan al desarrollo de la independencia cognoscitiva de los estudiantes de la carrera Medicina. Desarrollo Se exponen las características de las tareas docentes integradoras y los procedimientos para su elaboración a partir de la determinación de los nodos interdisciplinarios entre las asignaturas de Anatomía Patológica, Microbiología y Genética. Conclusiones: Los procedimientos que se presentan para la elaboración de las tareas docentes integradoras, orientan metodológicamente la actividad del profesor para desarrollar la independencia cognoscitiva de los estudiantes de la carrera Medicina.

There are two main types of strategies to identify target population for lung cancer screening: 1) strategies based on age and cumulative smoking criteria, 2) risk prediction models allowing the calculation of an individual risk. The objective of this study was to compare different strategies to identify the proportion of the Spanish population at high risk of developing lung cancer, susceptible to be included in a lung cancer screening programme.Cross-sectional study. We used the data of the Spanish National Interview Health Survey (ENSE) of 2011-2012 (21,006 individuals) to estimate the proportion of participants at high risk of developing lung cancer. This estimation was performed using the U.S. national lung screening trial (NLST) criteria and a 6-year prediction model (PLCOm2012), both independently and in combination.The prevalence of individuals at high risk of developing lung cancer according to the NLST criteria was 4.9% (7.9% for men, 2.4% for women). Among the 1,034 subjects who met the NLST criteria, 533 (427 men and 106 women) had a 6-year lung cancer risk ≥2.0%. The combination of these two selection strategies showed that 2.5% of the Spanish population had a high risk of developing lung cancer. However, this selection process did not take into account different groups of subjects

Objetivo: Describir los cánceres de intervalo y la sensibilidad de los programas de cribado de cáncer colorrectal. Métodos: Revisión sistemática de la literatura con búsqueda en MEDLINE. La estrategia de búsqueda combina los términos ‘cáncer de intervalo’, ‘falso negativo’, ‘cribado’, ‘cribado poblacional’, ‘detección precoz de cáncer’ y ‘cáncer colorrectal’. Los criterios de inclusión fueron programas poblacionales de cribado de cáncer colorrectal, artículos originales en inglés o español, y fechas de publicación comprendidas entre enero de 1999 y febrero de 2015. Se realizó una síntesis narrativa de los artículos incluidos, detallando las características de los programas de cribado y de los cánceres de intervalo, y la sensibilidad del cribado utilizando como indicador el número de cánceres detectados mediante el cribado dividido por el total de tumores diagnosticados en la población cribada (método tradicional) o la incidencia proporcional, calculada como la incidencia de cánceres de intervalo en relación con la incidencia esperada en ausencia de cribado. Resultados: Se incluyeron 13 artículos. La sensibilidad de los programas de cribado osciló entre el 42,2% y el 65,3% en los programas que utilizan el test del guayaco, y entre el 59,1% y el 87,0% con el test inmunológico. Se ha encontrado una mayor proporción de mujeres a las que se diagnosticó un cáncer de intervalo, y que estas lesiones estaban mayoritariamente localizadas en el colon proximal. Conclusión: Existe una gran variabilidad en la proporción de cánceres de intervalo en los programas poblacionales de cáncer colorrectal. Para garantizar la comparabilidad entre programas, es necesario un consenso en la definición operacional de cánceres de intervalo y en los métodos utilizados para su identificación y cuantificación.

La invasión estadounidense de Afganistán fue intensamente cubierta por la televisión pública española, TVE. Entre los enviados especiales desplazados sobre el terreno había tres mujeres, Rosa María Calaf, Almudena Ariza y Llucía Oliva. ¿Tuvo su discurso características específicas respecto al de sus homólogos masculinos? ¿Prestaron una especial atención a las mujeres locales y sus problemas? En suma, se trata de realizar una aproximación a este conflicto desde el punto de vista del género, que aquí se convierte en la categoría de análisis principal.Palabras clave: Afganistán; género; televisión______________Abstract:The U.S. invasion of Afghanistan was heavily covered by the Spanish public television, TVE. Among the displaced special envoys on the ground were three women, Rosa Maria Calaf, Almudena Ariza and Llucía Oliva. Did their speech presented special features compared to the one of their male counterparts? Did they pay special attention to local women and their problems? In sum, this is an approach to this conflict from the point of view of gender, which here becomes the main analytical category. Keywords: Afghanistan; gender; television

Serum IgG4 concentrations are commonly measured in clinical practice. The aim of this study was to investigate serum IgG4 concentrations in adults and their potential relationship with demographic, lifestyle, metabolic, and allergy-related factors.Serum IgG4 concentrations were measured with a commercial assay in 413 individuals (median age 55 years, 45% males) who were randomly selected from a general adult population.Median IgG4 concentration was 26.8 mg/dL. Five out of the 413 individuals (1.2%) exhibited IgG4 concentrations >135 mg/dL, and 17 out of 411 (4.1%) exhibited an IgG4/total IgG ratio >8%. Serum IgG4 concentrations were significantly higher in males than in females and decreased with age. After adjusting for age and sex, serum IgG4 concentrations were not significantly influenced by alcohol consumption, smoking or common metabolic abnormalities (obesity and the related metabolic syndrome). Serum IgG4 concentrations were not significantly correlated with serum concentrations of proinflammatory cytokines and inflammation markers. Serum IgG4 concentrations were significantly correlated with IgE concentrations. Serum IgG4 concentrations tended to be higher in atopics (individuals with IgE-mediated sensitization to aeroallergens) than in non-atopics, particularly among atopics without respiratory symptoms. Serum IgG4 concentrations were not significantly correlated with total eosinophil blood count. Cases of IgG4-related disease were neither present at baseline nor detected after a median of 11 years of follow-up.Studies aimed at defining reference IgG4 values should consider partitioning by age and sex. Further studies are needed to confirm the potential influence of atopy status on serum IgG4 concentrations.

Fundamentos: El cáncer de mama es el tumor más frecuente en mujeres. El objetivo de este estudio es describir el comportamiento de la mortalidad por cáncer de mama en España y en las Comunidades Autónomas (CCAA) desde 1980 a 2005 y estudiar la relación con la implantación de los programas de cribado poblacionales. Métodos: Se ha realizado un análisis de tendencia de la mortalidad por cáncer de mama a partir de los datos de mortalidad del Ministerio de Sanidad y Política Social. Se calcularon las tasas de mortalidad cruda, estandarizada, específica y truncada por 100.000 mujeres. El análisis de tendencia se realizó mediante un modelo de regresión joinpoint y se obtuvo el porcentaje de cambio anual (PCA). Resultados: Entre 1980 y 2005 en España se produjeron 131.746 defunciones por cáncer de mama. En España las tasas bruta, estandarizada, y truncada, presentaron un comportamiento creciente hasta 1992, año en el que se produjo un cambio de tendencia (PCA= -0,1; -0,9; -0,8 respectivamente). Conclusión: La mortalidad por cáncer de mama en las mujeres en España presenta un cambio de tendencia descendente a partir de 1992 que persistió hasta 2005 y que no fue homogénea en todos los grupos de edad.Esta reducción en la tasa de mortalidad también se observó en las CCAA con cierta variabilidad en el año donde se produce el cambio.

INTRODUCTION:Mammographic density (MD) is considered a strong predictor of Breast Cancer (BC). The objective of the present study is to explore the association between MD and the compliance with the World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) recommendations for cancer prevention. METHODS:Data of 3584 women attending screening from a population-based multicenter cross-sectional study (DDM-Spain) collected from October 7, 2007 through July 14, 2008, was used to calculate a score that measures the level of compliance with the WCRF/AICR recommendations: R1)Maintain adequate body weight; R2)Be physically active; 3R)Limit the intake of high density foods; R4)Eat mostly plant foods; R5)Limit the intake of animal foods; R6)Limit alcohol intake; R7)Limit salt and salt preserved food intake; R8)Meet nutritional needs through diet. The association between the score and MD (assessed by a single radiologist using a semi-quantitative scale) was evaluated using ordinal logistic models with random center-specific intercepts adjusted for the main determinants of MD. Stratified analyses by menopausal status and smoking status were also carried out. RESULTS:A higher compliance with the WCRF/AICR recommendations was associated with lower MD (OR1-unit increase = 0.93 95%CI:0.86;0.99). The association was stronger in postmenopausal women (OR = 0.91 95%CI:0.84;0.99) and nonsmokers (OR = 0.87;95%CI:0.80;0.96 for nonsmokers, OR = 1.01 95%CI:0.91;1.12 for smokers, P-interaction = 0.042). Among nonsmokers, maintaining adequate body weight (OR = 0.81 95%CI:0.65;1.01), practicing physical activity (OR = 0.68 95%CI:0.48;0.96) and moderating the intake of high-density foods (OR = 0.58 95%CI:0.40;0.86) and alcoholic beverages (OR = 0.76 95%CI:0.55;1.05) were the recommendations showing the strongest associations with MD. CONCLUSIONS:postmenopausal women and non-smokers with greater compliance with the WCRF/AICR guidelines have lower MD. These results may provide guidance to design specific recommendations for screening attendants with high MD and therefore at higher risk of developing BC.

BackgroundThe aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted Drug Resistance (TDR) defined by the 2009 update of the WHO SDRM list.MethodsWe analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain) between 2007-2011. Using the Stanford algorithm "Low-level resistance", "Intermediate resistance" and "High-level resistance" categories were considered as "Resistant".Results70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs [6.8% (95%Confidence Interval: 5.8-7.7)], and 221 harbored TDR using the WHO list [7.9% (6.9-9.0)]. Differences were due to a lower prevalence in clinically relevant resistance for NRTIs [2.3% (1.8-2.9) vs. 3.6% (2.9-4.3) by the WHO list] and PIs [0.8% (0.4-1.1) vs. 1.7% (1.2-2.2)], while it was higher for NNRTIs [4.6% (3.8-5.3) vs. 3.7% (3.0-4.7)]. While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02).ConclusionsPrevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations.