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Background: Cardiorespiratory fitness (CRF) is a powerful health marker recommended by the American Heart Association as a clinical vital sign. Comparing the predictive validity of objectively measured CRF (the "gold standard") and estimated CRF is clinically relevant because estimated CRF is more feasible. Our objective was to meta-analyze cohort studies to compare the associations of objectively measured, exercise-estimated, and non-exercise-estimated CRF with all-cause and cardiovascular disease (CVD) mortality in adults., Methods: Systematic searches were conducted in 9 databases (MEDLINE, SPORTDiscus, Embase, Scopus, PsycINFO, Web of Science, PubMed, CINAHL, and the Cochrane Library) up to April 11, 2024. We included full-text refereed cohort studies published in English that quantified the association (using risk estimates with 95% confidence intervals (95%CIs)) of objectively measured, exercise-estimated, and non-exercise-estimated CRF with all-cause and CVD mortality in adults. CRF was expressed as metabolic equivalents (METs) of task. Pooled relative risks (RR) for all-cause and CVD mortality per 1-MET (3.5 mL/kg/min) higher level of CRF were quantified using random-effects models., Results: Forty-two studies representing 35 cohorts and 3,813,484 observations (81% male) (362,771 all-cause and 56,471 CVD deaths) were included. The pooled RRs for all-cause and CVD mortality per higher MET were 0.86 (95%CI: 0.83-0.88) and 0.84 (95%CI: 0.80-0.87), respectively. For both all-cause and CVD mortality, there were no statistically significant differences in RR per higher MET between objectively measured (RR range: 0.86-0.90) and maximal exercise-estimated (RR range: 0.85-0.86), submaximal exercise-estimated (RR range: 0.91-0.94), and non-exercise-estimated CRF (RR range: 0.81-0.85)., Conclusion: Objectively measured and estimated CRF showed similar dose-response associations for all-cause and CVD mortality in adults. Estimated CRF could provide a practical and robust alternative to objectively measured CRF for assessing mortality risk across diverse populations. Our findings underscore the health-related benefits of higher CRF and advocate for its integration into clinical practice to enhance risk stratification., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Objective: This study explored whether assessing flexibility levels in clinical settings might predict the odds of oxytocin administration and caesarean section to stimulate labour. Methods: Pregnant women from the GESTAFIT Project (n = 157), participated in this longitudinal study. Maternal upper-body flexibility was assessed at 16 gestational weeks (g.w.) through the Back-scratch test. Clinical data, including oxytocin administration and type of birth, were registered from obstetric medical records. Results: Pregnant women who required oxytocin administration or had caesarean sections showed lower flexibility scores ( p < 0.05 and p < 0.01, respectively). The receiver operating characteristic curve analysis showed that the Back-scratch test was able to detect the need for oxytocin administration ((area under the curve [AUC] = 0.672 (95% confidence interval [CI]: 0.682 (95% CI: 0.59-0.78, p = 0.001)). The AUC to establish the ability of flexibility to discriminate between vaginal and caesarean section births was 0.672 (95% CI: 0.60-0.77, p = 0.002). A Back-scratch test worse than 4 centimetres was associated with a ~5 times greater increased odds ratio of requiring exogenous oxytocin administration (95% CI: 2.0-11.6, p = 0.001) and a ~4 times greater increased odds ratio of having a caesarean section (95% CI: 1.7-10.2, p = 0.002). Conclusions: These findings suggest that lower flexibility levels at the 16th g.w. discriminates between pregnant women who will require oxytocin and those who will not, and those with a greater risk of a caesarean section than those with a vaginal birth. Pregnant women below the proposed Back-scratch test cut-offs at 16th g.w. might specifically benefit from physical therapies that include flexibility training.

Pregnancy involves various physiological, physical, and social changes that can impact the mental health of the woman, causing her to have a stressful experience. Physical fitness (PF) is postulated as a powerful marker of health in this population. Therefore, this longitudinal study examined the association of PF with maternal emotional well-being and ill-being outcomes at 16th and 34th gestational weeks (g.w.) in a sample of 158 pregnant women (32.9 ± 4.7 years old). Self-reported PF was assessed with the valid and feasible International Fitness Scale [i.e., overall PF, cardiorespiratory fitness (CRF), muscular strength, speed-agility, and flexibility]; positive and negative affect, emotional intelligence, and resilience were measured using validated questionnaires specifically designed for this purpose. The results showed that women with greater overall PF and its components showed higher positive affect and lower negative affect (all, p < 0.05); greater emotional intelligence (all, p < 0.05); and greater resilience (all, p < 0.05), with similar results both in the 16th and the 34th g.w. These findings underscore the pivotal role of PF in promoting emotional health and resilience during pregnancy, thereby highlighting the need for integrating PF enhancement strategies in prenatal care programs.

Background: Health-related quality of life (HRQoL) may be altered during pregnancy due to pregnancy-related changes in all domains of women's health., Hypothesis: A supervised concurrent exercise-training program from the 17th gestational week until birth positively influences HRQoL., Study Design: Randomized controlled trial., Level of Evidence: Level 1., Methods: Eighty-six pregnant women (age, 33.1 ± 4.6 years; prepregnancy body mass index, 23.5 kg/m 2 ), divided into exercise (n = 41) and control (n = 45) groups, participated in this study (per-protocol basis). The exercise group followed a 60-min, 3 days/week, concurrent (aerobic + resistance) exercise training program. HRQoL was assessed with the 36-Item Short Form Health Survey (SF-36), where higher scores (0-100) indicate better HRQoL., Results: After adjusting for potential confounders, the exercise group decreased 16.1 points less than the control group in the SF-36 physical functioning domain [between-group differences (B): 95% confidence interval (CI), 9.02 to 23.22; P < 0.01], and 4.5 points less in the SF-36 physical component summary than the control group (between-group differences (B): 95% CI, 0.65 to 8.28; P = 0.02). Intention-to-treat basis analyses depicted similar results, where the exercise group decreased 10.03 points less than the control group the in the SF-36 social functioning domain (between-group differences (B): 95% CI, 0.39 to 19.68; P = 0.04)., Conclusion: A supervised concurrent exercise training program ameliorates HRQoL decreases along gestation. Although HRQoL decreased throughout pregnancy in both groups, this impact was less in the exercise group, especially in the SF-36 physical functioning, the SF-36 social functioning, and the SF-36 physical component summary., Clinical Relevance: Healthcare providers may encourage pregnant women to exercise in this physiological stage for a better HRQoL throughout pregnancy., Clinicaltrials.gov Identifier: NCT02582567; Date of registration: 20/10/2015., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.

This study aimed to examine the association of Mediterranean diet (MD) adherence and MD components with health-related quality of life (HRQoL) in pregnant women from Spain and Sweden. A total of 138 pregnant women from Spain (age: 32.9 ± 4.6 years old) and 302 pregnant women from Sweden (age: 31.3 ± 4.1 years old) were included. MD adherence was assessed with the Mediterranean food pattern (i.e., a MD index) at the 14-16th gestational weeks. HRQoL was assessed with the Spanish and Swedish versions of the 36-item Short-Form Health Survey (SF-36 and RAND-36, respectively) at the 14-16th and 34-37th gestational weeks. A greater MD adherence was associated with better physical functioning, bodily pain, vitality, emotional role, and mental health in cross-sectional associations (2nd trimester) in the Spanish sample (all p < 0.05). Furthermore, a greater MD adherence was associated with lower bodily pain in both Spanish and Swedish samples (both p < 0.05) in the 3rd trimester. The associations of MD adherence with pain seem to be explained by a greater intake of fiber, fish, fruits, nuts, and legumes (all p < 0.05). A greater MD adherence, driven by a higher intake of fiber, fish, fruits, nuts, and legumes, was associated with lower pain throughout pregnancy in both Mediterranean and non-Mediterranean populations.

We explored the association of physical fitness (PF) during pregnancy with maternal body composition indices along pregnancy and postpartum period. The study comprised 159 pregnant women (32.9 ± 4.7 years old). Assessments were carried out at the 16th and 34th gestational weeks (g.w.) and six weeks postpartum. Cardiorespiratory fitness (CRF), muscular strength (absolute and relative values) and flexibility were measured. Body composition indices were obtained by using dual-energy X-ray absorptiometry at postpartum. The results, after adjusting for potential covariates at the 16th g.w., indicated that greater CRF was associated with lower postpartum indices total fat mass, android and gynoid fat mass (all, p  < 0.05). Greater absolute upper-body muscular strength was associated with greater pre-pregnancy body mass index (BMI), gestational weight gain (GWG); and postpartum indices body weight, BMI, lean mass, fat free mass, fat mass, gynoid fat mass, T-score and Z-score bone mineral density (BMD) (all, p  < 0.05). Greater upper-body flexibility was associated with lower pre-pregnancy BMI; and postpartum indices body weight, BMI, lean mass, fat free mass, fat mass, android fat mass and gynoid fat mass, and with greater GWG (all, p  < 0.05). At the 34th g.w., greater CRF was additionally associated with greater postpartum T-score and Z-score BMD (both, p  < 0.05). In conclusion, this study reveals that greater PF levels, especially during early pregnancy, may promote a better body composition in the postpartum period. Therefore, clinicians and health promoters should encourage women to maintain or improve PF levels from early pregnancy.

Objective: The aim of the present study was to explore the influence of a concurrent exercise (aerobic + resistance) training program, from the 17th gestational week (g.w.) until birth on low back and sciatic pain, and pain disability. A total of 93 pregnant women divided into exercise (n = 49) and control (n = 44) groups followed a 60-min, 3 days/week, concurrent exercise training., Methods: Low back and sciatic pain were measured with a Visual Analogic Scale (VAS). The disability resulting from pain was assessed with the Oswestry Disability Index (ODI). Measures were performed at the 16th and 34th g.w., Results: The exercise group increased 21.9 mm less the VAS low back (between-group differences (B): 95% CI: -33.6 to -10.2; p < 0.001) and 12.9 mm less the VAS sciatica score (between-group differences: 95% CI (B): -21.8 to -4.0; p = 0.005) than the control group. Regarding the ODI questionnaire, the exercise group increased 0.7, 0.5, and 0.7 less than the control group in pain while sleeping (between-group differences (B): 95% CI: -1.4 to -0.01; p = 0.025), pain while lifting weight (between-group differences (B): 95% CI: -0.9 to -0.01; p = 0.016), and limitations of the social life due to pain (between-group differences(B): 95% CI: -1.3 to -0.06; p = 0.032). Furthermore, the exercise group suffered 6.9% less pain than the control group in the ODI total score (between-group differences (B): 95% CI: -13.9 to 0.053; p = 0.052)., Conclusion: This concurrent exercise training program adapted to pregnant women improved pain compared to controls., (© 2023 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

To develop a predictive model for successful cervical ripening in women that undergo induction of labour by means of a vaginal prostaglandin slow-release delivery system (Propess®).  Prospective observational study on 204 women that required induction of labour between February 2019 and May 2020 at "La Mancha Centro" hospital in Alcázar de San Juan, Spain. The main variable studied was effective cervical ripening (Bishop score > 6). Using multivariate analysis and binary logistic regression, we created three initial predictive models (model A: Bishop Score + Ultrasound cervical length + clinical variables (estimated fetal weight, premature rupture of membranes and body mass index)); model B: Ultrasound cervical lenght + clinical variables; and model C: Bishop score + clinical variables) to predict effective cervical ripening. All three predictive models obtained (A, B and C) presented good predictive capabilities, with an area under the ROC curve ≥ 0.76. Predictive model C, composed of the variables: gestational age (OR 1.55, 95% CI 1.18-2.03, p = 0.002), premature rupture of membranes (OR 3.21 95% CI 1.34-7.70, p = 0.09) body mass index (OR 0.93, 95% CI 0.87-0.98, p = 0.012), estimated fetal weight (OR 0.99, 95% CI 0.99-1.00, p = 0.068) and Bishop score (OR 1.49 95% CI 1.18-1.81, p = 0.001), is presented as the model of choice with an area under the ROC curve of 0.76 (95% CI 0.70-0.83, p < 0.001). A predictive model composed of the variables: gestational age, premature rupture of membranes, body mass index, estimated fetal weight and Bishop score upon admission presents good capabilities in predicting successful cervical ripening following administration of prostaglandins. This tool could be useful in making clinical decisions with regard to induction of labour., (© 2023. The Author(s).)

Objectives: To analyze the criterion-related validity and the reliability of fitness field tests for evaluating cardiorespiratory fitness in adults, by sex, age, and physical activity level., Design: Cross-sectional., Methods: During 3 weeks, sociodemographic, anthropometric measurements, a treadmill maximal test, the 2-km walk test, and the 20-m SRT were performed in 410 adults aged 18-64 years. Measured and estimated VO 2max (by Oja's and Leger's equations) were analyzed., Results: Measured VO 2max was associated with estimated VO 2max by the 2-km walk test and 20-m SRT (r = 0.784 and r = 0.875, respectively; both p < 0.01). Bland-Altman analysis showed a mean difference of -0.30 ml* kg -1 * min -1 (p < 0.001, d = -0.141) in the 2-km walk test, and 0.86 ml* kg -1 * min -1 (p = 0.051) in the 20-m SRT. Significant mean differences between test and retest were found in the time to complete the 2-km walk test (-1.48 ± 0.51 s, p = 0.004, d = -0.014) and in the final stage reached in the 20-m SRT (0.04 ± 0.01, p = 0.002, d = 0.015). Non-significant differences were found between test and retest in the estimated VO 2max by Oja's (-0.29 ± 0.20 ml* kg -1 * min -1 , p > 0.05) and Leger's eqs. (0.03 ± 0.04 ml* kg -1 * min -1 , p > 0.05). Moreover, both test results and estimated VO 2max equations showed a high test-retest reliability., Conclusions: Both tests were valid and reliable for evaluating cardiorespiratory fitness in adults aged 18-64 years, regardless of sex, age, and physical activity level., Competing Interests: Declaration of interest statement The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background-Aim: Most laboratory requests focus on the detection of possible vitamin B12 deficiency. In this context, methylmalonic acid (MMA) is reported as the best biomarker. The aim of our study was to establish the biological reference interval for MMA in urine, and assess the influence of age, sex, and vitamin B12 status on MMA concentrations., Methods: This is a prospective observational study considering individuals with normal results for blood count and liver and kidney function. Individuals who presented supplementation, any pathology or treatment that could cause cobalamin metabolism disorders, and pregnant women were excluded. Likewise, individuals whose vitamin B12 result presented antibody-mediated interference were excluded. Individuals were grouped by age-group and sex. Reference intervals were determined by non-parametric calculation (percentiles 1-99)., Results: It was established a single reference interval [0.52 (CI 90% : 0.50-0.54) - 5.75 (CI 90% : 5.57-6.17) mmolMMA/mol creatinine], with 100 % of individuals with MMA above the upper limit of reference presenting a total vitamin B12 concentration ≤ 238 pmol/L., Conclusion: The establishment of optimal reference intervals for methylmalonic acid excretion in urine is crucial in individuals with a suspicion of functional vitamin B12 deficiency. However, the possibility of establishing a cut-off value for total vitamin B12 suggesting subclinical deficiency remains a challenge for this magnitude., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The aim of the present study was to provide practical considerations for assessing MD adherence during pregnancy based on the association with cardiometabolic risk., Study Design: Longitudinal study., Main Outcome Measures: A food frequency questionnaire was fulfilled by 152 pregnant women at the 16th gestational week (g.w.). We calculated the Mediterranean Food Pattern (MFP), the MD Scale (MDScale), the Short MD questionnaire (SMDQ), the MD Score (MedDietScore), and the MD scale for pregnant women (MDS-P). The cardiometabolic risk score consisted of pre-pregnancy body mass index, blood pressure, glucose, triglycerides, and high-density lipoprotein-cholesterol (at 16th and 34th g.w.)., Results: Multiple linear regression models showed that the MFP, the MedDietScore, and the SMDQ were associated with lower cardiometabolic risk at the 16th and 34th g.w. (β's: -0.193 to -0.415, all p < 0.05); and the MDS-P at the 34th g.w. (β = -0.349, p < 0.01). A comparison of these models with the J test showed that the MFP and the MedDietScore outperformed the SMDQ at the 16th g.w. (p's < 0.05); while the MedDietScore outperformed the SMDQ, MFP, and MDS-P (p's < 0.05) at the 34th g.w. Receiver-Operating-Characteristic-derived thresholds for the MFP, MedDietScore and MDS-P indices were 21, 30, and 6 points, respectively, to identify women with high cardiometabolic risk., Conclusion: The MFP and MedDietScore are recommended to assess MD adherence during pregnancy, as these showed the strongest associations with cardiometabolic risk. Our validated thresholds might assist in the detection of poor dietary patterns during pregnancy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background-Aim: High vitamin B12 concentrations are considered a common finding in clinical practice. Thanks to immunoassay accessibility, vitamin B12 has become a usual test in routine health checkups. However, these analytical methods usually present antibody-mediated interferences. Our aim was to propose an algorithm for the screening of antibody-mediated analytical interferences on vitamin B12 immunoassays on the Alinity platform., Methods: Observational, prospective, case-control study was performed during 12 months. Individuals with persistently elevated cobalamin concentrations [>554 pmol/L] were considered as cases in the absence of supplementation or other justifying cause. Individuals under treatment with vitamin B12, or in the context of alcoholism were included as controls. A thorough interference study by macromolecules in immunoassays was performed in serum samples: PEG precipitation, rheumatoid factor, heterophile antibodies and gel permeation chromatography (GPC). Albumin, total B12, IgG and IgM were measured in every GPC collected fraction and chromatograms were drafted., Results: Up to 45% of cases presented interference by B12-immunocomplexes and the precipitation for all of them was >50%. The individual with the lowest interfered vitamin B12 result was 661 pmol/L., Conclusion: The presence of antibody-mediated interferences, mainly B12-immunocomplexes, is a relatively common phenomenon. A simple algorithm for the screening of interferences is useful and reliable in ruling out healthy individuals and highly cost-effective., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We explored the association of self-reported physical fitness with depressive symptoms and anxiety levels during pregnancy. One hundred fifty-five pregnant women (32.9 ± 4.7 years old) participated in the study. Self-reported physical fitness was assessed with the International Fitness Scale , depressive symptoms and state anxiety levels with the Center for Epidemiological Studies-Depression Scale and the State Trait Anxiety Index , respectively, at the 16 and 34 weeks of gestation. In model 1 (adjusted for age and gestational weight gain), greater overall self-reported physical fitness was associated with fewer depressive symptoms at the 16 weeks ( p  = .004). Greater self-reported cardiorespiratory fitness and muscular strength were associated with lower anxiety levels at the 16 weeks (all, p  > .05). Greater overall self-reported physical fitness, cardiorespiratory fitness and speed-agility were associated with lower anxiety levels at the 34 weeks (all, p  > .05). These results were also confirmed in model 2 (additionally adjusted for the exercise intervention, sleep quality, educational level, working status and cohabitating), except for cardiorespiratory fitness and anxiety levels at the 16 weeks ( p  = .09). Greater self-reported physical fitness was associated with lower psychological ill-being during pregnancy. Specifically, at the 16 weeks, greater self-reported overall physical fitness was associated with fewer depressive symptoms, greater self-reported muscular strength with lower anxiety levels; greater self-reported overall physical fitness and speed-agility with lower anxiety levels at the 34 weeks and greater self-reported cardiorespiratory fitness with lower anxiety levels during the pregnancy. Screening of physical fitness may reduce the risk of depression and anxiety and generally improve pregnancy mental health-related quality of life. Highlights Maternal depression and anxiety have prevalence rates between 8 and 36%.Physical fitness enhancement during pregnancy results in less depression and anxiety.Greater physical fitness may provide benefits for the mother mental health.Self-reported physical fitness screening during pregnancy may be useful in clinical settings.

Background: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice., Methods: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety., Results: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever)., Conclusions: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Objectives: This multicenter cross-sectional study was conducted to assess the psychosocial impact of COVID-19 on patients with inflammatory bowel disease (IBD) in Spain during lockdown and the first wave of the pandemic., Patients and Methods: A self-report questionnaire that integrated the Spanish version of the Depression, Anxiety and Stress Scale-21 items (DASS-21) and the Perceived Stress Questionnaire (PSS) was designed to gather sociodemographic data and information related to the effects of lockdown on the lives of IBD patients. Twelve IBD units invited their patients to answer the anonymous online survey between the 1st July and the 25th August 2020., Results: Of the 693 survey participants with IBD, 67% were women and the mean age was 43 (SD 12). Sixty-one percent had ulcerative colitis, 36% Crohn's disease and 3% indeterminate colitis. DASS-21 scores indicate that during lockdown the estimated prevalence of depression was 11% [95% CI 8.2-13%], anxiety 20% [95% CI 17 to 23%] and stress 18% [95% CI 8.2-13%]. Multivariate analysis showed that the perceived high risk of COVID-19 infection because of having IBD and maladaptation to government measures to reduce the spread of disease doubled the risk of anxiety and stress during lockdown., Conclusions: In the short-term, lockdown during the COVID-19 pandemic seemed to have an impact on the already affected mental health of our IBD patients in Spain., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.

Background and Aims: Patients with colonic inflammatory bowel disease (IBD) have a high risk of colorectal cancer (CRC). Current guidelines recommend endoscopic surveillance, yet epidemiological studies show poor compliance. The aims of our study were to analyse adherence to endoscopic surveillance, its impact on advanced colorectal lesions, and risk factors of non-adherence., Methods: A retrospective multicentre study of IBD patients with criteria for CRC surveillance, diagnosed between 2005 and 2008 and followed up to 2020, was performed. Following European guidelines, patients were stratified into risk groups and adherence was considered when surveillance was performed according to the recommendations (±1 year). Cox-proportional regression analyses were used to compare the risk of lesions. p-values below 0.05 were considered significant., Results: A total of 1031 patients (732 ulcerative colitis, 259 Crohn's disease and 40 indeterminate colitis; mean age of 36 ± 15 years) were recruited from 25 Spanish centres. Endoscopic screening was performed in 86% of cases. Adherence to guidelines was 27% (95% confidence interval, CI = 24-29). Advanced lesions and CRC were detected in 38 (4%) and 7 (0.7%) patients respectively. Adherence was associated with increased detection of advanced lesions (HR = 3.59; 95% CI = 1.3-10.1; p = 0.016). Risk of delay or non-performance of endoscopic follow-up was higher as risk groups increased (OR = 3.524; 95% CI = 2.462-5.044; p < 0.001 and OR = 4.291; 95%CI = 2.409-7.644; p < 0.001 for intermediate- and high- vs low-risk groups)., Conclusions: Adherence to endoscopic surveillance allows earlier detection of advanced lesions but is low. Groups at higher risk of CRC are associated with lower adherence., (© 2022 John Wiley & Sons Ltd.)

Objective: To investigate the influence of a supervised multicomponent exercise training program on menopause-related symptoms, particularly vasomotor symptoms (VMS), in middle-aged women., Methods: A total of 112 middle-aged women (mean age 52 ± 4 y old, age range 45-60 y) from the FLAMENCO project (exercise [n = 59] and counseling [n = 53] groups) participated in this randomized controlled trial (perprotocol basis). The exercise group followed a multicomponent exercise program composed of 60-minute sessions 3 days per week for 16 weeks. The 15-item Cervantes Menopause and Health Subscale was used to assess the frequency of menopause-related symptoms., Results: After adjusting for body mass index and Mediterranean diet adherence, the subscales measuring menopause-related symptoms and VMSs decreased 4.6 more in the exercise group compared to the counseling group (between-group differences [B]: 95% CI: -8.8 to -0.2; P  = 0.040). The exercise group also showed significant improvements in the subscales of couple relationships (between-group differences [B]: -1.87: 95% CI: -3.29 to - 0.45; P  = 0.010), psychological state (between-group differences [B]: -2.3: 95% CI: -5 to -0.2; P  = 0.035), and VMSs (between-group differences [B]: -4.5: 95% CI: -8.8 to -0.2; p  = 0.040) in the Cervantes Menopause and Health Subscale compared with the counseling group., Conclusions: A 16-week multicomponent physical exercise program showed a positive effect on menopause- related symptoms especially in couple relationships, psychological state, and VMS, among 45 to 60 year old women., Competing Interests: Financial disclosures/conflicts of interest: None reported., (Copyright © 2022 by The North American Menopause Society.)

Purpose: To evaluate the effect and safety of vaginal dinoprostone in pregnant women with PROM who undergo induction of labor (IoL). Materials and Methods: Prospective observational study conducted at La Mancha Centro hospital from 1 February 2019, to 30 August 2020. Obstetric and neonatal variables of 94 pregnant women with PROM who underwent IoL with vaginal dinoprostone were analyzed, and the results were compared with 330 patients without PROM who also underwent IoL. Bivariate and multivariate analyses were performed using binary and multiple linear regression. Results: A total of 424 women were included in this study. A greater response to cervical ripening (Bishop score > 6) with PGE2 was observed in the PROM group (odds ratio (OR) 2.73, 95% confidence interval (CI) 1.50−4.99, p = 0.001), as well as a shorter total duration of IoL (mean difference (MD) 2823.37 min (min), 95% CI 1257.30−4389.43, p < 0.001). Cesarean sections were performed in 28.7% (n = 27) of patients in the PROM group vs. 34.2% (n = 113) of patients in the non-PROM group, with no significant differences (OR 0.87%, 95% CI 0.47−1.60, p = 0.652). There were no significant differences in changes in the cardiotocographic record (CTG), postpartum hemorrhage (PPH), uterine rupture, or adverse neonatal outcomes between the two groups. Conclusions: The use of vaginal dinoprostone in pregnant women undergoing IoL with PROM is safe for the mother and the fetus, shortens the total delivery time, and does not increase the risk of cesarean section compared with pregnant women undergoing IoL without PROM.

Drug-induced liver injury (DILI) is one of the most common and serious adverse drug reactions and a major cause of drug development failure and withdrawal. Although different molecular mechanisms are implicated in DILI, enhanced ROS levels have been described as a major mechanism. Human-derived cell models are increasingly used in preclinical safety assessment because they provide quick and relatively inexpensive information in early stages of drug development. We have analyzed and compared the phenotype and functionality of two liver cell models (Upcyte human hepatocytes and HepaRG cells) to demonstrate their suitability for long-term hepatotoxicity assessments and mechanistic studies. The transcriptomic and functional analysis revealed the maintenance of phase I and phase II enzymes, and antioxidant enzymes along time in culture, although the differences found between both test systems underlie the differential sensitivity to hepatotoxins. The evaluation of several mechanisms of cell toxicity, including oxidative stress, by high-content screening, demonstrated that, by combining the stable phenotype of liver cells and repeated-dose exposure regimes to 12 test compounds at clinically relevant concentrations, both Upcyte hepatocytes and HepaRG offer suitable properties to be used in routine screening assays for toxicological assessments during drug preclinical testing., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We examined sociodemographic factors, lifestyle behaviors, and pregnancy-related determinants associated with adherence to the Mediterranean diet (MD) during pregnancy. A total of 152 Caucasian pregnant women were included in this cross-sectional study. Dietary habits and MD adherence were assessed with a food frequency questionnaire. Physical activity (PA) levels and physical fitness (PF) components (cardiorespiratory fitness, relative muscle strength, and flexibility) were objectively measured. A clustered overall PF index was calculated. Participants with a high MD adherence were older, had a lower body mass index (BMI), spent more time in moderate−vigorous PA, had a greater overall PF, cardiorespiratory fitness, and relative muscle strength compared to participants with low MD adherence (all, p < 0.05). When we explored factors associated with improved MD adherence with logistic regression analysis, we found that the following factors: lower pre-pregnancy BMI (OR = 2.337; p = 0.026), meeting PA recommendations (OR = 2.377; p = 0.045), higher relative muscle strength (OR = 2.265; p = 0.016), and higher overall PF (OR = 5.202; p = 0.004) increased the chances to adhere to the MD. Older age, lower BMI, greater PF, and meeting PA recommendations were associated with higher MD adherence. These factors should be considered for a better design of educational programs and guidelines focused on improving materno−fetal health status during pregnancy.

Motor fitness and flexibility have been linked to several health issues. We aimed to investigate the predictive validity of motor fitness and flexibility tests in relation to health outcomes in adults and older adults. Web of Science and PubMed databases were screened for studies published from inception to November 2020. Two authors systematically searched, evaluated, and extracted data from identified original studies and systematic reviews/meta-analysis. Three levels of evidence were constructed: strong, moderate, and limited/inconclusive evidence. In total, 1182 studies were identified, and 70 studies and 6 systematic reviews/meta-analysis were summarized. Strong evidence indicated that (i) slower gait speed predicts falls and institutionalization/hospitalization in adults over 60 years old, cognitive decline/impairment over 55 years old, mobility disability over 50 years old, disability in instrumental activities of daily living (IADL) over 54 years old, cardiovascular disease risk over 45 years old, and all-cause mortality over 35 years old; (ii) impaired balance predicts falls and disability in IADL/mobility disability in adults over 40 years old and all-cause mortality over 53 years old; (iii) worse timed up&go test (TUG) predicts falls and fear of falling over 40 years old. Evidence supports that slower gait speed, impaired balance, and worse TUG performance are significantly associated with an increased risk of adverse health outcomes in adults.

Background: We aimed to describe the effectiveness and safety of inhaled antibiotics in chronic obstructive pulmonary disease (COPD) patients, as well as the patient profile in which they are usually prescribed and the patient groups that can most benefit from this treatment., Methods: Multicentre retrospective observational cohort study in COPD patients who had received ≥1 dose of inhaled antibiotics in the last 5 years. Clinical data from the two years prior to and subsequent to the start of the treatment were compared., Primary Outcome: COPD exacerbations., Secondary Outcomes: side effects, symptomatology (sputum purulence, dyspnoea), microbiological profile and pathogen eradication., Results: Of 693 COPD patients analyzed (aged 74.1; 86.3% men; mean FEV 1 =43.7%), 71.7% had bronchiectasis and 46.6% presented chronic bronchial infection (CBI) by Pseudomonas aeruginosa (PA). After 1 year of treatment with inhaled antibiotics, there was a significant decrease in the number of exacerbations (-33.3%; P<.001), hospital admissions (-33.3%; P<.001) and hospitalization days (-26.2%; P=.003). We found no difference in effectiveness between patients with or without associated bronchiectasis. Positive patient outcomes were more pronounced in PA-eradicated patients. We found a significant reduction in daily expectoration (-33.1%; P=.024), mucopurulent/purulent sputum (-53.9%; P<.001), isolation of any potentially pathogenic microorganisms (PPM) (-16.7%; P<.001), CBI by any PPM (-37.4%; P<.001) and CBI by PA (-49.8%; P<.001). CBI by any PPM and ≥three previous exacerbations were associated with a better treatment response. 25.4% of patients presented non-severe side-effects, the most frequent of these being bronchospasm (10.5%), dyspnoea (8.8%) and cough (1.7%)., Conclusions: In COPD patients with multiple exacerbations and/or CBI by any PPM (especially PA), inhaled antibiotics appear to be an effective and safe treatment, regardless of the presence of bronchiectasis., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Vaginal dinoprostone (PGE 2 ) is currently used as the prostaglandin of choice in many obstetric units. However, few studies have evaluated its safety, especially in women who previously had a cesarean section., Objective: To evaluate the efficacy and safety of PGE 2 in pregnant women who are undergoing induction of labor (IOL), and who have had a previous cesarean section., Materials and Methods: A prospective observational study was conducted in La Mancha Centro Hospital in Alcázar de San Juan, Spain, from 1 February 2019 to 30 August 2020. Obstetric and neonatal outcomes, following IOL with PGE 2 , in 47 pregnant women who wanted a trial of labor after cesarean (TOLAC), and 377 pregnant women without a history of cesarean section, were analyzed. The outcomes were analyzed by bivariate and multivariate analyses using binary and multiple linear regression., Results: A total of 424 women were included in this study. The percentage of cesarean sections in the TOLAC group was 44.7% (21), compared with 31.6% (119) in the group without a history of cesarean section (adjusted odds ratio: 1.4; 95% CI: 0.68-2.86). In the multivariate analysis, no statistically significant differences were observed between both groups for obstetric and neonatal outcomes ( p > 0.05). However, two uterine ruptures (4.3%) occurred in the group of patients with a history of cesarean section who underwent IOL with PGE 2 ., Conclusions: The induction of labor with vaginal dinoprostone (PGE 2 ), in patients with a previous history of cesarean section, was not associated with worse obstetric or neonatal outcomes compared with the group of patients without a history of cesarean section in our study sample. However, further research is needed regarding this IOL method, and it should be used with caution in this population group.

Background: Sex hormone deprivation derived from menopause may affect exercise-induced muscle damage (EIMD). No studies have previously evaluated this response between postmpenopausal and premenopausal eumenorrheic women over the menstrual cycle., Hypothesis: Postmenopausal women will present higher EIMD markers than premenopausal women, especially in comparison with the menstrual cycle phases where sex hormone concentrations are higher., Study Design: Cross-sectional study., Level of Evidence: Level 3., Methods: Thirteen postmenopausal and 19 eumenorrheic women, all of them resistance-trained, performed an eccentric squat-based exercise. The postmenopausal group performed 1 bout of exercise, while the eumenorrheic group performed 3 bouts coinciding with the early follicular, late follicular, and mid-luteal phases ot their menstrual cycle. Muscle soreness, countermovement jump, creatine kinase (CK), myoglobin, lactate dehydrogenase, interleukin-6, tumor necrosis factor-α, and C-reactive protein were evaluated before and postexercise., Results: The expected differences in sex hormones were observed between groups ( P < 0.001) according to their reproductive status. Postexercise increases in CK, myoglobin, and muscle soreness (168.2 ± 45.5 U/L, 123.1 ± 41.5 µg/L, and 20.7 ± 21.3 mm, respectively) were observed in comparison with baseline (136.2 ± 45.5 U/L, 76.9 ± 13.8 µg/L, and 2.7 ± 4.2 mm, respectively). Myoglobin values at baseline in postmenopausal women were higher compared with premenopausal women in the aforementioned menstrual cycle phases, respectively (62.8 ± 8.2, 60.4 ± 7.2, and 60.1 ± 10.6 µg/L; P < 0.001 for all comparisons), which was supported by large effect sizes (0.72-1.08 standardized d units). No postexercise differences were observed between groups in any markers ( P > 0.05)., Conclusion: Despite higher resting levels of myoglobin and lower strength values in postmenopausal than in premenopausal women, EIMD was similar between both reproductive profiles. This suggests a potential benefit of being physically active despite aging and sex hormone deprivation., Clinical Relevance: Sex hormone deprivation derived from menopause seems not to influence muscle damage reponse to eccentric exercise in resistance-trained postmenopausal women.

Background: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab., Aims: To evaluate the impact of biologics on the risk of PC., Methods: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis., Results: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27)., Conclusions: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

We explored (a) the associations between self-reported maternal physical fitness and birth outcomes; (b) whether self-reported maternal physical fitness (PF) is related to the administration of oxytocin to induce or stimulate labour. Pregnant women from the GESTAFIT project randomized controlled trial (n = 117) participated in this prospective longitudinal study. Maternal physical fitness was assessed through the International Fitness Scale at the 34th gestational week. Maternal and neonatal birth outcomes and oxytocin administration were collected from the obstetric medical records. Umbilical arterial and venous cord blood gas were analysed immediately after birth. Self-reported overall fitness, cardiorespiratory fitness, muscular strength and flexibility were not related to any maternal and neonatal birth outcomes (all p > 0.05). Greater speed-agility was associated with a more alkaline arterial ( p = 0.04) and venous ( p = 0.02) pH in the umbilical cord blood. Women who were administered oxytocin to induce or stimulate labour reported lower cardiorespiratory fitness ( p = 0.013, Cohen's d = 0.55; 95% confidence interval (CI): 0.14, 0.93) and flexibility ( p = 0.040, Cohen´s d = 0.51; 95% CI: 0.09, 0.89) compared to women who were not administered oxytocin. Greater maternal physical fitness during pregnancy could be associated with better neonatal birth outcomes and lower risk of needing oxytocin administration.

Background and Aims: Studies regarding dietary patterns and cardiometabolic risk markers during pregnancy are scarce. The aim of the present study was to analyse whether different degrees of adherence to the Mediterranean diet (MD) and the MD components were associated with cardiometabolic markers and a clustered cardiometabolic risk during pregnancy., Methods and Results: This study comprised 119 pregnant women from the GEStation and FITness (GESTAFIT) project. Dietary habits were assessed with a food frequency questionnaire at the 16th and 34th gestational weeks (g.w.). The Mediterranean Diet Score was employed to assess MD adherence. The following cardiometabolic markers were assessed: pre-pregnancy body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, triglycerides and high-density lipoprotein cholesterol (HDL-C). A greater MD adherence was associated with a better cardiometabolic status in cross-sectional (16th g.w. and 34th g.w.) and prospective analyses (MD adherence at the 16th g.w. and cardiometabolic markers at the 34th g.w.; SBP, DBP and HDL-C; all, p < 0.05). Participants with the highest MD adherence (Tertile 3) had a lower clustered cardiometabolic risk than those with the lowest MD adherence (Tertile 1) at the 16th and 34th g.w. (both, p < 0.05). A higher intake of fruits, vegetables and fish and a lower intake of refined cereals and red meat and subproducts were associated with a lower cardiometabolic risk during pregnancy (all, p < 0.05)., Conclusion: A higher MD adherence, a greater intake of fruits, vegetables and fish and a lower intake of refined cereals and red meat and subproducts showed a cardioprotective effect throughout gestation., Competing Interests: Declaration of competing interest None of the authors have any conflict of interests., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery.

We explored the association of physical fitness (PF) with pregnancy-related symptoms, at the 16th and 34th gestational weeks (g.w.). The International Fitness Scale and the Pregnancy Symptoms Inventory were employed to assess self-reported PF and pregnancy-related symptoms, respectively. At the 16th g.w. greater self-reported overall PF was associated with lower incidence of urinary frequency ( p = 0.020); greater overall PF, cardiorespiratory fitness (CRF), muscular strength and speed-agility were associated with lower incidence of tiredness-fatigue (all, p < 0.05); greater overall PF and speed-agility were associated with lower incidence of poor sleep (both, p < 0.05); greater CRF and flexibility were associated with lower limitations by tiredness-fatigue (both, p < 0.05); and greater flexibility was associated with lower limitations by poor sleep ( p = 0.021). At the 34th g.w. greater self-reported overall PF, CRF and muscular strength were associated with lower incidence of tiredness-fatigue (all, p < 0.05); greater CRF was associated with lower incidence of poor sleep ( p = 0.019); and, greater flexibility was associated with lower incidence of increased vaginal discharge ( p = 0.023). Adequate levels of PF, especially CRF, may help women to cope with the most endorsed pregnancy-related symptoms and its limitations, especially tiredness-fatigue and poor sleep.

Objective: To analyze the influence of a supervised concurrent exercise program on emotional well-being and emotional distress in middle-aged women., Methods: This randomized controlled trial included 150 middle-aged women recruited for the FLAMENCO project. Participants were allocated into counseling (n = 75) or exercise (n = 75) groups. The counseling group attended conferences on healthy lifestyle (including diet and physical activity topics). The exercise group followed a 60-min concurrent (aerobic + resistance) exercise training 3 days/wk for 16 weeks. Emotional health was assessed with the Positive and Negative Affect Schedule (PANAS) in two diverse timeframes, state (PANAS-S) and trait (PANAS-T) ranging from 10 to 50, where higher scores reflect greater affective emotional health/experience (positive affect subscale) and greater emotional distress (negative affect subscale). The differences between the counseling and exercise groups in PANAS were analyzed by linear regression., Results: The total number of women for the per-protocol analyses was 111 divided into the counseling (n = 53) and exercise (n = 58) groups. After adjusting for body mass index and Mediterranean diet adherence, PANAS-S and PANAS-T-positive affect scores increased by 3.81 and 3.02, respectively, in the exercise group whereas they decreased by 0.15 and increased by 0.51 in the counseling group (both, P < 0.05). PANAS-T negative affect decreased by 4.10 in the exercise group whereas only decreased by 0.9 in the counseling group (P < 0.05)., Conclusion: A 16-week concurrent exercise program improved emotional experience in middle-aged women. Specifically, women in the exercise group significantly improved their emotional well-being and emotional distress through greater changes in positive affect and negative affect compared with the counseling group., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2021 by The North American Menopause Society.)

The aims of this cross-sectional study were to describe objectively measured sedentary time (ST) and physical activity (PA) levels in Spanish pregnant women, to analyze the degree of compliance with PA guidelines during the early second trimester of pregnancy and to explore sociodemographic and clinical factors associated with meeting these PA guidelines. One hundred and thirty-four Caucasian pregnant women were recruited between October 2015 and October 2017 to participate in this study. Triaxial accelerometers were used to analyze ST andPA levels for seven consecutive valid days. Womenspent512 ± 92.1 minutes daily in sedentary behaviors, and 85 ± 108.2 minutes in moderate-to-vigorous physical activity (MVPA) in bouts of at least 10 minutes. They walked on average 7436 ± 2410steps per day. Only 22% of the study sample complied with the PA guidelines. Having an University degree was related with threefold higher odds of compliance with the PA guidelines (95% confidence interval: 0.096-0.913, p < .05). Binary logistic regressions showed that being primiparous was associated with fivefold higher odds of compliance with the PA guidelines (95% confidence interval 1.658-18.039, respectively, p < .01). Maternal age, BMI, marital status, working status, and previous miscarriages were not associated with compliance with PA guidelines. Pregnant women spent more than a third of the day in sedentary behaviors and the compliance with PA guidelines was less than desirable. Finally, not having an university degree or having children could be factors related to lower odds of compliance with these guidelines, and therefore require special attention from healthcare professionals.

We examined the association of the dietary habits and the Mediterranean diet (MD) adherence with sleep quality during pregnancy. A food frequency questionnaire and the Mediterranean Food Pattern were employed to assess dietary habits and MD adherence, respectively. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) global score ( n = 150; mean age 32.9 ± 4.6 years). A higher consumption of fruits was associated with better sleep quality at the 16th gestational week (g.w.; p < 0.05). A greater olive oil consumption and a higher MD adherence were associated with better sleep quality at the 16th and 34th g.w. (all, p < 0.05). Contrarily, a higher red meat and subproducts consumption was associated with worse sleep quality at the 34th g.w. ( p < 0.05). The group with the highest adherence to the MD (Tertile 3) showed better sleep quality than the group with the lowest adherence (Tertile 1) at the 16th and 34th g.w. (both, p < 0.05). A higher adherence to the MD, a greater intake of fruits and olive oil and a lower intake of red meat and subproducts were associated with better sleep quality along the pregnancy course, especially among sedentary women.

Objective: To explore the association of dietary habits and Mediterranean diet adherence with menopausal symptoms., Methods: The present study included 172 women recruited from the FLAMENCO project. Menopausal symptoms were assessed with the Kupperman Menopausal Index and the Cervantes Menopause and Health Subscale from the validated Cervantes Scale. A food frequency questionnaire was employed to evaluate dietary habits. Adherence to the Mediterranean diet was assessed with the Mediterranean diet score., Results: Intake of poultry and skimmed dairy products was associated with a worse Kupperman Menopausal Index score (β: 0.17, P = 0.03 and β: 0.18, P = 0.01, respectively). On the contrary, soy milk consumption was associated with a better Kupperman Menopausal Index score (β: -0.17, P = 0.02). Poultry and skimmed dairy were associated with worse scores in the total Cervantes Menopause and Health Subscale score (β: 0.22, P = <0.01 and β: 0.19, P = 0.01, respectively), whereas soy milk and vegetables were associated with a better total Cervantes Menopause and Health Subscale score (β: -0.20, P = 0.01 and β: -0.17, P = 0.03, respectively). Regarding vasomotor symptoms, a greater consumption of poultry was associated with worse symptomatology (β: 0.18, P = 0.02), and soy milk consumption was associated with fewer vasomotor symptoms (β: -0.15, P = 0.04). In addition, women with numerous or severe vasomotor symptoms showed a greater consumption of skimmed dairy products (P < 0.05)., Conclusions: This study seems to indicate that some women with mild menopausal symptoms may derive benefit from lower consumption of poultry and skimmed dairy products and a greater consumption of vegetables and soy milk.

Objective: The aim of the study was to analyze the association of objectively measured sedentary time and physical activity with health-related quality of life in middle-aged women., Methods: The present cross-sectional analyses were performed in a total of 182 middle-aged women (52.6 ± 4.6 years old) from the Fitness League Against MENopause COst (FLAMENCO) project. Sedentary time and physical activity were objectively measured through accelerometry. Participants' health-related quality of life was assessed with the Short-Form Health Survey 36 (SF-36)., Results: Lower sedentary time was associated with a better SF-36 emotional role (B: -0.03; 95% confidence interval: -0.07 to -0.00). Greater light physical activity was associated with a better SF-36 emotional role (B: 0.04; 95% confidence interval: 0.00-0.08). Greater moderate-vigorous physical activity was associated with a greater SF-36 physical function (B: 0.01; 95% confidence interval: 0.00-0.02) and SF-36 vitality (B: 0.02; 95% confidence interval: 0.00-0.03). Greater vigorous physical activity was associated with a better SF-36 physical function (B: 0.34; 95% confidence interval: 0.02-0.66), SF-36-bodily pain (B: 0.63; 95% confidence interval: 0.02-1.25), and the SF-36 physical component scale (B: 0.20; 95% confidence interval: 0.00-0.39). Greater total physical activity was associated with a better SF-36 emotional role (B: 0.03; 95% confidence interval: 0.00-0.07). Moderate physical activity was not associated with any SF-36 dimension (all, P > 0.05)., Conclusions: Spending less time in sedentary behavior and greater physical activity levels, especially vigorous physical activity, are associated with better health-related quality of life in middle-aged women. Vigorous physical activity is associated with a better SF-36 physical component scale, which might mean a reduction in exercise time with similar improvements for women's quality of life.ClinicalTrials.gov Identifier: NCT02358109. Date of registration: 05/02/2015.

Objective: The aim of this study was to explore the association of self-reported physical fitness (PF) and its components with cardiometabolic and mental health in perimenopausal women., Methods: These cross-sectional analyses included 191 participants (53 ± 4 y old) from the FLAMENCO project. Self-reported PF was assessed with the International Fitness Scale (IFIS). Body mass index (BMI), fat mass (FM), waist circumference (WC), systolic and diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL-C), triglycerides, C-reactive protein (CRP), and glucose were measured. The Beck's Depression Inventory, State-Trait Anxiety Inventory, Pittsburgh Sleep Quality Index, Life Orientation Test Revised, and Positive and Negative Affect Schedule were used to assess mental health., Results: After adjusting for potential confounders, greater overall PF was associated with lower BMI, FM, WC (P < 0.001), DBP and CRP, and higher HDL-C (P < 0.05). Cardiorespiratory fitness (CRF), speed-agility, and flexibility were associated with lower BMI, WC, and FM (P < 0.001), and muscle strength (MS) with lower WC and FM (P < 0.05). In addition, CRF, MS, and speed-agility were associated with lower CRP (P < 0.01), and flexibility with enhanced triglycerides and HDL-C (P < 0.05). Overall PF and all its components were associated with lower depression, anxiety, and negative affect (P≤0.01), and greater positive affect (P≤0.05). Overall PF and MS were associated with better sleep quality (P < 0.05), and CRF, MS, and speed-agility with greater optimism (P≤0.05). Finally, overall PF showed evidence of significant association with less pharmaceutical expenditure (B = -7.2, β=-0.145, P = 0.08)., Conclusions: Self-reported PF was associated with better cardiometabolic and mental health in perimenopausal women. The IFIS might be proposed as an inexpensive, quick, and easy tool in clinical settings.

Aims: To explore the association of self-reported physical fitness with bodily, lumbar and sciatic pain, and pain disability during pregnancy., Methods: The present study sample comprised 159 pregnant women (32.9 ± 4.7 years old). Self-reported physical fitness was assessed with the International Fitness Scale (IFIS), where higher scores indicate greater physical fitness. Bodily pain was assessed with the 36-Item Short Form Health Survey (SF-36), where higher scores indicate lower pain. Lumbar and sciatic pain were measured with a visual analogue scale (VAS). The Oswestry Disability Index (ODI) questionnaire was employed to assess the disability resulting from pain. Measures were assessed at 16th and 34th gestational weeks (g. w.)., Results: Pregnant women showed low-moderate pain during pregnancy course. Most of them showed medium self-reported overall physical fitness. At 16th g. w., greater self-reported overall physical fitness and cardiorespiratory fitness were associated with less bodily and lumbar pain, and pain disability (all, P < 0.05). Greater muscular strength was associated with less bodily pain and pain disability (both, P < 0.05). Greater speed-agility was associated with less bodily pain (P < 0.01) and less pain disability (P < 0.05). Self-reported flexibility was not associated with any outcome (P > 0.05). At 34th g. w., greater overall physical fitness and its components were associated with less bodily and sciatic pain (all, P < 0.05)., Conclusion: Greater self-reported overall physical fitness and its components are associated with less bodily, lumbar and sciatic pain, and reduced pain disability during pregnancy. Future studies are needed to explore whether increasing physical fitness before and during pregnancy could decrease pain in this relevant stage., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: In assessing the patient with headache, clinicians are often faced with 2 important questions: Is this headache a migraine? Does this patient require neuroimaging? The aim of this study was to assess the validity and applicability of the mnemonic POUNDing rule in patients diagnosed with migraine., Patients and Methods: A descriptive, validation study of the POUNDing rule in patients with a diagnosis of migraines and with a brain imaging test (computed tomography or magnetic resonance imaging), in an urban health centre and a neurology clinic of the University Hospital of Badajoz., Results: A total of 116 patients were included (mean age 45.6 years; 79.3% women, 70 from the neurology clinics, and 46 from the health centre). The best validity parameters of the POUNDing rule were its positive predictive values: 90.9% (95% CI: 57.1-99.5%), 100% (95% CI: 73.2-99.3%), and 96.0% (95% CI: 77.7-99.8%) in the patients of the neurology clinic, the health centre and in the total population, respectively, and its low negative predictive values: 6.8% (95% CI: 2.2-17.3%), 3.1% (95% CI: 0.2-18.0%), and 5.5% (95% CI: 2.0-12.9%), also respectively in the patients of the neurology clinic, the health centre and in the total population., Conclusions: The POUNDing mnemonic rule has a high positive predictive values and can be a great help in accepting or rejecting a diagnosis of migraine, facilitating a more efficient use of neuroimaging tests., (Copyright © 2018 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

To review binocular and accommodative disorders documented after corneal or intraocular refractive surgery, in normal healthy prepresbyopic patients. A bibliographic revision was performed; it included works published before 1st July 2017 where accommodation and/or binocularity was assessed following any type of refractive surgical procedure. The search in Pubmed yielded 1273 papers, 95 of which fulfilled the inclusion criteria. Few publications reporting binocular vision and/or accommodative changes after refractive surgery in normal subjects were found. The reduction in fusional vergence is the most frequently reported alteration. Anisometropia is an important risk factor for postoperative binocular vision-related complaints. Most diplopia-related visual complaints, irrespective of the surgical procedure, were in fact misdiagnosed preoperative disorders. The preoperative evaluation of patients seeking spectacle/contact lens independence should include a complete binocular and accommodation assessment where parameters such as the phoric posture, accommodative amplitude and facility, near point of convergence, fusional reserves and accommodative convergence/accommodation coefficient are measured. This would allow the identification of risk factors that could compromise the success of the refractive surgery and cause clinical symptoms., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Drug-induced liver injury (DILI) constitutes one of the most frequent reasons of restricted-use warnings as well as withdrawals of drugs in postmarketing and poses an important concern for the pharmaceutical industry. The current hepatic in vivo and in vitro models for DILI detection have shown clear limitations, mainly for studies of long-term hepatotoxicity. For this reason, we here evaluated the potential of using Upcytes human hepatocytes (UHH) for repeated-dose long-term exposure to drugs. The UHH were incubated with 15 toxic and non-toxic compounds for up to 21 days using a repeated-dose approach, and, in addition to conventional examination of effects on viability, the mechanisms implicated in cell toxicity were also assessed by means of high-content screening. The UHH maintained the expression and activity levels of drug-metabolizing enzymes for up to 21 days of culture and became more sensitive to the toxic compounds after extended exposures, showing inter-donor differences which would reflect variability among the population. The assay also allowed to detect the main mechanisms implicated in the toxicity of each drug as well as identifying special susceptibilities depending on the donor. UHH can be used for a long-term repeated detection of DILI at clinically relevant concentrations and also offers key mechanistic features of drug-induced hepatotoxicity. This system is therefore a promising tool in preclinical testing of human relevance that could help to reduce and/or replace animal testing for drug adverse effects.

The term "bacterial dysbiosis" is being used quite extensively in metagenomic studies, however, the identification of harmful bacteria often fails due to large overlap between the bacterial species found in healthy volunteers and patients. We hypothesized that the pathogenic oral bacteria are individual-specific and they correlate with oxidative stress markers in saliva which reflect the inflammatory processes in the oral cavity. Temporally direct and lagged correlations between the markers and bacterial taxa were computed individually for 26 volunteers who provided saliva samples during one month (21.2 ± 2.7 samples/volunteer, 551 samples in total). The volunteers' microbiomes differed significantly by their composition and also by their degree of microbiome temporal variability and oxidative stress markers fluctuation. The results showed that each of the marker-taxa pairs can have negative correlations in some volunteers while positive in others. Streptococcus mutans , which used to be associated with caries before the metagenomics era, had the most prominent correlations with the oxidative stress markers, however, these correlations were not confirmed in all volunteers. The importance of longitudinal samples collections in correlation studies was underlined by simulation of single sample collections in 1000 different combinations which produced contradictory results. In conclusion, the distinct intra-individual correlation patterns suggest that different bacterial consortia might be involved in the oxidative stress induction in each human subject. In the future, decreasing cost of DNA sequencing will allow to analyze multiple samples from each patient, which might help to explore potential diagnostic applications and understand pathogenesis of microbiome-associated oral diseases., Competing Interests: The authors declare no competing interests.

The identification of patients with advanced and complex chronic diseases, and the fragmentation of care towards the end of life, requires the drawing up a long-term therapeutic plan. This should take into account the values and preferences of the patients, as well as the vital and functional prognosis. Having an adjustment tool for determining the diagnostic and therapeutic effort is helpful in the continuity of care, as well as in decision-making in the transitions and dynamic changes of patients as they approach the end of life process., (Copyright © 2018 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify metabolic phenotypes with increased susceptibility to DILI. To this end, HepG2 cells with different expression levels of specific drug-metabolism enzymes (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, GSTM1 and UGT2B7) were exposed to nine drugs with reported hepatotoxicity. A panel of pre-lethal mechanistic parameters (mitochondrial superoxide production, mitochondrial membrane potential, ROS production, intracellular calcium concentration, apoptotic nuclei) was used. Significant differences were observed according to the level of expression and/or the combination of several drug-metabolism enzymes in the cells created ad hoc according to the enzymes implicated in drug toxicity. Additionally, the main mechanisms implicated in the toxicity of the compounds were also determined showing also differences between the different types of cells employed. This screening tool allowed to mimic the variability in drug metabolism in the population and showed a highly efficient system for predicting human DILI, identifying the metabolic phenotypes associated with increased DILI risk, and indicating the mechanisms implicated in their toxicity.

Background: Knowing the cost of hospitalizations for exacerbation in bronchiectasis patients is essential to perform cost-effectiveness studies of treatments that aim to reduce exacerbations in these patients., Objectives: To find out the mean cost of hospitalizations due to exacerbations in bronchiectasis patients, and to identify factors associated with higher costs., Methods: Prospective, observational, multicenter study in adult bronchiectasis patients hospitalized due to exacerbation. All expenses from the patients' arrival at hospital to their discharge were calculated: diagnostic tests, treatments, transferals, home hospitalization, admission to convalescence centers, and hospitals' structural costs for each patient (each hospital's tariff for emergencies and 70% of the price of a bed for each day in a hospital ward)., Results: A total of 222 patients (52.7% men, mean age 71.8 years) admitted to 29 hospitals were included. Adding together all the expenses, the mean cost of the hospitalization was EUR 5,284.7, most of which correspond to the hospital ward (86.9%), and particularly to the hospitals' structural costs. The adjusted multivariate analysis showed that chronic bronchial infection by Pseudomonas aeruginosa, days spent in the hospital, and completing the treatment with home hospitalization were factors independently associated with a higher overall cost of the hospitalization., Conclusions: The mean cost of a hospitalization due to bronchiectasis exacerbation obtained from the individual data of each episode is higher than the cost per process calculated by the health authorities. The most determining factor of a higher cost is chronic bronchial infection due to P. aeruginosa, which leads to a longer hospital stay and the use of home hospitalization., (© 2018 S. Karger AG, Basel.)

Background: Oral vancomycin remains the mainstay of therapy for severe infections produced by Clostridium difficile, the most prevalent cause of healthcare-associated infectious diarrhoea in developed countries. However, its short- and long-term effects on the human intestinal microbiota remain largely unknown., Methods: We utilized high-throughput sequencing to analyse the effects of vancomycin on the faecal human microbiota up to 22 weeks post-antibiotic cessation. The clinical relevance of the observed microbiota perturbations was studied in mice., Results: During vancomycin therapy, most intestinal microbiota genera and operational taxonomic units (OTUs) were depleted in all analysed subjects, including all baseline OTUs from the phylum Bacteroidetes. This was accompanied by a vast expansion of genera associated with infections, including Klebsiella and Escherichia/Shigella. Following antibiotic cessation, marked differences in microbiota resilience were observed among subjects. While some individuals recovered a microbiota close to baseline composition, in others, up to 89% of abundant OTUs could no longer be detected. The clinical relevance of the observed microbiota changes was further demonstrated in mice, which developed analogous microbiota alterations. During vancomycin treatment, mice were highly susceptible to intestinal colonization by an antibiotic-resistant pathogen and, upon antibiotic cessation, a less-resilient microbiota allowed higher levels of pathogen colonization., Conclusions: Oral vancomycin induces drastic and consistent changes in the human intestinal microbiota. Upon vancomycin cessation, the microbiota recovery rate varied considerably among subjects, which could influence, as validated in mice, the level of susceptibility to pathogen intestinal colonization. Our results demonstrate the negative long-term effects of vancomycin, which should be considered as a fundamental aspect of the cost-benefit equation for antibiotic prescription., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Hepatotoxicity is the number one cause for agencies not approving and withdrawing drugs for the market. Drug-induced human hepatotoxicity frequently goes undetected in preclinical safety evaluations using animal models. Human-derived in vitro models represent a common alternative to in vivo tests to detect toxic effects during preclinical testing. Most current in vitro toxicity assays rely on the measurement of nonspecific or low sensitive endpoints, which result in poor concordance with human liver toxicity. Therefore, making more accurate predictions of the potential hepatotoxicity of new drugs remains a challenge. Metabolomics, whose aim is to globally assess all the metabolites present in a biological sample, may represent an alternative in the search for sensitive sublethal markers of drug-induced hepatotoxicity. To this end, a comprehensive LC-MS-based untargeted metabolite profiling analysis of HepG2 cells, exposed to a set of well-described model hepatotoxins and innocuous compounds, was performed. It allowed to determine meaningful metabolic changes triggered by a toxic insult and gave a first estimation of the main toxicity-related pathways. Based on these metabolic patterns, a partial least squares-discriminant analysis model, able to discriminate between nontoxic and hepatotoxic compounds, was constructed. The approach described herein may provide an alternative for animal testing in preclinical stages of drug development and a controlled experimental approach to gain a better understanding of the underlying causes of hepatotoxicity., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hepatocyte transplantation is an alternative therapy to orthotopic liver transplantation for the treatment of liver diseases. However, the supply of hepatocytes is limited given the shortage of organs available to isolate good-functioning quality cells. Neonatal livers may be a potential source alternative to adult livers to obtain good-performing hepatic cells for hepatocyte transplantation, which has not yet been explored profoundly. High-yield preparations of viable hepatocytes were isolated from 1- to 23-day-old liver donors, cryopreserved, and banked. Cell integrity and functional quality assessment were performed after thawing. Neonatal hepatocytes showed better postthawing recovery compared with adult hepatocytes, as shown by the viability values that did not differ significantly from freshly isolated cells, a higher expression of adhesion molecules (β1-integrin, β-catenin, and E-cadherin), better attachment efficiency, cell survival, and a lower number of apoptotic cells. The metabolic performance of thawed hepatocytes has been assessed by ureogenesis and drug-metabolizing capability (cytochrome P450 and UDP-glucuronosyltransferase enzymes). CYP2A6, CYP2C9, CYP2E1, and CYP3A4 activities were found in all cell preparations, while CYP1A2, CYP2B6, CYP2C19, and CYP2D6 activities were detected only in hepatocytes from a few neonatal donors. The expression of UGT1A1 and UGT1A9 (transcripts and protein) was detected in all hepatocyte preparations, while activity was measured only in some preparations, probably due to lack of maturity of the enzymes. However, isoforms UGT1A6 and UGT2B7 showed considerable activity in all preparations. Compared to adult liver, the hepatocyte isolation procedure in neonatal livers also provides thawed cell suspensions with a higher proportion of hepatic progenitor cells (EpCAM(+) staining), which could also participate in regeneration of liver parenchyma after transplantation. These results could imply important advantages of neonatal hepatocytes as a source of high-quality cells to improve human hepatocyte transplantation applicability.