Prioritizing Molecular Biomarkers in Asthma and Respiratory Allergy Using Systems Biology.

Highly prevalent respiratory diseases such as asthma and allergy remain a pressing health challenge. Currently, there is an unmet need for precise diagnostic tools capable of predicting the great heterogeneity of these illnesses. In a previous study of 94 asthma/respiratory allergy biomarker candidates, we defined a group of potential biomarkers to distinguish clinical phenotypes (i.e. nonallergic asthma, allergic asthma, respiratory allergy without asthma) and disease severity. Here, we analyze our experimental results using complex algorithmic approaches that establish holistic disease models (systems biology), combining these insights with information available in specialized databases developed worldwide. With this approach, we aim to prioritize the most relevant biomarkers according to their specificity and mechanistic implication with molecular motifs of the diseases. The Therapeutic Performance Mapping System (Anaxomics' TPMS technology) was used to generate one mathematical model per disease: allergic asthma (AA), non-allergic asthma (NA), and respiratory allergy (RA), defining specific molecular motifs for each. The relationship of our molecular biomarker candidates and each disease was analyzed by artificial neural networks (ANNs) scores. These analyses prioritized molecular biomarkers specific to the diseases and to particular molecular motifs. As a first step, molecular characterization of the pathophysiological processes of AA defined 16 molecular motifs: 2 specific for AA, 2 shared with RA, and 12 shared with NA. Mechanistic analysis showed 17 proteins that were strongly related to AA. Eleven proteins were associated with RA and 16 proteins with NA. Specificity analysis showed that 12 proteins were specific to AA, 7 were specific to RA, and 2 to NA. Finally, a triggering analysis revealed a relevant role for AKT1, STAT1, and MAPK13 in all three conditions and for TLR4 in asthmatic diseases (AA and NA). In conclusion, this study has enabled us to prioritize biomarkers depending on the functionality associated with each disease and with specific molecular motifs, which could improve the definition and usefulness of new molecular biomarkers.

Pelvic floor muscle training adapted for urinary incontinence in multiple sclerosis: a randomized clinical trial.

INTRODUCTION AND HYPOTHESIS: Lower urinary tract symptoms (LUTS) affect up to 80% of patients with multiple sclerosis (MS). The present randomized, open-label, clinical trial examines the effectiveness, as a conservative treatment for LUTS, of a physiotherapist-guided pelvic floor muscle training (PFMT) program adapted for patients with relapsing-remitting multiple sclerosis (RRMS) and urinary incontinence (UI). METHODS: Forty-eight patients with RRMS were randomly assigned to a 12-week PFMT program with or without physiotherapist guidance. The primary endpoint was the reduction in urinary leakages after 12 weeks of following the program. The secondary variables assessed were quality of life (QoL), UI severity, LUTS, and treatment adherence. RESULTS: Forty patients completed the program. No significant differences in baseline characteristics were seen between the two treatment groups. At 12 weeks, both groups reported a significantly reduced number of leakages compared with baseline (P < 0.001), with no significant differences seen between groups (P = 0.210). In the physiotherapist-guided group, significant differences were found in QoL, UI severity, and LUTS between baseline and 12 weeks, for both male and female subjects. No significant differences in adherence were seen between the two treatment groups. CONCLUSIONS: No difference in leakage reduction was seen between physiotherapist-guided and unguided PFMT. However, the physiotherapist-guided program was associated with improvements in UI severity, QoL, and LUTS in women and men. The guided PFMT group also showed a trend towards better adherence to treatment. CLINICAL TRIAL REGISTRATION: No. NCT03000647; Title: "Guided Versus Non-Guided Pelvic Floor Exercises for Urinary Incontinence in Relapsing-Remitting Multiple Sclerosis."

Thyroid Function in Health Care Workers Exposed to Ionizing Radiation.

OBJECTIVES: To analyze possible alterations of thyroid function related to dosimetric values in health care workers exposed to ionizing radiation. MATERIALS AND METHODS: Forty-six health care workers exposed to ionizing radiation at a tertiary hospital previously exposed to ionizing radiation were included in the study. Age, sex, history of thyroid diseases, thyroid hormones, work post, service, dosimetric values of previous year, and 5 y period were considered. Alterations of thyroid function and other variables were analyzed by exact logistic regression univariate model. RESULTS: 7.1% workers showed an increased serum thyroid-stimulating hormone without free T3 or free T4 alteration. A significant relationship between workers with increased thyroid-stimulating hormone and dosimetric values of previous year (odds ratio 6.35, 95% confidence interval 1.20-98.1, p = 0.021) and previous 5 y period of radiation exposure (odds ratio 1.72, 95% confidence interval 1.12-3.34, p = 0.007) was obtained. CONCLUSION: An increased risk of subclinical hypothyroidism related to radiation doses was observed in this pilot study on a group of health care workers exposed to ionizing radiation.

What factors influence motor complications in Parkinson disease?: a 10-year prospective study.

The causes and mechanism behind motor complications in Parkinson disease (PD) are still a subject of debate. Several factors including age at onset, evolution in years, and initial medication can influence the onset and severity of motor complications in PD.We studied patients with recent diagnosis of PD who were followed up prospectively for 10 years. Analysis included the progression of these patients, as measured by the Unified Parkinson Disease Rating Scale scores and the presence of motor complications (motors fluctuations, dyskinesias, and gait freezing) over time. The patient group was studied as a whole and by subgroups classified according to age at onset, initial treatment, and sex.By the end of the first decade, most patients exhibited dyskinesias (91%), motor fluctuations (62%), and freezing of gait (68%). An association was found between several patients' characteristics and presence of motor complications by 5 years, though not after 10 years of follow up. The apparition of motor fluctuations was mainly related to initial treatment (odds ratio [OR], 3.87). The development of dyskinesias was linked to initial treatment (OR, 8.31), age at onset (OR, 0.90), and sex (OR, 12.87).