Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson's Disease.

INTRODUCTION: The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients. METHODS: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson's disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems. RESULTS: The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 ± 28.8 vs 132.8 ± 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 ± 14 vs 13 ± 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 ± 0.5 vs 3.9 ± 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015-1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009-1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments. CONCLUSION: Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.

Walking in pregnancy and prevention of insomnia in third trimester using pedometers: study protocol of Walking_Preg project (WPP). A randomized controlled trial.

BACKGROUND: Previous studies in pregnancy have not focused in evaluating the effect of walking during pregnancy and prevention of insomnia. Our general objective is to determine the effect of a walking program in preventing the appearance of insomnia in the third trimester of pregnancy, increasing sleep quality and improving quality of life throughout pregnancy. METHODS: Randomized Controlled trial in parallel in healthy sedentary pregnant women (n = 265), Walking_Preg Project (WPP), from university hospital in Granada, Spain. At 12th gestational week (GW), they will be invited to participate and randomly assigned to one of the three arms of study: the intervention group I1 (pedometer, goal of 11,000 steps/day), intervention group I2 (pedometer, no goal) and control (no pedometer). Duration of intervention: 13-32 GW. At 12th, 19th and 31st GW the average steps/day will be measured in groups I1 and I2. At 13th, 20th and 32nd GW, Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI), Adherence to Mediterranean Diet (AMD), physical activity (short IPAQ), quality of life (PSI), and consumption of toxic substances (caffeine, illegal drugs, alcohol and tobacco) will be collected. Student t test or Mann-Whitney U will be used to compare 19th and 31st GW mean of daily steps between I1 and I2 groups. To compare differences between groups in terms of frequency of insomnia/quality of life for each trimester of pregnancy, Pearson's Chi-square test or Fisher's exact test will be used. To determine differences in hours of sleep and quality of sleep throughout each trimester of pregnancy, analysis of variance or Friedman test will be used. McNemar-Bowker test will be used to assess differences in life quality in pre-post analyses in the 3 arms. We will use Stata 15 statistical software. DISCUSSION: promoting walking in second half of pregnancy through use of pedometer and health pre-registration of a goal to be achieved -'10,000-11,000 steps a day'- should prevent appearance of insomnia in third trimester, will increase sleep quality and quality of life in pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03735381 . Registered 8th November, 2018.

Cardiac Magnetic Resonance Fingerprinting: Technical Developments and Initial Clinical Validation.

PURPOSE OF REVIEW: Magnetic resonance imaging (MRI) has enabled non-invasive myocardial tissue characterization in a wide range of cardiovascular diseases by quantifying several tissue specific parameters such as T1, T2, and T2* relaxation times. Simultaneous assessment of these parameters has recently gained interest to potentially improve diagnostic accuracy and enable further understanding of the underlying disease. However, these quantitative maps are usually acquired sequentially and are not necessarily co-registered, making multi-parametric analysis challenging. Magnetic resonance fingerprinting (MRF) has been recently introduced to unify and streamline parametric mapping into a single simultaneous, multi-parametric, fully co-registered, and efficient scan. Feasibility of cardiac MRF has been demonstrated and initial clinical validation studies are ongoing. Provide an overview of the cardiac MRF framework, recent technical developments and initial undergoing clinical validation. RECENT FINDINGS: Cardiac MRF has enabled the acquisition of co-registered T1 and T2 maps in a single, efficient scan. Initial results demonstrate feasibility of cardiac MRF in healthy subjects and small patient cohorts. Current in vivo results show a small bias and comparable precision in T1 and T2 with respect to conventional clinical parametric mapping approaches. This bias may be explained by several confounding factors such as magnetization transfer and field inhomogeneities, which are currently not included in the cardiac MRF model. Initial clinical validation for cardiac MRF has demonstrated good reproducibility in healthy subjects and heart transplant patients, reduced artifacts in inflammatory cardiomyopathy patients and good differentiation between hypertrophic cardiomyopathy and healthy controls. Cardiac MRF has emerged as a novel technique for simultaneous, multi-parametric, and co-registered mapping of different tissue parameters. Initial efforts have focused on enabling T1, T2, and fat quantification; however this approach has the potential of enabling quantification of several other parameters (such as T2*, diffusion, perfusion, and flow) from a single scan. Initial results in healthy subjects and patients are promising, thus further clinical validation is now warranted.

Partner smoking influences whether mothers quit smoking during pregnancy: a prospective cohort study.

OBJECTIVE: To analyse the prevalence and intensity of smoking among pregnant women and their partners, and factors associated with quitting smoking among pregnant women. DESIGN: A prospective cohort study, starting in 2013. SETTING: Andalusia, the south of Spain. SAMPLE: A cohort of 486 healthy pregnant women followed-up on three occasions during pregnancy. METHODS: Estimation of the proportions of women and partners who quit smoking at each trimester. MAIN OUTCOME MEASURES: To determine factors associated in a multivariable model, considering sociodemographic, obstetric, anthropometric, lifestyle variables, and the smoking habits of their partners. RESULTS: A high proportion of women quit smoking during pregnancy (61.08%; 95% confidence interval, 95% CI 53.61-68.55%). The smoking rate amongst mothers decreased from 36.06% (n = 167) before pregnancy to 14.08% (n = 65), 12.39% (n = 54), and 11.92% (n = 51) during the three pregnancy trimesters (P < 0.001), and consumption decreased from 8.71 cigarettes/day in the first trimester to 5.51 cigarettes/day in the second trimester (P < 0.001) and 5.96 cigarettes/day in third trimester (P = 0.0002 first versus third trimester). There was only a minimal decrease in the frequency of smoking among the partners, however: 38.44% (n = 178) before pregnancy, and 36.07% (n = 167), 32.72% (n = 143), and 31.85% (n = 136) during the three trimesters of pregnancy. The consumption of cigarettes did not decrease among partners: 11.75, 11.67, and 12.09 cigarettes/day (P = 0.4299 first versus second trimester; P = 0.654 first versus third trimester). Women whose partner smoked were less likely to quit (adjusted odds ratio, aOR 0.26; 95% CI 0.12-0.55). CONCLUSIONS: About one in ten pregnant women smoked and one in four was a passive smoker. Strategies to reduce tobacco exposure in pregnancy should include a focus on partner smoking. TWEETABLE ABSTRACT: Pregnant women quit smoking cigarettes in pregnancy. What about their partners?

Is it possible to prevent recurrent vulvovaginitis? The role of Lactobacillus plantarum I1001 (CECT7504).

The purpose of this study was to prospectively evaluate the impact of the use of L. plantarum I1001 applied vaginally on Vulvovaginal Candidiasis (VVC) time-until-recurrence after treatment with single-dose vaginal clotrimazole. This was a clinical open-label, prospective study of two non-randomized parallel cohorts with symptomatic acute VVC: (1) 33 sexually active women 18-50 years old, prescribed a standard single-dose 500 mg vaginal tablet of clotrimazole followed by vaginal tablets with L. plantarum I1001 as adjuvant therapy, and (2) 22 women of similar characteristics but prescribed single-dose clotrimazole only. Use of the probiotic and factors that might influence recurrence risk (age, recurrent VVC within previous year, antibiotic prior to study enrolment, diaphragm or IUD contraception, among others) were included in a multivariate Cox regression model to adjust for potential between-cohort differences. Probiotic use was associated with a three-fold reduction in the adjusted risk of recurrence (HR [95 %CI]: 0.30 [0.10-0.91]; P = 0.033). Adjusted free-survival recurrence was 72.83 % and 34.88 % for the probiotic and control groups, respectively. A higher cumulative recurrence was also observed in cases with use of antibiotics prior to enrolment (HR [95 %CI]: 10.46 [2.18-50.12]; P = 0.003). Similar findings were found at six months after azole treatment in women with RVVC. Overall, good compliance with the probiotic was reported for 91.3 % of women. The study suggests that follow-up therapy with vaginal tablets with L. plantarum I1001 could increase the effectiveness of single-dose 500 mg clotrimazole at preventing recurrence of VVC, an effect that was also observed in women with recurrent vulvovaginal candidiasis (RVVC) after six months of azole treatment.

Social costs associated with fibromyalgia in Spain.

BACKGROUND: Fibromyalgia is a chronic rheumatic disease of unknown aetiology, highly disabling and mainly affecting women. The aim of our work is to estimate, on a national scale, the economic impact of this disease on the employment of patients and non-professional (informal) care dimension. METHODS: Survey on Disabilities, Autonomy and Dependency carried out in Spain in 2020/21 was used to obtain information on disabled individuals with AD and their informal caregivers. Six estimation scenarios were defined as base case, depending on whether the maximum daily informal caregiving time was censored or not, and on the approach chosen for the valuation of informal caregiving time (contingent valuation and replacement time). Another six conservative scenarios were developed using the minimum wage for the estimation of labour losses. RESULTS: Our estimates range from 2,443.6 (willingness to pay, censored informal care time) to 7,164.8 million euros (replacement cost, uncensored informal care time) (base year 2021). Multivariate analyses identified that the degree of dependency of the person suffering from fibromyalgia is the main explanatory variable for both the probability of being employed and the time spent in informal care. Conservative scenarios estimates range from 1,807 to 6,528 million euros. CONCLUSIONS: The high economic impact revealed should help to position a health problem that is relatively unknown in society and for which there are significant research and care gaps to be filled.

Differential accumulation of human ß-amyloid and tau from enriched extracts in neuronal and endothelial cells.

While Aß and Tau cellular distribution has been largely studied, the comparative internalization and subcellular accumulation of Tau and Aß isolated from human brain extracts in endothelial and neuronal cells has not yet been unveiled. We have previously demonstrated that controlled enrichment of Aß from human brain extracts constitutes a valuable tool to monitor cellular internalization in vitro and in vivo. Herein, we establish an alternative method to strongly enrich Aß and Tau aggregates from human AD brains, which has allowed us to study and compare the cellular internalization, distribution and toxicity of both proteins within brain barrier endothelial (bEnd.3) and neuronal (Neuro2A) cells. Our findings demonstrate the suitability of human enriched brain extracts to monitor the intracellular distribution of human Aß and Tau, which, once internalized, show dissimilar sorting to different organelles within the cell and differential toxicity, exhibiting higher toxic effects on neuronal cells than on endothelial cells. While tau is strongly concentrated preferentially in mitochondria, Aß is distributed predominantly within the endolysosomal system in endothelial cells, whereas the endoplasmic reticulum was its preferential location in neurons. Altogether, our findings display a picture of the interactions that human Aß and Tau might establish in these cells.

Group sparse reconstruction using intensity-based clustering.

Compressed sensing has been of great interest to speed up the acquisition of MR images. The k-t group sparse (k-t GS) method has recently been introduced for dynamic MR images to exploit not just the sparsity, as in compressed sensing, but also the spatial group structure in the sparse representation. k-t GS achieves higher acceleration factors compared to the conventional compressed sensing method. However, it assumes a spatial structure in the sparse representation and it requires a time consuming hard-thresholding reconstruction scheme. In this work, we propose to modify k-t GS by incorporating prior information about the sorted intensity of the signal in the sparse representation, for a more general and robust group assignment. This approach is referred to as group sparse reconstruction using intensity-based clustering. The feasibility of the proposed method is demonstrated for static 3D hyperpolarized lung images and applications with both dynamic and intensity changes, such as 2D cine and perfusion cardiac MRI, with retrospective undersampling. For all reported acceleration factors the proposed method outperforms the original compressed sensing method. Improved reconstruction over k-t GS method is demonstrated when k-t GS assumptions are not satisfied. The proposed method was also applied to cardiac cine images with a prospective sevenfold acceleration, outperforming the standard compressed sensing reconstruction.

Current heart failure disease management and treatment in accredited units from cardiology and internal medicine in Spain.

BACKGROUND AND OBJECTIVES: Heart failure (HF) is a complex disease with high prevalence, incidence and mortality rates leading to high healthcare burden. In Spain, there are multidisciplinary HF units coordinated by cardiology and internal medicine. Our objective is to describe its current organizational model and their adherence to the latest scientific recommendations. MATERIALS AND METHODS: In late 2021, a scientific committee (with cardiology and internal medicine specialists) developed a questionnaire that was sent as an online survey to 110 HF units. 73 from cardiology (accredited by SEC-Excelente) and 37 from internal medicine, (integrated in UMIPIC program). RESULTS: We received 83 answers (75.5% total: 49 from cardiology and 34 from internal medicine). The results showed that HF units are mostly integrated by specialists from cardiology, internal medicine and specialized nurse practitioners (34.9%). Patient characteristics from HF units are widely different when comparing those in cardiology to UMIPIC, being the latter older, more frequently with preserved ejection fraction and higher comorbidity burden. Most HF units (73.5%) currently use a hybrid face-to-face/virtual model to perform patient follow-up. Natriuretic peptides are the biomarkers most commonly used (90%). All four disease-modifying drug classes are mainly implemented at the same time (85%). Only 24% of HF units hold fluent communication with primary care. CONCLUSIONS: Both models from cardiology and internal medicine HF units are complementary, they include specialized nursing, they use hybrid approach for patient follow-up and they display a high adherence to the latest guideline recommendations. Coordination with primary care remains as the major improvement area.

X-ray absorption and Mössbauer spectroscopies characterization of iron nanoclusters prepared by the gas aggregation technique.

Partially oxidized iron nanoclusters have been prepared by the gas-phase aggregation technique with typical sizes of 2-3 nm. This preparation technique has been reported to obtain clusters with interesting magnetic properties such as very large exchange bias. In this paper, a sample composition study carried out by Mössbauer and X-ray absorption spectroscopies is reported. The information reached by these techniques, which is based on the iron short range order, results to be an ideal way to have a characterization of the whole sample since the obtained data are an average over a very large amount of the clusters. In addition, our results indicate the presence of ferrihydrite, which is a compound typically ignored when studying this type of systems.

Hydroxypropyl methylcellulose-based micro- and nanostructures for encapsulation of melanoidins: Effect of electrohydrodynamic processing variables on morphological and physicochemical properties.

Electrohydrodynamic processing (EHDP) allows the use of a wide range of biopolymers and solvents, including food-grade biopolymers and green solvents, for the development of micro- and nanostructures. These structures present a high surface-area-to-volume ratio and different shapes and morphologies. The aim of this work was to design and produce hydroxypropyl methylcellulose (HPMC)-based micro- and nanostructures through EHD processing using green solvents, while exploring the influence of process and solution parameters, and incorporating a bioactive extracted from a food by-product. Low (LMW) and high (HMW) molecular weight HPMC have been used as polymers. The design-of-experiments methodology was used to determine the effects of process parameters (polymer concentration, flow rate, tip-to-collector distance, and voltage) of EHDP on the particle and fibre diameter, aspect ratio, diameter distribution, aspect ratio distribution, and percentage of fibre breakage. Additionally, melanoidins extracted from spent coffee grounds were encapsulated into the HPCM-based structures at a concentration of 2.5 mg melanoidins/mL of the polymer solution. Polymer solutions were characterised regarding their viscosity, surface tension and conductivity, and showed that the incorporation of melanoidins increased the viscosity and conductivity values of the polymer solutions. The developed structures were characterised regarding their thermal properties, crystallinity and morphology before and after melanoidin incorporation and it was observed that melanoidin incorporation did not significantly influence the characteristics of the produced micro- and nanostructures. Based on the results, it is possible to envision the use of the produced micro- and nanostructures in a wide range of applications, both in food and biomedical fields.

k-t Group sparse: a method for accelerating dynamic MRI.

Compressed sensing (CS) is a data-reduction technique that has been applied to speed up the acquisition in MRI. However, the use of this technique in dynamic MR applications has been limited in terms of the maximum achievable reduction factor. In general, noise-like artefacts and bad temporal fidelity are visible in standard CS MRI reconstructions when high reduction factors are used. To increase the maximum achievable reduction factor, additional or prior information can be incorporated in the CS reconstruction. Here, a novel CS reconstruction method is proposed that exploits the structure within the sparse representation of a signal by enforcing the support components to be in the form of groups. These groups act like a constraint in the reconstruction. The information about the support region can be easily obtained from training data in dynamic MRI acquisitions. The proposed approach was tested in two-dimensional cardiac cine MRI with both downsampled and undersampled data. Results show that higher acceleration factors (up to 9-fold), with improved spatial and temporal quality, can be obtained with the proposed approach in comparison to the standard CS reconstructions.

Patient preferences for osteoporosis in Spain: a discrete choice experiment.

UNLABELLED: In Spain, various treatments are available to prevent osteoporotic fractures. A discrete choice experiment (DCE) was used to investigate the importance of different treatment aspects and its influence on patients' preferences. All attributes included as type and place of drug administration as well as costs showed to be significant predictors of choice. Spanish osteoporosis patients have well-defined preferences and accept trade-offs among attributes. INTRODUCTION: This study was designed to identify patient preferences for different aspects of osteoporosis treatments in Spain. METHODS: Main attributes of severe osteoporosis treatments were determined by literature review and consultations with nurses. The discrete choice experiment included three attributes: type of drug administration, place of administration, plus a cost attribute in order to estimate willingness to pay for improvements in attribute levels. A pilot study with 50 patients was performed to identify the areas of misunderstanding. One hundred sixty-six patients with a diagnosis of osteoporosis and severe osteoporosis were presented with pairs of hypothetical treatment profiles with different type of administration levels, places of administration and costs. Questions to collect socio-demographic and disease-related treatment data were also included. Data were analysed using a random effects probit model. RESULTS: All attributes had the expected polarity and were significant predictors of choice. Patients were willing to pay 183 euro/month to have a subcutaneous injection once per day rather than an intravenous injection once per year. Patients with osteoporosis were willing to pay 121 euro/month to have medical support when administering the drug treatment at home rather than being admitted several hours to a hospital for drug administration. CONCLUSION: Spanish osteoporosis patients have well-defined preferences among treatment attributes and are willing to accept trade-offs among attributes. Participants indicated that they are willing to accept self medication with medical support rather than being hospitalised for several hours. The perspective of the patients should be taken into account when making treatment decisions.

Rituximab induces a rapid and sustained remission in Colombian patients with severe and refractory systemic lupus erythematosus.

Despite aggressive treatment for systemic lupus erythematosus (SLE) with high-dose glucocorticoids and immunosuppressive agents, a significant proportion of patients persist with activity or relapse. Although the results from randomized studies showed no beneficial effects of rituximab (RTX) in SLE, this treatment has proven promising results in open label trials including patients with severe and refractory disease. We report a prospective cohort of 42 Colombian patients with severe and refractory SLE treated with RTX after failure response to glucocorticoids and, at least, another immunosuppressive drug. We observed a reduction in steroid requirement [47.4 mg/day at 24 months (p < 0.001)]. Since the first three-month follow-up, 28% and 36% of the patients fulfilled criteria of complete or partial remission according to proteinuria, and 12.5% and 33% according to creatinine clearance, respectively. These response criteria remained at 12 months. Both neuropsychiatric and hematological sub-groups had a favorable clinical response. The median reinfusion-free survival time was 44 months (95% confidence interval: 10.1-50.1) and 80% of the patients did not require RTX reinfusion. Eleven adverse events were reported in 28 subjects. Most of these occurred during the first three-month follow-up, time during which patients were exposed to high-dose glucocorticoids.

Electrosprayed cashew gum microparticles for the encapsulation of highly sensitive bioactive materials.

This study focuses on the production and characterization of electrosprayed cashew gum (CG) microparticles that encapsulate ß-carotene. CG is an inexpensive, non-toxic polysaccharide obtained from Anacardium occidentale trees. Encapsulation of ß-carotene in CG was performed by electrospraying from two emulsion formulations (water : oil ratios 80:20 and 90:10 (v/v)) in which the dispersed phase consisted of ß-carotene dissolved in castor oil, and the continuous phase was a CG aqueous solution. Spherical particles with smooth surface and medium size between 3 and 6 µm were obtained. The particles produced from the 90:10 (v/v) emulsion showed a loading capacity of 0.075 ± 0.006 % and a minor amount of extractable ß-carotene, 10.75 ± 2.42 %. ATR-FTIR confirmed the absence of interaction between the particles' components. CG demonstrated to offer thermoprotection, and photoprotection for short periods of time. These results make CG a viable candidate to encapsulate bioactive compounds via electrospraying for agricultural, food and pharmaceutical applications.

Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions.

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-ß and α-synuclein pathology were rated on a scale of 0 (absent)-3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman's rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = - 0.27 to r = - 0.46), and (2) tau with BA35 (r = - 0.31) and SRLM thickness (r = - 0.33). In amyloid-ß and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = - 0.40), BA35 (r = - 0.55), subiculum (r = - 0.42) and CA1 thickness (r = - 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-ß suggests a role of Primary Age-Related Tauopathy in neurodegeneration.

Structural domain-domain interactions: assessment and comparison with protein-protein interaction data to improve the interactome.

Assessment and improvement of the reliability of protein-protein interaction (ppi) data is critical for the progress of the currently active research on interactomes. Some interesting questions in this respect are: How three-dimensional (3D) protein structural data is present in known ppi data?, and How this kind of information can be used to validate and improve the interactomes? To address this problem, analysis and unification of six structural domain-domain interaction (sddi) datasets is presented; followed by a comparative study of these sddi data in three ppi reference sets produced at different levels of confidence. The results show that protein structural and interactomic data are partially complementary and that a larger proportion of structural information is observed in more confident interactomes. We also present, focused on the human interactome, an analysis of the domains that are more frequently present in: (i) an interactome based on validation by at least two experimental methods versus (ii) another interactome based on validation by 3D structural interaction data. These results allow to distinguish between domain pairs associated to protein interactions supported by 3D structures and domain pairs that at present are not supported by structural information. The domain pairs exclusive of interactions without associated 3D data reveal interacting conserved modules that are probably flexible, disordered, and difficult to crystallize; and which are often found in proteins involved in signaling pathways and DNA processing.