QComics: Recommendations and Guidelines for Robust, Easily Implementable and Reportable Quality Control of Metabolomics Data.

The implementation of quality control strategies is crucial to ensure the reproducibility, accuracy, and meaningfulness of metabolomics data. However, this pivotal step is often overlooked within the metabolomics workflow and frequently relies on the use of nonstandardized and poorly reported protocols. To address current limitations in this respect, we have developed QComics, a robust, easily implementable and reportable method for monitoring and controlling data quality. The protocol operates in various sequential steps aimed to (i) correct for background noise and carryover, (ii) detect signal drifts and "out-of-control" observations, (iii) deal with missing data, (iv) remove outliers, (v) monitor quality markers to identify samples affected by improper collection, preprocessing, or storage, and (vi) assess overall data quality in terms of precision and accuracy. Notably, this tool considers important issues often neglected along quality control, such as the need of separately handling missing values and truly absent data to avoid losing relevant biological information, as well as the large impact that preanalytical factors may elicit on metabolomics results. Altogether, the guidelines compiled in QComics might contribute to establishing gold standard recommendations and best practices for quality control within the metabolomics community.

Scoring personalized molecular portraits identify Systemic Lupus Erythematosus subtypes and predict individualized drug responses, symptomatology and disease progression.

OBJECTIVES: Systemic Lupus Erythematosus is a complex autoimmune disease that leads to significant worsening of quality of life and mortality. Flares appear unpredictably during the disease course and therapies used are often only partially effective. These challenges are mainly due to the molecular heterogeneity of the disease, and in this context, personalized medicine-based approaches offer major promise. With this work we intended to advance in that direction by developing MyPROSLE, an omic-based analytical workflow for measuring the molecular portrait of individual patients to support clinicians in their therapeutic decisions. METHODS: Immunological gene-modules were used to represent the transcriptome of the patients. A dysregulation score for each gene-module was calculated at the patient level based on averaged z-scores. Almost 6100 Lupus and 750 healthy samples were used to analyze the association among dysregulation scores, clinical manifestations, prognosis, flare and remission events and response to Tabalumab. Machine learning-based classification models were built to predict around 100 different clinical parameters based on personalized dysregulation scores. RESULTS: MyPROSLE allows to molecularly summarize patients in 206 gene-modules, clustered into nine main lupus signatures. The combination of these modules revealed highly differentiated pathological mechanisms. We found that the dysregulation of certain gene-modules is strongly associated with specific clinical manifestations, the occurrence of relapses or the presence of long-term remission and drug response. Therefore, MyPROSLE may be used to accurately predict these clinical outcomes. CONCLUSIONS: MyPROSLE (https://myprosle.genyo.es) allows molecular characterization of individual Lupus patients and it extracts key molecular information to support more precise therapeutic decisions.

Association of dietary and nutritional factors with cognitive decline, dementia, and depressive symptomatology in older individuals according to a neurogenesis-centred biological susceptibility to brain ageing.

Hippocampal neurogenesis (HN) occurs throughout the life course and is important for memory and mood. Declining with age, HN plays a pivotal role in cognitive decline (CD), dementia, and late-life depression, such that altered HN could represent a neurobiological susceptibility to these conditions. Pertinently, dietary patterns (e.g., Mediterranean diet) and/or individual nutrients (e.g., vitamin D, omega 3) can modify HN, but also modify risk for CD, dementia, and depression. Therefore, the interaction between diet/nutrition and HN may alter risk trajectories for these ageing-related brain conditions. Using a subsample (n = 371) of the Three-City cohort-where older adults provided information on diet and blood biobanking at baseline and were assessed for CD, dementia, and depressive symptomatology across 12 years-we tested for interactions between food consumption, nutrient intake, and nutritional biomarker concentrations and neurogenesis-centred susceptibility status (defined by baseline readouts of hippocampal progenitor cell integrity, cell death, and differentiation) on CD, Alzheimer's disease (AD), vascular and other dementias (VoD), and depressive symptomatology, using multivariable-adjusted logistic regression models. Increased plasma lycopene concentrations (OR [95% CI] = 1.07 [1.01, 1.14]), higher red meat (OR [95% CI] = 1.10 [1.03, 1.19]), and lower poultry consumption (OR [95% CI] = 0.93 [0.87, 0.99]) were associated with an increased risk for AD in individuals with a neurogenesis-centred susceptibility. Increased vitamin D consumption (OR [95% CI] = 1.05 [1.01, 1.11]) and plasma γ-tocopherol concentrations (OR [95% CI] = 1.08 [1.01, 1.18]) were associated with increased risk for VoD and depressive symptomatology, respectively, but only in susceptible individuals. This research highlights an important role for diet/nutrition in modifying dementia and depression risk in individuals with a neurogenesis-centred susceptibility.

Neurodegeneration Biomarkers in Adult Spinal Muscular Atrophy (SMA) Patients Treated with Nusinersen.

The objective of this study is to evaluate biomarkers for neurodegenerative disorders in adult SMA patients and their potential for monitoring the response to nusinersen. Biomarkers for neurodegenerative disorders were assessed in plasma and CSF samples obtained from a total of 30 healthy older adult controls and 31 patients with adult SMA type 2 and 3. The samples were collected before and during nusinersen treatment at various time points, approximately at 2, 6, 10, and 22 months. Using ELISA technology, the levels of total tau, pNF-H, NF-L, sAPPß, Aß40, Aß42, and YKL-40 were evaluated in CSF samples. Additionally, plasma samples were used to measure NF-L and total tau levels using SIMOA technology. SMA patients showed improvements in clinical outcomes after nusinersen treatment, which were statistically significant only in walkers, in RULM (p = 0.04) and HFMSE (p = 0.05) at 24 months. A reduction in sAPPß levels was found after nusinersen treatment, but these levels did not correlate with clinical outcomes. Other neurodegeneration biomarkers (NF-L, pNF-H, total tau, YKL-40, Aß40, and Aß42) were not found consistently changed with nusinersen treatment. The slow progression rate and mild treatment response of adult SMA types 2 and 3 may not lead to detectable changes in common markers of axonal degradation, inflammation, or neurodegeneration, since it does not involve large pools of damaged neurons as observed in pediatric forms. However, changes in biomarkers associated with the APP processing pathway might be linked to treatment administration. Further studies are warranted to better understand these findings.

Childhood obesity, metabolic syndrome, and oxidative stress: microRNAs go on stage.

The incidence of childhood obesity and metabolic syndrome has grown notably in the last years, becoming major public health burdens in developed countries. Nowadays, oxidative stress is well-recognized to be closely associated with the onset and progression of several obesity-related complications within the framework of a complex crosstalk involving other intertwined pathogenic events, such as inflammation, insulin disturbances, and dyslipidemia. Thus, understanding the molecular basis behind these oxidative dysregulations could provide new approaches for the diagnosis, prevention, and treatment of childhood obesity and associated disorders. In this respect, the transcriptomic characterization of miRNAs bares great potential because of their involvement in post-transcriptional modulation of genetic expression. Herein, we provide a comprehensive literature revision gathering state-of-the-art research into the association between childhood obesity, metabolic syndrome, and miRNAs. We put special emphasis on the potential role of miRNAs in modulating obesity-related pathogenic events, with particular focus on oxidative stress.

Impaired hippocampal neurogenesis in vitro is modulated by dietary-related endogenous factors and associated with depression in a longitudinal ageing cohort study.

Environmental factors like diet have been linked to depression and/or relapse risk in later life. This could be partially driven by the food metabolome, which communicates with the brain via the circulatory system and interacts with hippocampal neurogenesis (HN), a form of brain plasticity implicated in depression aetiology. Despite the associations between HN, diet and depression, human data further substantiating this hypothesis are largely missing. Here, we used an in vitro model of HN to test the effects of serum samples from a longitudinal ageing cohort of 373 participants, with or without depressive symptomology. 1% participant serum was applied to human fetal hippocampal progenitor cells, and changes in HN markers were related to the occurrence of depressive symptoms across a 12-year period. Key nutritional, metabolomic and lipidomic biomarkers (extracted from participant plasma and serum) were subsequently tested for their ability to modulate HN. In our assay, we found that reduced cell death and increased neuronal differentiation were associated with later life depressive symptomatology. Additionally, we found impairments in neuronal cell morphology in cells treated with serum from participants experiencing recurrent depressive symptoms across the 12-year period. Interestingly, we found that increased neuronal differentiation was modulated by increased serum levels of metabolite butyrylcarnitine and decreased glycerophospholipid, PC35:1(16:0/19:1), levels - both of which are closely linked to diet - all in the context of depressive symptomology. These findings potentially suggest that diet and altered HN could subsequently shape the trajectory of late-life depressive symptomology.

Load and muscle group size influence the ergogenic effect of acute caffeine intake in muscular strength, power and endurance.

INTRODUCTION: Although acute caffeine intake seems to improve muscular strength-power-endurance performance, there is scarce evidence evaluating upper vs lower-body exercises at different loads. Thus, this study aimed to examine the effects of acute caffeine intake on upper and lower-body muscular strength, power and endurance performance at different loads. METHODS: Twenty resistance-trained athletes (male/female: 10/10; age: 23 ± 4 years; body mass: 70.6 ± 15.1) participated in a double-blind, placebo-controlled, cross-over and randomized study. Participants were provided with either 3 mg/kg of body mass of caffeine or maltodextrin (placebo). Sixty minutes after ingestion, they performed muscular strength and power assessment for bench press and back squat exercise at 25%, 50%, 75% and 90% 1-repetition-maximum (1RM), performing 3, 2, 1 and 1 repetitions respectively, followed by muscular endurance assessment for both exercises at 65% and 85% 1RM performing until task failure. Isometric handgrip, isometric mid-thigh pull and vertical jump tests were also performed. RESULTS: In muscular strength and power, compared to placebo, caffeine improved mean velocity (P = 0.045; pη2 = 0.101), mean power (P = 0.049; pη2 = 0.189) and rate of force development (RFD, P = 0.032; pη2 = 0.216), particularly in back squat exercise at 75% and 90% 1RM where mean velocity increased by 5-7% (P = 0.48-0.038; g = 0.348-1.413), mean power by 6-8% (P = 0.050-0.032; g = 0.547-0.818) and RFD by 17-97% (P = 0.042-0.046; g = 1.436-1.196). No differences were found in bench press exercise. In muscular endurance, caffeine improved the number of repetitions in all exercises and loads (P = 0.003; pη2 = 0.206), but only in back squat exercise at 85% 1RM, caffeine increased mean and peak velocity (8-9%, P = 0.006-0.004; g = 2.029-2.075), mean and peak power (10-13%, P = 0.006-0.003; g = 0.888-1.151) and force peak (3%, P = 0.009; g = 0.247). CONCLUSIONS: Acute caffeine intake (3 mg/kg) improved muscular strength, power and endurance performance, revealing a more pronounced effect at high-loads (≥ 75% 1RM) and in lower-body (back squat) than in upper-body exercise (bench press) according to muscle group size.

Beetroot juice ingestion does not improve neuromuscular performance and match-play demands in elite female hockey players: a randomized, double-blind, placebo-controlled study.

PURPOSE: Beetroot juice is a dietary supplement that contains high levels of inorganic nitrate (NO3-) and that its intake has proven effective at increasing blood nitric oxide (NO) concentrations improving endurance performance. However, the effect of this supplement in team sport performance, especially in female athletes, has been barely studied. This study aimed to compare the acute effects of beetroot juice supplementation on neuromuscular performance and match-play demands in elite female field hockey players. METHODS: Eleven elite female hockey players (22.8 ± 5.1 years) belonging to a bronze team medal in Eurohockey Club Champions Cup participated in this study. Participants were randomly divided into two groups undergoing a test battery with beetroot juice (70 mL, 6.4 mmol NO3-) or placebo (70 mL, 0.04 mmol NO3-) in two different days with one week between protocols. The neuromuscular test battery consisted of a countermovement jump, isometric handgrip strength (i.e., dominant hand), 20 m-sprint and repeated sprint ability test (RSA). Afterward, a simulated hockey match play (2 × 12.5 min) was performed and recorded by Global Positioning System (GPS). RESULTS: No statistically significant improvements were observed in any physical parameters analysed comparing beetroot juice compared to placebo ingestion, countermovement jump (p = 0.776, ES = 0.16), isometric handgrip strength (p = 0.829; ES = - 0.08), 20 m sprint test (p = 0.227; ES = - 0.23), mean repeated sprint ability (p = 0.955, ES = 0.03) and in any physical match demands measured by GPS (p = 0.243-1.000; ES = 0.02-0.47). CONCLUSION: Acute beetroot juice supplementation did not produce any statistically significant improvement in neuromuscular performance or match-play demands in elite female field hockey players. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov with the following ID: NCT05209139. The study was retrospectively registered by 26 January 2022.

Development of ASTM International D8405-Standard Test Method for Evaluating PM2.5 Sensors or Sensor Systems Used in Indoor Applications.

Sensors and sensor systems for monitoring fine particles with aerodynamic diameters smaller than 2.5 µm can provide real-time feedback on indoor air quality and thus can help guide actions to manage indoor air pollutant concentrations. Standardized verification of the performance and accuracy of sensors and sensor systems is crucial for predicting the efficacy of such monitoring. A new ASTM International standard test method (ASTM D8405) was created for this need and is the most exacting laboratory protocol published to date for evaluating indoor air quality sensors and sensor systems measuring particles smaller than 2.5 µm in diameter. ASTM D8405 subjects sensors and sensor systems to five test phases: (1) an initial particle concentration ramp; (2) exposure to various temperature and humidity conditions; (3) exposure to interfering particles; (4) temperature cycling; and (5) a final particle concentration ramp to assess drift. This paper discusses the development of the standard test method, key aspects of the testing process, example evaluation results, and a comparison of this standard test method against peer evaluation protocols.

Anthropometric characteristics of young elite sailors based on performance level.

Background: /Objectives: The aim of the present study was to analyse possible differences in anthropometric characteristics of elite sailors based on categories and performance level. Methods: ː A total of 42 young (aged 12-18 years) elite sailors (men = 31; women = 11) of the Monohull (n = 21) and Windsurfing (n = 21) categories composed the study sample. Testing was per-formed in one session the day before the start of an official and international competition. Body composition was measured using an octopolar and multi-frequency electrical bioimpedance analyser, and height was recorded using a telescopic measuring instrument. Cross-sectional study. The total sample was divided into two groups based on their performance level (ranking), 50th percentile (P1), and 100th percentile (P2). Results: ː P1 presented a lower BMI, total body fat mass, and body fat mass in the trunk, arms, and legs (p < 0.05). Similarly, P1 reported a higher total body muscle mass and body muscle mass on the trunk, arms, and legs compared to the less level performance group (p < 0.05). In addition, P2 sailors were taller and heavier (p < 0.05). Regarding categories, the Windsurf sailors presented statistically significantly lower arm fat mass than the Monohull (p < 0.05). The Windsurf sailors showed differences between the two performance-level groups (p < 0.05). Additionally, comparing the high-level performance group in both categories, higher arm muscle mass on the Windsurfing sailors was detected (p < 0.05). Conclusions: ː These findings could help to differentiate the anthropometric variables that determine sport performance in young elite sailors and could be used to differentiate the anthropometric variables in each category.

POMAShiny: A user-friendly web-based workflow for metabolomics and proteomics data analysis.

Metabolomics and proteomics, like other omics domains, usually face a data mining challenge in providing an understandable output to advance in biomarker discovery and precision medicine. Often, statistical analysis is one of the most difficult challenges and it is critical in the subsequent biological interpretation of the results. Because of this, combined with the computational programming skills needed for this type of analysis, several bioinformatic tools aimed at simplifying metabolomics and proteomics data analysis have emerged. However, sometimes the analysis is still limited to a few hidebound statistical methods and to data sets with limited flexibility. POMAShiny is a web-based tool that provides a structured, flexible and user-friendly workflow for the visualization, exploration and statistical analysis of metabolomics and proteomics data. This tool integrates several statistical methods, some of them widely used in other types of omics, and it is based on the POMA R/Bioconductor package, which increases the reproducibility and flexibility of analyses outside the web environment. POMAShiny and POMA are both freely available at https://github.com/nutrimetabolomics/POMAShiny and https://github.com/nutrimetabolomics/POMA, respectively.

Nusinersen in adult patients with 5q spinal muscular atrophy: A multicenter observational cohorts' study.

BACKGROUND AND PURPOSE: The aim was to assess the safety and efficacy of nusinersen in adult 5q spinal muscular atrophy (SMA) patients. METHODS: Patients older than 15 years and followed for at least 6 months with one motor scale (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb Module, RULM) in five referral centers were included. The clinical and patients' global impression of change (CGI-C and PGI-C) were recorded in treated patients at the last visit. Functional scales (Egen Klassification, EK2; Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R) and the percentage predicted forced vital capacity were collected when available. RESULTS: Seventy-nine SMA patients (39 treated with nusinersen) were included. Compared with untreated patients, treated patients showed a significant improvement of 2 points (±0.46) in RULM (p < 0.001) after 6 months. After a mean follow-up of 16 months, nusinersen treatment was associated with a significant improvement in HFMSE (odds ratio [OR] 1.15, p = 0.006), the 6-min walk test (OR = 1.07, p < 0.001) and the EK2 (OR = 0.81, p = 0.001). Compared with untreated patients, more treated patients experienced clinically meaningful improvements in all scales, but these differences were statistically significant only for RULM (p = 0.033), ALSFRS-R (p = 0.005) and EK2 (p < 0.001). According to the CGI-C and PGI-C, 64.1% and 61.5% of treated patients improved with treatment. Being a non-sitter was associated with less response to treatment, whilst a longer time of treatment was associated with better response. Most treated patients (77%) presented at least one adverse event, mostly mild. CONCLUSIONS: Nusinersen treatment is associated with some improvements in adult SMA patients. Most severely affected patients with complex spines are probably those with the most unfavorable risk-benefit ratio.

Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy.

BACKGROUND AND PURPOSE: Mos scales currently used to evaluate spinal muscular atrophy (SMA) patients have only been validated in children. The aim of this study was to assess the construct validity and responsiveness of several outcome measures in adult SMA patients. METHODS: Patients older than 15 years and followed up in five referral centres for at least 6 months, between October 2015 and August 2020, with a motor function scale score (Hammersmith Functional Motor Scale Expanded [HFMSE], Revised Upper Limb module [RULM]) were included. Bedside functional scales (Egen Klassification [EK2], Revised Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS-R]) were also collected when available. Spearman's rho correlations (rs) and Bangdiwala's concordance test (B) were used to evaluate the scales' construct validity. Monthly slopes of change were used to calculate their responsiveness of the scales. RESULTS: The study included 79 SMA patients, followed up for a mean of 16 months. All scales showed strong correlations with each other (rs > 0.70). A floor effect in motor function scales was found in the weakest patients (HFMSE < 5 and RULM < 10), and a ceiling effect was found in stronger patients (HFMSE > 60 and RULM > 35). The ALSFRS-R (B = 0.72) showed a strong ability to discriminate between walkers, sitters and non-sitters, and the HFMSE (B = 0.86) between walkers and sitters. The responsiveness was low overall, although in treated patients a moderate responsiveness was found for the ALSFRS-R and HFMSE in walkers (0.69 and 0.61, respectively) and for EK2 in sitters (0.65) and non-sitters (0.60). CONCLUSIONS: This study shows the validity and limitations of the scales most frequently used to assess adult SMA patients. Overall, bedside functional scales showed some advantages over motor scales, although all showed limited responsiveness.

Plasma exchange with albumin replacement and disease progression in amyotrophic lateral sclerosis: a pilot study.

BACKGROUND: Plasma exchange (PE) is used to treat a range of neurological disorders. Based on results demonstrated in Alzheimer's disease, we theorized that PE with albumin replacement (PE-A) might alter the metabolic profile of plasma and cerebrospinal fluid in patients with amyotrophic lateral sclerosis (ALS) by removing disease-inducing molecules. The aim of this study was to evaluate the effect of PE-A on disease progression in ALS. METHODS: In this open-label, non-controlled, single-arm, prospective pilot study, 13 adults with ALS had 6 months' treatment with PE-A 5% and 6 months' follow-up. Primary endpoints were changes from baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score and forced vital capacity (FVC) through 48 weeks. A post hoc analysis compared individual patient data with the expected ALSFRS-R progression slope. RESULTS: The median ALSFRS-R score declined throughout the study, although the rate of decline was slower than expected in seven patients at treatment end and in five patients at study end. Six patients remained in the same baseline slope progression category, and four patients improved their slope category at treatment end. Median FVC decreased significantly during the study. Treatment was well tolerated. Of 330 PE-A procedures, 0.9% were associated with potentially related adverse events. CONCLUSION: Although functional impairment progressed, about two-thirds of patients showed a slower than expected rate of decline at treatment end. Most patients had unaltered (54.5%) or reduced (36.4%) ALSFRS-R slope progression at treatment end. Further evaluation of PE-A in controlled studies involving more patients is warranted. EUDRACT NUMBER: 2013-004842-40. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02479802.

Training-intensity Distribution on Middle- and Long-distance Runners: A Systematic Review.

Training-intensity distribution (TID) is considered the key factor to optimize performance in endurance sports. This systematic review aimed to: I) characterize the TID typically used by middle-and long-distance runners; II) compare the effect of different types of TID on endurance performance and its physiological determinants; III) determine the extent to which different TID quantification methods can calculate same TID outcomes from a given training program. The keywords and search strategy identified 20 articles in the research databases. These articles demonstrated differences in the quantification of the different training-intensity zones among quantification methods (i. e. session-rating of perceived exertion, heart rate, blood lactate, race pace, and running speed). The studies that used greater volumes of low-intensity training such as those characterized by pyramidal and polarized TID approaches, reported greater improvements in endurance performance than those which used a threshold TID. Thus, it seems that the combination of high-volume at low-intensity (≥ 70% of overall training volume) and low-volume at threshold and high-intensity interval training (≤ 30%) is necessary to optimize endurance training adaptations in middle-and long-distance runners. Moreover, monitoring training via multiple mechanisms that systematically encompasses objective and subjective TID quantification methods can help coaches/researches to make better decisions.

Key performance indicators of Olympic windsurfers during a World Cup: RS:X class®.

The aim of this study was to analyse differences in velocity, distance travelled and manoeuvres performed by Olympic sailors of the RS:X class using a GPS device. Fifty-three Olympic sailors of the RS:X class (28 males and 25 females) who competed in a World Championship were selected. The sample was divided into tertiles (T1, T2 and T3) according to their classification in the competition. Using a GPS device during the competition, mean velocity (VM), velocity made good (VMG), manoeuvres and distances in three different courses (upwind, reaching and downwind) were assessed during a regatta. Significant differences were found based on performance level in upwind (p < 0.001; ηp2 = 0.288), sailors of T1 covering a shorter distance compared to those of T2 (p < 0.009) and T3 (p < 0.001). Regarding VMG, an effect was observed for performance level in upwind (p < 0.001; ηp2 = 0.718), reaching (p < 0.001; ηp2 = 0.469) and downwind (p < 0.001; ηp2 = 0.575). Females covered a shorter distance compared to the males in upwind (p < 0.001; ηp2 = 0.639) and downwind (p < 0.001; ηp2 = 0.903). Distance and VMG are significant variables for establishing differences in performance level among Olympic sailors of the RS:X class when the wind speed is in a range of 8-21 knots.

The serum metabolome mediates the concert of diet, exercise, and neurogenesis, determining the risk for cognitive decline and dementia.

INTRODUCTION: Diet and exercise influence the risk of cognitive decline (CD) and dementia through the food metabolome and exercise-triggered endogenous factors, which use the blood as a vehicle to communicate with the brain. These factors might act in concert with hippocampal neurogenesis (HN) to shape CD and dementia. METHODS: Using an in vitro neurogenesis assay, we examined the effects of serum samples from a longitudinal cohort (n = 418) on proxy HN readouts and their association with future CD and dementia across a 12-year period. RESULTS: Altered apoptosis and reduced hippocampal progenitor cell integrity were associated with exercise and diet and predicted subsequent CD and dementia. The effects of exercise and diet on CD specifically were mediated by apoptosis. DISCUSSION: Diet and exercise might influence neurogenesis long before the onset of CD and dementia. Alterations in HN could signify the start of the pathological process and potentially represent biomarkers for CD and dementia.

Elevated Cerebrospinal Fluid Proteins and Albumin Determine a Poor Prognosis for Spinal Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease, both in its onset phenotype and in its rate of progression. The aim of this study was to establish whether the dysfunction of the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) measured through cerebrospinal fluid (CSF) proteins and the albumin-quotient (QAlb) are related to the speed of disease progression. An amount of 246 patients diagnosed with ALS were included. CSF and serum samples were determined biochemically for different parameters. Survival analysis based on phenotype shows higher probability of death for bulbar phenotype compared to spinal phenotype (p-value: 0.0006). For the effect of CSF proteins, data shows an increased risk of death for spinal ALS patients as the value of CSF proteins increases. The same model replicated for CSF albumin yielded similar results. Statistical models determined that the lowest cut-off value for CSF proteins able to differentiate patients with a good prognosis and worse prognosis corresponds to CSF proteins ≥ 0.5 g/L (p-value: 0.0189). For the CSF albumin, the QAlb ≥0.65 is associated with elevated probability of death (p-value: 0.0073). High levels of QAlb are a bad prognostic indicator for the spinal phenotype, in addition to high CSF proteins levels that also act as a marker of poor prognosis.

Caffeine supplementation improves physical performance without affecting fatigue level: a double-blind crossover study.

This study examined the effect of caffeine supplementation (CAFF) in a Wingate test (WT), and the behaviour of blood lactate concentrations (BLa) and neuromuscular fatigue (NMF), measured as reduced countermovement jump (CMJ) performance, in response to the WT. In a double-blind crossover study, 16 participants attended the laboratory twice, separated by a 72-hour window. In the sessions, participants first ingested 6 mg·kg-1 of either CAFF or placebo (PLAC), and then performed a WT. BLa was measured before (L-pre), and 0.5 min (L-post-0.5) and 3.5 min (L-post-3.5) after conducting the WT. The CMJ test was conducted before (CMJ pre), after (CMJ post), and 3 min after completing (CMJ post-3) the WT. The results indicated that CAFF enhanced peak power (Wpeak: + 3.22%; p = 0.040), time taken to reach Wpeak (T_Wpeak: -18.76%; p = 0.001) and mean power (Wmean: + 2.7%; p = 0.020). A higher BLa was recorded for CAFF at L-post-0.5 (+ 13.29%; p = 0.009) and L-post-3.5 (+ 10.51%; p = 0.044) compared to PLAC. CAFF improved peak power (PP; + 3.44%; p = 0.003) and mean power (MP; + 4.78%; p = 0.006) at CMJ pre, compared to PLAC, whereas PP and MP were significantly diminished at CMJ post and CMJ post-3 compared to pre (p < 0.001 for all comparisons) under both the CAFF and PLAC conditions. PP and MP were increased at post-3 compared to post (p < 0.001 for all comparisons) for both conditions. In conclusion, CAFF increased WT performance and BLa without affecting NMF measured by CMJ. Thus, CAFF may allow athletes to train with higher workloads and enhance the supercompensation effects after an adequate recovery period.

A comprehensive database for integrated analysis of omics data in autoimmune diseases.

BACKGROUND: Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic options. In the last decade, several omics studies have provided significant insights into the molecular mechanisms of these diseases. Nevertheless, data from different cohorts and pathologies are stored independently in public repositories and a unified resource is imperative to assist researchers in this field. RESULTS: Here, we present Autoimmune Diseases Explorer ( https://adex.genyo.es ), a database that integrates 82 curated transcriptomics and methylation studies covering 5609 samples for some of the most common autoimmune diseases. The database provides, in an easy-to-use environment, advanced data analysis and statistical methods for exploring omics datasets, including meta-analysis, differential expression or pathway analysis. CONCLUSIONS: This is the first omics database focused on autoimmune diseases. This resource incorporates homogeneously processed data to facilitate integrative analyses among studies.