Juvenile polyposis syndrome in children: The impact of SMAD4 and BMPR1A mutations on clinical phenotype and polyp burden.

OBJECTIVE: A constitutional disease-causing variant (DCV) in the SMAD4 or BMPR1A genes is present in 40%-60% of patients with juvenile polyposis syndrome (JPS). The aim of this study was to characterize the clinical course and polyp burden in children with DCV-positive JPS compared to DCV-negative JPS. METHODS: Demographic, clinical, genetic, and endoscopic data of children with JPS were compiled from eight international centers in the ESPHGAN/NASPGHAN polyposis working group. RESULTS: A total of 124 children with JPS were included: 69 (56%) DCV-negative and 55 (44%) DCV-positive (53% SMAD4 and 47% BMPR1A) with a median (interquartile range) follow-up of 4 (2.8-6.4) years. DCV-positive children were diagnosed at an older age compared to DCV-negative children [12 (8-15.7) years vs. 5 (4-7) years, respectively, p < 0.001], had a higher frequency of family history of polyposis syndromes (50.9% vs. 1.4%, p < 0.001), experienced a greater frequency of extraintestinal manifestations (27.3% vs. 5.8%, p < 0.001), and underwent more gastrointestinal surgeries (16.4% vs. 1.4%, p = 0.002). The incidence rate ratio for the development of new colonic polyps was 6.15 (95% confidence interval 3.93-9.63, p < 0.001) in the DCV-positive group compared to the DCV-negative group, with an average of 12.2 versus 2 new polyps for every year of follow-up. There was no difference in the burden of polyps between patients with SMAD4 and BMPR1A mutations. CONCLUSIONS: This largest international cohort of pediatric JPS revealed that DCV-positive and DCV-negative children exhibit distinct clinical phenotype. These findings suggest a potential need of differentiated surveillance strategies based upon mutation status.

mTOR inhibitors reduce enteropathy, intestinal bleeding and colectomy rate in patients with juvenile polyposis of infancy with PTEN-BMPR1A deletion.

Ultra-rare genetic disorders can provide proof of concept for efficacy of targeted therapeutics and reveal pathogenic mechanisms relevant to more common conditions. Juvenile polyposis of infancy (JPI) is caused by microdeletions in chromosome 10 that result in haploinsufficiency of two tumor suppressor genes: phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A). Loss of PTEN and BMPR1A results in a much more severe phenotype than deletion of either gene alone, with infantile onset pan-enteric polyposis and a high mortality rate. No effective pharmacological therapy exists. A multi-center cohort analysis was performed to characterize phenotype and investigate the therapeutic effect of mammalian target of rapamycin (mTOR) inhibition (adverse events, disease progression, time to colectomy and mortality) in patients with JPI. Among 25 JPI patients identified (mean age of onset 13 months), seven received mTOR inhibitors (everolimus, n = 2; or sirolimus, n = 5). Treatment with an mTOR inhibitor reduced the risk of colectomy (hazard ratio = 0.27, 95% confidence interval = 0.07-0.954, P = 0.042) and resulted in significant improvements in the serum albumin level (mean increase = 16.3 g/l, P = 0.0003) and hemoglobin (mean increase = 2.68 g/dl, P = 0.0077). Long-term mTOR inhibitor treatment was well tolerated over an accumulated follow-up time of 29.8 patient years. No serious adverse events were reported. Early therapy with mTOR inhibitors offers effective, pathway-specific and personalized treatment for patients with JPI. Inhibition of the phosphoinositol-3-kinase-AKT-mTOR pathway mitigates the detrimental synergistic effects of combined PTEN-BMPR1A deletion. This is the first effective pharmacological treatment identified for a hamartomatous polyposis syndrome.

Low-Density Plastic Debris Dispersion beneath the Mediterranean Sea Surface.

Plastic is a widespread marine pollutant, with most studies focusing on the distribution of floating plastic debris at the sea surface. Recent evidence, however, indicates a significant presence of such low density plastic in the water column and at the seafloor, but information on its origin and dispersion is lacking. Here, we studied the pathways and fate of sinking plastic debris in the Mediterranean Sea, one of the most polluted world seas. We used a recent Lagrangian plastic-tracking model, forced with realistic parameters, including a maximum estimated sinking speed of 7.8 m/d. Our simulations showed that the locations where particles left the surface differed significantly from those where they reached the seafloor, with lateral transport distances between 119 and 282 km. Furthermore, 60% of particles deposited on the bottom coastal strip (20 km wide) were released from vessels, 20% from the facing country, and 20% from other countries. Theoretical considerations furthermore suggested that biological activities potentially responsible for the sinking of low density plastic occur throughout the water column. Our findings indicate that the responsibility for seafloor plastic pollution is shared among Mediterranean countries, with potential impact on pelagic and benthic biota.

New Insights into Acylhydrazones E/Z Isomerization: An Experimental and Theoretical Approach.

A family of acylhydrazones have been prepared and characterized with the aim of investigating their potential as information storage systems. Their well-established synthetic methodologies allowed for the preparation of seven chemically stable acylhydrazones in excellent yields that have been photophysically and photochemically characterized. In addition, DFT and TD-DFT calculations have been performed to gain more insights into the structural, energetic and photophysical properties of the E/Z isomers. Our results reveal that E/Z configurational isomerization upon irradiation is highly dependent on the stabilization of the E or Z isomers due to the formation of intramolecular H bonds and the electronic/steric effects intrinsically related to their structures. In addition, Raman spectroscopy is also used to confirm the molecular structural changes after the formation of hydrogen bonds in the isomers.

Polygenic early-onset colorectal cancer in pediatric patients.

Colorectal cancer in the pediatric population is a rare but transpirable phenomenon. The occurrence should prompt suspicion for underlying genetic mutations in the setting of a hereditary cancer predisposition syndrome. In this series, we outline three pediatric patients with colonic adenocarcinoma who were found to have one or more germline mutations. The presence of compound mutations may lead to a hypermutator phenotype resulting in earlier presentation of colorectal cancer in childhood and adolescence. The diagnosis of colorectal cancer in pediatric patients warrants timely recognition, multigene panel testing, genetic counseling for the patient and family, and increased surveillance for intestinal and extra-intestinal tumors.

A landscape-scale framework to identify refugia from multiple stressors.

From a conservation perspective, quantifying potential refugial capacity has been predominantly focused on climate refugia, which is critical for maintaining the persistence of species and ecosystems. However, protection from other stressors, such as human-induced changes in fire and hydrology, that cause habitat loss, degradation, and fragmentation is also necessary to ensure that conservation efforts focused on climate are not undermined by other threats. Thus, conceptual and methodological advances for quantifying potential refugia from multiple anthropogenic stressors are important to support conservation efforts. We devised a new conceptual approach, the domains of refugia, for assessing refugial capacity that identifies areas where exposure to multiple stressors is low. In our framework, patterns of environmental variability (e.g., increased frequency of warm summers), thresholds of resilience, and extent and intensity of stressors are used to identify areas of potential refugia from a suite of ongoing anthropogenic stressors (e.g., changes in fire regime). To demonstrate its utility, we applied the framework to a Southern California landscape. Sites with high refugial capacity (super-refugia sites) had on average 30% fewer extremely warm summers, 20% fewer fire events, 10% less exposure to altered river channels and riparian areas, and 50% fewer recreational trails than the surrounding landscape. Our results suggest that super-refugia sites (∼8200 km2 ) for some natural communities are underrepresented in the existing protected area network, a finding that can inform efforts to expand protected areas. Our case study highlights how considering exposure to multiple stressors can inform planning and practice to conserve biodiversity in a changing world.

Marco Conceptual a para Identificar Refugios de Múltiples Amenazas a Escala de Paisaje Resumen Desde la perspectiva de la conservación, la cuantificación de la capacidad potencial de refugio se ha enfocado principalmente en los refugios climáticos, los cuales son críticos para mantener la persistencia de las especies y los ecosistemas. Sin embargo, la protección ante otros factores estresantes, como los cambios inducidos por los humanos en los incendios y la hidrología, que causan la pérdida, degradación y fragmentación del hábitat, también son necesarios para asegurar que los esfuerzos de conservación enfocados en el clima no sean afectados por otras amenazas. Por lo tanto, los avances conceptuales y metodológicos para cuantificar los refugios potenciales ante múltiples factores estresantes causados por el humano son importantes para asegurar que los esfuerzos de conservación logren sus objetivos. Diseñamos una nueva estrategia conceptual, los dominios de los refugios, para evaluar la capacidad de refugio de un paisaje donde la exposición a múltiples factores estresantes es baja. En nuestro marco conceptual usamos los patrones de variabilidad ambiental (p. ej.: incremento en la frecuencia de veranos cálidos), los umbrales de resiliencia y la extensión e intensidad de los factores estresantes para identificar las áreas de refugios potenciales a partir de un conjunto de factores antropogénicos persistentes (p. ej.: cambios en el régimen de incendios). Para demostrar su utilidad, aplicamos el marco conceptual a un paisaje del sur de California. Los sitios con una alta capacidad de refugio (sitios de súper-refugios) tuvieron en promedio un 30% menos veranos extremadamente cálidos, 20% menos eventos de incendios y 50% menos senderos recreativos que el paisaje circundante. Nuestros resultados sugieren que los sitios de súper-refugios (∼ 8,200 km2 ) para algunas comunidades naturales están subrepresentados en la red existente de áreas protegidas, un resultado que puede orientar los esfuerzos por expandir las áreas protegidas. Nuestro estudio de caso resalta que considerar la exposición a múltiples amenazas puede guiar la planificación y la práctica de la conservación de la biodiversidad en un mundo cambiante.

Effects of Biofilms and Particle Physical Properties on the Rising and Settling Velocities of Microplastic Fibers and Sheets.

Vertical dynamics of microplastics (MPs) in the water column are complex and not fully understood due to the diversity of environmental MPs and the impact of weathering and biofouling on their dynamical properties. In this study, we investigate the effects of the particle properties and biofilm on the vertical (settling or rising) velocity of microplastic sheets and fibers under laboratory conditions. The experiments focus on three types of MPs (polyester PES fibers, polyethylene terephthalate PET sheets, and polypropylene PP sheets) of nine sizes and two degrees of biological colonization. Even though pristine PES fibers and PET sheets had a similar density, the sinking velocity of fibers was much smaller and independent of their length. The settling or rising velocity of sheets increased with the particle size up to a threshold and then decreased in the wake of horizontal oscillations in large particles. Biofilms had unexpected effects on vertical velocities. Irregular biofilm distributions can trigger motion instabilities that decrease settling velocities of sheets despite the increase in density. Biofilms can also modify the orientation of fibers, which may increase their settling velocity. Finally, we selected the most performant theoretical formulation for each type of particle and proposed modifications to consider the effect of biofilm distribution.

Patterns of response and drugs involved in hypersensitivity reactions to beta-lactams in children.

BACKGROUND: Beta-lactams generate different allergenic determinants that induce selective or cross-reactive drug hypersensitivity reactions (DHRs). We aimed to identify the drugs involved, the selectivity of the response, the mechanism, and the value of the different diagnostic tests for establishing a diagnosis in children evaluated for DHRs to beta-lactams. METHODS: Prospective study evaluating children aged under 16 years reporting DHRs to beta-lactams. Reactions were classified as immediate and non-immediate reactions. The workup included sIgE, skin testing, and drug provocation tests (DPTs) for immediate reactions and patch testing and DPTs for non-immediate ones. RESULTS: Of the 510 children included, 133 were evaluated for immediate reactions and confirmed in 8.3%. Skin test/in vitro IgE contributed to diagnosing half of the cases. Selective reactions occurred with amoxicillin (63%), followed by common penicillin determinants (27%) and cephalosporins (0.9%). Among non-immediate reactions (11.4% of the 377 children evaluated), most required DPTs, 52.7% of which were positive at 6-7 days of drug challenge. Selective reactions were identified with amoxicillin (80%), penicillin G (7.5%), cephalosporins (7.5%), and clavulanic acid (5%). Urticaria and maculopapular exanthema were the most frequent entities. CONCLUSIONS: There were few confirmed cases of either type of reaction. Skin testing proved less valuable in non-immediate reactions, over half of which would also have been lost in a short DPT protocol. Selective responders to amoxicillin were more likely to have non-immediate reactions, while clavulanic acid selectivity was exclusive to the non-immediate typology. Over half the cases with DPTs required 6-7 days of treatment for DHR confirmation.

Paediatric polyposis syndromes: burden of disease and current concepts.

PURPOSE OF REVIEW: Polyposis syndromes are rare but significant entities that often present during childhood and adolescence. Polyposis syndromes should remain high on the differential diagnoses for any child presenting with rectal bleeding, protein-losing enteropathy or intussusception in the setting of multiple polyps in the gastrointestinal tract. There are three primary paediatric polyposis syndromes: Juvenile polyposis syndrome (JPS), Familial adenomatous polyposis (FAP) and Peutz-Jeghers syndrome (PJS). This review will cover recent guidelines for these conditions and advances in genetic testing. RECENT FINDINGS: The first set of paediatric guidelines were released in 2019 by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) for FAP, JPS and PJS. Even with advances in genetic testing, a significant proportion of patients with polyposis syndromes have no identifiable genetic mutations. Recent research has shown that polyps behave differently in patients with and without disease-causing variants, emphasizing the role of genetic testing in the diagnosis and management of polyposis syndromes. SUMMARY: Polyposis syndromes in the paediatric population are growing due to increased recognition and advances in genetic testing. A timely diagnosis and surveillance of a paediatric polyposis syndrome are pivotal for the management of disease burden and early identification of cancers within the gastrointestinal tract and beyond. Paediatricians, paediatric gastroenterologists, paediatric oncologists and paediatric surgeons should be familiar with the presentation and comorbidities of polyposis syndromes in children and adolescents. Further research into genotype-phenotype correlations is needed to tailor the care for paediatric patients with polyposis syndromes.

Assessing the potential risk and relationship between microplastics and phthalates in surface seawater of a heavily human-impacted metropolitan bay in northern China.

The impacts of microplastics (MPs) and phthalates (PAEs), a class of MP-associated contaminants, on the marine environment are not thoroughly understood despite concern over their adverse effects on humans and ecosystems. Field studies linking MPs and PAEs in seawater have not yet been reported. We investigate for the first time the correlation between MPs contamination and the presence of PAEs in the surface seawater of Jiaozhou Bay (JZB), a semi-enclosed metropolitan bay in northern China heavily impacted by human activity. The abundance of MPs, dominated by polyethylene and polyethylene terephthalate mostly smaller than 2 mm, ranged between 24.44 items/m3 and 180.23 items/m3, with the majority being black and transparent fibers and fragments. Concentrations of PAEs varied from 129.96 ng/L to 921.22 ng/L. Relatively higher abundances of MPs and higher concentrations of PAEs were generally found in areas near riverine inputs and sewage treatment plants. There was a strong correlation between PAEs concentration and MPs abundance, suggesting that they are closely linked. In a risk assessment combining PAEs and MPs, the risk quotients (RQs) indicated that the ecological risk of di-n-butyl phthalate in JZB was relatively high (0.046

Psychosocial job factors and biological cardiovascular risk factors in Mexican workers.

BACKGROUND: Psychosocial job factors (PJF) have been implicated in the development of cardiovascular disease. The paucity of data from developing economies including Mexico hampers the development of worksite intervention efforts in those regions. METHODS: This cross-sectional study of 2,330 Mexican workers assessed PJF (job strain [JS], social support [SS], and job insecurity [JI]) and biological cardiovascular disease risk factors [CVDRF] by questionnaire and on-site physical examinations. Alternative formulations of the JS scales were developed based on factor analysis and literature review. Associations between both traditional and alternative job factor scales with CVDRF were examined in multiple regression models, adjusting for physical workload, and socio-demographic factors. RESULTS: Alternative formulations of the job demand and control scales resulted in substantial changes in effect sizes or statistical significance when compared with the original scales. JS and JI showed hypothesized associations with most CVDRF, but they were inversely associated with diastolic blood pressure and some adiposity measures. SS was mainly protective against CVDRF. CONCLUSION: Among Mexican workers, alternative PJF scales predicted health outcomes better than traditional scales, and psychosocial stressors were associated with most CVDRF.

SABIO-RK--database for biochemical reaction kinetics.

SABIO-RK (http://sabio.h-its.org/) is a web-accessible database storing comprehensive information about biochemical reactions and their kinetic properties. SABIO-RK offers standardized data manually extracted from the literature and data directly submitted from lab experiments. The database content includes kinetic parameters in relation to biochemical reactions and their biological sources with no restriction on any particular set of organisms. Additionally, kinetic rate laws and corresponding equations as well as experimental conditions are represented. All the data are manually curated and annotated by biological experts, supported by automated consistency checks. SABIO-RK can be accessed via web-based user interfaces or automatically via web services that allow direct data access by other tools. Both interfaces support the export of the data together with its annotations in SBML (Systems Biology Markup Language), e.g. for import in modelling tools.

Mucosal prolapse syndrome mimicking Peutz-Jeghers syndrome in a pediatric patient.

Mucosal prolapse syndrome (MPS) is a rare group of benign conditions characterized by a set of unifying histologic findings thought to be the result of repeated mucosal shearing and submucosal vascular congestion caused by straining. This set of conditions is often misdiagnosed as other polyposis syndromes, inflammatory bowel disease, or malignancy due to its clinical presentation, appearance, and rarity. We report a case of a 15-year-old male who presented with painless rectal bleeding. He was found to have four rectal polyps thought to be due to Peutz-Jeghers syndrome. A repeat colonoscopy with biopsies a year later revealed a diagnosis of MPS. Our case highlights the morphologic similarity between hamartomatous polyp and mucosal prolapse histology. Since MPS is a rare diagnosis even among the adult population, it has not been well described in pediatrics. This syndrome should be on the differential diagnosis for pediatric rectal polyps to prevent unnecessary invasive testing and a delay in treatment.

Trajectory, fate, and magnitude of continental microplastic loads to the inner shelf: A case study of the world's largest coastal shallow lagoon.

The Patos Lagoon estuary is a highly significant ecosystem where freshwater from a vast and densely populated area continuously flows into the Atlantic Ocean by coastal plumes, exporting not only freshwater but also sediment, nutrients, plastics, and other contaminants. In this work, numerical modeling tools together with field data were used to assess for the first time the capacity of the coastal plume to export microplastics (MPs) to the inner shelf under different hydrodynamic conditions. Two field surveys were conducted during plume events to quantify MP concentrations and validate the model approach. A bottom-up approach was employed to estimate the potential MP export from the estuary's domain to the Atlantic Ocean. MP concentration in surface plume waters ranged from 0.20 items m-3 to 1.37 items m-3, confirmed by FTIR as synthetic polymers in a 90 %, being Polypropylene (PP) and Polyethylene (PE) the most abundant in a 73 %. The accumulation pattern was observed on the plume's frontal system, consistent with simulation results. The estimated average MP potential export rate attained 9.0 million items day-1 during moderate plume events and 47.5 million items day-1 during high discharge plume events. Strong discharge events, coupled with intense northeast winds, facilitated rapid southwestward export of MPs. Conversely, moderate to weak discharge events retained MPs closer to the estuary's mouth, enabling either longer trajectories or earlier deposition. Significant MP accumulation hotspots were identified in the gyre between the jetties and Cassino beach, as well as in the saline front within the plume boundaries. These accumulation zones may function as reservoirs for MP particles, potentially posing threats to local ecosystems. Understanding these dynamics is crucial for ongoing monitoring efforts to assess potential harmful interactions over time.

Physical processes matters! Recommendations for sampling microplastics in estuarine waters based on hydrodynamics.

Monitoring the abundance and characteristics of microplastics in estuarine waters is crucial for understanding the fate of microplastics at the land-sea continuum, and for developing policies and legislation to mitigate associated risks. However, if protocols to monitor microplastic pollution in ocean waters or beach sediments are well established, they may not be adequate for estuarine environments, due to the complex 3D hydrodynamics. In this note, we review and discuss sampling methods and strategies in relation to the main environmental forcing, estuarine hydrodynamics, and their spatio-temporal scales of variability. We propose recommendations about when, where and how to sample microplastics to capture the most representative picture of microplastic pollution. This note opens discussions on the urgent need for standardized methods and protocols to routinely monitor microplastics in estuaries which should, at the same time, be easily adaptable to the different systems to ensure consistency and comparability of data across different studies.

Spatial distribution of anthropogenic particles and microplastics in a meso-tidal lagoon (Arcachon Bay, France): A multi-compartment approach.

Assessment of microplastic (MP) contamination is still needed to evaluate this threat correctly and tackle this issue. Here, MP contamination was assessed for a meso-tidal lagoon of the Atlantic coast (Arcachon Bay, France). Sea surface, water column, intertidal sediments and wild oysters were sampled. Five different stations were studied to assess the spatial distribution of the contamination. Two were outside of the bay and three were inside the bay (from the inlet to the back). A distinction was made between all anthropogenic particles (AP, i.e. visually sorted) and MP (i.e. plastic polymer confirmed by ATR-FTIR spectroscopy). The length of particles recovered in this study ranged between 17 µm and 5 mm. Concentration and composition in sea surface and water column samples showed spatial variations while sediment and oyster samples did not. At outside stations, the sea surface and the water column presented a blended composition regarding shapes and polymers and low to high concentrations (e.g. 0.16 ± 0.08 MP.m-3 and 561.7 ± 68.5 MP.m-3, respectively for sea surface and water column), which can be due to coastal processes and nearby input sources. The inlet station displayed a well-marked pattern only at the sea surface. High AP and MP concentrations were recorded, and fragments along with polyethylene overwhelmed (respectively 76.0 % and 73.2 %). Higher surface currents could explain this pattern. At the bay back, AP and MP concentrations were lower and fibers were mainly recorded. Weaker hydrodynamics in this area was suspected to drive this contamination profile. Overall, fragments and buoyant particles were mainly detected at the sea surface while fibers and negatively buoyant particles prevailed in other compartments. Most of the studied samples presented an important contribution of fiber-shaped particles (from 31.5 % to 94.2 %). Finally, contamination was ubiquitous as AP and MP were found at all stations in all sample types.

Clavulanic Acid Is a Leading Culprit Beta-Lactam in Immediate Allergic Reactions to Penicillins.

PURPOSE: Clavulanate, a beta-lactam associated with amoxicillin, is frequently prescribed in patients at all ages. Recent data implicate amoxicillin-clavulanate in up to 80% of beta-lactam allergy cases. We assessed clavulanate's role in inducing allergic reactions to this combination treatment, with a focus on selective immediate reactions. METHODS: Adults (≥ 16 years) reporting a history of immediate reactions to amoxicillin-clavulanate were evaluated through a beta-lactam allergological workup, using modified European Academy of Allergy and Clinical Immunology guidelines. Patients first underwent skin testing, and if negative, drug provocation tests. Expected outcomes were: Group A, subjects with immediate reaction to classical penicillin group determinants (penicilloyl polylysine, minor determinants mixture, and/or penicillin G); Group B, subjects with selective immediate reaction to amoxicillin; Group C, subjects with selective immediate reaction to clavulanate and Group D, those immediate reactions with co-sensitization to clavulanate plus penicillin group determinants or amoxicillin. RESULTS: Of 1,170 included patients, 104 had immediate reactions: 36.5% to penicillin group determinants (Group A), 26.9% to amoxicillin (Group B), 32.7% to clavulanate (Group C), and 3.8% to clavulanate plus penicillin determinants or amoxicillin (Group D). Diagnosis was made by skin testing in 79%, 75% and 47% of the patients, respectively, in the first 3 groups (P < 0.001). Drug provocation tests were necessary to establish most other diagnoses. Anaphylaxis predominated over urticaria/angioedema in all groups. CONCLUSIONS: Selective immediate reactions to clavulanate accounted for over a third of cases with confirmed reactions after amoxicillin-clavulanate intake, with more than half experiencing anaphylaxis. Within this group, skin test sensitivity was below 50%. People taking amoxicillin-clavulanate may also be co-sensitized to both drugs.

Polymorphisms in ARNTL/BMAL1 and CLOCK Are Not Associated with Multiple Sclerosis in Spanish Population.

Disrupted circadian cycle has been reported in multiple sclerosis (MS). Previous genome-wide association studies (GWAS) singled out over 230 variants associated with MS. A study performed in a Slavic population identified two new single nucleotide polymorphisms (SNPs), rs6811520 (CLOCK) and rs3789327 (ARNTL/BMAL1), associated with MS risk. However, these regions that codify the capital regulators of circadian rhythm had not been linked to the disease before, so replication in independent populations is warranted to ascertain possible geographical differences. Our aim was to replicate the associations reported in the ARNTL/BMAL1 and CLOCK genes in a Spanish cohort with a maximum of 974 MS patients and 626 controls. In this study, 956 MS patients and 612 controls were successfully genotyped for rs6811520 and 943 MS patients and 598 controls for rs3789327.Clinical variables (age at disease onset, EDSS, or relapses) were collected in a maximum of 549 patients. No statistically significant differences were found between cases and controls for the analyzed SNPs, even after stratifications by sex, clinical form, or HLA-DRB1*15:01 status. No influence of the SNPs was found on age at disease onset, EDSS, or annual relapse rate at 5 years after onset. In conclusion, our study does not replicate the associations observed in the previously investigated Slavic population.

The streaming of plastic in the Mediterranean Sea.

Plastic debris is a ubiquitous pollutant on the sea surface. To date, substantial research efforts focused on the detection of plastic accumulation zones. Here, a different paradigm is proposed: looking for crossroad regions through which large amounts of plastic debris flow. This approach is applied to the Mediterranean Sea, massively polluted but lacking in zones of high plastic concentration. The most extensive dataset of plastic measurements in this region to date is combined with an advanced numerical plastic-tracking model. Around 20% of Mediterranean plastic debris released every year passed through about 1% of the basin surface. The most important crossroads intercepted plastic debris from multiple sources, which had often traveled long distances. The detection of these spots could foster understanding of plastic transport and help mitigation strategies. Moreover, the general applicability and the soundness of the crossroad approach can promote its application to the study of other pollutants.

Profiling Physical Fitness of Physical Education Majors Using Unsupervised Machine Learning.

The academic curriculum has shown to promote sedentary behavior in college students. This study aimed to profile the physical fitness of physical education majors using unsupervised machine learning and to identify the differences between sexes, academic years, socioeconomic strata, and the generated profiles. A total of 542 healthy and physically active students (445 males, 97 females; 19.8 [2.2] years; 66.0 [10.3] kg; 169.5 [7.8] cm) participated in this cross-sectional study. Their indirect VO2max (Cooper and Shuttle-Run 20 m tests), lower-limb power (horizontal jump), sprint (30 m), agility (shuttle run), and flexibility (sit-and-reach) were assessed. The participants were profiled using clustering algorithms after setting the optimal number of clusters through an internal validation using R packages. Non-parametric tests were used to identify the differences (p < 0.05). The higher percentage of the population were freshmen (51.4%) and middle-income (64.0%) students. Seniors and juniors showed a better physical fitness than first-year students. No significant differences were found between their socioeconomic strata (p > 0.05). Two profiles were identified using hierarchical clustering (Cluster 1 = 318 vs. Cluster 2 = 224). The matching analysis revealed that physical fitness explained the variation in the data, with Cluster 2 as a sex-independent and more physically fit group. All variables differed significantly between the sexes (except the body mass index [p = 0.218]) and the generated profiles (except stature [p = 0.559] and flexibility [p = 0.115]). A multidimensional analysis showed that the body mass, cardiorespiratory fitness, and agility contributed the most to the data variation so that they can be used as profiling variables. This profiling method accurately identified the relevant variables to reinforce exercise recommendations in a low physical performance and overweight majors.