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Abstract Background Demand for home care services has increased considerably, along with the growing complexity of cases and variability among resources and providers. Designing services that guarantee co-ordination and integration for providers and levels of care is of paramount importance. The aim of this study is to determine the effectiveness of a new case-management based, home care delivery model which has been implemented in Andalusia (Spain). Methods Quasi-experimental, controlled, non-randomised, multi-centre study on the population receiving home care services comparing the outcomes of the new model, which included nurse-led case management, versus the conventional one. Primary endpoints: functional status, satisfaction and use of healthcare resources. Secondary endpoints: recruitment and caregiver burden, mortality, institutionalisation, quality of life and family function. Analyses were performed at base-line, and at two, six and twelve months. A bivariate analysis was conducted with the Student's t-test, Mann-Whitney's U, and the chi squared test. Kaplan-Meier and log-rank tests were performed to compare survival and institutionalisation. A multivariate analysis was performed to pinpoint factors that impact on improvement of functional ability. Results Base-line differences in functional capacity – significantly lower in the intervention group (RR: 1.52 95%CI: 1.05–2.21; p = 0.0016) – disappeared at six months (RR: 1.31 95%CI: 0.87–1.98; p = 0.178). At six months, caregiver burden showed a slight reduction in the intervention group, whereas it increased notably in the control group (base-line Zarit Test: 57.06 95%CI: 54.77–59.34 vs. 60.50 95%CI: 53.63–67.37; p = 0.264), (Zarit Test at six months: 53.79 95%CI: 49.67–57.92 vs. 66.26 95%CI: 60.66–71.86 p = 0.002). Patients in the intervention group received more physiotherapy (7.92 CI95%: 5.22–10.62 vs. 3.24 95%CI: 1.37–5.310; p = 0.0001) and, on average, required fewer home care visits (9.40 95%CI: 7.89–10.92 vs.11.30 95%CI: 9.10–14.54). No differences were found in terms of frequency of visits to A&E or hospital re-admissions. Furthermore, patients in the control group perceived higher levels of satisfaction (16.88; 95%CI: 16.32–17.43; range: 0–21, vs. 14.65 95%CI: 13.61–15.68; p = 0,001). Conclusion A home care service model that includes nurse-led case management streamlines access to healthcare services and resources, while impacting positively on patients' functional ability and caregiver burden, with increased levels of satisfaction. Trial registration ISRCTN44054549

IL-6 is an important cytokine involved in metabolic, immunological, and cell-fate responses. It is released upon stimulation by skeletal muscle cells through partially characterized mechanisms. In some cell types, IL-6 has been reported to activate a positive feedback loop involving endocytic vesicles, but evidence is mostly based on transcription and signal transduction mechanisms and is very scarce in muscle cells. Our aim was to directly demonstrate the presence of positive feedback in the ATP-induced release of IL-6 into the supernatant of human skeletal muscle cultures. The total release (production) of IL-6 was reduced for higher volumes of supernatant, when the secreted IL-6 molecules are more diluted, and enhanced when the supernatant volume was lower. In addition, secretion was impaired both by tocilizumab, a blocker of human IL-6 receptors, and by the soluble form of the receptor. The secretion in response to ATP was also inhibited by treatment with the endocytosis inhibitor dynasore, and by disruption of the acidic gradient of the endocytic compartment using different methods (chloroquine, NH4Cl or monensin). IL-6 secretion was also impaired by NED-19, a specific inhibitor of the two pore channels receptor mediating Ca 2+ release from the endolysosomal compartment. IL-6 and ATP increased IL-6 mRNA levels, an effect blocked by tocilizumab. Altogether, our results demonstrate that ATP-secreted IL-6 activates a positive loop based on IL-6 receptors, endocytosis, two pore channels and IL-6 transcription. Given the importance of muscle IL-6 as a systemic regulator and as an inflammatory mediator, our study can help to understand muscle pathophysiology., Competing Interests: Declaration of competing interest Authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The study aims to analyze scientific publications on the association between social networks, social relationships, and social support for sports coaches. It seeks to identify the types and levels of social support provided by various agents, and to understand the impact of this support on coaches' wellbeing. The goal is to help coaches better utilize social support, thereby enhancing their quality of life, work, and performance., Methods: This study systematically reviewed 11 scientific articles to investigate the association between social support, social networks, and social relationships in sports coaches. It aimed to identify the types and levels of social support offered to coaches by family members, peers, and friends. Our research utilized the PRISMA guidelines for systematic reviews and assessed study quality using the STROBE Statement. Eligibility was determined by the PECOS criterion based on the search strategy terms., Results: Our findings indicate that social support has significant positive effects on sports coaches. It enhances selfcompassion, prevents burnout symptoms, boosts job and life satisfaction, and reduces stress levels. Organizational support, characterized by clear guidelines, guidance, and autonomy, yielded positive outcomes. Conversely, the absence of social support correlated with negative outcomes for coaches, including lower self-compassion, increased stress and burnout symptoms, reduced job and life satisfaction, and heightened work-family conflict. Coaches' social networks encompassed family members, peers, friends, and other sources, with friends perceived as the most influential. Maintaining an effective social support network is crucial for coaches' performance and psychological wellbeing., Discussion: This systematic review emphasizes the importance of social support for coaches in both their personal and professional lives, noting its positive effects and the negative consequences of its absence. Given the demanding nature of coaching, improving social support systems can enhance coaches' wellbeing and the success of sports activities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ferreira, Rodrigues, Sobreiro, Silva, Santos, Carvalho, Hernández Mendo and Rodrigues.)

Introduction: Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast growth factor 23 (FGF23) by a tumor., Material and Methods: We conducted a systematic review to identify all case reports of TIO, focusing on those associated with mesenchymal tumors. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) consensus, and we included patients with a diagnosis of TIO and histological confirmation of phosphaturic mesenchymal tumors or resolution of the condition after treatment of the tumor. Bibliographical searches were carried out until December 2023 in the Cochrane Library, Medline and Embase, as well as congress abstracts online., Results: We identified 769 articles with 1979 cases reported. Most patients were adults, with a higher incidence on men. Disease duration before diagnosis is a mean of 4.8 years. Most tumors were histologically classified as PMT. Lower limbs were the predominant location. Hypophosphatemia was present in 99.8 % of patients. The FGF23 was elevated at diagnosis in 95.5 %. Resection of the tumor was the treatment of choice in most of patients. After resection, there was a clinical improvement in 97.6 % of cases, and serum phosphorus and FGF23 levels returned to normal ranges in 91.5 % and 81.4 % of the patients, respectively., Conclusion: TIO is usually misdiagnosed with rheumatological or musculoskeletal disorders. The diagnosis should be suspected in patients with hypophosphatemic osteomalacia, and the measurement of serum FGF23 can be useful for diagnosis and management., Competing Interests: None of the authors has conflicts of interest., (© 2024 The Authors. Published by Elsevier Inc.)

Background: Delay in diagnosis and therapy in patients with arthritis commonly leads to progressive articular damage. The study aimed to investigate the immunohistochemical reactivity of synovial cytokines associated with inflammation and the bone erosives/neoformatives processes among individuals diagnosed with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and radiographic axial spondyloarthritis (r-axSpA), with the intention of identifying potential biomarkers., Methods: Specimens were collected from the inflamed knee joints of patients referred for arthroscopic procedures, and the synovial tissue (ST) was prepared for quantifying protein expression through immunohistochemical analysis (% expressed in Ratio_Area-Intensity) for TGF-β1, IL-17A, Dkk1, BMP2, BMP4, and Wnt5b. The collected data underwent thorough analysis and examination of their predictive capabilities utilising receiver operating characteristic (ROC) curves., Results: Valid synovial tissue samples were acquired from 40 patients for IHC quantification analysis. Initially, these patients had not undergone treatment with biologics. However, after 5 years, 4 out of 13 patients diagnosed with PsA and two out of nine patients diagnosed with RA had commenced biologic treatments. Individuals with early PsA who received subsequent biologic treatment exhibited significantly elevated IHC reactivity in ST for TGF-β1 ( p = 0.015). Additionally, patients with both PsA and RA who underwent biologic therapy displayed increased IHC reactivity for IL-17A ( p = 0.016), TGF-β1 ( p = 0.009), and Dkk1 ( p = 0.042). ROC curve analysis of IHC reactivity for TGF-β1, Dkk1, and IL-17A in the synovial seems to predict future treatment with biologics in the next 5 years with the area under the curve (AUC) of a combined sum of the three values: AUC: 0.828 (95% CI: 0.689-0.968; p 0.005) S 75% E 84.4%., Conclusions: Higher synovial immunohistochemistry reactivity of IL-17A, Dkk1, and TGF-β1 in patients with early psoriatic arthritis and rheumatoid arthritis may serve as potential indicators for predicting the necessity of utilising biologic treatments.

Navigation in the Mediterranean in the Neolithic is studied here through the boats that were used, the degree of technical specialisation in their construction and, above all, their chronology. After a brief explanation of the exceptional site of La Marmotta, the characteristics and chronology of the five canoes found at the settlement and one of the nautical objects linked to Canoe 1 are discussed. This will allow a reflection on the capability of Neolithic societies for navigation owing to their high technological level. This technology was an essential part in the success of their expansion, bearing in mind that in a few millennia they occupied the whole Mediterranean from Cyprus to the Atlantic seaboard of the Iberian Peninsula., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gibaja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Subdural hemorrhages (SDHs) in the pediatric population are associated with a high mortality and morbidity and may present in the context of abusive head trauma. Diagnostic investigations for such cases often include evaluation for rare genetic and metabolic disorders that can have associated SDH. Sotos syndrome is an overgrowth syndrome associated with macrocephaly and increased subarachnoid spaces and rarely with neurovascular complications. Here, we report two cases of Sotos syndrome, one with SDH during infancy who underwent repeated evaluation for suspected child abuse prior to the Sotos syndrome diagnosis and the other with enlarged extra-axial cerebrospinal fluid spaces, demonstrating a possible mechanism for SDH development in this setting. These cases suggest that some individuals with Sotos syndrome may be at elevated risk of developing SDH in infancy and that Sotos syndrome should be on the differential diagnosis during a medical genetics evaluation in cases of unexplained SDH, especially in the setting of macrocephaly., Competing Interests: None declared., (Thieme. All rights reserved.)

Background and Objectives : Research on female soccer players that analyzes playing status is scarce and has previously only examined load monitoring, while other markers, such as physical (i.e., strength, power, and agility), physiological (i.e., maximal oxygen uptake), and body composition (i.e., body fat mass, fat-free mass, body water, and phase angle) markers, warrant further investigation. Thus, the study aims were to (a) compare physical, physiological, body composition, and load markers between starters and non-starters; (b) compare measurements pre- and post-training intervention (five weeks); and (c) analyze any relationships between physical, physiological, body composition, and load markers in an elite female soccer team. Materials and Methods : Fourteen first-team players participated in the study (age 23.29 ± 3.19 years, weight 59.14 ± 6.87 kg, height 1.66 ± 0.08 m). Several physical ( n = 15), physiological ( n = 1), body composition ( n = 11), and load markers ( n = 14) were collected. In addition, participants were sub-divided into starters ( n = 7) and non-starters ( n = 7). Results : No differences were revealed between starters and non-starters in any of the examined variables. Moreover, following the training intervention, a significantly lower value was found for total body water/fat-free mass ratio (p = 0.043; ES = 0.582). In addition, there were several correlations detected between load and physical/physiological markers ( n = 28); load and body composition markers ( n = 6); physical/physiological and body composition markers ( n = 34); and physical and physiological markers ( n = 42). Conclusions: In conclusion, only a slight tendency of higher load values for starters than non-starters was observed. In addition, no differences in physical, physiological, and body composition markers were found between starters and non-starters, possibly suggesting that five weeks were not enough to improve such variables. Finally, the present results provide novel information assessing the effects of the pre-season in elite female Portuguese soccer players and contribute to a better understanding of the associations between different types of measurements.

Objective: To determine whether a combination of a single intramuscular (IM) dose of pentamidine (7 mg/kg) followed by oral tamoxifen 40 mg/day for 20 days is non-inferior to three IM doses of pentamidine 7 mg/kg in the treatment of cutaneous leishmaniasis with a margin of 15%., Methods: Phase II, randomised, controlled, open-label, non-inferiority clinical trial. Primary outcome was the complete healing of the lesions 6 months after starting treatment. Secondary outcomes were healing 3 months after starting treatment and determining the presence and severity of adverse effects (AE)., Results: The research was concluded with 49 patients; Leishmania (Viannia) guyanensis was the most frequent species isolated. In the primary outcome, 18 (72%) (95% CI: 52.4%-85.7%) of the 25 patients allocated to the intervention group and 24 (100%) (95% CI: 86.2%-100%) of the control group (p = 0.015) met the established criteria of cure. There was no AE with tamoxifen., Conclusion: Although a 72% cure rate presented by the combination of tamoxifen and pentamidine was lower than in the control group that achieved a 100% cure, it is still a safe and is a clinically relevant result. It indicates that the therapeutic scheme evaluated may be a promising option for populations in remote areas, however it should be further studied, in order to include a larger number of patients., (© 2023 John Wiley & Sons Ltd.)

The phase of the quantum-mechanical wave function can encode a topological structure with wide-ranging physical consequences, such as anomalous transport effects and the existence of edge states robust against perturbations. While this has been exhaustively demonstrated for electrons, properties associated with the elementary quasiparticles in magnetic materials are still underexplored. Here, we show theoretically and via inelastic neutron scattering experiments that the bulk ferromagnet Mn 5 Ge 3 hosts gapped topological Dirac magnons. Although inversion symmetry prohibits a net Dzyaloshinskii-Moriya interaction in the unit cell, it is locally allowed and is responsible for the gap opening in the magnon spectrum. This gap is predicted and experimentally verified to close by rotating the magnetization away from the c-axis with an applied magnetic field. Hence, Mn 5 Ge 3 realizes a gapped Dirac magnon material in three dimensions. Its tunability by chemical doping or by thin film nanostructuring defines an exciting new platform to explore and design topological magnons. More generally, our experimental route to verify and control the topological character of the magnons is applicable to bulk centrosymmetric hexagonal materials, which calls for systematic investigation., (© 2023. The Author(s).)

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a biodegradable and biocompatible biopolymer that has gained popularity in the field of biomedicine. This review provides an overview of recent advances and potential applications of PHBV, with special emphasis on drug encapsulation and scaffold construction. PHBV has shown to be a versatile platform for drug delivery, offering controlled release, enhanced therapeutic efficacy, and reduced side effects. The encapsulation of various drugs, such as anticancer agents, antibiotics, and anti-inflammatory drugs, in PHBV nanoparticles or microspheres has been extensively investigated, demonstrating enhanced drug stability, prolonged release kinetics, and increased bioavailability. Additionally, PHBV has been used as a scaffold material for tissue engineering applications, such as bone, cartilage, and skin regeneration. The incorporation of PHBV into scaffolds has been shown to improve mechanical properties, biocompatibility, and cellular interactions, making them suitable for tissue engineering constructs. This review highlights the potential of PHBV in drug encapsulation and scaffold fabrication, showing its promising role in advancing biomedical applications.

The systemic effects of physical activity are mediated by the release of IL-6 and other myokines from contracting muscle. Although the release of IL-6 from muscle has been extensively studied, the information on the cellular mechanisms is fragmentary and scarce, especially regarding the role of Ca 2+ signals. The aim of this study was to characterize the role of the main components of Ca 2+ signals in human skeletal muscle cells during IL-6 secretion stimulated by the Ca 2+ mobilizing agonist ATP. Primary cultures were prepared from surgical samples, fluorescence microscopy was used to evaluate the Ca 2+ signals and the stimulated release of IL-6 into the medium was determined using ELISA. Intracellular calcium chelator Bapta, low extracellular calcium and the Ca 2+ channels blocker La 3+ reduced the ATP-stimulated, but not the basal secretion. Secretion was inhibited by blockers of L-type (nifedipine, verapamil), T-type (NNC55-0396) and Orai1 (Synta66) Ca 2+ channels and by silencing Orai1 expression. The same effect was achieved with inhibitors of ryanodine receptors (ryanodine, dantrolene) and IP3 receptors (xestospongin C, 2-APB, caffeine). Inhibitors of calmodulin (calmidazolium) and calcineurin (FK506) also decreased secretion. IL-6 transcription in response to ATP was not affected by Bapta or by the T channel blocker. Our results prove that ATP-stimulated IL-6 secretion is mediated at the post-transcriptional level by Ca 2+ signals, including the mobilization of calcium stores, the activation of store-operated Ca 2+ entry, and the subsequent activation of voltage-operated Ca 2+ channels and calmodulin/calcineurin pathways.

This study aimed to apply an incremental tethered swimming test (ITT) with workloads (WL) based on individual rates of front crawl mean tethered force (Fmean) for the identification of the upper boundary of heavy exercise (by means of respiratory compensation point, RCP), and therefore to describe oxygen uptake kinetics (VO 2 k) and time limit (t Lim ) responses to WL corresponding to peak oxygen uptake (WLVO 2peak ). Sixteen swimmers of both sexes (17.6 ± 3.8 years old, 175.8 ± 9.2 cm, and 68.5 ± 10.6 kg) performed the ITT until exhaustion, attached to a weight-bearing pulley-rope system for the measurements of gas exchange threshold (GET), RCP, and VO 2peak . The WL was increased by 5% from 30 to 70% of Fmean at every minute, with Fmean being measured by a load cell attached to the swimmers during an all-out 30 s front crawl bout. The pulmonary gas exchange was sampled breath by breath, and the mathematical description of VO 2 k used a first-order exponential with time delay (TD) on the average of two rest-to-work transitions at WLVO 2peak . The mean VO 2peak approached 50.2 ± 6.2 mL·kg -1 ·min -1 and GET and RCP attained (respectively) 67.4 ± 7.3% and 87.4 ± 3.4% VO 2peak . The average t Lim was 329.5 ± 63.6 s for both sexes, and all swimmers attained VO 2peak (100.4 ± 3.8%) when considering the primary response of VO 2 (A 1' = 91.8 ± 6.7%VO 2peak ) associated with the VO 2 slow component (SC) of 10.7 ± 6.7% of end-exercise VO 2 , with time constants of 24.4 ± 9.8 s for A 1' and 149.3 ± 29.1 s for SC. Negative correlations were observed for t Lim to VO 2peak , WLVO 2peak , GET, RCP, and EEVO 2 (r = -0.55, -0.59, -0.58, -0.53, and -0.50). Thus, the VO 2 k during tethered swimming at WLVO 2peak reproduced the physiological responses corresponding to a severe domain. The findings also demonstrated that t Lim was inversely related to aerobic conditioning indexes and to the ability to adjust oxidative metabolism to match target VO 2 demand during exercise.

The enhanced separation power and identification capabilities make comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC - ToF MS) a valuable instrumental alternative for non-target analysis (NTA). In the present study, GC × GC - ToF MS has been used for the NTA of chlorine- and bromine-containing compounds in composite livers of two scarcely investigated Mediterranean deep-sea fish species, hollowsnout grenadier (Coelorinchus caelorhincus) and roughsnout grenadier (Trachyrhinchus trachyrhinchus). Attention focused on the identification of organohalogenated compounds with structural characteristics similar to those of persistent organic pollutants (POPs). In total, 116 Cl-, Br- and mixed Cl/Br-compounds were either positively or tentatively identified in the analyzed liver samples. Up to 88 of these compounds were legacy POPs, being polychlorinated biphenyls (PCBs) and organochlorinated pesticides (OCPs) the most abundant and frequently detected families. The other 28 identified POP-like compounds were analytes not considered by current regulation and environmental monitoring programs, including, among others, degradation products of specific OCPs, naturally produced organohalogen compounds and several perchlorinated diethyldiphenylmethane-derivatives whose presence in the investigated species is reported here for the first time. The presence of other naturally occurring brominated and mixed halogenated compounds in these fish species is also described for the first time. Our results also showed differences in the accumulation profile of the identified compounds in both species. Thereby, anthropogenic POPs showed higher relative abundances in the livers of roughsnout grenadiers than those in hollowsnout grenadiers, while for naturally occurring compounds the opposite trend or similar levels were found in both species., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

This study presents a methodology that combines experimental tests and the finite element method, which is able to analyse the influence of the geometry on the mechanical behaviour of stents made of bioabsorbable polymer PLA (PolyLactic Acid) during their expansion in the treatment of coarctation of the aorta (CoA). Tensile tests with standardized specimen samples were conducted to determine the properties of a 3D-printed PLA. A finite element model of a new stent prototype was generated from CAD files. A rigid cylinder simulating the expansion balloon was also created to simulate the stent opening performance. A tensile test with 3D-printed customized stent specimens was performed to validate the FE stent model. Stent performance was evaluated in terms of elastic return, recoil, and stress levels. The 3D-printed PLA presented an elastic modulus of 1.5 GPa and a yield strength of 30.6 MPa, lower than non-3D-printed PLA. It can also be inferred that crimping had little effect on stent circular recoil performance, as the difference between the two scenarios was on average 1.81%. For an expansion of diameters ranging from 12 mm to 15 mm, as the maximum opening diameter increases, the recoil levels decrease, ranging from 10 to 16.75% within the reported range. These results point out the importance of testing the 3D-printed PLA under the conditions of using it to access its material properties; the results also indicate that the crimping process could be disregarded in simulations to obtain fast results with lower computational cost and that new proposed stent geometry made of PLA might be suitable for use in CoA treatments-the approach that has not been applied before. The next steps will be to simulate the opening of an aorta vessel using this geometry.

This research aims to provide an overview of the growing number of scientific literature publications related to Physical Activity and Healthy Habits. A bibliometric analysis between 1990 and 2022 in the Web of Science was carried out, following the bibliometric analysis law, using Microsoft Excel and VosViewer Software for analysis and data processing. A total of 276 documents (262 primary studies and 14 revisions) related to the topic under study were located. The results reveal an exponential growth of scientific production by 48% between 2006 and 2022. Public Environmental Occupational Health, Kaprio, J., and the USA were the knowledge field, author, and country most productive, respectively. A great thematic diversity was found related to the most used keywords by the authors, such as "physical activity", "health habits", "exercise", and "obesity". Thus, the research related to this theme is really in an exponential phase, with great interest in the importance of physical activity and healthy habits, implying practical decisions in policies to develop programs to promote physical activity and healthy habits.

Background: Epidermolysis bullosa (EB) is frequently complicated by skin infection, which can lead to bacteremia. However, bloodstream infections (BSI) in patients with EB have not been well described., Methods: Retrospective study of BSI in children 0-18 years with EB from a national reference unit in Spain, in 2015-2020., Results: Among 126 children with EB, we identified 37 BSI episodes in 15 patients (14 recessive dystrophic EB, 1 junctional EB). The most frequent microorganisms were Pseudomonas aeruginosa (n = 12) and Staphylococcus aureus (n = 11). Five P. aeruginosa isolates were ceftazidime-resistant (42%), 4 of which were also resistant to meropenem and quinolones (33%). As for S. aureus , 4 (36%) were methicillin-resistant and 3 (27%) clindamycin-resistant. In 25 (68%) BSI episodes skin cultures had been performed in the previous 2 months. The most frequent isolates were also P. aeruginosa (n = 15) and S. aureus (n = 11). In 13 cases (52%), smear and blood cultures grew the same microorganism, with the same antimicrobial resistance pattern in 9 isolates. Twelve patients (10%) died during follow-up (9 RDEB and 3 JEB). BSI was the cause of death in 1 case. In patients with severe RDEB, a history of BSI was associated with higher mortality (OR 6.1, 95% CI: 1.33-27.83, P = 0.0197)., Conclusions: BSI is an important cause of morbidity in children with severe forms of EB. The most frequent microorganisms are P. aeruginosa and S. aureus , with high rates of antimicrobial resistance. Skin cultures can help guide treatment decisions in patients with EB and sepsis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

This study sought to assess the relationship between different jumping asymmetries and associated performance variables in high-level male senior and professional football players. Nineteen football players with at least 12 years of training experience (23.2 ± 3.1 years of age; 75.2 ± 4.8 kg of body mass and 181 ± 0.06 cm of height) participated in this study performing countermovement jump (CMJ), squat jump (SJ), single-leg CMJ and drop jump (DJ), associated performance variable eccentric utilization ratio (EUR), stretch-shortening cycle (SSC), bilateral deficit (BLD), and limb symmetry index (LSI) were determined. High correlations were observed between different methodologies of jump tests and associated performance indicators (SSC, BLD, EUR), except LSI. Moreover, CMJ and SJ results were different ( p < 0.05), but no differences were found between interlimb in CMJ ( p = 0.19) and DJ ( p = 0.14). Between the same limbs and different jumps differences were detected in CMJ and DJ ( p < 0.01), and it has also been found that the laterality effect size on strength was small in CMJ ( ES = 0.30) and DJ ( ES = 0.35). LSI between CMJ and DJ was not different despite higher mean values in CMJ, and although mean BLD was positive (>100%), the results highlight the need for individual evaluation since eight players scored negatively. An in-depth and accurate analysis of performance in preseason screening jump tests should be considered, aiming to detect injury risk, specifically evaluating different jumping test methodologies, and determining jumping associated performance variables for each test, namely EUR, SSC, BLD, and LSI. Specific muscle-strengthening exercises could be implemented based on this study results and outcomes, aiming to reduce injury risks and lower extremity asymmetries and to enhance individual football performance in high-level male senior and professional football players. Sports institutions should pay special attention regarding potential health problems in athletes exposed to daily high training loads.

Background: Immune and non-immune cells contribute to the pathology of chronic arthritis, and they can contribute to tissue remodeling and repair as well as disease pathogenesis. The present research aimed to analyze inflammation and bone destruction/regeneration biomarkers in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and ankylosing spondylitis (AS)., Methods: Samples were obtained from the inflamed knee of patients with knee arthritis who had been referred for undergoing arthroscopies. The synovial membrane was processed for pathological description, IHC analysis, and quantification of mRNA expression ratio by qRT-PCR. Serum levels of TGF-β1, IL-23, IL-6, IL-17 A, IL-22, Dkk1, Sclerostin, BMP2, BMP4, Wnt1, and Wnt5a were measured by ELISA. All these data were analyzed and compared with the demographic, clinical, blood tests, and radiological characteristics of the patients., Results: The synovial membrane samples were obtained from 42 patients for IHC, extraction, and purification of RNA for synovial mRNA expression analysis, and serum for measuring protein levels from 38 patients. IHC reactivity for TGF-β1 in the synovial tissue was higher in patients with psoriatic arthritis (p 0.036) and was positively correlated with IL-17 A (r = 0.389, p = 0.012), and Dkk1 (r = 0.388, p = 0.012). Gene expression of the IL-17 A was higher in PsA patients (p = 0.018) and was positively correlated with Dkk1 (r = 0.424, p = 0.022) and negatively correlated with BMP2 (r = -0.396, p = 0.033) and BMP4 (r = -0.472, p = 0.010). It was observed that IHC reactivity for TGF-β1 was higher in patients with erosive PsA (p = 0.024)., Conclusions: The IHC reactivity of TGF-β1 in synovial tissue was higher in patients with erosive psoriatic arthritis, and TGF-β1 was in relation to higher levels of gene expression of IL-17 A and Dkk1., (© 2023. The Author(s).)

Analogues of palytoxin (PLTX), one of the most potent marine biotoxins, are produced by some species of the marine dinoflagellates of the genus Ostreopsis . The proliferation of these species in different coastal zones represents a potential threat of seafood poisoning in humans because the produced toxins can be transferred through marine food webs. Thus, the determination of the concentration of PLTX analogues (ovatoxins-OVTXs, ostreocins-OSTs and isobaric PLTX) in different matrices (seawater, marine fauna, etc. ) is necessary to protect human health. This study is addressed to overcome some of the challenges that the chemical complexity of these molecules poses to their quantification by ultra-high-performance liquid chromatography high-resolution mass spectrometry-based techniques (UHPLC-HRMS). In particular, the mass spectra of the palytoxin analogues show the presence of a large number of ions (including mono- and multiply charged ions) whose nature, relative abundances and behavior can lead to quantitation errors if the correct ions are not selected. In this work, the variability of the PLTX and OVTX profiles under different instrument conditions, including the use of diverse electrospray generation sources and different quantitation methods, is studied. Moreover, the extraction protocol in seawater containing Ostreopsis sp. ovata cells is also evaluated. The use of a heated electrospray operating at 350 °C and a quantitative method including ions from different multiply charged species provides a more robust and reliable method for overcoming the problems due to the variability in the toxin's mass spectrum profile. A single MeOH : H 2 O (80 : 20, v/v) extraction is proposed as the best and reliable procedure. The overall method proposed was applied to quantify OVTXs (-a to -g) and iso-PLTX along the 2019 Ostreopsis cf. ovata bloom. The cells contained a total toxin concentration of up to 20.39 pg per cell.

A new species of Liotyphlops Peters, 1881, Liotyphlopspalauophis sp. nov. , is described from the neighborhoods of Bogota, Colombia from a previous syntype of L.anops , and a lectotype is designated for the latter species. The new species is readily distinguished from congeners by having the frontal scale divided (vs single), and a central foramen in the parabasisphenoid (vs foramen absent). High-resolution x-ray computed tomography (HRXCT) was used to study and present data on the skull of the holotype of the new species, the lectotype of L.anops , and the holotype of L.ternetzii . Additionally, extensive study of skull characters and external morphology failed to find diagnostic characters to differentiate L.beui and L.ternetzii , and the former is here considered a junior synonym of L.ternetzii , which is also redescribed., (Fidélis Júnio Marra Santos.)

Introduction: This study aimed to compare athletes practicing exercise in different environments with non-active young and elderly men and women regarding bone mineral density (BMD), hypothesizing that BMD values differ between athletes according to the environment of exercise practice, but those training in a low-gravitational environment have no different stimuli to BMD increasing if compared with healthy peers experiencing reduced exercise involvement, whatever the age group and sex., Materials and Methods: 104 participants of both sexes were selected according to the environment of exercise practice [swimmers (N = 26) and judo fighters (N = 26)], and exercise level of involvement [non-active young (N = 26) and older adults (N = 26)]. Dual-energy X-ray absorptiometry provided BMD, lean mass, and fat mass (FM) for the whole body (WB), upper (UL), and lower limbs (LL)., Results: For the BMD in WB, UL and LL no effects of group and sex were observed (p > 0.05). Post-hoc analyses detected higher values of BMD in UL for female swimmers compared to non-active older adults (p < 0.05), while judo fighters showed higher BMD in WB, UL, and LL than other participants whatever the sex (p < 0.01). Lower FM was observed for WB, UL, and LL when swimmers and judo fighters were compared to non-active young and older female peers (p < 0.01)., Conclusion: The findings emphasized that BMD stimuli with swimming are reduced when compared to judo, and despite the stimuli in swimming is not distinguishable from that affecting BMD in WB, UL and LL of non-active young, it is effective in differing BMD in UL among non-active older for women., (© 2022. The Japanese Society Bone and Mineral Research.)

Resistance training (RT) has been considered an intervention with effective stimulus on bone mineral formation and is, therefore, recommended to decrease the rate of bone morpho-functional proprieties loss with aging. Thus, this meta-analysis aimed to analyze the effectiveness of RT protocols in promoting changes in bone mineral density (BMD) in older adults. The systematic reviews and meta-analysis followed the PRISMA guidelines (PROSPERO CRD42020170859). The searches were performed in the electronic databases using descriptors according to the PICO strategy. The methodological quality and risk of bias were assessed with the PEDro scale, and the magnitude of the results was determined by Hedges' g. Seven studies involving 370 elderlies, with the RT planned as a unique exercise mode of intervention, showed designs with four to five exercises for upper- and lower-limbs musculature, two to three sets per exercise, eight to twelve repetitions to failure at 70-90% 1 RM, 60-120 s of rest between sets, and executed three times per week for 12-52 weeks. The RT protocols were classified between good and excellent and evidenced a positive effect on the BMD at the hip (0.64%) and spine (0.62%) but not in the femoral neck (-0.22%) regardless of the intervention length. The narrow range of either positive or negative changes in the BMD after the RT intervention support, at best, a preventive effect against the increasing risk of bone frailty in an older population, which is evident beyond 12 weeks of RT practice engagement.

The cycling literature is filled with reports of electromyography (EMG) analyses for a better understanding of muscle function during cycling. This research is not just limited to performance, as the cyclist’s goal may be rehabilitation, recreation, or competition, so a bicycle that meets the rider’s needs is essential for a more efficient muscular activity. Therefore, the purpose of this study was to understand the contribution of the activity of each of the following muscles: TD (trapezius descending), LD (latissimus dorsi), GM (gluteus maximus), and AD (anterior deltoid) in response to different bicycle-rider systems (handlebar height; bicycle frame length) and intensities in a bicycle equipped with a potentiometer. Surface EMG signals from muscles on the right side of the body were measured. A general linear model test was used to analyze the differences between muscle activation in the test conditions. Effect sizes were calculated using a partial Eta2 (η2). The level of significance was set at 0.05. Muscle activation of different muscles differs, depending on the cycling condition (Pillai’s trace = 2.487; F (36.69) = 9.300; p < 0.001. η2 = 0.958), mostly during low intensities. In high intensities, one specific pattern emerges, with a greater contribution of GM and TD and weaker participation of LD and AD, enhancing the cycling power output.

In this work, paper spray (PS) is combined with atmospheric pressure photoionization-mass spectrometry (PS-APPI-MS) for the determination of non-polar and low polar compounds, such as the neutral per- and polyfluorinated alkyl substances (PFAS). The proposed PS-APPI-MS method has been developed for the analysis of fluorotelomer alcohols (FTOHs), fluoroctanesulfonamides (FOSAs) and fluorooctane sulfonamido-ethanols (FOSEs), using both negative ion mode and high-resolution mass spectrometry (HRMS). The most critical working parameters (i.e., UV-krypton lamp position, sample drying time, spray dopant solvent and spray voltage) have been evaluated to study both the ionization behaviour and ionization efficiency. The best results were achieved using dopant-assisted PS-APPI-HRMS with toluene as dopant solvent. The most intense ions observed in the mass spectra, [M‒H] ‒ for FOSAs and [M+O 2 ] ‒• for FTOHs and FOSEs, were selected and proposed for fast screening and quantitative analysis of target compounds in waterproof impregnation sprays samples using internal standard calibration method and being able to detect down to μg L -1 levels. The satisfactory values of the method quality parameters (detection capability, repeatability, trueness and linearity) demonstrated the good performance of the PS-APPI-HRMS method and allowed the identification and quantitation of some FTOHs (6:2 FTOH, 7-Me-6:2 FTOH, 8:2 FTOH, 10:2 FTOH) and N-MeFOSE at mg L -1 in some of the waterproof impregnation spray products analyzed. This low-cost PS-APPI-HRMS method allows a fast screening, with minimum sample preparation, of non-polar and low polar compounds simultaneously, which can significantly improve the throughput on routine laboratories., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

This work describes the development of an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of 23 primary aromatic amines (PAAs) that can potentially migrate from food contact materials. The chromatographic separation was performed in a pentafluorophenylpropyl (PFPP) column achieving the separation of all PAAs in less than 6.5 min using water to acetonitrile (0.1% acetic acid in both solvents) as mobile phase and a gradient elution. The feasibility of atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) was evaluated as alternative to electrospray ionization (ESI) for the analysis of PAAs. Results showed that for most of the compounds, better responses were obtained with APCI, which shows the advantage of being less susceptible to matrix effects. Tandem mass spectrometry (MS/MS) fragmentation studies of [M + H] + allowed for the selection of the two most characteristic and abundant product ions of the 23 PAAs which led to the development of a selective and sensitive UHPLC-APCI-MS/MS method with limits of detection ranging from 0.2 to 2 μg kg -1 . Moreover, intra-day and inter-day precisions of the method in terms of relative standard deviation (RSD%) were lower than 10% and 15%, while trueness as relative error was <15% for most of the compounds. The UHPLC-APCI-MS/MS method was applied to the analysis of twenty black Nylon kitchenware samples that were submitted to migration tests using food simulant B (3% acetic acid, w/v), and the presence of PAAs were detected in eighteen samples at concentrations above the legislated limit (2 μg kg -1 of food or food simulants)., (© 2022. The Author(s).)

This study aimed to analyze whether the relationship between regional and whole-body fat-free mass (FFM) and strength is related to FFM distribution and area according to limb involvement. Thirty well-trained male young adults underwent one-repetition maximum test (1RM) to assess the strength in arm curl (AC), bench press (BP), seated row (SR), leg press 45° (LP45), knee extension (KE), and leg curl (LC). Dual-energy X-ray absorptiometry was used to evaluate FFM. The values for 1RM in AC, BP, and R correlated to FFM in upper limb (R 2 = 0.69, 0.84 and 0.75), without an effect of appendicular mass index (API) or area. For 1RM in KE, the correlation with FFM in lower limb increased with thigh area (R 2 = 0.56), whereas 1RM in LC and LP45 correlation to whole-body FFM increased with API (R 2 = 0.64 and 0.49). The upper limb's FFM may be reliable for indexing the arms and upper trunk strengths, whereas the relationships between FFM and strength in lower limb improve as muscle mass and thigh area increases between subjects.

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in ABCD1 , which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the disease is particularly devastating. Early diagnosis and intervention improve outcomes. Because newborn screening facilitates identification of at-risk individuals during their asymptomatic period, X-ALD was added to the Pennsylvania newborn screening program in 2017. We analyzed outcomes from the first four years of X-ALD newborn screening, which employed a two-tier approach and reflexive ABCD1 sequencing. There were 51 positive screens with elevated C26:0-lysophosphatidylcholine on second-tier screening. ABCD1 sequencing identified 21 hemizygous males and 24 heterozygous females, and clinical follow up identified four patients with peroxisomal biogenesis disorders. There were two false-positive cases and one false-negative case. Three unscreened individuals, two of whom were symptomatic, were diagnosed following their young siblings' newborn screening results. Combined with experiences from six other states, this suggests a U.S. incidence of roughly 1 in 10,500, higher than had been previously reported. Many of these infants lack a known family history of X-ALD. Together, these data highlight both the achievements and challenges of newborn screening for X-ALD.

Gull eggs are excellent bioindicators of environmental pollution as reflect the contamination levels of coastal areas, especially of persistent and bioacumulative compounds such as perfluoroalkyl substances (PFAS). This study aims to evaluate the geographical distribution and 10-year temporal trends (2009-2018) of 17 PFAS in eggs of two gull species (Larus michahellis and Larus audouinii) from 5 main Spanish colonies. ∑PFAS ranged from 13.7 ± 5.9 to 164 ± 17 ng g -1 wet weight and higher concentrations were observed in L. audouinii than in L. michahellis. Perfluorooctane sulfonate (PFOS) was the predominant compound in all samples, followed by perfluoroundecanoic acid (PFUnA) and perfluorotridecanoic acid (PFTriDA). Perfluorododecanoic acid (PFDoA), perfluorodecanoic acid (PFDA) and perfluorooctanoic acid (PFNA) were also found in all studied areas but at lower concentrations, while perfluorooctanoic acid (PFOA) was only detected in the Medes Islands. Principal Component Analysis revealed the co-occurrence of the 6 detected PFAS, and differentiated samples from Ebro Delta and Medes Islands, both located in the North-Eastern Mediterranean Sea, with high contribution of all PFAS, from Chafarinas and Atlantic Islands with lower concentration levels and variability. Also, different patterns were observed among colonies, suggesting the fish-based diet plays an important role in PFAS bioaccumulation. In all colonies, except for the Medes Islands, ∑PFAS decreased through the 10-year study period, with PFOS, PFUnA, and PFTriDA showing a significant concentration reduction in a colony-specific manner. This study demonstrates the usefulness and importance of continuous systematic long-term monitoring to determine the geographical distribution and temporal variations of PFAS in marine protected areas using gull eggs as bioindicators of environmental pollution., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hi-C enables the characterization of the 0conformation of the genome in the three-dimensional nuclear space. This technique has revolutionized our ability to detect interactions between linearly distant genomic sites on a genome-wide scale. Here, we detail a protocol to carry out in situ Hi-C in plants and describe a straightforward bioinformatics pipeline for the analysis of such data, in particular for comparing samples from different organs or conditions., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The bosonic analogs of topological insulators have been proposed in numerous theoretical works, but their experimental realization is still very rare, especially for spin systems. Recently, two-dimensional (2D) honeycomb van der Waals ferromagnets have emerged as a new platform for topological spin excitations. Here, via a comprehensive inelastic neutron scattering study and theoretical analysis of the spin-wave excitations, we report the realization of topological magnon insulators in CrXTe 3 (X = Si, Ge) compounds. The nontrivial nature and intrinsic tunability of the gap opening at the magnon band-crossing Dirac points are confirmed, while the emergence of the corresponding in-gap topological edge states is demonstrated theoretically. The realization of topological magnon insulators with intrinsic gap-unability in this class of remarkable 2D materials will undoubtedly lead to new and fascinating technological applications in the domain of magnonics and topological spintronics.

In this work, a new gas chromatography-high-resolution mass spectrometry (GC-HRMS) method based on atmospheric pressure photoionisation (APPI) has been developed for the accurate determination of short-chain chlorinated paraffins (SCCPs) as a reliable alternative to the established methods. To the best of our knowledge, this is the first time these compounds has been analysed by GC-MS using atmospheric pressure photoionisation (APPI). Efficient ionisation of SCCPs was achieved using the new GC-APPI source by the formation of [M+Cl] - adduct ions in negative ion mode using dopant-assisted APPI with a mixture of acetone/CCl 4 (3:1, v/v). Operating at a resolution of 70,000 FWHM (full width at half maximum) and monitoring the [M+Cl] - adduct ions for each congener group, a selective determination of the SCCPs was achieved, avoiding isobaric interferences between homologue groups with different carbon chain length and chlorination degree. Moreover, the GC-APPI-HRMS response of each congener group was mainly influenced by its concentration and did not depend on the number of chlorine atoms in the molecule as occurs with the GC-MS methods based on the electron-capture negative ionisation (ECNI). Thus, the contribution of the different carbon and chlorine homologue groups in the SCCP mixtures was determined by the internal normalization method, and the quantification was performed independently of the chlorine content of the SCCP standard mixture employed. The developed GC-APPI-HRMS method offers some interesting advantages over the existing methods, particularly the possibility to quantify individual SCCP congener groups, the use of a simple calibration method for quantification, and an important time-saving in the data processing, especially over ECNI-based traditional methods. The GC-APPI-HRMS method allowed the determination of SCCPs at low concentration levels in fish samples with low method limits of detection (17-34 pg g -1 wet weight for total SCCPs), good precision (RSD < 7%) and trueness (relative error < 8%) and can be proposed as a reliable alternative of the established methods for the determination of these pollutants in environmental samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study sought to evaluate the training load in different age category soccer players associated with distinct pitch size small-sided games (SSGs). Twenty-four soccer players (eight in each age category: U-12, U-15, and U-23) performed three consecutive 4 vs. 4 ball possession SSGs (SSG1: 16 × 24 m; SSG2: 20 × 30 m; and SSG3: 24 × 36 m) all with 3 min duration and 3 min rest. Subjects carried ultra-wideband-based position-tracking system devices (WIMU PRO, RealTrack System). Total distance covered increased from SSG1 to SSG3 in all age categories and predominantly in running speeds below 12 km·h -1 . Moreover, distance covered in 12-18 km·h -1 running speed was different in all performed SSGs and age categories. Residual or null values were observed at 18-21 km·h -1 or above running speed, namely in U-12, the only age category where metabolic power and high metabolic load distance differences occurred throughout the performed SSGs. Edwards' TRIMP differences between age categories was only observed in SSG2 (U-12 < U-15). The design of SSGs must consider that the training load of the players differs according to their age category and metabolic assessment should be considered in parallel to external load evaluation in SSGs. Wearable technology represents a fundamental support in soccer.

Purpose: Diffuse leptomeningeal glioneuronal tumour (DLGT) is an infrequent entity. Diagnosis is made with biopsy but with so few cases described management, prognosis remains undefined. There are not currently any articles regarding most effective place to biopsy., Methods: Current literature review and introduction of the case of a 3-year-old male presenting at the emergency room with irritability, vomiting and nuchal rigidity. A head CT was made showing tetraventricular enlargement and a posterior fossa cyst., Results: Patient underwent urgent ventriculoperitoneal shunting surgery with complete symptomp resolution. Brain MRI showed diffuse leptomeningeal enhancing, predominantly in basal cisterns, and multiple cystic-solid lesions along the neural axis. After ruling other conditions, a biopsy among intraoperative samples, was obtained of a PET positive gadolinium spinal enhancing lesion at D8 level, with the final diagnosis of DLGT., Conclusion: DLGT can present as acute hydrocephalus. Biopsy stablishes the diagnosis but the place to take the sample can be difficult to select. Our experience suggests that PET-CT and intraoperative biopsy analysis can improve the effectivity of a representative sample.

This study analyzed whether 100- and 200-m interval training (IT) in swimming differed regarding temporal, perceptual, and physiological responses. The IT was performed at maximal aerobic velocity (MAV) until exhaustion and time spent near to maximalVO 2 peak oxygen uptake (⩒O 2 peak), total time limit (t Lim ), peak blood lactate [La - ] peak, ⩒O 2 kinetics (⩒O 2 K), and rate of perceived exertion (RPE) were compared between protocols. Twelve swimmers (seven males 16.1 ± 1.1 and five females 14.2 ± 1 years) completed a discontinuous incremental step test for the second ventilatory threshold (VT 2 ), ⩒O 2 peak, and MAV assessment. The swimmers subsequently completed two IT protocols at MAV with 100- and 200-m bouts to determine the maximal ⩒O 2 (peak-⩒O 2 ) and time spent ≥VT 2 , 90, and 95% of ⩒O 2 peak for the entire protocols (IT 100 and IT 200 ) and during the first 800-m of each protocol (IT 8x100 and IT 4x200 ). A portable apparatus (K4b 2 ) sampled gas exchange through a snorkel and an underwater led signal controlled the velocity. RPE was also recorded. The Peak-⩒O 2 attained during IT 8x100 and IT 4x200 (57.3 ± 4.9 vs. 57.2 ± 4.6 ml·kg -1 ·min -1 ) were not different between protocols ( p = 0.98) nor to ⩒O 2 peak (59.2 ± 4.2 ml·kg -1 ·min -1 , p = 0.37). The time constant of ⩒O 2 K (24.9 ± 8.4 vs. 25.1 ± 6.3-s, p = 0.67) and [La - ] peak (7.9 ± 3.4 and 8.7 ± 1.5 mmol·L -1 , p = 0.15) also did not differ between IT 100 and IT 200 . The time spent ≥VT 2 , 90, and 95%⩒O 2 peak were also not different between IT 8x100 and IT 4x200 ( p = 0.93, 0.63, and 1.00, respectively). The RPE for IT 8x100 was lower than that for IT 4x200 (7.62 ± 2 vs. 9.5 ± 0.7, p = 0.01). Both protocols are considered suitable for aerobic power enhancement, since ⩒O 2 peak was attained with similar ⩒O 2 K and sustained with no differences in t Lim . However, the fact that only the RPE differed between the IT protocols suggested that coaches should consider that nx100-m/15-s is perceived as less difficult to perform compared with nx200-m/30-s for the first 800-m when managing the best strategy to be implemented for aerobic power training., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Almeida, Pessôa Filho, Espada, Reis, Sancassani, Massini, Santos and Alves.)

This paper reports the development of an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC‒MS/MS) method to determine eight banned dyes (Sudan I-IV, Sudan Orange, Sudan Red 7B, Para Red, Rhodamine B) in turmeric, curry, and chili products. For this purpose, the feasibility of electrospray (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) for the ionization of these compounds was evaluated. The tandem mass spectrometry (MS/MS) fragmentation of all targeted compounds was studied and both multistage mass spectrometry and high-resolution mass spectrometry were used to establish the fragmentation pathways and identify common fragmentation behaviors. Among the most significant ions, the most characteristic and abundant product ions observed on the triple quadrupole were selected to propose a selective and sensitive UHPLC‒MS/MS method (multiple reaction monitoring mode, MRM) of these target compounds in spices samples after a quick and easy extraction with acetonitrile. Matrix effect (ME) studies carried out in the three atmospheric pressure ionization sources have demonstrated that APCI showed the best performance with ME values ranging from 2 to 25%. Furthermore, the estimated quality parameters indicated the good performance of the proposed method, providing low method limits of detection (MLODs) (1-48 μg kg -1 ), good intra-day precision (RSD % < 15%), and accurate quantitation (relative error % < 15%). Finally, the applicability of the developed method was demonstrated by the analysis of turmeric, curry, and chili products. In total, 36 diverse samples coming from different countries were analyzed and although none of these compounds were detected above the MLODs, the analysis of spiked samples showed that the method was able to detect this family of compounds at low μg kg -1 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

After Candida albicans , Candida glabrata is one of the most common fungal species associated with candidemia in nosocomial infections. Rapid acquisition of nutrients from the host is important for the survival of pathogens which possess the metabolic flexibility to assimilate different carbon and nitrogen compounds. In Saccharomyces cerevisiae , nitrogen assimilation is controlled through a mechanism known as Nitrogen Catabolite Repression (NCR). NCR is coordinated by the action of four GATA factors; two positive regulators, Gat1 and Gln3, and two negative regulators, Gzf3 and Dal80. A mechanism in C. glabrata similar to NCR in S. cerevisiae has not been broadly studied. We previously showed that in C. glabrata , Gln3, and not Gat1, has a major role in nitrogen assimilation as opposed to what has been observed in S. cerevisiae in which both factors regulate NCR-sensitive genes. Here, we expand the knowledge about the role of Gln3 from C. glabrata through the transcriptional analysis of BG14 and gln3Δ strains. Approximately, 53.5% of the detected genes were differentially expressed (DEG). From these DEG, amino acid metabolism and ABC transporters were two of the most enriched KEGG categories in our analysis (Up-DEG and Down-DEG, respectively). Furthermore, a positive role of Gln3 in AAA assimilation was described, as was its role in the transcriptional regulation of ARO8 . Finally, an unexpected negative role of Gln3 in the gene regulation of ABC transporters CDR1 and CDR2 and its associated transcriptional regulator PDR1 was found. This observation was confirmed by a decreased susceptibility of the gln3Δ strain to fluconazole.

Here, a new gas chromatography-atmospheric pressure photoionization-high-resolution mass spectrometry (GC-APPI-HRMS) method combined with selective pressurized liquid extraction (sPLE) has been developed for the selective determination of Dechlorane Plus (DP) and its related compounds in gull egg samples used as a bioindicator of contamination. To the best of our knowledge, this is the first time these compounds have been analyzed by GC-MS using atmospheric pressure photoionization (APPI). Negative ion dopant-assisted APPI using vapors of diethyl ether and a source temperature of 250 °C provided high ionization efficiencies and mass spectra characterized by intense in-source fragment ions as well as the presence of molecular ion and characteristic cluster ions containing oxygen atoms in their chemical structure. This made it possible to improve the selectivity in the determination of these compounds compared to that obtained with traditional GC-MS ion sources. Under optimized conditions, the sPLE GC-APPI-HRMS (Orbitrap) method provided high recoveries (> 91%), good precisions (RSD% < 12%), and low method limits of detection (0.1-3.5 pg g -1 wet weight). The developed methodology has been applied to the determination of DP and related compounds in eggs of two gull species (L. michahellis and L. audouinii) from several Spanish protected areas. The results obtained showed significant differences in the DP concentration profiles in eggs from different gull breeding locations and between gull species of the same protected area. These results demonstrated the good performance of the GC-APPI-HRMS system to achieve a selective and sensitive determination of DP and related compounds in complex environmental samples.

Purpose: Heterozygous pathogenic variants in various FOXP genes cause specific developmental disorders. The phenotype associated with heterozygous variants in FOXP4 has not been previously described., Methods: We assembled a cohort of eight individuals with heterozygous and mostly de novo variants in FOXP4: seven individuals with six different missense variants and one individual with a frameshift variant. We collected clinical data to delineate the phenotypic spectrum, and used in silico analyses and functional cell-based assays to assess pathogenicity of the variants., Results: We collected clinical data for six individuals: five individuals with a missense variant in the forkhead box DNA-binding domain of FOXP4, and one individual with a truncating variant. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia, cervical spine abnormalities, and ptosis. Luciferase assays showed loss-of-function effects for all these variants, and aberrant subcellular localization patterns were seen in a subset. The remaining two missense variants were located outside the functional domains of FOXP4, and showed transcriptional repressor capacities and localization patterns similar to the wild-type protein., Conclusion: Collectively, our findings show that heterozygous loss-of-function variants in FOXP4 are associated with an autosomal dominant neurodevelopmental disorder with speech/language delays, growth defects, and variable congenital abnormalities.

Aim: To assess the experience with health care among patients with type 2 diabetes (T2DM) and to evaluate patients' demographic variables and healthcare-related characteristics which may affect their experience., Methods: A cross-sectional survey was delivered to T2DM adults. Patient experiences were assessed with the 'Instrument for Evaluation of the Experience of Chronic Patients' (IEXPAC) questionnaire, a validated 12-item survey, which describes patient experience within the last 6 months (items 1-11) and hospitalization in the last 3 years (item 12), with possible scores ranging from 0 (worst) to 10 (best experience)., Results: A total of 451 T2DM patients responded to the survey (response rate 72.3%; mean age 69.5 ± 10.1 years, 67.8% men). The mean overall IEXPAC score was 5.92 ± 1.80. Mean scores were higher for productive interactions (7.92 ± 2.15) and self-management (7.08 ± 2.27) than for new relational model (1.72 ± 2.01). Only 32.8% of patients who had been hospitalized in the past 3 years reported having received a follow-up call or visit after discharge. Multivariate analyses identified that regular follow-up by the same physician and follow-up by a nurse were associated with a better patient experience. Continuity of healthcare score was higher only in those patients requiring help from others., Conclusions: The areas of T2DM care which may need to be addressed to ensure better patient experience are use of the Internet, new technologies and social resources for patient information and interaction with healthcare professionals, closer follow-up after hospitalization, and a comprehensive multidisciplinary approach with regular follow-up by the same physician and a nurse., Competing Interests: DOB received payment for lectures including services on speakers’ bureaus from MSD, Sanofi, Novo Nordisk, Lilly. MJGP has been consultant to Gilead and Janssen, received or have grants pending to Janssen, received payment for lectures including service on speakers’ bureaus from Gilead, Janssen, MSD, AbbVie, received payment for development of educational presentations from MSD, Janssen, Gilead. IMJ has been board membership, consultant and received payment for lectures including service on speakers’ bureaus to AbbVie, Chiesi, FAES Farma, Falk‐Pharma, Ferring, Gebro Pharma, Hospira, Janssen, MSD, Otsuka Pharmaceutical, Pfizer, Shire, Takeda, Tillots and UCB Pharma. AGG, RLR, GF and KFC are full‐time employees at Merck Sharp & Dohme Spain. The other authors declare no conflict of interest related to this manuscript., (© 2021 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)