Switching from immediate- to extended-release cysteamine in patients with nephropathic cystinosis: from clinical trials to clinical practice.

Background: The purpose of this study is to evaluate the effectiveness and safety of switching from immediate-release (IR) to extended-release (ER) cysteamine in patients with nephropathic cystinosis (NC) in Spain. Methods: We conducted an observational, retrospective, multicentre study in NC patients who received IR cysteamine for at least 12 months, switched to ER cysteamine, and received it for at least 6 months before inclusion. Results: Data were collected from nine patients (four children, five adults) 36 months before and after the switch. Despite the highly selected population, an improvement in growth, particularly in children and a significant reduction in hospitalization days was observed. A decrease in halitosis, body odour and gastrointestinal effects was reported in most of the patients who suffered before the switch, and the use of proton pump inhibitors (PPIs) decreased in some patients. The estimated glomerular filtration rate (eGFR) remained stable in patients with preserved kidney function. No significant changes in white blood cell (WBC) cystine levels were observed after the switch. There was no significant difference in the cysteamine dose received. However, some patients were receiving <50% of the recommended dose of cysteamine before and after the switch and showed elevated levels of WBC cystine. Conclusions: Switching from IR to ER cysteamine in clinical practice reduces hospital stays, improves nutritional status and growth in paediatric patients and could help to enhance treatment tolerability by reducing side effects. Furthermore, the dosing of ER cysteamine could promote therapeutic compliance and positively affect the quality of life of the NC population.

Differential effects of attachment security on visual fixation to facial expressions of emotion in 14-month-old infants: an eye-tracking study.

Introduction: Models of attachment and information processing suggest that the attention infants allocate to social information might occur in a schema-driven processing manner according to their attachment pattern. A major source of social information for infants consists of facial expressions of emotion. We tested for differences in attention to facial expressions and emotional discrimination between infants classified as securely attached (B), insecure-avoidant (A), and insecure-resistant (C). Methods: Sixty-one 14-month-old infants participated in the Strange Situation Procedure and an experimental task of Visual Habituation and Visual Paired-Comparison Task (VPC). In the Habituation phase, a Low-Arousal Happy face (habituation face) was presented followed by a VPC task of 6 trials composed of two contrasting emotional faces always involving the same actress: the one used in habituation (trial old face) and a new one (trial new face) portraying changes in valence (Low-Arousal Angry face), arousal (High-Arousal Happy face), or valence + arousal (High-Arousal Angry face). Measures of fixation time (FT) and number of fixations (FC) were obtained for the habituation face, the trial old face, the trial new face, and the difference between the trial old face and the trial new face using an eye-tracking system. Results: We found a higher FT and FC for the trial new face when compared with the trial old face, regardless of the emotional condition (valence, arousal, valence + arousal contrasts), suggesting that 14-month-old infants were able to discriminate different emotional faces. However, this effect differed according to attachment pattern: resistant-attached infants (C) had significantly higher FT and FC for the new face than patterns B and A, indicating they may remain hypervigilant toward emotional change. On the contrary, avoidant infants (A) revealed significantly longer looking times to the trial old face, suggesting overall avoidance of novel expressions and thus less sensitivity to emotional change. Discussion: Overall, these findings corroborate that attachment is associated with infants' social information processing.

Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors.

This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered.

Contemporary practices of Portuguese and Brazilian soccer coaches in designing and applying small-sided games.

This descriptive study aimed to investigate the current practices of Portuguese and Brazilian soccer coaches in the design and implementation of small-sided games (SSGs) in soccer. A total of 187 male coaches participated in the online survey, consisting of 82 Portuguese and 105 Brazilian individuals. These coaches held various positions within the technical staff, with 63 serving as head coaches, 38 as assistant coaches, 38 as physical trainers, and 48 in other roles related to the technical staff. Additionally, the participants represented both youth (n = 102) and adult competitive levels (n = 59), along with some who were not currently associated with a specific group. The survey consisted of 32 questions divided into three main sections: (i) the timing of SSG application, (ii) the methods used for applying SSGs, and (iii) the reasons for applying SSGs. The Chi-square test revealed a statistically significant association between nationality and the frequency of SSGs used in training sessions during the pre-season (p = 0.039) and in-season (p < 0.001). Moreover, significant association between nationality and the time allocated to employing SSGs for targeting aerobic training (p < 0.001) was found. There was a significant association between nationality and the weekly frequency of SSGs use for targeting sprint training (p = 0.019). The Chi-square test identified significant associations between nationality and the use of SSGs for targeting technical training (p = 0.002), as well as for tactical training (p = 0.002). In summary, this study underscores that SSGs are primarily employed to enhance aerobic fitness, change of direction, technical skills, and tactical behaviors. Coaches generally favor employing SSGs two to three times a week, with typical sessions lasting between 16 to 30 minutes. Notably, the major discrepancies between nationalities lie in the importance assigned to the use of SSGs. However, in practice, the formats and objectives for implementing SSGs remain relatively similar.

Higher-order functional connectivity analysis of resting-state functional magnetic resonance imaging data using multivariate cumulants.

Blood-level oxygenation-dependent (BOLD) functional magnetic resonance imaging (fMRI) is the most common modality to study functional connectivity in the human brain. Most research to date has focused on connectivity between pairs of brain regions. However, attention has recently turned towards connectivity involving more than two regions, that is, higher-order connectivity. It is not yet clear how higher-order connectivity can best be quantified. The measures that are currently in use cannot distinguish between pairwise (i.e., second-order) and higher-order connectivity. We show that genuine higher-order connectivity can be quantified by using multivariate cumulants. We explore the use of multivariate cumulants for quantifying higher-order connectivity and the performance of block bootstrapping for statistical inference. In particular, we formulate a generative model for fMRI signals exhibiting higher-order connectivity and use it to assess bias, standard errors, and detection probabilities. Application to resting-state fMRI data from the Human Connectome Project demonstrates that spontaneous fMRI signals are organized into higher-order networks that are distinct from second-order resting-state networks. Application to a clinical cohort of patients with multiple sclerosis further demonstrates that cumulants can be used to classify disease groups and explain behavioral variability. Hence, we present a novel framework to reliably estimate genuine higher-order connectivity in fMRI data which can be used for constructing hyperedges, and finally, which can readily be applied to fMRI data from populations with neuropsychiatric disease or cognitive neuroscientific experiments.

Centrality measures in psychological networks: A simulation study on identifying effective treatment targets.

The network theory of psychopathology suggests that symptoms in a disorder form a network and that identifying central symptoms within this network might be important for an effective and personalized treatment. However, recent evidence has been inconclusive. We analyzed contemporaneous idiographic networks of depression and anxiety symptoms. Two approaches were compared: a cascade-based attack where symptoms were deactivated in decreasing centrality order, and a normal attack where symptoms were deactivated based on original centrality estimates. Results showed that centrality measures significantly affected the attack's magnitude, particularly the number of components and average path length in both normal and cascade attacks. Degree centrality consistently had the highest impact on the network properties. This study emphasizes the importance of considering centrality measures when identifying treatment targets in psychological networks. Further research is needed to better understand the causal relationships and predictive capabilities of centrality measures in personalized treatments for mental disorders.

Autistic traits and event-related potentials in the general population: A scoping review and meta-analysis.

BACKGROUND: Differences in short and long-latency Event-Related Potentials (ERPs) can help us infer abnormalities in brain processing, considering early and later stages of stimuli processing across tasks and conditions. In autism research, the adult population remains largely understudied compared to samples at early stages of development. In this context, this scoping review briefly summarises what has been described in community and subclinical adult samples of autism. METHOD: The current scoping review and meta-analysis includes 50 records (N = 1652) and comprehensively explores short and long-latency ERP amplitudes and their relationship with autistic traits in adult community samples. RESULTS: This meta-analysis identified, with small to medium effect sizes, distinctive patterns in late ERP amplitudes, indicating enhanced responses to visual stimuli and the opposite patterns to auditory tasks in the included sample. Additionally, a pattern of higher amplitudes was also found for the component P3b in autistic traits. DISCUSSION: Differential effects in visual and auditory domains are explored in light of the predictive processing framework for Autism. It remains possible that different brain mechanisms operate to explain symptoms related with different sensory modalities. P3b is discussed as a possible component of interest in future studies as it revealed a more robust effect for differentiating severity in the expression of autistic traits in adulthood.

An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH).

Pathogenic variants in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report a pooled analysis of clinical and laboratory records of 304 individuals from 145 kindreds, including 20 previously unreported HHRH kindreds, in which two novel SLC34A3 pathogenic variants were identified. Compound heterozygous/homozygous carriers show above 90% penetrance for kidney and bone phenotypes. The biochemical phenotype for heterozygous carriers is intermediate with decreased serum phosphate, tubular reabsorption of phosphate (TRP (%)), fibroblast growth factor 23, and intact parathyroid hormone, but increased serum 1,25-dihydroxy vitamin D, and urine calcium excretion causing idiopathic hypercalciuria in 38%, with bone phenotypes still observed in 23% of patients. Oral phosphate supplementation is the current standard of care, which typically normalizes serum phosphate. However, although in more than half of individuals this therapy achieves correction of hypophosphatemia it fails to resolve the other outcomes. The American College of Medical Genetics and Genomics score correlated with functional analysis of frequent SLC34A3 pathogenic variants in vitro and baseline disease severity. The number of mutant alleles and baseline TRP (%) were identified as predictors for kidney and bone phenotypes, baseline TRP (%) furthermore predicted response to therapy. Certain SLC34A3/NPT2c pathogenic variants can be identified with partial responses to therapy, whereas with some overlap, others present only with kidney phenotypes and a third group present only with bone phenotypes. Thus, our report highlights important novel clinical aspects of HHRH and heterozygous carriers, raises awareness to this rare group of disorders and can be a foundation for future studies urgently needed to guide therapy of HHRH.

7.1',8.3'- and 7.3',8.5'-Connected Bicyclo[3.2.1]octanoids and Oxabicyclo[3.2.2]nonane-Type Neolignans from Ocotea aciphylla: Structures and Absolute Configurations.

The phytochemical investigation of the leaves and trunk bark of a specimen of Ocotea aciphylla collected in the southern portion of the Amazon forest led to the isolation of an oxabicyclo[3.2.2]nonane-type neolignan and 15 bicyclo[3.2.1]octanoid neolignans, 14 of which are unreported compounds (2-15), including one with an unusual oxidation pattern of the side chain at C-1' and two rare 7.1',8.3'-connected bicyclo[3.2.1]octanoid derivatives. Their structures and relative configurations were determined by extensive spectrometric analysis based on 1D- and 2D-NMR spectroscopy and HRESIMS data, while their absolute configurations were unambiguously assigned using electronic and vibrational circular dichroism data assisted by density functional theory calculations. Additionally, known sesquiterpenes, phenylpropanoids, and phytosterols were also isolated.

The relationship between pathological brain activity and functional network connectivity in glioma patients.

PURPOSE: Glioma is associated with pathologically high (peri)tumoral brain activity, which relates to faster progression. Functional connectivity is disturbed locally and throughout the entire brain, associating with symptomatology. We, therefore, investigated how local activity and network measures relate to better understand how the intricate relationship between the tumor and the rest of the brain may impact disease and symptom progression. METHODS: We obtained magnetoencephalography in 84 de novo glioma patients and 61 matched healthy controls. The offset of the power spectrum, a proxy of neuronal activity, was calculated for 210 cortical regions. We calculated patients' regional deviations in delta, theta and lower alpha network connectivity as compared to controls, using two network measures: clustering coefficient (local connectivity) and eigenvector centrality (integrative connectivity). We then tested group differences in activity and connectivity between (peri)tumoral, contralateral homologue regions, and the rest of the brain. We also correlated regional offset to connectivity. RESULTS: As expected, patients' (peri)tumoral activity was pathologically high, and patients showed higher clustering and lower centrality than controls. At the group-level, regionally high activity related to high clustering in controls and patients alike. However, within-patient analyses revealed negative associations between regional deviations in brain activity and clustering, such that pathologically high activity coincided with low network clustering, while regions with 'normal' activity levels showed high network clustering. CONCLUSION: Our results indicate that pathological activity and connectivity co-localize in a complex manner in glioma. This insight is relevant to our understanding of disease progression and cognitive symptomatology.

Impact of an active lifestyle on cardiovascular autonomic modulation and oxidative stress in males with overweight and parental history of hypertension.

Family history of hypertension is associated with early autonomic dysfunction and increased oxidative stress. These alterations have been found to be reinforced by the overweight factor. Conversely, an active lifestyle is effective in improving the mechanisms regulating blood pressure control. Hence, we ought to investigate the effects of an active lifestyle on the hemodynamic, autonomic and oxidative stress parameters in individuals carrying both family history of hypertension and overweight risk factors. Fifty-six normotensive males were divided into four groups: eutrophic offspring of normotensive parents (EN, n = 12), eutrophic and inactive with hypertensive parents (EH, n = 14), overweight and inactive with hypertensive parents (OH, n = 13), and overweight and physically active with hypertensive parents (OAH, n = 17). Cardiovascular autonomic modulation was assessed by heart rate (HRV) and blood pressure (BPV) variability indexes. Oxidative stress included pro/antioxidant markers and nitrite concentration. Inactive offspring of hypertensive parents (EH and OH) showed higher LFSBP (vs EN), an indicator of sympathetic outflow to the vasculature and reduced anti-oxidant activity (vs EN), while higher pro-oxidant markers were found exclusively in OH (vs EN and EH). Conversely, the OAH group showed bradycardia, higher vagally-mediated HFabs index (vs OH and EN), lower sympathovagal balance (vs OH) and preserved LFSBP. Yet, the OAH showed preserved pro/antioxidant markers and nitrite levels. Our findings indicates that overweight offspring of hypertensive parents with an active lifestyle have improved hemodynamic, cardiac autonomic modulation and oxidative stress parameters compared to their inactive peers.

Adaptations to infer fitness interdependence promote the evolution of cooperation.

The evolution of cooperation is a major question in the biological and behavioral sciences. While most theoretical studies model cooperation in the context of an isolated interaction (e.g., a Prisoner's Dilemma), humans live in heterogeneous social environments, characterized by large variations in fitness interdependence-the extent to which one's fitness is affected by others. Theoretical and experimental work indicates that humans can infer, and respond to, variations in interdependence. In a heterogeneous ancestral environment, these psychological mechanisms to infer fitness interdependence could have provided a selective advantage, allowing individuals to maximize their fitness by deciding when and with whom to cooperate. Yet, to date, the link between cognitive inference, variation in fitness interdependence, and cooperation remains unclear. Here we introduce a theoretical framework to study the evolution of inference and cooperation in heterogeneous social environments, where individuals experience interactions with varying levels of corresponding interests. Using a combination of evolutionary game theory and agent-based modeling, we model the evolution of adaptive agents, who incur a cost to infer interdependence, in populations of fixed-behavior agents who always cooperate or defect. Our results indicate that natural selection could promote the evolution of psychological mechanisms to infer fitness interdependence, provided that there is enough variation in fitness interdependence to offset the cost of inference. Under certain conditions, the fixation of adaptive agents results in higher levels of cooperation. This depends crucially on the type of inference performed and the features of the interdependence landscape.

The Effects of Pre-Season and Relationships with Physical, Physiological, Body Composition, and Load Markers: A Case Study Comparing Starters versus Non-Starters from an Elite Female Professional Soccer Team.

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.

Seroprevalence of Hantavirus among Manual Cane Cutters and Epidemiological Aspects of HPS in Central Brazil.

Hantavirus pulmonary syndrome (HPS) is a rodent-borne zoonotic disease that is endemic throughout the Americas. Agricultural activities increase exposure to wild rodents, especially for sugarcane cutters. We carried out a survey of the epidemiological aspects of HPS and investigated the prevalence of hantavirus infection in the sugarcane cutter population from different localities in the Brazilian Midwest region. We conducted a retrospective study of all confirmed HPS cases in the state of Goiás reported to the National HPS surveillance system between 2007 and 2017, along with a seroepidemiological study in a population of sugarcane cutters working in Goiás state in 2016, using the anti-hantavirus (Andes) ELISA IgG. A total of 634 serum samples from cane cutters were tested for hantavirus antibodies, with 44 (6.9%) being IgG-reactive according to ELISA. The destination of garbage was the only statistically significant variable (p = 0.03) related to the detection of hantavirus IgG (p < 0.05). We described the epidemiological profile of reported hantavirus cases in Goiás-a highly endemic area for HPS, and where the seroepidemiological study was conducted. Our results increase our knowledge about hantavirus infections in Brazil and highlight the vulnerability of sugarcane cutters to a highly lethal disease that, to date, has no specific treatment or vaccination.

Development of New Hybrid Composites for High-Temperature Applications.

Nowadays, in the automation and aircraft industries, there is a challenge in minimizing the weight of components of vehicles without losing the original properties. In this study, we fabricate hybrid composites based on fiber metal laminates; these materials could be promising composites for high-performance applications. This work is focused on analyzing the effect of high temperature (175 °C) on the mechanical properties of these kind of materials, by introducing NaOH and silane adhesion treatments between metal and prepreg layers and by using vacuum molding processes. Fabricated FML (NaOH treatment) shows a significant improvement in tensile strength in comparison with the ARALL and GLARE reported by ESA. Moreover, developed FMLs at 175 °C kept more than 70% of their tensile strength and modulus and kept 4% of tensile strain at room temperature. The prominent conclusion achieved in this work has been that excellent candidates have been obtained for a wide range of applications, including but not limited to space and aerospace applications.

Amplitude modulation of the contingent negative variation in psychopathy: A systematic review and meta-analysis.

The CNV is analyzed in tasks related to EEG studies, often with participants presenting psychopathic personality traits. A systematic search of the literature was conducted, to solve some inconsistencies regarding CNV amplitude modulation by psychopathy. Nine studies (N = 317) were retrieved for analysis. Three meta-analyses were run - CNV, iCNV, tCNV. A qualitative analysis - reporting CNV amplitudes modulated by psychopathy dimensional features - was also featured. Overall effects for CNV and iCNV were not significant. Larger tCNV amplitudes were found in participants reporting higher psychopathy traits, g = -0.58, 95% CI [- 0.94, - 0.22]. These findings were surprising when confronted with previous assumptions in the literature, especially considering that no significant heterogeneity between studies was found. Neither of the studies' characteristics was a significant moderator. Findings require the need to discuss key differences between adaptive/(mal)adjustment patterns in participants presenting psychopathic traits. Future studies dissociating iCNV and tCNV modulation by psychopathy, especially in community samples and through a dimensional lens, could help to better understand the construct of psychopathy.

Assessment of the Virulence of the Burkholderia mallei Strain BAC 86/19 in BALB/c Mice.

Burkholderia mallei is an aerobic, Gram-negative, non-motile bacillus. As an obligate mammalian pathogen, it primarily affects solipeds. Although rarely transmitted to humans, the disease it causes, glanders, is classified as a zoonosis. The bacterium was officially eradicated in Brazil in 1969; however, it reemerged after three decades. This study aims to assess the virulence of a specific B. mallei strain, isolated in Brazil, in BALB/c mice through intranasal infection. The strain, B. mallei BAC 86/19, was obtained from the tracheal secretion of a young mare displaying positive serology but no clinical signs of glanders. Post-mortem examinations revealed macroscopic lesions consistent with the disease, however. In mice, the LD50 was determined to be approximately 1.59 × 105 colony-forming units (CFU)/animal. Mice exposed to either 0.1 × LD50 or 1 × LD50 displayed transient weight loss, which resolved after three or five days, respectively. B. mallei persisted within the liver and lung for five days post-infection and in the spleen for seven days. These findings underscore the detectable virulence of the Brazilian B. mallei BAC 86/19 strain in mice, which are relatively resilient hosts. This research points to the importance of the continued investigation of the virulence mechanisms and potential countermeasures associated with B. mallei infections, including their Brazilian isolates.

Positive youth development as a guiding framework in sport research: Is it time to plan for a transition?

Positive youth development is a popular guiding framework for studying the psychosocial development of youth. In sport research, for more than two decades, this framework has enhanced our understanding of the mechanisms involved in successful shifts from youth to adulthood. Nonetheless, scholars have recently taken a more critical stance on the positive youth development framework by elucidating some of its shortcomings. To help determine whether it may be warranted to plan for a transition from the positive youth development framework in sport research, a critical commentary is offered. The purpose of this commentary lies in situating three ontologically distinct arguments that depict the shortcomings of the positive youth development framework, namely the operationalization argument, the social justice argument, and the posthumanist argument. This paper is offered as an open invitation to instigate dialogue on what may come next for youth development in sport research and whether planning for a transition is warranted.