IL-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma.

BACKGROUND: Asthma is often accompanied by type 2 immunity rich in IL-4, IL-5, and IL-13 cytokines produced by TH2 lymphocytes or type 2 innate lymphoid cells (ILC2s). IL-2 family cytokines play a key role in the differentiation, homeostasis, and effector function of innate and adaptive lymphocytes. OBJECTIVE: IL-9 and IL-21 boost activation and proliferation of TH2 and ILC2s, but the relative importance and potential synergism between these γ common chain cytokines are currently unknown. METHODS: Using newly generated antibodies, we inhibited IL-9 and IL-21 alone or in combination in various murine models of asthma. In a translational approach using segmental allergen challenge, we recently described elevated IL-9 levels in human subjects with allergic asthma compared with nonasthmatic controls. Here, we also measured IL-21 in both groups. RESULTS: IL-9 played a central role in controlling innate IL-33-induced lung inflammation by promoting proliferation and activation of ILC2s in an IL-21-independent manner. Conversely, chronic house dust mite-induced airway inflammation, mainly driven by adaptive immunity, was solely dependent on IL-21, which controlled TH2 activation, eosinophilia, total serum IgE, and formation of tertiary lymphoid structures. In a model of innate on adaptive immunity driven by papain allergen, a clear synergy was found between both pathways, as combined anti-IL-9 or anti-IL-21 blockade was superior in reducing key asthma features. In human bronchoalveolar lavage samples we measured elevated IL-21 protein within the allergic asthmatic group compared with the allergic control group. We also found increased IL21R transcripts and predicted IL-21 ligand activity in various disease-associated cell subsets. CONCLUSIONS: IL-9 and IL-21 play important and nonredundant roles in allergic asthma by boosting ILC2s and TH2 cells, revealing a dual IL-9 and IL-21 targeting strategy as a new and testable approach.

Density of Sphingosine-1-Phosphate Receptors Is Altered in Cortical Nerve-Terminals of Insulin-Resistant Goto-Kakizaki Rats and Diet-Induced Obese Mice.

Sphingosine-1-phosphate (S1P) is a phosphosphingolipid with pleiotropic biological functions. S1P acts as an intracellular second messenger, as well as extracellular ligand to five G-protein coupled receptors (S1PR1-5). In the brain, S1P regulates neuronal proliferation, apoptosis, synaptic activity and neuroglia activation. Moreover, S1P metabolism alterations have been reported in neurodegenerative disorders. We have previously reported that S1PRs are present in nerve terminals, exhibiting distinct sub-synaptic localization and neuromodulation actions. Since type 2 diabetes (T2D) causes synaptic dysfunction, we hypothesized that S1P signaling is modified in nerve terminals. In this study, we determined the density of S1PRs in cortical synaptosomes from insulin-resistant Goto-Kakizaki (GK) rats and Wistar controls, and from mice fed a high-fat diet (HFD) and low-fat-fed controls. Relative to their controls, GK rats showed similar cortical S1P concentration despite higher S1P levels in plasma, yet lower density of S1PR1, S1PR2 and S1PR4 in nerve-terminal-enriched membranes. HFD-fed mice exhibited increased plasma and cortical concentrations of S1P, and decreased density of S1PR1 and S1PR4. These findings point towards altered S1P signaling in synapses of insulin resistance and diet-induced obesity models, suggesting a role of S1P signaling in T2D-associated synaptic dysfunction.

Resequencing of Brazilian locally adapted cattle breeds revealed variants in candidate genes and transcription factors for meat fatty acid profile.

The beef cattle industry has experienced a shift driven by a market demand for healthier meat, cost efficiency and environmental sustainability in recent years. Consequently, there has been a growing focus on the fatty acids content and functions of meat in cattle breeding programmes. Besides, a deeper understanding of the biological mechanisms influencing the expression of different phenotypes related to fatty acid profiles is crucial. In this study, we aimed to identify Single-Nucleotide Variants (SNV) and Insertion/Deletion (InDels) DNA variants in candidate genes related to fatty acid profiles described in genomic, transcriptomic and proteomic studies conducted in beef cattle breeds. Utilizing whole-genome re-sequencing data from Brazilian locally adapted bovine breeds, namely Caracu and Pantaneiro, we identified SNVs and InDels associated with 23,947 genes. From these, we identified 318 candidate genes related to fatty acid profiles that contain variants. Subsequently, we select only genes with SNVs and InDels in their promoter, 5' UTR and coding region. Through the gene-biological process network, approximately 19 genes were highlighted. Furthermore, considering the studied trait and a literature review, we selected the main transcription factors (TF). Functional analysis via gene-TF network allowed us to identify the 30 most likely candidate genes for meat fatty acid profile in cattle. LIPE, MFSD2A and SREBF1 genes were highlighted in networks due to their biological importance. Further dissection of these genes revealed 15 new variants found in promoter regions of Caracu and Pantaneiro sequences. The gene networks facilitated a better functional understanding of genes and TF, enabling the identification of variants potentially related to the expression of candidate genes for meat fatty acid profiles in cattle.

Active biloma and the use of hepatobiliary specific MR contrast agent.

We present a case of a woman in her 70s, with right upper quadrant pain and jaundice, who underwent laparoscopic cholecystectomy 14 days, previously. The ultrasound and computer tomography scan revealed a fluid lesion in the gallbladder fossa with intrahepatic extension. At this point a wide differential diagnosis was possible. In order to reach a definitive diagnosis, a magnetic resonance imaging exam with a biliary excretion contrast agent - gadoxetate disodium (hepatobiliary specific paramagnetic gadolinium-based contrast) was obtained, which showed a lesion with delayed, but important contrast enhancement, 4 hours after contrast injection, demonstrating leaking of bile reaching the final diagnosis of biloma. Our patient was successfully treated with ultrasound-guided percutaneous drainage.

Futile therapeutic nursing interventions in adult intensive care: A descriptive study.

Background: Despite the progress made in recent decades on the phenomenon of futility in adult intensive care, recognizing it during clinical care practice remains a complex and sensitive process, during which questions are often raised for which concrete answers are difficult to find. Aims: To analyze the frequency with which futile nursing interventions are implemented in critically ill patients admitted to adult intensive care in specific situations and how often futile autonomous and interdependent nursing interventions are implemented in the same population, as perceived by adult intensive care nurses. Research design: Cross-sectional, quantitative, and descriptive study, which employed a questionnaire constructed specifically for this research to assess the perception of therapeutic futility in nursing in adult intensive care. Following an evaluation of the psychometric properties, the questionnaire was made available in an electronic format on the EUSurvey platform between August and October 2024. The data was analyzed between November 2023 and March 2024 using the statistical software packages SPSS and R. Participants and research context: A simple random sample of nurses working in level II and level III intensive care units in Portugal. Ethical considerations: Research ethical approvals were obtained, and the participants provided informed consent. Findings/results: Four hundred and fourteen valid questionnaires were obtained. The results allow the identification of thirty-three statistically significant associations, the inference of intervals for the mean and median for the perception of futility of nursing interventions with a 95% confidence interval, and enable the hierarchization of nursing interventions implemented in critically ill patients admitted to adult intensive care units according to the nurses' perception of their futility. Conclusion: There is a balance in nurses' perception of the futility of their interventions in the specific situations analyzed. There is statistically significant evidence that interdependent nursing interventions are, in general, more frequently perceived as futile when compared to autonomous nursing interventions.

Exploring Limit Cycles of Differential Equations through Information Geometry Unveils the Solution to Hilbert's 16th Problem.

The detection of limit cycles of differential equations poses a challenge due to the type of the nonlinear system, the regime of interest, and the broader context of applicable models. Consequently, attempts to solve Hilbert's sixteenth problem on the maximum number of limit cycles of polynomial differential equations have been uniformly unsuccessful due to failing results and their lack of consistency. Here, the answer to this problem is finally obtained through information geometry, in which the Riemannian metrical structure of the parameter space of differential equations is investigated with the aid of the Fisher information metric and its scalar curvature R. We find that the total number of divergences of |R| to infinity provides the maximum number of limit cycles of differential equations. Additionally, we demonstrate that real polynomial systems of degree n≥2 have the maximum number of 2(n-1)(4(n-1)-2) limit cycles. The research findings highlight the effectiveness of geometric methods in analyzing complex systems and offer valuable insights across information theory, applied mathematics, and nonlinear dynamics. These insights may pave the way for advancements in differential equations, presenting exciting opportunities for future developments.

Evaluating performance on the Glittre-ADL test in men with long COVID 3 years after a SARS-CoV-2 infection.

Background/objective: Many COVID-19 survivors, especially those who have been hospitalized, have been suffering numerous complications that limit their activities of daily living, although changes that persist 3 years after infection are still not known. We aimed to investigate the impact of long COVID on the Glittre-ADL test (TGlittre) 3 years after acute infection in men who needed hospitalization and explore whether the performance on the TGlittre is associated with impairments in lung function, muscle strength, physical function and quality of life (QoL). Methods: Cross-sectional study with 42 men with long COVID who took the TGlittre. They underwent pulmonary function tests and measurements of handgrip strength and quadriceps strength (QS). Additionally, they also completed the Saint George Respiratory Questionnaire (SGRQ) and Functional Independence Measure (FIM). Results: The mean age was 52 ± 10.6 years, while the mean time after diagnosis of COVID-19 was 37 ± 3.5 months. The mean TGlittre time was 3.3 (3.1-4.1) min, which was 10% greater than the time expected for normal individuals to complete it. The TGlittre time was correlated significantly with the QS (rs = -0.397, p = 0.009), pulmonary diffusion (rs = - 0.364, p = 0.017), FIM (rs = -0.364, p = 0.017) and the "activity" domain score of the SGRQ (rs = 0.327, p = 0.034). Conclusion: Functional capacity on exertion as measured by the TGlittre time is normal in most men with long COVID 3 years after hospitalization. However, this improvement in functional capacity does not seem to be reflected in muscle strength or QoL, requiring continued monitoring even after 3 years.

Effects of different ischemic pressures on bar velocity during the bench press exercise: A randomized crossover trial.

The main objective of this study was to evaluate the effects of different ischemic pressures applied during rest intervals on bar velocity during the bench press exercise. 10 resistance-trained males (age = 23.2 ± 2.7 years; body mass = 83.9 ± 9 kg; body height = 181 ± 5.2 cm; bench press 1 repetition maximum (1RM) = 125 ± 16.4 kg; training experience = 5.4 ± 3.4 years) participated in the study. During 4 experimental sessions, following a randomized crossover design, the subjects performed 5 sets of 3 repetitions of the bench press exercise with a load of 60% 1RM under conditions: with ischemia (50% or 80% of arterial occlusion pressure), with SHAM ischemia (20 mmHg) and without ischemia (control condition). For the ischemic conditions cuffs were applied before each set for 6.5 min and released 30 s before the start of the set as reperfusion (6.5 min ischemia + 0.5 min reperfusion). In the control condition, ischemia was not applied. The two-way repeated measures ANOVA showed no significant condition × set interaction for mean bar velocity (MV; p = 0.17) and peak bar velocity (PV; p = 0.66). There was also no main effect of condition for MV (p = 0.58) and PV (p = 0.61). The results indicate that ischemic or SHAM treatment (6.5 minutes ischemia or SHAM + 30 s reperfusion) does not affect mean and peak bar velocity during the bench press exercise regardless of the applied pressure.

Taurine and N-acetylcysteine treatments prevent memory impairment and metabolite profile alterations in the hippocampus of high-fat diet-fed female mice.

Background: Obesity constitutes a risk factor for cognitive impairment. In rodent models, long-term exposure to obesogenic diets leads to hippocampal taurine accumulation. Since taurine has putative cyto-protective effects, hippocampal taurine accumulation in obese and diabetic models might constitute a counteracting response to metabolic stress. Objective: We tested the hypothesis that treatment with taurine or with N-acetylcysteine (NAC), which provides cysteine for the synthesis of taurine and glutathione, prevent high-fat diet (HFD)-associated hippocampal alterations and memory impairment. Methods: Female mice were fed either a regular diet or HFD. Some mice had access to 3%(w/v) taurine or 3%(w/v) NAC in the drinking water. After 2 months, magnetic resonance spectroscopy (MRS) was used to measure metabolite profiles. Memory was assessed in novel object and novel location recognition tests. Results: HFD feeding caused memory impairment in both tests, and reduced concentration of lactate, phosphocreatine-to-creatine ratio, and the neuronal marker N-acetylaspartate in the hippocampus. Taurine and NAC prevented HFD-induced memory impairment and N-acetylaspartate reduction. NAC, but not taurine, prevented the reduction of lactate and phosphocreatine-to-creatine ratio. MRS revealed NAC/taurine-induced increase of hippocampal glutamate and GABA levels. Conclusion: NAC and taurine can prevent memory impairment, while only NAC prevents alterations of metabolite concentrations in HFD-exposed female mice.

Acute Responses in Blood Flow Restriction Low-intensity Aerobic Training: A Meta-analysis.

The purpose was to determine the effect low-intensity training with blood flow restriction (LI-BFR) versus high-intensity aerobic training (HIT) on acute physiological and perceptual responses. The Cumulative Index to Nursing and Allied Health Literature, National Library of Medicine, Scopus, SPORTDiscus and Web of Science databases and the reference list of eligible studies were consulted to identify randomized experimental studies, published until July 4, 2022, that analyzed physiological or perceptual responses between LI-BFR versus HIT in healthy young individuals. Mean difference (MD) and standardized mean difference (SMD) were used as effect estimates and random effects models were applied in all analyses. Twelve studies were included in this review. During exercise sessions, HIT promoted higher values of heart rate (MD=28.9 bpm; p<0.00001; I 2 =79%), oxygen consumption (SMD=4.01; p<0.00001; I 2 =83%), ventilation (MD=48.03 l/min; p=0.0001; I 2 =97%), effort (SMD=1.54; p=0.003; I 2 =90%) and blood lactate (MD=3.85 mmol/L; p=0.002; I 2 =97%). Perception of pain/discomfort was lower in HIT (SMD=-1.71; p=0.04; I 2 =77.5%). In conclusion, LI-BFR promotes less pronounced physiological responses than HIT but with greater perception of pain.

Plasma Galectin-4 Levels Are Increased after Stroke in Mice and Humans.

Epidemiological studies have associated plasma galectin-4 (Gal-4) levels with prevalent and incident diabetes, and with an increased risk of coronary artery disease. To date, data regarding possible associations between plasma Gal-4 and stroke are lacking. Using linear and logistic regression analyses, we tested Gal-4 association with prevalent stroke in a population-based cohort. Additionally, in mice fed a high-fat diet (HFD), we investigated whether plasma Gal-4 increases in response to ischemic stroke. Plasma Gal-4 was higher in subjects with prevalent ischemic stroke, and was associated with prevalent ischemic stroke (odds ratio 1.52; 95% confidence interval 1.01-2.30; p = 0.048) adjusted for age, sex, and covariates of cardiometabolic health. Plasma Gal-4 increased after experimental stroke in both controls and HFD-fed mice. HFD exposure was devoid of impact on Gal-4 levels. This study demonstrates higher plasma Gal-4 levels in both experimental stroke and in humans that experienced ischemic stroke.

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

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

Variations in the compartmental location of the superficial fibular nerve: a cadaveric study with meta-analysis.

PURPOSE: To investigate variations in the course of the superficial fibular nerve (SFN) and its branches-the medial dorsal cutaneous nerve (MDCN) and intermediate dorsal cutaneous nerve (IDCN)-concerning the leg compartments by means of a meta-analysis supplemented with an original anatomical study. MATERIALS AND METHODS: A literature survey was conducted in the PubMed, Scopus, Web of Science, and Lilacs databases on October 14th, 2021, to obtain anatomical data, and the PRISMA statement was adopted as a methodological guideline. We used MetaXL software for data analysis. We classified the anatomical data into three location patterns: in Type 1, the SFN courses through the lateral compartment; in Type 2, the SFN courses through the anterior compartment; in Type 3, the MDCN courses through the anterior compartment and the IDCN courses in the lateral compartment. RESULTS: Twelve studies (n = 837 lower limbs) comprised the current review. The SFN location was normal (Type 1 variation) in 77% (95% CI 72.9-78.9) of the cases, while Type 2 had a pooled prevalence of 14.3% (95% CI 11.1-15.9). Type 3 was the less common course, with a prevalence of 8.7% (95% CI 5.9-9.7). We found differences among the geographical subgroups analyzed. CONCLUSIONS: The SFN courses through the lateral compartment of the leg most times, and the prevalence of this pattern varies significantly between the different geographical subgroups evaluated. These results are of great clinical and surgical relevance.

Branching patterns of the superficial fibular nerve: an anatomical study with meta-analysis.

PURPOSE: To review variations regarding the branching patterns of the superficial fibular nerve (SFN) concerning the deep fascia of leg and to the ankle joint level. METHODS: Searches were conducted in PubMed, Scopus, Lilacs, and Web of Science databases on October 14th, 2021. We followed the PRISMA guidelines to report this review. Articles with data on SFN variations prevalence were included. The data were extracted and pooled into a meta-analysis. We also dissected 60 formalin-fixed Brazilian fetuses (n = 120 lower limbs). RESULTS: Twenty-five studies (n = 1272 lower limbs) comprised this review. Concerning the SFN branching at the deep fascia, Type 1 variation (in which the SFN pierces the fascia as a single nerve trunk) had a pooled prevalence of 86.4% (95% CI 84.5-88.2), while Type 2 had a pooled prevalence of 13.6% (95% CI 11.8-15.5). At the ankle joint level, Type 2 variation (in which the SFN branches off below the joint level) was the most common anatomical pattern, with a pooled prevalence of 78.7% (95% CI 74.5-82.7). CONCLUSION: Typically, the SFN branches off between its exit from the deep fascia and the ankle joint level. The SFN variations have great importance for surgeries, such as arthroscopies and fascia release surgeries, regional anesthesia, and clinical evaluation of SFN entrapment syndrome.

The impact of COVID-19 on air passenger demand and CO2 emissions in Brazil.

This paper estimates the impact of the COVID-19 on air travel demand and emissions in Brazil, the largest aviation market in Latin America. Combining detailed flight data and data on combustion emission factors, we estimate the CO2 emissions of domestic flights. A Bayesian structural time-series model was used to estimate the impact of COVID-19 on daily trends of air travel demand and emissions. The COVID-19 caused a reduction of 68% in national passengers and 63% in total CO2 emissions compared to what would have occurred if the pandemic had not happened. Despite such a sharp drop, fuel efficiency decreased after the COVID-19 outbreak, and passenger demand recovered to 64.2% of pre-pandemic levels by the end of 2020. The fast recovery in domestic flights by December 2020 indicates that the emissions could soon return to pre-pandemic levels, demonstrating the challenges of reducing emissions in the aviation sector in the short term.

Effects of Foot Orthoses on Pain and the Prevention of Lower Limb Injuries in Runners: Systematic Review and Meta-Analysis.

CONTEXT: A variety of approaches have been proposed to prevent lower limb injuries in runners. However, the evidence for the effectiveness of interventions to reduce lower limb pain and injury after intensive running is very weak. OBJECTIVE: The authors performed a systematic review to investigate the effects of foot orthoses on pain and the prevention of lower limb injuries in runners. EVIDENCE ACQUISITION: The authors searched the MEDLINE/PubMed, Physiotherapy Evidence Database, Scielo, and Cochrane Central (from inception to February 2022) databases for randomized controlled trials that evaluated the effects of foot orthoses in runners. The authors then calculated mean differences and 95% confidence intervals from these trials. Heterogeneity was assessed using the I2 test. Furthermore, the authors compared the criteria between runners with foot orthoses and ones with no intervention (control group). EVIDENCE SYNTHESIS: Twelve studies (5321 runners) met our review criteria. The control and the foot orthoses group sustained 721 (37%) and 238 (24%) injuries, respectively. Compared with the control group, the use of foot orthoses resulted in a significant reduction in lower limb injury risk (risk ratio = 0.6; 95% confidence interval, 0.5-0.7; P = .00001, I2 = 54%; 7 studies, N = 2983: moderate-quality evidence). Moreover, the foot orthoses group corresponded to a 40% reduction in the risk of developing lower limb injuries. CONCLUSIONS: The use of foot orthoses may help reduce the incidence of lower limb injuries and pain in runners.

The sugar-responsive circadian clock regulator bZIP63 modulates plant growth.

Adjustment to energy starvation is crucial to ensure growth and survival. In Arabidopsis thaliana (Arabidopsis), this process relies in part on the phosphorylation of the circadian clock regulator bZIP63 by SUCROSE non-fermenting RELATED KINASE1 (SnRK1), a key mediator of responses to low energy. We investigated the effects of mutations in bZIP63 on plant carbon (C) metabolism and growth. Results from phenotypic, transcriptomic and metabolomic analysis of bZIP63 mutants prompted us to investigate the starch accumulation pattern and the expression of genes involved in starch degradation and in the circadian oscillator. bZIP63 mutation impairs growth under light-dark cycles, but not under constant light. The reduced growth likely results from the accentuated C depletion towards the end of the night, which is caused by the accelerated starch degradation of bZIP63 mutants. The diel expression pattern of bZIP63 is dictated by both the circadian clock and energy levels, which could determine the changes in the circadian expression of clock and starch metabolic genes observed in bZIP63 mutants. We conclude that bZIP63 composes a regulatory interface between the metabolic and circadian control of starch breakdown to optimize C usage and plant growth.

Motor skill acquisition during a balance task as a process of optimization of motor primitives.

It has been argued that the central nervous system relies on combining simple movement elements (i.e. motor primitives) to generate complex motor outputs. However, how movement elements are generated and combined during the acquisition of new motor skills is still a source of debate. Herein, we present results providing new insights into the role of movement elements in the acquisition of motor skills that we obtained by analysing kinematic data collected while healthy subjects learned a new motor task. The task consisted of playing an interactive game using a platform with embedded sensors whose aggregate output was used to control a virtual object in the game. Subjects learned the task over multiple blocks. The analysis of the kinematic data was carried out using a recently developed technique referred to as "movement element decomposition." The technique entails the decomposition of complex multi-dimensional movements in one-dimensional elements marked by a bell-shaped velocity profile. We computed the number of movement elements during each block and measured how closely they matched a theoretical velocity profile derived by minimizing a cost function accounting for the smoothness of movement and the cost of time. The results showed that, in the early stage of motor skill acquisition, two mechanisms underlie the improvement in motor performance: 1) a decrease in the number of movement elements composing the motor output and 2) a gradual change in the movement elements that resulted in a shape matching the velocity profile derived by using the above-mentioned theoretical model.

Health utilities and quality of life in individuals with tuberous sclerosis complex (TSC) who experience epileptic seizures: A web-based survey.

OBJECTIVES: Individuals with tuberous sclerosis complex (TSC) experience a wide range of health impacts, including epileptic seizures, negatively impacting their health-related quality of life (HRQoL). Health state utility values (HSUVs) are index values representing HRQoL and are used as key inputs for health economic analyses. Such data are currently very limited in the TSC population. The objective of this study was to generate HSUVs for TSC health states, defined by the number and type of seizures experienced in the previous week, and to compare with UK normative values. METHODS: This cross-sectional study involved 186 participants (individuals with TSC = 61, caregivers reporting for individuals with TSC = 125) from Europe and North America who completed a web-based survey. Participants completed the [EuroQol - 5 dimensions - 3 levels] (self-report version for individuals with TSC or proxy version 1 for caregivers). RESULTS: The mean age of individuals with TSC was 27.3 years (self-reported: 41.3 years, caregiver-reported: 20.5 years); 56% were males. Most individuals with TSC (71%) reported experiencing between one and ten seizures in the week prior to participating in the study. The most frequently reported type of seizure was focal: simple partial (50%). Across all participants (combined self-report and caregiver-report), the mean HSUV was 0.474 (95% confidence interval [CI]: 0.424-0.524), significantly lower than the UK norm (0.856, 95%CI: 0.848-0.864) [1]. Mean HSUV and HRQoL scores were consistently lower when reported by caregivers than when self-reported by individuals with TSC (HSUV = 0.351 vs. 0.727). This is in part because caregivers reported for individuals with TSC who experienced more frequent and severe seizures than those who were able to self-report. HSUVs incrementally decreased with the experience of more frequent (1-5 per week: HSUV = 0.666 vs. >20: HSUV = 0.290) and more severe seizures (focal: simple partial: HSUV = 0.450 vs. generalized: convulsive: HSUV = 0.194). CONCLUSIONS: The HRQoL and HSUV index scores indicate substantial impairment among individuals with TSC; HSUVs were shown to decrease considerably with increases in seizure frequency or seizure severity, indicating that more burdensome seizure health states are associated with poorer HRQoL.

Coastal zone use and migratory behaviour of the southern population of Mugil liza in Brazil.

We analysed the ratios Sr:Ca and Ba:Ca in the otoliths of 55 adults of the southern population of Mugil liza in Brazil (Paraná to Rio Grande do Sul) to investigate its coastal zone use and migratory behaviour. All individual M. liza analysed had Sr:Ca and Ba:Ca values indicating that their birth was in the marine environment, which is consistent with the southern population migration to spawn in the ocean,. Juveniles exhibited at least three coastal use and recruitment strategies (contingents): the majority (89%) of M. liza juveniles migrated toward brackish water. They entered the estuary before completing the first year of life (64%) or after (25%) their first year of life. The remaining 11% did not appear to enter brackish or freshwater water as a nursery or at any point in their life cycle. Some adults returned to the estuary after spawning in the ocean but others (of both sexes) never returned to the estuary after spawning, remaining in the marine environment. The pattern of juvenile habitat use in the Brazilian southern population of M. liza seems to be recurrent throughout the extent of its distribution as a consequence of the reproductive spawning aggregation behaviour, which mixes all contingents (with marine or estuarine preferences).