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Olfactory dysfunction is a common non-motor symptom associated with Parkinson's disease (PD). This condition usually appears before the onset of the cardinal motor symptoms and is still poorly understood. Here, we generated a mouse model of early-stage PD based on partial 6-hydroxydopamine (6-OHDA) lesion of the dorsal striatum to reproduce the olfactory deficit and associated cellular and electrophysiological anomalies observed in patients. Using this model, we investigated the effect of long-term, continuous administration of pramipexole, a dopamine D2/3 selective agonist, on olfactory dysfunction. We found that pramipexole reverted the impairment of odor discrimination displayed by the mouse model in the habituation/dishabituation test. In line with similar observations in PD patients, the mouse model showed an increase of dopamine cells paralleled by augmented levels of the dopamine marker, tyrosine hydroxylase, in the olfactory bulb (OB). These changes, which have been proposed to contribute to olfactory dysfunction, were abolished by oral administration of pramipexole. Local field potential recording in the OB of 6-OHDA lesion mice showed reduced oscillations in the beta frequency range, in comparison to healthy control mice. This abnormality, which is suggestive of defective long range OB transmission, was also counteracted by pramipexole. Altogether these findings indicate that prolonged pharmacological stimulation of dopamine D2-like receptors rescues olfactory discrimination observed in experimental parkinsonism. Moreover, they show that this protective effect is exerted in parallel to a normalization of dopamine neurons and beta band oscillations in the OB, providing information on the potential mechanisms involved in PD-related olfactory dysfunction., Competing Interests: 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., (© 2024 The Authors.)

Social memory impairments in Mecp2 knockout (KO) mice result from altered neuronal activity in the monosynaptic projection from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC). The hippocampal network is hyperactive in this model for Rett syndrome, and such atypically heightened neuronal activity propagates to the mPFC through this monosynaptic projection, resulting in altered mPFC network activity and social memory deficits. However, the underlying mechanism of cellular dysfunction within this projection between vHIP pyramidal neurons (PYR) and mPFC PYRs and parvalbumin interneurons (PV-IN) resulting in social memory impairments in Mecp2 KO mice has yet to be elucidated. We confirmed social memory (but not sociability ) deficits in Mecp2 KO mice using a new 4-chamber social memory arena, designed to minimize the impact of the tethering to optical fibers required for simultaneous in vivo fiber photometry of Ca 2+ -sensor signals during social interactions. mPFC PYRs of wildtype (WT) mice showed increases in Ca 2+ signal amplitude during explorations of a novel toy mouse and interactions with both familiar and novel mice, while PYRs of Mecp2 KO mice showed smaller Ca 2+ signals during interactions only with live mice. On the other hand, mPFC PV-INs of Mecp2 KO mice showed larger Ca 2+ signals during interactions with a familiar cage-mate compared to those signals in PYRs, a difference absent in the WT mice. These observations suggest atypically heightened inhibition and impaired excitation in the mPFC network of Mecp2 KO mice during social interactions, potentially driving their deficit in social memory.

Objective: To compare the thermographic pattern of regions of interest (ROI) of respiratory muscles in young asthmatics with and without bronchospasm induced by eucapnic voluntary hyperpnea (EVH)., Materials and Methods: Cross-sectional study carried out with 55 young (55% male and 45% females) aged 12.5 ± 3.3 years, divided in nine nonasthmatics, 22 asthmatics without exercise-induced bronchospasm compatible response (EIB-cr) and 24 asthmatics with EIB-cr. The diagnosis of EIB was given to subjects with a fall in forced expiratory volume in the first second (FEV 1 ) ≥ 10% compared to baseline. Thermographic recordings of respiratory muscles were delimited in ROI of the sternocleidomastoid (SCM), pectoral, and rectus abdominis intention area. Thermal captures and FEV 1 were taken before and 5, 10, 15 and 30 min after EVH., Results: Twenty-four (52.1%) of asthmatics had EIB-cr. There was a decrease in temperature at 10 min after EVH test in the SCM, pectoral and rectus abdominis ROIs in all groups (both with p < 0.05). There was a decrease in temperature (% basal) in asthmatic with EIB-cr compared to nonasthmatics in the rectus abdominis area (p < 0.05)., Conclusion: There was a decrease in temperature in the ROIs of different muscle groups, especially in asthmatics. The greater drop in FEV 1 observed in individuals with EIB-cr was initially associated with a decrease in skin temperature, with a difference between the nonasthmatics in the abdominal muscle area. It is likely that this decrease in temperature occurred due to a temporary displacement of blood flow to the most used muscle groups, with a decrease in the region of the skin evaluated in the thermography., (© 2024 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in MECP2, which encodes methyl-CpG-binding protein 2, a transcriptional regulator of many genes, including brain-derived neurotrophic factor (BDNF). BDNF levels are lower in multiple brain regions of Mecp2-deficient mice, and experimentally increasing BDNF levels improve atypical phenotypes in Mecp2 mutant mice. Due to the low blood-brain barrier permeability of BDNF itself, we tested the effects of LM22A-4, a brain-penetrant, small-molecule ligand of the BDNF receptor TrkB (encoded by Ntrk2), on dendritic spine density and form in hippocampal pyramidal neurons and on behavioral phenotypes in female Mecp2 heterozygous (HET) mice. A 4-week systemic treatment of Mecp2 HET mice with LM22A-4 restored spine volume in MeCP2-expressing neurons to wild-type (WT) levels, whereas spine volume in MeCP2-lacking neurons remained comparable to that in neurons from female WT mice. Female Mecp2 HET mice engaged in aggressive behaviors more than WT mice, the levels of which were reduced to WT levels by the 4-week LM22A-4 treatment. These data provide additional support to the potential usefulness of novel therapies not only for RTT but also to other BDNF-related disorders., Competing Interests: Competing interests F.M.L. is listed as an inventor on patents relating to LM22A-4, which are assigned to the University of North Carolina and the University of California, San Francisco, and is eligible for royalties distributed by the assigned universities. He has financial interest in and serves as a board member for PharmatrophiX, a company focused on the development of small-molecule ligands for neurotrophin receptors, which has licensed several of these patents. F.M.L. also serves as an advisor for Pfizer Ventures. The remaining authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

The lack of affordable and effective therapeutics against cognitive impairment has promoted research toward alternative approaches to the treatment of neurodegeneration. In recent years, a bidirectional pathway that allows the gut to communicate with the central nervous system has been recognized as the gut-brain axis. Alterations in the gut microbiota, a dynamic population of trillions of microorganisms residing in the gastrointestinal tract, have been implicated in a variety of pathological states, including neurodegenerative disorders such as Alzheimer's disease (AD). However, probiotic treatment as an affordable and accessible adjuvant therapy for the correction of dysbiosis in AD has not been thoroughly explored. Here, we sought to correct the dysbiosis in an AD mouse model with probiotic supplementation, with the intent of exploring its effects on disease progression. Transgenic 3xTg-AD mice were fed a control or a probiotic diet ( Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 ) for 12  weeks, with the latter leading to a significant increase in the relative abundance of Bacteroidetes . Cognitive functions were evaluated via Barnes Maze trials and improvements in memory performance were detected in probiotic-fed AD mice. Neural tissue analysis of the entorhinal cortex and hippocampus of 10-month-old 3xTg-AD mice demonstrated that astrocytic and microglial densities were reduced in AD mice supplemented with a probiotic diet, with changes more pronounced in probiotic-fed female mice. In addition, elevated numbers of neurons in the hippocampus of probiotic-fed 3xTg-AD mice suggested neuroprotection induced by probiotic supplementation. Our results suggest that probiotic supplementation could be effective in delaying or mitigating early stages of neurodegeneration in the 3xTg-AD animal model. It is vital to explore new possibilities for palliative care for neurodegeneration, and probiotic supplementation could provide an inexpensive and easily implemented adjuvant clinical treatment for AD., 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 © 2024 Medeiros, McMurry, Pfeiffer, Newsome, Testerman, Graf, Silver and Sacchetti.)

L-serine (Ser) and L-glycine (Gly) are critically important for the overall functioning of primary metabolism. We investigated the interaction of the phosphorylated pathway of Ser biosynthesis (PPSB) with the photorespiration-associated glycolate pathway of Ser biosynthesis (GPSB) using Arabidopsis thaliana PPSB-deficient lines, GPSB-deficient mutants, and crosses of PPSB with GPSB mutants. PPSB-deficient lines mainly showed retarded primary root growth. Mutation of the photorespiratory enzyme Ser-hydroxymethyltransferase 1 (SHMT1) in a PPSB-deficient background resumed primary root growth and induced a change in the plant metabolic pattern between roots and shoots. Grafting experiments demonstrated that metabolic changes in shoots were responsible for the changes in double mutant development. PPSB disruption led to a reduction in nitrogen (N) and sulfur (S) contents in shoots and a general transcriptional response to nutrient deficiency. Disruption of SHMT1 boosted the Gly flux out of the photorespiratory cycle, which increased the levels of the one-carbon (1C) metabolite 5,10-methylene-tetrahydrofolate and S-adenosylmethionine. Furthermore, disrupting SHMT1 reverted the transcriptional response to N and S deprivation and increased N and S contents in shoots of PPSB-deficient lines. Our work provides genetic evidence of the biological relevance of the Ser-Gly-1C metabolic network in N and S metabolism and in interorgan metabolic homeostasis., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Vertebrates have diverse morphologies and various anatomical novelties that set them apart from their closest invertebrate relatives. A conspicuous head housing a large brain, paired sense organs, and protected by a skeleton of cartilage and bone is unique to vertebrates and is a defining feature of this taxon. Gans and Northcutt (1980s) proposed that the evolution of this "new head" was dependent on two key developmental innovations: neural crest cells (NCCs) and ectodermal placodes. NCCs are migratory embryonic cells that form bone, cartilage, and neurons in the new head. Based on genome size, Ohno (1970s) proposed a separate hypothesis, stating that vertebrate genome content was quadrupled via two rounds (2R) of whole genome duplications (WGDs), and the surplus of genetic material potentiated vertebrate morphological diversification. While both hypotheses offer explanations for vertebrate success, it is unclear if, and how, the "new head" and "2R" hypotheses are linked. Here, we consider both hypotheses and evaluate the experimental evidence connecting the two. Overall, evidence suggests that while the origin of the NC GRN predates the vertebrate WGDs, these genomic events may have potentiated the evolution of distinct genetic subnetworks in different neural crest subpopulations. We describe the general composition of the NC GRN and posit that its increased developmental modularity facilitated the independent evolution of NC derivatives and the diversification of the vertebrate head skeleton. Lastly, we discuss experimental strategies needed to test whether gene duplications drove the diversification of neural crest derivatives and the "new head".

Background: The pulmonary impairment in patients with bronchoconstriction induced by eucapnic voluntary hyperpnea(EVH) goes beyond the respiratory system, also impairing autonomic nervous modulation. This study aimed to evaluate the behavior of cardiac autonomic modulation in young asthmatics with and without EIB after the EVH test., Research Design and Methods: A cross-sectional study design using 54 asthmatics(51.9% female), aged between 10 and 19 years, investigated with the EVH test. Forced expiratory volume in one second(FEV 1 ) was measured at 5, 10, 15, and 30 min after EVH. Heart rate variability(HRV) measures of time were assessed pre and 30 min-post EVH. The diagnosis of Exercise-Induced bronchoconstriction with underlying clinical asthma(EIB A ) was confirmed by a fall in FEV 1 ≥10% compared to baseline., Results: Thirty(55.5%) asthmatics had EIB A . Subjects with EIB A have reduced mean of the R-R intervals in relation to baseline until 15 minutes after EVH. Individuals without EIB A had increased parasympathetic activity compared to baseline(rMSSD) from 5 min after EVH( p  < 0.05). This parasympathetic activity increase in relation to baseline was seen in individuals with EIB A after 25 minutes (rMSSD = 49.9 ± 5.3 vs 63.5 ± 7.2, p  < 0.05)., Conclusion: Young asthmatics with EIB A present a delay in the increase of the parasympathetic component after EVH when compared to asthmatics without EIB A .

Objective: The aim of this study was to evaluate the effects of obstetric simulation training on undergraduate medical students to improve their self-confidence., Methods: Fifth-year undergraduate medical students were invited to a 2-week course of simulation in obstetrics during their clerkship. The sessions included were as follows: (1) care for the second and third periods of childbirth, (2) partograph analysis and pelvimetry, (3) premature rupture of membranes at term, and (4) diagnosis and management of third-trimester bleeding. Before the first session and at the end of the training period, a questionnaire about self-confidence in obstetric procedures and skills was applied., Results: A total of 115 medical students were included, of whom 60 (52.2%) were male and 55 (47.8%) were female. Comparing initial and final scores, the median results of the subscales "comprehension and preparation" (18 vs. 22, p<0.001), "knowledge of procedures" (14 vs. 20, p<0.001), and "expectation" (22 vs. 23, p<0.01) were significantly higher at the end of the training period in all items of the questionnaire than in the beginning. Differences were found based on the students' gender, i.e., female students had a significantly higher sum of scores than the male students in the initial subscale for "expectation" (median, 24 vs. 22, p<0.001) and "interest" (median, 23 vs. 21, p=0.032), and a higher sum of scores in the subscale for "expectation" (median, 23 vs. 21, p=0.010) in the final questionnaire., Conclusion: Obstetric simulation enhances the improvement of students' self-confidence in understanding both the physiology of childbirth and the obstetric care procedures. Further studies are needed to understand the influence of gender on obstetric care.

Dopamine has a significant role in motor and cognitive function. The dopaminergic pathways originating from the midbrain have received the most attention; however, the relevance of the cerebellar dopaminergic system is largely undiscovered. Here, we show that the major cerebellar astrocyte type Bergmann glial cells express D1 receptors. Dopamine can be synthesized in Purkinje cells by cytochrome P450 and released in an activity-dependent fashion. We demonstrate that activation of D1 receptors induces membrane depolarization and Ca 2+ release from the internal store. These astrocytic activities in turn modify Purkinje cell output by altering its excitatory and inhibitory synaptic input. Lastly, we show that conditional knockout of D1 receptors in Bergmann glial cells results in decreased locomotor activity and impaired social activity. These results contribute to the understanding of the molecular, cellular, and circuit mechanisms underlying dopamine function in the cerebellum, revealing a critical role for the cerebellar dopaminergic system in motor and social behavior., (© 2023. The Author(s).)

Standalone Virtual Reality (VR) headsets can be used when travelling in cars, trains and planes. However, the constrained spaces around transport seating can leave users with little physical space in which to interact using their hands or controllers, and can increase the risk of invading other passengers' personal space or hitting nearby objects and surfaces. This hinders transport VR users from using most commercial VR applications, which are designed for unobstructed 1-2m 360 ° home spaces. In this paper, we investigated whether three at-a-distance interaction techniques from the literature could be adapted to support common commercial VR movement inputs and so equalise the interaction capabilities of at-home and on-transport users: Linear Gain, Gaze-Supported Remote Hand, and AlphaCursor. First, we analysed commercial VR experiences to identify the most common movement inputs so that we could create gamified tasks based on them. We then investigated how well each technique could support these inputs from a constrained 50x50cm space (representative of an economy plane seat) through a user study (N=16), where participants played all three games with each technique. We measured task performance, unsafe movements (play boundary violations, total arm movement) and subjective experience and compared results to a control 'at-home' condition (with unconstrained movement) to determine how similar performance and experience were. Results showed that Linear Gain was the best technique, with similar performance and user experience to the 'at-home' condition, albeit at the expense of a high number of boundary violations and large arm movements. In contrast, AlphaCursor kept users within bounds and minimised arm movement, but suffered from poorer performance and experience. Based on the results, we provide eight guidelines for the use of, and research into, at-a-distance techniques and constrained spaces.

Passengers spend considerable periods of time in shared transit spaces, relying on smartphones and laptops for work. However, these displays are limited in size and ergonomics compared to typical multi-monitor setups used in the office, impairing productivity. Augmented Reality (AR) headsets could provide large, flexible virtual workspaces during travel, enabling passengers to work more efficiently. This paper investigates the factors affecting how passengers choose to layout virtual displays in car, train, subway and plane environments, studying the affordances of each mode of transport and the presence of others. Results from our experiment showed: significant usage of the physical environment to align displays; strong social effects meant avoiding placing displays over other passengers or their belongings; and use of displays for shielding oneself from others. Our findings show the unique challenges posed by the mode of transport and presence of others on the use of AR for mobile productivity in the future.

Introduction: Impulse oscillometry (IOS) parameters are obtained more easily and effortlessly in comparison to forced expiratory volume in the first second (FEV1)., Objective: To compare IOS parameters to FEV1 in exercise-induced bronchoconstriction (EIB) diagnosis., Methods: Seventy-four (60.8% male; 39.2 female) young asthmatics aged between 7 and 17 years (mean 12.6 ± 2.8 years) were evaluated. EIB was defined as a reduction in FEV1 ≥ 10% compared with basal after standardized challenge by treadmill running (TR). IOS parameters and FEV1 were obtained at baseline and 5,15, and 30 min after TR. The area under the receiver operator characteristic curve (AUC) was calculated from the reduction in FEV1 ≥ 10% to evaluate the best psychometric characteristics of IOS parameters., Results: Twenty-four individuals (32.4%) were diagnosed with EIB. A moderate inverse correlation was found between the IOS and FEV1 variables immediately after the TR, with resistance at 5 Hz (R5Hz), resonant frequency (Fres), and reactance area (AX), (r = -0.64, r = -0.53 and r = -0.69, respectively, all with p < 0.05). An increase of 25 kPa/l/s in R5 Hz, of 19k Pa/l/s in AX and 21 Hz in Fres were found to best correlate with EIB diagnosis by FEV1 (sensitivity 67% and specificity 62%, sensitivity 84% and specificity 50%, and sensitivity 84% and specificity 60%, respectively)., Conclusion: IOS parameters have a significant inverse correlation with FEV1. This study presents cut-off points for EIB diagnosis for R5Hz, AX, and Fres, however, the findings in IOS parameters should be used and interpreted carefully if the goal is to replace spirometry., (© 2022 Wiley Periodicals LLC.)

Altering plant water use efficiency (WUE) is a promising approach for achieving sustainable crop production in changing climate scenarios. Here, we show that WUE can be tuned by alleles of a single gene discovered in elite maize (Zea mays) breeding material. Genetic dissection of a genomic region affecting WUE led to the identification of the gene ZmAbh4 as causative for the effect. CRISPR/Cas9-mediated ZmAbh4 inactivation increased WUE without growth reductions in well-watered conditions. ZmAbh4 encodes an enzyme that hydroxylates the phytohormone abscisic acid (ABA) and initiates its catabolism. Stomatal conductance is regulated by ABA and emerged as a major link between variation in WUE and discrimination against the heavy carbon isotope (Δ13C) during photosynthesis in the C4 crop maize. Changes in Δ13C persisted in kernel material, which offers an easy-to-screen proxy for WUE. Our results establish a direct physiological and genetic link between WUE and Δ13C through a single gene with potential applications in maize breeding., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Rationale: Cardiovascular exercise is an effective method to improve cardiovascular health outcomes, but also promote neuroplasticity during stroke recovery. Moderate-intensity continuous cardiovascular training (MICT) is an integral part of stroke rehabilitation, yet it may remain a challenge to exercise at sufficiently high intensities to produce beneficial adaptations to neuroplasticity. High-intensity interval training (HIIT) could provide a viable alternative to achieve higher intensities of exercise by using shorter bouts of intense exercise interspersed with periods of recovery., Methods and Design: This is a two-arm, parallel-group multi-site RCT conducted at the Jewish Rehabilitation Hospital (Laval, Québec, Canada) and McMaster University (Hamilton, Ontario, Canada). Eighty participants with chronic stroke will be recruited at both sites and will be randomly allocated into a HIIT or MICT individualized exercise program on a recumbent stepper, 3 days per week for 12 weeks. Outcomes will be assessed at baseline, at 12 weeks post-intervention, and at an 8-week follow-up., Outcomes: The primary outcome is corticospinal excitability, a neuroplasticity marker in brain motor networks, assessed with transcranial magnetic stimulation (TMS). We will also examine additional markers of neuroplasticity, measures of cardiovascular health, motor function, and psychosocial responses to training., Discussion: This trial will contribute novel insights into the effectiveness of HIIT to promote neuroplasticity in individuals with chronic stroke., Trial Registration: ClinicalTrials.gov NCT03614585 . Registered on 3 August 2018., (© 2022. The Author(s).)

Individuals who experience stress can engage in health-risk behaviours that may decrease work performance. The aim of this study was to determine perceived stress levels in Brazilian workers and verify whether perceived stress was associated with health-risk behaviours. Stress levels of 1,270 workers (1,019 men, 251 women) were assessed using the Perceived Stress Scale. The health-risk behaviours investigated were low intake of vegetables and fruits, daily smoking, high-risk alcohol consumption, physical inactivity, and the presence of obesity. The Student's  t -test or one-way analysis of variance was used to assess differences in stress levels. Ordinal regression was used to determine the association between the degrees of stress and health-risk behaviours. Women had higher perceived stress levels than men. In addition, perceived stress levels were higher in those who had low socioeconomic status, were unmarried, had a negative perception of their health, were smokers, or had obesity. Smoking and the presence of two or more health-risk behaviours were associated with 1.84 (95% CI: 1.24-2.73) times and 1.49 (95% CI: 1.18-1.89) times higher odds of experiencing higher degrees of stress, respectively. In women, such an association was observed with the presence of obesity (odds ratio: 2.0; 95% CI: 1.01-3.98).

Purpose: Exercise-induced bronchoconstriction (EIB) affects approximately 50% of young asthma patients, impairing their participation in sports and physical activities. Eucapnic voluntary hyperpnea (EVH) is an approved surrogate challenge to exercise for objective EIB diagnosis, but the required minimum target hyperventilation rates remain unexplored in this population. This study aimed to evaluate the association between the achieved ventilation rates (VRs) during a challenge and EIB-compatible response (EIB-cr) in young asthma patients., Methods: This cross-sectional study included 72 asthma patients aged 10-20 years. Forced expiratory volume in the first second (FEV1) was measured before and 5, 15, and 30 min after the EVH. The target VR was set at 21 times the individual's baseline FEV1. A decrease of > 10% in FEV1 after the challenge was considered an EIB-cr. The challenge was repeated after 48-72 h in those without an EIB-cr., Results: Thirty-six individuals had an EIB-cr at initial evaluation. The median VRs achieved was not different between individuals with and without an EIB-cr (19.8 versus 17.9; p = 0.619). The proportion of individuals with an EIB-cr was nor different comparing those who achieved (12/25) or not (24/47) the calculated target VRs (p = 0.804). At the repeated EVH challenge an EIB-cr was observed in 14/36 individuals with a negative response in the first evaluation, with no differences in achieved VRs between the two tests (p = 0.463)., Conclusion: Irrespective of the achieved VR, an EIB-compatible response after an EVH challenge must be considered relevant for clinical and therapeutic judgment and negative tests should be repeated., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

2-Methyl-1,3-butadiene (isoprene), released from biogenic sources, accounts for approximately a third of hydrocarbon emissions and is mainly removed by hydroxyl radicals, OH, the primary initiator of atmospheric oxidation. In situ measurements in clean tropical forests (high isoprene and low NO x ) have measured OH concentrations up to an order of magnitude higher than model predictions, which impacts our understanding of global oxidation. In this study, direct, laser flash photolysis, laser-induced fluorescence measurements at elevated temperatures have observed OH recycling in the presence of isoprene and oxygen under conditions where interference from secondary or heterogeneous chemistry is minimal. Our results provide the first direct, time-resolved, experimental validation of the theory-based Leuven Isoprene Mechanism (LIM1), based on isomerization of isoprene-RO 2 radicals and OH regeneration, that partially accounts for model:measurement divergence in OH. While our data can be fit with only minor alterations in important LIM1 parameters, and the overall rate of product formation is similar to LIM1, there are differences with the recent experimental study by Teng et al . J. Am. Chem. Soc. 2017 , 139 , 5367-5377. In addition, our study indicates that the dihydroperoxide products are significantly enhanced over previous estimates. Dihydroperoxides are chemical and photochemical sources of OH, and the implications of enhanced hydroperoxide formation on the agreement between models and observations in tropical forests are examined., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

C4 photosynthesis concentrates CO2 around Rubisco in the bundle sheath, favouring carboxylation over oxygenation and decreasing photorespiration. This complex trait evolved independently in >60 angiosperm lineages. Its evolution can be investigated in genera such as Flaveria (Asteraceae) that contain species representing intermediate stages between C3 and C4 photosynthesis. Previous studies have indicated that the first major change in metabolism probably involved relocation of glycine decarboxylase and photorespiratory CO2 release to the bundle sheath and establishment of intercellular shuttles to maintain nitrogen stoichiometry. This was followed by selection for a CO2-concentrating cycle between phosphoenolpyruvate carboxylase in the mesophyll and decarboxylases in the bundle sheath, and relocation of Rubisco to the latter. We have profiled 52 metabolites in nine Flaveria species and analysed 13CO2 labelling patterns for four species. Our results point to operation of multiple shuttles, including movement of aspartate in C3-C4 intermediates and a switch towards a malate/pyruvate shuttle in C4-like species. The malate/pyruvate shuttle increases from C4-like to complete C4 species, accompanied by a rise in ancillary organic acid pools. Our findings support current models and uncover further modifications of metabolism along the evolutionary path to C4 photosynthesis in the genus Flaveria., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Objective: Identify associated factors for recurrent wheezing (RW) in male and female infants., Methods: Cross-sectional multicentric study using the standardized questionnaire from the Estudio Internacional sobre Sibilancias en Lactantes (EISL). The questionnaire was applied to parents of 9345 infants aged 12-15 months at the time of immunization/routine visits., Results: One thousand two hundred and sixty-one (13.5%) males and nine hundred sixty-three (10.3%) females have had RW (≥3 episodes), respectively (p10 colds episodes (OR = 3.46; IC 95% 2.35-5.07), air pollution (OR = 1.33; IC 95% 1.12-1.59), molds at home (OR = 1.23; IC 95% 1.03-1.47), Afro-descendants (OR = 1.42; IC 95% 1.20-1.69), bronchopneumonia (OR = 1.41; IC; 1.11-1.78), severe episodes of wheezing in the first year (OR = 1.56; IC 95% 1.29-1.89), treatment with bronchodilators (OR = 1.60; IC 95% 1.22-2,1) and treatment with oral corticosteroids (OR = 1,23; IC 95% 0.99-1,52). Associated factors for RW for females were passive smoking (OR = 1.24; IC 95% 1.01-1,51), parents diagnosed with asthma (OR = 1.32; IC 95% 1,08-1,62), parents with allergic rhinitis (OR = 1.26; IC 95% 1.04-1.53), daycare attendance (OR = 1.48; IC 95% 1.17-1,88), colds in the first 6 months of life (OR = 2.19; IC 95% 1.69-2.82), personal diagnosis of asthma (OR = 1.84; IC 95% 1.39-2.44), emergency room visits (OR = 1.78; IC 95% 1.44-2.21), nighttime symptoms (OR = 2.89; IC 95% 2.34-3.53) and updated immunization (OR = 0.62; IC 95% 0.41-0.96)., Conclusion: There are differences in associated factors for RW between genders. Identification of these differences could be useful to the approach and management of RW between boys and girls., (Copyright © 2021 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Corresponding lighting and reflectance between real and virtual objects is important for spatial presence in augmented and mixed reality (AR and MR) applications. We present a method to reconstruct real-world environmental lighting, encoded as a reflection map (RM), from a conventional photograph. To achieve this, we propose a stacked convolutional neural network (SCNN) that predicts high dynamic range (HDR) 360 ° RMs with varying roughness from a limited field of view, low dynamic range photograph. The SCNN is progressively trained from high to low roughness to predict RMs at varying roughness levels, where each roughness level corresponds to a virtual object's roughness (from diffuse to glossy) for rendering. The predicted RM provides high-fidelity rendering of virtual objects to match with the background photograph. We illustrate the use of our method with indoor and outdoor scenes trained on separate indoor/outdoor SCNNs showing plausible rendering and composition of virtual objects in AR/MR. We show that our method has improved quality over previous methods with a comparative user study and error metrics.

Objective: The aim of this study was to assess the diaphragm kinetics, respiratory function, and serum dosage of leptin and inflammatory cytokines (IL-6 and TNF-α) in three clinical groups: obese, asthmatic, and healthy., Methods: This is a clinical exploratory study performed on 73 youths (12-24 years of age, 42.5% male) allocated into three groups: obesity (OG, n=33), body mass index (BMIz-score) ≥ +2, asthmatic (AG, n=26) controlled mild asthmatics, classified by GINA, and Healthy Control Group (CG, n=14). The participants were subjected to diaphragmatic ultrasound, spirometry, maximal respiratory pressure, serum leptin levels, and IL-6 and TNF-α whole blood cell culture levels., Results: Diaphragm thickness was higher in OG in comparison to AG and CG (2.0±0.4 vs 1.7±0.5 and 1.6±0.2, both with p<0.05). Maximal voluntary ventilation (MVV) was significantly lower in OG and AG in relation to the CG (82.8±21.4 and 72.5±21.2 vs 102.8±27.3, both with p<0.05). OG has the highest leptin rate among the groups (with the other two groups had p<0.05). All groups had similar TNF-α and IL-6 levels., Conclusion: The muscular hypertrophy found in the diaphragm of the obese individuals can be justified by the increase in respiratory work imposed by the chronic condition of the disease. Such increase in thickness did not occur in controlled mild asthmatics. The IL-6 and TNF-α markers detected no evidence of muscle inflammation, even though leptin was expected to be altered in obese individuals. Both obese and asthmatic patients had lower pulmonary resistance than the healthy ones.

Objectives: We measured the production of cytokines, chemokines and antibodies involved in allergic responses and sCD23 levels during Schistosoma mansoni infection., Methods: Individuals (n = 164) were selected using the ISAAC questionnaire and parasitological exams. The subjects were divided as follows: those infected individuals with allergy-related symptoms (A-I), those with allergy-related symptoms only (A-NI); those only infected (NA-I); and those non-infected individuals without allergy-related symptoms (NA-NI). We used supernatants from cell culture (mitogenic stimulation) to measure cytokine and chemokine levels using cytometric bead arrays. Serum levels of anti-Ascaris lumbricoides (Asc) and anti-Blomia tropicalis IgE were measured using ImmunoCAP, and sCD23 was measured using ELISA., Results: Schistosoma mansoni infection was associated with a lower risk of allergy-related symptoms. In A-I, there were higher levels of TNF-α, IL-10, IL-6, IFN-γ and CXCL8 than in NA-NI group, with TNF-α and IL-6 also at higher levels compared to A-NI group. Levels of IL-6, CXCL8, total and anti-Asc IgE, as well as the numbers of eosinophils, were higher in NA-I than in NA-NI, and the antibodies were also lower in A-NI than in NA-I group. In AI and NA-I, there was less production of CCL2 than in NA-NI. There were no differences in the levels of IL-2, IL-4, IL-17, CCL5, sCD23 and anti-Blomia IgE., Conclusions: Patients with allergy-related symptoms and infected (simultaneously) had higher levels of IL-10; due to the infection, there was increased production of IL-6 and CXCL8 and less CCL2. These data may characterize deviation to Th1 or attenuation of the Th2 response in allergy sufferers in areas endemic for schistosomiasis., (© 2021 John Wiley & Sons Ltd.)

The idea of the epileptic brain being highly excitable and facilitated to synchronic activity has guided pharmacological treatment since the early twentieth century. Although tackling epilepsy's seizure-prone feature, by tonically modifying overall circuit excitability and/or connectivity, the last 50 years of drug development has not seen a substantial improvement in seizure suppression of refractory epilepsies. This review presents a new conceptual framework for epilepsy in which the temporal dynamics of the disease plays a more critical role in both its understanding and therapeutic strategies. The repetitive epileptiform pattern (characteristic during ictal activity) and other well-defined electrographic signatures (i.e., present during the interictal period) are discussed in terms of the sequential activation of the circuit motifs. Lessons learned from the physiological activation of neural circuitry are used to further corroborate the argument and explore the transition from proper function to a state of instability. Furthermore, the review explores how interfering in the temporally dependent abnormal connectivity between circuits may work as a therapeutic approach. We also review the use of probing stimulation to access network connectivity and evaluate its power to determine transitional states of the dynamical system as it moves towards regions of instability, especially when conventional electrographic monitoring is proven inefficient. Unorthodox cases, with little or no scalp electrographic correlate, in which ictogenic circuitry and/or seizure spread is temporally restricted to neurovegetative, cognitive, and motivational areas are shown as possible explanations for sudden death in epilepsy (SUDEP) and other psychiatric comorbidities. In short, this review presents a paradigm shift in the way that we address the disease and is aimed to encourage debate rather than narrow the rationale epilepsy is currently engaged in. This article is part of the Special Issue "NEWroscience 2018"., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: This study aimed to assess the quality of life associated with gender inequalities in formal workers and to determine the effect of sociodemographic, clinical, and behavioral factors on the quality of life (QOL)., Methods: This cross-sectional study involved 1270 workers. Quality of life was measured using the EUROHIS-QOL 8-Item and assessed in terms of psychological, environmental, social, and physical domains, while demographic, socioeconomic, behavioral, and clinical variables served as explanatory variables. Analyses were performed using an ordinal logistic regression model whose significance level was 5%., Results: Of the participants, 80.2% were men, and 19.8% were women; the mean age was 34 (standard deviation: ±10) and 32 (±9) years, respectively. In all prediction scenarios, men were more likely to have a higher quality of life, especially in the physical (odds ratio: 2.16; 95% confidence interval: 1.60-2.93) and psychological (odds ratio: 2.09; 95% confidence interval: 1.51-2.91) domains., Conclusions: Men and women had significantly different levels of quality of life, and sociodemographic, clinical, and behavioral variables partially clarified these differences, which were possibly established by a socio-historical process of construction of the work role determined by gender issues.

ACT's low levels of Plasmodium parasitemia clearance are worrisome since it is the last treatment option against P. falciparum. This scenario has led to investigations of compounds with different mechanisms of action for malaria treatment. Natural compounds like ursolic acid (UA) and betulinic acid (BA), distinguished by their activity against numerous microorganisms, including P. falciparum, have become relevant. This study evaluated the antiplasmodial activity of imidazole derivatives of UA and BA against P. falciparum in vitro. Eight molecules were obtained by semisynthesis and tested against P. falciparum strains (NF54 and CQ-resistant 106/cand isolated in Porto Velho, Brazil); 2a and 2b showed activity against NF54 and 106/cand strains with IC 50  < 10 µM. They presented high selectivity indexes (SI > 25) and showed synergism when combined with artemisinin. 2b inhibited the parasite's ring and schizont forms regardless of when the treatment began. In silico analysis presented a tight bind of 2b in the topoisomerase II-DNA complex. This study demonstrates the importance of natural derivate compounds as new candidates for malarial treatment with new mechanisms of action. Semisynthesis led to new triterpenes that are active against P. falciparum and may represent new alternatives for malaria drug development., (© 2021 John Wiley & Sons Ltd.)

Background: Ultra-processed foods are industrial formulations made from food extracts or constituents with little or no intact food and often containing additives that confer hyper-palatability. The consumption of these products increases the risk of chronic non-communicable diseases. Stressed people may engage in unhealthy eating as a way to cope. This study aimed to verify whether ultra-processed food consumption was associated with perceived stress levels in industrial and retail workers from Vitoria da Conquista, Brazil., Methods: This was a cross-sectional study carried out between July 2017 and August 2018. During the study period, 1270 participants completed a survey administered by an interviewer. Stress levels were assessed using the Perceived Stress Scale. Information regarding weekly ultra-processed food consumption was collected. Ultra-processed foods were classified into four groups: sugary drinks; sugary foods; fast foods; and canned foods, frozen foods, or processed meat. The Student's t -test or one-way analysis of variance was used to assess the differences in stress levels and ultra-processed food consumption. Ordinal regression was used to determine the association between the degrees of stress and ultra-processed food consumption levels., Results: Factors such as a young age, being unmarried, smoking, high-risk alcohol consumption, negative health perception, and high perceived stress level indicated higher rates of ultra-processed food consumption. Ordinal regression analysis showed that high stress levels were associated with increased odds of higher ultra-processed food consumption (odds ratio: 1.94; 95% CI: 1.54-2.45)., Conclusions: These findings could help identify appropriate target areas for interventions aimed at mental health promotion and healthier food consumption.

Background: This study aimed to identify the factors associated with the quality of life of young workers of a Social Work of Industry Unit., Methods: This was a cross-sectional study conducted on 1270 workers. Data were collected using a digital questionnaire built on the KoBoToolbox platform that included the EUROHIS-QOL eight-item index to assess quality of life. Demographic, socioeconomic, behavioral, and clinical variables were considered explanatory. The associations were analyzed using the ordinal logistic regression model at a 5% significance level., Results: Men and women had a mean quality of life of 31.1 and 29.4, respectively. Workers that rated their health as "very good" had an odds ratio of 7.4 (95% confidence interval (CI) = 5.17-10.81), and those who rated it as "good" had an odds ratio of 2.9 (95% CI = 2.31-3.77). Both these groups of workers were more likely to have higher levels of quality of life as compared to workers with "regular", "poor", or "very poor" self-rated health. Physically active individuals were 30% more likely to have higher levels of quality of life (odds ratio = 1.3; 95% CI = 1.08-1.65). After adjusting the model by gender, age group, marital status, socioeconomic class, self-rated health, nutritional status, and risky alcohol consumption, the odds ratio of active individuals remained stable (odds ratio = 1.3; 95% CI = 1.05-1.66)., Conclusions: In the present study, self-rated health, physical activity, and gender were associated with young workers' quality of life.

Objectives: In contrast to spirometry, which requires active participation of the individual and is challenging for the preschool age group, the impulse oscillometry system comprises a test that minimizes the degree of coordination required. The study aimed to compare the results of Impulse Oscillometry System (IOS) in children with and without respiratory symptoms., Methods: A cross-sectional study was conducted in children aged between 3 and 6 years. A short version of the ATS-DLD-78-C questionnaire validated for Brazilian children was applied to identify two groups: children with and without respiratory symptoms. The IOS analysis was carried out measuring the following parameters in triplicate: resistance at 5 Hz (R5Hz) and 20 Hz (R20Hz), respiratory reactance at 5 Hz (X5Hz), and R5-R20Hz before and after bronchodilator application., Results: A total of 76 preschoolers were selected, 55 (72.4%) of whom had respiratory complaints. The coefficient of variability of R5Hz was ≤17% in 70/76 (92.1%) of the children. Resistances at R5Hz and R5-R20Hz in the children with respiratory complaints reached values higher than those of children without symptoms before bronchodilation., Conclusions: The results obtained for resistance using IOS in children with respiratory symptoms were higher in the pre-bronchodilator examination for R5Hz and R5-R20Hz compared to those of children without respiratory symptoms., Expert Opinion: Prospective investigations suggest that irreversible changes in lung function begin in infancy, before reaching school age. Pulmonary function follow-up in children with recurrent wheezing or asthma is important for confirmation of diagnosis and evaluation of the disease severity. The Impulse Oscillometry System (IOS) can be useful in assessing children's pulmonary function since it requires minimal patient cooperation and can be successfully applied to preschool children being an alternative to individuals who have difficulty performing spirometry.

Objectives: The characteristics of critically ill HIV-positive patients and the causes of their admission to intensive care units (ICUs) are only known through retrospective and unicentric studies. This study aims to fill this knowledge gap., Methods: This is a prospective, multicentre cohort study of short- and medium-term prognostic factors. The setting consisted of ICUs of three tertiary referral hospitals from the three largest metropolitan areas in Brazil in the period January 2014 to November 2015. In all, 161 HIV patients over 18 years old were included., Results: The clinical data of the outcomes (ICU mortality, hospital mortality and 90-day survival) were extracted from medical records using the REDCap ®️ web-based form and analysed with the MedCalc ® ️ application. Median age was 41.7 [interquartile range (IQR): 34-50] years, the Simplified Acute Physiologic Score 3 (SAPS 3) was 64 (IQR: 56-74), and the Sequential Organ Failure Assessment Score (SOFA) was 6 (IQR: 4-9) points. The main causes of admission were sepsis (54.5%) and acute respiratory failure (13.7%). ICU and hospital mortality rates were 32.3% and 40.4%, respectively. In a multivariate analysis, time until ICU admission ≥ 3 days (P = 0.0013), performance status (Eastern Cooperative Oncology Group score, P = 0.0344), coma (Glasgow Coma Scale ≤ 8 points, P = 0.0213) and sepsis (P = 0.0003) were associated with increased hospital mortality. Coma (P = 0.0002) and sepsis (P = 0.0008) were independently associated with 90-day survival., Conclusions: Delayed ICU admission and the severity of critical illness determine the short- and medium-term mortality rates of HIV-infected patients admitted to the ICU, rather than factors associated with HIV infection. These results suggest that prognostic factors of HIV-infected patients in the ICU are similar to those of non-HIV-infected populations., (© 2020 British HIV Association.)

Isougenol is a phytoconstituent found in several essential oils. Since many natural products are potent antimicrobials, the synthesis of hybrid molecules-combining the chemical skeleton of the phytochemical with synthetic groups-can generate substances with enhanced biological activity. Based on this, the objective of this study was to evaluate the antifungal activity of isoeugenol and hybrid acetamides against Candida albicans isolated from the oral cavity. The methodologies used were the determination of minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), action on fungal micromorphology, interaction test with nystatin by the checkerboard method and molecular docking study with important enzymes in the maintenance of fungal viability. The synthetic molecules did not demonstrate significant antifungal activity in vitro. The isoeugenol MIC and MFC varied between 128 and 256 µg/mL, being the phytoconstituent able to interfere in the formation of blastoconid and chlamydoconid structures, important in the pathogenic process of the species. The molecular docking study revealed that isoeugenol is a potential inhibitor of the enzymes 14-α-demethylase and delta-14-sterol reductase, interfering in the fungal cell membrane biosynthesis. Thus, this research provides clearer expectations for future pharmacological studies with isoeugenol and derived molecules, aiming at its therapeutic application against infections caused by Candida spp.

Locomotion in virtual environments is currently a difficult and unnatural task to perform. Normally, researchers tend to devise ground- or floor-based metaphors to constrain the degrees of freedom (DoFs) during motion. These restrictions enable interactions that accurately emulate the human gait to provide high interaction fidelity. However, flying allows users to reach specific locations in a virtual scene more expeditiously. Our experience suggests that even though flying is not innate to humans, high-interaction-fidelity techniques may also improve the flying experience since flying requires simultaneously controlling additional DoFs. We present the Magic Carpet, an approach to flying that combines a floor proxy with a full-body representation to avoid balance and cybersickness issues. This design space enables DoF separation by treating direction indication and speed control as two separate phases of travel, thereby enabling techniques with higher interaction fidelity. To validate our design space, we conducted two complementary studies, one for each of the travel phases. In this paper, we present the results of both studies and report the best techniques for use within the Magic Carpet design space. To this end, we use both objective and subjective measures to evaluate the efficiency, embodiment effect, and side effects, such as physical fatigue and cybersickness, of the tested techniques in our design space. Our results show that the proposed approach enables high-interaction-fidelity techniques while improving the user experience.

Background: Maternal exposure to antibodies, cytokines or parasitic antigens during gestation may alter the degree of immune competence of offspring. Here we describe the production of cytokines and chemokines, and the ability to activation of the immune response in infants from mothers sensitized to helminths., Methods: It were selected five infants born to helminth-seropositive mothers but who were negative for current helminth infection. Whole blood was cultured without stimulus, with phytohemagglutinin mitogen (5 μg/ml, 24 h) or with purified protein derivative (PPD) (1 μg/ml, 24 h), and the supernatant was assessed for presence of Th1/Th2 cytokines (IFN-γ, TNF-α, IL-10, IL-5, IL-4 and IL-2) and chemokines (CXCL10, CCL2, CXCL9, CCL5 and CXCL8) by cytometric bead array., Results: All infants produced CCL5. Two infants demonstrated a mixed profile of Th1 (CXCL9) and Th2 (CCL2) chemokines in the presence of CXCL10, while one infant showed skewing towards Th2 without CXCL10 and two of them had been impaired immune response (children from sensitized to Schistosoma mansoni mothers)., Conclusion: Infants with Th1 and Th2 profile chemokines demonstrated a good response to vaccination, indicated by CXCL10 levels, but not infants predominantly Th2-skewed profile. These results highlight that children from mothers sensitized to S. mansoni may lead to ineffective immune response to PPD, while mothers sensitized to Ascaris lumbricoides showed no such impairment., (Copyright © 2018. Published by Elsevier B.V.)

The presence of anti-Ascaris (anti-Asc) immunoglobin isotypes alters the risk of allergic asthma. In this study, we analyzed the relationships between serum levels of anti-Asc IgE, IgG1, and IgG4, without concurrent infection by the parasite, and the presence of asthma. We measured cytokine levels from Th1, Th2, and Th17 profiles. Children aged 2-14 years old, asthmatics (n = 64), and non-asthmatics (n = 40) were selected according to the International Study of Asthma and Allergies in Childhood criteria. Asthmatic patients who had positive skin allergy tests were considered to have allergic asthma. Stool exams were performed to exclude children who were parasitized by helminths/protozoans and blood samples were collected in non-parasitized individuals. We performed peripheral blood leukocyte counts and in vitro culture following mitogenic stimulation. Levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17) in the supernatants were measured using a cytometric bead array. Titration of serum total IgE and IgE specific to Ascaris were obtained using ImmunoCAP; IgG1 and IgG4 titers were measured using enzyme-linked immunosorbent assays. Anti-Asc IgE was associated with a higher risk of asthma and an increase in the number of eosinophils and neutrophils. By contrast, anti-Asc IgG1 could be considered a protective factor against asthma, associated with lower levels of circulating neutrophils. There were high levels of IL-6 and TNF-α in asthmatics. Levels of IL-6, but not TNF-α, depended on the presence of anti-Asc IgG1 in serum. Anti-Asc IgE appears to increase risk of asthma, and anti-Asc IgG1 appears to favor decreased neutrophil counts and increased IL-6 levels., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest, (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Staphylococcus aureus is able to rapidly develop mechanisms of resistance to various drugs and to form strong biofilms, which makes it necessary to develop new antibacterial drugs. The essential oil of Melaleuca alternifolia is used as an antibacterial, a property believed to be mainly due to the presence of terpinen-4-ol. Based on this, the objective of this study was to evaluate the antibacterial and antibiofilm potential of terpinen-4-ol against S. aureus . The Minimal Inhibitory and Minimal Bactericidal Concentrations (MIC and MBC) of terpinen-4-ol were determined, and the effect of its combination with antibacterial drugs as well as its activity against S. aureus biofilms were evaluated. In addition, an in silico analysis of its pharmacokinetic parameters and a molecular docking analysis were performed. Terpinen-4-ol presented a MIC of 0.25% ( v/v ) and an MBC of 0.5% ( v/v ) (bactericidal action); its association with antibacterials was also effective. Terpinen-4-ol has good antibiofilm activity, and the in silico results indicated adequate absorption and distribution of the molecule in vivo. Molecular docking indicated that penicillin-binding protein 2a is a possible target of terpinen-4-ol in S. aureus . This work highlights the good potential of terpinen-4-ol as an antibacterial product and provides support for future pharmacological studies of this molecule, aiming at its therapeutic application.

Laser flash photolysis coupled with laser-induced fluorescence observation of OH has been used to observe the equilibration of OH + C 2 H 4 ↔ HOC 2 H 4 over the temperature range 563-723 K and pressures of bath gas (N 2 ) from 58 to 250 Torr. The time-resolved OH traces have been directly and globally fitted with a master equation in order to extract Δ R H 0 0 , the binding energy of the HOC 2 H 4 adduct, with respect to reagents. The global approach allows the role that OH abstraction plays at higher temperatures to be identified. The resultant value ofΔ R H 0 0 , 111.8 kJ mol -1 , is determined to be better than 2 kJ mol -1 and is in agreement with our ab initio calculations (carried out at the CCSD(T)/CBS//M06-2X/aug-cc-pVTZ level), 111.4 kJ mol -1 , and other state of the art calculations. Parameters for the abstraction channel are also in good agreement with previous experimental studies. To effect this analysis, the MESMER master equation code was extended to directly incorporate secondary chemistry: diffusional loss from the observation region and reaction with the photolytic precursor. These extensions, which, among other things, resolve issues related to the merging of chemically significant and internal energy relaxation eigenvalues, are presented.

Telecollaboration involves the teleportation of a remote collaborator to another real-world environment where their partner is located. The fidelity of the environment plays an important role for allowing corresponding spatial references in remote collaboration. We present a novel asymmetric platform, Augmented Virtual Teleportation (AVT), which provides high-fidelity telepresence of a remote VR user (VR-Traveler) into a real-world collaboration space to interact with a local AR user (AR-Host). AVT uses a 360° video camera (360-camera) that captures and live-streams the omni-directional scenes over a network. The remote VR-Traveler watching the video in a VR headset experiences live presence and co-presence in the real-world collaboration space. The VR-Traveler's movements are captured and transmitted to a 3D avatar overlaid onto the 360-camera which can be seen in the AR-Host's display. The visual and audio cues for each collaborator are synchronized in the Mixed Reality Collaboration space (MRC-space), where they can interactively edit virtual objects and collaborate in the real environment using the real objects as a reference. High fidelity, real-time rendering of virtual objects and seamless blending into the real scene allows for unique mixed reality use-case scenarios. Our working prototype has been tested with a user study to evaluate spatial presence, co-presence, and user satisfaction during telecollaboration. Possible applications of AVT are identified and proposed to guide future usage.

A major issue in modern agriculture is water loss through stomata during photosynthetic carbon assimilation. In water-limited ecosystems, annual plants have strategies to synchronize their growth and reproduction to the availability of water. Some species or ecotypes of flowers are early to ensure that their life cycles are completed before the onset of late season terminal drought ("drought escape"). This accelerated flowering correlates with low water-use efficiency (WUE). The molecular players and physiological mechanisms involved in this coordination are not fully understood. We analyzed WUE using gravimetry, gas exchange, and carbon isotope discrimination in florigen deficient (sft mutant), wild-type (Micro-Tom), and florigen over-expressing (SFT-ox) tomato lines. Increased florigen expression led to accelerated flowering time and reduced WUE. The low WUE of SFT-ox was driven by higher stomatal conductance and thinner leaf blades. This florigen-driven effect on WUE appears be independent of abscisic acid (ABA). Our results open a new avenue to increase WUE in crops in an ABA-independent manner. Manipulation of florigen levels could allow us to produce crops with a life cycle synchronized to water availability., (© 2019 John Wiley & Sons Ltd.)

Evidence suggests that the pathophysiology associated with epileptic susceptibility may disturb the functional connectivity of neural circuits and compromise the brain functions, even when seizures are absent. Although memory impairment is a common comorbidity found in patients with epilepsy, it is still unclear whether more caudal structures may play a role in cognitive deficits, particularly in those cases where there is no evidence of hippocampal sclerosis. This work used a genetically selected rat strain for seizure susceptibility (Wistar audiogenic rat, WAR) and distinct behavioral (motor and memory-related tasks) and electrophysiological (inferior colliculus, IC) approaches to access acoustic primary integrative network properties. The IC neural assemblies' response was evaluated by auditory transient (focusing on bottom-up processing) and steady-state evoked response (ASSR, centering on feedforward and feedback forces over neural circuitry). The results show that WAR displayed no disturbance in motor performance or hippocampus-dependent memory tasks. Nonetheless, WAR animals exhibited significative impairment for auditory fear conditioning (AFC) along with no indicative of IC plastic changes between the pre-conditioning and test phases (ASSR coherence analysis). Furthermore, WAR's IC response to transient stimuli presented shorter latency and higher amplitude compared with Wistar; and the ASSR analysis showed similar results for WAR and Wistar animals under subthreshold dose of pentylenetetrazol (pro-convulsive drug) for seizure-induction. Our work demonstrated alterations at WAR IC neural network processing, which may explain the associated disturbance on AFC memory., (Copyright © 2019 Pinto, Oliveira Lucas, Carvalho, Mourão, Guarnieri, Mendes, Medeiros and Moraes.)

The current status of policies on illicit drugs has implications for Collective Health that need to be discussed in depth. This essay aims to explore, in light of the best evidence, the public health impact of drug policies focused on the criminalization of growing, selling, and consuming psychoactive substances. Brazil provides the context for the main analysis. The principal points addressed in this work include drugs as a social issue and the definition of the prohibitionist paradigm, evidence of the unhealthy relationship between this paradigm and the population's health, the issue of a model of care for users of psychoactive substances focused on therapeutic communities, and future paths to be explored to overcome the prohibition of illicit drugs as the principal approach to the issue. Among the main problematic elements in the repressive approach in the Brazilian context, the study highlights violence and homicides, the health impacts of incarceration and blocked access to the health system, and potential new therapies derived from currently banned psychoactive substances. As proposals for future policy changes, the study highlights decriminalization of the use, possession, and small-scale sale of drugs; the reduction of the violence and discrimination associated with policing; focus on harm reduction policies; approach to gender-related specificities; and inclusion of social variables as metrics for successful treatment of problematic drug use. In conclusion, it is relevant that the social issue and drug policy have become the object of more studies in the field of Collective Health.

Crotonrizzinii Farias & Riina, sp. nov. is a new species from Serra dos Órgãos National Park in the Atlantic Rain Forest domain (Rio de Janeiro state, Brazil). It is known from the municipalities of Guapimirim, Teresópolis and Petrópolis, where it grows in montane ombrophilous dense forest, between 500 and 1500 m elevation. This arborescent species belongs to CrotonsectionCyclostigma Griseb., a Neotropical lineage distributed in forest habitats from Mexico to northern Argentina. It is mainly characterised by its laciniate-glandular stipules, bracts with two inconspicuous glands (colleters) at the base and campanulate pistillate flowers with sepals covering the ovary. We describe and illustrate the new species, and compare it with close relatives occurring in the Atlantic Rain Forest. We also provide a distribution map, habitat information and suggestions for the assessment of its conservation status.

From bacteria to mammals, nearly all organisms have adapted their physiology and behavior to a daily rhythm. These circadian (daily) rhythms influence virtually all aspects of physiological architecture (i.e., from gene expression to organismal behavior). Therefore, it is not surprising that several features of the immune response are regulated in a time-of-day dependent manner. The field of chrono-immunology has expanded tremendously over the past decade. In this abridged review, we present studies from the past five years that have revealed new parameters of the immune system that demonstrate daily variations in the control of pathogens and response to microbial components. These studies analyzed how the disruption of circadian rhythms impairs immune function, how microbial components alter the circadian clock, and how immune responses demonstrate daily variations in human subjects. Further elucidating the intricate connections between the circadian clock and the immune system will hopefully provide opportunities for chrono-immunotherapy in disease treatment and prevention.

Purpose: To review available evidence in the literature on impulse oscillometry in the assessment of lung function in children with respiratory diseases, especially asthma., Data Collection: Research in the Medline, PubMed, and Lilacs databases, with the keywords forced oscillation, impulse oscillometry, asthma and impulse oscillometry., Results: The Impulse Oscillometry System (IOS) allows the measurement of resistance and reactance of airways and is used as a diagnostic resource. A significant association between the findings of the IOS and those of spirometry is observed. In asthma, the IOS has already been used to assess the bronchodilator response and the therapeutic response to different drugs and has shown to be a sensitive technique to evaluate disease control. There are limitations to this assessment, such as children with attention deficit and in some cases it is difficult to interpret the results from a clinical point of view., Conclusion: The IOS is a useful tool for the measurement of the lung function of children. It is an easy test, although its interpretation is not straightforward., (Copyright © 2018. Published by Elsevier España, S.L.U.)

The etiology of severe hemolytic anemia in most patients with recessive hereditary spherocytosis (rHS) and the related disorder hereditary pyropoikilocytosis (HPP) is unknown. Whole exome sequencing of DNA from probands of 24 rHS or HPP kindreds identified numerous mutations in erythrocyte membrane α-spectrin (SPTA1). Twenty-eight mutations were novel, with null alleles frequently found in trans to missense mutations. No mutations were identified in a third of SPTA1 alleles (17/48). Whole genome sequencing revealed linkage disequilibrium between the common rHS-linked α-spectrinBug Hill polymorphism and a rare intron 30 variant in all 17 mutation-negative alleles. In vitro minigene studies and in vivo splicing analyses revealed the intron 30 variant changes a weak alternate branch point (BP) to a strong BP. This change leads to increased utilization of an alternate 3' splice acceptor site, perturbing normal α-spectrin mRNA splicing and creating an elongated mRNA transcript. In vivo mRNA stability studies revealed the newly created termination codon in the elongated transcript activates nonsense mediated decay leading to spectrin deficiency. These results demonstrate a unique mechanism of human genetic disease contributes to the etiology of a third of cases of rHS, facilitating diagnosis and treatment of severe anemia, and identifying a new target for therapeutic manipulation.

Background: TRACK (Test for Respiratory and Asthma Control in Kids) questionnaire is an instrument developed and validated in English to evaluate the control of respiratory symptoms in children under 5 years of age., Objective: To validate the Portuguese version of the TRACK questionnaire., Methods: The validation was done in an observational, prospective and multicenter evaluation (six centers in Brazil) in children with recurrent respiratory symptoms. Children were classified according to symptoms, GINA criteria and medical evaluation. Parents and doctors rated child respiratory symptom control in the last month (VAS). Approval from the Institutional Review Board was obtained in each centre, and written informed consent was obtained from parents., Results: Data from 299 children were obtained at baseline, and 195 at follow-up. The median score of the TRACK questionnaire was 65 and Cronbach's α was 0.70. TRACK scores showed significant correlation with the medical and family opinions about symptom control (r: 0.74 and r: 0.61). TRACK scores were significantly lower in children who had used systemic steroids (median [IQR]: 45 [30-65] vs 75 [55-80]; p  < 0.001) and had an emergency visit in the last month (45 [35-60] vs 70 [55-80]; p  < 0.001). TRACK scores were also significantly different when children were separated by the medical opinion, GINA criteria and symptoms. Comparison of different respiratory symptom control cut-off points showed that the cut-off of 80 points had the highest area under ROC curve (0.800)., Conclusion: We have demonstrated that the Portuguese version of the TRACK questionnaire has satisfactory reliability (internal consistency), adequate criterion validity (compared against GINA levels of control) and constructive validity (compared against respiratory symptoms and medical opinion), showing that it can be a useful tool to discriminate among children with different levels of respiratory symptom control., Trial Registration: ClinicalTrials.gov: NCT03290222., Competing Interests: The study was approved by Universidade Federal de São Paulo Ethics Committee (CAAE: 57313416.1.1001.5505).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.