Tissue folding at the organ-meristem boundary results in nuclear compression and chromatin compaction.

Artificial mechanical perturbations affect chromatin in animal cells in culture. Whether this is also relevant to growing tissues in living organisms remains debated. In plants, aerial organ emergence occurs through localized outgrowth at the periphery of the shoot apical meristem, which also contains a stem cell niche. Interestingly, organ outgrowth has been proposed to generate compression in the saddle-shaped organ-meristem boundary domain. Yet whether such growth-induced mechanical stress affects chromatin in plant tissues is unknown. Here, by imaging the nuclear envelope in vivo over time and quantifying nucleus deformation, we demonstrate the presence of active nuclear compression in that domain. We developed a quantitative pipeline amenable to identifying a subset of very deformed nuclei deep in the boundary and in which nuclei become gradually narrower and more elongated as the cell contracts transversely. In this domain, we find that the number of chromocenters is reduced, as shown by chromatin staining and labeling, and that the expression of linker histone H1.3 is induced. As further evidence of the role of forces on chromatin changes, artificial compression with a MicroVice could induce the ectopic expression of H1.3 in the rest of the meristem. Furthermore, while the methylation status of chromatin was correlated with nucleus deformation at the meristem boundary, such correlation was lost in the h1.3 mutant. Altogether, we reveal that organogenesis in plants generates compression that is able to have global effects on chromatin in individual cells.

Associations between cortical ß-amyloid burden, fornix microstructure and cognitive processing of faces, places, bodies and other visual objects in early Alzheimer's disease.

Using two imaging modalities, that is, Pittsburgh compound B (PiB) positron emission tomography (PET) and diffusion tensor imaging (DTI) the present study tested associations between cortical amyloid-beta (Aß) burden and fornix microstructural changes with cognitive deficits in early Alzheimer's disease (AD), namely deficits in working memory (1-back) processing of visual object categories (faces, places, objects, bodies and verbal material). Second, we examined cortical Aß associations with fornix microstructure. Seventeen early AD patients and 17 healthy-matched controls were included. Constrained spherical deconvolution-based tractography was used to segment the fornix and a control tract the central branch of the superior longitudinal fasciculus (CB-SLF) previously implicated in working memory processes. Standard uptake value ratios (SUVR) of Aß were extracted from 45 cortical/subcortical regions from the AAL atlas and subject to principal component analysis for data reduction. Patients exhibited (i) impairments in cognitive performance (ii) reductions in fornix fractional anisotropy (FA) and (iii) increases in a component that loaded highly on cortical Aß. There were no group differences in CB-SLF FA and in a component loading highly on subcortical Aß. Partial correlation analysis in the patient group showed (i) positive associations between fornix FA and performance for all the visual object categories and (ii) a negative association between the cortical Aß component and performance for the object categories but not for the remaining classes of visual stimuli. A subsequent analysis showed a positive association between overall cognition (performance across distinct 1-back task conditions) with fornix FA but no association with cortical Aß burden, in keeping with influential accounts on early onset AD. This indicates that the fornix degenerates early in AD and contributes to deficits in working memory processing of visual object categories; though it is also important to acknowledge the importance of prospective longitudinal studies with larger samples. Overall, the effect sizes of fornical degeneration on visual working memory appeared stronger than the ones related to amyloid burden.

Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche.

Cell size and growth kinetics are fundamental cellular properties with important physiological implications. Classical studies on yeast, and recently on bacteria, have identified rules for cell size regulation in single cells, but in the more complex environment of multicellular tissues, data have been lacking. In this study, to characterize cell size and growth regulation in a multicellular context, we developed a 4D imaging pipeline and applied it to track and quantify epidermal cells over 3-4 d in Arabidopsis thaliana shoot apical meristems. We found that a cell size checkpoint is not the trigger for G2/M or cytokinesis, refuting the unexamined assumption that meristematic cells trigger cell cycle phases upon reaching a critical size. Our data also rule out models in which cells undergo G2/M at a fixed time after birth, or by adding a critical size increment between G2/M transitions. Rather, cell size regulation was intermediate between the critical size and critical increment paradigms, meaning that cell size fluctuations decay by ∼75% in one generation compared with 100% (critical size) and 50% (critical increment). Notably, this behavior was independent of local cell-cell contact topologies and of position within the tissue. Cells grew exponentially throughout the first >80% of the cell cycle, but following an asymmetrical division, the small daughter grew at a faster exponential rate than the large daughter, an observation that potentially challenges present models of growth regulation. These growth and division behaviors place strong constraints on quantitative mechanistic descriptions of the cell cycle and growth control.

Effect of Flexible Family Visitation on Delirium Among Patients in the Intensive Care Unit: The ICU Visits Randomized Clinical Trial.

Importance: The effects of intensive care unit (ICU) visiting hours remain uncertain. Objective: To determine whether a flexible family visitation policy in the ICU reduces the incidence of delirium. Design, Setting and Participants: Cluster-crossover randomized clinical trial involving patients, family members, and clinicians from 36 adult ICUs with restricted visiting hours (<4.5 hours per day) in Brazil. Participants were recruited from April 2017 to June 2018, with follow-up until July 2018. Interventions: Flexible visitation (up to 12 hours per day) supported by family education (n = 837 patients, 652 family members, and 435 clinicians) or usual restricted visitation (median, 1.5 hours per day; n = 848 patients, 643 family members, and 391 clinicians). Nineteen ICUs started with flexible visitation, and 17 started with restricted visitation. Main Outcomes and Measures: Primary outcome was incidence of delirium during ICU stay, assessed using the CAM-ICU. Secondary outcomes included ICU-acquired infections for patients; symptoms of anxiety and depression assessed using the HADS (range, 0 [best] to 21 [worst]) for family members; and burnout for ICU staff (Maslach Burnout Inventory). Results: Among 1685 patients, 1295 family members, and 826 clinicians enrolled, 1685 patients (100%) (mean age, 58.5 years; 47.2% women), 1060 family members (81.8%) (mean age, 45.2 years; 70.3% women), and 737 clinicians (89.2%) (mean age, 35.5 years; 72.9% women) completed the trial. The mean daily duration of visits was significantly higher with flexible visitation (4.8 vs 1.4 hours; adjusted difference, 3.4 hours [95% CI, 2.8 to 3.9]; P < .001). The incidence of delirium during ICU stay was not significantly different between flexible and restricted visitation (18.9% vs 20.1%; adjusted difference, -1.7% [95% CI, -6.1% to 2.7%]; P = .44). Among 9 prespecified secondary outcomes, 6 did not differ significantly between flexible and restricted visitation, including ICU-acquired infections (3.7% vs 4.5%; adjusted difference, -0.8% [95% CI, -2.1% to 1.0%]; P = .38) and staff burnout (22.0% vs 24.8%; adjusted difference, -3.8% [95% CI, -4.8% to 12.5%]; P = .36). For family members, median anxiety (6.0 vs 7.0; adjusted difference, -1.6 [95% CI, -2.3 to -0.9]; P < .001) and depression scores (4.0 vs 5.0; adjusted difference, -1.2 [95% CI, -2.0 to -0.4]; P = .003) were significantly better with flexible visitation. Conclusions and Relevance: Among patients in the ICU, a flexible family visitation policy, vs standard restricted visiting hours, did not significantly reduce the incidence of delirium. Trial Registration: ClinicalTrials.gov Identifier: NCT02932358.

Effectiveness and Safety of an Extended ICU Visitation Model for Delirium Prevention: A Before and After Study.

OBJECTIVES: To evaluate the effect of an extended visitation model compared with a restricted visitation model on the occurrence of delirium among ICU patients. DESIGN: Prospective single-center before and after study. SETTING: Thirty-one-bed medical-surgical ICU. PATIENTS: All patients greater than or equal to 18 years old with expected length of stay greater than or equal to 24 hours consecutively admitted to the ICU from May 2015 to November 2015. INTERVENTIONS: Change of visitation policy from a restricted visitation model (4.5 hr/d) to an extended visitation model (12 hr/d). MEASUREMENTS AND MAIN RESULTS: Two hundred eighty-six patients were enrolled (141 restricted visitation model, 145 extended visitation model). The primary outcome was the cumulative incidence of delirium, assessed bid using the confusion assessment method for the ICU. Predefined secondary outcomes included duration of delirium/coma; any ICU-acquired infection; ICU-acquired bloodstream infection, pneumonia, and urinary tract infection; all-cause ICU mortality; and length of ICU stay. The median duration of visits increased from 133 minutes (interquartile range, 97.7-162.0) in restricted visitation model to 245 minutes (interquartile range, 175.0-272.0) in extended visitation model (p < 0.001). Fourteen patients (9.6%) developed delirium in extended visitation model compared with 29 (20.5%) in restricted visitation model (adjusted relative risk, 0.50; 95% CI, 0.26-0.95). In comparison with restricted visitation model patients, extended visitation model patients had shorter length of delirium/coma (1.5 d [interquartile range, 1.0-3.0] vs 3.0 d [interquartile range, 2.5-5.0]; p = 0.03) and ICU stay (3.0 d [interquartile range, 2.0-4.0] vs 4.0 d [interquartile range, 2.0-6.0]; p = 0.04). The rate of ICU-acquired infections and all-cause ICU mortality did not differ significantly between the two study groups. CONCLUSIONS: In this medical-surgical ICU, an extended visitation model was associated with reduced occurrence of delirium and shorter length of delirium/coma and ICU stay.

Transcriptional regulation of lineage commitment--a stochastic model of cell fate decisions.

Molecular mechanisms employed by individual multipotent cells at the point of lineage commitment remain largely uncharacterized. Current paradigms span from instructive to noise-driven mechanisms. Of considerable interest is also whether commitment involves a limited set of genes or the entire transcriptional program, and to what extent gene expression configures multiple trajectories into commitment. Importantly, the transient nature of the commitment transition confounds the experimental capture of committing cells. We develop a computational framework that simulates stochastic commitment events, and affords mechanistic exploration of the fate transition. We use a combined modeling approach guided by gene expression classifier methods that infers a time-series of stochastic commitment events from experimental growth characteristics and gene expression profiling of individual hematopoietic cells captured immediately before and after commitment. We define putative regulators of commitment and probabilistic rules of transition through machine learning methods, and employ clustering and correlation analyses to interrogate gene regulatory interactions in multipotent cells. Against this background, we develop a Monte Carlo time-series stochastic model of transcription where the parameters governing promoter status, mRNA production and mRNA decay in multipotent cells are fitted to experimental static gene expression distributions. Monte Carlo time is converted to physical time using cell culture kinetic data. Probability of commitment in time is a function of gene expression as defined by a logistic regression model obtained from experimental single-cell expression data. Our approach should be applicable to similar differentiating systems where single cell data is available. Within our system, we identify robust model solutions for the multipotent population within physiologically reasonable values and explore model predictions with regard to molecular scenarios of entry into commitment. The model suggests distinct dependencies of different commitment-associated genes on mRNA dynamics and promoter activity, which globally influence the probability of lineage commitment.

Detection of encephalitis-causing viruses reveals predominance of chikungunya virus in the state of Bahia, Brazil.

OBJECTIVES: Encephalitis is a severe neurological syndrome for which herpesvirus and enteroviruses are the most common etiological agents. Arboviruses, a wildly diverse group of pathogens, are also critical epidemiological agents associated with encephalitis. In Brazil, little is known about the causative agents of encephalitis. METHODS: We conducted a hospital surveillance for encephalitis between 2020 and 2022. Molecular (RT-PCR and qPCR) and serological (virus-specific IgM and viral antigens) techniques were performed in cerebrospinal fluid and serum samples obtained from study participants. RESULTS: In the 43 participants evaluated, the etiologic agent or the presence of IgM was detected in 16 (37.2%). Nine (20.9%) cases were positive for chikungunya virus (CHIKV), three (7.0%) for dengue virus, two (4.7%) for human adenovirus, one (2.3%) for varicella-zoster virus, and one (2.3%) for enterovirus. Whole-genome sequencing revealed that the CHIKV identified belongs to the East/Central/South African lineage. CONCLUSION: Herein, CHIKV is a common pathogen identified in encephalitis cases. Our results reinforce previous evidence that chikungunya represents a significant cause of encephalitis during CHIKV outbreaks and epidemics and add to existing information on the epidemiology of encephalitis in Brazil.

Factors associated with small ruminant lentivirus infection in goat herds from Pernambuco state, Northeast region of Brazil.

Serum samples (n = 1532) were collected between May 2011 to April 2012 from goats from 76 herds (49 from dairy farms and 27 herds for genetic improvement) from three geographical regions from the state of Pernambuco, Brazil: Zona da Mata, Agreste, and Sertão. Samples were processed using agar gel immunodiffusion test, with p28 CAEV antigen. The objective was to determine the risk factors for small ruminant lentivirus (SRLV) in dairy goats and goats with high genetic value. Overall, seroprevalence was 13.7% (210/1532) [95% CI: 12-15.4%] in animals and 67.1% (51/76) [95% CI: 56.5%- 77.7%] in herds. In dairy farms the seroprevalence was 73.5% (36/49) [95% CI: 61.1%- 85.8%], and in properties with animals of high genetic value it was 55.6% (15/27) [95% CI: 36.8%- 74.3%]. Robust Poisson regression analysis adjusted by the random effect of the herd showed that risk factors were: importing bucks from another Brazilian state (prevalence ratio [PR] = 4.73 [95% CI: 2.05; 10.88]), not isolating sick animals (PR = 3.27 [95% CI: 2.24; 4.76]), and participating in fairs/animal crowding (PR = 1.52 [95% CI: 1.09; 2.11]). Prevalence results show that SRLV is present in caprine herds in the state of Pernambuco and identified risk factors are strongly related to animal transit. Considering the epidemiological situation, the first step for mitigating the consequences of this disease would be controlling animal transit.

Frontoparietal microstructural damage mediates age-dependent working memory decline in face and body information processing: Evidence for dichotomic hemispheric bias mechanisms.

Age-associated damage in the microstructure of frontally-based connections (e.g. genu of the corpus callosum and superior longitudinal fasciculus) is believed to lead to impairments in processing speed and executive function. Using mediation analysis, we tested the potential contribution of callosal and frontoparietal association tracts to age-dependent effects on cognition/executive function as measured with 1-back working memory tasks for visual stimulus categories (i.e. faces and non-emotional bodies) in a group of 55 healthy adults (age range 23-79 years). Constrained spherical deconvolution-based tractography was employed to reconstruct the genu/prefrontal section of the corpus callosum (GCC) and the central/second branch of the superior longitudinal fasciculus (CB-SLF). Age was associated with (i) reductions in fractional anisotropy (FA) in the GCC and in the right and left CB-SLF and (iii) decline in visual object category processing. Mediation analysis revealed that microstructural damage in right hemispheric CB-SLF is associated with age-dependent decline in face processing likely reflecting the stimulus-specific/holistic nature of face processing within dedicated/specialized frontoparietal routes. By contrast, microstructural damage in left hemispheric CB-SLF associated with age-dependent decline in non-emotional body processing, consistent with the more abstract nature of non-emotional body categories. In sum, our findings suggest that frontoparietal microstructural damage mediates age-dependent decline in face and body information processing in a manner that reflects the hemispheric bias of holistic vs. abstract nature of face and non-emotional body category processing.

Structural impairments in hippocampal and occipitotemporal networks specifically contribute to decline in place and face category processing but not to other visual object categories in healthy aging.

BACKGROUND: Functional neuroimaging studies have identified a set of nodes in the occipital-temporal cortex that preferentially respond to faces in comparison with other visual objects. By contrast, the processing of places seems to rely on parahippocampal cortex and structures heavily implicated in memory (e.g., the hippocampus). It has been suggested that human aging leads to decreased neural specialization of core face and place processing areas and impairments in face and place perception. METHODS: Using mediation analysis, we tested the potential contribution of micro- and macrostructure within the hippocampal and occipitotemporal systems to age-associated effects in face and place category processing (as measured by 1-back working memory tasks) in 55 healthy adults (age range 23-79 years). To test for specific contributions of the studied structures to face/place processing, we also studied a distinct tract (i.e., the anterior thalamic radiation [ATR]) and cognitive performance for other visual object categories (objects, bodies, and verbal material). Constrained spherical deconvolution-based tractography was used to reconstruct the fornix, the inferior longitudinal fasciculus (ILF), and the ATR. Hippocampal volumetric measures were segmented from FSL-FIRST toolbox. RESULTS: It was found that age associates with (a) decreases in fractional anisotropy (FA) in the fornix, in right ILF (but not left ILF), and in the ATR (b) reduced volume in the right and left hippocampus and (c) decline in visual object category processing. Importantly, mediation analysis showed that micro- and macrostructural impairments in the fornix and right hippocampus, respectively, associated with age-dependent decline in place processing. Alternatively, microstructural impairments in right hemispheric ILF associated with age-dependent decline in face processing. There were no other mediator effects of micro- and macrostructural variables on age-cognition relationships. CONCLUSION: Together, the findings support specific contributions of the fornix and right hippocampus in visuospatial scene processing and of the long-range right hemispheric occipitotemporal network in face category processing.

Characteristics and outcomes of patients with cancer requiring admission to intensive care units: a prospective multicenter study.

OBJECTIVE: To evaluate the characteristics and outcomes of patients with cancer admitted to several intensive care units. Knowledge on patients with cancer requiring intensive care is mostly restricted to single-center studies. DESIGN: : Prospective, multicenter, cohort study. SETTING: Intensive care units from 28 hospitals in Brazil. PATIENTS: A total of 717 consecutive patients included over a 2-mo period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 667 (93%) patients with solid tumors and 50 (7%) patients had hematologic malignancies. The main reasons for intensive care unit admission were postoperative care (57%), sepsis (15%), and respiratory failure (10%). Overall hospital mortality rate was 30% and was higher in patients admitted because of medical complications (58%) than in emergency (37%) and scheduled (11%) surgical patients (p < .001). Adjusting for covariates other than the type of admission, the number of hospital days before intensive care unit admission (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01-1.37), higher Sequential Organ Failure Assessment scores (OR, 1.25; 95% CI, 1.17-1.34), poor performance status (OR, 3.40; 95% CI, 2.19 -5.26), the need for mechanical ventilation (OR, 2.42; 95% CI, 1.51-3.87), and active underlying malignancy in recurrence or progression (OR, 2.42; 95% CI, 1.51-3.87) were associated with increased hospital mortality in multivariate analysis. CONCLUSIONS: This large multicenter study reports encouraging survival rates for patients with cancer requiring intensive care. In these patients, mortality was mostly dependent on the severity of organ failures, performance status, and need for mechanical ventilation rather than cancer-related characteristics, such as the type of malignancy or the presence of neutropenia.

Delirium epidemiology in critical care (DECCA): an international study.

INTRODUCTION: Delirium is a frequent source of morbidity in intensive care units (ICUs). Most data on its epidemiology is from single-center studies. Our aim was to conduct a multicenter study to evaluate the epidemiology of delirium in the ICU. METHODS: A 1-day point-prevalence study was undertaken in 104 ICUs from 11 countries in South and North America and Spain. RESULTS: In total, 975 patients were screened, and 497 fulfilled inclusion criteria and were enrolled (median age, 62 years; 52.5% men; 16.7% and 19.9% for ICU and hospital mortality); 64% were admitted to the ICU because of medical causes, and sepsis was the main diagnosis (n = 76; 15.3%). In total, 265 patients were sedated with the Richmond agitation and sedation scale (RASS) deeper than -3, and only 232 (46.6%) patients could be evaluated with the confusion-assessment method for the ICU. The prevalence of delirium was 32.3%. Compared with patients without delirium, those with the diagnosis of delirium had a greater severity of illness at admission, demonstrated by higher sequential organ-failure assessment (SOFA (P = 0.004)) and simplified acute physiology score 3 (SAPS3) scores (P < 0.0001). Delirium was associated with increased ICU (20% versus 5.7%; P = 0.002) and hospital mortality (24 versus 8.3%; P = 0.0017), and longer ICU (P < 0.0001) and hospital length of stay (LOS) (22 (11 to 40) versus 7 (4 to 18) days; P < 0.0001). Previous use of midazolam (P = 0.009) was more frequent in patients with delirium. On multivariate analysis, delirium was independently associated with increased ICU mortality (OR = 3.14 (1.26 to 7.86); CI, 95%) and hospital mortality (OR = 2.5 (1.1 to 5.7); CI, 95%). CONCLUSIONS: In this 1-day international study, delirium was frequent and associated with increased mortality and ICU LOS. The main modifiable risk factors associated with the diagnosis of delirium were the use of invasive devices and sedatives (midazolam).

Drumming Motor Sequence Training Induces Apparent Myelin Remodelling in Huntington's Disease: A Longitudinal Diffusion MRI and Quantitative Magnetization Transfer Study.

BACKGROUND: Impaired myelination may contribute to Huntington's disease (HD) pathogenesis. OBJECTIVE: This study assessed differences in white matter (WM) microstructure between HD patients and controls, and tested whether drumming training stimulates WM remodelling in HD. Furthermore, it examined whether training-induced microstructural changes are related to improvements in motor and cognitive function. METHODS: Participants undertook two months of drumming exercises. Working memory and executive function were assessed before and post-training. Changes in WM microstructure were investigated with diffusion tensor magnetic resonance imaging (DT-MRI)-based metrics, the restricted diffusion signal fraction (Fr) from the composite hindered and restricted model of diffusion (CHARMED) and the macromolecular proton fraction (MPF) from quantitative magnetization transfer (qMT) imaging. WM pathways linking putamen and supplementary motor areas (SMA-Putamen), and three segments of the corpus callosum (CCI, CCII, CCIII) were studied using deterministic tractography. Baseline MPF differences between patients and controls were assessed with tract-based spatial statistics. RESULTS: MPF was reduced in the mid-section of the CC in HD subjects at baseline, while a significantly greater change in MPF was detected in HD patients relative to controls in the CCII, CCIII, and the right SMA-putamen post-training. Further, although patients improved their drumming and executive function performance, such improvements did not correlate with microstructural changes. Increased MPF suggests training-induced myelin changes in HD. CONCLUSION: Though only preliminary and based on a small sample size, these results suggest that tailored behavioural stimulation may lead to neural benefits in early HD, that could be exploited for delaying disease progression.

Assessing the Role of the Left Dorsal Frontal Cortex in Working Memory Guidance: Attentional or Mnemonic? A Neurostimulation Study.

Perceptual selection can be guided by the contents of working memory (WM). Neuroimaging and neuropsychological data point to a role of a fronto-parietal and fronto-thalamic networks in WM guidance. Here we assessed the effect of transcranial direct current stimulation of the left dorsal frontal cortex (lDFC) in a combined WM/attention paradigm. We asked the extent to which the lDFC is implicated in mnemonic and selective attention functions during WM guidance of behavior. Observers were asked to keep information in memory while searching for a visual target, while the validity of WM contents for the search task varied. We tested the effects of lDFC-tDCS on the strength of WM guidance of search, whether any tDCS effect is dependent on the amount of WM load, and whether lDFC-tDCS primarily influences how WM contents are retained, the process of selective attention in search task, or both. Consistent with prior behavioral findings, we found that (i) selection of items that matched the contents of WM was facilitated relative to non-matching items and (ii) this WM guidance effect was reduced when the level processing/cognitive load in WM was higher. Notably, across two experiments we found that lDFC-tDCS modulated WM guidance of visual selection in the context of high processing loads in WM. No effects of tDCS were observed in WM accuracy. These findings suggest that the role of the left dorsal frontal cortex in WM guidance is associated with selective attentional control rather than mnemonic processing.

Myelin Breakdown in Human Huntington's Disease: Multi-Modal Evidence from Diffusion MRI and Quantitative Magnetization Transfer.

Huntington's disease (HD) leads to white matter (WM) degeneration that may be due to an early breakdown in axon myelination but in vivo imaging correlates of demyelination remain relatively unexplored in HD compared to other neurodegenerative diseases. This study investigated HD-related effects on a putative marker of myelin, the macromolecular proton fraction (MMPF) from quantitative magnetization transfer and on fractional anisotropy, axial and radial diffusivity from diffusion tensor MR-imaging. Microstructural differences were studied in WM pathways of the basal ganglia and motor systems known to be impaired in HD: the corpus callosum, the cortico-spinal tract, the anterior thalamic radiation, fibers between prefrontal cortex and caudate and between supplementary motor area and putamen. Principal component analysis was employed for dimensionality reduction. Patients showed reductions in a component with high loadings on MMPF in all WM pathways and a trend for increases in a component loading on axial and radial diffusivities but no differences in a component loading on fractional anisotropy. While patients' performance in executive functioning was impaired, their working memory span was preserved. Inter-individual differences in the diffusivity component correlated with patients' performance in clinical measures of the United Huntington Disease Rating Scale. In summary, HD-related reductions in MMPF suggest that myelin breakdown contributes to WM impairment in human HD and emphasize the potential of quantitative MRI metrics to inform about disease pathogenesis. Disease severity in manifest HD, however, was best captured by non-specific diffusivity metrics sensitive to multiple disease and age-related changes.

Study protocol to assess the effectiveness and safety of a flexible family visitation model for delirium prevention in adult intensive care units: a cluster-randomised, crossover trial (The ICU Visits Study).

INTRODUCTION: Flexible intensive care unit (ICU) visiting hours have been proposed as a means to improve patient-centred and family-centred care. However, randomised trials evaluating the effects of flexible family visitation models (FFVMs) are scarce. This study aims to compare the effectiveness and safety of an FFVM versus a restrictive family visitation model (RFVM) on delirium prevention among ICU patients, as well as to analyse its potential effects on family members and ICU professionals. METHODS AND ANALYSIS: A cluster-randomised crossover trial involving adult ICU patients, family members and ICU professionals will be conducted. Forty medical-surgical Brazilian ICUs with RFVMs (<4.5 hours/day) will be randomly assigned to either an RFVM (visits according to local policies) or an FFVM (visitation during 12 consecutive hours per day) group at a 1:1 ratio. After enrolment and follow-up of 25 patients, each ICU will be switched over to the other visitation model, until 25 more patients per site are enrolled and followed. The primary outcome will be the cumulative incidence of delirium among ICU patients, measured twice a day using the Confusion Assessment Method for the ICU. Secondary outcome measures will include daily hazard of delirium, ventilator-free days, any ICU-acquired infections, ICU length of stay and hospital mortality among the patients; symptoms of anxiety and depression and satisfaction among the family members; and prevalence of burnout symptoms among the ICU professionals. Tertiary outcomes will include need for antipsychotic agents and/or mechanical restraints, coma-free days, unplanned loss of invasive devices and ICU-acquired pneumonia, urinary tract infection or bloodstream infection among the patients; self-perception of involvement in patient care among the family members; and satisfaction among the ICU professionals. ETHICS AND DISSEMINATION: The study protocol has been approved by the research ethics committee of all participant institutions. We aim to disseminate the findings through conferences and peer-reviewed journals. TRIAL REGISTRATION: NCT02932358.

Quality of life after intensive care unit: a multicenter cohort study protocol for assessment of long-term outcomes among intensive care survivors in Brazil. / Qualidade de vida pós-unidades de terapia intensiva: protocolo de estudo de coorte multicêntrico para avaliação de desfechos em longo prazo em sobreviventes de internação em unidades de terapia intensiva brasileiras.

OBJECTIVE: To establish the prevalence of physical, cognitive and psychiatric disabilities, associated factors and their relationship with the qualities of life of intensive care survivors in Brazil. METHODS: A prospective multicenter cohort study is currently being conducted at 10 adult medical-surgical intensive care units representative of the 5 Brazilian geopolitical regions. Patients aged ≥ 18 years who are discharged from the participating intensive care units and stay 72 hours or more in the intensive care unit for medical or emergency surgery admissions or 120 hours or more for elective surgery admissions are consecutively included. Patients are followed up for a period of one year by means of structured telephone interviews conducted at 3, 6 and 12 months after discharge from the intensive care unit. The outcomes are functional dependence, cognitive dysfunction, anxiety and depression symptoms, posttraumatic stress symptoms, health-related quality of life, rehospitalization and long-term mortality. DISCUSSION: The present study has the potential to contribute to current knowledge of the prevalence and factors associated with postintensive care syndrome among adult intensive care survivors in Brazil. In addition, an association might be established between postintensive care syndrome and health-related quality of life.

OBJETIVO: Avaliar a prevalência de incapacidades físicas, cognitivas e psiquiátricas, fatores associados e sua relação com qualidade de vida em pacientes sobreviventes de internação em unidades de terapia intensiva brasileiras. MÉTODOS: Um estudo de coorte prospectivo multicêntrico está sendo conduzido em dez unidades de terapia intensiva adulto clínico-cirúrgicas representativas das cinco regiões geopolíticas do Brasil. Pacientes com idade ≥ 18 anos que receberam alta das unidades de terapia intensiva participantes e permaneceram internados na unidade de terapia intensiva por 72 horas ou mais, nos casos de internação clínica ou cirúrgica de urgência, e por 120 horas ou mais, nos casos de internação cirúrgica eletiva, serão incluídos de forma consecutiva. Estes pacientes serão seguidos por 1 ano, por meio de entrevistas telefônicas estruturadas 3, 6 e 12 meses pós-alta da unidade de terapia intensiva. Dependência funcional, disfunção cognitiva, sintomas de ansiedade e depressão, sintomas de estresse pós-traumático, qualidade de vida relacionada à saúde, re-hospitalizações e mortalidade em longo prazo serão avaliados como desfechos. DISCUSSÃO: O presente estudo tem o potencial de contribuir para o conhecimento a respeito da prevalência e dos fatores associados à síndrome pós-cuidados intensivos na população de pacientes adultos sobreviventes de internação em unidades de terapia intensiva brasileiras. Ademais, a associação entre síndrome pós-cuidados intensivos e qualidade de vida relacionada à saúde poderá ser estabelecida.

Fluctuations of the transcription factor ATML1 generate the pattern of giant cells in the Arabidopsis sepal.

Multicellular development produces patterns of specialized cell types. Yet, it is often unclear how individual cells within a field of identical cells initiate the patterning process. Using live imaging, quantitative image analyses and modeling, we show that during Arabidopsis thaliana sepal development, fluctuations in the concentration of the transcription factor ATML1 pattern a field of identical epidermal cells to differentiate into giant cells interspersed between smaller cells. We find that ATML1 is expressed in all epidermal cells. However, its level fluctuates in each of these cells. If ATML1 levels surpass a threshold during the G2 phase of the cell cycle, the cell will likely enter a state of endoreduplication and become giant. Otherwise, the cell divides. Our results demonstrate a fluctuation-driven patterning mechanism for how cell fate decisions can be initiated through a random yet tightly regulated process.

Inter-relação entre direito e alimentação: percepções de consumidores sobre seus direitos / Interrelations between law and food: consumer perceptions of their rights

A concretização do direito à alimentação saudável implica a necessidade de pesquisas acerca de mecanismos que favoreçam a construção de uma cultura apta a reforçar a adoção de atitudes positivas em prol dessa conquista. A presente pesquisa analisou o conhecimento acerca de direitos fundamentais/consumeristas, identificando aspectos relacionados às práticas alimentares cotidianas do consumidor de alimentos em restaurantes de um mercado público. Tratou-se de pesquisa qualitativa, com notas de observação em diário de campo e roteiro de entrevista. Na análise das narrativas, foi produzido o mapa analítico que entrelaçou as falas dos participantes com as categorias mais relevantes: direitos e alimentação; disponibilidade de informações; exigência de informações pelo consumidor; desistência do consumo devido às condições do local. Observou-se que os entrevistados apresentaram desconhecimento sobre os direitos relacionados à alimentação. Tempo, preço, sabor, praticidade e higiene foram valores destacados nas narrativas, porém, não se mostrou compromisso em publicizar dados importantes sobre produtos e serviços oferecidos nos restaurantes. A compreensão dos resultados aponta a necessidade de uma educação em direito à segurança alimentar e nutricional na cadeia de produção e comercialização de alimentos, uma vez que a alimentação precisa ser pensada de modo multidimensional.

The realization of the right to healthy eating implies the need for research on mechanisms that favor the construction of a culture capable of reinforcing the adoption of positive attitudes in favor of this achievement. This research analyzed the knowledge about fundamental rights/consumers, identifying aspects related to the daily eating practices of the food consumer in restaurants in a public market. It is a qualitative research, with observation notes in a field diary and an interview script. In the analysis of the narratives, an analytical map was produced that intertwined the speeches of the participants (3 men and 2 women) with the most relevant categories: rights and food; availability of information; consumer demand for information; consumer demand for information; withdrawal from consumption due to local conditions. It was observed that with regard to knowledge of law related to food, the interviewees showed ignorance. Time, price, flavor, practicality and hygiene were values highlighted in the showed ignorance. Time, price, flavor, practicality and hygiene were values highlighted in the narratives, but there is no commitment to publicize important data about products and showed ignorance. Time, price, flavor, practicality and hygiene were values highlighted in the narratives, but there is no commitment to publicize important data about products and services offered in restaurants. Understanding the results shows the need for education in the right to food and nutrition security in the food production and marketing chain, since food needs to be thought of in a multidimensional way.