Perceived cognitive functioning in breast cancer patients treated with chemotherapy compared to matched healthy women: Evidence from a Portuguese study.

AIM: Cognitive concerns are one of the most frequently reported symptoms by breast cancer survivors. This study aimed to evaluate perceived cognitive functioning in Portuguese women with breast cancer treated with chemotherapy. METHODS: A cross-sectional study enrolling 146 women (73 with breast cancer and 73 healthy) was conducted from August to October 2017, invited to participate through online dissemination. Participants completed self-reported questionnaires to collect sociodemographic and clinical data and assess perceived cognitive functioning and psychological adjustment variables (anxiety and depression). RESULTS: Compared to healthy women, women with breast cancer showed significantly lower scores on the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) subscales and higher levels of depression. Both groups showed significant negative correlations between perceived cognitive functioning and anxiety and depression. Health status and depression seem to better explain perceived cognitive functioning, with health status adding significantly more explained variance beyond sociodemographic and psychological adjustment variables. CONCLUSION: The current findings provide evidence for the existence of more cognitive complaints among Portuguese women with breast cancer, compared to healthy individuals. Anxiety, depression, age and education also explain perceived cognitive functioning. Considering that health status and psychological adjustment seem to significantly explain perceived cognitive functioning, special attention should be given by health-care professionals, including nurses, to designing clinical interventions for breast cancer patients to help manage cognitive impairment.

Multi-walled carbon nanotubes increase antibody-producing B cells in mice immunized with a tetravalent vaccine candidate for dengue virus.

BACKGROUND: In recent times, studies have demonstrated that carbon nanotubes are good candidates for use as vehicles for transfection of exogenous material into the cells. However, there are few studies evaluating the behavior of carbon nanotubes as DNA vectors and few of these studies have used multi-walled carbon nanotubes (MWCNTs) or carboxylated MWCNTs. Thus, this study aims to assess the MWCNTs' (carboxylated or not) efficiency in the increase in expression of the tetravalent vaccine candidate (TVC) plasmid vector for dengue virus in vitro using Vero cells, and in vivo, through the intramuscular route, to evaluate the immunological response profile. RESULTS: Multi-walled carbon nanotubes internalized by Vero cells, have been found in the cytoplasm and nucleus associated with the plasmid. However, it was not efficient to increase the messenger ribonucleic acid (mRNA) compared to the pure vaccine candidate associated with Lipofectamine(®) 2000. The in vivo experiments showed that the use of intramuscular injection of the TVC in combination with MWCNTs reduced the immune response compared to pure TVC, in a general way, although an increase was observed in the population of the antibody-producing B cells, as compared to pure TVC. CONCLUSIONS: The results confirm the data found by other authors, which demonstrate the ability of nanotubes to penetrate target cells and reach both the cytoplasm and the cell nucleus. The cytotoxicity values are also in accordance with the literature, which range from 5 to 20 µg/mL. This has been found to be 10 µg/mL in this study. Although the expression levels are higher in cells that receive the pure TVC transfected using Lipofectamine(®) 2000, the nanotubes show an increase in B-cells producing antibodies.

Neurofibromin is the major ras inactivator in dendritic spines.

In dendritic spines, Ras plays a critical role in synaptic plasticity but its regulation mechanism is not fully understood. Here, using a fluorescence resonance energy transfer/fluorescence lifetime imaging microscopy-based Ras imaging technique in combination with 2-photon glutamate uncaging, we show that neurofibromin, in which loss-of-function mutations cause Neurofibromatosis Type 1 (NF1), contributes to the majority (∼90%) of Ras inactivation in dendritic spines of pyramidal neurons in the CA1 region of the rat hippocampus. Loss of neurofibromin causes sustained Ras activation in spines, which leads to impairment of spine structural plasticity and loss of spines in an activity-dependent manner. Therefore, deregulation of postsynaptic Ras signaling may explain, at least in part, learning disabilities associated with NF1.

Centaurin-α1-Ras-Elk-1 signaling at mitochondria mediates ß-amyloid-induced synaptic dysfunction.

Alzheimer's disease is thought to be caused by ß-amyloid peptide (Aß)-dependent synaptic dysfunction. However, the signaling pathways connecting Aß and synaptic dysfunction remain elusive. Here we report that Aß transiently increases the expression level of centaurin-α1 (CentA1) in neurons, which induces a Ras-dependent association of Elk-1 with mitochondria, leading to mitochondrial and synaptic dysfunction in organotypic hippocampal slices of rats. Downregulation of the CentA1-Ras-Elk-1 pathway restored normal mitochondrial activity, spine structural plasticity, spine density, and the amplitude and frequency of miniature EPSCs in Aß-treated neurons, whereas upregulation of the pathway was sufficient to decrease spine density. Elevations of CentA1 and association of Elk-1 with mitochondria were also observed in transgenic mice overexpressing a human mutant form of amyloid precursor protein. Therefore, the CentA1-Ras-Elk-1 signaling pathway acts on mitochondria to regulate dendritic spine density and synaptic plasticity in response to Aß in hippocampal neurons, providing new pharmacological targets for Alzheimer's disease.

Impaired NMDA receptor transmission alters striatal synapses and DISC1 protein in an age-dependent manner.

NMDA receptors are key regulators of synaptic plasticity, and their hypofunction is thought to contribute to the pathophysiology of CNS disorders. Furthermore, NMDA receptors participate in the formation, maintenance, and elimination of synapses. The consequences of NMDA receptor hypofunction on synapse biology were explored in a genetic mouse model, in which the levels of NMDA receptors are reduced to 10% of normal levels (i.e., NR1-knockdown mice). In these mice, synapse number is reduced in an age-dependent manner; reductions are observed at the postpubertal age of 6 wk, but normal at 2 wk of age. Efforts to uncover the biochemical underpinnings of this phenomenon reveal synapse-specific reductions in 14-3-3ε protein and in Disrupted in Schizophrenia-1 (DISC1), two schizophrenia susceptibility factors that have been implicated in the regulation of spine density. Subchronic administration of MK-801, an NMDA receptor antagonist, produces similar synaptic reductions in both spine density and DISC1, indicating that synaptic levels of DISC1 are regulated by NMDA receptor function. The synaptic reduction of DISC1 and 14-3-3ε is developmentally correlated with the age-dependent decrease in striatal spine density.

CanCOG®: Cultural Adaptation of the Evidence-Based UCLA Cognitive Rehabilitation Intervention Program for Cancer Survivors in Portugal.

Cognitive difficulties are highly prevalent and negatively impact cancer survivors' quality of life. The UCLA Cognitive Rehabilitation Intervention Program (in short, UCLA program) is an evidence-based intervention developed and tested in the US to address the cognitive complaints of cancer survivors. Since there are no cognitive rehabilitation programs available for Portuguese cancer-related settings, this study aimed to culturally adapt the UCLA program to Portugal. Nine steps were implemented for this cultural adaptation: needs assessment, initial contacts, translation, cultural adaptation, independent review by a panel of experts (n = 6), focus group discussions with cancer survivors (n = 11), systematization of inputs and improvement of the final materials, fidelity check, and preliminary acceptability assessment. The findings suggested that changes to the original materials were needed. A Portuguese name, "CanCOG®-Reabilitação Cognitiva no Cancro" (in English "CanCOG®-Cognitive Rehabilitation in Cancer"), and a logo were created to make it more memorable and appealing for the Portuguese population. The language was adjusted to ensure content accessibility and semantic and conceptual equivalence. Finally, references to several cultural aspects, such as habits, customs, and traditions, were adapted to fit the new cultural context. The UCLA program may be a promising tool to help alleviate the cognitive difficulties reported by cancer survivors in different cultural contexts. Future research is needed to confirm the feasibility, acceptability, and preliminary efficacy of its Portuguese version, "CanCOG®-Reabilitação Cognitiva no Cancro".

Cognitive functioning and work-related outcomes of non-central nervous system cancer survivors: protocol for a systematic review with meta-analysis.

INTRODUCTION: In recent years, growing attention has been given to the study of the impact of cancer-related cognitive impairment (CRCI) in working non-central nervous system (CNS) cancer survivors. Available literature has shown that working cancer survivors identify cognitive problems at work as very problematic and worrisome. Some reviews have discussed the association between CRCI and work-related outcomes; however, none to date have investigated this association through comprehensive systematic review with meta-analysis. Hence, this work will comprehensively summarise existing evidence from quantitative studies assessing the relationship between CRCI and work-related outcomes of adult non-CNS cancer survivors at working age. METHODS AND ANALYSIS: The systematic review procedures and its report will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Electronic searches in the databases Web of Science, Scopus, PubMed, ProQuest, PsycINFO and CINAHL, complemented by a manual search of other relevant articles, will be performed from 2000 onwards to identify relevant publications. Two independent reviewers will assess studies for inclusion and extract data from each article using a standardised form. Studies eligible for inclusion must be quantitative, contain adult non-CNS cancer survivors with CRCI, and a measure of cognitive functioning and work-related outcomes. To assess risk of bias, the Joanna Briggs Institute Critical Appraisal Tool Studies checklists will be independently used by the two researchers. Synthesis of the included articles will be conducted using a narrative method and through meta-analysis. Meta-analysis will be reported via correlation for the association between CRCI and work-related outcomes. The cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation system. ETHICS AND DISSEMINATION: Ethics approval is not required since individual patient data will not be collected. The findings will be published in a peer-review indexed journal, presented at scientific meetings and included in a chapter of a Doctoral thesis. PROSPERO REGISTRATION NUMBER: CRD42020165458.

Validation study of the Functional Assessment of Cancer Therapy-Cognitive Function-Version 3 for the Portuguese population.

BACKGROUND: Cancer-related cognitive impairment is a common and potentially debilitating symptom experienced by patients with non-central nervous system (CNS) cancers, with negative impact on their quality of life. The Functional Assessment of Cancer Therapy-Cognitive Function-Version 3 (FACT-Cog-v3) is the most extensively used instrument specifically developed to evaluate cognitive complaints in adult cancer patients. Nevertheless, this self-report measure is not yet validated for the Portuguese population. Therefore, the purpose of this study was to evaluate the psychometric properties of the FACT-Cog-v3 among patients with non-CNS cancers in Portugal. METHODS: The validation study was conducted based on a convenience sample of 281 patients with non-CNS cancers, aged between 18 and 65 years, recruited online. A confirmatory factor analysis (CFA) was used to test the factor structure of the Portuguese FACT-Cog-v3 version; internal consistency analysis was also conducted. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30-version 3) and the Hospital Anxiety and Depression Scale (HADS) were also used to test the concurrent, convergent, and discriminant validity of the scale. RESULTS: CFA supported a four-factor model with good fix indexes and internal consistencies: perceived cognitive impairments (α = 0.97), comments from others (α = 0.92), perceived cognitive abilities (α = 0.93), and impact on quality of life (α = 0.92). Concurrent, convergent, and discriminant validities were confirmed. Moderate and strong correlations were found between the FACT-Cog-v3 subscales and the QLQ-C30 cognitive functioning subscale. Good convergent validity, with moderate correlations, was found between the FACT-Cog-v3 subscales and the HADS-A, HADS-D, and QLQ-C30 fatigue, sleep disturbance, and global health status subscales. Acceptable discriminant validity, with weak and moderate correlations, was demonstrated between the FACT-Cog-v3 subscales and the QLQ-C30 pain and nausea/vomiting subscales. CONCLUSIONS: The Portuguese FACT-Cog-v3 version can be considered a reliable and valid measure to assess cognitive concerns of patients with non-CNS cancers, with relevance for research and clinical practice.

Positive aspects of care in informal caregivers of community-dwelling dementia patients.

WHAT IS KNOWN ON THE SUBJECT?: Positive aspects of care are considered an essential part of caregiving research. They have been related to a wide range of dimensions of the caregiving circumstances, but there are few valid, reliable and brief measures to assess them. One of the most frequently used internationally is the Positive Aspects of Caregiving (PAC) scale, whose psychometric properties have received little attention. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: The present study analyses the psychometric properties of the Portuguese version of the PAC scale in a sample of informal caregivers of someone with dementia and further explores the association of different factors (e.g. caregiver health, sociodemographic variables) with the PAC. The Portuguese version of PAC scale presented good psychometric characteristics, and the factor analysis revealed the presence of two factors: affirming self and enriching life. Our study also verified that higher levels of PAC are more likely to be associated with better caregiver health perception, lower levels of psychological distress and burden, the care recipient's older age, providing care to more than one care recipient, not receiving social support services and not considering institutionalizing the care recipient. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Findings from this study can assist professionals, including mental health nurses, to develop and implement effective interventions that help dementia caregivers to maintain their emotional health by identifying and focusing specific positive aspects of care. The study stresses the Portuguese version of the PAC scale as a reliable and valid measure for practice. ABSTRACT: Introduction Positive aspects of care refer to the psychosocial benefits of caregiving. The Positive Aspects of Caregiving (PAC) scale is one of the instruments most frequently used internationally, but its psychometric properties and correlates within the caregiving experience have received limited attention. Aim To examine the factorial structure of the Portuguese version of PAC scale and to analyse background and contextual factors that are more likely to be associated with higher levels of PAC. Method The PAC scale, a sociodemographic questionnaire and measures assessing burden and physical and mental health were administered to 204 informal caregivers of dementia patients. Results Exploratory factor analysis revealed a two-factor structure; internal consistency was adequate. Higher scores were negatively correlated with caregiver burden and distress. Better health perception, care recipient's older age, providing care to more than one care recipient and overall self-reliance were correlated with higher levels of PAC. Discussion The PAC scale was found to be a reliable and valid measure. Dementia caregiving circumstances and caregivers' and care receivers' characteristics play an important role for the presence of PAC, but relate distinctively with its dimensions. Implications for Practice Findings can help mental health nurses to recognize distinctive relations between PAC and caregiving variables.

Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia.

Friedreich ataxia is an autosomal recessive neurodegenerative disease associated with a high diabetes prevalence. No treatment is available to prevent or delay disease progression. Friedreich ataxia is caused by intronic GAA trinucleotide repeat expansions in the frataxin-encoding FXN gene that reduce frataxin expression, impair iron-sulfur cluster biogenesis, cause oxidative stress, and result in mitochondrial dysfunction and apoptosis. Here we examined the metabolic, neuroprotective, and frataxin-inducing effects of glucagon-like peptide-1 (GLP-1) analogs in in vivo and in vitro models and in patients with Friedreich ataxia. The GLP-1 analog exenatide improved glucose homeostasis of frataxin-deficient mice through enhanced insulin content and secretion in pancreatic ß cells. Exenatide induced frataxin and iron-sulfur cluster-containing proteins in ß cells and brain and was protective to sensory neurons in dorsal root ganglia. GLP-1 analogs also induced frataxin expression, reduced oxidative stress, and improved mitochondrial function in Friedreich ataxia patients' induced pluripotent stem cell-derived ß cells and sensory neurons. The frataxin-inducing effect of exenatide was confirmed in a pilot trial in Friedreich ataxia patients, showing modest frataxin induction in platelets over a 5-week treatment course. Taken together, GLP-1 analogs improve mitochondrial function in frataxin-deficient cells and induce frataxin expression. Our findings identify incretin receptors as a therapeutic target in Friedreich ataxia.

Violence against women by their intimate partner and common mental disorders.

The World Health Organization considers gender violence a cause of anxiety, depression and suicidal thoughts among women. This study investigated the association between violence committed against women by their intimate partners, defined by psychologically, physically and sexually abusive acts, and common mental disorders, assessed by using the Self Reporting Questionnaire (SRQ-20). A population-based household survey was carried out among women aged 15-49 years in two sites: São Paulo, the largest Brazilian city, and Zona da Mata of Pernambuco, a region with both urban and rural areas in the Northeast of the country. A large proportion of women reported violence (50.7%). The most frequent forms were psychological violence alone (18.8%) or accompanied by physical violence (16.0%). The prevalence of mental disorders was 49.0% among women who reported any type of violence and 19.6% among those who did not report violence (p<0.0001). After adjustment for demographic and socioeconomic characteristics, the nature of the relationship, stressful life events and social support, all the forms of violence studied, with the exception of sexual violence alone or accompanied by either physical or psychological violence (p=0.09), were significantly associated with mental disorders: physical violence alone (OR1.91; CI 95%1.2-3.0), psychological violence alone (OR 2.00; CI 95% 1.5-2.6), sexual violence alone or accompanied by either physical or psychological violence (OR1.80; CI95% 0.9-3.6), both psychological and physical violence (OR 2.56; CI 95% 1.9-3.5) and all three forms of violence (OR 2.68; CI 95% 1.8-4.0). This is the first population-based study on the association between intimate partner violence and mental health in Brazil. It contributes to the existing body of research and confirms that violence, frequently experienced by women in the country, is associated with mental disorders. Policies and strategies aimed at reducing gender-based violence are necessary for preventing and reducing anxiety and depression among women.

The Mouse Superior Colliculus as a Model System for Investigating Cell Type-Based Mechanisms of Visual Motor Transformation.

The mouse superior colliculus (SC) is a laminar midbrain structure involved in processing and transforming multimodal sensory stimuli into ethologically relevant behaviors such as escape, defense, and orienting movements. The SC is unique in that the sensory (visual, auditory, and somatosensory) and motor maps are overlaid. In the mouse, the SC receives inputs from more retinal ganglion cells than any other visual area. This makes the mouse SC an ideal model system for understanding how visual signals processed by retinal circuits are used to mediate visually guided behaviors. This Perspective provides an overview of the current understanding of visual motor transformations operated by the mouse SC and discusses the challenges to be overcome when investigating the input-output relationships in single collicular cell types.

Metabotropic glutamate receptor 1 blockade impairs acquisition and retention in a spatial Water maze task.

Metabotropic glutamate receptors, including the mGlu1 receptor, have received considerable attention as potential targets for anxiolytic, antidepressant, antipsychotic and antinociceptive drugs. mGlu1 receptors have also been suggested to play a role in the modulation of cognitive processes, but knowledge is still very limited. In the present study the effects of the selective mGlu1 receptor antagonist 3,4-dihydro-2H-pyrano[2,3]beta-quinolin-7-yl)(cis-4-methoxycyclohexyl)methanone (JNJ16259685, 0.63-10 mg/kg s.c.) on more or less spatially demanding learning and spatial memory (retention and re-acquisition) were investigated in mice performing in a water maze. Selective mGlu1 receptor blockade with JNJ16259685 impaired spatial acquisition processes, irrespective of spatial load, as well as spatial re-acquisition, already at the lowest dose tested (0.63 mg/kg). In contrast, effects on spatial retention performance were relatively mild in mice that had learned to locate the position of the escape platform prior to treatment. Thigmotaxic behaviour and locomotor activity appeared to be unaffected by JNJ16259685. These data suggest that blockade of the mGlu1 receptor primarily affects learning of new information, but leaves retention of spatial information relatively unaffected. Blockade of the mGlu5 receptor with MPEP also impaired spatial learning, although only at the highest dose tested (10 mg/kg). An ex vivo receptor occupancy study in rats revealed that MPEP occupied central mGlu5 receptors with an ED(50) of 2.0 mg/kg one hour after subcutaneous administration. This is 50-150 times higher than the ED(50) reported for JNJ16259685 at central mGlu1 receptors and suggests that one reason why the two compounds cause cognitive effects at different doses might be due to differences in central mGlu receptor occupancy, rather than fundamentally different roles of mGlu1 and mGlu5 receptors in the modulation of cognitive function.

Imaging the activity of Ras superfamily GTPase proteins in small subcellular compartments in neurons.

Resolving the spatiotemporal dynamics of intracellular signaling is important for understanding the molecular mechanisms of various cellular processes induced by extracellular signals. Two-photon fluorescence lifetime imaging microscopy (2pFLIM) in combination with a fluorescence resonance energy transfer (FRET)-based signaling sensors allows one to image signaling within small subcellular compartments, such as dendritic spines of neurons, with high sensitivity and spatiotemporal resolution. In this protocol, we describe the procedures and equipment required for imaging intracellular signaling activity, with a particular focus on signaling mediated by the Ras superfamily of small GTPase proteins.

Microglia change from a reactive to an age-like phenotype with the time in culture.

Age-related neurodegenerative diseases have been associated with chronic neuroinflammation and microglia activation. However, cumulative evidence supports that inflammation only occurs at an early stage once microglia change the endogenous characteristics with aging and switch to irresponsive/senescent and dystrophic phenotypes with disease progression. Thus, it will be important to have the means to assess the role of reactive and aged microglia when studying advanced brain neurodegeneration processes and age-associated related disorders. Yet, most studies are done with microglia from neonates since there are no adequate means to isolate degenerating microglia for experimentation. Indeed, only a few studies report microglia isolation from aged animals, using either short-term cultures or high concentrations of mitogens in the medium, which trigger microglia reactivity. The purpose of this study was to develop an experimental process to naturally age microglia after isolation from neonatal mice and to characterize the cultured cells at 2 days in vitro (DIV), 10 DIV, and 16 DIV. We found that 2 DIV (young) microglia had predominant amoeboid morphology and markers of stressed/reactive phenotype. In contrast, 16 DIV (aged) microglia evidenced ramified morphology and increased matrix metalloproteinase (MMP)-2 activation, as well as reduced MMP-9, glutamate release and nuclear factor kappa-B activation, in parallel with decreased expression of Toll-like receptor (TLR)-2 and TLR-4, capacity to migrate and phagocytose. These findings together with the reduced expression of microRNA (miR)-124, and miR-155, decreased autophagy, enhanced senescence associated beta-galactosidase activity and elevated miR-146a expression, are suggestive that 16 DIV cells mainly correspond to irresponsive/senescent microglia. Data indicate that the model represent an opportunity to understand and control microglial aging, as well as to explore strategies to recover microglia surveillance function.

An improved Ras sensor for highly sensitive and quantitative FRET-FLIM imaging.

Ras is a signaling protein involved in a variety of cellular processes. Hence, studying Ras signaling with high spatiotemporal resolution is crucial to understanding the roles of Ras in many important cellular functions. Previously, fluorescence lifetime imaging (FLIM) of fluorescent resonance energy transfer (FRET)-based Ras activity sensors, FRas and FRas-F, have been demonstrated to be useful for measuring the spatiotemporal dynamics of Ras signaling in subcellular micro-compartments. However the predominantly nuclear localization of the sensors' acceptor has limited its sensitivity. Here, we have overcome this limitation and developed two variants of the existing FRas sensor with different affinities: FRas2-F (K(d)∼1.7 µM) and FRas2-M (K(d)∼0.5 µM). We demonstrate that, under 2-photon fluorescence lifetime imaging microscopy, FRas2 sensors provide higher sensitivity compared to previous sensors in 293T cells and neurons.

Diagnóstico e intervenção nutricional em crianças hospitalizadas atendidas em Enfermaria de Infectologia Pediátrica / Nutritional diagnostic and intervention of children hospitalized in a pediatric infectology ward

Objetivos: O presente estudo se propõe a descrever a evolução e intervenção nutricional de crianças atendidas em enfermaria de infectologia pediátrica, segundo o tipo de doença: aguda ou crônica. Métodos: Ensaio terapêutico sem grupo controle. Fizeram parte deste estudo crianças admitidas na Enfermaria de Infectologia Pediátrica do Hospital São Paulo, com idade de 6 a 36 meses de vida, de março de 2001 a dezembro de 2002. A análise estatística utilizada foi a não-paramétrica. Resultados: A amostra foi composta de 125 crianças. A mediana de idade foi 17 meses e a do tempo de internação de dez dias. Doenças agudas foram prevalentes (70 por cento). A queixa de diminuição do apetite após o início da doença foi de 52,8 por cento; 60 por cento das crianças tiveram ingestão energética média durante a internação maior do que a recomenda por quilo de peso para idade; apresentaram desnutrição 25 por cento das crianças e risco para baixa estatura e baixa estatura, 43,2 por cento. Realizaram terapia nutricional 21,6 por cento das crianças. Crianças com diagnóstico de doenças crônicas permaneceram mais tempo internadas (p<0,01) e tiveram melhor evolução nutricional (p=0,027), comparadas às crianças com doenças agudas. Conclusão: As crianças com diagnóstico de doenças crônicas encontraram-se mais desnutridas do que as com diagnóstico de doenças agudas, necessitando de maior tempo de internação, sendo ainda maiores candidatas a realizarem terapia nutricional, evoluindo com melhora do estado nutricional ainda no período de internação.