Structure-activity relationship of anticancer and antiplasmodial gold bis(dithiolene) complexes.

Monoanionic gold bis(dithiolene) complexes were recently shown to display activity against ovarian cancer cells, Gram-positive bacteria, Candida strains and the rodent malaria parasite, P. berghei. To date, only monoanionic gold(III) bis(dithiolene) complexes with a thiazoline backbone substituted with small alkyl chains have been evaluated for biomedical applications. We now analyzed the influence of the length and the hydrophobicity vs. hydrophilicity of these complexes' alkyl chain on their anticancer and antiplasmodial properties. Isomer analogues of these monoanionic gold(III) bis(dithiolene) complexes, this time with a thiazole backbone, were also investigated in order to assess the influence of the nature of the heterocyclic ligand on their overall chemical and biological properties. In this report we present the total synthesis of four novel monoanionic gold(III) bis(dithiolene) complexes with a long alkyl chain and a polyoxygenated (PEG) chain aiming to improve their solubility and biological properties. Our results showed that the complexes with a PEG chain showed promising anticancer and antiplasmodial activities beside improved solubility, a key parameter in drug discovery and development.

Long-term developmental outcomes of children with congenital Zika syndrome.

BACKGROUND: Eight years after the epidemics in Brazil, children with congenital Zika syndrome (CZS) and their families confront ongoing health challenges. OBJECTIVE: This study aims to characterize how virally induced prenatal brain injury impacts development and functional outcomes among children diagnosed with CZS. METHODS: We performed a cross-sectional study of a consecutive series of children diagnosed with CZS. Using validated neurodevelopmental assessments, we evaluated gross motor function, manual ability, communication, eating and drinking, and visual function. RESULTS: Sixty children (29 males, and 31 females) met the inclusion criteria for the study. Comorbidities such as epilepsy (90.0%) and undernutrition (38.3%), along with clinical conditions including dysphagia (68.3%) and dependence on tube feeding (31.7%), were observed. Our results demonstrate a majority of children at level V - the most severe level within a five-tier system - in the Gross Motor Function (86.7%), Manual Ability (85.0%), Communication Function (68.3%), Eating and Drinking Ability (40.0%) Classification Systems, and level IV in the Visual Function Classification System (38.3%). CONCLUSION: CZS is associated with severe functional impairments and comorbidities, adversely impacting child development and quality of life. These findings reveal persistent challenges affecting the functioning of children with CZS, underscoring the need for continued support and specialized care. IMPACT: This study aimed to characterize the long-term clinical and functional characteristics of a subset of children with Congenital Zika Syndrome (CZS). We found that eight years after the Brazilian Zika epidemic, this subset of children with CZS continues to demonstrate major functional limitations impacting mobility, vision, and the ability to eat and drink. Our analysis documented a very high level of disability in several key functional classification systems. Notably, applying a new instrument for visual ability among children diagnosed with cerebral palsy, we found that more than 60% of the study group have poor or very poor visual function.

Building a growing genomic data repository for maternal and fetal health through the PING Consortium.

Background: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Discordant outcomes among dizygotic twins could be explained by genetic susceptibly or protection. Among several well-recognized threats to the developing brain, Zika is a mosquito-borne, positive-stranded RNA virus that was originally isolated in Uganda and spread to cause epidemics in Africa, Asia, and the Americas. In the Americas, the virus caused congenital Zika syndrome and a multitude of neurodevelopmental disorders. As of now, there is no preventative treatment or cure for the adverse outcomes caused by prenatal Zika infection. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium was initiated in 2016 to identify factors modulating prenatal brain injury and postnatal neurodevelopmental outcomes for Zika and other prenatal viral infections. Methods: The Consortium has pooled information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic data repository. This repository is being mined to search for modifiers of virally induced brain injury and developmental outcomes. Multilateral partnerships include commitments with Children's National Hospital (USA), Instituto Nacional de Salud (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), and Zika Instituto Fernandes Figueira (Brazil), in addition to the Centers for Disease Control and Prevention and the National Institutes of Health. Discussion: Our goal in bringing together these sets of patient data was to test the hypothesis that personal and populational genetic differences affect the severity of brain injury after a prenatal viral infection and modify neurodevelopmental outcomes. We have enrolled 4,102 mothers and 3,877 infants with 3,063 biological samples and clinical data covering over 80 phenotypic fields and 5,000 variables. There were several notable challenges in bringing together cohorts enrolled in different studies, including variability in the timepoints evaluated and the collected clinical data and biospecimens. Thus far, we have performed whole exome sequencing on 1,226 participants. Here, we present the Consortium's formation and the overarching study design. We began our investigation with prenatal Zika infection with the goal of applying this knowledge to other prenatal infections and exposures that can affect brain development.

Teaching and Learning Clinical Reasoning in Nursing Education: A Student Training Course.

Clinical reasoning is an essential component of nursing. It has emerged as a concept that integrates the core competencies of quality and safety education for nurses. In cooperation with five European partners, Instituto Politécnico de Setúbal (IPS) realized the "Clinical Reasoning in Nursing and Midwifery Education and Practice" project as part of the Erasmus+ project. As a partner, our team designed a multiplier event-the student training course. The aim of this report is to describe the construction and development of this clinical reasoning training course for nursing students. We outline the pedagogical approach of an undergraduate training course on clinical reasoning in 2023, which we separated into four stages: (i) welcoming, (ii) knowledge exploration, (iii) pedagogical learning, and (iv) sharing experience. This paper presents the learning outcomes of the collaborative reflection on and integration of the clinical reasoning concept among nursing students. This educational experience fostered reflection and discussion within the teaching team of the nursing department regarding the concept, models, and teaching/learning methods for clinical reasoning, with the explicit inclusion of clinical reasoning content in the nursing curriculum. We highlight the importance of implementing long-term pedagogical strategies in nursing education.

Acute-on-chronic liver failure: a retrospective review of cases at a transplantation center in Brazil.

PURPOSE: Acute-on-chronic liver failure (ACLF) is a leading cause of death in cirrhotic patients. This study aims to describe the outcomes of in-patients with ACLF at a liver transplantation (LT) center in Brazil. METHODS: Retrospective study analyzing patient data from 2017 to 2022. Re-transplant cases and patients without previous chronic liver disease were excluded. The ACLF diagnosis was based on the European Association for the Study of the Liver-Chronic Liver Failure criteria and assessments repeated on days 3 and 7 after the initial diagnosis. RESULTS: Among 381 patients, 10.49% (n = 40) were diagnosed with ACLF. Bacterial infection was the most common precipitating factor (45%). Kidney failure occurred in 65% of the cases. The 28-day mortality rate was 35% and varied according to ACLF severity at diagnosis, from single organ failure (ACLF-1) at 22% to three organ failures (ACLF-3) at 60%. Eighteen patients (45%) were transplanted with a 100% 28-day survival rate. For ACLF-3 cases at diagnosis (n = 15), the 28-day and 1-year survival rates with a transplant (n = 4) were 100% and 80%, respectively, and without transplant (n = 11), 10 and 0%, respectively. CONCLUSIONS: ACLF was associated with high mortality rates. LT was an effective therapeutic option, particularly for ACLF-3 cases.

Dual FGFR-targeting and pH-activatable ruthenium-peptide conjugates for targeted therapy of breast cancer.

Dysregulation of Fibroblast Growth Factor Receptors (FGFRs) signaling has been associated with breast cancer, yet employing FGFR-targeted delivery systems to improve the efficacy of cytotoxic agents is still sparsely exploited. Herein, we report four new bi-functional ruthenium-peptide conjugates (RuPCs) with FGFR-targeting and pH-dependent releasing abilities, envisioning the selective delivery of cytotoxic Ru complexes to FGFR(+)-breast cancer cells, and controlled activation at the acidic tumoral microenvironment. The antiproliferative potential of the RuPCs and free Ru complexes was evaluated in four breast cancer cell lines with different FGFR expression levels (SKBR-3, MDA-MB-134-VI, MCF-7, and MDA-MB-231) and in human dermal fibroblasts (HDF), at pH 6.8 and pH 7.4 aimed at mimicking the tumor microenvironment and normal tissues/bloodstream pHs, respectively. The RuPCs showed higher cytotoxicity in cells with higher level of FGFR expression at acidic pH. Additionally, RuPCs showed up to 6-fold higher activity in the FGFR(+) breast cancer lines compared to the normal cell line. The release profile of Ru complexes from RuPCs corroborates the antiproliferative effects observed. Remarkably, the cytotoxicity and releasing ability of RuPCs were shown to be strongly dependent on the conjugation of the peptide position in the Ru complex. Complementary molecular dynamic simulations and computational calculations were performed to help interpret these findings at the molecular level. In summary, we identified a lead bi-functional RuPC that holds strong potential as a FGFR-targeted chemotherapeutic agent.

Lead to hit ruthenium-cyclopentadienyl anticancer compounds: Cytotoxicity against breast cancer cells, metabolic stability and metabolite profiling.

The successful choice of hit compounds during drug development programs involves the integration of structure-activity relationship (SAR) studies with pharmacokinetic determinations, including metabolic stability assays and metabolite profiling. A panel of nine ruthenium-cyclopentadienyl (RuCp) compounds with the general formula [Ru(η5-C5H4R)(PPh3)(bipyR')]+ (with R = H, CHO, CH2OH; R' = H, CH3, CH2OH, CH2Biotin) has been tested against hormone-dependent MCF-7 and triple negative MDA-MB-231 breast cancer cells. In general, all compounds showed important cytotoxicity against both cancer cell lines and were able to inhibit the formation of MDA-MB-231 colonies in a dose-dependent manner, while showing selectivity for cancer cells over normal fibroblasts. Among them, four compounds stood out as lead structures to be further studied. Cell distribution assays revealed their preference for the accumulation at cell membrane (Ru quantification by ICP-MS) and the mechanism of cell death seemed to be mediated by apoptosis. Potential structural liabilities of lead compounds were subsequently flagged upon in vitro metabolic stability assays and metabolite profiling. The implementation of this integrated strategy led to the selection of RT151 as a promising hit compound.

Acute-on-chronic liver failure: a retrospective review of cases at a transplantation center in Brazil

ABSTRACT Purpose: Acute-on-chronic liver failure (ACLF) is a leading cause of death in cirrhotic patients. This study aims to describe the outcomes of in-patients with ACLF at a liver transplantation (LT) center in Brazil. Methods: Retrospective study analyzing patient data from 2017 to 2022. Re-transplant cases and patients without previous chronic liver disease were excluded. The ACLF diagnosis was based on the European Association for the Study of the Liver-Chronic Liver Failure criteria and assessments repeated on days 3 and 7 after the initial diagnosis. Results: Among 381 patients, 10.49% (n = 40) were diagnosed with ACLF. Bacterial infection was the most common precipitating factor (45%). Kidney failure occurred in 65% of the cases. The 28-day mortality rate was 35% and varied according to ACLF severity at diagnosis, from single organ failure (ACLF-1) at 22% to three organ failures (ACLF-3) at 60%. Eighteen patients (45%) were transplanted with a 100% 28-day survival rate. For ACLF-3 cases at diagnosis (n = 15), the 28-day and 1-year survival rates with a transplant (n = 4) were 100% and 80%, respectively, and without transplant (n = 11), 10 and 0%, respectively. Conclusions: ACLF was associated with high mortality rates. LT was an effective therapeutic option, particularly for ACLF-3 cases.

The Effects of Stress on Hippocampal Neurogenesis and Behavior in the Absence of Lipocalin-2.

Lipocalin-2 (LCN2) is an acute phase protein able to bind iron when complexed with bacterial siderophores. The recent identification of a mammalian siderophore also suggested a physiological role for LCN2 in the regulation of iron levels and redox state. In the central nervous system, the deletion of LCN2 induces deficits in neural stem cells proliferation and commitment, with an impact on the hippocampal-dependent contextual fear discriminative task. Additionally, stress is a well-known regulator of cell genesis and is known to decrease adult hippocampal cell proliferation and neurogenesis. Although voluntary running, another well-known regulator of neurogenesis, is sufficient to rescue the defective hippocampal neurogenesis and behavior in LCN2-null mice by promoting stem cells' cell cycle progression and maturation, the relevance of LCN2-regulated hippocampal neurogenesis in response to stress has never been explored. Here, we show a lack of response by LCN2-null mice to the effects of chronic stress exposure at the cellular and behavioral levels. Together, these findings implicate LCN2 as a relevant mediator of neuronal plasticity and brain function in the adult mammalian brain.

Exploiting click-chemistry: backbone post-functionalisation of homoleptic gold(I) 1,2,3-triazole-5-ylidene complexes.

The synthesis of a homoleptic azide-functionalised Au(I) bis-1,2,3-triazole-5-ylidene complex is reported, starting from a backbone-modified 1,2,3-triazolium salt ligand precursor. The incorporated azide handle allows for a straightforward modification of the complex according to click-chemistry protocols without impacting the steric shielding around the metal center, demonstrating the superiority of the presented triazole ligand framework over imidazole based systems. Employing the SPAAC and the CuAAC reactions, post-modification of the complex is facilitated with two model substrates, while retaining very high antiproliferative activity (nanomolar range IC50 values) in A2780 and MCF-7 human cancer cells.

A hitchhikers' guide to the terminology of accreditation processes for health professionals and institutions.

Accreditation processes for health care professions are designed to ensure that individuals and programs in these fields meet established standards of quality and effectiveness. The accelerating pace of globalization in the health care professions has increased the need for a shared understanding of the vocabulary of evaluation, assessment, and accreditation. The psychometric principles of valid and reliable assessment are commonly accepted, but the terminology is confusing. We believe that all stakeholders - evaluators, faculty, students but also the community - will benefit from a shared language and common set of definitions. We recognize that not all readers will agree with the definitions we propose, but we hope that this guide will help to ensure clarity, consistency, transparency, and fairness, and that it will promote through the stimulation of a debate greater collaboration across national and international boundaries.

Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that presents a largely unknown etiopathology. The presence of reactive astrocytes in MS lesions has been described for a long time; however, the role that these cells play in the pathophysiology of MS is still not fully understood. Recently, we used an MS animal model to perform high-throughput sequencing of astrocytes' transcriptome during disease progression. Our data show that astrocytes isolated from the cerebellum (a brain region typically affected in MS) showed a strong alteration in the genes that encode for proteins related to several metabolic pathways. Specifically, we found a significant increase in glycogen degradation, glycolytic, and TCA cycle enzymes. Together with these alterations, we detected an upregulation of genes that characterize "astrocyte reactivity". Additionally, at each disease time point we also reconstructed the morphology of cerebellum astrocytes in non-induced controls and in EAE animals, near lesion regions and in the normal-appearing white mater (NAWM). We found that near lesions, astrocytes presented increased length and complexity compared to control astrocytes, while no significant alterations were observed in the NAWM. How these metabolic alterations are linked with disease progression is yet to be uncovered. Herein, we bring to the literature the hypothesis of performing metabolic reprogramming as a novel therapeutic approach in MS.

Evaluation of the Antiproliferative Properties of CpRu Complexes Containing N-Methylated Triazaphosphaadamantane Derivatives.

Piano-stool-{CpRu} complexes containing 1,3,5-triaza-7-phosphaadamantane (PTA), N-methyl-1,3,5-triaza-7-phosphaadamantane (mPTA), and 3,7-dimethyl-1,3,7-triaza-5-phosphabyciclo[3.3.1]nonane (dmoPTA) were evaluated as drugs against breast cancer. The evaluated compounds include two new examples of this family, the complexes [RuCp(DMSO-κS)(HdmoPTA)(PPh3)](CF3SO3)2 (8) and [RuCp(PPh3)2-µ-dmoPTA-1κP-2κ2N,N'-PdCl2](CF3SO3) (11), which have been synthesized and characterized by NMR, IR, and single-crystal X-ray diffraction. The cytotoxic activity of compounds was evaluated against MDA-MB-231 breast cancer cells, and the three most active complexes were further tested against the hormone-dependent MCF-7 breast cancer cell line. Their cell death mechanism and ruthenium uptake were also evaluated, as well as their binding ability to human serum albumin.

Relações de amizade nos transtornos alimentares: revisão integrativa da literatura / Friendship relationships in eating disorders: an integrative literature review / Relaciones de amistad en los trastornos alimentarios: revisión integradora

Ainda é desconhecido o papel da amizade enquanto constitutiva da rede de apoio social nos transtornos alimentares (TAs). Esta revisão integrativa teve por objetivo analisar a produção científica sobre relações de amizade em pessoas com TAs. Foram consultadas as bases PubMed/MEDLINE, LILACS, PsycINFO, Web of Science e EMBASE, de 2010 a 2020. Dos 1126 artigos recuperados, 15 preencheram os critérios de elegibilidade. A maioria tem abordagem qualitativa e delineamento transversal, sem indicar referencial teórico. Aspectos qualitativos das relações de amizade foram associados com redução da frequência e intensidade de sintomas quando o vínculo era considerado de boa qualidade. Já amizades que envolviam comentários depreciativos e influências negativas acerca do corpo e hábitos alimentares foram considerados fatores de risco para desencadeamento dos transtornos. Investir na qualidade dos relacionamentos entre pares pode contribuir para fortalecer a rede de proteção social e reduzir a vulnerabilidade psicossocial de adolescentes com risco para desenvolver TAs. (AU)

There is still little knowledge about the role of friendship within the social support network in eating disorders (EDs). This integrative review aimed to analyze the scientific production about friendship relationships in people with EDs. The literature review was conducted using the PubMed/MEDLINE, LILACS, PsycINFO, Web of Science, and EMBASE databases in the period from 2010 to 2020. Among the 1126 articles retrieved, 15 met the eligibility criteria, most with a qualitative approach and cross-sectional design, without indicating a theoretical framework. The qualitative aspects of friendship were associated with a reduced frequency and intensity of symptoms when the bond was considered to be of good quality. On the other hand, friendships that involved derogatory comments and negative influences related to body image and eating habits emerged as potential risk factors for triggering disorders. Investing in the quality of peer relationships can contribute to strengthening the social safety net and reducing the psychosocial vulnerability of adolescents at higher risk for developing EDs. (AU)

El papel de la amistad como constitutiva de la red de apoyo social en los trastornos alimentarios (TAs) es aún desconocido. Este estudio tiene como objetivo analizar la producción científica sobre las relaciones de amistad en personas con TAs. Se consultaron las bases PubMed/MEDLINE, LILACS, PsycINFO, Web of Science e EMBASE, entre 2010 y 2020. De los 1126 artículos recuperados, 15 cumplían los criterios de elegibilidad. La mayoría tiene enfoque cualitativo y diseño transversal, sin indicar el marco teórico. Los aspectos cualitativos de las relaciones de amistad se asociaron con una menor frecuencia/intensidad de los síntomas cuando el vínculo se consideraba de buena calidad. Amistades que implicaban comentarios despectivos e influencias negativas sobre el cuerpo y los hábitos alimentarios se consideraron factores de riesgo. Invertir en la calidad de las relaciones entre pares puede contribuir a reforzar la red de protección social y reducir la vulnerabilidad de adolescentes con riesgo de desarrollar TAs. (AU)

Comparison between intraoral scanning and direct visual analysis for the assessment of developmental defects of enamel.

OBJECTIVE: To compare direct visual analysis (DVA) and intraoral scanning (IOS) for the assessment of developmental defects of the enamel (DDE). METHODS: Thirty-nine extracted permanent human teeth with DDE were selected by an experienced examiner and digitised using IOS. The scanning was recorded using the OBS Studio software parallel to the IOS software to obtain a coloured high-definition MP4 file of the process. Two other experienced, blinded, and calibrated examiners randomly analysed the same teeth through DVA and IOS. A third examiner resolved any disagreements between the two examiners. Descriptive statistics were used to analyse the frequencies of the scores. Cohen's kappa test was used to determine whether the DVA scores were different from those assigned using IOS. Spearman's test was used to verify non-random examiner errors. The Chi-square test was used to compare score frequencies. Statistical significance was set at p <0.05. RESULTS: Scores indicating more severe and extended DDE (p <0.05) were more frequently assigned with IOS than with DVA (IOS: 25.64%, 25.64%, 38.46%, and 35.90% between one-third to two-third of the lingual, occlusal, mesial, and distal surfaces, respectively; vs. DVA: 10.26%, 7.69%, 15.38%, and 10.26% for the respective aforementioned tooth surfaces). Contrarily, 'no visible enamel defect' was significantly less assigned for IOS than for DVA (IOS: 15.38%, 43.59%, 35.90%, 15.38%, and 17.95% for buccal, lingual, occlusal, mesial, and distal surfaces, respectively; vs. DVA: 38.46%, 66.67%, 56.41%, 51.28%, and 43.59% for the respective aforementioned tooth surfaces). Kappa agreement ranged from fair to moderate when comparing DVA and IOS; the correlation between both methods was positive, indicating that the examiners assigned the scores properly and the differences arose from employing different methods. CONCLUSION: The assessment of DDE differed depending on the method used. IOS scores indicated more severe and extended DDE than DVA scores. Clinical investigation is the next step in validating the use of IOS for DDE diagnosis. CLINICAL SIGNIFICANCE: This study showed that DDE can be assessed differently using IOS. It is clinically relevant as it directly affects the determination of the severity of the defect and dental treatment planning.

The selection of indicator species of birds and mammals for the monitoring of restoration areas in a highly fragmented forest landscape.

Indicator species are frequently used to monitor restoration areas. However, species of conservation concern are usually absent in highly fragmented landscapes, making the selection of indicator species a challenging task. Here, we select indicator species of birds and mammals to be used for the evaluation of restoration sites in a highly fragmented landscape, the Capivara-Taquaruçu Dams region located in north Paraná, Brazil. By using the Index of Biotic Integrity (IBI), we show that the Capivara-Taquaruçu Dams landscape has low IBI values and bird richness when compared with two other landscapes in the north of Paraná. Therefore, we used the Individual Indicate Value to identify birds and mammals associated with forest fragments in the Capivara-Taquaruçu Dams landscape. Six bird and four mammal species were selected as indicators of forest fragments, none of which were of conservation concern. However, monitoring of these species could help evaluate the recovery of restoration sites in the Capivara-Taquaruçu Dams region. Lastly, several species of birds and mammals were frequently recorded in the restoration sites, including vulnerable species such as the lowland tapir (Tapirus terrestris). This is indicative that restoration sites can be important habitats in highly fragmented landscapes despite the loss of biodiversity.

Learning the Biochemical Basis of Axonal Guidance: Using Caenorhabditis elegans as a Model.

AIM: Experimental models are a powerful aid in visualizing molecular phenomena. This work reports how the worm Caenorhabditis elegans (C. elegans) can be effectively explored for students to learn how molecular cues dramatically condition axonal guidance and define nervous system structure and behavior at the organism level. Summary of work: A loosely oriented observational activity preceded detailed discussions on molecules implied in axonal migration. C. elegans mutants were used to introduce second-year medical students to the deleterious effects of gene malfunctioning in neuron response to extracellular biochemical cues and to establish links between molecular function, nervous system structure, and animal behavior. Students observed C. elegans cultures and associated animal behavior alterations with the lack of function of specific axon guidance molecules (the soluble cue netrin/UNC-6 or two receptors, DCC/UNC-40 and UNC-5H). Microscopical observations of these strains, in combination with pan-neuronal GFP expression, allowed optimal visualization of severely affected neurons. Once the list of mutated genes in each strain was displayed, students could also relate abnormal patterns in axon migration/ventral and dorsal nerve cord neuron formation in C. elegans with mutated molecular components homologous to those in humans. SUMMARY OF RESULTS: Students rated the importance and effectiveness of the activity very highly. Ninety-three percent found it helpful to grasp human axonal migration, and all students were surprised with the power of the model in helping to visualize the phenomenon.

Age-related changes in mice behavior and the contribution of lipocalin-2.

Aging causes considerable changes in the nervous system, inducing progressive and long-lasting loss of physiological integrity and synaptic plasticity, leading to impaired brain functioning. These age-related changes quite often culminate in behavioral dysfunctions, such as impaired cognition, which can ultimately result in various forms of neurodegenerative disorders. Still, little is known regarding the effects of aging on behavior. Moreover, the identification of factors involved in regenerative plasticity, in both the young and aged brain, is scarce but crucial from a regenerative point of view and for our understanding on the mechanisms that control the process of normal aging. Recently, we have identified the iron-trafficking protein lipocalin-2 (LCN2) as novel regulator of animal behavior and neuronal plasticity in the young adult brain. On the other hand, others have proposed LCN2 as a biological marker for disease progression in neurodegenerative disorders such as Alzheimer's disease and multiple sclerosis. Still, and even though LCN2 is well accepted as a regulator of neural processes in the healthy and diseased brain, its contribution in the process of normal aging is not known. Here, we performed a broad analysis on the effects of aging in mice behavior, from young adulthood to middle and late ages (2-, 12-, and 18-months of age), and in the absence of LCN2. Significant behavioral differences between aging groups were observed in all the dimensions analyzed and, in mice deficient in LCN2, aging mainly reduced anxiety, while sustained depressive-like behavior observed at younger ages. These behavioral changes imposed by age were further accompanied by a significant decrease in cell survival and neuronal differentiation at the hippocampus. Our results provide insights into the role of LCN2 in the neurobiological processes underlying brain function and behavior attributed to age-related changes.

Health-related quality of life in children with cerebral palsy associated with congenital Zika infection.

OBJECTIVE: To describe the health-related quality of life (QOL) in children with cerebral palsy (CP) associated with congenital Zika infection. METHODS: Cross-sectional study of a consecutive series of children, followed in a referral multicentric rehabilitation network in Brazil. We invited the caregivers to respond to the Brazilian version of the Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILDTM) questionnaire. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS) 26.0™. We used absolute and relative frequencies for categorical variables and mean and standard deviation for continuous variables. RESULTS: The sample consisted of 193 children, at mean age of 50.3±7.6 months. We observed a predominance of children with cerebral palsy (CP) with Gross Motor Function Classification System (GMFCS) level V (93.7%). Epilepsy (88.4%) was the most common comorbidity. CPCHILDTM mean scores were activities of daily living (ADL)/personal care 43.2±12.6; positioning, transferring and mobility 33.7±16.5; comfort and emotions 84.4±15.2; communication and social interaction (CoSI) 48.2±24.3; health 70.9±17.1; and overall quality of life (OQOL) 72.1±17.1. Total score was 54.8±11.3. CONCLUSIONS: Among children with cerebral palsy (CP) related to congenital Zika syndrome, the quality of life (QOL) scores were very similar to other populations with cerebral palsy (CP). The activities of positioning, transferring and mobility had the greatest impact on health-related quality of life (QOL). Rehabilitation strategies and public policies should prioritize aspects related to mobility for this population.