Advances in surface design and biomedical applications of magnetic nanoparticles.

Despite significant efforts by scientists in the development of advanced nanotechnology materials for smart diagnosis devices and drug delivery systems, the success of clinical trials remains largely elusive. In order to address this biomedical challenge, magnetic nanoparticles (MNPs) have gained attention as a promising candidate due to their theranostic properties, which allow the simultaneous treatment and diagnosis of a disease. Moreover, MNPs have advantageous characteristics such as a larger surface area, high surface-to-volume ratio, enhanced mobility, mass transference and, more notably, easy manipulation under external magnetic fields. Besides, certain magnetic particle types based on the magnetite (Fe3O4) phase have already been FDA-approved, demonstrating biocompatible and low toxicity. Typically, surface modification and/or functional group conjugation are required to prevent oxidation and particle aggregation. A wide range of inorganic and organic molecules have been utilized to coat the surface of MNPs, including surfactants, antibodies, synthetic and natural polymers, silica, metals, and various other substances. Furthermore, various strategies have been developed for the synthesis and surface functionalization of MNPs to enhance their colloidal stability, biocompatibility, good response to an external magnetic field, etc. Both uncoated MNPs and those coated with inorganic and organic compounds exhibit versatility, making them suitable for a range of applications such as drug delivery systems (DDS), magnetic hyperthermia, fluorescent biological labels, biodetection and magnetic resonance imaging (MRI). Thus, this review provides an update of recently published MNPs works, providing a current discussion regarding their strategies of synthesis and surface modifications, biomedical applications, and perspectives.

Dental pain in Brazilian preschool children: association with the severity of dental caries and impact on oral health-related quality of life.

PURPOSE: This study aimed to verify the association between dental pain and severity of dental caries (caries morbidity stages) and the impact on oral health-related quality of life (OHRQoL) in preschool children. METHODS: A cross-sectional study with 199 children (2-5 years old) enrolled at preschools in Capão do Leão-RS, Brazil. The self-report of mothers of children with a history of dental pain in the last 6 months and perception of their child's OHRQoL (ECOHIS) were obtained through a structured questionnaire. This questionnaire also collected independent variables. Children's oral examination was performed using the CAST instrument to determine caries morbidity stage. Crude and adjusted Poisson regression analysis was performed. RESULTS: The prevalence of dental pain was 14.57%. The chance of the occurrence of dental pain was higher among children diagnosed in morbidity [Prevalence ratio-PR: 5.29 (95% confidence interval-95% CI 1.91-14.61); p = 0.001] and severe morbidity [RP = 6.12 (95 CI% 2.25-16.64); p < 0.001] stages. Children with dental pain presented higher scores in the total ECOHIS [rate ratio = 7.11 (95% CI 4.55-11.09); p < 0.001] and in all of the domains of this instrument. Furthermore, children with a history of dental trauma [PR = 2.41 (95% CI 1.15-5.04); p < 0.001] and those whose reason for last visit to the dental office was for restorative/endodontic/extraction treatment [PR = 1.29 (95% CI 1.01-6.19); p = 0.049] had a higher prevalence of dental pain. CONCLUSION: A substantial prevalence of dental pain in the last 6 months and negative impact on children's OHRQoL was identified in this sample. Children diagnosed with carious dentin lesions and abscess and fistula were more likely to have dental pain.

Acute murine-betacoronavirus infection impairs testicular steroidogenesis and the quality of sperm production.

Although several testicular alterations promoted by coronavirus infection have been demonstrated, the extent, causes, and players of testicular pathogenesis are not totally understood. The present study aimed to investigate the short-term effects on male fertility of intranasally administered murine hepatitis virus strain 3 (MHV-3), a member of the genus Betacoronavirus, which causes a severe systemic acute infection. This mouse model might be used as a in vivo prototype for investigating the impact of betacoronavirus on the endocrine and exocrine testicular functions with the advantage to be performed in a biosafety level 2 condition. Herein, we performed virological, histopathological, and molecular studies regarding the testicular spermatogenesis and the spermatic quality analyses in an MHV-3-infected C57BL/6 mice. The main outcomes showed that MHV-3 infects mouse testis and induces a testicular inflammatory state, impairing the steroidogenic pathway. The infection led to several alterations in the testicular parenchyma, such as: seminiferous epithelium sloughing, retention of residual bodies, germ cell apoptosis, alterations in intercellular junction proteins, and worse spermatogenic parameters. Moreover, the levels of plasmatic testosterone as well as the quality of sperm production reduced. Therefore, the present data suggest that the viral/inflammatory impairment of the steroidogenic pathway and the consequent imbalance of androgen levels is critical in testicular pathology, disturbing the SC barrier function and the germ cell differentiation. Our study is important for comprehending the effects of beta coronavirus infections on testis function in order to develop treatments that could prevent virus-mediated male infertility.

Citizen science through a recreational underwater diving project supports the collection of large-scale marine litter data: The Oceania case study.

In recent years, a growing body of literature on seafloor macro-litter has been produced worldwide. However, the spatial coverage of these studies is still limited and highly unbalanced, resulting in considerable knowledge gaps in some regions. To address this lack of information in Oceania, we extracted data from the Citizen Science project Dive Against Debris® to characterize marine debris collected by volunteer scuba divers on the coastal seafloor. Overall, the average litter density was 58.22 items/100m2, with plastics accounting for approximately 50 % of the total abundance and Single Use Plastics accounting for nearly 17 %. Notably, 36 % of the total litter abundance consisted of lost Fishing Gear including fishing lines, sinkers, baits and hooks as the most abundant debris items. To reduce lost fishing gear, clean-up initiatives by divers along with management actions such as education programs for fishermen, gear restrictions and the identification of designated fishing sites are recommended.

Horismenus camobiensis (Hym.: Eulophidae), a new hyperparasitoid of Cotesia invirae (Hym.: Braconidae) in Opsiphanes invirae (Lep.: Nymphalidae) pupae

Abstract Horismenus camobiensis sp. nov. (Hymenoptera: Eulophidae), is described based on morphological, molecular and ecological data; this new species of chalcid wasp acts as hyperparasitoid of Opsiphanis invirae (Hübner, 1818) (Lepidoptera: Nymphalidae) in its parasitoid Cotesia invirae Salgado-Neto and Whitfield, 2019 (Hymenoptera: Braconidae). Diagnoses with morphological and molecular characters and illustrations are provided.

Resumo Horismenus camobiensis sp. nov. (Hymenoptera: Eulophidae) é descrita com base em dados morfológicos, moleculares e ecológicos; esta nova espécie Chalcididae atua como hiperparasitoide de Opsiphanis invirae (Hübner, 1818) (Lepidoptera: Nymphalidae) em pupas de seu parasitoide Cotesia invirae Salgado-Neto and Whitfield, 2019 (Hymenoptera: Braconidae). Caracteres diagnósticos morfológicos e moleculares e ilustrações de H. camobiensis são fornecidos.

Horismenus camobiensis (Hym Eulophidae), a new hyperparasitoid of Cotesia invirae (Hym Braconidae) in Opsiphanes invirae (Lep Nymphalidae) pupae / Horismenus camobiensis (Hym Eulophidae), um novo hiperparasitóide de Cotesia invirae (Hym Braconidae) em pupas de Opsiphanes invirae (Lep Nymphalidae)

Abstract Horismenus camobiensis sp. nov. (Hymenoptera: Eulophidae), is described based on morphological, molecular and ecological data; this new species of chalcid wasp acts as hyperparasitoid of Opsiphanis invirae (Hübner, 1818) (Lepidoptera: Nymphalidae) in its parasitoid Cotesia invirae Salgado-Neto and Whitfield, 2019 (Hymenoptera: Braconidae). Diagnoses with morphological and molecular characters and illustrations are provided.

Resumo Horismenus camobiensis sp. nov. (Hymenoptera: Eulophidae) é descrita com base em dados morfológicos, moleculares e ecológicos; esta nova espécie Chalcididae atua como hiperparasitoide de Opsiphanis invirae (Hübner, 1818) (Lepidoptera: Nymphalidae) em pupas de seu parasitoide Cotesia invirae Salgado-Neto and Whitfield, 2019 (Hymenoptera: Braconidae). Caracteres diagnósticos morfológicos e moleculares e ilustrações de H. camobiensis são fornecidos.

Electron microscopy approach to the wetting dynamics of single organosilanized mesopores.

Columnar mesoporous silicon (PSi) with hydrophobic vs. hydrophilic chemistries was chosen as a model for the local (pore-by-pore) study of water-pore interactions. Tomographic reconstructions provided a 3D view of the ramified pore structure. An in situ study of PSi wetting was conducted for categorized pore diameters by environmental scanning TEM. An appropriate setting of the contrast allows for the normalization of the gray scale in the images as a function of relative humidity (RH). This allows constructing an isotherm for each single pore and a subsequent averaging provides an isotherm for each pore size range. The isotherms systematically point to an initial adsorption through the formation of water adlayers, followed by a capillary filling process at higher RH. The local isotherms correlate with (global) gravimetric determination of wetting. Our results point at the validation of a technique for the study of aging and stability of single-pore nanoscale devices.

Social capital and dental caries among 3-5-year-old Indian children. A cross-sectional study.

AIM: The aim of the study is to investigate the association between social capital and dental caries among 3-5-year-old preschool children in a rural region of southern India. METHODS: A cross-sectional study was conducted among 260 children ranging from 3 to 5 years-old and their parents from 13 preschools of the Udupi region of south India between December 2018, and February 2019. A 16-item Social Capital Scale (SCS) was used to collect data from the children's parents regarding their social capital. The diet history was collected from the parents and the children were examined for dental caries using the dmft index in their schools. CONCLUSION: Dental caries among preschool children had a negative association with parental social capital, and significantly contributed to variances in dental caries along with socioeconomic and dietary factors.

Do photosynthetic metabolism and habitat influence foliar water uptake in orchids?

Epiphytic and rupicolous plants inhabit environments with limited water resources. Such plants commonly use Crassulacean Acid Metabolism (CAM), a photosynthetic pathway that accumulates organic acids in cell vacuoles at night, so reducing their leaf water potential and favouring water absorption. Foliar water uptake (FWU) aids plant survival during drought events in environments with high water deficits. We hypothesized that FWU represents a strategy employed by epiphytic and rupicolous orchids for water acquisition and that CAM will favour increased water absorption. We examined 6 epiphyte, 4 terrestrial and 6 rupicolous orchids that use C3 (n = 9) or CAM (n = 7) pathways. Five individuals per species were used to evaluate FWU, structural characteristics and leaf water balance. Rupicolous species with C3 metabolism had higher FWU than other species. FWU (Cmax and k) could be related to succulence, SLM and leaf RWC. The results indicated that high orchid leaf densities favoured FWU, as area available for water storage increases with leaf density. Structural characteristics linked to water storage (e.g. high RWC, succulence), on the other hand, could limit leaf water absorption by favouring high internal leaf water potentials. Epiphytic, rupicolous and terrestrial orchids showed FWU. Rupicolous species had high levels of FWU, probably through absorption from mist. However, succulence in plants with CAM appears to mitigate FWU.

Are there differences in the attention of elite football players concerning playing positions?

PURPOSE: This study aimed to compare the attention performance, by playing position, in elite Brazilian football players. METHODS: A total of 66 professional players competing in the first division of the Brazilian Championship were evaluated. They were grouped according to their playing positions into 7 goalkeepers, 8 defenders, 15 fullbacks, 8 defensive midfielders, 13 attacking midfielders, and 15 forwards. The attention was evaluated using the QuotientTM ADHD System equipment. The group performances were compared using the Kruskal-Wallis Test and the post-hoc analysis using the Mann-Whitney Test. RESULTS: Fullbacks showed less attentive behavior than defenders (U = 9.000, p = 0.001), defensive midfielders (U = 12.500, p = 0.002), offensive midfielders (U = 48.000, p = 0.007) and forwards (U = 27.000, p = 0.001). Fullbacks also had impulsive behavior longer than defenders (U = 10.500, p = 0.001) and defensive midfielders (U = 12.000, p = 0.002), as well as offensive midfielders had impulsive behavior longer than defenders (U = 16.0000, p = 0.004) and defensive midfielders (U = 19.500, p = 0.009). CONCLUSION: Players of defensive positions, as defenders and defensive midfielders, were more attentive and less impulsive than players of hybrid positions, responsible for both defensive and offensive actions, such as fullbacks and attacking midfielders. The present finding indicates that the defenders were the players who maintained the attention level for more time, while the fullbacks maintained for less time. Players in offensive playing positions (fullbacks and attacking midfielders) maintained their impulsive behavior for longer when compared to defensive positions (defenders and defensive midfielders).

Horismenus camobiensis (Hym.: Eulophidae), a new hyperparasitoid of Cotesia invirae (Hym.: Braconidae) in Opsiphanes invirae (Lep.: Nymphalidae) pupae.

Horismenus camobiensis sp. nov. (Hymenoptera: Eulophidae), is described based on morphological, molecular and ecological data; this new species of chalcid wasp acts as hyperparasitoid of Opsiphanis invirae (Hübner, 1818) (Lepidoptera: Nymphalidae) in its parasitoid Cotesia invirae Salgado-Neto and Whitfield, 2019 (Hymenoptera: Braconidae). Diagnoses with morphological and molecular characters and illustrations are provided.

First list of parasitoids in flies of medical, veterinary, and forensic importance in Rio Grande do Sul - Brazil / Primeira lista de parasitoides em moscas de importância médica, veterinária e forense no Rio Grande do Sul - Brasil

Necrophagous flies are of great importance for human and animal health. In places where their development occurs, parasitoids can be used as a tool to control these dipterans. In Brazil, the fauna of these parasitoids has been investigated in some regions. However, in Rio Grande do Sul, it is known the occurrence of only one species. Thus, this study aimed to create the first list of parasitoids in flies of medical and veterinary importance in Southern Brazil. Collections took place in the municipality of Pelotas (31º 42' S; 52º 18' W). Three replicates consisting of a 500 g bovine liver chunk placed in a tray were exposed to open air for 20 days. Then pupae were individualized and observed until their emergence. We identified 4,882 adult flies of Calliphoridae, Fanniidae, Muscidae, and Sarcophagidae. 4,040 parasitoids emerged, belonging to eight species, of which Nasonia vitripennis, Spalangia cameroni, Spalangia chontalensis, and Tachinephagus zealandicus are new records in Rio Grande do Sul state. Also, three undescribed species of the genus Aphaereta were collected. In spite of being the first attempt to inventory the fauna of hymenopteran parasitoids, this study may help in the development of management programs of these dipterans in the region.

Moscas necrófagas possuem grande importância para a sanidade humana e animal. Onde estas se desenvolvem ocorrem parasitoides que podem ser utilizados como ferramentas para o controle desses dípteros. No Brasil, a fauna desses parasitoides vem sendo investigada em algumas regiões e no Rio Grande do Sul é conhecida a ocorrência de apenas uma espécie. Portanto, o objetivo deste estudo foi criar a primeira lista de espécies de parasitoides de moscas de importância médica e veterinária ocorrentes no extremo sul do Brasil. As coletas foram realizadas no município de Pelotas (31º 42' S; 52º 18' O). Foram montadas três réplicas de bandejas contendo, cada uma, 500 g de fígado bovino, expostas ao ar livre durante 20 dias. Na sequência, as pupas foram individualizadas e observadas até a emergência. Foram identificados 4.882 adultos pertencentes às famílias Calliphoridae, Fanniidae, Muscidae e Sarcophagidae. Emergiram 4.040 parasitoides, pertencentes a oito espécies, das quais Nasonia vitripennis, Spalangia cameroni, Spalangia chontalensis e Tachinephagus zealandicus são novas ocorrências para o Rio Grande do Sul. Foram coletadas três espécies ainda não descritas do gênero Aphaereta. Apesar de ainda ser um primeiro esforço de inventariar a fauna de himenópteros parasitoides, este estudo pode auxiliar no desenvolvimento de programas de manejos desses dípteros na região.

First list of parasitoids in flies of medical, veterinary, and forensic importance in Rio Grande do Sul – Brazil / Primeira lista de parasitoides em moscas de importância médica, veterinária e forense no Rio Grande do Sul - Brasil

Necrophagous flies are of great importance for human and animal health. In places where their development occurs, parasitoids can be used as a tool to control these dipterans. In Brazil, the fauna of these parasitoids has been investigated in some regions. However, in Rio Grande do Sul, it is known the occurrence of only one species. Thus, this study aimed to create the first list of parasitoids in flies of medical and veterinary importance in Southern Brazil. Collections took place in the municipality of Pelotas (31º 42' S; 52º 18' W). Three replicates consisting of a 500 g bovine liver chunk placed in a tray were exposed to open air for 20 days. Then pupae were individualized and observed until their emergence. We identified 4,882 adult flies of Calliphoridae, Fanniidae, Muscidae, and Sarcophagidae. 4,040 parasitoids emerged, belonging to eight species, of which Nasonia vitripennis, Spalangia cameroni, Spalangia chontalensis, and Tachinephagus zealandicus are new records in Rio Grande do Sul state. Also, three undescribed species of the genus Aphaereta were collected. In spite of being the first attempt to inventory the fauna of hymenopteran parasitoids, this study may help in the development of management programs of these dipterans in the region.

Moscas necrófagas possuem grande importância para a sanidade humana e animal. Onde estas se desenvolvem ocorrem parasitoides que podem ser utilizados como ferramentas para o controle desses dípteros. No Brasil, a fauna desses parasitoides vem sendo investigada em algumas regiões e no Rio Grande do Sul é conhecida a ocorrência de apenas uma espécie. Portanto, o objetivo deste estudo foi criar a primeira lista de espécies de parasitoides de moscas de importância médica e veterinária ocorrentes no extremo sul do Brasil. As coletas foram realizadas no município de Pelotas (31º 42' S; 52º 18' O). Foram montadas três réplicas de bandejas contendo, cada uma, 500 g de fígado bovino, expostas ao ar livre durante 20 dias. Na sequência, as pupas foram individualizadas e observadas até a emergência. Foram identificados 4.882 adultos pertencentes às famílias Calliphoridae, Fanniidae, Muscidae e Sarcophagidae. Emergiram 4.040 parasitoides, pertencentes a oito espécies, das quais Nasonia vitripennis, Spalangia cameroni, Spalangia chontalensis e Tachinephagus zealandicus são novas ocorrências para o Rio Grande do Sul. Foram coletadas três espécies ainda não descritas do gênero Aphaereta. Apesar de ainda ser um primeiro esforço de inventariar a fauna de himenópteros parasitoides, este estudo pode auxiliar no desenvolvimento de programas de manejos desses dípteros na região.

First list of parasitoids in flies of medical, veterinary, and forensic importance in Rio Grande do Sul Brazil

Abstract Necrophagous flies are of great importance for human and animal health. In places where their development occurs, parasitoids can be used as a tool to control these dipterans. In Brazil, the fauna of these parasitoids has been investigated in some regions. However, in Rio Grande do Sul, it is known the occurrence of only one species. Thus, this study aimed to create the first list of parasitoids in flies of medical and veterinary importance in Southern Brazil. Collections took place in the municipality of Pelotas (31º 42 S; 52º 18 W). Three replicates consisting of a 500 g bovine liver chunk placed in a tray were exposed to open air for 20 days. Then pupae were individualized and observed until their emergence. We identified 4,882 adult flies of Calliphoridae, Fanniidae, Muscidae, and Sarcophagidae. 4,040 parasitoids emerged, belonging to eight species, of which Nasonia vitripennis, Spalangia cameroni, Spalangia chontalensis, and Tachinephagus zealandicus are new records in Rio Grande do Sul state. Also, three undescribed species of the genus Aphaereta were collected. In spite of being the first attempt to inventory the fauna of hymenopteran parasitoids, this study may help in the development of management programs of these dipterans in the region.

Resumo Moscas necrófagas possuem grande importância para a sanidade humana e animal. Onde estas se desenvolvem ocorrem parasitoides que podem ser utilizados como ferramentas para o controle desses dípteros. No Brasil, a fauna desses parasitoides vem sendo investigada em algumas regiões e no Rio Grande do Sul é conhecida a ocorrência de apenas uma espécie. Portanto, o objetivo deste estudo foi criar a primeira lista de espécies de parasitoides de moscas de importância médica e veterinária ocorrentes no extremo sul do Brasil. As coletas foram realizadas no município de Pelotas (31º 42 S; 52º 18 O). Foram montadas três réplicas de bandejas contendo, cada uma, 500 g de fígado bovino, expostas ao ar livre durante 20 dias. Na sequência, as pupas foram individualizadas e observadas até a emergência. Foram identificados 4.882 adultos pertencentes às famílias Calliphoridae, Fanniidae, Muscidae e Sarcophagidae. Emergiram 4.040 parasitoides, pertencentes a oito espécies, das quais Nasonia vitripennis, Spalangia cameroni, Spalangia chontalensis e Tachinephagus zealandicus são novas ocorrências para o Rio Grande do Sul. Foram coletadas três espécies ainda não descritas do gênero Aphaereta. Apesar de ainda ser um primeiro esforço de inventariar a fauna de himenópteros parasitoides, este estudo pode auxiliar no desenvolvimento de programas de manejos desses dípteros na região.

Difference Between the Profiles Presented by Yeasts that Colonize the Vaginal Mucosa or Cause Primary or Recurrent Candidiasis.

Candida yeasts are the most frequent in the vaginal content. This yeast may be a normal microbiota but also causes candidiasis. In symptomatic cases, primary candidiasis (VVC) or recurrence (RVVC) can be considered. This study aims to compare the frequency and in vitro sensitivity profile of Candida species isolated in the vaginal content with the different stages of the presence of yeasts. A total of 258 non-pregnant patients with/without VVC were prospectively screened at a teaching Health Centre of the Faculty of Medicine, in the University of Sao Paulo. The vaginal isolates were identified by traditional and molecular methods. Yeasts were isolated in 160 women. 34% were asymptomatic, 34% with vulvovaginal candidiasis (VVC), and 32% recurrent vulvovaginal candidiasis (RVVC). C. albicans was the most frequent species with 50.1% (82/160), followed by C. parapsilosis 13.7%(22/160), C. glabrata 12.5% (20/160), and C. tropicalis (6.2%). Analysis by the group showed that, in the asymptomatic group, eight yeast species were isolated, C. albicans 44.5% (24/54), C. glabrata 20% (11/54), C. parapsilosis and Rhodotorula rubra being the most frequent. In the VVC group, 11 yeast species were identified. Most isolates were C. albicans 68.5% (37/54), C. tropicalis 7.5% (4/54), and C. parapsilosis 5.5% (3/54). In the RVVC group, ten species were identified, the most frequent being C. albicans 38.5% (20/52), C. parapsilosis 17% (9/52), C. glabrata 4% (8/52), and C. tropicalis 6% (3/52). Less frequent species, such as C. haemulonii and Trichosporon spp, were isolated in the VVC and RVVC groups, C. kefyr was isolated in the three groups studied, and Rhodotorula spp was isolated in the control and RVVC groups. Candida metapsilosis was present in two isolates from the RVVC group. Most isolates were considered sensitive to the tested antifungals. Less sensitivity was seen for caspofungin. In this study, we were able to verify that the most common species of yeasts found in vaginal secretion were isolated in the three groups studied; however, there was the diversity of species in VVC and RVVC. Cryptic species C. haemulonii and were isolated in symptomatic patients. High levels of MICs, some of the antifungals tested, in the control group, draw attention in the group of asymptomatic women. We would like to emphasize that this research aims to assist clinicians and gynecologists, as well as assist in the epidemiological studies of candidiasis, in our country, how to draw attention to the profile of sensitivity/resistance to antifungals.

CNS-3 status remains an independent adverse prognosis factor in children with acute lymphoblastic leukemia (ALL) treated without cranial irradiation: Results of EORTC Children Leukemia Group study 58951.

AIM: To evaluate the prognostic significance of initial central nervous system (CNS) involvement of children with acute lymphoblastic leukemia (ALL) enrolled in the EORTC 58951 trial. PATIENTS AND METHODS: From 1998 to 2008, 1930 ALL patients were included in the randomized EORTC 58951 trial. Overall treatment intensity was adjusted according to known prognostic factors including the level of minimal residual disease after induction treatment. CNS-directed therapy comprised four to 11 courses of i.v. methotrexate (5g/m2), and 10 to 19 intrathecal chemotherapy injections, depending on risk group and CNS status. Cranial irradiation was omitted for all patients. RESULTS: The overall 8-year event-free survival (EFS) and overall survival (OS) rates were 81.3% and 88.1%, respectively. In the CNS-1, TPL+, CNS-2, and CNS-3 groups, the 8-year EFS rates were 82.1%, 77.1%, 78.3%, and 57.4%, respectively. Multivariable analysis indicated that initial CNS-3 status, but not CNS-2 or TLP+, was an independent adverse predictor of outcome. The 8-year incidence of isolated CNS relapse was 1.7% and of isolated or combined CNS relapse it was 3.7%. NCI high-risk group, male sex, CNS-2 and CNS-3 status were independent predictors for a higher incidence of any CNS relapse. CONCLUSIONS: CNS-3 status remains associated with poor prognosis and requires intensification of both systemic and CNS-directed therapy. This trial was registered at https://clinicaltrials.gov/under/NCT00003728.