The molecular landscape of ETMR at diagnosis and relapse.

Embryonal tumours with multilayered rosettes (ETMRs) are aggressive paediatric embryonal brain tumours with a universally poor prognosis1. Here we collected 193 primary ETMRs and 23 matched relapse samples to investigate the genomic landscape of this distinct tumour type. We found that patients with tumours in which the proposed driver C19MC2-4 was not amplified frequently had germline mutations in DICER1 or other microRNA-related aberrations such as somatic amplification of miR-17-92 (also known as MIR17HG). Whole-genome sequencing revealed that tumours had an overall low recurrence of single-nucleotide variants (SNVs), but showed prevalent genomic instability caused by widespread occurrence of R-loop structures. We show that R-loop-associated chromosomal instability can be induced by the loss of DICER1 function. Comparison of primary tumours and matched relapse samples showed a strong conservation of structural variants, but low conservation of SNVs. Moreover, many newly acquired SNVs are associated with a mutational signature related to cisplatin treatment. Finally, we show that targeting R-loops with topoisomerase and PARP inhibitors might be an effective treatment strategy for this deadly disease.

Toxicity potential of a pyraclostrobin-based fungicide in plant and green microalgae models.

Pyraclostrobin-based fungicides play an effective role in controlling fungal diseases and are extensively used in agriculture. However, there is concern regarding the potential adverse effects attributed to exposure to these fungicides on non-target organisms and consequent influence exerted on ecosystem functioning. Thus, it is essential to conduct studies with model organisms to determine the impacts of these fungicides on different groups of living organisms. The aim of this study was to examine the ecotoxicity associated with exposure to commercial fungicides containing pyraclostrobin. The focus of the analysis involved germination and initial development of seedlings of 4 plant models (Lactuca sativa, Raphanus sativus, Pennisetum glaucum and Triticum aestivum), in addition to determining the population growth rate and total carbohydrate content in microalga Raphidocelis subcapitata. The fungicide pyraclostrobin adversely influenced growth and development of the tested plants, indicating a toxic effect. The fungicide exerted a significant impact on the initial development of seedlings of all model species examined with T. aestivum plants displaying the greatest susceptibility to pyraclostrobin. Plants of this species exhibited inhibitory effects on both aerial parts and roots when treated with a concentration of 4.75 mg/L pyraclostrobin. In addition, the green microalga R. subcapitata was also significantly affected by the fungicide, especially at relatively high concentrations as evidenced by a reduction in total carbohydrate content. This commercial fungicide demonstrated potential phytotoxicity for the tested plant models and was also considered toxic to the selected microalgae, indicating an ecotoxic effect that might affect other organisms in aquatic environments.

Somatic mutational profiling and clinical impact of driver genes in Latin-Iberian medulloblastomas: Towards precision medicine.

Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity. Among the patients, 66.7% were MBSHH, 13.0% MBWNT, 7.3% MBGrp3, and 13.0% MBGrp4. Among the 63 variants found, 54% were classified as Tier I/II and 31.7% as oncogenic/likely oncogenic. We observed 33.3% of cases harboring at least one mutation. TP53 (23.2%, 16/69) was the most mutated gene, followed by PIK3CA (5.8%, 4/69), KIT (4.3%, 3/69), PDGFRA (2.9%, 2/69), EGFR (1.4%, 1/69), ERBB2 (1.4%, 1/69), and NRAS (1.4%, 1/69). Approximately 41% of MBSHH tumors exhibited mutations, TP53 (32.6%) being the most frequently mutated gene. Tier I/II and oncogenic/likely oncogenic TP53 variants were associated with relapse, progression, and lower survival rates. Potentially actionable variants in the PIK3CA and KIT genes were identified. Latin-Iberian medulloblastomas, particularly the MBSHH, exhibit higher mutation frequencies than other populations. We corroborate the TP53 mutation status as an important prognostic factor, while PIK3CA and KIT are potential therapeutic targets.

Oxidative stress induction by essential oil from Piper alatipetiolatum (Piperaceae) triggers lethality in the larvae of Culex quinquefasciatus (Diptera: Culicidae).

Culex quinquefasciatus is the main vector of lymphatic filariasis in Brazil, which present resistance to commercial insecticides. Nowadays, essential oils (EOs) exhibiting larvicidal activity, such as those derived from Piper alatipetiolatum, provide a promising alternative for vector control, including Culex species. This study aimed to investigate the larvicidal activity and the oxidative stress indicators of the EO from P. alatipetiolatum in Cx. quinquefasciatus larvae. The EO was extracted from P. alatipetiolatum leaves using the hydrodistillation method, resulting in a yield of 7.2 ± 0.1%, analysed by gas chromatography coupled with spectrometry and gas chromatography coupled with flame ionization detector (GC-MS and GC-FID), and evaluated against Cx. quinquefasciatus larvae. Reactive Oxygen and Nitrogen Species (RONS), Catalase (CAT), glutathione-S-transferase (GST), acetylcholinesterase (AChE), and Thiol levels were used as oxidative stress indicators. Analysis by CG-MS and CG-FID revealed that the main compound in the EO was the oxygenated sesquiterpene ishwarone, constituting 78.6% of the composition. Furthermore, the EO exhibited larvicidal activity, ranging from 26 to 100%, with an LC50 of 4.53 µg/mL and LC90 of 15.37 µg/mL. This activity was accompanied by a significant increase in RONS production, alterations in CAT, GST, AChE activity, and thiol levels compared to the control groups (p < 0.05). To the best of our knowledge, this is the first report describing the larvicidal activity and oxidative stress induced by the EO from P. alatipetiolatum against Cx. quinquefasciatus larvae. Therefore, we propose that this EO shows promise as larvicidal agent for the effective control of Cx. quinquefasciatus larvae.

How much time of sedentary behavior is associated with depressive symptoms in community-dwelling older adults in southern Brazil?

AIMS: Identify sedentary behavior (SB) cut-off points to screen for depressive symptoms in older adults and verify the association between these conditions. METHODS: A cross-sectional survey of 308 community-dwelling older adults was conducted. The outcome was the presence of depressive symptoms (≥6 points on the Geriatric Depression Scale-15). The exposure was SB using the self-reported time on a weekday and weekend (International Physical Activity Questionnaire). The cut-off points for SB categorization were determined by the receiver operating characteristic curve and multivariate logistic regression to verify the association. RESULTS: Older adults who spent ≥4.5 hours/day in SB (sensitivity = 48.8%; specificity = 67.8%) were 1.81 times more likely (95%CI: 1.03;3.15) to have depressive symptoms compared to those who stayed for shorter periods. CONCLUSIONS: There was an association between SB and depressive symptoms; therefore, older adults must have SB <4.5 hours/day to reduce the chances of developing depressive symptoms.

Tropical grass silages with spineless cactus in diets of Holstein × Zebu heifers in the semiarid region of Brazil.

One of the factors that limit ruminant production in the semiarid region is the lack of roughage in the dry season. The management of forage plants adapted to edaphoclimatic conditions is a strategy to improve animal production. This study was conducted to examine the effects of biomass sorghum silage (BSS; Sorghum bicolor (L.) Moench) and BRS capiaçu grass silage (CGS; Pennisetum purpureum Schum) with or without spineless cactus (Opuntia spp.) in crossbred Holstein × Zebu heifers' diets on the intake, apparent digestibility of the nutrients and animal performance (e.g., final weight, daily weight gain) (experiment 1). Also, to evaluate the ruminal kinetics of dry matter (DM) and neutral detergent fiber (NDF) of roughages used in diets using two animals cannulated in the rumen (experiment 2). In experiment 1, ten heifers with an initial body weight of 200 ± 2.74 kg (mean ± standard deviation) and a mean age of 10 months were used. The animals were distributed in an experimental design in two simultaneous 5 × 5 Latin squares. Five experimental diets were used: diet 1, Volumax sorghum silage (VSS); diet 2, biomass sorghum silage (BSS); diet 3, BRS capiaçu silage (CGS); diet 4, biomass sorghum silage (60%) with spineless cactus (40%) (BSS + SC); and diet 5, BRS capiaçu grass silage (60%) with spineless cactus (40%) (CGS + SC). The diets were formulated with sorghum silage or BRS capiaçu grass silage with or without spineless cactus (roughage) and a maize- and soybean-based concentrate (75:25 roughage-to-concentrate ratio) on DM basis. The experiment lasted 105 days, divided into five periods of 21 days (17 days for the adaptation of the animals to the diets and management and 4 for data collection and samples). The diets containing CGS and CGS + SC resulted in lower dry matter intake (DMI; 5.61 kg day-1; P < 0.01), which was 19.4% lower than the diets with VSS, BSS, and BSS + SC (7.00 kg day-1). The BSS + SC and CGS + SC diets showed higher crude protein digestibility (P < 0.01) at 21.9% than the other treatments (Volumax, BSS, CGS). The different diets did not change the final weight or the daily weight gain of the heifers. The BRS 716 biomass sorghum silage and BRS capiaçu grass combined with spineless cactus increased (P < 0.05) the intake of nonfibrous carbohydrates and did not interfere (P > 0.05) with the final weight or average daily gain of the crossbred Holstein × Zebu heifers. The standardized potentially degradable fraction (Bp) of the NDF was 13.91% higher (P < 0.01) for BSS and BSS + SC (61.6%) compared to the others (53.0%). A diet based on BSS + SC is recommended for feeding crossbred heifers in the growing phase.

Characterization of highly proliferative decidual precursor cells during the window of implantation in human endometrium.

Pregnancy depends on the wholesale transformation of the endometrium, a process driven by differentiation of endometrial stromal cells (EnSC) into specialist decidual cells. Upon embryo implantation, decidual cells impart the tissue plasticity needed to accommodate a rapidly growing conceptus and invading placenta, although the underlying mechanisms are unclear. Here we characterize a discrete population of highly proliferative mesenchymal cells (hPMC) in midluteal human endometrium, coinciding with the window of embryo implantation. Single-cell transcriptomics demonstrated that hPMC express genes involved in chemotaxis and vascular transmigration. Although distinct from resident EnSC, hPMC also express genes encoding pivotal decidual transcription factors and markers, most prominently prolactin. We further show that hPMC are enriched around spiral arterioles, scattered throughout the stroma, and occasionally present in glandular and luminal epithelium. The abundance of hPMC correlated with the in vitro colony-forming unit activity of midluteal endometrium and, conversely, clonogenic cells in culture express a gene signature partially conserved in hPMC. Cross-referencing of single-cell RNA-sequencing data sets indicated that hPMC differentiate into a recently discovered decidual subpopulation in early pregnancy. Finally, we demonstrate that recurrent pregnancy loss is associated with hPMC depletion. Collectively, our findings characterize midluteal hPMC as novel decidual precursors that are likely derived from circulating bone marrow-derived mesenchymal stem/stromal cells and integral to decidual plasticity in pregnancy.

Single nCounter assay for prediction of MYCN amplification and molecular classification of medulloblastomas: a multicentric study.

PURPOSE: Medulloblastoma is the most frequent pediatric malignant brain tumor, and is divided into four main subgroups: WNT, SHH, group 3, and group 4. MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single assay. METHODS: It was included 209 medulloblastomas from 205 patients (Brazil, Argentina, and Portugal), divided into training (n = 50) and validation (n = 159) sets. A nCounter assay was carried out using a custom panel for molecular classification, with additional genes, including MYCN. nSolver 4.0 software and the R environment were used for profiling and MYCN mRNA analysis. MYCN amplification by FISH was performed in 64 cases. RESULTS: The 205 medulloblastomas were classified in SHH (44.9%), WNT (15.6%), group 3 (18.1%) and group 4 (21.4%). In the training set, MYCN amplification was detected in three SHH medulloblastomas by FISH, which showed significantly higher MYCN mRNA counts than non-FISH amplified cases, and a cutoff for MYCN amplification was established ([Formula: see text] + 4σ = 11,124.3). Applying this threshold value in the validation set, we identified MYCN mRNA counts above the cutoff in three cases, which were FISH validated. CONCLUSION: We successfully stratified medulloblastoma molecular subgroups and predicted MYCN amplification using a single nCounter assay without the requirement of additional biological tissue, costs, or bench time.

Intoxication by 3-MeO-PCP and O-desmethyltramadol: an unusual NPS mix.

Over the past few years, the new psychoactive substances' phenomenon has been continuously studied. Its dynamic context is characterized by a broad diversity of substances, including several groups, such as synthetic cathinones, synthetic opiates, and synthetic cannabinoids. However, and due both to this diversity and to the low number of detected cases, information on intoxication reports is always important, in order to understand their biological mechanisms. In this case, a male individual was found unresponsive, with some different powders and paraphernalia near him. After toxicological analysis to the powders, paraphernalia, and whole blood samples, five different compounds were identified. From these, two of them (3-MeO-PCP and o-desmethyltramadol) were identified and quantitated in the whole blood sample. The obtained results suggested that death was due to the presence and action of these two substances, in what may be considered an unusual mix of NPS. This case highlights the value of evaluating all the traces found in the scene investigation and the need of sending all the paraphernalia found for toxicological examination, together with all the possible information obtained on the scene, namely by relatives or witnesses. On the other hand, this case shows the significance of broad-spectrum analytical methods, in order to detect and identify, as specifically as possible, eventual substances present and used by victims.

A RETROSPECTIVE STUDY OF HEPATIC HEMOSIDEROSIS AND IRON STORAGE DISEASE IN SEVERAL CAPTIVE AND FREE-RANGING AVIAN SPECIES.

Some wild species of mammals and birds are prone to excessive iron accumulation, especially when maintained in human care. Hemosiderosis is the process of intracellular accumulation of iron without evidence of toxicity, whereas hemochromatosis is characterized by severe iron accumulation with accompanying organ damage. Iron storage disease (ISD) occurs when organ damage is severe and causing clinical signs. This retrospective study investigated the occurrence of hemosiderosis and ISD across a variety of avian taxa, including captive and free-ranging birds. Archived paraffin-embedded hepatic samples from 103 birds from Belo Horizonte Zoo that died naturally in the period of 2008 to 2018 were re-evaluated with histologic and morphometric techniques, focusing on the identification and scoring of iron deposits in hepatocytes and the quantification of total affected hepatic area. The birds represented 13 orders, 22 families, and 52 genera, and 66 (64.0%) had some degree of iron accumulation in their liver. Importantly, no statistical difference was observed in the occurrence of iron accumulation between families, orders, or origin (free-ranging or captive). Direct and positive correlation was observed between the total area affected by the iron deposits and the histologic score. In this study, there were two cases with severe iron accumulation and clinical signs compatible with ISD: a barefaced curassow (Crax fasciolata) and a channel-billed toucan (Ramphastos vitellinus). This study indicates that iron accumulation may occur in a wide range of avian species, with frequencies and intensities that are similar between free-ranging birds and those in human care. It describes for the first time the occurrence of ISD in a Galliform species.

High Prevalence of Anal High-Grade Squamous Intraepithelial Lesions, and Prevention Through Human Papillomavirus Vaccination, in Young Men Who Have Sex With Men Living With Human Immunodeficiency Virus.

BACKGROUND: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)-related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. METHODS: Two hundred and sixty MSMLWH aged 18-26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. RESULTS: Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type-associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18-associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. CONCLUSIONS: 18-26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type-associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.

Histone deacetylase inhibitor panobinostat induces antitumor activity in epithelioid sarcoma and rhabdoid tumor by growth factor receptor modulation.

BACKGROUND: Epithelioid sarcomas and rhabdoid tumors are rare, aggressive malignancies with poor prognosis. Both are characterized by INI1 alterations and deregulation of growth factor receptors albeit their interaction has not been elucidated. METHODS: In this study, we investigated the activity of a panel of epigenetic modulators and receptor tyrosine kinase inhibitors in vitro on respective cell lines as well as on primary patient-derived epithelioid sarcoma cells, and in vivo on xenografted mice. Focusing on histone deacetylase (HDAC) inhibitors, we studied the mechanism of action of this class of agents, its effect on growth factor receptor regulation, and changes in epithelial-to-mesenchymal transition by using cell- and RT-qPCR-based assays. RESULTS: Pan-HDAC inhibitor panobinostat exhibited potent anti-proliferative activity at low nanomolar concentrations in A204 rhabdoid tumor, and VAESBJ/GRU1 epithelioid sarcoma cell lines, strongly induced apoptosis, and resulted in significant tumor growth inhibition in VAESBJ xenografts. It differentially regulated EGFR, FGFR1 and FGFR2, leading to downregulation of EGFR in epithelioid sarcoma and to mesenchymal-to-epithelial transition whereas in rhabdoid tumor cells, EGFR was strongly upregulated and reinforced the mesenchymal phenotype. All three cell lines were rendered more susceptible towards combination with EGFF inhibitor erlotinib, further enhancing apoptosis. CONCLUSIONS: HDAC inhibitors exhibit significant anticancer activity due to their multifaceted actions on cytotoxicity, differentiation and drug sensitization. Our data suggest that the tailored, tissue-specific combination of HDAC inhibitors with therapeutics which target cellular salvage mechanisms might increase their therapeutic relevance.

Clinical evidence for a biological effect of epigenetically active decitabine in relapsed or progressive rhabdoid tumors.

BACKGROUND: Refined therapy has helped to improve survival rates in rhabdoid tumors (RT). Prognosis for patients with chemoresistant, recurrent, or progressive RT remains dismal. Although decitabine, an epigenetically active agent, has mainly been evaluated in the management of hematologic malignancies in adults, safety in children has also been demonstrated repeatedly. MATERIALS AND METHODS: A retrospective series of patients who received decitabine upon relapse or progression following therapy according to the EU-RHAB regimen is presented. Due to the retrospective nature of analyses, response was defined as measurable regression of at least one lesion on imaging. 850k methylation profiling was done whenever tumor tissue was available. RESULTS: A total of 22 patients with RT of any anatomical localization were included. Most patients (19/22) presented with metastases. All received low-dose decitabine with or preceding conventional chemotherapy. Patients received a median of two (1-6) courses of decitabine; 27.3% (6/22) demonstrated a radiological response. Molecular analyses revealed increased methylation levels in tumors from responders. No excessive toxicity was observed. Clinical benefits for responders included eligibility for early phase trials or local therapy. Responders showed prolonged time to progression and overall survival. Due to small sample size, statistical correction for survivorship bias demonstrated no significant effect on survival for responders. CONCLUSIONS: Patients with RT demonstrate promising signs of antitumor activity after multiagent relapse therapy including decitabine. Analyses of methylation data suggest a specific effect on an epigenetic level. We propose to consider decitabine and other epigenetic drugs as candidates for further clinical investigations in RT.

A poorer nutritional status impacts quality of life in a sample population of elderly cancer patients.

RATIONALE: Quality of Life (QoL) is impaired in cancer, and the elderly are particularly vulnerable to malnutrition. A diagnosis of cancer in elderly patients further exacerbates risks of negative health outcomes. Here we investigated associations between QoL and nutritional status in a sample population of mostly socially deprived elderly cancer patients. METHOD: 432 cancer patients were recruited for this cross-sectional study at point of admission to a tertiary referral hospital for cancer treatment. Patient-generated subjective global assessment (PG-SGA) assessed nutritional status. Functional assessment of cancer therapy- general (FACT-G) quantified QoL. Relationship between PG-SGA and QoL was assessed by Spearman correlation. PG-SGA outcomes were compared against FACT-G scores employing Mann-Whitney test. Bivariate Linear Regression Model was employed to investigate influences of sociodemographic, clinical and nutritional status upon QoL. RESULTS: 37.5% of participants were malnourished or at risk. 39% were illiterate and 54.6% had family income lower than minimum wage. Malnourished patients showed lower FACT-G scores (76.8 vs. 84.7; p = 0.000). Poor nutritional diagnosis was inversely correlated with all QoL domains. Bivariate regression analysis showed that lower PG-SGA scores (ßo = - 1.00; p = 0.000) contributed to FACT-G score deterioration, the male gender showed better QoL scores, and other clinical and sociodemographic variables did not show relationship. CONCLUSION: Poorer nutritional status was significantly associated with worsened physical, social, emotional and functional well-being QoL domains in elderly cancer patients. Poorer nutritional status is an independent risk factor for worsened QoL. Future policies aimed at particularly vulnerable populations may improve QoL and health outcomes.

Using the Robson classification to assess caesarean section rates in Brazil: an observational study of more than 24 million births from 2011 to 2017.

BACKGROUND: Applying the Robson classification to all births in Brazil, the objectives of our study were to estimate the rates of caesarean section delivery, assess the extent to which caesarean sections were clinically indicated, and identify variation across socioeconomic groups. METHODS: We conducted a population-based study using routine records of the Live Births Information System in Brazil from January 1, 2011, to December 31, 2017. We calculated the relative size of each Robson group; the caesarean section rate; and the contribution to the overall caesarean section rate. We categorised Brazilian municipalities using the Human Development Index to explore caesarean section rates further. We estimated the time trend in caesarean section rates. RESULTS: The rate of caesarean sections was higher in older and more educated women. Prelabour caesarean sections accounted for more than 54 % of all caesarean deliveries. Women with a previous caesarean section (Group 5) made up the largest group (21.7 %). Groups 6-9, for whom caesarean sections would be indicated in most cases, all had caesarean section rates above 82 %, as did Group 5. The caesarean section rates were higher in municipalities with a higher HDI. The general Brazilian caesarean section rate remained stable during the study period. CONCLUSIONS: Brazil is a country with one of the world's highest caesarean section rates. This nationwide population-based study provides the evidence needed to inform efforts to improve the provision of clinically indicated caesarean sections. Our results showed that caesarean section rates were lower among lower socioeconomic groups even when clinically indicated, suggesting sub-optimal access to surgical care.

Targeted Phytohormone Profiling Identifies Potential Regulators of Spikelet Sterility in Rice under Combined Drought and Heat Stress.

Rice cultivated under rainfed or semi-irrigated ecosystems is frequently exposed to a combination of drought and heat stress. As a sensitive crop at the reproductive stage, exposure to combined drought and heat stress will have a deleterious effect on yield. In this study, two rice cultivars with contrasting spikelet sterility, AVT2-5315 (low sterility) and AC35027 (high sterility), under combined stress were selected for physiological characterization and phytohormonal profiling at anthesis. Under combined stress, both cultivars did not differ in the physiological parameters such as relative water content, photosynthetic rate, light-adapted chlorophyll fluorescence and biomass, suggesting a similar source activity under stress. However, AVT2-5315 showed better yield due to better pollen and spikelet fertility than AC35027, suggesting its intrinsic tolerance ability under combined stress. Targeted profiling of 15 phytohormones from drought, heat and combined stress-treated flag leaf and spikelet tissues using LC-MS/MS showed increased accumulation of auxins (indole 3-acetic acid and indole 3-butyric acid) in flag leaves and jasmonic acid in spikelets of AVT2-5315, while there was increased accumulation of ethylene in flag leaves and methyl-jasmonate in spikelets of AC35027. Increased accumulation of these hormones correlated with key biosynthetic pathway genes. In the flag leaves, increased accumulation of auxins was correlated with increased transcript levels of YUCCA-like gene 1 (OsYUCCA1) and fish bone (OsFIB), in AVT2-5315 under combined stress. In AC35027, increased ethylene content was correlated with expression of 1-aminocyclopropane-1-carboxylate synthase 1 (OsASC1) and aminocyclopropane-1-carboxylic acid oxidase 2 (OsACO2). Similarly, in spikelets, increased accumulation of jasmonic acid in AVT2-5315 was correlated with expression of allene oxide cyclase (OsAOC) and 12-oxophytodienoic acid reductase 1 (OsOPR1). The mechanism of regulating spikelet sterility by these hormones needs further investigation towards improving rice tolerance to combined stress.

ACUTE NECROTIZING AND EOSINOPHILIC MYOCARDITIS IN A CHIMPANZEE (PAN TROGLODYTES).

Cardiac disease is of importance in captive chimpanzee (Pan troglodytes) health. Here we report an eosinophilic and necrotizing myocarditis in a 17-y-old chimpanzee with no previous history of cardiac disease that progressed to death within 48 h. Toxic and infectious causes were ruled out. The chimpanzee had eosinophilia at different occasions in previous years. The animal had a severe, diffuse, and acute monophasic necrotizing myocarditis, with a moderate lymphoplasmacytic infiltrate that was rich in eosinophils. Ante- and postmortem investigations are compatible with an unusual eosinophilic myocarditis with clinical evolution and morphology comparable with human eosinophilic myocarditis secondary to hypereosinophilic syndrome.

Platinum-drugs Ototoxicity in Pediatric Patients With Brain Tumors: A 10-Year Review.

PURPOSE: Platinum-derived chemotherapy is one of the cornerstones in the treatment of central nervous system tumors in children. We aimed to assess the incidence of hearing loss in children after the exposure to platinum drugs. MATERIAL AND METHODS: Retrospective study of prospectively collected data on children consecutively diagnosed with brain tumors and treated with platinum derivatives at a tertiary referral hospital between January 2006 and December 2015. We analyzed multiples variables, such as: age at diagnosis, tumor location, hydrocephalus, platinum drug type, radiotherapy, and follow-up time. The final sample size was 51 patients. RESULTS: The median age at diagnosis was 6 years. The median overall follow-up time was 75 months. The incidence of ototoxicity was 23.5%. Rates of hearing loss with carboplatinum were lower than with cisplatinum. A statistically significant association occurred between the presence of hydrocephalus, radiotherapy exposure, infratentorial tumor location, and ototoxicity after treatment with platinum derivatives. CONCLUSIONS: Childhood central nervous system tumors nowadays exhibit improved cure and survival rates. However, the ototoxicity resulting from the chemotherapy treatment may accompany patients for the rest of their lives. This study reveals that this occurrence is not negligible, and the association of radiotherapy and the presence of hydrocephalus can be potentiating factors.

Nutritional efficiency of feed-restricted F1 Holstein/Zebu cows in early lactation.

The quantitative feed restriction of lactating cows has been used in intensive production systems as a strategy to reduce production costs. However, the effects of this restriction in F1 Holstein/Zebu cows are unclear. The objective of this work was to evaluate the effect of quantitative feed restriction on nutrient intake and digestibility, nitrogen balance, feed efficiency, feed behavior, and productive performance in F1 Holstein/Zebu cows during early lactation. Sixty F1 Holstein × Zebu cows were used at the stage of initial lactation (50 ± 13 days of lactation), and they had an initial body weight (BW) of 482 ± 43 kg. The experimental arrangement adopted was a completely randomized design, with five feed restriction levels (3.39, 2.75, 2.50, 2.25, and 2.00% of BW) and 12 cows in each treatment group. In the short term (63 days), there were reductions of 45.9% and 47.2% in dry matter intake (P < 0.01) and crude protein (P < 0.01), respectively, when the diet supply was limited from 3.39% BW to 2.00% of BW. There were declines in intake of ether extract (P < 0.01) and nonfibrous carbohydrates (P < 0.01), but there was no change in daily milk production (P = 0.44) nor the daily milk production corrected to 3.5% fat (P = 0.12); the averages were 14.01 kg/day and 13.25 kg/day, respectively. Considering the lower body weight loss, feed restriction is recommended up to 2.5% of the BW.

Productive and reproductive performance of females F1 Holstein x Gir daughters of proven bulls.

Records of 234 lactations from F1 Holstein x Gyr daughters of proven bulls were used in this study for the evaluation of productive and reproductive characteristics of cows. Data were collected from a private farm located in the municipality of Santo Antônio do Monte, MG, Brazil. The objective of this study was to evaluate the effects of Holstein bull's PTA milk (predicted transmitting ability) calving year, season, and parity on the productive and reproductive characteristics of F! cows. The productive characteristics analyzed were total milk production (TMP), average daily production (ADP), days in milk (DIM), and milk yield per day of calving interval (MYDCI). The studied reproductive characteristics were service interval (SI), calving interval (CI), and gestation length (GL). The results were subjected to statistical analysis and means for significant effects were compared using Duncan's test at a significance level of 5%. F1 animals efficiently expressed their genetic potential for milk production with an average total milk production of 7842.61 kg and average daily production of 24.53 kg. Means for days in milk, milk yield per day of calving interval, service interval, calving interval, and gestation length were 322.52 days, 20.73 kg, 106.0 days, 383.23 days, and 276.18 days, respectively. Properly managed F1 Holstein x Gyr daughters of proven bulls fed a balanced diet efficiently expressed their genetic potential for milk production without adverse effects on reproduction. Moreover, Holstein x Gyr cows should be selected based on parents' PTA for milk traits and other factors such as environmental conditions and management.