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Several studies highlighted the complexity of mixing pesticides present in Amazonian aquatic environments today. There is evidence that indicates that ongoing climate change can alter the pattern of pesticide use, increasing the concentration and frequency of pesticide applications. It is known that the combination of thermal and chemical stress can induce interactive effects in aquatic biota, which accentuates cell and molecular damage. However, considering that the effects of climate change go beyond the increase in temperature the objective of this study was to evaluate the effect of climate change scenarios proposed by 6 th IPCC report and a mixture of pesticides on the tambaqui (Colossoma macropomum). The hypothesis of this study is that the negative effects will be accentuated by the combination of an extreme climate changes scenario and a mixture of pesticides. To test the hypothesis, juvenile tambaqui were exposed to a combination of four pesticides (chlorpyrifos, malathion, carbendazim and atrazine) in two scenarios, one that simulates current environmental conditions and another that predicted the environmental scenario for the year 2100. Fish were subjected to the experimental conditions for 96 h. At the end of the experiment, samples of blood, gills, liver, brain, and muscle were obtained for hematological, genotoxic, biochemical, and histopathological analyses. The results demonstrate that environmentally realistic concentrations of pesticides, when mixed, can alter the biochemical responses of tambaqui. The extreme scenario promotes hematological adjustments, but impairs branchial antioxidant enzymes. There is an interaction between the mixture of pesticides and the extreme scenario, accentuating liver tissue damage, which demonstrates that even increased activity of antioxidant and biotransformation enzymes were not sufficient to prevent liver damage., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Different classes of pesticides such as fungicides, herbicides, and insecticides, can induce differential expression of genes that are involved in tumorigenesis events in fish, including the expression of tumor suppressor tp53. The degree and duration of the stressful condition is decisive in defining which tp53-dependent pathway will be activated. Herein we evaluate the target genes expression that participates in the regulation pathway of the tumor suppressor tp53 and in the cancerous processes in tambaqui after exposure to malathion. Our hypothesis is that malathion promotes a gene response that is differentially regulated over time, with positive regulation of tp53 target genes related to the apoptotic pathway and a negative regulation of genes that promote antioxidant responses. The fish were exposed to a sublethal concentration of the insecticide for 6 and 48 h. Liver samples were used to analyze the expression of 11 genes using real-time PCR. Overall, the malathion promoted over time increases in tp53 expression and differential expression of tp53 related genes. The exposure resulted in the activation of damage response related genes, caused a positive expression of atm/atr genes. The pro-apoptotic gene bax was up-regulated and the anti-apoptotic bcl2 was down-regulated. Increased expression of mdm2 and sesn1 in the first hours of exposure and no effect on the antioxidant genes sod2 and gpx1 were also observed. We also witnessed an increase in the expression of the hif-1α gene, with no effect on ras proto-oncogene. The extension of this stressful condition accentuated tp53 transcription, and minimized the levels of mdm2, sens1 and bax; however, it down regulated the levels of bcl2 and the bcl2/bax ratio, which indicates the maintenance of the apoptotic response to the detriment of an antioxidant response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to evaluate the time in days between symptom onset and first positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) result for COVID-19., Methods: This systematic review was conducted in the MEDLINE (PubMed), Embase, and Scopus databases using the following descriptors: "COVID-19", "SARS-CoV-2", "coronavirus", "RT-PCR", "real time PCR", and "diagnosis"., Results: The included studies were conducted in 31 different countries and reported on a total of 6831 patients. The median age of the participants was 49.95 years. The three most common symptoms were fever, cough, and dyspnea, which affected 4012 (58.68%), 3192 (46.69%), and 2009 patients (29.38%), respectively. Among the 90 included studies, 13 were prospective cohorts, 15 were retrospective cohorts, 36 were case reports, 20 were case series, and six were cross-sectional studies. The overall mean time between symptom onset and positive test result was 6.72 days. Fourteen articles were analyzed separately for the temporal profile of RT-PCR test results; the best performance was on days 22-24, when 98% of test results were positive., Conclusion: These findings corroborate the RT-PCR COVID-19 testing practices of some health units. In addition, the most frequently described symptoms of these patients can be considered the initial symptoms of infection and used in decision-making about RT-PCR testing., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: To describe epilepsy after congenital Zika virus infection (ZIKV) and its relationship with structural neuroimaging findings., Methods: This was a cross-sectional study in children (aged 13-42 months) who were born with microcephaly due to ZIKV infection between 2015-2017. Patients underwent a brain imaging scan (magnetic resonance) and a video-EEG study., Results: Among the patients (n = 43), 55.8 % were male, 88.4 % were born at term, mean head circumference at the birth was 29.7 ± 1.8 cm, and 44.8 % were infected in the first trimester of pregnancy. Neuroimaging was moderately abnormal in 30.2 % and severely abnormal in 46.5 % of patients. Early seizures (<6 months of age) were observed in 41.9 %. EEG background was abnormal when asleep or awake in 72.1 % and during sleep in 62.8 %. The interictal epileptogenic activity was recorded on 41/43 of the EEGs and was predominantly multifocal (62.8 %). An ictal EEG was obtained in 22 patients and 31.8 % had more than one seizure type. Sleep EEG (background) patterns, interictal epileptogenic activity (p = 0.046), interictal discharge localization (p = 0.015), type of ictal epileptogenic activity (p = 0.002), and localization of ictal discharge (p = 0.024) were significantly different between neuroimaging groups. The mild neuroimaging group had a higher chance of having more frequently normal sleep EEG patterns, no interictal epileptogenic activity and a further increase in the probability of walking without limitations, and less neurodevelopment delay., Conclusion: In patients with congenital Zika virus syndrome, epilepsy tended to be early and refractory. EEG features correlated with degree of neuroimaging abnormalities., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Global warming caused by greenhouse gases accumulation, in particular carbon dioxide, is the major current environmental challenge, as it will affect all life forms over the next decades. Aquaculture, a fast growing food production sector, is already facing the effects of global warming. The fish immune system is expected to be especially affected by increased temperature and carbon dioxide, mainly when associated to infectious diseases outbreaks. Here, we experimentally investigated the associated effects of an extreme climate scenario and two levels of monogenean parasitism on the hematological and immunological response of an important Amazon fish for continental aquaculture: Colossoma macropomum. Individuals of C. macropomum with low and high levels of parasitism were exposed to current and extreme climate scenarios (4.5 °C and 900 ppm CO 2 above current levels). We characterized their hematological profile using classical methods, and their immune-related gills gene expression (HSP70, IL-1β and IL-10) using quantitative real-time polymerase chain reaction (qPCR). After 7 days of exposure, we observed that exposure to extreme climate scenario caused rapid increase of parasitism intensity and likely acute inflammation, indicated by the higher expression of HSP70 and IL-1β. The IL-10 gene was downregulated in both groups exposed to extreme climate scenario, contrasting with animals exposed to current scenario. Thus, in the current scenario, the parasitized tambaqui showed a response to the tissue damage, which was not observed in the animals exposed to the extreme scenario., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Sepsis is characterized by a severe and disseminated inflammation. In the central nervous system, sepsis promotes synaptic dysfunction and permanent cognitive impairment. Besides sepsis-induced neuronal dysfunction, glial cell response has been gaining considerable attention with microglial activation as a key player. By contrast, astrocytes' role during acute sepsis is still underexplored. Astrocytes are specialized immunocompetent cells involved in brain surveillance. In this context, the potential communication between the peripheral immune system and astrocytes during acute sepsis still remains unclear. We hypothesized that peripheral blood mononuclear cell (PBMC) mediators are able to affect the brain during an episode of acute sepsis. With this in mind, we first performed a data-driven transcriptome analysis of blood from septic patients to identify common features among independent clinical studies. Our findings evidenced pronounced impairment in energy-related signaling pathways in the blood of septic patients. Since astrocytes are key for brain energy homeostasis, we decided to investigate the communication between PBMC mediators and astrocytes in a rat model of acute sepsis, induced by cecal ligation and perforation (CLP). In the CLP animals, we identified widespread in vivo brain glucose hypometabolism. Ex vivo analyses demonstrated astrocyte reactivity along with reduced glutamate uptake capacity during sepsis. Also, by exposing cultured astrocytes to mediators released by PBMCs from CLP animals, we reproduced the energetic failure observed in vivo. Finally, by pharmacologically inhibiting phosphoinositide 3-kinase (PI3K), a central metabolic pathway downregulated in the blood of septic patients and reduced in the CLP rat brain, we mimicked the PBMC mediators effect on glutamate uptake but not on glucose metabolism. These results suggest that PBMC mediators are capable of directly mediating astrocyte reactivity and contribute to the brain energetic failure observed in acute sepsis. Moreover, the evidence of PI3K participation in this process indicates a potential target for therapeutic modulation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Engineered skin coverings have been adopted clinically to support extensive and deep wounds that result in fewer healthy skin remaining and therefore take longer to heal. Nonetheless, these biomaterials demand intensive labor and an expensive final cost. In comparison to conventional bandages, which do not meet all the requirements of wound care, electrospun fiber mats could potentially provide an excellent environment for healing. In this work, we developed two nanostructured scaffolds based on polyamide-6 (PA-6) to be tested as a wound covering in a rat model of full-thickness incisional wound healing. The central idea was to create a bioconstruct that is simple to implement and biologically safe, with a high survival rate, which provides physical support and biological recognition for new functional tissues. An unmodified PA-6 and a soybean-modified PA-6 were employed as nanofibrillar matrices in this study. The biomaterials showed a dimensional homology to natural extracellular matrix components and neither in vitro toxicity nor in vivo side effects. Both polymeric scaffolds were resistant to the sterilization process and could promote the attachment of 3T3 fibroblast cells, besides successfully incorporating the growth factor PDGF-BB, which had its bioactivity extended for up to 12 h under simulated conditions. The modification of PA-6 chains with a fatty acid derivative increased the scaffold's surface free energy, favoring cell proliferation, collagen formation, and ECM secretion. These results confirm the potential of these materials as a topical dermal covering for skin regeneration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Peptide YY (PYY) belongs to the neuropeptide Y (NPY) family, which also includes the pancreatic polypeptide (PP) and NPY. PYY is secreted by the intestinal L cells, being present in the blood stream in two active forms capable of crossing the blood brain barrier, PYY (1-36) and its cleavage product, PYY (3-36). PYY is a selective agonist for the Y2 receptor (Y2R) and these receptors are abundant in the hippocampus. Here we investigated the mechanisms by which PYY (3-36) regulates intracellular Ca 2+ concentrations ([Ca 2+ ] i ) in hippocampal neurons by employing a calcium imaging technique in hippocampal cultures. Alterations in [Ca 2+ ] i were detected by changes in the Fluo-4 AM reagent emission. PYY (3-36) significantly increased [Ca 2+ ] from the concentration of 10 -11 M as compared to the controls (infusion of HEPES-buffered solution (HBS) solution alone). The PYY (3-36)-increase in [Ca 2+ ] i remained unchanged even in Ca 2+ -free extracellular solutions. Sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase pump (SERCA pump) inhibition partially prevent the PYY (3-36)-increase of [Ca 2+ ] i and inositol 1,4,5-triphosphate receptor (IP3R) inhibition also decreased the PYY (3-36)-increase of [Ca 2+ ] i . Taken together, our data strongly suggest that PYY (3-36) mobilizes calcium from the neuronal endoplasmic reticulum (ER) stores towards the cytoplasm. Next, we showed that PYY (3-36) inhibited high K + -induced increases of [Ca 2+ ] i , suggesting that PYY (3-36) could also act by activating G-protein coupled inwardly rectifying potassium K + channels. Finally, the co-infusion of the Y2 receptor (Y2R) antagonist BIIE0246 with PYY (3-36) abolished the [Ca 2+ ] i increase induced by the peptide, suggesting that PYY (3-36)-induced [Ca 2+ ] i increase in hippocampal neurons occurs via Y2Rs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Copaifera langsdorffii Desf. (Fabaceae, Caesalpinioideae), popularly known as "copaiba" or "pau d'óleo", is a species of tree that is found throughout Brazil. The leaves of this tree are used in folk medicine to treat kidney stones. Galloylquinic acid derivatives and flavonoids are the main secondary metabolites found in C. langsdorffii leaves and are likely to be responsible for the effectiveness of this treatment. As an attempt to produce a phytotherapic, we have developed a reliable HPLC-UV method for the quality control of C. langsdorffii leaves. Phenolic compounds were extracted from C. langsdorffii leaves using 70% aqueous ethanol as the extraction solvent. HPLC-UV analyses were carried out on a Synergi Polar-RP column (100×3.0mm, 2.5μm), and the mobile phase was made up of formic acid-water (0.1:99.9, solvent A), and isopropanol-methanol-acetonitrile (5:40:60, solvent B). The elution gradient was A:B (90:10 to 85:15) in 8.0min, followed by A:B (85:15 to 64:36) up to 30.0min, using a flow rate of 0.7mL/min, and UV detection at 280nm. This method was used to quantify nine galloylquinic acid derivatives and two flavonoids, which gave a good detection response and linearity in the range of 1.88-110.0μg/mL. Furthermore, the detection and quantification limits ranged from 0.070 to 0.752μg/mL, and 0.211-2.278μg/mL respectively, with a maximum RSD of 4.18%. The method is reliable for the quality control of C. langsdorffii raw material, its hydroethanolic extract, and could potentially be used to quantify these compounds in other Copaifera species., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Animal venoms have been widely recognized as a major source of biologically active molecules. Bothriurus bonariensis, popularly known as black scorpion, is the arthropod responsible for the highest number of accidents involving scorpion sting in Southern Brazil. Here we reported the first attempt to investigate the neurobiology of B. bonariensis venom (BBV) in the insect and mammalian nervous system. BBV (32 μg/g) induced a slow neuromuscular blockade in the in vivo cockroach nerve-muscle preparations (70 ± 4%, n = 6, p < 0.001), provoking repetitive twitches and significantly decreasing the frequency of spontaneous leg action potentials (SNCAPs) from 82 ± 3 min(-1) to 36 ± 1.3 min(-1) (n = 6, p < 0.05), without affecting the amplitude. When tested in primary cultures of rat hippocampal cells, BBV induced a massive increase of Ca(2+) influx (250 ± 1% peak increase, n = 3, p < 0.0001). The disturbance of calcium homeostasis induced by BBV on the mammalian central nervous system was not accompanied by cellular death and was prevented by the co-treatment of the hippocampal cells with tetrodotoxin, a selective sodium channel blocker. The results suggest that the biological activity of BBV is mostly related to a modulation of sodium channels function. Our biological activity survey suggests that BBV may have a promising insecticidal and therapeutic potential., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Ureases of Canavalia ensiformis are natural insecticides with a still elusive entomotoxic mode of action. We have investigated the mechanisms involved in the neurotoxicity induced by Jack Bean Urease (JBU) in Nauphoeta cinerea (Olivier)., Methods: To carry out this study we have employed biochemical and neurophysiological analysis of different cockroach organ systems., Results and Conclusions: The injection of the insects with JBU (0.75-6μg/g animal), although not lethal within 24h, caused significant inhibition of the brain acetylcholinesterase activity (60±5%, p<0.05, n=6). JBU (1.5μg/200μL), acetylcholine (0.3μg/200μL) or neostigmine (0.22μg/200μL), induced a positive cardiac chronotropism (∼25%) in the cockroaches (p<0.05, n=9). JBU (6μg/g) increased the insects' grooming activity (137±7%), similarly to octopamine (15μg/g) (p<0.05, n=30, respectively). Pretreating the insects with phentolamine (0.1μg/g) prevented the JBU- or octopamine-induced increase of grooming activity. JBU (6μg/g) caused 65±9% neuromuscular blockade in the cockroaches, an effect prevented by bicuculline (5μg/g) (p<0.05, n=6). JBU (6μg/g) decreased the frequency whilst increasing the amplitude of the spontaneous neural compound action potentials (1425±52.60min -1 , controls 1.102±0.032mV, p<0.05, n=6, respectively). Altogether the results indicate that JBU induces behavioral alterations in Nauphoeta cinerea cockroaches probably by interfering with the cholinergic neurotransmission. The neuromuscular blocking activity of JBU suggests an interplay between acetylcholine and GABA signaling., General Significance: The search for novel natural molecules with insecticide potential has become a necessity more than an alternative. Understanding the mode of action of candidate molecules is a crucial step towards the development of new bioinsecticides. The present study focused on the neurotoxicity of Canavalia ensiformis urease, a natural insecticide, in cockroaches and revealed interferences on the cholinergic, octopaminergic and GABA-ergic pathways as part of its entomotoxic mode of action., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The use of cell-based therapies for spinal cord injuries has recently gained prominence as a potential therapy or component of a combination strategy. Experimental and clinical studies have been performed using mesenchymal stem cell therapy to treat spinal cord injuries with encouraging results. However, there have been reports on the adverse effects of these stem cell-based therapies, especially in the context of tumor modulation. This article surveys the literature relevant to the potential of mesenchymal autologous stem cells for spinal cord injuries and their clinical implications., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Alzheimer's and Parkinson's diseases are severe neurodegenerative conditions triggered by complex biochemical routes. Many groups are currently pursuing the search for valuable biomarkers to either perform early diagnostic or to follow the disease's progress. Several studies have reported relevant findings regarding environmental issues and the progression of such diseases. Here the etiology and mechanisms of these diseases are briefly reviewed. Approaches that might reveal candidate biomarkers and environmental stressors associated to the diseases were analyzed under a proteomic perspective. This article is part of a Special Issue entitled: Environmental and structural proteomics., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: To evaluate electroencephalogram (EEG) patterns in very low birth weight premature newborns when reaching term-to-term neonates, thereby comparing extra uterine to intra uterine development., Methods: EEG recordings were obtained between 2 and 14 days of life in 47 preterm (<37 weeks) very low birth weight (⩽1500 g) newborns and repeated when reaching term age (38-42 weeks) in a subsample (n=22). EEG recordings were also obtained in term newborns. Clinical evaluation was performed at birth and at 6 and 12 months., Results: Relative to the first EEG, preterm newborns showed a reduction in delta brushes and interburst intervals and increased interhemispheric synchrony, suggesting an improvement in EEG maturation. Further organization in sleep patterns, like a reduction in total sleep time and phase shifts, were also observed. However, when reaching term, preterm newborns still had less mature EEG patterns, phase shifts and transitional sleep than matched controls. Background abnormalities and dysmaturity in preterm newborns during the first EEG predicted adverse neurological outcome later on., Conclusions: EEG patterns in preterm very low birth weight newborns might be influenced by extra uterine development. Specific EEG abnormalities are related to increased risk of neurological disorders., Significance: Extra uterine development of very low birth weight delays the acquisition of maturational EEG patterns., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: The detection of molecular and cytogenetic alterations is important for the diagnosis, prognosis and classification of myeloproliferative neoplasms., Objectives: THE AIM OF THIS STUDY WAS TO DETECT THE FOLLOWING MUTATIONS: JAK2 V617F, JAK2 exon 12 and MPL W515K/L, besides chromosomal abnormalities. Furthermore, molecular and cytogenetic alterations were correlated with the leukocyte and platelet counts, hemoglobin levels and age in all patients and with the degree of fibrosis in primary myelofibrosis cases., Methods: Twenty cases of polycythemia vera, 17 of essential thrombocythemia and 21 of primary myelofibrosis were selected in the Hematology Department of the Universidade Federal de São Paulo (UNIFESP) between February 2008 and December 2009. The JAK2 V617F, JAK2 exon 12 mutations, MPL W515K and MPL W515L mutations were investigated by real-time PCR and direct sequencing. G-band karyotyping and fluorescence in situ hybridization were used to detect chromosomal abnormalities., Results: Chromosomal abnormalities were observed only in polycythemia vera (11.8%) and primary myelofibrosis cases (17.6%), without correlation to clinical data. Chromosomal abnormalities were not detected by fluorescence in situ hybridization. The JAK2 V617F mutation was observed in polycythemia vera (90%), primary myelofibrosis (42.8%) and essential thrombocythemia (47%). Patients with JAK2 V617F-negative polycythemia vera had lower platelet and leukocyte counts compared to V617F-positive polycythemia vera (p-value = 0.0001 and p-value = 0.023, respectively). JAK2 V617F-positive and MPL W515L-positive primary myelofibrosis cases had a higher degree of fibrosis than V617F-negative cases (p-value = 0.022). JAK2 exon 12 mutations were not detected in polycythemia vera patients. The MPL W515L mutation was observed in one case of primary myelofibrosis and in one of essential thrombocythemia. The MPL W515K mutation was not found in patients with essential thrombocythemia or primary myelofibrosis. The MPL W515L-positive patient with primary myelofibrosis had more severe anemia than other patients with primary myelofibrosis., Conclusions: This study demonstrates that karyotyping for JAK2 and MPL mutations is useful in the diagnosis of myeloproliferative neoplasms. The precise pathogenetic contribution of these alterations is still unclear. However, this study adds more information about the pathophysiology of polycythemia vera, essential thrombocythemia and primary myelofibrosis.

Objective: To evaluate the outcomes of acute myeloid leukemia patients who were older than 60 years of age at the time of diagnosis following the implementation of a treatment algorithm based on age, performance status, and cytogenetic results., Methods: We retrospectively compared the results of 31 elderly acute myeloid leukemia patients (median age of 74 years) who were treated according to the new algorithm., Results: Fifteen patients with a good performance status and no unfavorable karyotypes were treated with either intensive cytotoxic chemotherapy (<70 years, nine cases) or adapted etoposide, 6-thioguanine and idarubicine (>70 years, six cases); 16 cases with a poor performance status or unfavorable cytogenetics received supportive care only. Six patients achieved a complete remission and two achieved a partial remission after chemotherapy. There were three toxic deaths during induction, two in the adapted etoposide, 6-thioguanine and idarubicine group and one in the intensive cytotoxic chemotherapy group. The overall median survival time was 2.96 months, 1.3 months in the supportive care group, and 4.6 months in the treatment group., Conclusions: Our results illustrate the importance of treatment guidelines adapted to local resources in an attempt to improve the survival of elderly acute myeloid leukemia patients in developing countries.

Objective: To verify the relationship of ictal activity and sleep organization (REM/NREM stages) in the neonatal EEG., Methods: A retrospective study was developed with 41 high-risk newborns, with clinical history suggestive of seizures and ictal activity identified by the EEG. In each EEG, sleep organization and number/duration of sleep stages were determined. Sleep stages (REM, NREM) were scored following behavior and EEG activity. When it was impossible to recognize stages the epoch was classified as unrecognizable sleep stages (UNSS). Ictal activity was classified according to morphology and correlated with sleep epochs. Density of ictal activity was calculated as the duration of the discharge divided by the duration of the sleep epoch., Results: Unrecognizable sleep stages were observed in 21 EEGs (51.2%). Comparing NREM X REM states there was a significant predominance of ictal activity in REM sleep (P = 0.01). Duration of discharges was longer on REM epochs; however, differences were not significant. Considering the type of discharges there was a predominance of monomorphic rhythmic discharges in all sleep epochs., Conclusions: In this sample, epileptogenic activity occurred more frequently in UNSS, where sleep organization was already disrupted. When it was possible to recognize sleep stages, ictal activity was more frequently during REM sleep., Significance: This study speculates the relationship between sleep organization and ictal activity and raises the hypothesis that the expression of ictal activity in relation to sleep stages (REM/NREM) may have age-dependent mechanisms in the developing brain.

Objective: Periodic breathing is a respiratory pattern typical of preterm infants, but its clinical significance has not been clarified yet. The present study was designed to investigate whether the presence of periodic breathing is specifically associated to low post-conceptional ages, preterm birth, or common clinical disorders related to preterm birth., Methods: The study included 271 consecutive infants submitted to neonatal polysomnography, of whom 138 were born before 37 complete gestational weeks (preterm) and 133 were full-term. The main outcome measure was periodic breathing. A multivariate analysis was performed to test the specific impact of preterm birth, respiratory distress syndrome and hypoxic-ischemic encephalopathy on the occurrence of periodic breathing, with adjustment for potential confounding factors such as the post-conceptional age by the time of the polysomnography., Results: Periodic breathing was twice more frequent in infants born before term (83/138 [60%]) than in full-term babies (41/133 [31%], chi2 = 22.3, P < 0.0001). The presence of periodic breathing was not significantly associated to either hypoxic-ischemic encephalopathy or respiratory distress syndrome. After a multivariate analysis, only preterm birth remained in the regression model as a specific risk factor for periodic breathing (adjusted odds ratio=5.62, P < 0.0001)., Conclusions: Periodic breathing is a respiratory pattern independently associated with preterm birth, and this association cannot be imputed to the coexistence of either respiratory distress syndrome or hypoxic-ischemic encephalopathy among preterm infants., Significance: The finding of periodic breathing in neonatal polysomnography correlates with preterm birth but not with its associated clinical disorders.

Objective: To find out if there is a difference in P50 suppression between patients using typical antipsychotic drugs and those using clozapine, as well as to confirm the findings of abnormal P50 suppression in patients with schizophrenia, when compared to healthy volunteers., Methods: Fifty patients with schizophrenia and 25 healthy volunteers were divided into 3 groups: group 1 - patients using typical antipsychotics; group 2 - patients using clozapine; group 3 - controls. Before the examination, all patients were interviewed by a psychiatrist using the Brief Psychiatry Rating Scale (BPRS)., Results: The average S2/S1 ratio was 0.82+/-0.45 in group 1, 0.57+/-0.41 in group 2, and 0.44+/-0.27 in group 3 (P=0.003). Statistical analysis showed a significant difference when the results of group 1 were compared to those of groups 2 (P=0.045) and 3 (P=0.001). There was no significant difference between groups 2 and 3 (P=0.182). There was a significant difference in the S1-S2 difference only between groups 1 and 3 (P=0.007), but a non-significant trend towards a similar difference was found between groups 1 and 2 (P=0.067). There was no correlation between the BPRS values and any P50 parameter., Conclusions: The suppression of P50 among patients using clozapine was significantly greater than that obtained in patients using typical antipsychotics., Significance: This study confirms, in a more evident way, the improvement of the suppression of P50 potential in schizophrenics using clozapine. Additionally, it discusses the physiopathological mechanism involved.

Development of some immune-mediated disorders may depend on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. To explore neuropsychologic mechanisms in relation to the abnormal endocrine reactivity in patients with systemic lupus erythematosus (SLE) and chronic hepatitis C (CHC) we used the corticotropin releasing hormone (CRH) test, the Minnesota Multiphasic Personality Inventory (MMPI), and the Edinburgh Inventory of Manual Preference Inventory (EIMP). Compared to controls, the adrenocorticotrophic hormone (ACTH) response to CRH was reduced in CHC, while SLE presented reduced baseline dehydroepiandrosterone sulfate levels; higher neurotic scores were found in SLE and higher behavior deviant scores in CHC. Peak ACTH levels were a significant factor for the MMPI profile variability, while the manual preference score was a significant factor for the ACTH response. Personality and manual preference contribute to neuroendocrine abnormalities. Different behavioral and neuroimmunoendocrine models emerge for these disorders., (Copyright 2001 Elsevier Science (USA).)

Seizures are one of the most frequent problems in the neonatal period, and are frequently associated with high mortality and morbidity rates. On the other hand, neonatal seizures may represent a first or even the only sign of central nervous system dysfunction. However, establishing the diagnosis of neonatal seizures poses several problems, and clinical observation is not sufficient in many cases. Neonatal polysomnography is a valuable tool both in the diagnostic and in the prognostic assessment of neonatal seizures. The present text reviews some technical aspects related to neonatal polysomnographies, and its usefulness in the area of suspected neonatal seizures. Moreover, some questions are raised regarding rhythmic discharges and their significance as a possible ictal and interictal epileptic pattern in the neonate.

Objective: This study aimed at identifying the characteristics - especially the duration - of rhythmic discharges in neonatal EEG, and their association with clinical neonatal problems. Specifically, we aimed at testing the diagnostic and prognostic validity of using 10 s as minimal duration for defining electroencephalographic seizures., Design and Methods: The polysomnographies of 340 neonates were reviewed, and episodes of rhythmic discharges were identified, analyzed, and quantified. The study sample was divided into 3 groups: one in which the maximal duration of rhythmic discharges was shorter than 10 s (brief rhythmic discharges, BRD), a second one in which there were rhythmic discharges longer than 10 s (long rhythmic discharges, LRD), and finally a group in which no rhythmic discharge was found (No-RD). These 3 groups of subjects were compared for the baseline and outcome clinical data., Results: From the 340 neonates studied, 210 did not present any form of rhythmic discharge, 67 (19. 7%) had only BRD episodes, and 63 (18.5%) had at least one LRD episode. Prevalence of rhythmic discharges was low among healthy full term newborns, and was significantly higher among preterm and high-risk newborns. Electrophysiological characteristics of rhythmic discharges did not differ between healthy neonates and high-risk ones. Accompanying clinical manifestations were present in 26.3% of the LRD group, but also in 15.9% of the BRD group. The presence of BRD was significantly associated with leukomalacia and with hypoglycemia in the cross-sectional analysis of baseline data, and with an increased risk for abnormal neurodevelopmental outcome after a mean follow-up period of 47 months (adjusted relative risk=4.90, P<0.01)., Conclusions: The present data demonstrate an association between BRD and clinical history of hypoxic-ischemic encephalopathy, especially when complicated by leukomalacia, and also with a prognosis of increased risk for abnormal neurodevelopmental outcome. The clinical and prognostic significance of isolated BRD justifies the need to include these brief episodes in future studies of neonatal seizures.

Objective: This study focuses on the characteristics of frontal sharp transients (FST), a normal variant of neonatal EEG, in newborns with hypoglycemia., Methods: The EEG from 20 newborns with symptomatic hypoglycemia were compared with a control group of normal newborns matched by conceptional age. The dynamics of these transients were evaluated concerning sleep stages. The density, type and bilateral synchrony of FST were also calculated. The results were compared in the two groups by Student's t test., Results: When compared with controls, hypoglycemic newborns have increased density of frontal sharp transients in all sleep stages but less bilateral synchrony (P<0.05). FST density was even higher in small for gestational age newborns., Conclusions: The data suggests that normal patterns of neonatal EEG as FST can be influenced by systemic disturbances.

We analyzed the relationship between normal neonatal EEG features and gestational age and conceptional age, and evaluated the normal aspects of EEG maturation in preterm babies compared to term babies. We report 46 newborns, divided into two groups. Group I consisted of 11 newborns with gestational age between 30 and 32 weeks, followed with weekly polysomnograms until they reach 42 weeks' conceptional age. Group II (control) consisted of 35 newborns with gestational ages of 34 weeks (n = 5), 36 weeks (n = 10), 38 weeks (n = 10) and 40 weeks (n = 10) evaluated with one polysomnogram in their first 24-48 h of life. In each examination one 5 min epoch in REM and NREM sleep was analyzed to quantify the number of delta brushes, the presence of frontal and temporal sharp transients, the presence of delta frontal rhythmic activity, the grade of concordance between EEG patterns and sleep stages, the percent of interhemispheric synchrony and the duration of interburst interval. The age dependent variability of the EEG patterns was evaluated during the subsequent weeks with group comparisons at weeks 34, 36, 38 and 40. Our results show that the number of delta brushes and the duration of the interburst interval decrease as gestational and conceptional age increase. The percent of interhemispheric synchrony increases with gestational and conceptional age. The presence of frontal sharp transients and delta frontal rhythmic activity suggest that the newborn is fullterm. The presence of temporal sharp transients suggest a preterm newborn. The degree of concordance between behavioral sleep patterns and EEG was more helpful in recognizing sleep stages than in estimating gestational or conceptional age. Although the EEG patterns were comparable between the groups at the same age, analyses of the behavioral patterns of concordance in NREM sleep showed that newborns in Group I had a more immature behaviour than newborns in Group II. Our results also suggest that extrauterine life of preterm babies does not seem to accelerate EEG maturation but may influence the acquisition of behavioral patterns during NREM sleep.

We examined the significance and frequency of occurrence of rhythmic epileptiform discharges (REDs) on the scalp EEGs of 74 patients with intractable partial epilepsy. We also analyzed the relationship of this abnormality to the continuous epileptiform discharges (CEDs) recorded on ECoG. Both REDs and CEDs had been found to be highly specific and sensitive indicators of focal cortical dysplastic lesions. Thirty-four patients (group I) had focal cortical dysplastic lesions (FCDLs) and 40 (group II) had non-dysplastic structural lesions. REDs were observed in 15 (44%) of the 34 patients of group I and in none of group II. REDs did not occur in isolation, were associated with more intermittent interictal spikes involving other regions, but had a greater (P < 0.05) significance for the localization of the epileptogenic area. A strong relationship was observed between the presence of REDs on scalp EEG and the occurrence of CEDs on ECoG recordings. Twelve (80%) of 15 patients with REDs had CEDs. Focal cortical dysplastic lesions are likely to be present when rhythmic epileptiform discharges are found.

We describe a case of Salmonella tricuspid endocarditis in an intravenous drug abuser with human immunodeficiency virus infection. He was successfully treated with antibiotics with no clinical relapse. To our knowledge, this is the first case of this kind reported in the literature. Physicians should be on the alert for this potentially curable cardiac complication of human immunodeficiency virus infection.