A Multicentric Brazilian Investigative Study of Copy Number Variations in Patients with Congenital Anomalies and Intellectual Disability.

Genomic imbalances are the most common cause of congenital anomalies (CA) and intellectual disability (ID). The aims of this study were to identify copy number variations (CNVs) in 416 patients with CA and ID from 5 different genetics centers within 4 different states by using the Multiplex Ligation-dependent Probe Amplification (MLPA) technique and to apply the chromosomal microarray (CMA) methodology in selected cases. The samples were analyzed by MLPA kits P064, P036, P070 and P250. Positive results were found in 97/416 (23.3%) patients. CMA was applied in 14 selected cases. In 6/14 (42.85%) patients, CMA detected other copy number variations not detected by the MLPA studies. Although CMA is indispensable for genotype refinement, the technique is still unfeasible in some countries as a routine analysis due to economic and technical limitations. In these cases, clinical evaluation followed by karyotyping and MLPA analysis is a helpful and affordable solution for diagnostic purposes.

Auras as a prognostic factor in anterior temporal lobe resections for mesial temporal sclerosis.

BACKGROUND AND PURPOSE: Anterior temporal lobectomy for mesial temporal sclerosis (MTS) is a very effective measure for the control of seizures, and the probability of becoming seizure-free is approximately 70-90%. However, 30% of patients still experience seizures after surgery. An aura is a subjective ictal phenomenon that may precede an observable seizure. However, there are few studies on the prognostic factor aura although, being the initial symptoms of epileptic seizures, many types of auras have significant localizing or lateralizing value. This study hypothesized that the type of pre-operative aura may predict the post-surgical outcome in patients with medically refractory temporal lobe epilepsy due to MTS. METHODS: Of 1214 patients evaluated for surgery in the Epilepsy Center of Faculdade de Medicina de São Jose do Rio Preto (FAMERP), a tertiary Brazilian epilepsy center, 400 underwent anterior temporal lobectomy (ATL) for MTS. The number and type of auras were analyzed and compared with the Engel classification for outcome. RESULTS: Analyzing the patients by the type of aura, those who had extratemporal auras had the worst post-surgical result according to the Engel classification. Although mesial auras are apparently a good prognostic factor, patients without aura also had a worse prognosis. There were no differences between simple and multiple auras. To identify the most appropriate candidates for ATL, it is very important to consider the favorable prognostic factors for counseling patients in daily practice. CONCLUSIONS: Patients with symptoms and clinical signs that suggest extratemporal involvement may have unfavorable outcomes.

Effect of a specific exercise strategy on strength and proprioception in volleyball players with infraspinatus muscle atrophy.

Infraspinatus muscle atrophy is common in professional volleyball players, but it is unclear whether commonly observed strength and proprioception deficits can be reversed with training. Fifty-four participants were recruited into an infraspinatus atrophy group (IAG, n = 18) and a non-atrophy group (NAG, n = 18) of elite volleyballers plus a healthy non-athletic control group (CG, n = 18). IAG were trained with a progressive, specific shoulder external rotator strengthening routine for 32 sessions over 8 weeks. Shoulder external rotation peak torque (SERPT) and threshold to detect passive movement (TTDPM) and joint position sense (JPS) were measured before and after the intervention. At baseline, no significant difference was detected in strength or proprioception between the injured and control groups, but the normal athletes were stronger and had better proprioception than either IAG or CG (P < .001). IAG (d = 2.78) and NAG (d = 0.442) improved strength significantly after training. IAG improved TTDM and JPS (P < .001, d = -0.719 and -2.942, respectively) but were still worse than NAG (P < .001). Elite volleyball players with Infraspinatus muscle atrophy have strength and proprioception deficits which can be improved by a specific exercise program to normal but not elite athlete control levels.

One Hundred Consecutive Liver Transplants Using Institutes Georges Lopez-1 Preservation Solution: Outcomes and Prognostic Factors.

BACKGROUND: There are only 4 prior studies reporting on outcomes of liver transplantation (LT) using Institutes Georges Lopez-1 (IGL-1) preservation solution. Detection of negative predictors of LT using IGL-1 may help finding strategies to protect selected recipients at higher risk of graft failure and death. METHODS: Review of all consecutive adult patients who underwent a first whole-graft LT using IGL-1 at authors' institution from 2013 to 2016. Primary end point was graft failure within the first 90 postoperative days (PODs). Graft losses due to any cause (including all deaths with a functioning graft) were recorded as graft failures. RESULTS: Of all 100 patients included in this study, 37 were women; median age was 58 years (range 18-71). There were 12 graft losses during the first 90 PODs (including 3 cases of primary nonfunction of the liver allograft), and 10 of the 12 graft losses occurred on first 30 PODs. All 12 patients who experienced graft loss (including 1 patient who underwent liver retransplantation) died within the first 90 PODs. Of the total 100 patients, 14 experienced biliary complications. Univariate analysis revealed prolonged warm ischemic time (WIT) as the only predictor of 90-day graft failure (odds ratio = 23.5, confidence interval = 1.29-430.18, P = .03). The cutoff by receiver operating characteristic curve for WIT was 38 minutes (area under the curve = 0.70). Positive predictive value for WIT >38 minutes was 94.3%. CONCLUSIONS: LT using IGL-1 can be performed safely. Similar to prior reports on LT using other preservation solutions, prolonged WIT was associated with adverse outcomes.

Mesophotic fishes of the Abrolhos Shelf, the largest reef ecosystem in the South Atlantic.

Fishes inhabiting rhodolith beds and reefs at mesophotic depths on the Abrolhos Shelf, which encompasses the largest and richest coral reef formation in the South Atlantic Ocean, were assessed through technical diving and remotely operated vehicles (ROVs). A total of 74 fish species were recorded, including at least one new species, one new record for the south-western Atlantic and six new records for the Abrolhos region. Overfishing, mining and port activities are already threatening many endangered and commercially important species recorded on the mesophotic reefs of Abrolhos Shelf, and the establishment of marine protected areas and off-reserve fisheries regulations are urgently needed.

Are adverse effects of antiepileptic drugs different in symptomatic partial and idiopathic generalized epilepsies? The Portuguese-Brazilian validation of the Liverpool Adverse Events Profile.

We report the results of administration of the Portuguese-Brazilian translation of the Liverpool Adverse Events Profile (LAEP) to 100 patients (mean age=34.5, SD=12.12; 56 females), 61 with symptomatic partial epilepsy (SPE) and 39 with idiopathic generalized epilepsy (IGE) (ILAE, 1989) who were on a stable antiepileptic drug (AED) regimen and being treated in a Brazilian tertiary epilepsy center. Carbamazepine was the most commonly used AED (43.0%), followed by valproic acid (32.0%). Two or more AEDs were used by 69.0% of patients. The mean LAEP score (19 questions) was 37.6 (SD=13.35). The most common adverse effects were sleepiness (35.0%), memory problems (35.0%), and difficulty in concentrating (25.0%). Higher LAEP scores were associated with polytherapy with three or more AEDs (P=0.005), female gender (P<0.001), older age (P<0.001), and uncontrolled seizures (P=0.045). The intraclass coefficient (test-retest reliability) for LAEP overall score was 0.848 (95% CI=0.782-0.895), with a range from 0.370 (unsteadiness) to 0.750 (memory problems). Cronbach's α coefficient (internal consistency) was 0.903. The LAEP was highly correlated with Quality of Life in Epilepsy-31 inventory (r=-0.804, P>0.001) and Hospital Anxiety and Depression Scale (Depression: r=0.637, P<0.001; Anxiety: r=0.621, P<0.001) dimensions. LAEP overall scores were similar in people with SPE and IGE and were not helpful in differentiating adverse effects in these two groups. Clinical variables that influenced global LAEP were seizure frequency (P=0.050) and generalized tonic-clonic seizures in the last month (P=0.031) in the IGE group, and polytherapy with three or more AEDs (P=0.003 and P=0.003) in both IGE and SPE groups.

Espectroscopia por ressonância magnética de prótons em epilepsia mioclônica juvenil sugere o comprometimento de uma rede neuronal específica / Proton magnetic resonance spectroscopy study of juvenile myoclonic epilepsy patients suggests involvement of a specific neuronal network

OBJECTIVES: The neuroanatomical basis and the neurochemical abnormalities that underlay juvenile myoclonic epilepsy (JME) are not fully defined. While the thalamus plays a central role in synchronization of widespread regions of the cerebral cortex during a seizure, emerging evidence suggests that all cortical neurons may not be homogeneously involved. The purpose of this study was to investigate the cerebral metabolic differences between patients with JME and normal controls. METHODS: All patients had a JME diagnosis based on seizure history and semiology, EEG recording, normal magnetic resonance neuroimaging (MRI) and video-EEG. Forty JME patients (JME-P) were submitted to 1.5 T MRI proton spectroscopy (1H-MRS), multi-voxel with PRESS sequence (TR/TE = 1500/30 ms) over the following locations: prefrontal cortex (PC), frontal cortex (FC), thalamus, basal nuclei, posterior cingulate gyrus (PCG), insular, parietal and occipital cortices. We determined ratios for integral values of N-acetyl aspartate (NAA) and glutamine-glutamate (GLX) over creatine-phosphocreatine (Cr). The control group (CTL) consisted of 20 age and sex-matched healthy volunteers. RESULTS: Group analysis demonstrated a tendency for lower NAA/Cr ratio of JME-P compared to CTL predominantly on FC, PC, thalamus and occipital cortex. When compared to CTL, JME-P had a statistically significant difference in GLX/Cr on FC, PC, insula, basal nuclei, PCG and on thalamus. When evaluating the relationship among the various components of this epileptic network among JME-P, the strongest correlation occurred between thalamus and PC. Also, we found a significant negative correlation between NAA/Cr and duration of epilepsy. CONCLUSION: Reductions in NAA may represent loss or injury of neurons and/or axons, as well as metabolic dysfunction while glutamate is considered to be an excitatory neurotransmitter in the brain which is involved in the pathogenesis of epileptogenic seizures.

Heavy metals in benthic organisms from Todos os Santos Bay, Brazil.

The marine ecosystems of Todos os Santos Bay (TSB, The State of Bahia, Brazil) have been impacted by the presence on its coast of a large metropolitan area as well as of chemical and petrochemical activities. Despite its ecological importance, there is a lack of scientific information concerning metal contamination in TSB marine biota. Thus, we analyzed concentrations of metals in four species of marine benthic organisms (two seaweeds, Padina gymnospora and Sargassum sp. one seagrass, Halodule wrightii and one oyster, Crassostrea rhizophorae) in three sites from the TSB region that have been most affected by industrial activities. The concentrations of Al, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn were determined by Atomic Absorption Spectrophometry. The obtained data indicates that cadmium and copper in seaweeds, oysters and seagrass, as well as Ni concentrations in oysters, were in range of contaminated coastal areas. Cadmium and copper are available to organisms through suspended particles, dissolved fraction of water column and bottom sediment interstitial water. As oysters and other mollusks are used as food sources by the local population, the metal levels found in oysters in TSB may constitute a health risk for this population. Our results suggest implanting a heavy metals biomonitoring program in the TSB marine ecosystems.

Intra-cellular storage, transport and exocytosis of halogenated compounds in marine red alga Laurencia obtusa.

The production of secondary metabolites in seaweed have been related to a capability to partition compounds into cellular specialized storage structures, like gland cells and the corps en cerise (CC) or cherry bodies. The possible mechanisms that bring these compounds to the thallus surface remain poorly understood. Therefore, the aim of this work is perform a characterization of the CC and determine the intra-cellular dynamics of halogenated compounds in Laurencia obtusa. The dynamics of CC and the mechanisms related to the intra-cellular transport of halogenated compounds were evaluated by using optical tweezers and time-lapse video microscopy. The CC were isolated and its elemental composition was characterized using X-ray microanalysis. The cellular distribution of halogenated compounds was also demonstrated by fluorescence microscopy. Three-dimensional reconstruction technique was used to provide a visualization of the structures that connect CC to cell periphery. As main findings, we confirmed that the halogenated compounds are mainly found in CC and also in vesicles distributed along the cytoplasm and within the chloroplasts. We demonstrated that CC is mechanically fixed to cell periphery by a stalk-like connection. A vesicle transport though membranous tubular connections was seen occurring from CC to cell wall region. We also demonstrated a process of cortical cell death event, resulting in degradation of CC. We suggested that the vesicle transportation along membranous tubular connections and cell death events are related to the mechanisms of halogenated compounds exudation to the thallus surface and consequently with defensive role against herbivores and fouling.

Heavy metals in benthic organisms from Todos os Santos Bay, Brazil

The marine ecosystems of Todos os Santos Bay (TSB, The State of Bahia, Brazil) have been impacted by the presence on its coast of a large metropolitan area as well as of chemical and petrochemical activities. Despite its ecological importance, there is a lack of scientific information concerning metal contamination in TSB marine biota. Thus, we analyzed concentrations of metals in four species of marine benthic organisms (two seaweeds, Padina gymnospora and Sargassum sp. one seagrass, Halodule wrightii and one oyster, Crassostrea rhizophorae) in three sites from the TSB region that have been most affected by industrial activities. The concentrations of Al, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn were determined by Atomic Absorption Spectrophometry. The obtained data indicates that cadmium and copper in seaweeds, oysters and seagrass, as well as Ni concentrations in oysters, were in range of contaminated coastal areas. Cadmium and copper are available to organisms through suspended particles, dissolved fraction of water column and bottom sediment interstitial water. As oysters and other mollusks are used as food sources by the local population, the metal levels found in oysters in TSB may constitute a health risk for this population. Our results suggest implanting a heavy metals biomonitoring program in the TSB marine ecosystems.

A Baía de Todos os Santos (TSB, Estado da Bahia, Brasil), vem sendo impactada pela presença, em seu entorno, de uma extensa área metropolitana e por atividades químicas e petroquímicas. Apesar de sua importância ecológica, existe pouca informação sobre a contaminação da biota marinha da TSB por metais pesados. Neste contexto, foram analisadas as concentrações de metais em quatro espécies de organismos bentônicos: duas algas, Padina gymnospora e Sargassum sp.; uma grama marinha, Halodule wrightii; e uma ostra, Crassostrea rhizophorae, em três locais das regiões da TSB mais afetadas pelas atividades industriais. As concentrações de Al, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn foram determinadas por espectrofotometria de absorção atômica. Os resultados obtidos indicaram que o cádmio e o cobre em algas, gramas marinhas e ostras, assim como o níquel em ostras estão, em concentrações de áreas contaminadas. Pelos resultados obtidos o cádmio e o cobre estão biodisponíveis a partir das partículas de sedimento em suspensão, fração dissolvida da coluna da água e da água intersticial do sedimento de fundo. Como ostras e outros moluscos são utilizados como fonte de alimento pelas populações locais, as concentrações de metais encontradas nas ostras da TSB podem constituir risco para as populações humanas locais. Os resultados obtidos sugerem a necessidade de implementação de um programa de monitoramento das concentrações de metais pesados em organismos dos ecossistemas marinhos da TSB.

Topiramate for the treatment of juvenile myoclonic epilepsy

OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of topiramate (TPM) in juvenile myoclonic epilepsy (JME). METHOD: We assessed seizure control and adverse effects of TPM in 22 patients (18 females) aged 13 to 53 years. Target TPM dosage was up to 200 mg/day. The patients were subdivided into 3 groups: those treated with seizure control plus side effects (n=4); treated with non-controlled seizures (n=15) and with JME newly diagnosed (n=3). RESULTS: Sixteen patients completed the first year of the follow-up. Generalized tonic-clonic seizures were completely controlled in 10 (62.5%); more than 50% of reduction in 4 (25.0%) and less than 50% in 2 (12.5%). Myoclonia were controlled in 11 (68.8%) and persisted in 5 (31.2%) patients. Absence seizures were present in 5 (22.7%) of whom 2 (9.0%) showed more than 50% of seizure reduction while 3 (13.6%) presented worsening. Discontinuations were due to inadequate seizure control and adverse events (N=4), low compliance and loss of follow-up (N=2) and subject choice (N=1). CONCLUSION: TPM showed to be an effective and well-tolerated drug in the treatment of JME. Although frequently observed, TPM side effects were tolerable and the drug could be maintained in the majority of patients.

OBJETIVO: Avaliar a eficácia e tolerabilidade do topiramato (TPM) na epilepsia mioclônica juvenil (EMJ). MÉTODO: Avaliamos a resposta terapêutica e efeitos colaterais do TPM em 22 pacientes (18 mulheres) com idades entre 13 e 53 anos. A dose alvo utilizada foi até 200 mg/dia. Os pacientes foram divididos em 3 grupos no início do tratamento: aqueles com controle das crises mas que apresentavam efeitos colaterais (n=4); com crises não controladas (n=15) e com EMJ recém diagnosticada (n=3). RESULTADOS: Dezesseis pacientes completaram o primeiro ano de acompanhamento. Crises tônico-clonicas generalizadas foram completamente controladas em 10 (62,5%), tiveram redução maior de 50% em 4 (25,0%) e menor de 50% em 2 (12,5%). Mioclonias foram controladas em 11 (68,8%) e persistiram em 5 (31.2%) pacientes. As crises de ausências, presentes em 5 (22,7%) pacientes, tiveram redução maior do que 50% em 2 (9,0%) e agravamento em 3 (13,6%). A retirada do estudo foi devida principalmente ao controle inadequado das crises e efeitos colaterais indesejáveis (n=4), pouca adesão e perda do seguimento (n=2) e escolha do paciente (n=1). CONCLUSÃO: TPM foi considerada droga eficaz e bem tolerada no tratamento da EMJ. Apesar de freqüentemente observados, os efeitos colaterais do TPM foram toleráveis e a medicação pode ser mantida na maioria dos pacientes.

Zinc accumulation in phosphate granules of Ucides cordatus hepatopancreas.

Amorphous phosphate granules are present in vertebrate and invertebrate organisms. The functions attributed to these structures depend on their mineral contents and organic matrix composition. In the present study we have determined zinc concentrations in the hepatopancreas of the crab Ucides cordatus from regions contaminated with zinc, and the elemental composition of hepatopancreal phosphate granules. Organisms were collected from the contaminated areas of Sepetiba Bay (SB) and Guanabara Bay (GB), and from a non-contaminated area, Ribeira Bay (RB). The first two sites are located near the metropolitan region of Rio de Janeiro city, Brazil. Atomic absorption spectroscopy (AAS) showed a significant difference (P<0.05) for zinc concentration in the hepatopancreas from organisms collected at the contaminated sites GB (210 +/- 20 microg/g dry weight) and SB (181 +/- 16 microg/g dry weight) compared to the non-contaminated site RB (76 +/- 14 microg/g dry weight). Phosphate granules isolated from hepatopancreatic tissue were studied by electron diffraction (ED), energy dispersive X-ray analysis (EDX) and electron spectroscopic imaging (ESI). ED of granules presented no diffraction spots, indicating that these structures are in an amorphous state, while EDX of granules isolated from a contaminated area contained P, Ca and Zn. Mg, Cl and Fe were also found in some of the spectra. ESI showed that O, P and Ca were colocalized in the mineralized layers of most granules observed. The correlation between the results obtained by AAS and those obtained by microanalytical techniques suggests that the hepatopancreatic granules of U. cordatus may be related to the phenomenon of heavy metal retention.

Zinc accumulation in phosphate granules of Ucides cordatus hepatopancreas

Amorphous phosphate granules are present in vertebrate and invertebrate organisms. The functions attributed to these structures depend on their mineral contents and organic matrix composition. In the present study we have determined zinc concentrations in the hepatopancreas of the crab Ucides cordatus from regions contaminated with zinc, and the elemental composition of hepatopancreal phosphate granules. Organisms were collected from the contaminated areas of Sepetiba Bay (SB) and Guanabara Bay (GB), and from a non-contaminated area, Ribeira Bay (RB). The first two sites are located near the metropolitan region of Rio de Janeiro city, Brazil. Atomic absorption spectroscopy (AAS) showed a significant difference (P<0.05) for zinc concentration in the hepatopancreas from organisms collected at the contaminated sites GB (210 + or - 20 µg/g dry weight) and SB (181 + or - 16 µg/g dry weight) compared to the non-contaminated site RB (76 + or - 14 µg/g dry weight). Phosphate granules isolated from hepatopancreatic tissue were studied by electron diffraction (ED), energy dispersive X-ray analysis (EDX) and electron spectroscopic imaging (ESI). ED of granules presented no diffraction spots, indicating that these structures are in an amorphous state, while EDX of granules isolated from a contaminated area contained P, Ca and Zn. Mg, Cl and Fe were also found in some of the spectra. ESI showed that O, P and Ca were colocalized in the mineralized layers of most granules observed. The correlation between the results obtained by AAS and those obtained by microanalytical techniques suggests that the hepatopancreatic granules of U. cordatus may be related to the phenomenon of heavy metal retention

Effects on growth and accumulation of zinc in six seaweed species.

Seaweed species from a coastal area contaminated by heavy metals (Sepetiba Bay) in Rio de Janeiro State (Brazil) presented different levels of Zn concentrations. In some species the levels were 20 times higher than that from a noncontaminated area. The present study was undertaken to investigate the capability of different species to tolerate and accumulate zinc. For this purpose six species, Ulva lactuca, Enteromorpha flexuosa, Padina gymnospora, Sargassum filipendula, Hypnea musciformis, and Spyridia filamentosa, were cultivated under laboratory semistatic conditions in five Zn concentrations in seawater, 10, 20, 100, 1000, and 5000 micrograms.liter-1 for a period of 21 days. All species died at 5000 micrograms.liter-1 of Zn, two species (U. lactuca and E. flexuosa) died at 1000 micrograms.liter-1, and one, H. musciformis, died with 100 micrograms.liter-1. The lowest concentration of Zn that presented growth inhibition in the six species was 20 micrograms.liter-1. The brown alga P. gymnospora presented the highest accumulation level of Zn, and H. musciformis the lowest level. The results of tolerance and accumulation under laboratory conditions, associated with field results, indicate the species of Padina and Sargassum as the best species for monitoring heavy metals in tropical coastal areas, and the potential use of their biomass to remove heavy metals from wastewaters.

[Metal concentrations in benthic marine algae in 3 regions of the state of Rio de Janeiro]. / Concentrações de metais em algas marinhas bentônicas de três regiões do estado do Rio de Janeiro.

The concentrations of zinc, cadmium and copper were determined in different benthic algal species from some sites located in Guanabara Bay, Sepetiba Bay and Ribeira Bay (State of Rio de Janeiro). The aim is to verify the possibility of using algae as indicators of metallic contamination in these areas. According to our results, the highest concentrations of Zn and Cd in algae were observed in Sepetiba Bay. In this region, the differences among the concentrations of the metals were analysed in three sampling sites. Padina gymnospora was the species recommended to monitor the contamination of Zn and Cd in Sepetiba Bay, for the following reasons: 1) its great abundance and distribution in the areas, and 2) its high ability to accumulate metals. More studies are suggested to evaluate the levels of metals in Guanabara Bay.

Trace metal accumulation by algae in Sepetiba Bay, Brazil.

Trace metal concentrations (Zn, Cd, Pb, Cr and Cu) were determined in some benthic algae from Sepetiba Bay, Brazil. This region has been modified by the increase of industrial activities during the last 30 years. Among species sampled the brown algae Padina gymnospora contained the greatest amount of Zn. The Bioconcentration Factor for Zn in P. gymnospora was found to be 10(4) under laboratory conditions. The absorption of (65)Zn depended on exposure time and increased with Zn concentrations in the medium. An insignificant amount of Zn desorbed from algae suggested a very high affinity with cellular binding sites. Zinc uptake by P. gymnospora is discussed by considering field and laboratory conditions.