Anemia and brain oxygen after severe traumatic brain injury.

PURPOSE: To investigate the relationship between hemoglobin (Hgb) and brain tissue oxygen tension (PbtO(2)) after severe traumatic brain injury (TBI) and to examine its impact on outcome. METHODS: This was a retrospective analysis of a prospective cohort of severe TBI patients whose PbtO(2) was monitored. The relationship between Hgb-categorized into four quartiles (≤9; 9-10; 10.1-11; >11 g/dl)-and PbtO(2) was analyzed using mixed-effects models. Anemia with compromised PbtO(2) was defined as episodes of Hgb ≤ 9 g/dl with simultaneous PbtO(2) < 20 mmHg. Outcome was assessed at 30 days using the Glasgow outcome score (GOS), dichotomized as favorable (GOS 4-5) vs. unfavorable (GOS 1-3). RESULTS: We analyzed 474 simultaneous Hgb and PbtO(2) samples from 80 patients (mean age 44 ± 20 years, median GCS 4 (3-7)). Using Hgb > 11 g/dl as the reference level, and controlling for important physiologic covariates (CPP, PaO(2), PaCO(2)), Hgb ≤ 9 g/dl was the only Hgb level that was associated with lower PbtO(2) (coefficient -6.53 (95 % CI -9.13; -3.94), p < 0.001). Anemia with simultaneous PbtO(2) < 20 mmHg, but not anemia alone, increased the risk of unfavorable outcome (odds ratio 6.24 (95 % CI 1.61; 24.22), p = 0.008), controlling for age, GCS, Marshall CT grade, and APACHE II score. CONCLUSIONS: In this cohort of severe TBI patients whose PbtO(2) was monitored, a Hgb level no greater than 9 g/dl was associated with compromised PbtO(2). Anemia with simultaneous compromised PbtO(2), but not anemia alone, was a risk factor for unfavorable outcome, irrespective of injury severity.

A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains.

BACKGROUND: The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms. RESULTS: We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems. CONCLUSIONS: Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.

Gastric banding interferes with esophageal motility and gastroesophageal reflux.

BACKGROUND: Gastroesophageal reflux and progressive esophageal dilatation can develop after gastric banding (GB). HYPOTHESIS: Gastric banding may interfere with esophageal motility, enhance reflux, or promote esophageal dilatation. DESIGN: Before-after trial in patients undergoing GB. SETTING: University teaching hospital. PATIENTS AND METHODS: Between January 1999 and August 2002, 43 patients undergoing laparoscopic GB for morbid obesity underwent upper gastrointestinal endoscopy, 24-hour pH monitoring, and stationary esophageal manometry before GB and between 6 and 18 months postoperatively. MAIN OUTCOME MEASURES: Reflux symptoms, endoscopic esophagitis, pressures measured at manometry, esophageal acid exposure. RESULTS: There was no difference in the prevalence of reflux symptoms or esophagitis before and after GB. The lower esophageal sphincter was unaffected by surgery, but contractions in the lower esophagus weakened after GB, in correlation with preoperative values. There was a trend toward more postoperative nonspecific motility disorders. Esophageal acid exposure tended to decrease after GB, with fewer reflux episodes. A few patients developed massive postoperative reflux. There was no clear correlation between preoperative testing and postoperative esophageal acid exposure, although patients with abnormal preoperative acid exposure tended to maintain high values after GB. CONCLUSIONS: Postoperative esophageal dysmotility and gastroesophageal reflux are not uncommon after GB. Preoperative testing should be done routinely. Low amplitude of contraction in the lower esophagus and increased esophageal acid exposure should be regarded as contraindications to GB. Patients with such findings should be offered an alternative procedure, such as Roux-en-Y gastric bypass.

Variabilidade espacial de atributos mineralógicos de um latossolo sob diferentes formas do relevo: I - mineralogia da fração argila

A distribuição dos minerais da fração argila depende de condições pedoambientais específicas. O estudo das relações entre atributos desses minerais e locais específicos de sua ocorrência na paisagem torna-se importante para o entendimento das relações entre a mineralogia e os demais atributos do solo. Este trabalho teve como objetivo avaliar os atributos cristalográficos, as razões Gt/(Gt+Hm) e Ct/(Ct+Gb) dos minerais da fração argila (hematita, goethita, caulinita e gibbsita) e o padrão de distribuição espacial destes em um Latossolo Vermelho eutroférrico sob cultivo de cana-de-açúcar há mais de 30 anos, com colheita no sistema cana crua. As amostras de solo foram coletadas nos pontos de cruzamento de uma malha, georreferenciados, com intervalos regulares de 10 m, e dimensão de 100 x 100 m, na profundidade de 0,2-0,4 m, totalizando 119 pontos, em uma área de 1 ha. As amostras de solos foram analisadas quimicamente. Posteriormente, a fração argila foi submetida à difração de raios X. Foram feitas as análises estatísticas e geoestatísticas dos atributos cristalográficos dos minerais analisados. Mapas de krigagem foram realizados para a visualização da variabilidade espacial dos atributos. Todos os atributos estudados apresentaram dependência espacial, e os atributos mineralógicos apresentaram-se relacionados com variações das formas do relevo. A gibbsita apresentou o maior diâmetro médio do cristal (DMC) entre os minerais da fração argila estudados, e a goethita foi o mineral que apresentou a maior variação do DMC e da largura à meia altura. Os maiores valores do DMC da goethita, hematita e gibbsita foram encontrados no compartimento II, caracterizado por uma área côncavo-convexa.

Variabilidade espacial de atributos mineralógicos de um latossolo sob diferentes formas do relevo: II - correlação espacial entre mineralogia e agregados

A caulinita (Ct), a gibbsita (Gb), a goethita (Gt) e a hematita (Hm) são os principais minerais da fração argila dos Latossolos brasileiros. A cristalinidade desses minerais interfere nos atributos físicos do solo, que são dependentes do relevo. Este trabalho teve como objetivo correlacionar espacialmente a estabilidade e o diâmetro médio geométrico dos agregados com os atributos cristalográficos dos minerais da fração argila de um Latossolo Vermelho eutroférrico sob cultivo de cana-de-açúcar com colheita no sistema cana crua. As amostras de solo foram coletadas nos pontos de cruzamento de uma malha, georreferenciados, com intervalos regulares de 10 m e dimensão de 100 x 100 m, na profundidade de 0,2- 0,4 m, totalizando 119 pontos, em uma área de 1 ha, onde as variações da forma do relevo foram mapeadas. Foram determinados o diâmetro médio geométrico e a percentagem de agregados retidos nas classes > 2 e < 1 mm das amostras, e a mineralogia da fração argila foi caracterizada por difratometria de raios X. Esses resultados foram submetidos à análise estatística e geoestatística. Buscando correlacionar a estabilidade e as diferentes classes de tamanho dos agregados com a cristalinidade dos minerais da fração argila do solo, foram realizados semivariogramas cruzados. Observou-se que goethitas de menor grau de cristalinidade se relacionam espacialmente com agregados de maior diâmetro médio geométrico e tamanho dos agregados e que os atributos estudados e suas relações são dependentes das formas do relevo.

Prognostic value of continuous eeg monitoring during therapeutic hypothermia in patients with coma after cardiac arrest

INTRODUCTION: Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome. METHODS: From April 2009 to April 2010, we prospectively studied 34 consecutive comatose patients treated with TH after CA who were monitored with cEEG, initiated during hypothermia and maintained after rewarming. EEG background reactivity to painful stimulation was tested. We analyzed the association between cEEG findings and neurologic outcome, assessed at 2 months with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). RESULTS: Continuous EEG recording was started 12 ± 6 hours after CA and lasted 30 ± 11 hours. Nonreactive cEEG background (12 of 15 (75%) among nonsurvivors versus none of 19 (0) survivors; P < 0.001) and prolonged discontinuous "burst-suppression" activity (11 of 15 (73%) versus none of 19; P < 0.001) were significantly associated with mortality. EEG seizures with absent background reactivity also differed significantly (seven of 15 (47%) versus none of 12 (0); P = 0.001). In patients with nonreactive background or seizures/epileptiform discharges on cEEG, no improvement was seen after TH. Nonreactive cEEG background during TH had a positive predictive value of 100% (95% confidence interval (CI), 74 to 100%) and a false-positive rate of 0 (95% CI, 0 to 18%) for mortality. All survivors had cEEG background reactivity, and the majority of them (14 (74%) of 19) had a favorable outcome (CPC 1 or 2). CONCLUSIONS: Continuous EEG monitoring showing a nonreactive or discontinuous background during TH is strongly associated with unfavorable outcome in patients with coma after CA. These data warrant larger studies to confirm the value of continuous EEG monitoring in predicting prognosis after CA and TH.

Gênese de latossolos e cambissolos desenvolvidos de rochas pelíticas do grupo Bambuí - Minas Gerais

Considerando a expressividade de Cambissolos (rasos, adensados e siltosos) e Latossolos argilosos e muito argilosos desenvolvidos de rochas pelíticas do Grupo Bambuí, bem como os poucos estudos relacionados à gênese e potencialidade agrícola desses solos, selecionaram-se duas áreas no município de Curvelo-MG, cujo objetivo foi estudar suas características físicas, químicas e mineralógicas. Para isso, foram descritos e coletados perfis de Cambissolos Háplicos (CX), Latossolos Vermelho-Amarelos (LVA) e Latossolos Vermelhos (LV), sendo a TFSA submetida às análises físicas e químicas de rotina, digestão total e sulfúrica, além das análises mineralógicas. Os difratogramas de raios X (DRX) e o índice de intemperismo (Ki) dos CX indicaram menor grau de pedogênese e maior proporção de caulinita e ilita na fração argila (comparativamente aos Latossolos), que coexistem com gibbsita (Gb) e vermiculita com Al-hidroxi entrecamadas (VHE). Nesse caso, a ocorrência de gibbsita não é um bom indicativo de intemperização acentuada. Nos CX, os elevados teores de silte associados à possibilidade de forte ajuste face a face de caulinita/ilita podem ser os principais fatores que interferem na quase ausência de organização estrutural, no adensamento, na pouca percolação de água e na formação de selamento superficial. Na fração argila dos Latossolos foi constatada coexistência de argilominerais e óxidos de Fe e Al muito semelhante à encontrada para os CX, porém com menores proporções de ilita e maiores de gibbsita, inferidos pelos resultados do Ki em torno de 1,4. Ainda que não haja diferenciações químicas e físicas marcantes entre os Latossolos, constatou-se em LV magnetização considerável na fração areia, cujo DRX confirmou a presença de magnetita, fato pouco comum em Latossolos desenvolvidos de rochas pelíticas do Grupo Bambuí, mas constatado em estudos anteriores.

EGASP: the human ENCODE Genome Annotation Assessment Project.

BACKGROUND: We present the results of EGASP, a community experiment to assess the state-of-the-art in genome annotation within the ENCODE regions, which span 1% of the human genome sequence. The experiment had two major goals: the assessment of the accuracy of computational methods to predict protein coding genes; and the overall assessment of the completeness of the current human genome annotations as represented in the ENCODE regions. For the computational prediction assessment, eighteen groups contributed gene predictions. We evaluated these submissions against each other based on a 'reference set' of annotations generated as part of the GENCODE project. These annotations were not available to the prediction groups prior to the submission deadline, so that their predictions were blind and an external advisory committee could perform a fair assessment. RESULTS: The best methods had at least one gene transcript correctly predicted for close to 70% of the annotated genes. Nevertheless, the multiple transcript accuracy, taking into account alternative splicing, reached only approximately 40% to 50% accuracy. At the coding nucleotide level, the best programs reached an accuracy of 90% in both sensitivity and specificity. Programs relying on mRNA and protein sequences were the most accurate in reproducing the manually curated annotations. Experimental validation shows that only a very small percentage (3.2%) of the selected 221 computationally predicted exons outside of the existing annotation could be verified. CONCLUSION: This is the first such experiment in human DNA, and we have followed the standards established in a similar experiment, GASP1, in Drosophila melanogaster. We believe the results presented here contribute to the value of ongoing large-scale annotation projects and should guide further experimental methods when being scaled up to the entire human genome sequence.

Incidence and mechanisms of cerebral ischemia in early clinical head injury.

Antemortem demonstration of ischemia has proved elusive in head injury because regional CBF reductions may represent hypoperfusion appropriately coupled to hypometabolism. Fifteen patients underwent positron emission tomography within 24 hours of head injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), and oxygen extraction fraction (OEF). We estimated the volume of ischemic brain (IBV) and used the standard deviation of the OEF distribution to estimate the efficiency of coupling between CBF and CMRO2. The IBV in patients was significantly higher than controls (67 +/- 69 vs. 2 +/- 3 mL; P < 0.01). The coexistence of relative ischemia and hyperemia in some patients implies mismatching of perfusion to oxygen use. Whereas the saturation of jugular bulb blood (SjO2) correlated with the IBV (r = 0.8, P < 0.01), SjO2 values of 50% were only achieved at an IBV of 170 +/- 63 mL (mean +/- 95% CI), which equates to 13 +/- 5% of the brain. Increases in IBV correlated with a poor Glasgow Outcome Score 6 months after injury (rho = -0.6, P < 0.05). These results suggest significant ischemia within the first day after head injury. The ischemic burden represented by this "traumatic penumbra" is poorly detected by bedside clinical monitors and has significant associations with outcome.

Induction of a geochemical barrier for As, Fe and S immobilization in a sulfide substrate

Acid mine drainage (AMD) is an environmental concern due to the risk of element mobilization, including toxic elements, and inclusion in the food chain. In this study, three cover layers were tested to minimize As, Fe and S mobilization from a substrate from former gold mining, containing pyrite and arsenopyrite. For this purpose, different layers (capillary break, sealant and cover layer) above the substrate and the induction of a geochemical barrier (GB) were used to provide suitable conditions for adsorption and co-precipitation of the mobilized As. Thirteen treatments were established to evaluate the leaching of As, Fe and S from a substrate in lysimeters. The pH, As, Fe, S, Na, and K concentrations and total volume of the leachates were determined. Mineralogical analyses were realized in the substrate at the end of the experimental period. Lowest amounts of As, Fe and S (average values of 5.47, 48.59 and 132.89 g/lysimeter) were leached in the treatments that received Na and K to induce GB formation. Mineralogical analyses indicated jarosite formation in the control treatment and in treatments that received Na and K salts. However, the jarosite amounts in these treatments were higher than in the control, suggesting that these salts accelerated the GB formation. High amounts of As, Fe and S (average values of 11.7, 103.94 and 201.13 g/lysimeter) were observed in the leachate from treatments without capillary break layer. The formation of geochemical barrier and the use of different layers over the sulfide substrate proved to be efficient techniques to decrease As, Fe and S mobilization and mitigate the impact of acid mine drainage.

Mineralogy of the clay fraction of Alfisols in two slope curvatures: III - spatial variability

A good knowledge of the spatial distribution of clay minerals in the landscape facilitates the understanding of the influence of relief on the content and crystallographic attributes of soil minerals such as goethite, hematite, kaolinite and gibbsite. This study aimed at describing the relationships between the mineral properties of the clay fraction and landscape shapes by determining the mineral properties of goethite, hematite, kaolinite and gibbsite, and assessing their dependence and spatial variability, in two slope curvatures. To this end, two 100 × 100 m grids were used to establish a total of 121 regularly spaced georeferenced sampling nodes 10 m apart. Samples were collected from the layer 0.0-0.2 m and analysed for iron oxides, and kaolinite and gibbsite in the clay fraction. Minerals in the clay fraction were characterized from their X-ray diffraction (XRD) patterns, which were interpreted and used to calculate the width at half height (WHH) and mean crystallite dimension (MCD) of iron oxides, kaolinite, and gibbsite, as well as aluminium substitution and specific surface area (SSA) in hematite and goethite. Additional calculations included the goethite and hematite contents, and the goethite/(goethite+hematite) [Gt/(Gt+Hm)] and kaolinite/(kaolinite+gibbsite) [Kt/(Kt+Gb)] ratios. Mineral properties were established by statistical analysis of the XRD data, and spatial dependence was assessed geostatistically. Mineralogical properties differed significantly between the convex area and concave area. The geostatistical analysis showed a greater number of mineralogical properties with spatial dependence and a higher range in the convex than in the concave area.

Advanced age increases the failure rate of non-operative management of blunt splenic injuries

Introduction: Non-operative management (NOM) of blunt splenic injuries in hemodynamically stable patients is nowadays considered the standard treatment. Material and Methods: The aim was to clarify the criteria used for primary operative management (OM) and planned NOM. Furthermore, the study aimed to identify risk factors for failure of NOM. All adult patients with blunt splenic injuries treated from 2000-2008 were reviewed and a logistic regression analysis employed. Results: There were 206 patients (146 men, 70.9%). Mean age was 38.2 ± 19.1 years. The mean Injury Severity Score (ISS) was 30.9 ± 11.6. The American Association for the Surgery of Trauma (AAST) classification of the splenic injury was: grade I, n = 43 (20.9%); grade II, n = 52 (25.2%); grade III, n = 60 (29.1%), grade IV, n = 42 (20.4%) and grade V, n = 9 (4.4%). 47 patients (22.8%) required immediate surgery (OM). More than 5 units of red cell transfusions (odds ratio [OR] 13.72, P < 0.001), a Glasgow Coma Scale < 11 (OR 9.88, P = 0.009) and age ? 55 years (OR 3.29, P = 0.038) were associated with primary OM. 159 patients (77.2%) qualified for a non-surgical approach (NOM), which was successful in 89.9% (143/159). The overall splenic salvage rate amounted to 69.4% (143/206). Multiple logistic regression analysis found age ? 40 years to be the only factor significantly and independently related to the failure of NOM (OR 13.58, P = 0.001). Conclusion: Advanced age is associated with an increased failure rate of NOM in patients with blunt splenic injuries.

Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest.

Introduction: Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome. Methods: From April 2009 to April 2010, we prospectively studied 34 consecutive comatose patients treated with TH after CA who were monitored with cEEG, initiated during hypothermia and maintained after rewarming. EEG background reactivity to painful stimulation was tested. We analyzed the association between cEEG findings and neurologic outcome, assessed at 2 months with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). Results: Continuous EEG recording was started 12 ± 6 hours after CA and lasted 30 ± 11 hours. Nonreactive cEEG background (12 of 15 (75%) among nonsurvivors versus none of 19 (0) survivors; P < 0.001) and prolonged discontinuous "burst-suppression" activity (11 of 15 (73%) versus none of 19; P < 0.001) were significantly associated with mortality. EEG seizures with absent background reactivity also differed significantly (seven of 15 (47%) versus none of 12 (0); P = 0.001). In patients with nonreactive background or seizures/epileptiform discharges on cEEG, no improvement was seen after TH. Nonreactive cEEG background during TH had a positive predictive value of 100% (95% confidence interval (CI), 74 to 100%) and a false-positive rate of 0 (95% CI, 0 to 18%) for mortality. All survivors had cEEG background reactivity, and the majority of them (14 (74%) of 19) had a favorable outcome (CPC 1 or 2). Conclusions: Continuous EEG monitoring showing a nonreactive or discontinuous background during TH is strongly associated with unfavorable outcome in patients with coma after CA. These data warrant larger studies to confirm the value of continuous EEG monitoring in predicting prognosis after CA and TH.