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Plants adjust their development and architecture to small variations in ambient temperature. In a time in which temperatures are rising world-wide, the mechanism by which plants are able to sense temperature fluctuations and adapt to it, is becoming of special interest. By performing RNA-sequencing on two Arabidopsis accession and one Brassica species exposed to temperature alterations, we showed that alternative splicing is an important mechanism in ambient temperature sensing and adaptation. We found that amongst the differentially alternatively spliced genes, splicing related genes are enriched, suggesting that the splicing machinery itself is targeted for alternative splicing when temperature changes. Moreover, we showed that many different components of the splicing machinery are targeted for ambient temperature regulated alternative splicing. Mutant analysis of a splicing related gene that was differentially spliced in two of the genotypes showed an altered flowering time response to different temperatures. We propose a two-step mechanism where temperature directly influences alternative splicing of the splicing machinery genes, followed by a second step where the altered splicing machinery affects splicing of downstream genes involved in the adaptation to altered temperatures.

Given the public health significance of poorly treatable co-morbid major depressive disorders (MDD) among patients with type 2 diabetes mellitus (DM2) and coronary heart disease (CHD), we need to investigate whether strategies to prevent the development of major depression could reduce its burden of disease. We therefore evaluated the effectiveness of a stepped-care program for subthreshold depression in comparison with usual care in patients with DM2 and/or CHD.A cluster randomized controlled trial, with 27 primary care centers serving as clusters. A total of 236 DM2 and/or CHD patients with subthreshold depression (nine item Patient Health Questionnaire (PHQ-9) score ≥ 6, no current MDD according to DSM-IV criteria) were allocated to the intervention group (N = 96) or usual care group (n = 140). The stepped-care program was delivered by trained practice nurses during one year and consisted of four sequential treatment steps: watchful waiting, guided self-help, problem solving treatment and referral to the general practitioner. The primary outcome was the 12-month cumulative incidence of MDD as measured with the Mini International Neuropsychiatric Interview (MINI). Secondary outcomes included severity of depression (measured by PHQ-9) at 3, 6, 9 and 12 months.Of 236 patients (mean age, 67,5 (SD 10) years; 54.7% men), 210 (89%) completed the MINI at 12 months. The cumulative incidence of MDD was 9 of 89 (10.1%) participants in the intervention group and 12 of 121 (9.9%) participants in the usual care group. We found no statistically significant overall effect of the intervention (OR = 1.21; 95% confidence interval (0.12 to 12.41)) and there were no statistically significant differences in the course or severity of depressive symptoms between the two groups.This study suggest that Step-Dep was not more effective in preventing MDD than usual care in a primary care population with DM2 and/or CHD and subthreshold depression.

Disentangling the mechanisms that shape community assembly across diversity gradients is a central matter in ecology. While many studies have explored community assembly through species average trait values, there is a growing understanding that intraspecific trait variation (ITV) can also play a critical role in species coexistence. Classic biodiversity theory hypothesizes that higher diversity at species-rich sites can arise from narrower niches relative to species-poor sites, which would be reflected in reduced ITV as species richness increases. To explore how ITV in woody plant communities changes with species richness, we compiled leaf trait data (leaf size and specific leaf area) in a total of 521 woody plant species from 21 forest communities that differed dramatically in species richness, ranging from boreal to tropical rainforests. At each forest, we assessed ITV as an estimate of species niche breadth and we quantified the degree of trait overlap among co-occurring species as a measure of species functional similarity. We found ITV was relatively invariant across the species richness gradient. In addition, we found that species functional similarity increased with diversity. Contrary to the expectation from classic biodiversity theory, our results rather suggest that neutral processes or equalizing mechanisms can be acting as potential drivers shaping community assembly in hyperdiverse forests.

Parenteral glutamine supplementation in acute inflammatory conditions is controversial. We evaluated the inflammatory and survival responses after parenteral glutamine infusion in sodium taurocholate-induced acute pancreatitis (AP) model. Lewis rats received 1 g/kg parenteral glutamine (n=42), saline (n=44), or no treatment (n=45) for 48 h before AP induction. Blood, lung, and liver samples were collected 2, 12, and 24 h after AP to measure serum cytokines levels and tissue heat shock protein (HSP) expression. From each group, 20 animals were not sacrificed after AP for a 7-day mortality study. Serum cytokine levels did not differ among groups at any time point, but the intragroup analysis over time showed higher interferon-γ only in the nontreatment and saline groups at 2 h (versus 12 and 24 h; both p≤0.05). The glutamine group exhibited greater lung and liver HSP90 expression than did the nontreatment group at 2 and 12 h, respectively; greater liver HSP90 and HSP70 expression than did the saline group at 12 h; and smaller lung HSP70 and liver HSP90 expression than did the nontreatment group at 24 h (all p≤0.019). The 7-day mortality rate did not differ among groups. In experimental AP, pretreatment with parenteral glutamine was safe and improved early inflammatory mediator profiles without affecting mortality.

RACIONAL: A lesão de isquemia e reperfusão hepática é um evento comum e responsável por considerável morbidade e mortalidade. OBJETIVO: Avaliar efeitos de inibidor da glicoproteína IIb/IIIa, cloridrato de tirofiban, nas alterações hepáticas e pulmonares da lesão de isquemia e reperfusão de fígado de ratos. MÉTODO: Vinte e três ratos Wistar divididos em três grupos: laparotomia (n = 6), isquemia e reperfusão que receberam solução fisiológica (n = 8), e submetidos a isquemia e reperfusão e tratados com o cloridrato de tirofiban (n = 9). Foram realizadas dosagens das aminotransferases e análise histológica hepática. Avaliação pulmonar foi realizada pelo teste do azul de Evans e pela dosagem tecidual da mieloperoxidase no parênquima pulmonar. A oxidação e fosforilação mitocondrial das células hepáticas também foram avaliadas. RESULTADOS: O grupo tratado com cloridrato de tirofiban apresentou menores níveis de aminotransferases, assim como alterações histológicas menos intensas. Avaliação pulmonar demonstrou diminuição no teste de azul de Evans no grupo tratado com cloridrato de tirofiban. Grupo tratado com cloridrato de tirofiban apresentou aumento significativo do estado 3 da respiração mitocondrial e das relações adenosina difosfato utilizado para fosforilação sobre o oxigênio consumido na reação e de coeficiente respiratório. CONCLUSÕES: O uso do cloridrato de tirofiban exerceu papel protetor da lesão hepática de isquemia e reperfusão e impediu o aumento da permeabilidade vascular secundária à lesão de reperfusão hepática.BACKGROUND Hepatic ischemia-reperfusion injury is responsible for a considerable morbidity and mortality. Aim - To evaluate the effect of a platelet glycoprotein IIb/IIIa receptor inhibitor (tirofiban) on hepatic and pulmonary disturbances associated with hepatic ischemia-reperfusion injury. METHODS: Twenty-three Wistar rats divided in three groups: rats sham-operated (n = 6), rats submitted to ischemia-reperfusion that received saline solution (n = 8), and rats submitted to ischemia-reperfusion treated with 0.7 mg/kg of tirofiban (n = 9). Serum aminotransferases (AST and ALT) were also determined, and the study of hepatic tissue histology was carried out. The evaluation of the pulmonary disturbances was done using the Evans blue test and the tissular determination of myeloperoxidase. Hepatic mitochondrial oxidation and phosphorylation were also measured. RESULTS: There was an increase in the state 3 respiration, ADP/O ratio and respiration control rate in the group treated with tirofiban. This group had also lower levels of aminotransferases and the histological findings were significantly less intense. Pulmonary evaluation demonstrated decrease of the Evans blue test in the tirofiban group and an increase of its tissular determination of myeloperoxidase. CONCLUSION: The inhibition of glycoprotein IIb/IIIa receptor with tirofiban protected the hepatic disturbances and prevented the increase of pulmonary vascular permeability secondary to the ischemia-reperfusion injury of the liver.

During orthotopic liver transplantation for fulminant hepatic failure, some patients may develop sudden deterioration of cerebral perfusion and oxygenation, mainly due to increased intracranial pressure and hypotension, which are likely responsible for postoperative neurological morbidity and mortality. In the present study, we hypothesized that the favorable effects of hypertonic saline solution (NaCl 7.5%, 4 mL/kg) infusion on both systemic and cerebral hemodynamics, demonstrated in laboratory and clinical settings of intracranial hypertension and hemorrhagic shock resuscitation, may attenuate the decrease in cerebral perfusion pressure that often occurs during orthotopic liver transplantation for fulminant hepatic failure. METHODS: 10 patients with fulminant hepatic failure in grade IV encephalopathy undergoing orthotopic liver transplantation with intracranial pressure monitoring were included in this study. The effect on cerebral and systemic hemodynamics in 3 patients who received hypertonic saline solution during anhepatic phase (HSS group) was examined, comparing their data with historical controls obtained from surgical procedure recordings in 7 patients (Control group). The maximal intracranial pressure and the corresponding mean arterial pressure values were collected in 4 time periods: (T1) the last 10 min of the dissection phase, (T2) the first 10 minutes at the beginning of anhepatic phase, (T3) at the end of the anhepatic phase, and (T4) the first 5 minutes after graft reperfusion. RESULTS: Immediately after hypertonic saline solution infusion, intracranial pressure decreased 50.4%. During the first 5 min of reperfusion, the intracranial pressure remained stable in the HSS group, and all these patients presented an intracranial pressure lower than 20 mm Hg, while in the Control group, the intracranial pressure increased 46.5% (P < 0.001). The HSS group was the most hemodynamically stable; the mean arterial pressure during the first 5 min of reperfusion increased 21.1% in the HSS group and decreased 11.1% in the Control group (P < 0.001). During the first 5 min of reperfusion, cerebral perfusion pressure increased 28.3% in the HSS group while in the Control group the cerebral perfusion pressure decreased 28.5% (P < 0.001). Serum sodium at the end of the anhepatic phase and 3 hours after reperfusion was significantly higher in the HSS group (153.00 ± 2.66 and 149.00 ± 1.73 mEq/L) than in the Control group (143.71 ± 3.30 and 142.43 ± 1.72 mEq/L), P = 0.003 and P < 0.001 respectively. CONCLUSION: Hypertonic saline solution can be successfully used as an adjunct in the neuroprotective strategy during orthotopic liver transplantation for fulminant hepatic failure, reducing intracranial pressure while restoring arterial blood pressure, promoting sustained increase in the cerebral perfusion pressure.Neste estudo testamos a hipótese de que os efeitos benéficos decorrentes da administração da solução salina hipertônica (NaCl 7,5%, 4 mL/kg) sobre a hemodinâmica sistêmica e cerebral na hipertensão intracraniana e no choque hemorrágico, possam atenuar a diminuição da pressão de perfusão cerebral que freqüentemente acompanha o transplante do fígado para hepatite fulminante. MÉTODO: Foram estudados 10 pacientes com hepatite fulminante em encefalopatia grau IV e monitorização de pressão intracraniana submetidos ao transplante do fígado. A hemodinâmica sistêmica e cerebral de 3 pacientes que receberam solução salina hipertônica durante a fase anepática (Grupo SSH) foi analisada comparando com os dados obtidos de 7 pacientes transplantados anteriormente nas mesmas condições (Grupo Controle). Os valores de pressão intracraniana máxima e a correspondente pressão arterial média foram coletados em quatro tempos: (T1) nos últimos 10 min da fase de disseccão, (T2) nos primeiros 10 minutos da fase anepática, (T3) no final da fase anepática e (T4) nos primeiros 5 min da reperfusão RESULTADO: Imediatamente após a infusão da solução salina hipertônica a pressão intracraniana diminuiu 50,4%. Nos primeiros 5 min da reperfusão a pressão intracraniana no Grupo SSH se manteve estável e todos os pacientes apresentavam pressão intracraniana menor que 20 mmHg enquanto no Grupo Controle a pressão intracraniana aumentou 46,5% (p

Descreve-se experiência inicial e resultados imediatos da hepatectomia laparoscópica no tratamento de metástases hepáticas em quatro pacientes. Uma paciente foi submetida a hepatectomia direita e três foram submetidas a bissegmentectomia 6-7. O tempo médio cirúrgico foi de 360 minutos e 4 dias de internação. Uma paciente apresentou fístula biliar autolimitada. Mortalidade operatória foi nula. Conclui-se que hepatectomia maior laparoscópica é factível, segura e apresenta excelentes resultados imediatos, com retorno precoce às atividades profissionais. Entretanto, ainda são necessários estudos com maior número de casos e trabalhos comparativos para se estabelecer limites e indicações deste procedimento em metástases hepáticas.The authors describe their initial experience and immediate results with laparoscopic liver resection in the treatment of four patients with liver metastasis. Three patients underwent laparoscopic anatomic bisegmentectomy 6-7 and one laparoscopic right hemihepatectomy. Mean operation time was 360 minutes and median hospital stay was 4 days. One patient developed bile leakage that was treated conservatively. No postoperative mortality was observed. This initial experience demonstrates that laparoscopic liver resection can be safely done with excellent immediate results. However larger and comparative studies are still needed to establish indications and limits for laparoscopy in the treatment of liver metastasis.

BACKGROUND: There is a well recognized association between depression and diabetes. However, there is little empirical data about the prevalence of depressive symptoms and anxiety among different groups of glucose metabolism in population based samples. The aim of this study was to determine whether the prevalence of increased levels of depression and anxiety is different between patients with type 2 diabetes and subjects with impaired glucose metabolism (IGM) and normal glucose metabolism (NGM). METHODOLOGY/PRINCIPAL FINDINGS: Cross-sectional data from a population-based cohort study of 2667 residents, 1261 men and 1406 women aged 40-65 years from the Hoorn region, the Netherlands. Depressive symptoms and anxiety were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D, score >or=16) and the Hospital Anxiety and Depression Scale--Anxiety Subscale (HADS-A, score >or=8), respectively. Glucose metabolism status was determined by oral glucose tolerance test. In the total study population the prevalence of depressive symptoms and anxiety for the NGM, IGM and type 2 diabetes were 12.5, 12.2 and 21.0% (P = 0.004) and 15.0, 15.3 and 19.9% (p = 0.216), respectively. In men, the prevalence of depressive symptoms was 7.7, 9.5 and 19.6% (p

Financial time series have been analyzed with a wide variety of models and approaches, some of which can forecast with great accuracy. However, most of these models, especially the machine learning ones, cannot show additional information for the decision maker or the financial analyst. The notion of causality is a concept that provides a more complete understanding of a problem beyond improved forecasts. In this study, we propose integrating the treatment/control concept of causality into a forecasting framework to better predict financial time series. Our results show that the proposed methodology outperforms classic econometric approaches such as ARIMA and Random Walk, as well as machine learning approaches without the proposed methodology. This improvement is statistically significant, as indicated by the Model Confidence Set test in the complete test set and quarterly analysis. [ABSTRACT FROM AUTHOR]