The effects of electrical hippocampal kindling of seizures on amino acids and kynurenic acid concentrations in brain structures

Our study demonstrated that the development of seizures during the electrically induced kindling of seizures is associated with significant changes in the concentration of kynurenic acid (KYNA) and its precursor, tryptophan (TRP). The primary finding of our study was an increase in KYNA levels and the KYNA/TRP ratio (a theoretical index of activity of the kynurenine pathway) in the amygdala and hippocampus of kindled animals. We also found decreases in the concentration of tryptophan in the hippocampus and prefrontal cortex. Changes in the concentration of KYNA and TRP in the amygdala were accompanied by a significant decrease in γ-Aminobutryic Acid (GABA) levels and an increase in the glutamate/GABA ratio. Moreover, we found a significant negative correlation between the local concentrations of KYNA and glutamate in the amygdala of kindled rats. However, there were no changes in the local concentrations of the following amino acids: glutamate, aspartate, glutamine, glycine, taurine and alanine. In conclusion, these new results suggest a modulatory influence of KYNA on the process of epileptogenesis, characterized by a negative relationship between the KYNA and glutamate systems in the amygdala

Determinants of outcome in operatively and non-operatively treated Weber-B ankle fractures

Introduction: Treatment of ankle fractures is often based on fracture type and surgeon's individual judgment. Literature concerning the treatment options and outcome are dated and frequently contradicting. The aim of this study was to determine the clinical and functional outcome after AO-Weber B-type ankle fractures in operatively and conservatively treated patients and to determine which factors influenced outcome. Patients and methods: A retrospective cohort study in patients with a AO-Weber B-type ankle fracture. Patient, fracture and treatment characteristics were recorded. Clinical and functional outcome was measured using the Olerud-Molander Ankle Score (OMAS), the American Orthopaedic Foot and Ankle Society ankle-hindfoot score (AOFAS) and a Visual Analog Score (VAS) for overall satisfaction (range 0-10). Results: Eighty-two patients were treated conservatively and 103 underwent operative treatment. The majority was female. Most conservatively treated fractures were AO-Weber B1.1 type fractures. Fractures with fibular displacement (mainly AO type B1.2 and Lauge-Hansen type SER-4) were predominantly treated operatively. The outcome scores in the non-operative group were OMAS 93, AOFAS 98, and VAS 8. Outcome in this group was independently negatively affected by age, affected side, BMI, fibular displacement, and duration of plaster immobilization. In the surgically treated group, the OMAS, AOFAS, and VAS scores were 90, 97, and 8, respectively, with outcome negatively influenced by duration of plaster immobilization. Conclusion: Treatment selection based upon stability and surgeon's judgment led to overall good clinical outcome in both treatment groups. Reducing the cast immobilization period may further improve outcome

Infection of Anopheles gambiae mosquitoes with entomopathogenic fungi: effect of host age and blood-feeding status

Physiological characteristics of insects can influence their susceptibility to fungal infection of which age and nutritional status are among the most important. An understanding of host–pathogen interaction with respect to these physiological characteristics of the host is essential if we are to develop fungal formulations capable of reducing malaria transmission under field conditions. Here, two independent bioassays were conducted to study the effect of age and blood-feeding status on fungal infection and survival of Anopheles gambiae s.s. Giles. Mosquitoes were exposed to 2 × 1010 conidia m−2 of oil-formulated Metarhizium anisopliae ICIPE-30 and of Beauveria bassiana I93-825, respectively, and their survival was monitored daily. Three age groups of mosquitoes were exposed, 2–4, 5–8, and 9–12 days since emergence. Five groups of different feeding status were exposed: non-blood-fed, 3, 12, 36, and 72 h post-blood feeding. Fungal infection reduced the survival of mosquitoes regardless of their age and blood-feeding status. Although older mosquitoes died relatively earlier than younger ones, age did not tend to affect mosquito susceptibility to fungal infection. Non-blood-fed mosquitoes were more susceptible to fungus infection compared to all categories of blood-fed mosquitoes, except for those exposed to B. bassiana 72 h post-blood feeding. In conclusion, formulations of M. anisopliae and B. bassiana can equally affect mosquitoes of different age classes, with them being relatively more susceptible to fungus infection when non-blood-fed

The Role of Imported Cases and Favorable Meteorological Conditions in the Onset of Dengue Epidemics

Dengue/dengue hemorrhagic fever is the world's most widely spread mosquito-borne arboviral disease and threatens more than two-thirds of the world's population. Cases are mainly distributed in tropical and subtropical areas in accordance with vector habitats for Aedes aegypti and Ae. albopictus. However, the role of imported cases and favorable meteorological conditions has not yet been quantitatively assessed. This study verified the correlation between the occurrence of indigenous dengue and imported cases in the context of weather variables (temperature, rainfall, relative humidity, etc.) for different time lags in southern Taiwan. Our findings imply that imported cases have a role in igniting indigenous outbreaks, in non-endemics areas, when favorable weather conditions are present. This relationship becomes insignificant in the late phase of local dengue epidemics. Therefore, early detection and case management of imported cases through timely surveillance and rapid laboratory-diagnosis may avert large scale epidemics of dengue/dengue hemorrhagic fever. An early-warning surveillance system integrating meteorological data will be an invaluable tool for successful prevention and control of dengue, particularly in non-endemic countries

FHL2 interacts with CALM and is highly expressed in acute erythroid leukemia

The t(10;11)(p13;q14) translocation results in the fusion of the CALM (clathrin assembly lymphoid myeloid leukemia protein) and AF10 genes. This translocation is observed in acute myeloblastic leukemia (AML M6), acute lymphoblastic leukemia (ALL) and malignant lymphoma. Using a yeast two-hybrid screen, the four and a half LIM domain protein 2 (FHL2) was identified as a CALM interacting protein. Recently, high expression of FHL2 in breast, gastric, colon, lung as well as in prostate cancer was shown to be associated with an adverse prognosis. The interaction between CALM and FHL2 was confirmed by glutathione S-transferase-pulldown assay and co-immunoprecipitation experiments. The FHL2 interaction domain of CALM was mapped to amino acids 294–335 of CALM. The transcriptional activation capacity of FHL2 was reduced by CALM, but not by CALM/AF10, which suggests that regulation of FHL2 by CALM might be disturbed in CALM/AF10-positive leukemia. Extremely high expression of FHL2 was seen in acute erythroid leukemia (AML M6). FHL2 was also highly expressed in chronic myeloid leukemia and in AML with complex aberrant karyotype. These results suggest that FHL2 may play an important role in leukemogenesis, especially in the case of AML M6

Volcanic impacts on the Holocene vegetation history of Britain and Ireland? A review and meta-analysis of the pollen evidence

Volcanic ash layers show that the products of Icelandic volcanism reached Britain and Ireland many times during the Holocene. Historical records suggest that at least one eruption, that of Laki in a.d. 1783, was associated with impacts on vegetation. These results raise the question: did Icelandic volcanism affect the Holocene vegetation history of Britain and Ireland? Several studies have used pollen data to address this issue but no clear consensus has been reached. We re-analyse the palynological data using constrained ordination with various representations of potential volcanic impacts. We find that the palynological evidence for volcanic impacts on vegetation is weak but suggest that this is a case of absence of evidence and is not necessarily evidence of absence of impact. To increase the chances of identifying volcanic impacts, future studies need to maximise temporal resolution, replicate results, and investigate a greater number of tephras in a broader range of locations, including more studies from lake sediments

Time series analysis of dengue incidence in Guadeloupe, French West Indies: Forecasting models using climate variables as predictors

BACKGROUND: During the last decades, dengue viruses have spread throughout the Americas region, with an increase in the number of severe forms of dengue. The surveillance system in Guadeloupe (French West Indies) is currently operational for the detection of early outbreaks of dengue. The goal of the study was to improve this surveillance system by assessing a modelling tool to predict the occurrence of dengue epidemics few months ahead and thus to help an efficient dengue control. METHODS: The Box-Jenkins approach allowed us to fit a Seasonal Autoregressive Integrated Moving Average (SARIMA) model of dengue incidence from 2000 to 2006 using clinical suspected cases. Then, this model was used for calculating dengue incidence for the year 2007 compared with observed data, using three different approaches: 1 year-ahead, 3 months-ahead and 1 month-ahead. Finally, we assessed the impact of meteorological variables (rainfall, temperature and relative humidity) on the prediction of dengue incidence and outbreaks, incorporating them in the model fitting the best. RESULTS: The 3 months-ahead approach was the most appropriate for an effective and operational public health response, and the most accurate (Root Mean Square Error, RMSE = 0.85). Relative humidity at lag-7 weeks, minimum temperature at lag-5 weeks and average temperature at lag-11 weeks were variables the most positively correlated to dengue incidence in Guadeloupe, meanwhile rainfall was not. The predictive power of SARIMA models was enhanced by the inclusion of climatic variables as external regressors to forecast the year 2007. Temperature significantly affected the model for better dengue incidence forecasting (p-value = 0.03 for minimum temperature lag-5, p-value = 0.02 for average temperature lag-11) but not humidity. Minimum temperature at lag-5 weeks was the best climatic variable for predicting dengue outbreaks (RMSE = 0.72). CONCLUSION: Temperature improves dengue outbreaks forecasts better than humidity and rainfall. SARIMA models using climatic data as independent variables could be easily incorporated into an early (3 months-ahead) and reliably monitoring system of dengue outbreaks. This approach which is practicable for a surveillance system has public health implications in helping the prediction of dengue epidemic and therefore the timely appropriate and efficient implementation of prevention activities

Systems biology of platelet-vessel wall interactions

Platelets are small, anucleated cells that participate in primary hemostasis by forming a hemostatic plug at the site of a blood vessel's breach, preventing blood loss. However, hemostatic events can lead to excessive thrombosis, resulting in life-threatening strokes, emboli, or infarction. Development of multi-scale models coupling processes at several scales and running predictive model simulations on powerful computer clusters can help interdisciplinary groups of researchers to suggest and test new patient-specific treatment strategies

The DAC system and associations with acute leukemias and myelodysplastic syndromes

Imbalances of histone acetyltransferase (HAT) and deacetylase activity (DAC) that result in deregulated gene expression are commonly observed in leukemias. These alterations provide the basis for novel therapeutic approaches that target the epigenetic mechanisms implicated in leukemogenesis. As the acetylation status of histones has been linked to transcriptional regulation of genes involved particularly in differentiation and apoptosis, DAC inhibitors (DACi) have attracted considerable attention for treatment of hematologic malignancies. DACi encompass a structurally diverse family of compounds that are being explored as single agents as well as in combination with chemotherapeutic drugs, small molecule inhibitors of signaling pathways and hypomethylating agents. While DACi have shown clear evidence of activity in acute myeloid leukemia, myelodysplastic syndromes and lymphoid malignancies, their precise role in treatment of these different entities remain to be elucidated. Successful development of these compounds as elements of novel targeted treatment strategies for leukemia will require that clinical studies be performed in conjunction with translational research including efforts to identify predictive biomarkers