Efficacy and tolerability of vigabatrin in West syndrome

West syndrome (WS) is a severe epileptic encephalopathy of childhood, characterized by spasms, developmental deterioration and hipsarhythymia. Objective: To evaluate the safety and efficacy of vigabatrin (VGB) in the treatment of WS. Method: We evaluated every patient diagnosed with WS seen at the pediatric epilepsy clinic and exposed to VGB. Patients were interviewed according to a semistructured questionnaire and we analyzed gender, age, etiology (cryptogenic or symptomatic), associated diseases, age of seizure onset, neuroimaging findings, EEG prior and after VGB, use of other antiepileptic drugs, time for seizure control, electroretinogram, visual complaints, adverse events and family history of epilepsy. Results: Twenty-three patients were evaluated, 16 boys, ages ranging from 1.25 years to 11.5 years (mean=5y3m). Sixteen (69.5%) patients were seizure free, five (22%) had partial seizure control and in two (8.5%) there was no improvement. Only one patient presented gabaergic retinopathy. Six (26%) patients presented adverse events: somnolence, aggressivity or retinopathy. Patients with seizure onset after 6 months of age presented better results after VGB introduction (p 0.05). After VGB, no patient presented hipsarrhythymia and 50% had a normal EEG. Conclusion: Although VGB may be associated with serious adverse events such as gabaergic retinopathy, our results show that it should be considered in the treatment of WS.632B46947

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

The H1N1 influenza pandemic of 2009 has claimed over 18,000 lives. During this pandemic, development of drug resistance further complicated efforts to control and treat the widespread illness. This research utilizes traditional Chinese medicine Database@Taiwan (TCM Database@Taiwan) to screen for compounds that simultaneously target H1 and N1 to overcome current difficulties with virus mutations. The top three candidates were de novo derivatives of xylopine and rosmaricine. Bioactivity of the de novo derivatives against N1 were validated by multiple machine learning prediction models. Ability of the de novo compounds to maintain CoMFA/CoMSIA contour and form key interactions implied bioactivity within H1 as well. Addition of a pyridinium fragment was critical to form stable interactions in H1 and N1 as supported by molecular dynamics (MD) simulation. Results from MD, hydrophobic interactions, and torsion angles are consistent and support the findings of docking. Multiple anchors and lack of binding to residues prone to mutation suggest that the TCM de novo derivatives may be resistant to drug resistance and are advantageous over conventional H1N1 treatments such as oseltamivir. These results suggest that the TCM de novo derivatives may be suitable candidates of dual-targeting drugs for influenza.National Science Council of Taiwan (NSC 99-2221-E-039-013-)Committee on Chinese Medicine and Pharmacy (CCMP100-RD-030)China Medical University and Asia University (CMU98-TCM)China Medical University and Asia University (CMU99-TCM)China Medical University and Asia University (CMU99-S-02)China Medical University and Asia University (CMU99-ASIA-25)China Medical University and Asia University (CMU99-ASIA-26)China Medical University and Asia University (CMU99-ASIA-27)China Medical University and Asia University (CMU99-ASIA-28)Taiwan Department of Health. Clinical Trial and Research Center of Excellence (DOH100-TD-B-111-004)Taiwan Department of Health. Cancer Research Center of Excellence (DOH100-TD-C-111-005

Baropodometry on women suffering from chronic pelvic pain - a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Previous studies have associated chronic pelvic pain with a stereotyped pattern of movement and posture, lack of normal body sensations, a characteristic pain distribution. We aimed at evaluating if these postural changes are detectable in baropodometry results in patients with chronic pelvic pain.</p> <p>Methods</p> <p>We performed a prospective study in a university hospital. We selected 32 patients suffering from chronic pelvic pain (study group) and 30 women without this pathology (regular gynecological work out - control group). Pain scores and baropodometric analysis were performed.</p> <p>Results</p> <p>As expected, study group presented higher pain scores than control group. Study and control groups presented similar averages for the maximum pressures to the left and right soles as well as soles supports in the forefeet and hind feet. Women suffering from chronic pelvic pain did not present differences in baropodometric analysis when compared to healthy controls.</p> <p>Conclusions</p> <p>This data demonstrates that postural abnormalities resulting from CPP could not be demonstrated by baropodometric evaluation. Other postural measures should be addressed to evaluate pelvic pain patients.</p

Biflorin: an o-naphthoquinone of clinical significance

Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plant Capraria biflora L. (Schrophulariaceae), indigenous of the West Indies and South America, which is located in temperate or tropical areas. This compound has shown to be strongly active against grampositive and alcohol-acid-resistant bacteria. It has been efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8 and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important cytotoxic effects. In this article, information related to the first structural characterization studies are presented, as well as the latest reports concerning the biological activity of this molecule

Geographical presences and absences. The role of Spanish academic geography in geopolitical debates

A set of factors has converged to create geopolitical issues of great importance in contemporary Spain. These relate as much to the incorporation of Spain in the process of globalization as to the internal organization of the Spanish State. This chapter examines the contribution of Spanish academic geography in the first two decades of this century to research and debate in the feld of political geography. The chapter has been prepared on the basis of a systematic review of the main Spanish academic journals in the feld, as well as references to a very considerable bibliography. The chapter comprises fve sections: the introduction presents the importance of geopolitical factors in contemporary Spain and states the hypothesis and methodology adopted to develop the chapter; the second section looks at the output of Spanish academic geography on the geopolitical position of the Iberian countries with respect to various geographical areas; the third focuses on studies concerning the borders of the Spanish state; the fourth section examines the work dealing with the institutional organization of what the 1978 Spanish Constitution calls 'nationalities and regions'; and fnally, the ffth section homes in on research into the spatial aspects of local and metropolitan governments. The chapter is then rounded off by a few brief conclusions

Let the people decide:citizen deliberation on the role of GMOs in Mali’s agriculture

This paper describes and critically reflects on a participatory policy process which resulted in a government decision not to introduce genetically modified (GM) cotton in farmers’ fields in Mali (West Africa). In January 2006, 45 Malian farmers gathered in Sikasso to deliberate on GM cotton and the future of farming in Mali. As an invited policy space convened by the government of Sikasso region, this first-time farmers’ jury was unique in West Africa. It was known as l’ECID—Espace Citoyen d’Interpellation Démocratique (Citizen’s Space for Democratic Deliberation)—and it had an unprecedented impact on the region. In this Deliberative and Inclusive Process (DIP), the ECID combined the citizens’ jury method with indigenous methods for debate and dialogue, including the traditional African palaver. The ECID brought together male and female producers representing every district in the Sikasso region of southern Mali, specialist witnesses from various continents and a panel of independent observers, as well as resource persons and members of the national and international press and media. As an experiment in deliberative democracy, the ECID of Sikasso aimed to give men and women farmers the opportunity to share knowledge on the benefits and risks of GM cotton, and make policy recommendations on the future of GM technol- ogy in Malian agriculture. Designed as a bottom-up and participatory process, the ECID’s outcomes significantly changed national policy on the release of GM technology and have had an enduring influence in Mali. In this paper, we describe our positionality as action researchers and co-organisers of the ECID. We explain the methodology used for the ECID of Sikasso and critically reflect on the safeguards that were put in place to ensure a balanced and trustworthy deliberative process. The ECID and its key outcomes are discussed in the context of the political economy of GM cotton in West Africa. Last, we briefly highlight the relevance of the ECID for current international debates on racism in the theory and practice deliberative democracy; the production of post-normal transdisciplinary knowledge for technology risk-assessments; and the politics of knowledge in participatory policy-making for food and agriculture

Controlled membrane translocation provides a mechanism for signal transduction and amplification.

Transmission and amplification of chemical signals across lipid bilayer membranes is of profound significance in many biological processes, from the development of multicellular organisms to information processing in the nervous system. In biology, membrane-spanning proteins are responsible for the transmission of chemical signals across membranes, and signal transduction is often associated with an amplified signalling cascade. The ability to reproduce such processes in artificial systems has potential applications in sensing, controlled drug delivery and communication between compartments in tissue-like constructs of synthetic vesicles. Here we describe a mechanism for transmitting a chemical signal across a membrane based on the controlled translocation of a synthetic molecular transducer from one side of a lipid bilayer membrane to the other. The controlled molecular motion has been coupled to the activation of a catalyst on the inside of a vesicle, which leads to a signal-amplification process analogous to the biological counterpart.We thank the University of Cambridge Oppenheimer Fund for an Early Career Research Fellowship (M.J.L); the Wiener-Anspach Foundation (FWA) for postdoctoral fellowship (FK) ; and Franziska Kundel and David Klenerman for TIRFM imaging experiments

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years