Development and in vitro evaluation of a novel lipid nanocapsule formulation of etoposide.

Small cell lung cancer (SCLC) is the most aggressive carcinoma in thoracic oncology, unfortunately, despite chemotherapy, relapse is constant. The effect of etoposide, a major drug used against SCLC, can potentially be enhanced after its encapsulation in nanocarriers. The aim of this study was to use the technology of lipid nanocapsules (LNCs) to obtain nanocarriers with drug loadings compatible with clinical use and with an industrial process. Solubility studies with different co-solvent were first performed, then several process were developed to obtain LNCs. LNCs were then characterized (size, zeta potential, and drug loading). The best formulation called Ω-LNCs had a size of 54.1±2.0 nm and a zeta potential of -5.8±3.5 mV and a etoposide drug loading of 5.7±0.3mg/g. The characteristics of this formulation were maintained after freeze drying and after a 15× scale-up. Release studies in a media mimicking plasma composition showed that 40% of the drug was released from the LNCs after 48 h. Moreover the activity of etoposide after encapsulation was enhanced on H209 cells, IC50 was 100 μM and 2.5 μM for etoposide and etoposide LNCs respectively. Unfortunately the formulation failed to be more cytotoxic than etoposide alone on H69AR cells that are resistant to etoposide. This study showed that is was possible to obtain a new etoposide nanocarrier without the use of organic solvent, that the process is suitable for scale-up and freeze drying and finally that etoposide activity is maintained which is very promising for future treatment of SCLC

Procedural Complications During Early Versus Late Endovascular Treatment in Acute Stroke: Frequency and Clinical Impact

BACKGROUND AND PURPOSE: Endovascular treatment (EVT) in acute ischemic stroke is effective in the late time window in selected patients. However, the frequency and clinical impact of procedural complications in the early versus late time window has received little attention. METHODS: We retrospectively studied all acute ischemic strokes from 2015 to 2019 receiving EVT in the Acute Stroke Registry and Analysis of Lausanne. We compared the procedural EVT complications in the early (<6 hours) versus late (6-24 hours) window and correlated them with short-term clinical outcome. RESULTS: Among 695 acute ischemic strokes receiving EVT (of which 202 were in the late window), 113 (16.3%) had at least one procedural complication. The frequency of each single, and for overall procedural complications was similar for early versus late EVT (16.2% versus 16.3%, Padj=0.90). Procedural complications lead to a significantly less favorable short-term outcome, reflected by the absence of National Institutes of Health Stroke Scale improvement in late EVT (delta-National Institutes of Health Stroke Scale-24 hours, -2.5 versus 2, Padj=0.01). CONCLUSIONS: In this retrospective analysis of consecutive EVT, the frequency of procedural complications was similar for early and late EVT patients but very short-term outcome seemed less favorable in late EVT patients with complications

Early-versus-Late Endovascular Stroke Treatment: Similar Frequencies of Nonrevascularization and Postprocedural Cerebrovascular Complications in a Large Single-Center Cohort Study.

Endovascular treatment of acute ischemic stroke is now performed more frequently in the late window in radiologically selected patients. However, little is known about whether the frequency and clinical impact of incomplete recanalization and postprocedural cerebrovascular complications differ between early and late windows in the real world. We retrospectively reviewed all patients with acute ischemic stroke receiving endovascular treatment within 24 hours from 2015 to 2019 and included in the Acute STroke Registry and Analysis of Lausanne. We compared rates of incomplete recanalization and postprocedural cerebrovascular complications (parenchymal hematoma, ischemic mass effect, and 24-hour re-occlusion) in the early (&lt;6 hours) versus late window (6-24 hours, including patients with unknown onset) populations and correlated them with the 3-month clinical outcome. Among 701 patients with acute ischemic stroke receiving endovascular treatment, 29.2% had late endovascular treatment. Overall, incomplete recanalization occurred in 56 patients (8%), and 126 patients (18%) had at least 1 postprocedural cerebrovascular complication. The frequency of incomplete recanalization was similar in early and late endovascular treatment (7.5% versus 9.3%, adjusted P =.66), as was the occurrence of any postprocedural cerebrovascular complication (16.9% versus 20.5%, adjusted P = .36). When analyzing single postprocedural cerebrovascular complications, rates of parenchymal hematoma and ischemic mass effect were similar (adjusted P = .71, adjusted P = .79, respectively), but 24-hour re-occlusion seemed somewhat more frequent in late endovascular treatment (4% versus 8.3%, unadjusted P = .02, adjusted P = .40). The adjusted 3-month clinical outcome in patients with incomplete recanalization or postprocedural cerebrovascular complications was comparable between early and late groups (adjusted P = .67, adjusted P = .23, respectively). The frequency of incomplete recanalization and of cerebrovascular complications occurring after endovascular treatment is similar in early and well-selected late patients receiving endovascular treatment. Our results demonstrate the technical success and safety of endovascular treatment in well-selected late patients with acute ischemic stroke

Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines

BACKGROUND: Acute malaria has been associated with a decreased antibody response to tetanus and diphtheria toxoids, meningococcal, salmonella, and Hib vaccines. Interest in giving malaria drug therapy and prevention at the time of childhood immunizations has increased greatly following recent trials of intermittent preventive therapy during infancy (IPTi), stimulating this re-analysis of unpublished data. The effect of malaria chemoprophylaxis on vaccine response was studied following administration of measles vaccines and diphtheria-tetanus-whole cell pertussis (DTP) vaccines. METHODS: In 1975, six villages divided into two groups of children ≤74 months of age from Burkina Faso, were assigned to receive amodiaquine hydrochloride chemoprophylaxis (CH+) every two weeks for seven months or no chemoprophylaxis (CH-). After five months, children in each group received either one dose of measles or two doses of DTP vaccines. RESULTS: For recipients of the measles vaccine, the seroconversion rates in CH+ and CH- children, respectively, were 93% and 96% (P > 0.05). The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05) and 77% and 91% for tetanus toxoid (P > 0.05). In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05). While analysis for pertussis showed a 43% (CH+) and 67% (CH-) response (P < 0.05), analyses using logistic regression to control for sex, age, chemoprophylaxis, weight-for-height Z-score, and pre-vaccination geometric mean titer (GMT), demonstrated that chemoprophylaxis was not associated with a significantly different conversion rate following DTP and measles vaccines. Seven months of chemoprophylaxis decreased significantly the malaria IFA and ELISA GMTs in the CH+ group. CONCLUSION: Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine

Advances in crop insect modelling methods—Towards a whole system approach

A wide range of insects affect crop production and cause considerable yield losses. Difficulties reside on the development and adaptation of adequate strategies to predict insect pests for their timely management to ensure enhanced agricultural production. Several conceptual modelling frameworks have been proposed, and the choice of an approach depends largely on the objective of the model and the availability of data. This paper presents a summary of decades of advances in insect population dynamics, phenology models, distribution and risk mapping. Existing challenges on the modelling of insects are listed; followed by innovations in the field. New approaches include artificial neural networks, cellular automata (CA) coupled with fuzzy logic (FL), fractal, multi-fractal, percolation, synchronization and individual/agent based approaches. A concept for assessing climate change impacts and providing adaptation options for agricultural pest management independently of the United Nations Intergovernmental Panel on Climate Change (IPCC) emission scenarios is suggested. A framework for estimating losses and optimizing yields within crop production system is proposed and a summary on modelling the economic impact of pests control is presented. The assessment shows that the majority of known insect modelling approaches are not holistic; they only concentrate on a single component of the system, i.e. the pest, rather than the whole crop production system. We suggest system thinking as a possible approach for linking crop, pest, and environmental conditions to provide a more comprehensive assessment of agricultural crop production.Peer reviewe

e-Pilly TROP Maladies infectieuses tropicales

L’e-Pilly TROP est un ouvrage d’infectiologie tropicale destiné aux médecins et aux étudiants en médecine des pays francophones du Sud. La prise en compte des différents niveaux de la pyramide sanitaire dans ces pays le rend aussi accessible aux infirmiers des centres de santé communautaires urbains et des structures de santé intermédiaires des zones rurales. Par définition, les Pays En Développement accroissant progressivement leurs capacités de diagnostic biologique et de traitement, les outils de prise en charge correspondent aux moyens des niveaux périphériques comme à ceux des niveaux hospitaliers de référence