Amphotericin B is a lifesaving polyene antibiotic used in the treatment of systemic mycoses. Unfortunately, the pharmacological applicability of this drug is limited because of its severe toxic side effects. At the same time, the lack of a well-defined mechanism of selectivity hampers the efforts to rationally design safer derivatives. As the drug primarily targets the biomembranes of both fungi and humans, new insights into the binding of amphotericin B to lipid membranes can be helpful in unveiling the molecular mechanisms underlying both its pharmacological activity and toxicity. We use fluorescence-lifetime-imaging microscopy combined with fluorescence-emission spectroscopy in the microscale to study the interaction of amphotericin B with single lipid bilayers, using model systems based on giant unilamellar liposomes formed with three lipids: dipalmitoylphosphatidylcholine (DPPC), dimirystoylphosphatidylcholine (DMPC), and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC). The results show that amphotericin B introduced into the water phase as a DMSO solution binds to the membrane as dimers and small-molecular aggregates that we identify as tetramers and trimers. Fluorescence-detected linear-dichroism measurements revealed high orientational freedom of all the molecular-organization forms with respect to the membrane plane, which suggests that the drug partially binds to the membrane surface. The presence of sterols in the lipid phase (cholesterol but particularly ergosterol at 30 mol %) promotes the penetration of drug molecules into the lipid membrane, as concluded on the basis of the decreased orientation angle of amphotericin B molecules with respect to the axis normal to the membrane plane. Moreover, ergosterol facilitates the association of amphotericin B dimers into aggregated structures that can play a role in membrane destabilization or permeabilization. The presence of cholesterol inhibits the formation of small aggregates in the lipid phase of liposomes, making this system a promising candidate for a low-toxicity antibiotic-delivery system. Our conclusions are supported with molecular simulations that reveal the conformational properties of AmB oligomers in both aqueous solution and lipid bilayers of different compositions.

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Heart CT has undergone substantial development from the use of calcium scores performed on electron beam CT to modern 256+-row CT scanners. The latest big step in its evolution was the invention of dual-energy scanners with much greater capabilities than just performing better ECG-gated angio-CT. In this review, we present the unique features of dual-energy CT in heart diagnostics.

Background Mechanical thrombectomy (MT) is well-established in the treatment of acute ischemic anterior circulation stroke. However, there is no evidence from randomized trials or meta-analyses that MT is safe and effective in the treatment of patients with acute ischemic posterior circulation stroke (PCS). Purpose To evaluate the clinical and procedural factors associated with recanalization and outcome of patients with PCS treated with MT. Material and Methods Forty-three patients with PCS (median age 73 years) who underwent treatment with MT were included. Data including demographics, baseline stroke severity, radiological imaging, procedure and post-procedure complications were documented. Clinical outcome was evaluated using the modified Rankin Scale (mRS). The patients were classified into two groups based on clinical outcome (favorable vs. unfavorable mRS after 90 days). Results Median baseline National Institute of Health Stroke Scale (NIHSS) was 17. Twenty patients were eligible for intravenous thrombolysis and received recombinant tissue plasminogen activator before MT. Successful recanalization was observed in 88.4% of patients. After 90 days, favorable outcome (defined as mRS 0–2) was achieved in 26 patients; six patients had an unfavorable outcome (mRs >2). Final mortality rate was 25.5%. Baseline NIHSS, onset to reperfusion time, procedure duration, and successful recanalization had a statistically significant association with outcome. Failed recanalization and occurrence of intracranial hemorrhage were found to be associated with a higher mortality rate. Conclusion MT is feasible and effective method in treatment of PCS. Baseline NIHSS and onset to reperfusion time were found to be independent predictive factors of clinical outcome.

Background Mechanical thrombectomy (MT) became a standard of care for patients with acute ischemic stroke (AIS) with its efficacy demonstrated by meta-analysis and randomized studies. Although ischemic stroke is associated more with older patients, it may also have devastating neurological effects on young patients. Purpose To present our experience with stroke patients aged <50 years treated with endovascular means and to evaluate clinical and procedural factors associated with outcome and mortality. Material and Methods This study was conducted on 34 young stroke patients treated with MT. Clinical features including baseline results, radiological imaging, procedural details, and outcome results were documented and evaluated. Recanalization was assessed according to the TICI score. The clinical condition was evaluated after three months using mRS. Mortality rate was calculated. Results The rate of successful recanalization (TICI ≥2c) was 79% (27/34). Symptomatic intracranial hemorrhage (sICH) was observed in 5 (15%) patients. After 90 days, the mortality rate was 12%. Favorable clinical outcome (mRs 0–2) was regained in 65% of the patients whereas satisfactory clinical outcome was seen in 85%. Poor clinical outcome (mRs >2) was observed in 9 (23.7%) patients. Conclusion In conclusion, the results of this study demonstrate that MT for AIS in young patients is feasible and provides an excellent rate of arterial recanalization and high rate of favorable outcomes. Statistical analysis showed that shorter time from onset to arrival and reperfusion, successful recanalization and absence of hemorrhagic transformation are the predictors of favorable clinical outcome and overall survival rate.