AndersenTawil syndrome Overlapping clinical characteristics together with Noonan affliction

The leishmaniases are a group of diseases caused by protozoan parasites from Leishmania species. Effectiveness therapies for cutaneous leishmaniasis (CL), the most common form, are still needed to be developed since the available drugs such as meglumine antimoniate (MA) present severe adverse reactions. Here, we develop and characterize maltodextrin polymeric colloidal nanocarriers containing MA (PCN-MA) for topical CL treatment. PCN-MA is composed of 5 to 8% maltodextrin, 0.3% NaCl, 1% MA in 21% of water as aqueous-internal phase, containing or no 3% Kolliphor® P-188, and 10% SF1540 dispersed in a silicone-based external phase. It formed a colloidal system dispersed in silicone with high encapsulation efficiency (87% to 92%) and composite spherical-shaped particles with the smooth and regular surface within the nanosized scale, which was confirmed by scanning electron microscopy (SEM) and dynamic light scattering (DLS) analysis. Ex vivo cutaneous retention studies using pig ears skin on Franz diffusion cells revealed that the MA cutaneous retention is improved when delivered by PCN. Topical PCN-MA evaluation in murine leishmaniasis model showed similar efficacy than the intraperitoneal injection of the reference medicine (Glucantime®) regarding parasite titer reduction and superior healing activity in terms of collagen area deposition. Our results suggest that this sugar-based PCN is a promising agent for topical delivery of meglumine antimoniate. This study aims to create and evaluate a kaempferol (KAE) ophthalmic solution based on polyvinylpyrrolidone (PVP) nanocomplexes. KAE can be highly complexed with PVP K-17PF (17PF) to formulate an aqueous ophthalmic solution named 17PF-KAE. The optimized 17PF-KAE displays high complexing efficiency, an ultra-small size (8.628 ± 0.066 nm), and good aqueous dispersibility. 17PF-KAE did not show any obvious cytotoxicity or in vivo ocular tissue toxicity. Further, 17PF-KAE was observed to facilitate significant improvement in in vitro parallel artificial membrane permeability, in vitro cellular uptake, and ex vivo corneal permeation of KAE. Regarding the in vivo ocular absorption test, the KAE levels in the cornea and aqueous humor determined from the 17PF-KAE group were much higher than those in the free KAE solution group in addition to conjunctiva and the iris-ciliary body at certain time points. 17PF-KAE was also observed to promote remarkable improvement in in vitro antioxidant activity and in vivo anti-inflammatory activity. Moreover, a topical 17PF-KAE solution in mice eyes showed significant improvement in the treatment efficacy of corneal alkali burns over the free KAE solution. The therapeutic mechanism was also associated with inhibiting the production of key mediators of inflammation (CD54, IL-6, and TGF-β1) and angiogenic factors (VEGF). Therefore, these results demonstrate that 17PF-KAE may be a promising new ophthalmic formulation for the prophylaxis and treatment of oxidative stress and inflammation-related ocular diseases. 2,3-Butanedione-2-monoxime mouse BACKGROUND Re-irradiation (re-RT) for locoregionally recurrent esophageal and gastroesophageal junction (GEJ) cancer and de novo esophageal/GEJ cancer arising in-field after a course of prior radiation poses significant treatment challenges given the sensitivity of surrounding organs at risk (OARs). Guidelines for treatment of this presentation are not well-established. Pencil-beam scanning (PBS) proton therapy has the ability to decrease radiation dose to OARs relative to photon plans. We present the first published series to date of re-RT with PBS for esophageal/GEJ malignancies and hypothesize that re-RT with proton PBS will be feasible and improve the safety profile of re-RT for this cohort of patients. METHODS Consecutive esophageal/GEJ cancers treated with PBS re-irradiation within a single institution were analyzed. Comparative volumetric-modulated arc therapy (VMAT) photon plans were generated. Seventeen patients were included for analysis. RESULTS At a median follow up of 11.6 months, 1-year local control was 75.3% and overall survival was 68.9%. There were 5 (27.8%) grade ≥ 3 late toxicities. When matched for CTV coverage, proton PBS plans delivered significantly lower doses to the spinal cord, lungs, liver, and heart (all p less then 0.05); 5 VMAT plans would have been undeliverable based on physician-specified OAR constraints. CONCLUSIONS Re-irradiation for de novo or recurrent malignancies of the esophagus/GEJ, when delivered with PBS proton therapy, yields high rates of local control with acceptable acute and late toxicities in a high-risk population and decreased radiation dose to OARs relative to comparative photon plans. This is the largest series of proton re-RT for esophageal malignancies and the first exclusively using PBS. BACKGROUND Posterior circulation stroke due to atlantoaxial dislocation (AAD), although uncommon is a well described entity. The normally coursed V3 segment of the vertebral artery (VA) is likely to be stretched due to C1-C2 dislocation, and further compromised by the C1-C2 translational mobility. The persistent first intersegmental artery (PFIA), an anomalous variant does not course through the C1 transverse foramen, rather crosses the posterior C1-C2 joints and is unlikely to be affected by the C1-C2 dislocation. Therefore, a patient with AAD and anomalous VA presenting with stroke should be evaluated for other etiologies of VA compromise. CASE DESCRIPTION We report a patient of AAD with PFIA who presented with posterior circulation stroke. Careful radiological evaluation revealed a loose body (LB) adjacent to the medial aspect of the left C1-C2 facet compressing the anomalous VA. Intraoperatively, there was a large LB on the postero-medial border of the joint, compressing the VA. The anomalous VA was mobilized, and the offending element removed followed by fixation of the C1-C2. CONCLUSION One should be aware of such an etiology of arterial compromise in cases of AAD with co-existent anomalous VA. An underlying LB or large osteophytes due to instability may be the offending cause, and needs to be dealt with, as fusion alone may not benefit the patient.