Krebsbuck3728

Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence. Currently, surgery combined with chemotherapy is the main treatment for osteosarcoma. However, the long-term survival of patients with metastatic osteosarcoma is unsatisfactory. Therefore, new treatment methods to improve the prognosis of patients with osteosarcoma are required. The present study aimed to develop nanocarriers with both tumor targeting and reduction responsiveness abilities, and to improve the therapeutic effect and reduce toxicity by loading traditional small molecule antitumor drugs. The tumor targeting peptide-decorated, doxorubicin (DOX)-loaded mPEG-P(Phe-co-Cys) nanoparticles were developed successfully through the ring-opening polymerization of amino acids. The peptide VATANST (STP) can specifically bind with vimentin, which is highly expressed on the osteosarcoma cell surface, resulting in tumor targeting effects. The nanoparticle is core-shell structured to protect the loaded DOX during blood flow. The disulfide bonds within the nanoparticles are sensitive to the osteosarcoma microenvironment, which has high glutathione (GSH) levels. Under the enhanced permeability and retention and active tumor targeting effects, the STP-decorated DOX-loaded nanoparticles accumulated in tumor tissues. High GSH levels can rupture disulfide bonds, resulting in the controlled release of DOX, which will cause necrosis of tumor cells. The characteristics of the synthesized nanoparticles, DOX release profiles in vitro and in vivo, cytotoxicity analysis, animal study, and safety evaluation were performed. The nanoparticles could increase the tumor inhibition efficiency against osteosarcoma and reduce the side effects of DOX to major organs. The STP-decorated mPEG-P(Phe-co-Cys) nanoparticles might be a suitable drug delivery system for DOX to treat osteosarcoma.The study aimed to develop lipid nanoparticles using excipients compatible with carvedilol (CARV) for enhanced transdermal drug delivery. Nanostructured lipid carriers (NLC) were successfully obtained and fully characterised. Franz diffusion cells were used for release and in vitro permeation studies in the porcine epidermis (EP) and full-thickness rat skin. NLC4 and NLC5 (0.5 mg/mL of CARV) presented small size (80.58 ± 1.70 and 116.80 ± 12.23 nm, respectively) and entrapment efficiency of 98.14 ± 0.79 and 98.27 ± 0.99%, respectively. CARV-loaded NLC4 and NLC5 controlled drug release. NLC4 allowed CAR permeation through porcine EP in greater amounts than NLC5, i.e. 11.83 ± 4.71 µg/cm2 compared to 3.06 ± 0.79 µg/cm2. NLC4 increased CARV permeation by 2.5-fold compared to the unloaded drug in rat skin studies (13.73 ± 4.12 versus 5.31 ± 1.56 µg/cm2). NLC4 seems to be a promising carrier for the transdermal delivery of CARV.Cerebrospinal fluid (CSF) diversion for hydrocephalus via ventriculoperitoneal (VP) shunting is one of the most commonly performed neurosurgical procedures. Unfortunately, VP shunting also carries a high complication rate. this website While long-term complications of VP shunting are generally well-described, the literature on more acute, iatrogenic injury during shunt placement is essentially limited to easily identifiable intracranial bleeds. Herein is presented the first reported case of iatrogenic abdominal wall vessel injury as a consequence of blind distal VP shunt catheter placement causing a critical haemoperitoneum that necessitated multiple transfusions. Presentation and recognition of this bleed was delayed as it occurred over a number of days. Injury to the inferior epigastric artery, or potentially a distal branch of the superficial epigastric artery, is suspected to have occurred during either blind subcutaneous tunnelling of the shunt catheter passage or during penetration of the peritoneum. Haemoperitoneum as a potential complication of procedures involving manipulation or penetration of the abdominal wall (i.e. paracentesis) is well-described in the medical and general surgical literature, and ultrasound-guidance has been widely adopted to mitigate bleeding in these cases. Familiarity with intra-abdominal haemorrhage as a potential complication of VP shunting and an understanding of its presentation is critical for timely identification of this phenomenon. Furthermore, the use of real-time ultrasound-guidance for tunnelling and distal shunt catheter placement may decrease the incidence of intrabdominal complications after shunt placement more generally and should be considered an area of future study.Purpose To evaluate the ophthalmic features of Rathke's cleft cyst (RCC) and its association with radiological characteristics. Methods In this retrospective single-center study, patients who showed typical findings suggestive of RCC on magnetic resonance imaging (MRI) and underwent relevant ophthalmic examination were recruited retrospectively. Patients were stratified into two groups according to the presence or absence of ophthalmic symptoms related to RCC. We reviewed patients' demographic information, initial symptoms, endocrinological status, ophthalmic features, and characteristics of MRI. Height, size and location of RCC, as well as the optic chiasm displacement assessed from MRI. Results Thirty-three patients (20 women and 13 men) were included in this study from among 335 patients with RCC on MRI. Fifteen patients had ophthalmic manifestation related to the cyst (Ophthalmic group), whereas 18 patients were not (Non-ophthalmic group). Headache was the most common initial symptom (15 patients, 45.5%), followed by visual disturbance (7, 21.2%), diplopia (1, 3.0%), retro-orbital pain (1, 3.0%), galactorrhea (1, 3.0%), and peripheral extremity discomfort (1, 3.0%). In seven asymptomatic patients (21.2%), the lesion was an incidental finding during a regular medical examination. Ophthalmic manifestation included visual field defect (14 patients, 93.3%) and diplopia (1 patient, 6.7%). The height, volume, and the coronal and sagittal displacements were larger in the ophthalmic group (P less then .001, all). Eleven patients who manifested ophthalmic symptoms underwent excision surgeries and nine of them (81.8%) experienced visual function improvement. Conclusion Appropriate ophthalmic examinations are warranted in patients with RCC, and treatment should be actively considered in patients with ophthalmic manifestations.Background Based on our Phantom study on transcranial direct current stimulation (tDCS), we hypothesized that EEG band power and field confinement would be greater following left dorsolateral prefrontal cortex (DLPFC - F3) tDCS using circular vs. rectangular electrodes.Methods Double-blind-randomized trial comparing tDCS with anode over left DLPFC (groups rectangular electrodes, circular electrodes, sham) and 2 active subgroup references (right shoulder vs. right DLPFC).Results Twenty-four randomized participants were assessed. We indeed found higher average EEG power spectral density (PSD) across bands for circular vs. rectangular electrodes, largely confined to F3 and there was a significant increase at AF3 for low alpha (p = 0.037). Significant differences included increased PSD in low beta (p = 0.024) and theta bands (p = 0.021) at F3, and in theta (p = 0.036) at FC5 for the right DLPFC vs. shoulder with no coherence changes. We found PSD differences between active vs. sham tDCS at Fz for alpha (p = 0.043), delta (p = 0.036), high delta (p = 0.030); and at FC1 for alpha (p = 0.031), with coherence differences for F3-Fz in beta (p = 0.044), theta (p = 0.044), delta (p = 0.037) and high delta (p = 0.009).Conclusion This pilot study despite low statistical power given its small sample size shows that active left DLPFC tDCS modulates EEG frontocentrally and suggests that electrode shapes/reference locations affect its neurophysiological effects, such as increased low alpha power at AF3 using circular vs. rectangular electrodes. Further research with more participants is warranted.Approximately 3% of intracranial aneurysm ruptures result in an associated subdural hematoma (SDH). SDH from intracranial aneurysm rupture without radiographic evidence of SAH, however, is rare. We report a case of an isolated retroclival SDH secondary to an intracranial aneurysm rupture.This study aims to describe chronic lymphocytic leukemia (CLL) epidemiology, treatment patterns and outcomes in a 2.3-million-member healthcare provider database (Maccabi Healthcare Services, Israel). Newly-diagnosed CLL patients (1999-2017) were followed through 31/3/2018. A total of 1857 newly-diagnosed CLL patients were included. Annual incidence was 5.82 per 100,000 population. Median overall survival (OS) was 12.7 (95%CI 11.8-13.5) years since diagnosis. Approximately 1/3 initiated treatment within 5 y. A statistical trend (p = 0.066) for improved OS over time was observed among younger patients (age less then 70 y) treated in 2009-2017 vs. 1999-2008). Among patients treated since 2009 (n = 411; median age = 68y), fludarabine-cyclophosphamide-rituximab (FCR), bendamustine-rituximab and obinutuzumab ± chlorambucil accounted for 19.5%, 12.2% and 11.4% of first line, respectively. Median (95%CI) time to next treatment and OS were 3.1(2.6-3.6) and 7.0(6.3-7.7) years, respectively. CLL incidence in Israel is comparable to developed countries. Real-world data suggest a trend of improved survival over the last decade among patients treated before age 70.

Paeoniflorin (Pae), a water-soluble monoterpene glucoside, has high potential clinical value in autoimmune and inflammatory diseases. However, the extremely low oral bioavailability of Pae (approximately 3%-4%) limits its formulation development and clinical application. This study aimed to develop micelles using the glycyrrhizic acid (GL) as the carrier to improve the oral absorption of Pae.

Pae-loaded GL micelles were prepared by the ultrasonic dispersion method and its formulation was optimized by single-factor tests. Characterizations of Pae-loaded GL micelles including particle size, zeta potential, entrapment efficiency (EE), drug loading (DL), morphology, and drug release

were carried out. The single-pass intestinal perfusion and pharmacokinetic studies of Pae-loaded GL micelles were also evaluated in rats and compared with Pae solution and the mixed solution of Pae and GL.

The optimized Pae-loaded GL micelles had EE of (42.21 ± 0.89)%, particle size of (58.89 ± 4.24) nm with PDI of (0.194 ± 0.010), zeta potential of (-24.40 ± 1.90) mV. Pae-loaded GL micelles showed a nearly spherical shape under TEM. Drug release of micelles demonstrated a delayed drug release compared to Pae solution. The single-pass intestinal perfusion study showed a significantly higher permeability of Pae in duodenum (

 < 0.05), jejunum (

 < 0.05), ileum (

 < 0.01) and colon (

 < 0.01) intestine after perfusion of Pae-loaded GL micelles as compared to Pae solution. The

pharmacokinetics demonstrated that the C

and AUC

values of Pae-loaded GL micelles were approximately 2.18- and 3.64-fold superior than the Pae solution.

These results suggested GL could be a potential carrier for the oral delivery of Pae.

These results suggested GL could be a potential carrier for the oral delivery of Pae.