Beyond hydrophilic polymers in amphiphilic polymer-based self-assembled NanoCarriers: Small hydrophilic carboxylate-capped disulfide drug delivery system and its multifunctionality and multispatial targetability.

Due to increasing safety and intracellular delivery concerns about hydrophilic polymers in amphiphilic polymer-based nanoparticles (NPs), this study investigates small hydrophilic molecule-stabilized NPs for effective intracellular delivery with multiorganelle targetability and dual responsiveness to acidic pH/glutathione (GSH). In the construction of small hydrophilic molecule-stabilized NP (MSPCL-NP), the A-B-A-type amphiphilic polymer (MSPCL-P) is composed of two short hydrophilic carboxylate-capped disulfide derivatives (A) that replace hydrophilic polymers and assist in providing colloidal stability and preventing antibody (e.g., at least anti-PEG antibody)-mediated specific interactions and complement activation in the plasma and a hydrophobic multiple disulfide-containing poly(ε-caprolactone) block (B) that carries hydrophobic drugs. The carboxylates on the surface of MSPCL-NP target the acidic extratumoral/endolysosomal milieu by sensing and buffering acidic pH values, and the hydrophobic carboxylic acids improve adsorptive endocytosis and effective endosomal escape. Multiple disulfide linkages selectively target cytosolic GSH, resulting in rapid drug release from the destroyed MSPCL-NP via the cleavage of disulfide bonds in MSPCL-P. Doxorubicin (DOX)-loaded NP (DOX@MSPCL-NP) exerts strong effects on killing cells in vitro and inhibits tumor growth in HCT116 xenograft tumor-bearing mice. In conclusion, the multifunctionality and multispatial targetability of MSPCL-NP might effectively overcome various sequential drug delivery hurdles, ranging from blood circulation to drug release. Furthermore, the introduction of small hydrophilic molecules represents a potential strategy to make self-assembled NPs without the use of hydrophilic polymers.

Surgical results of tympanoplasty after conversion to the endoscopic approach performed by a surgeon experienced in microscopic surgery.

PURPOSE: The aim of this study was to analyze the surgical outcomes of endoscopic tympanoplasty (ET) type I, and to investigate the learning curve of ET type I in a surgeon experienced in microscopic surgery. METHODS: We retrospectively studied patients with tympanic membrane perforations who had undergone ET type I from January 2015 to June 2020. All procedures were performed by a single senior surgeon with considerable microscopic experience. We compared the perforation closure rate in relation to age, previous ear surgery history, graft material, size, and location of perforation. We compared the operation time according to the number of operated patients. RESULTS: A total of 399 patients were enrolled. The success rate of ET type I was 92.7%. Age, prior ear surgery, graft material, size, and location of perforation did not influence the surgical outcomes. The surgical time for the initial ten cases was the longest (78.3 min), and stabilized after the first 100 cases to under 60 min. The surgical success rate was 96.0% in the first 50 cases, and decreased to approximately 92% afterwards. CONCLUSION: The surgical time largely decreased with the number of operated patients. Since the operations were performed by a surgeon experienced in microscopy, the success rate of initial cases was not low, even though the operation time of these initial cases was longer. We believe that endoscope provides a new perspective on ear surgery if it could overcome the difficulties in the early stage.

Correlation between structural phase transition and surface chemical properties of thin film SrRuO3/SrTiO3 (001).

The correlation between the structural phase transition (SPT) and oxygen vacancy in SrRuO3 (SRO) thin films was investigated by in situ X-ray diffraction (XRD) and ambient pressure X-ray photoelectron spectroscopy (AP-XPS). In situ XRD shows that the SPT occurs from a monoclinic SRO phase to a tetragonal SRO phase near ∼200 °C, regardless of the pressure environment. On the other hand, significant core level shifts in both the Ru and Sr photoemission spectra are found under ultrahigh vacuum, but not under the oxygen pressure environment. The directions and behavior of the core level shift of Ru and Sr are attributed to the formation of oxygen vacancy across the SPT temperature of SRO. The analysis of in situ XRD and AP-XPS results provides an evidence for the formation of metastable surface oxide possibly due to the migration of internal oxygen atoms across the SPT temperature, indicating the close relationship between oxygen vacancy and SPT in SRO thin films.

Incremental Treatment Costs Attributable to Overweight and Obesity in Patients with Diabetes: Quantile Regression Approach.

OBJECTIVE: This study aimed to estimate treatment costs attributable to overweight and obesity in patients with diabetes who were less than 65 years of age in the United States. METHODS: This study used data from the Medical Expenditure Panel Survey from 2001 to 2013. Patients with diabetes were identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification code (250), clinical classification codes (049 and 050), or self-reported physician diagnoses. Total treatment costs attributable to overweight and obesity were calculated as the differences in the adjusted costs compared with individuals with diabetes and normal weight. Adjusted costs were estimated by using generalized linear models or unconditional quantile regression models. RESULTS: The mean annual treatment costs attributable to obesity were $1,852 higher than those attributable to normal weight, while costs attributable to overweight were $133 higher. The unconditional quantile regression results indicated that the impact of obesity on total treatment costs gradually became more significant as treatment costs approached the upper quantile. CONCLUSIONS: Among patients with diabetes who were less than 65 years of age, patients with diabetes and obesity have significantly higher treatment costs than patients with diabetes and normal weight. The economic burden of diabetes to society will continue to increase unless more proactive preventive measures are taken to effectively treat patients with overweight or obesity.

Depth resolved lattice-charge coupling in epitaxial BiFeO3 thin film.

For epitaxial films, a critical thickness (tc) can create a phenomenological interface between a strained bottom layer and a relaxed top layer. Here, we present an experimental report of how the tc in BiFeO3 thin films acts as a boundary to determine the crystalline phase, ferroelectricity, and piezoelectricity in 60 nm thick BiFeO3/SrRuO3/SrTiO3 substrate. We found larger Fe cation displacement of the relaxed layer than that of strained layer. In the time-resolved X-ray microdiffraction analyses, the piezoelectric response of the BiFeO3 film was resolved into a strained layer with an extremely low piezoelectric coefficient of 2.4 pm/V and a relaxed layer with a piezoelectric coefficient of 32 pm/V. The difference in the Fe displacements between the strained and relaxed layers is in good agreement with the differences in the piezoelectric coefficient due to the electromechanical coupling.

Lemierre syndrome caused by acute isolated sphenoid sinusitis and its intracranial complications.

Classically, Lemierre syndrome is a rare clinical entity in which acute oropharyngeal infection causes septic internal jugular vein thrombosis and leads to septic lesions to distant organs, such as the lung. Lemierre syndrome also presents with odontogenic infections, mastoiditis, parotitis, and sinusitis. We report the first case of Lemierre syndrome following acute isolated sphenoid sinusitis that was complicated with cavernous sinus thrombophlebitis and bilateral infectious aneurysms of the intracavernous internal carotid artery. Treatment with endoscopic sphenoidotomy, culture-directed antibiotics, heparinization, and endovascular GDC coiling were performed and the patient recovered without major neurologic morbidity. Immediate and intensive treatment with careful evaluation to localize the primary infectious focus of the head and neck, including the paranasal sinus, improves the prognosis of patients with rhinogenic Lemierre syndrome.