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An abstract of the article "Miringoplasty and Tympanoplasty without Mastoidectomy" by Alejandro Harguindey Antolí-Candela and colleagues is presented.

An abstract of the article "Surgical treatment of cholesteatoma: Criteria for the selection of the surgical technique" by Alejandro Harguindey Antolí-Candela and others is presented.

Congenital quadricuspid aortic valve is very uncommon, and is often associated with other cardiac disorders, such as patent ductus, ventricular septal defect, pulmonary stenosis, mitral valve malformation, hypertrophic cardiomyopathy and coronary abnormalities. We report a patient with congenital quadricuspid aortic valve associated with congenital complete heart block. To our knowledge, this association has not been reported so far. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved. [ABSTRACT FROM AUTHOR]

COVID-19, a pandemic disease caused by a viral infection, is associated with a high mortality rate. Most of the signs and symptoms, e.g. cytokine storm, electrolytes imbalances, thromboembolism, etc., are related to mitochondrial dysfunction. Therefore, targeting mitochondrion will represent a more rational treatment of COVID-19. The current work outlines how COVID-19's signs and symptoms are related to the mitochondrion. Proper understanding of the underlying causes might enhance the opportunity to treat COVID-19. [ABSTRACT FROM AUTHOR]

Background and objectives: In addition to the myocardium, the microvasculature may be also damaged in acute myocardial infarction. The aim was to evaluate the capability of myocardial contrast echocardiography in the detection of microvasculature damage after myocardial infarction. Patients and methods: Twelve patients with recent acute myocardial infarction and five control subjects with normal coronary arteries and without history of myocardial infarction were studied. Myocardial contrast echocardiography with power modulation was performed, and quantitative data were measured off-line. Power modulation uses a combination of low (0.1) and high (1.7) mechanical indexes, allowing a real-time evaluation of myocardial perfusion. Contrast agent was administered as a 3-min bolus. The quantitative analysis was performed off-line by a different blinded investigator. The refilling velocity was calculated as the difference between the peak myocardial refilling value and the value at 1 s after the impulse divided by the time from the first second after the impulse to the peak refilling value. Results: Eighty-one myocardial segments (75%) were analysed qualitatively and quantitatively in AMI patients, and 18 (60%) in control subjects (P=NS). The peak refilling intensity was not significantly different in patients and control subjects (6.62±5.85 vs. 7.53±4.06 dB, respectively). However, time to peak refilling intensity was significantly longer (5.25±1.57 vs. 4.00±0.53, P=0.004) and the velocity of refilling was significantly lower (2.74±5.34 vs. 6.58±8.02, P=0.028) in patients with myocardial infarction. Conclusion: There is microvasculature damage after myocardial infarction that is reflected as a delayed velocity of refilling in myocardial contrast echocardiography. [Copyright &y& Elsevier]

Objective: This study sought to evaluate the prognostic significance of the presence of DNA of Chlamydia pneumoniae in the coronary atherosclerotic lesions of patients with unstable angina. Background: C. pneumoniae has been implicated in the pathogenesis of coronary artery disease by serological and pathological studies, but whether antichlamydial antibodies and the presence of this pathogen in the coronary atherosclerotic tissue are related to prognosis in unstable angina remains unclear. Methods: A total 76 coronary specimens from 45 patients with unstable angina undergoing bypass surgery were subjected to nested polymerase chain reaction (PCR) for C. pneumoniae. Antichlamydial immunoglobulin G (IgG), A (IgA) and M (IgM) were also examined by an enzyme immunoassay. Patients were followed during a 2-year period to determine the incidence of adverse cardiovascular events. Results: DNA of C. pneumoniae was detected in 57 (75%) of 76 atherosclerotic lesions: 39 patients showed a positive PCR result in at least one plaque. Of the 45 patients, 44 (97.7%) showed a positive serological result: IgG was positive in 39 (86.6%) patients, IgM in five (11.1%) patients and IgA in 42 (93.3%). Clinical characteristics and serologic results were similarly distributed in patients with and without infected lesions at enrollment. At least one adverse event occurred in 21 (46.6%) of the 45 patients at 2 years: death in nine (20%), recurrent angina in 12 (26.6%), revascularization in six (13.3%) and myocardial infarction in two (4.4%) patients. The composite endpoint of death, myocardial infarction, recurrent angina and revascularization at 2-year follow-up did not differ according to the PCR or serologic results. Conclusions: The presence of C. pneumoniae in coronary atherosclerotic plaques of patients with unstable angina undergoing coronary bypass grafting does not have prognostic significance. In addition, serology does not allow us to differentiate those patients with plaque infection by C. pneumoniae and also does not provide any prognostic information in these patients. [Copyright &y& Elsevier]

Efficient intracellular delivery of biomacromolecules such as proteins continues to remain a challenge despite its potential for medicine. In this work, we show that mScarlet, a non cytotoxic red fluorescent protein (RFP) conjugated to Click Nucleic Acid (CNA), a synthetic analog of DNA, undergo cell uptake significantly more than either native proteins or proteins conjugated with similar amounts of DNA in MDA-MB-468 cells. We further demonstrate that the process of cell uptake is metabolically driven and that scavenger receptors and caveolae mediated endocytosis play a significant role. Co-localization studies using anti-scavenger receptor antibodies suggest that scavenger receptors are implicated in the mechanism of uptake of CNA modified proteins.

We illustrate how intermolecular interactions facilitate ATP-free electron transfer between either native or engineered MoFe protein (MoFeP) from nitrogenase and a CdS nanorod (NR) by following the reduction of H + to H 2 . First, by varying the charge on the surface of the NR, we show the role of electrostatic interactions on MoFeP binding to the particle surface and subsequent H + reduction. Next, the role of strong, semicovalent thiol-CdS interactions was tested using free cysteines on the MoFeP. By blocking free cysteines, we show that the presence of free thiols on the protein has little to no influence on CdS binding and resultant photocatalytic activity. We next studied methods to covalently bind the protein to CdS by modifying the free cysteines with dibenzocyclooctyne (DBCO) and reacting the CdS NRs capped with a mixture of negatively charged thioglycolic acid and thiol-PEG3-azide ligands. As compared to that of the unmodified proteins, a 32.2 ± 1.5% and 61.7 ± 2.1% increase in H 2 production was observed from MoFeP and C-MoFeP, respectively. At last, to test the effect of both charge and covalent tethering, positively charged cysteamine/azide CdS NRs were reacted with DBCO-modified C-MoFeP, which showed little improvement over native C-MoFeP alone under irradiation. These results show the importance of both electrostatic associations between the NR and protein and covalently tethering the protein to the semiconductor surface for enhanced electron transfer and photodriven activity.

In this work, we show that a prodrug enzyme covalently photoconjugated to live cell receptors survives endosomal proteolysis and retains its catalytic activity over multiple days. Here, a fusion protein was designed with both an antiepidermal growth factor receptor (EGFR) affibody and the prodrug enzyme cytosine deaminase, which can convert prodrug 5-fluorocytosine to the anticancer drug 5-fluorouracil. A benzophenone group was added at a site-specific mutation within the affibody, and the fusion protein was selectively photoconjugated to EGFR receptors expressed on membranes of MDA-MB-468 breast cancer cells. The fusion protein was next labeled with two dyes for tracking uptake: AlexaFluor 488 and pH-sensitive pHAb. Flow cytometry showed that fusion proteins photo-cross-linked to EGFR first underwent receptor-mediated endocytosis within 12 h, followed by recycling back to the cell membrane within 24 h. These findings were also confirmed by confocal microscopy. The unique cross-linking of the affibody-enzyme fusion proteins was utilized for two anticancer treatments. First, the covalent linking of the protein to the EGFR led to inhibition of ERK signaling over a two-day period, whereas conventional antibody therapy only led to 6 h of inhibition. Second, when the affibody-CodA fusion proteins were photo-cross-linked to EGFR overexpressed on MDA-MB-468 breast cancer cells, prodrug conversion was found even 48 h postincubation without any apparent decrease in cell killing, while without photo-cross-linking no cell killing was observed 8 h postincubation. These studies show that affinity-mediated covalent conjugation of the affibody-enzymes to cell receptors allows for prolonged expression on membranes and retained enzymatic activity without genetic engineering.

The simultaneous delivery of multiple therapeutics to a single site has shown promise for cancer targeting and treatment. However, because of the inherent differences in charge and size between drugs and biomolecules, new approaches are required for colocalization of unlike components in one delivery vehicle. In this work, we demonstrate that triblock copolymers containing click nucleic acids (CNAs) can be used to simultaneously load a prodrug enzyme (cytosine deaminase, CodA) and a chemotherapy drug (doxorubicin, DOX) in a single polymer nanoparticle. CNAs are synthetic analogs of DNA comprised of a thiolene backbone and nucleotide bases that can hybridize to complementary strands of DNA. In this study, CodA was appended with complementary DNA sequences and fluorescent dyes to allow its encapsulation in PEG-CNA-PLGA nanoparticles. The DNA-modified CodA was found to retain its enzyme activity for converting prodrug 5-fluorocytosine (5-FC) to active 5-fluorouracil (5-FU) using a modified fluorescent assay. The DNA-conjugated CodA was then loaded into the PEG-CNA-PLGA nanoparticles and tested for cell cytotoxicity in the presence of the 5-FC prodrug. To study the effect of coloading DOX and CodA within a single nanoparticle, cell toxicity assays were run to compare dually loaded nanoparticles with nanoparticles loaded only with either DOX or CodA. We show that the highest level of cell death occurred when both DOX and CodA were simultaneously entrapped and delivered to cells in the presence of 5-FC.

Near infrared (NIR)-absorbing noble metal nanostructures are being extensively studied as theranostic agents, in particular for photoacoustic imaging and photothermal therapy. Because of the electric field enhancement at the tips of anisotropic metal nanostructures, positioning photoactive species at these sites can lead to increased energy absorption. Herein, we show the site-specific placement of NIR-active photosensitizers at the ends of gold nanorods (AuNRs) by growing porous TiO 2 caps. The surface plasmon resonance of the AuNRs was carefully tuned to overlap with the exciton absorption of indocyanine green (ICG), a NIR photosensitizer with low quantum yields and poor photostability. In conjugating high amounts of ICG to the TiO 2 caps, increased amounts of singlet oxygen ( 1 O 2 ) were generated as compared to when ICG was attached to sidewalls of the AuNRs. Because the AuNRs also cause local increases in temperature upon NIR excitation, DNA strands were next attached to the AuNRs sidewalls and loaded with doxorubicin (DOX). We found that the synergistic effect of increased 1 O 2 and photothermal-induced drug delivery led to significant improvements in tumor cell killing. This work demonstrates that with careful design over hybrid nanostructure synthesis, higher levels of tumor therapy may be achieved.

Co-delivery of both chemotherapy drugs and siRNA from a single delivery vehicle can have a significant impact on cancer therapy due to the potential for overcoming issues such as drug resistance. However, the inherent chemical differences between charged nucleic acids and hydrophobic drugs have hindered entrapment of both components within a single carrier. While poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers have been used successfully for targeted delivery of chemotherapy drugs, loading of DNA or RNA has been poor. It is demonstrated that significant amounts of DNA can be encapsulated within PLGA-containing nanoparticles through the use of a new synthetic DNA analog, click nucleic acids (CNAs). First, triblock copolymers of PEG-CNA-PLGA are synthesized and then formulated into polymer nanoparticles from oil-in-water emulsions. The CNA-containing particles show high encapsulation of DNA complementary to the CNA sequence, whereas PEG-PLGA alone shows minimal DNA loading, and non-complementary DNA strands do not get encapsulated within the PEG-CNA-PLGA nanoparticles. Furthermore, the dye pyrene can be successfully co-loaded with DNA and lastly, a complex, larger DNA sequence that contains an overhang complementary to the CNA can also be encapsulated, demonstrating the potential utility of the CNA-containing particles as carriers for chemotherapy agents and gene silencers., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)