Notes

Enhancing the Leveling Probable regarding Lyophilization with regard to Extracellular Vesicles.
To observe the macular pigment (MP) appearances in eyes with macular hole (MH) and clarify the origin of the appearances. The mechanisms underlying the development of MH are discussed based on the observation of MP.

This observational case series included 33 eyes of 31 patients with MH who underwent vitrectomy. The MP optical density was measured using the two-wavelength fundus autofluorescence technique. The exact localization of MP was evaluated by comparing MP distribution images and optical coherent tomography B-scan images.

MP was missing at the MH. The area of the MP defect corresponded with the area of the defect of outer plexiform layer. MP was present in the retinal flap in stage 2 MH that included glia (Müller cells) and plexiform layers and in the operculum in stage 3 MH, which mainly comprised Müller cells. Cystic spaces in the outer plexiform layer surrounding stage 3 and 4 MHs showed a honeycomb appearance on MP images. MP reappeared to form an irregularly shaped pigment plane after surgical closure of MH. The MP optical volume did not change before and after surgery. Fellow eyes with a central dip in MP distribution subsequently developed MH.

The characteristic appearances of MP at the MH were attributed to MP in the plexiform layers and Müller cell cones. A central dip of MP distribution might be a sign of Müller cell cone damage that proceeds with MH formation.

Observation of MP was useful for understanding the mechanisms of MH formation.
Observation of MP was useful for understanding the mechanisms of MH formation.
The purpose of this study was to propose a new algorithm for the segmentation and thickness measurement of pathological corneas with irregular layers using a two-stage graph search and ray tracing.

In the first stage, a graph, with only gradient edge-cost, is used to segment the air-epithelium and endothelium-aqueous boundaries. In the second stage, a graph, with gradient, directional, and multiplier edge-cost, is used to correct segmentation. The optical coherence tomography (OCT) image is flattened using the air-epithelium boundary and a graph search is used to segment the epithelium-Bowman's and Bowman's-stroma boundaries. Then, the OCT image is flattened using the endothelium-aqueous boundary and a graph search is used to segment the Descemet's membrane. Ray tracing is used to correct the inter-boundary distances, then the thickness is measured using the shortest distance. The proposed algorithm was trained and evaluated using 190 OCT images manually segmented by trained operators.

The mean and standard deviation of the unsigned errors of the algorithm-operator and inter-operator were 0.89 ± 1.03 and 0.77 ± 0.68 pixels in segmentation and 3.62 ± 3.98 and 2.95 ± 2.52 µm in thickness measurement.

Our proposed algorithm can produce accurate segmentation and thickness measurements compared with the manual operators.

Our algorithm could be potentially useful in the clinical practice.
Our algorithm could be potentially useful in the clinical practice.
COVID-19 has placed a huge burden on healthcare systems which has led to widespread cancellation elective surgical care. Ireland is recovering from the first wave of COVID-19 and as such the expeditious return of elective surgical care is important. This is the first study to examine the attitudes of patients to undergoing total joint arthroplasty during the COVID-19 crisis.

A prospective qualitative study was undertaken in our institution during the week 13/05/2020-20/05/2020. 65 patients completed a questionnaire assessing attitudes, awareness, and behavioral changes associated with COVID-19, a Charlson Comorbidity Index, modified-Harris Hip Score, and a Short Form-12 score.

86% of patients felt that they were at little to no risk of COVID-19 infection. The majority of patients were happy to proceed with surgery at the current level of COVID-19 related threat (86%). Patients with higher mHHS were more likely to postpone their operation than those with lower mHHS scores. Our cohort had low patient reported outcome measures in both mHHS and SF-12, indicating the significant burden of hip osteoarthritis on both physical and mental health.

Patients reported a significant disease-related impairment of physical function and subsequent deterioration in mental health as a result of hip osteoarthritis. Patients with worse hip function, as measured by the mHHS are more willing to proceed with surgery than those with superior hip function. This offers a potential mechanism by which to triage patients once elective surgical pathways reopen in the coming months.
Patients reported a significant disease-related impairment of physical function and subsequent deterioration in mental health as a result of hip osteoarthritis. Patients with worse hip function, as measured by the mHHS are more willing to proceed with surgery than those with superior hip function. This offers a potential mechanism by which to triage patients once elective surgical pathways reopen in the coming months.Homeostasis of the biogenic polyamines spermine (Spm) and spermidine (Spd), present in μM-mM concentrations in all eukaryotic cells, is precisely regulated by coordinated activities of the enzymes of polyamine synthesis, degradation, and transport, in order to sustain normal cell growth and viability. Spermine oxidase (SMOX) is the key and most recently discovered enzyme of polyamine metabolism that plays an essential role in regulating polyamine homeostasis by catalyzing the back-conversion of Spm to Spd. The development of many types of epithelial cancer is associated with inflammation, and disease-related inflammatory stimuli induce SMOX. MDL72527 is widely used in vitro and in vivo as an irreversible inhibitor of SMOX, but it is also potent towards N1-acetylpolyamine oxidase. Although SMOX has high substrate specificity, Spm analogues have not been systematically studied as enzyme inhibitors. Here we demonstrate that 1,12-diamino-2,11-bis(methylidene)-4,9-diazadodecane (2,11-Met2-Spm) has, under standard assay conditions, an IC50 value of 169 μM towards SMOX and is an interesting instrument and lead compound for studying polyamine catabolism.A series of uracil derivatives containing a 4-oxoquinazoline fragment bound to the nitrogen atom N3 of the pyrimidine ring by a short methylene bridge was synthesized to search for new antiviral agents. Some compounds in this series are shown to exhibit high inhibitory activity against human cytomegalovirus and the varicella zoster virus in a HEL cell culture.At early stages of carcinogenesis, the regulatory regions of some tumor suppressor genes become aberrantly methylated at RCGY sites, which are substrates of DNA methyltransferase Dnmt3. Identification of aberrantly methylated sites in tumor DNA is considered to be the first step in the development of epigenetic PCR test systems for early diagnosis of cancer. Recently, we have developed a GLAD-PCR assay, a method for detecting the R(5mC)GY site in the genome position of interest even at significant excess of DNA molecules with a non-methylated RCGY site in this location. The aim of the present work is to use the GLAD-PCR assay to detect the aberrantly methylated R(5mC)GY sites in the regulatory regions of tumor suppressor genes (brinp1, bves, cacna2d3, cdh11, cpeb1, epha7, fgf2, galr1, gata4, hopx, hs3st2, irx1, lrrc3b, pcdh10, rprm, runx3, sfrp2, sox17, tcf21, tfpi2, wnt5a, zfp82, and znf331) in DNA samples obtained from gastric cancer (GC) tissues. The study of the DNA samples derived from 29 tumor and 25 normal gastric tissue samples demonstrated a high diagnostic potential of the selected RCGY sites in the regulatory regions of the irx1, cacna2d3, and epha7 genes; the total indices of sensitivity and specificity for GC detection being 96.6% and 100%, respectively.The Middle East Respiratory Syndrome (MERS) is an acute inflammatory disease of the respiratory system caused by the MERS-CoV coronavirus. The mortality rate for MERS is about 34.5%. Due to its high mortality rate, the lack of therapeutic and prophylactic agents, and the continuing threat of the spread of MERS beyond its current confines, developing a vaccine is a pressing task, because vaccination would help limit the spread of MERS and reduce its death toll. We have developed a combined vector vaccine for the prevention of MERS based on recombinant human adenovirus serotypes 26 and 5. 4ChloroDLphenylalanine Studies of its immunogenicity have shown that vaccination of animals (mice and primates) induces a robust humoral immune response that lasts for at least six months. Studies of the cellular immune response in mice after vaccination showed the emergence of a specific CD4+ and CD8+ T cell response. A study of the vaccine protectivity conducted in a model of transgenic mice carrying the human DPP4 receptor gene showed that our vaccination protected 100% of the animals from the lethal infection caused by the MERS-CoV virus (MERS-CoV EMC/2012, 100LD50 per mouse). Studies of the safety and tolerability of the developed vaccine in rodents, rabbits, and primates showed a good safety profile and tolerance in animals; they revealed no contraindications for clinical testing.Today, it has become apparent that innovative treatment methods, including those involving simultaneous diagnosis and therapy, are particularly in demand in modern cancer medicine. The development of nanomedicine offers new ways of increasing the therapeutic index and minimizing side effects. The development of photoactivatable dyes that are effectively absorbed in the first transparency window of biological tissues (700-900 nm) and are capable of fluorescence and heat generation has led to the emergence of phototheranostics, an approach that combines the bioimaging of deep tumors and metastases and their photothermal treatment. The creation of near-infrared (NIR) light-activated agents for sensitive fluorescence bioimaging and phototherapy is a priority in phototheranostics, because the excitation of drugs and/or diagnostic substances in the near-infrared region exhibits advantages such as deep penetration into tissues and a weak baseline level of autofluorescence. In this review, we focus on NIR-excited dyes and discuss prospects for their application in photothermal therapy and the diagnosis of cancer. Particular attention is focused on the consideration of new multifunctional nanoplatforms for phototheranostics which allow one to achieve a synergistic effect in combinatorial photothermal, photodynamic, and/or chemotherapy, with simultaneous fluorescence, acoustic, and/or magnetic resonance imaging.This study reviews the findings of recent experiments designed to investigate the cytokine profile after a spinal cord injury. The role played by key cytokines in eliciting the cellular response to trauma was assessed. The results of the specific immunopathogenetic interaction between the nervous and immune systems in the immediate and chronic post-traumatic periods are summarized. It was demonstrated that it is reasonable to use the step-by-step approach to the assessment of the cytokine profile after a spinal cord injury and take into account the combination of the pathogenetic and protective components in implementing the regulatory effects of individual cytokines and their integration into the regenerative processes in the injured spinal cord. This allows one to rationally organize treatment and develop novel drugs.
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