Exosome Structures Supported by Machine Learning Can Be Used as a Promising Diagnostic Tool

Principal component analysis (PCA) as a machine-learning technique could serve in disease diagnosis and prognosis by evaluating the dynamic morphological features of exosomes via Cryo-TEM-imaging. This hypothesis was investigated after the crude isolation of similarly featured exosomes derived from the extracellular vehicles (EVs) of immature dendritic cells (IDCs) JAWSII. It is possible to identify functional molecular groups by FTIR, but the unique physical and morphological characteristics of exosomes can only be revealed by specialized imaging techniques such as cryo-TEM. On the other hand, PCA has the ability to examine the morphological features of each of these IDC-derived exosomes by considering software parameters such as various membrane projections and differences in Gaussians, Hessian, hue, and class to assess the 3D orientation, shape, size, and brightness of the isolated IDC-derived exosome structures. In addition, Brownian motions from nanoparticle tracking analysis of EV IDC-derived exosomes were also compared with EV IDC-derived exosome images collected by scanning electron microscopy and confocal microscopy. Sodium-Dodecyl-Sulphate-Polyacrylamide-Gel-Electrophoresis (SDS-PAGE) was performed to separate the protein content of the crude isolates showing that no considerable protein contamination occurred during the crude isolation technique of IDC-derived-exosomes. This is an important finding because no additional purification of these exosomes is required, making PCA analysis both valuable and novel.     

Ideal Suggestions for Discharge Training and Telephone Counseling of Patients With Coronary Artery Bypass Graft Surgery: A Randomized Controlled and Experimental Study

BackgroundIn this context, discharge training and telephone counseling given to patients who underwent coronary artery bypass graft surgery increase the ability of patients to cope with and adapt to their self-care.MethodsThis study was a randomized controlled, experimental design. Both experimental and control groups consisted of 35 individuals with G*power analysis (n = 70). Patients in the experimental group were given discharge training and telephone counseling for two months. At the end of the process, data collection forms were administered to both groups for the last time. Necessary ethical approvals were taken and consent was taken from the patients.ResultsAfter the discharge training and telephone counseling given to the experimental group, the mean Exercise of Self-Care Agency Scale (ESCA) score of the patients increased by 13.94; the mean Coping and Adaptation Processing Scale (CAPS) increased by 13.6. The mean ESCA score of the control group increased by 7.86; the mean CAPS score increased by 9.14. The effect size that occurred for both groups was statistically significant (P < 0.05).ConclusionPositive results were achieved in the experimental group which received given discharge training and telephone counseling.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT05104996","term_id":"NCT05104996"}}NCT05104996     

Identification of RAD51–BRCA2 Inhibitors Using N-Acylhydrazone-Based Dynamic Combinatorial Chemistry

RAD51 is an ATP-dependent recombinase, recruited by BRCA2 to mediate DNA double-strand breaks repair through homologous recombination and represents an attractive cancer drug target. Herein, we applied for the first-time protein-templated dynamic combinatorial chemistry on RAD51 as a hit identification strategy. Upon design of N-acylhydrazone-based dynamic combinatorial libraries, RAD51 showed a clear templating effect, amplifying 19 N-acylhydrazones. Screening against the RAD51–BRCA2 protein–protein interaction via ELISA assay afforded 10 inhibitors in the micromolar range. Further ¹⁹F NMR experiments revealed that 7 could bind RAD51 and be displaced by BRC4, suggesting an interaction in the same binding pocket of BRCA2. These results proved not only that ptDCC could be successfully applied on full-length oligomeric RAD51, but also that it could address the need of alternative strategies toward the identification of small-molecule PPI inhibitors.     

Comment on “The effect of omalizumab on hematological and inflammatory parameters in patients with chronic spontaneous urticarial”: reply from authors

Abstract

We read Cosansu’s commentary entitled “Effectiveness of the new inflammatory parameters in patients with chronic spontaneous urticarial” to our study with great interest. The author remarked that a limited number of patients had C-reactive protein levels and it was not specified whether there were any other drugs used by the patients and no information was given about the severity of the disease in our study.     

Effects of subchronic exposure to zinc nanoparticles on tissue accumulation,serum biochemistry,and histopathological changes in tilapia (Oreochromis niloticus)

Zinc nanoparticles (ZnNPs) are among the least investigated NPs and thus their toxicological effects are not known. In this study, tilapia (Oreochromis niloticus) were exposed to 1 and 10 mg/L suspensions of small size (SS, 40–60 nm) and large size (LS, 80–100 nm) ZnNPs for 14 days under semi‐static conditions. Total Zn levels in the intestine, liver, kidney, gill, muscle tissue, and brain were measured. Blood serum glucose (GLU), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) were examined to elucidate the physiological disturbances induced by ZnNPs. Organ pathologies were examined for the gills, liver, and kidney to identify injuries associated with exposure. Significant accumulation was observed in the order of intestine, liver, kidney, and gills. Zn levels exhibited time‐ and concentration‐dependent increase in the organs. Accumulation in kidney was also dependent on particle size; NPs SS‐ZnNPs were trapped more effectively than LS‐ZnNPs. No significant accumulation occurred in the brain (p > 0.05) while Zn levels in muscle tissue increased only marginally (p ≥ 0.05). Significant disturbances were noted in serum GOT and LDH (p < 0.05). The GPT levels fluctuated and were not statistically different from those of controls (p > 0.05). Histopathological tubular deformations and mononuclear cell infiltrations were observed in kidney sections. In addition, an increase in melano‐macrophage aggregation intensity was identified on the 7th day in treatments exposed to LS‐ZnNPs. Mononuclear cell infiltrations were identified in liver sections for all treatments. Both ZnNPs caused basal hyperplasia in gill sections. Fusions appeared in the gills after the 7th day in fish treated with 10 mg/L suspensions of SS‐ZnNPs. In addition, separations in the secondary lamella epithelia were observed. The results indicated that exposure to ZnNPs could lead to disturbances in blood biochemistry and cause histopathological injuries in the tissues of O. niloticus. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1213–1225, 2017.     

Antibacterial activity of triclosan chitosan coated graft on hernia graft infection model

The use of mesh in hernia repair has become common, because of lower recurrence rate and simple application. Data from the meta-analysis and the multi-central studies support the use of meshes in hernia repair. One of the complications due to the hernia repair with mesh is the infection. The incidence range is between 1 and 10%. Triclosan embedded commercial absorbable suture materials are used to reduce surgical site infection rate. This study was planned on mesh infection model, because of the low incidence rate. The agent isolated from mesh infections was mostly Staphylococcus aureus and thus it was used as the infecting agent in this research. To achieve a better therapeutic efficacy, triclosan was formulated in chitosan gels. Chitosan is an attractive biopolymer because of its biocompatible, biodegradable, bioadhesive properties. Gel formulations using chitosans (low, medium and high molecular weight) were prepared in 1% (v/v) acetic acid solution and in vitro release profiles were evaluated. Gel formulations showed release profile extended up to 7 days and high molecular weight chitosan gel formulation was released higher quantity drug than other formulations. Meshes coated with triclosan loaded chitosan gel were used to reduce bacterial count and to prevent mesh infection in the study. 24 h and simultaneous bacteria inoculation was used to model mesh infection. The rats were observed for 8 days by means of surgical site infection. On the eighth day, the animals were sacrificed and the grafts were removed. Tissue squeezers were used to liberate bacterias from removed grafts. The isolated suspensions were cultured on blood agar plates and colony-forming units were counted overnight. Grafts coated with triclosan loaded chitosan gel presented satisfactory preventive effect against graft infection.     

A Long-Term Comparison of Presenting Characteristics of Children with Newly Diagnosed Type 1 Diabetes Before and During the COVID-19 Pandemic

Objective:Diabetic ketoacidosis (DKA) - a potentially preventable complication of type 1 diabetes mellitus (T1D) - is one of the most common chronic childhood diseases, and is associated with a significant risk of morbidity and mortality. The limited use of healthcare services due to fear of Coronavirus disease-2019 (COVID-19) transmission during the pandemic has raised concerns of delays in T1D diagnosis, among other diseases. This study investigated the presenting characteristics of newly diagnosed T1D patients assessed in a single clinic during the pandemic and compares them with the pre-pandemic period.Methods:For the purpose of this study, the first year of the pandemic is referred to as the “pandemic period”, and the previous three years as the “pre-pandemic period”. Patient files were reviewed retrospectively, the demographic and clinical characteristics and laboratory findings of the patients were recorded, and the findings from both periods were compared.Results:The number of patients diagnosed with T1D in the pandemic period was 44, and in the pre-pandemic period 39 in 2017, 22 in 2018 and 18 in 2019. The two groups had similar age, sex, pubertal stage and anthropometric characteristics (p>0.05). Regarding the type of presentation, the frequency of DKA was significantly higher in the pandemic period (68.2%) than in the pre-pandemic period (40.5%) (p=0.006), and this difference was also observed in the comparison by years (p=0.016). The duration of symptoms (16.5±10.7 vs. 23.5±17.6 days) and the length of hospital stay (10±3.9 vs. 15.2±5.5 days) were significantly shorter in the pandemic period (p=0.032, and p<0.001, respectively). There was no difference in the frequency of severe DKA between the pandemic (46.7%) and the pre-pandemic (37.5%) periods (p>0.05). However, pH (7.17±0.16 vs. 7.26±0.14) and bicarbonate (12.8±6.3 vs. 16.6±6.3) levels were significantly lower in the pandemic period (p<0.005). Additional signs of infection on admission were less frequent in the pandemic period (9.1%) than in the pre-pandemic period (27.8%) (p=0.027). The groups did not differ in terms of hemoglobin A1c, C-peptide, concurrent thyroid autoantibodies and tissue transglutaminase antibodies (p>0.05). The rate of anti-glutamic acid decarboxylase positivity was higher in the pandemic period (73.8% vs. 39.2%) (p=0.001) while the frequency of other diabetes-associated autoantibodies was similar between the groups (p>0.05). The polymerase chain reaction test for COVID-19 was negative in six patients with a history of contact.Conclusion:There was an increased frequency and severity of DKA in children with newly diagnosed T1D in the pandemic period, and these findings justify concerns related to the diagnosis of other diseases during the pandemic. Studies to raise awareness of diabetes symptoms during the pandemic should be continued regularly to reach all segments of society. Our study provides an additional contribution to the literature in its coverage of the one-year period during the pandemic and its comparison with the previous three years.