Exosomes biogenesis was increased in metformin-treated human ovary cancer cells; possibly to mediate resistance.

BACKGROUND: Exosomes derived from tumor cells contribute to the pathogenesis of cancers. Metformin, the most usually used drug for type 2 diabetes, has been frequently investigated for anticancer effects. Here, we examined whether metformin affects exosomes signaling in human ovary cancer cells in vitro. METHODS: Human ovary cancer cells, including A2780 and Skov3 cells, were treated with metformin for either 24-48 h. Cell viability and caspase-3 activity were determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and colorimetric assays respectively. Oil-Red-O staining and in vitro, scratch assays were used to examine cellular toxicity and wound healing rate. After treatment with metformin, exosomes were isolated from cells and quantified by acetylcholinesterase (AChE) assay, Dynamic Light Scattering (DLS), and their markers. Genes related to exosomes signaling were analyzed by real-time PCR or western blotting. RESULTS: Our results showed that metformin decreased the viability of both cells dose/time-dependently (P < 0.05). Metformin increased the activity of caspase-3 (P < 0.05) as well as the number of Oil-Red-O positive cells in both cell lines. In vitro scratch assay showed that the cell migration rate of metformin-treated cells was decreased (P < 0.05), whereas AChE activity of exosomes from metformin-treated cells was increased (P < 0.05). Concurrent with an increase in CD63 protein levels, expression of Alix, CD63, CD81, Lamp-2, and Rab27b up-regulated in treated cells (P < 0.05). CONCLUSION: Results indicated that metformin had a cytotoxic effect on ovary cancer cells and enhanced exosome biogenesis and secretion.

Tumor immune escape: extracellular vesicles roles and therapeutics application.

BACKGROUND: Immune escape, a process by which tumor cells evade immune surveillance, remains a challenge for cancer therapy. Tumor cells produce extracellular vesicles (EVs) that participate in immune escape by transferring bioactive molecules between cells. EVs refer to heterogeneous vesicles that participate in intercellular communication. EVs from tumor cells usually carry tumor antigens and have been considered a source of tumor antigens to induce anti-tumor immunity. However, evidence also suggests that these EVs can accelerate immune escape by carrying heat shock proteins (HSPs), programmed death-ligand 1 (PD-L1), etc. to immune cells, suppressing function and exhausting the immune cells pool. EVs are progressively being evaluated for therapeutic implementation in cancer therapies. EVs-based immunotherapies involve inhibiting EVs generation, using natural EVs, and harnessing engineering EVs. All approaches are associated with advantages and disadvantages. The EVs heterogeneity and diverse physicochemical properties are the main challenges to their clinical applications. SHORT CONCLUSION: Although EVs are criminal; they can be useful for overcoming immune escape. This review discusses the latest knowledge on EVs population and sheds light on the function of tumor-derived EVs in immune escape. It also describes EVs-based immunotherapies with a focus on engineered EVs, followed by challenges that hinder the clinical translation of EVs that are essential to be addressed in future investigations. Video Abstract.

A hierarchical deep learning approach for diagnosing impacted canine-induced root resorption via cone-beam computed tomography.

OBJECTIVES: Canine-induced root resorption (CIRR) is caused by impacted canines and CBCT images have shown to be more accurate in diagnosing CIRR than panoramic and periapical radiographs with the reported AUCs being 0.95, 0.49, and 0.57, respectively. The aim of this study was to use deep learning to automatically evaluate the diagnosis of CIRR in maxillary incisors using CBCT images. METHODS: A total of 50 cone beam computed tomography (CBCT) images and 176 incisors were selected for the present study. The maxillary incisors were manually segmented and labeled from the CBCT images by two independent radiologists as either healthy or affected by root resorption induced by the impacted canines. We used five different strategies for training the model: (A) classification using 3D ResNet50 (Baseline), (B) classification of the segmented masks using the outcome of a 3D U-Net pretrained on the 3D MNIST, (C) training a 3D U-Net for the segmentation task and use its outputs for classification, (D) pretraining a 3D U-Net for the segmentation and transfer of the model, and (E) pretraining a 3D U-Net for the segmentation and fine-tuning the model with only the model encoder. The segmentation models were evaluated using the mean intersection over union (mIoU) and Dice coefficient (DSC). The classification models were evaluated in terms of classification accuracy, precision, recall, and F1 score. RESULTS: The segmentation model achieved a mean intersection over union (mIoU) of 0.641 and a DSC of 0.901, indicating good performance in segmenting the tooth structures from the CBCT images. For the main classification task of detecting CIRR, Model C (classification of the segmented masks using 3D ResNet) and Model E (pretraining on segmentation followed by fine-tuning for classification) performed the best, both achieving 82% classification accuracy and 0.62 F1-scores on the test set. These results demonstrate the effectiveness of the proposed hierarchical, data-efficient deep learning approaches in improving the accuracy of automated CIRR diagnosis from limited CBCT data compared to the 3D ResNet baseline model. CONCLUSION: The proposed approaches are effective at improving the accuracy of classification tasks and are helpful when the diagnosis is based on the volume and boundaries of an object. While the study demonstrated promising results, future studies with larger sample size are required to validate the effectiveness of the proposed method in enhancing the medical image classification tasks.

Tumor cells-derived exosomal noncoding RNAs in cancer angiogenesis: Molecular mechanisms and prospective.

Exosomes, heterogeneous, membrane-bound nanoparticles that originated from eukaryotic cells, contribute to intracellular communication by transferring various biomolecules both on their surface and as internal cargo. One of the most significant current discussions on cancer progression is noncoding RNAs cargo of exosomes, which can regulate angiogenesis in tumor. A growing body of evidence shows that exosomes from tumor cells contain various microRNAs, long noncoding RNAs, and circular RNAs that can promote tumor progression by inducing angiogenesis. However, some noncoding RNAs may inhibit cancer angiogenesis. Targeting angiogenic noncoding RNA of exosomes may serve as a hopeful implement for cancer therapy. In this review, we discuss the latest knowledge of the roles of exosomal noncoding RNAs in tumor angiogenesis Understanding the biology of exosomal noncoding RNAs can help scientists plan exosomes-based innovations for the treatment of cancer angiogenesis and cancer biomarkers.

Management of pleural empyema in a 12-year-old obese patient with COVID-19: a pediatric case report.

BACKGROUND: With the ongoing coronavirus disease (COVID-19) pandemic, along with the development of new mutations of the virus and an increase in the number of cases among pediatrics, physicians should be aware and alerted on the atypical presentations of the disease, especially in less expected individuals. CASE PRESENTATION: Here we present a 12-year-old obese boy (BMI = 37.5 kg/m2) who presented with empyema, which was following SARS-CoV-2 infection. The patient had no history of fever. Due to the onset of dyspnea, a chest tube was inserted for him which was later altered to a pleural drainage needle catheter. CONCLUSION: Our case is the first report of COVID-19 presenting as empyema among pediatrics. Pleural empyema should be considered as a rare complication of COVID-19. Since there is still no guideline in the management of empyema in the context of COVID-19, delay in diagnosis and intervention may cause morbidity and mortality in children.

Evaluating physicians' perspectives on the efficiency and effectiveness of the electronic prescribing system.

BACKGROUND: The implementation of the electronic prescribing system follows certain objectives, and users' perspectives can contribute to understanding the efficiency and effectiveness of this system. This study aimed to evaluate physicians' perspectives on the efficiency and effectiveness of the electronic prescribing system. METHODS: This study was conducted on all physicians using the electronic prescribing system in clinics and hospitals affiliated with the treatment deputy of the Social Security Organization (SSO) in Sistan and Baluchistan Province in Iran. Data were collected using a self-administered questionnaire containing three sections: (i) Six items related to demographic data and clinical experience, (ii) Specific questions based on a five-point Likert scale-related physicians' perspectives about efficiency (19 questions) and effectiveness (13 questions), and (iii) Open-ended questions about the positive and negative aspects of using the electronic prescribing system. RESULTS: The mean and standard deviation of the efficiency and effectiveness of the electronic prescribing system were 3.68 ± 0.67 and 3.84 ± 0.65, respectively. Patient safety had the highest mean score among all dimensions (4.0 ± 0.64). Most participants (n = 55, 79%) considered the efficiency and effectiveness of this system high. More than 90 percent of the physicians (n = 63) believed that the electronic prescribing system enables a better medication prescription by providing alerts and access to patients' medication history. CONCLUSION: The findings showed that most physicians believed that the electronic prescribing system of Iran's SSO has high efficiency and effectiveness. In particular, physicians believed that using this system improves patient safety and reduces costs.

Confidentiality of Information Stored on the Desktop of Computers in a Psychiatric Hospital: Before and After an Intervention.

The aim of this before-after study was to evaluate the effect of an educational intervention on the confidentiality status of unprotected information stored on computer desktop in a psychiatric hospital. All switched-on computer systems were inspected in 2017-2018 at the baseline and 7 months after placing an educational poster. The log-in conditions and files stored on the desktop were reviewed using a researcher-made checklist; moreover, users answered questions about the possible mechanism of deleting information stored on the desktop. The number of files stored on desktops, the number of systems left switched on and unused, and the number of systems without a log-in password decreased in the second phase than the first phase of this study. Furthermore, automatic locking of computers after a specified period increased. The educational intervention reduced significantly the storage of information on desktops and improved security mechanisms such as using passwords and autolock. This study showed using an educational poster can encourage users to preserve the security of information, comply with security guidelines such as locking unused computers, and prevent access to confidential information.

In vitro and in vivo activity of cinnamaldehyde against Eimeria kofoidi in chukar partridge (Alectoris chukar).

One hundred and twenty one-day-old chukar partridges were randomly divided into eight groups which received diets with different supplementations. There were four unchallenged groups. One group received salinomycin (50 ppm), two groups received cinnamaldehyde (CINN) (100 and 200 mg/kg of diet), and another one received only the basal diet from the 1st to the 31st day. There were also four corresponding groups orally challenged by 3 × 105Eimeria kofoidi sporulated oocysts at the 21st day. Three samplings were done at the 24th, 26th, and 31st days of rearing for pathological and biochemical assessments. Fecal samples were daily taken to check the pattern of oocyst shedding from the 26th to 31st day. The body weight of birds was measured at 21st and 31st days. Along with the in vivo experiment, an in vitro sporulation inhibition test was carried out. The in vitro results showed that CINN decreased sporulation rate at 1 and 0.5 mg/ml. In vivo, it was found that CINN did not prevent the oocyst shedding. Furthermore, the histopathological findings revealed that CINN and salinomycin had no effect on infection establishment. However, our findings showed that CINN (200 mg/kg of diet) could enhance the body weight and improve antioxidant status. Although our results did not support the in vivo anticoccidial activity of CINN, it had a promising potential to improve antioxidant status and body weight in the chukar partridge.

Investigating the attitude of patients with chronic diseases about using mobile health.

BACKGROUND: Mobile health (mHealth) due to its popularity and accessibility can be widely applied in different health areas such as the management of chronic diseases. However, its success depends on the acceptance of their users. Therefore, the aim of this study was to survey the attitudes of patients with chronic disease toward mHealth technology and their willingness to use it. METHODS: This study was conducted within a 2-year period (2016-2018) to determine and compare the attitude and willingness of patients with asthma, diabetes, and multiple sclerosis (MS) toward using mHealth technology in a province in Iran. RESULTS: In total, 222 patients participated in this study. More than 93 percent of the patients with diabetes and MS, and 65 percent of the asthmatic patients preferred using mHealth services rather than consulting a physician (p < .0001). About 98, 94, and 49 percent of the MS, diabetic, and asthmatic patients, respectively felt comfortable if their health conditions checked by physicians through mHealth technology (p < .0001). CONCLUSIONS: Our results showed that the majority of the patients felt comfortable and preferred using mHealth technology rather than consulting the physicians. The attitudes of diabetic and MS patients toward mHealth technology were rather more positive compared to asthmatic patient attitude. These results may be helpful for the developers of mHealth technology, and researchers who design mHelath interventions for patients with chronic disease.

Investigating the satisfaction level of physicians in regards to implementing medical Picture Archiving and Communication System (PACS).

BACKGROUND: User satisfaction with PACS is considered as one of the important criteria for assessing success in using PACS. The objective of this study was to determine the level of user satisfaction with PACS and to compare its functional features with traditional film-based systems. METHODS: This study was conducted in 2017. Residents at three large university hospitals in Kerman filled-out a self-administered questionnaire consisting of three parts: demographic information of participants, user satisfaction with PACS, comparing features of the two digital and traditional imaging systems. The validity of this questionnaire was approved by five medical informatics, radiology, and health information management specialists and its reliability was confirmed by Cronbach's alpha (86%). Data were analyzed using descriptive statistics and the Spearman, Mann Whitney U and Kruskal-Wallis statistical tests. RESULTS: The mean of the participants' ages was 31.4 (±4.4) years and 59% of the participants were females. The mean of physicians' satisfaction with PACS' had no significant relationship with their age (P = 0.611), experience of using PACS (P = 0.301), specialty (P = 0.093), and percent of interpretation of images with PACS (P = 0.762). It had a significant relationship with the participants' computer skills (P = 0.022). CONCLUSIONS: The mean of physicians' satisfaction with PACS was at a moderate to a high level, yet there are still problems in the successful implementation of these systems and establishing interoperability between them. PACS has not fully met all the demands of physicians and has not achieved its predetermined objectives, such as all-access from different locations.