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An imbalance between regulatory T (Treg) and T-helper (Th)-17 cells has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) exert immunomodulatory properties through secreting exosomes. This study aimed to assess the effect of MSC-derived exosomes (MSC-Exo) on the differentiation of peripheral blood mononuclear cells (PBMCs) into  Tregs from patients with COVID-19. Exosomes were isolated from adipose tissue-derived MSCs. PBMCs were separated from the whole blood of COVID-19 patients (n=20). Treg frequency was assessed before and 48 hours after treatment of PBMCs with MSC-Exo using flow cytometry. Expression of FOXP3 and cytokine genes, and the concentration of cytokines associated with Tregs, were assessed before and after treatment with MSC-Exo. The frequency of CD4+CD25+CD127-  Tregs was significantly higher after treating PBMCs with MSC-Exo (6.695±2.528) compared to before treatment (4.981±2.068). The expressions of transforming growth factor (TGF)-β1, interleukin (IL)-10, and FOXP3 were significantly upregulated in MSC-Exo-treated PBMCs. The concentration of IL-10 increased significantly after treatment (994.7±543.9 pg/mL) of PBMCs with MSC-Exo compared with before treatment (563.5±408.6 pg/mL). The concentration of TGF-β was significantly higher in the supernatant of PBMCs after treatment with MSC-Exo (477.0±391.1 pg/mL) than PBMCs before treatment (257.7±226.3 pg/mL). MSC-Exo has the potential to raise anti-inflammatory responses by induction of  Tregs, potentiating its therapeutic effects in COVID-19.

Background: In Iran, tracking of patients and its associated data recording in private healthcare centers are poor, and thus a majority of patients suffering from Covid-19 are treated without any control on the isolation and quarantine processes. The present study aims to investigate the factors contributed to referral to private or public healthcare centers that provide Covid-19 care services., Methods: This cross-sectional study was conducted from November 2021 to January 2022 in Tabriz, Iran. We invited a total of 258 and 202Covid-19 patients from governmental and private healthcare centers, respectively, to participate in the study by convenient sampling method. Applying a self-administered questionnaire, we collected data on the reason of referring to the healthcare centers, patient's waiting time, quality of healthcare services received by the patients, patients' level of satisfaction, accessibility, insurance coverage, perceived severity of the disease, and the level of staff compliance from health protocols. Logistic regression model was used for data analysis by using SPSS-26 software., Results: Adjusted for other variables, higher socio-economic status (AOR (Adjusted Odds Ratio) = 6.64), older age (AOR = 1.02), referral of friends and family members (AOR = 1.52), shorter waiting time (AOR = 1.02) and higher satisfaction (AOR = 1.02) were contributed to referral to private centers. Better accessibility (AOR = 0.98) and wider insurance coverage (AOR = 0.99) were also contributed to referral to governmental centers., Conclusion: Providing more appropriate insurance coverage by private healthcare centers, and promoting their level of accessibility seems to promote patients' referral to such centers. Moreover, establishing an accurate system for recording patients' information and follow up in private centers might promote the role of private healthcare centers in managing the overload of patients on healthcare system during such epidemics., (© 2023. The Author(s).)

Statement of the Problem: Mast cells are round to elliptical cells that originate from bone marrow stem cells and enter the peripheral blood. By releasing inflammatory mediators, these cells are involved in type I hypersensitivity, wound healing, defense against pathogens, increased blood vessel formation, and destruction of the extracellular matrix. There are contradictory results regarding the role of mast cells in tumor lesions., Purpose: Considering the contradictory results and few studies on the density of mast cells in salivary tumors, the present study investigated and compared the density of mast cells in two common salivary gland tumors., Materials and Method: In the cross-sectional study after reviewing the records of patients referred to the Pathology Department of the School of Dentistry and Shahid Sadoughi Hospital in Yazd, 15 blocks of each of the mucoepidermoid carcinoma and pleomorphic adenoma tumors were taken. After Giemsa staining of the samples, the average of stained cells in 10 random fields under 400× magnification was counted. The results were analyzed using statistical tests of t-test, ANOVA, Chi-square, and Mann-Whitney in SPSS ver. 22., Results: The average mast cell counts in pleomorphic adenoma (4.2) was higher than muco-epidermoid carcinoma (1.7) but there was no significant relationship ( p = 0.305). In mucoepidermoid carcinoma, the numbers of mast cells increased with increasing tumor grade (low: 0/467 moderate: 1/567 high: 2/983) and there was a significant relationship ( p = 0.009)., Conclusion: According to the results of the present study, it seems that the mast cells accumulation may be secondarily associated with inflammatory responses due to cell accumulation and tissue destruction by tumor cells., Competing Interests: Authors declare that there are no conflicts of interest in this study., (Copyright: © Journal of Dentistry.)

Objectives: Migraine is a common disorder in children, and its prophylaxis with minimal side effects is momentous. This study aimed to compare the efficacy of Pregabalin and Sodium Valproate in preventing migraine attacks., Material & Methods: Sixty-four children (aged 6-18) with migraines were recruited, as defined by Internation Headache Criteria (ICHD-III). They were randomly assigned to two groups: Sodium Valproate (n=32) and Pregabalin (n=32). The minimum dosage of drugs was prescribed in both groups. The patients were followed for four months. The parameters such as frequency, intensity, duration of migraine attacks, and the number of painkillers that the patients used monthly were recorded. The Spence Children's anxiety scale was also used to evaluate medications' effect on patients' anxiety levels., Results: Two medications were equally effective in reducing the intensity and duration of attacks. Additionally, their effect on reducing the anxiety level of patients was equal. There was a significant difference between the effect of drugs on the frequency of migraine attacks at the end of the first and fourth months and the number of painkillers used at the end of the fourth month. The frequency of attacks was decreased by more than 50% in twenty-eight patients (90%) of Pregabalin recipients and twenty-one patients (84%) of Sodium Valproate recipients., Conclusion: Considering the better effect of Pregabalin in the reduction of frequency of migraine attacks and pain-reducing medications consumption, Pregabalin could be a proper substitute for Sodium Valproate for prophylactic migraine treatment in children., Competing Interests: The authors declared no conflict of interest.

Rationale: Craniofacial and pharyngeal morphology influences risk for obstructive sleep apnea (OSA). Quantitative photography provides phenotypic information about these anatomical factors and is feasible in large samples. However, whether associations between morphology and OSA severity differ among populations is unknown. Objectives: The aim of this study was to examine this question in a large sample encompassing people from different ancestral backgrounds. Methods: Participants in SAGIC (Sleep Apnea Global Interdisciplinary Consortium) with genotyping data were included ( N  = 2,393). Associations between photography-based measures and OSA severity were assessed using linear regression, controlling for age, sex, body mass index, and genetic ancestry. Subgroups (on the basis of 1000 Genomes reference populations) were identified: European (EUR), East Asian, American, South Asian, and African (AFR). Interaction tests were used to assess if genetically determined ancestry group modified these relationships. Results: Cluster analysis of genetic ancestry proportions identified four ancestrally defined groups: East Asia (48.3%), EUR (33.6%), admixed (11.7%; 46% EUR, 27% Americas, and 22% AFR), and AFR (6.4%). Multiple anatomical traits were associated with more severe OSA independent of ancestry, including larger cervicomental angle (standardized β [95% confidence interval (CI)] = 0.11 [0.06-0.16]; P  < 0.001), mandibular width (standardized β [95% CI] = 0.15 [0.10-0.20]; P  < 0.001), and tongue thickness (standardized β [95% CI] = 0.06 [0.02-0.10]; P  = 0.001) and smaller airway width (standardized β [95% CI] = -0.08 [-0.15 to -0.002]; P  = 0.043). Other traits, including maxillary and mandibular depth angles and lower face height, demonstrated different associations with OSA severity on the basis of ancestrally defined subgroups. Conclusions: We confirm that multiple facial and intraoral photographic measurements are associated with OSA severity independent of ancestral background, whereas others differ in their associations among the ancestrally defined subgroups.

Background: Retinopathy of diabetes is a chronic diabetes mellitus complication affecting retinal vessels, and some ocular complications' molecular mechanisms remain obscure., Objective: To evaluate the expression of HLA-G1, HLA-G5, miRNA-181a, and miRNA-34a in the lens epithelial cells of patients with retinopathy of diabetes., Methods: In a case-control study, 30 diabetic patients with retinopathy, 30 diabetic patients without retinopathy, and 30 cataract patients without diabetes mellitus as the control group were enrolled after a full description with details about the study methods and objectives. The expression of HLA G1, HLA G5, miRNA-181a, and miRNA-34a in lens epithelial cells was assessed by quantitative RT PCR. Moreover, the levels of HLA-G protein in aqueous humor were evaluated by the ELISA method., Results: HLA-G1 expression was significantly upregulated in the retinopathy group (P=0.003). The aqueous humor of diabetic retinopathy patients contained significantly higher levels of HLA-G protein compared with the non-diabetic patients (P=0.001). miRNA-181a was significantly downregulated in the diabetic retinopathy group compared with the patients without diabetes (P=0.001). In addition, miRNA-34a was upregulated in the retinopathy group (P=0.009)., Conclusion: Taken together, the present results showed that HLA-G1 and miRNA-34a can be valuable markers for diabetic retinopathy. Our data offers new perspectives for improving the control of inflammation in the lens epithelial cells by considering HLA-G and miRNA.

Background: Dental caries is a disease which is caused by the acidic by-products of the metabolic processes of dental plaque. Silver components are one of the clinical solutions to prevent caries. This study aimed to investigate the effect of silver diamine fluoride (SDF) application on the shear bond strength of glass ionomer to primary teeth enamel., Materials and Methods: In this in vitro study, a total of 48 anterior sound primary teeth were randomly divided into four groups ( n = 12). The control group (G1) consisted of healthy primary teeth, and the three experimental groups (G2-G4) were composed of demineralized primary teeth. The second group did not undergo SDF treatment, the third group underwent SDF treatment, and the fourth group underwent SDF treatment plus polishing. Glass ionomer cylinders were bonded to all specimens and subsequently tested by a universal testing machine to measure the glass ionomer shear bond strength. The type of fracture was examined by a stereomicroscope. Data analysis was carried out using the SPSS 22 statistical software. Data were analyzed by one-way analysis of variance and posthoc Tukey tests (α =0.05)., Results: The mean shear bond strength of the glass ionomer was significantly higher in the control group than in the other three groups ( P < 0.05). The mean shear bond strength of glass ionomer was significantly higher in the SDF-treated group than in the non-SDF treated and SDF-treated and polished groups ( P < 0.05)., Conclusion: Although the glass ionomer bond strength to sound enamel was higher than other groups by a significant margin, the application of SDF increases the shear bond strength of the glass ionomer to remineralized white spot enamel in primary teeth., Competing Interests: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or nonfinancial in this article., (Copyright: © 2023 Dental Research Journal.)

Purslane ( Portulaca oleracea L .) is a herbal remedy with wide range of pharmaceutic properties. Although the beneficial effect of purslane on the treatment of Type 2 Diabetes Mellitus (T2DM) has been shown, there is an inconsistency among the results of previous studies. Therefore, this study is aimed at conducting a systematic review and meta-analysis on the effect of purslane on glycemic profile and oxidative stress markers. A systematic search was performed in the Scopus, Web of science, PubMed and the Cochrane Library to find articles related to the effect of the purslane on Malondialdehyde (MDA) and Total Antioxidant Capacity (TAC), Fasting Blood Sugar (FBS), Hemoglobin A1c (HbA1c), insulin resistance, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) up to September 2022. Among the 611 initial studies that were identified from searching electronic databases, 16 Randomized Clinical Trials (RCTs) involving 1122 participants (557 cases and 565 controls) were included for data analysis. The results of random-effects modeling demonstrated that purslane consumption significantly reduced FBS ( p  < .001), MDA ( p  < .001) and increased TAC ( p  < .001). However, purslane consumption did not affect HbA1c ( p  < .109), fasting insulin ( p  = .298) and HOMA-IR ( p  = .382). Meta-analyses were performed using both the random- and fixed-effects model where appropriate, and I 2 index was used to evaluate the heterogeneity. This meta-analysis study suggests that purslane has beneficial effects on oxidative stress markers and glycemic parameter. Therefore, it may be a promising adjuvant therapy in T2DM because of its benefits and negligible adverse effects., Competing Interests: The authors declared that there is no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

One important area for consideration especially in terms of combating the ongoing never ending opioid crisis, relates to novel newer assessments for all addictive behaviors both substance and non-substance behaviors (RDS). It is very important to identify early in one's life the possibility of, because of known DNA antecedents, the presence of pre-addiction. The development of the Genetic Addiction Risk Severity (GARS) test, Blum's group believes that this type of testing should be the "standard of care" following additional studies. Understandably that while polymorphisms in the Mu-Opioid receptor (MOR) is of real concern in terms of setting people up for predisposition to opioid dependence, the genetic and epigenetic status of dopaminergic function must be considered as well. While this sounds bold (which it is) the results should be protected by the G.I. N. A. law enacted in the USA in 2011. One avenue of further investigation, instead of providing powerful opioids for opioid dependence, is to seek out non-addictive alternatives. Accordingly, other non-addictive modalities including genetic guided KB220 (amino-acid-enkephalinase-N-acetylcysteine-NAD), non-invasive rTMS for psychiatry and pain, epigenetic remodeling, gene edits, non-invasive H-wave for pain management and enhanced functionality, brain spotting, cognitive behavioral therapy awarenesss integration therapy, NUCALM, trauma therapy, awareness tools, genograms, exercise, sports, fitness programs (one hour per day), light therapy and even laughing therapy as well as any other known modalities that can induce reward symmetry. While the short term use of opioids for opioid dependence to reduce harm is certainly acceptable, clinicians should consider a better long-term plan., Competing Interests: Conflict of Interest K.B. is a consultant for Electronic Waveform Lab Inc. Other authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

It is with a saddened heart that we are dedicating this article to the loving memory of our dear departed friend and associate B. William Downs. Bill was well known in the nutritional space worldwide for his major contributions to the health and welfare of millions around the globe. The founder of Victory Nutrition International (VNI) in conjunction with Kim Downs, as well as so many contributions to scientific literature, to those that knew him personally will forever be touched. Bill was a highly spirited human with a never ending love for caring and helping so many individuals. To know Bill is to walk in the face of a music lover playing drums, trained as a martial artist, and riding through the winds of a Beamer driven by an iconic man driven to victory. Our hearts may be saddened but Bills spirit to those that know him will be forever. In this article we discuss and review some potential futuristic concepts and technological advancements in terms of geneospirituality engineering to help prevent relapse and or even protect against an unwanted predisposition to RDS behaviors. Futuristic development may contribute to an attenuation of both DNA antecedents as well as epigenetic reward system insults leading to unwanted substance and non-substance addictive behaviors.

Marine invertebrates are multicellular organisms consisting of a wide range of marine environmental species. Unlike vertebrates, including humans, one of the challenges in identifying and tracking invertebrate stem cells is the lack of a specific marker. Labeling stem cells with magnetic particles provides a non-invasive, in vivo tracking method using MRI. This study suggests antibody-conjugated iron nanoparticles (NPs), which are detectable with MRI for in vivo tracking, to detect stem cell proliferation using the Oct4 receptor as a marker of stem cells. In the first phase, iron NPs were fabricated, and their successful synthesis was confirmed using FTIR spectroscopy. Next, the Alexa Fluor anti-Oct4 antibody was conjugated with as-synthesized NPs. Their affinity to the cell surface marker in fresh and saltwater conditions was confirmed using two types of cells, murine mesenchymal stromal/stem cell culture and sea anemone stem cells. For this purpose, 106 cells of each type were exposed to NP-conjugated antibodies and their affinity to antibodies was confirmed by an epi-fluorescent microscope. The presence of iron-NPs imaged with the light microscope was confirmed by iron staining using Prussian blue stain. Next, anti-Oct4 antibodies conjugated with iron NPs were injected into a brittle star, and proliferating cells were tracked by MRI. To sum up, anti-Oct4 antibodies conjugated with iron NPs not only have the potential for identifying proliferating stem cells in different cell culture conditions of sea anemone and mouse cell cultures but also has the potential to be used for in vivo MRI tracking of marine proliferating cells.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which has emerged as a global health crisis. Recently, more than 50 different types of potential COVID-19 vaccines have been developed to elicit a strong immune response against SARS-CoV-2. However, genetic mutations give rise to the new variants of SARS-CoV-2 which is highly associated with the reduced effectiveness of COVID-19 vaccines. There is still no efficient antiviral agent to specifically target the SARS-CoV-2 infection and treatment of COVID-19. Therefore, understanding the molecular mechanisms underlying the pathogenesis of SARS-CoV-2 may contribute to discovering a novel potential therapeutic approach to the management of COVID-19. Recently, extracellular vesicle (EV)-based therapeutic strategies have received great attention on account of their potential benefits in the administration of viral diseases. EVs are extracellular vesicles containing specific biomolecules which play an important role in cell-to-cell communications. It has been revealed that EVs are involved in the pathogenesis of different inflammatory diseases such as cancer and viral infections. EVs are released from virus-infected cells which could mediate the interaction of infected and uninfected host cells. Hence, these extracellular nanoparticles have been considered a novel approach for drug delivery to mediate the treatment of a wide range of diseases including, COVID-19. EVs are considered a cell-free therapeutic strategy that could ameliorate the cytokine storm and its complications in COVID-19 patients. Furthermore, EV-based cargo delivery such as immunomodulatory agents in combination with antiviral drugs may have therapeutic benefits in patients with SARS-CoV-2 infection. In this review, we will highlight the potential of EVs as a therapeutic candidate in the diagnosis and treatment of COVID-19. Also, we will discuss the future perspectives regarding the beneficial effects of Evs in the development of COVID-19 vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Electroencephalography (EEG) signals are considered one of the oldest techniques for detecting disorders in medical signal processing. However, brain complexity and the non-stationary nature of EEG signals represent a challenge when applying this technique. The current paper proposes new geometrical features for classification of seizure (S) and seizure-free (SF) EEG signals with respect to the Poincaré pattern of discrete wavelet transform (DWT) coefficients. DWT decomposes EEG signal to four levels, and thus Poincaré plot is shown for coefficients. Due to patterns of the Poincaré plot, novel geometrical features are computed from EEG signals. The computed features are involved in standard descriptors of 2‑D projection (STD), summation of triangle area using consecutive points (STA), as well as summation of shortest distance from each point relative to the 45-degree line (SSHD), and summation of distance from each point relative to the coordinate center (SDTC). The proposed procedure leads to discriminate features between S and SF EEG signals. Thereafter, a binary particle swarm optimization (BPSO) is developed as an appropriate technique for feature selection. Finally, k-nearest neighbor (KNN) and support vector machine (SVM) classifiers are used for classifying features in S and SF groups. By developing the proposed method, we have archived classification accuracy of 99.3 % with respect to the proposed geometrical features. Accordingly, S and SF EEG signals have been classified. Also, Poincaré plot of SF EEG signals has more regular geometrical shapes as compared to S group. As a final remark, we notice that the Poincaré plot of coefficients in S EEG signals has occupied more space as compared to SF EEG signals (Tab. 3, Fig. 11, Ref. 57). Text in PDF www.elis.sk Keywords: EEG signal, DWT, Poincaré plot, geometrical feature, BPSO, SVM, KNN.

In the USA alone, opioid use disorder (OUD) affects approximately 27 million people. While the number of prescriptions may be declining due to increased CDC guidance and prescriber education, fatalities due to fentanyl-laced street heroin are still rising. Our laboratory has extended the overall concept of both substance and non-substance addictive behaviors, calling it "Reward Deficiency Syndrome (RDS)." Who are its victims, and how do we get this unwanted disorder? Is RDS caused by genes (Nature), environment (Neuro-epigenetics, Nurture), or both? Recent research identifies resting-state functional connectivity in the brain reward circuitry as a crucial factor. Analogously, it is of importance to acknowledge that the cumulative discharge of dopamine, governed by the nucleus accumbens (NAc) and modulated by an array of additional neurotransmitters, constitutes a cornerstone of an individual's overall well-being. Neuroimaging reveals that high-risk individuals exhibit a blunted response to stimuli, potentially due to DNA polymorphisms or epigenetic alterations. This discovery has given rise to the idea of a diminished 'thrill,' though we must consider whether this 'thrill' may have been absent from birth due to high-risk genetic predispositions for addiction. This article reviews this issue and suggests the general concept of the importance of "induction of dopamine homeostasis." We suggest coupling a validated genetic assessment (e.g., GARS) with pro-dopamine regulation (KB220) as one possible frontline modality in place of prescribing potent addictive opioids for OUD except for short time harm reduction. Could gene editing offer a 'cure' for this undesirable genetic modification at birth, influenced by the environment and carried over generations, leading to impaired dopamine and other neurotransmitter imbalances, as seen in RDS? Through dedicated global scientific exploration, we hope for a future where individuals are liberated from pain and disease, achieving an optimal state of well-being akin to the proverbial 'Garden of Eden'., Competing Interests: Conflict of Interest Dr. Kenneth Blum is the inventor of both GARS and KB220 which has been assigned to Transplicegen Holdings, Inc. There are no other conflicts of interest.

Background: Considering the important role of fluoride in preventing caries by reducing the number and activity of cariogenic bacteria and introducing new fluoride-releasing tooth-colored restorative materials, this study was performed to compare and evaluate fluoride ion release and antibacterial activity of resin-modified GI, zirconomer, giomer (Beautifil), and Cention N., Materials and Methods: In this experimental in vitro study, eighty samples (20 samples in each group) were prepared, 10 samples for fluoride testing and 10 samples for antibacterial activity. To evaluate the release of fluoride (PPM), fluoride ion-selective electrode was used on days 1 st , 3 rd , 7 th , 14 th , and 21 st ; and antibacterial activities against Streptococcus mutans were examined using direct contact test by absorption of light hourly once every 5 h and days 1 st , 2 nd , and 7 th using an ELISA reader with a microplate reader of 800 TS at a wavelength of 630 nm. The results were analyzed using one-way ANOVA, Tamhane post hoc test, and paired t -test in SPSS software (IBM, Somers, NJ, USA) at a significant level of ( P < 0.05)., Results: The release of fluoride from materials showed a statistically significant difference ( P < 0.001). The maximum mean of fluoride released during the 1 st , 3 rd and 7 th days belonged to the zirconomer group and the minimum for the giomer group. During the measurement period of light absorption from 0 to 24 h after planting, light absorption of foursubstances together was found to be statistically significant ( P <.001). Zirconomer light absorption increased on the 7 th day, unlike other substances, but still, the minimum light absorption was related to zirconomer., Conclusion: The highest fluoride release was in zirconomer, Cention N, fuji II LC, and giomer, sequentially. Zirconomer showed maximum and giomer showed minimum antibacterial activities., Competing Interests: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or non-financial in this article., (Copyright: © 2022 Dental Research Journal.)

Thalassemia syndromes are the most prevalent monogenic hemoglobinopathy in the world. In Iran, thalassemia is a public health problem because this country has been located on the thalassemia belt. In recent decades, considering that the life expectancy of patients with thalassemia has dramatically improved, some unrecognized complications have emerged in these individuals. One of these complications is a hypercoagulable state that may lead to thromboembolic events (TEE). The TEE may involve any organ in the body, including the central nervous system. Ischemic cerebrovascular events in thalassemic patients have been divided into two categories, namely overt stroke and silent cerebral infarcts (SCI). Overt stroke often develops in patients with beta-thalassemia major; however, patients with thalassemia intermedia usually suffer from SCI. This review article discusses brain vascular involvement., Competing Interests: The author has no conflict of interest with the subject matter of the present study.

Comorbid Type 2 diabetes (T2D), a metabolic complication of obesity, associates with worse cancer outcomes for prostate, breast, head and neck, colorectal and several other solid tumors. However, the molecular mechanisms remain poorly understood. Emerging evidence shows that exosomes carry miRNAs in blood that encode the metabolic status of originating tissues and deliver their cargo to target tissues to modulate expression of critical genes. Exosomal communication potentially connects abnormal metabolism to cancer progression. Here, we hypothesized that T2D plasma exosomes induce epithelial-mesenchymal transition (EMT) and immune checkpoints in prostate cancer cells. We demonstrate that plasma exosomes from subjects with T2D induce EMT features in prostate cancer cells and upregulate the checkpoint genes CD274 and CD155 . We demonstrate that specific exosomal miRNAs that are differentially abundant in plasma of T2D adults compared to nondiabetic controls (miR374a-5p, miR-93-5p and let-7b-3p) are delivered to cancer cells, thereby regulating critical target genes. We build on our previous reports showing BRD4 controls migration and dissemination of castration-resistant prostate cancer, and transcription of key EMT genes, to show that T2D exosomes require BRD4 to drive EMT and immune ligand expression. We validate our findings with gene set enrichment analysis of human prostate tumor tissue in TGCA genomic data. These results suggest novel, non-invasive approaches to evaluate and potentially block progression of prostate and other cancers in patients with comorbid T2D.

Introduction: The global increase of the aging population presents major challenges to healthcare service delivery. Further, the COVID-19 pandemic exposed older adults' vulnerability to rapid deterioration of health when deprived of access to care due to the need for social distancing. Robotic technology advancements show promise to improve provision of quality care, support independence for patients and augment the capabilities of clinicians to perform tasks remotely., Aim: This study explored the feasibility and end-user acceptance of using a novel human-like tele-robotic system with touch feedback to conduct a remote medical examination and deliver safe care., Method: Testing of a remotely controlled robot was conducted with in-person clinician support to gather ECG readings of 11 healthy participants through a digital medical device. Post-study feedback about the system and the remote examinations conducted was obtained from study participants and study clinicians., Results: The findings demonstrated the system's capability to support remote examination of participants, and validated the system's perceived acceptability by clinicians and end-users who all reported feeling safe interacting with the robot and 72% preferred remote robotic exam over in-person examination., Conclusion: This paper discusses potential implications of robot-assisted telehealth for patients including older adults who are precluded from having in-person medical visits due to geographic distance or mobility, and proposes next steps for advancing robot-assisted telehealth delivery., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: As a natural antioxidant, uric acid plays a protective role against neurodegenerative disorders, including Parkinson's disease (PD). Therefore, the risk of PD has been found to be lower in people with hyperuricemia. In this article, we conducted a systematic review and meta-analysis to investigate whether gout affects the future risk of developing PD., Methods: We searched PubMed, Scopus, the Web of Science, and Google Scholar to find relevant studies, up to March 16, 2022. Studies investigating the risk of PD, following a gout diagnosis, were included if they were cross-sectional, case-control or cohort studies. The Newcastle Ottawa Scale (NOS) checklist was used to assess the quality of all included studies. The meta-analysis was performed using STATA 17.0., Results: Ten studies were included, which were comprised of three case-controls, six cohort studies and one nested case-control study. We found no significant association between gout and the risk of PD among both sexes (RR = 0.94, 95% CI: 0.86-1.04), although the association was significant for females (RR = 1.09; 95% CI: 1.02-1.17). Subgroup analysis also showed no significant findings by age group, whether they were receiving treatment for gout, study design, quality assessment score, and method of gout ascertainment. In contrast, the studies that defined PD according to the use of drugs showed significant results (RR = 0.82; 95% CI: 0.76-0.89). There was a significant publication bias on the association between gout and PD., Conclusions: The presence of gout had no significant effect on the risk of subsequently developing PD. Further analyses are recommended to investigate the effects of demographic and behavioral risk factors., (© 2022. The Author(s).)

Exosomes, known as a type of extracellular vesicles (EVs), are lipid particles comprising heterogeneous contents such as nucleic acids, proteins, and DNA. These bi-layered particles are naturally released into the extracellular periphery by a variety of cells such as neoplastic cells. Given that exosomes have unique properties, they can be used as vectors and carriers of biological and medicinal particles like drugs for delivering to the desired areas. The proteins and RNAs being encompassed by the circulating exosomes in B-cell malignancies are deemed as the promising sources for diagnostic and prognostic biomarkers, as well as therapeutic agents. Exosomes can also provide a "snapshot" view of the tumor and metastatic landscape at any particular time. Further, clinical research has shown that exosomes are produced by immune cells such as dendritic cells can stimulate the immune system, so these exosomes can be used in antitumor vaccines. Despite the great potential of exosomes in the fields of diagnostic and treatment, further studies are in need for these purposes to reach a convergence notion. This review highlights the applications of exosomes in multiple immune-related diseases, including chronic lymphocytic leukemia, multiple sclerosis, and arthritis rheumatoid, as well as explaining sundry aspects of exosome therapy and the function of exosomes in diagnosing diseases., (© 2022. The Author(s).)

Background: The newly emerged pandemic of coronavirus disease-2019 (COVID-19) is the world's main health challenge because infected patients become vulnerable to a variety of opportunistic diseases., Objective: This study aimed to assess clinical outcomes, diagnosis, utilized drug therapies, and ongoing COVID-19 practices in Iranian cases co-infected with COVID-19 and mucormycosis., Participants and Methods: A case-series analysis was conducted in the presence of 10 patients with COVID-19 and mucormycosis co-infection (two men and eight women; mean age of 48.8 years) from March to October 2020. Demographic variables, signs/symptoms, and comorbidities of all patients were recorded. COVID-19 was confirmed with reverse transcription polymerase chain reaction (RT-PCR) nasopharyngeal swab tests and high-resolution computed tomography (HR-CT)&#95; scans., Results: All patients had a positive RT-PCR for SARS-CoV-2. Eight patients had a history of diabetes, while three of them exhibited a hypertension history. Remarkable laboratory findings were elevated fasting blood sugar in 6 cases and anaemia in four patients. A rhino-orbital-cerebral of mucormycosis in all patients was detected based on HR-CT scans and otorhinolaryngological or ophthalmological examinations. Neurological disorders including facial, trigeminal, optic, and oculomotor nerve involvement resulted in paraesthesia, pain, ptosis, no light perception, blurred vision, and papilledema in five cases. Maxillary and ethmoid sinuses were the most common sites of involvement., Conclusion: Vulnerable COVID-19 patients with comorbidities, any facial involvements, or treated by excessive doses of glucocorticoids and antibiotics should undergo precise examinations during the appearance of early signs and hospitalization to diagnose and treat mucormycosis using the standard care and antifungal treatments.

Bioactive glasses are a group of bioceramic materials that have extensive clinical applications. Their properties such as high biocompatibility, antimicrobial features, and bioactivity in the internal environment of the body have made them useful biomaterials in various fields of medicine and dentistry. There is a great variation in the main composition of these glasses and some of them whose medical usage has been approved by the US Food and Drug Administration (FDA) are called Bioglass. Bioactive glasses have appropriate biocompatibility with the body and they are similar to bone hydroxyapatite in terms of calcium and phosphate contents. Bioactive glasses are applied in different branches of dentistry like periodontics, orthodontics, endodontics, oral and maxillofacial surgery, esthetic and restorative dentistry. Also, some dental and oral care products have bioactive glasses in their compositions. Bioactive glasses have been used as dental implants in the human body in order to repair and replace damaged bones. Other applications of bioactive glasses in dentistry include their usage in periodontal disease, root canal treatments, maxillofacial surgeries, dental restorations, air abrasions, dental adhesives, enamel remineralization, and dentin hypersensitivity. Since the use of bioactive glasses in dentistry is widespread, there is a need to find methods and extensive resources to supply the required bioactive glasses. Various techniques have been identified for the production of bioactive glasses, and marine sponges have recently been considered as a rich source of it. Marine sponges are widely available and many species have been identified around the world, including the Persian Gulf. Marine sponges, as the simplest group of animals, produce different bioactive compounds that are used in a wide range of medical sciences. Numerous studies have shown the anti-tumor, anti-viral, anti-inflammatory, and antibiotic effects of these compounds. Furthermore, some species of marine sponges due to the mineral contents of their structural skeletons, which are made of biosilica, have been used for extracting bioactive glasses., (© 2022. The Author(s).)

Ever since the Cairo Declaration in 1994, women's Sexual and Reproductive Health (SRH) has become a priority and substantial efforts have been made to improve it. Men's contribution to promote the SRH of women is essential. Therefore, this study aimed to identify the best solutions to increase the men's participation in the SRH of women in Iran, using an analytic hierarchy process (AHP) approach. A cross-sectional study was conducted among 150 married men in Iran. The data was collected using a questionnaire. To determine the best solutions to improve the men's participation in women's SRH, the opinions of an expert group from academia, Ministry of Health (MOH) were employed and the best solution were selected based on the scores, applying analytic hierarchy process (AHP) approach. The statistical analysis was performed using SPSS V.20 and Expert Choice software. In the final analysis 'Well-oriented sex education focused on men's involvement', 'Well-trained professional employment' and 'Sex education in society, schools, and universities' were the solutions with highest coefficients, respectively.Impact statement What is already known on this subject? SRH of women, is a major part of primary efforts regarding the increase of SRH's quality; among which, the role and place of men is of utmost importance. Struggling to participate men in issues related to the health of women can not only promote inter family relationships, but also can affect the quality of relationship between man and woman in the society. What do the results of this study add? According to results of the study, one of the main obstacles of men participation was educational and information barriers, regarding which, having adjusted and improved educational systems, opportunity could be prepared for men participation. Current centres for educating those who are already getting married are the first and main places where men can be educated to meet their educational needs in their marriage life such as SRH. Through integrating three selected approaches in the experts' meetings in the educational program of before marriage, men participation can be increased in SRH. What are the implications of these findings for clinical practice and/or future research? The findings could inform and guide the policies in formulating effective solutions to improve the men's participation in SRH in Iran.

Background: Intestinal parasitic infections (IPIs) are still considered a public health problem of mankind, particularly in immunocompromised patients. We aimed to determine the prevalence of IPIs with an emphasis on immunocompromised patients in a referral hospital in Tehran Province, Iran., Methods: In this cross-sectional study, 442 fecal specimens were collected randomly from patients, referred to Baqiyatallah Hospital in Tehran Province, Iran from May to September 2020. The collected specimens were examined using wet-mount, trichrome and modified Ziehl-Neelsen staining, formalin-ether concentration, and agar plate culture., Results: The prevalence of IPIs was found 17.0% (95% CI: 13.6-20.8%). The prevalence of protozoan parasites (16.3%; 95% CI: 13.0-20.1%) was significantly higher than helminthic parasites (0.7%; 95% CI: 0.1-2.0%). Blastocystis spp., Giardia lamblia , and Entamoeba coli were the most common intestinal protozoan with a prevalence of 12.2%, 1.6%, and 1.4%, respectively. E. histolytica/E. dispar/E. moshkovskii , Iodamoeba bütschlii , Cryptosporidium spp., Chilomastix mesnili as protozoan species and Hymenolepis nana, Dicrocoelium dendriticum, and Ascaris lumbricoides as helminthic species were the other detected parasites. Multiple logistic regression revealed a significant association of IPIs infections with stool consistency and the status of immune system., Conclusion: The prevalence of IPIs among the patients who are immunocompromised was significantly higher than immunocompetent patients ( P < 0.05). Periodic stool examinations for screening of IPIs should be included as a part of routine medical check-up in these patients., Competing Interests: Conflict of interest The authors assert that they have no competing interest., (Copyright © 2022 Zarei et al. Published by Tehran University of Medical Sciences.)

Objectives: Stuttering is a common problem at all ages that is required to be treated since childhood. Atomoxetine is currently used for the treatment of attention deficit hyperactivity disorder (ADHD). It can be effective for the treatment of stuttering due to its selective inhibition of norepinephrine reuptake and dopaminergic properties. Therefore, this randomized controlled trial aimed to evaluate the effect of atomoxetine on children's stuttering., Materials & Methods: The children aged 4-12 years and diagnosed with stuttering, referred to Pediatric Neurology and Psychology clinics , were randomly divided into experimental (n=50) and control (n=50) groups. One group received atomoxetine plus speech therapy, and the other group received only speech therapy. Both groups completed the Stuttering Severity Instrument-Fourth Edition at the baseline (on the first visit) and 3 months after the intervention. The results were compared between the two groups using SPSS software (version 21)., Results: Most of the children (67%) were male. Moreover, 24%, 46%, and 30% of the subjects were within the age ranges of < 60, 60-95, and > 95 months, respectively. Nearly half of the patients (52%) had a positive family history of stuttering. Stuttering severity was the highest within the age range of 60-95 months, in left-handed children, in those who used formula, and in those who felt insecure in the family; however, there was no difference in stuttering severity based on child's gender, concomitant ADHD, multilingualism, facial or movement tics, sleeping hours, and using teats. The mean stuttering severity reduced in both groups (P<0.001), with a greater decrease in the experimental group, compared to that of the control group (P=0.011)., Conclusion: Atomoxetine plus speech therapy is effective for the treatment of children's stuttering and can be used as a complementary treatment strategy in such patients., Competing Interests: The present study wasnt financially supported by anyone, (© 2022 The Authors.)

The COVID-19 pandemic presented challenges to the healthcare system while catalyzing the adoption of virtual care. The need for remote assessment and real-time monitoring of physiological vital signs has driven towards a need for virtual care solutions. This paper presents the outcome of a multidisciplinary collaboration to ensure clinical usability of a remote contactless sensing technology, VitalSeer, and to help close gaps between emerging technologies and clinical practice. The paper describes the user-centric data-driven clinical approach to address the needs as identified by clinical experts through the iterative and agile development cycle. It highlights findings from preliminary studies to validate proof-of-concept VitalSeer's adoptability, accessibility and usability. The studies on volunteers demonstrated the accuracy of VitalSeer's heart rate model at a low MAE of 0.74 (bpm) and a RMSE of 1.2 bpm, below the threshold of clinical grade contact-based sensors. The paper concludes with a discussion on the technology implications in emergency medicine and community care., (©2022 AMIA - All rights reserved.)

Background: Seventeen medical homes (MHs) were established in the Local Health Authority (LHA) of Parma (about 450,000 residents), Emilia Romagna, Italy, between 2011 and 2016., Objective: To estimate the effects of MH implementation on healthcare utilization., Design: We conducted a longitudinal cohort study (01/2011-12/2017) using the Parma LHA administrative healthcare database., Participants: Residents for ≥1 year and older than 14 years of age with a documented primary care physician (PCP) in Parma LHA., Intervention: MH exposure status was classified for each resident as either receiving care from a PCP that (1) eventually practices in an MH (pre-MH), (2) is currently in an MH (post-MH), or (3) does not join an MH (non-MH)., Main Outcome Measures: Risks of ordinary inpatient hospital admissions, day hospital admissions, admissions for ambulatory care sensitive conditions (ACSCs), all-cause emergency department (ED) visits, and deferrable ED visits were compared using Cox proportional hazards regression and risks of all-cause 30- and 90-day readmissions for congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) were compared using logistic regression., Key Results: Prior to MH implementation, the risk of all-cause ED visits for pre-MH residents was 0.93 (95% CI: 0.92-0.94) that of non-MH residents. After MH implementation, the relative risk for post-MH versus non-MH was 0.86 (95% CI: 0.85-0.87) and, over time, post-MH versus pre-MH was 0.93 (95% CI: 0.92-0.94). Hospitalization risks were generally lower among the pre-MH and post-MH, compared to non-MH. However, hospitalizations and HF or COPD readmissions were not generally lower post-MH compared to pre-MH., Conclusions: This MH initiative was associated with a 7% reduction in risk of ED visits. More research is necessary to understand if ED visit risk will continue to improve and how other aspects of healthcare utilization might change as more MHs open and the length of exposure to MHs increases., (© 2021. Society of General Internal Medicine.)

This data article includes datasets collected at three sections of the Guadalupe River, Brazos River, and Colorado River in Texas, USA, almost ten months post Hurricane Harvey. Instruments used include a Portable Free Fall Penetrometer (PFFP), Chirp Sonar, Side Scan Sonar (SSS), Acoustic Doppler Current Profiler (ADCP) and sediment grab sampler. Measurements were collected from small vessels such as canoes and a 6-feet inflatable zodiac and were supported by long term hydrodynamic data from local river water level and discharge gages. Laboratory testing performed on samples collected included grain size analysis, Atterberg test, and erodibility testing using an Erosion Function Apparatus (EFA). Data collected were analyzed to estimate sediment strength derived from the PFFP, backscatter intensity recorded by the chirp sonar, and soil sample characteristics. The dataset includes raw and processed data for the measurements recorded by the instruments, location of measurements, and laboratory testing grouped for each river with a readme file which gives a potential for reuse by other researchers for further analysis if needed. This data article is representing supplementary data to the following research article published in Engineering Geology [1]: Jaber, R., Stark, N., Jafari, N., & Ravichandran, N. "Combined Portable Free Fall Penetrometer and Chirp Sonar Measurements of three Texas River Sections Post Hurricane Harvey." Raw data was published [2]: Stark, N. Jafari, N. Ravichandran, R. Jaber, R. (2020). Combined Geotechnical and Geophysical Investigation of Texas Rivers Post Hurricane Harvey. in Combined Geotechnical and Geophysical Investigation of Texas Rivers Post Hurricane Harvey. DesignSafe-CI. https://doi.org/10.17603/ds2-835m-zp94., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2022 The Author(s).)

Directed cell migration arises from cells following a microenvironmental gradient (e.g. of a chemokine) or polarizing feature (e.g. a linear structure). However cells not only follow, but in many cases, also generate directionality cues by modifying their microenvironment. This bi-directional relationship is seen in the alignment of extracellular matrix (ECM) fibers ahead of invading cell masses. The forces generated by many migrating cells cause fiber alignment, which in turn promotes further migration in the direction of fiber alignment via contact guidance and durotaxis. While this positive-feedback relationship has been widely described for cells invading en masse, single cells are also able to align ECM fibers, as well as respond to contact guidance and durotaxis cues, and should therefore exhibit the same relationship. In this study, we directly tested this hypothesis by studying the migration persistence of individual HT-1080 fibrosarcoma cells migrating in photocrosslinked collagen matrices with limited remodeling potential. Our results demonstrate that this positive-feedback relationship is indeed a fundamental aspect of cell migration in fibrillar environments. We observed that the cells' inability to align and condense fibers resulted in a decrease in persistence relative to cells in native collagen matrices and even relative to isotropic (glass) substrates. Further experiments involving 2D collagen and electrospun polymer scaffolds suggest that substrates composed of rigid, randomly oriented fibers reduce cells' ability to follow another directionality cue by forcing them to meander to follow the available adhesive area (i.e. fibers). Finally, our results demonstrate that the bi-directional relationship between cell remodeling and migration is not a "dimensionality" effect, but a fundamental effect of fibrous substrate structure., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The most important complication in kidney transplant is acute/chronic rejection. In this study, we investigated the factors affecting kidney rejection and transplant survival., Materials and Methods: In this survival analysis study, 352 patients (mean follow-up of 12.9 ± 4.4 years) who underwent renal biopsy due to increased creatinine level from 2012 to 2016 were identified by glomerular filtration rate level and rejection. Probable factors affecting renal function and survival rate after transplant rejection were assessed. P < .05 was considered as significant., Results: Among our study patients, 40.9% developed early and 59.1% developed late acute kidney injury. Graft survival rates at 1 and 5 years were 98.9% and 68.5%, respectively, which was significant when rejection type was considered (P = .002). In addition, patient survival rates at 1 and 5 years were 99.7% and 98.6%, respectively. Graft survival at 5 years was significantly lower among older subjects, those with diabetes, those who received deceased donor organs, and those with late acute kidney injury (P < .002). Patient survival was significantly higher among young patients, those with systemic lupus erythematosus, those who received living donor organs, and those without cytomegalovirus infection (P < .003)., Conclusions: We observed that recipient age, type of donor, underlying disease, infection, and late acute kidney injury had great negative impacts on renal dysfunction and survival. In our center, because of the large number of kidney transplants from deceased donors, the necessity of antithymocyte globulin induction therapy was considered, since this study showed that patients who received rabbit antithymocyte globulin induction had better outcomes.

Background: Once COVID-19 is transmitted, the corresponding civil responsibility should be clarified by the identification of the transmitter, compensation of the damage and detection of the causal relationship between the damage or harm and the harmful act. Methods: This research has been prepared by descriptive analytical method and its data has been collected by documentary library tools. Results: What makes this relationship meaningful and suable is the existence of fault. By definition, fault refers to any deviation from the normal or conventional behavior. On this basis, a COVID-infected person is considered faulty if he or she does not care about public health and transmits the disease to others by avoiding safety measures and violating hygienic protocols. This lack of care for others is a concrete example of deviation from normal civil behavior. One cannot claim civility unless the safety measures prescribed by the law are taken. Violating the law in this case, which leads to disease transmission, is considered as a fault. Conclusion: If an infected person is incautious enough to make others sick, the law holds him or her faulty; the harm done by the undue lack of causation Based on this obvious causal relationship, the faulty individual is held responsible for the loss or damage compensation, as by incurring the treatment costs.The most important challenges in respect of covid are the non-recognition of certain transporter to the victim of covid 19 and proof of causation., (© 2022 Iran University of Medical Sciences.)

This study was carried out to investigate the effects of methanolic extract of nettle (Urtica dioica) on growth, reproduction, biochemical and immunological parameters of female convict cichlid (Amatitlania nigrofasciata). For this purpose, 54 fish were distributed in 3 treatments included: without supplementation (control), 0.1 g (NE0.1), and 0.5 g (NE0.5) nettle extract per kilogram feed over 56 days. The highest final weight (4.2 ± 0.1 g), weight gain (2.8 ± 0.1 g), and specific growth rate (2.0 ± 0.0% day -1 ) were recorded in NE0.1 group. Higher and lower feed conversion ratio were obtained in control and NE0.1 treatments, respectively. Hepatosomatic and viscerosomatic indices in NE0.1 treatment were significantly lower compared with control treatment. Fish fed NE0.1 showed significantly lower glucose (55.2 ± 6.5 mg g -1 ), cholesterol (28.4 ± 3.3 mg g -1 ), and triglyceride (211.5 ± 39.0 mg g -1 ) levels. Total protein (36.3 ± 3.4 mg g -1 ) and albumin (2.7 ± 0.1 mg g -1 ) showed a marked increase in NE0.1 treatment. Same trend was observed in C3, C4, and IgM concentrations. NE0.1 showed the highest number of eggs per female (183.7 ± 10.2), hatching rate (97 ± 0.7%), and larval survival rate at 3 days post hatch (86.3 ± 0.6%) compared with the other treatments. These findings indicated that 0.1 g methanolic extract of nettle kg feed -1 could enhance growth, improve metabolic, and immune function of convict cichlid. Moreover, this study confirmed that appropriate dose of nettle can positively promote reproductive performance which makes it as a valuable and cost-effective herb in aquaculture industry., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Colorectal cancer is the 2nd leading cause of death in humans because of cancer. This rank of death could be due to the high rate of incidence from one hand, and the lack of sufficient diagnostic and therapeutic approaches from the other hand. Thus, molecular tools have been emerging as the potential biomarker to improve the early diagnosis and therapeutic management that subsequently could lead to the heightened survival rate of colorectal cancer patients. Long non-coding RNA (lncRNAs) have shown promising capabilities to be used in clinics. The profiling methods could identify novel aberrantly expressed lncRNAs in colorectal cancer. We, thus, performed a comprehensive and unbiased approach to shortlist the dysregulated lncRNAs based on the colon adenocarcinoma TCGA data. An unbiased in silico method was used to rank the yet to profiled lncRNAs in colorectal cancer. qPCR was used to measure the expression level of selected lncRNAs. Our results nominated ESRG, LINC00518, PWRN1, and TTTY14 lncRNAs as the top-hit novel lncRNAs with aberrant expression in colon cancer. The qPCR method was used to profile these lncRNAs that showed the up-regulation of ESRG and LINC00518, and down-regulation of TTTY14 in thirty paired colorectal cancer specimens. The statistical analyses demonstrated that ESRG, LINC00518 and PWRN1 could distinguish the tumor from normal samples. Moreover, ESRG showed a negative correlation with the overall survival of patients. These diagnostic and prognostic results suggest that profiling ESRG, LINC00518 and PWRN1 s may have implications in clinics., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The oral cavity as the second most various microbial community in the body contains a broad spectrum of microorganisms which are known as the oral microbiome. The oral microbiome includes different types of microbes such as bacteria, fungi, viruses, and protozoa. Numerous factors can affect the equilibrium of the oral microbiome community which can eventually lead to orodental infectious diseases. Periodontitis, dental caries, oral leukoplakia, oral squamous cell carcinoma are some multifactorial infectious diseases in the oral cavity. In defending against infection, the immune system has an essential role. Depending on the speed and specificity of the reaction, immunity is divided into two different types which are named the innate and the adaptive responses but also there is much interaction between them. In these responses, different types of immune cells are present and recent evidence demonstrates that these cell types both within the innate and adaptive immune systems are capable of secreting some extracellular vesicles named exosomes which are involved in the response to infection. Exosomes are 30-150 nm lipid bilayer vesicles that consist of variant molecules, including proteins, lipids, and genetic materials and they have been associated with cell-to-cell communications. However, some kinds of exosomes can be effective on the pathogenicity of various microorganisms and promoting infections, and some other ones have antimicrobial and anti-infective functions in microbial diseases. These discrepancies in performance are due to the origin of the exosome. Exosomes can modulate the innate and specific immune responses of host cells by participating in antigen presentation for activation of immune cells and stimulating the release of inflammatory factors and the expression of immune molecules. Also, mesenchymal stromal/stem cells (MSCs)-derived exosomes participate in immunomodulation by different mechanisms. Ease of expansion and immunotherapeutic capabilities of MSCs, develop their applications in hundreds of clinical trials. Recently, it has been shown that cell-free therapies, like exosome therapies, by having more advantages than previous treatment methods are emerging as a promising strategy for the treatment of several diseases, in particular inflammatory conditions. In orodental infectious disease, exosomes can also play an important role by modulating immunoinflammatory responses. Therefore, MSCs-derived exosomes may have potential therapeutic effects to be a choice for controlling and treatment of orodental infectious diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jafari, Khoradmehr, Moghiminasr and Seyed Habashi.)

Melanoma is the most aggressive of skin cancer derived from genetic mutations in the melanocytes. Current therapeutic approaches include surgical resection, chemotherapy, photodynamic therapy, immunotherapy, biochemotherapy, and targeted therapy. However, the efficiency of these strategies may be decreased due to the development of diverse resistance mechanisms. Here, it has been proven that therapeutic monoclonal antibodies (mAbs) can improve the efficiency of melanoma therapies and also, cancer vaccines are another approach for the treatment of melanoma that has already improved clinical outcomes in these patients. The use of antibodies and gene vaccines provides a new perspective in melanoma treatment. Since the tumor microenvironment is another important factor for cancer progression and metastasis, in recent times, a mechanism has been identified to provide an opportunity for melanoma cells to communicate with remote cells. This mechanism is involved by a novel molecular structure, named extracellular vesicles (EVs). Depending on the functional status of origin cells, exosomes contain various cargos and different compositions. In this review, we presented recent progress of exosome applications in the treatment of melanoma. Different aspects of exosome therapy and ongoing efforts in this field will be discussed too., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A self-report questionnaire survey was conducted online to collect big data from over 16000 Iranian families (who were the residents of 1000 urban and rural areas of Iran). The resulting data storage contained over 1 M records of data and over 1G records of automatically inferred information. Based on this data storage, a series of machine learning experiments was conducted to investigate the relationship between nutrition and the risk of contracting COVID-19. With highly accurate scores, the findings strongly suggest that foods and water sources containing certain natural bioactive and phytochemical agents may help to reduce the risk of apparent COVID-19 infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Few studies have been performed to investigate the association between vitamin D and respiratory problems in premature neonates., Methods: In this cohort study, a low serum level of vitamin D was considered as exposure and respiratory problems and associated interventions were considered as outcome. All patients were followed during their hospital stay. All preterm neonates admitted to the neonatal intensive care unit of a general hospital in Iran during one-year period from January 2018 were enrolled in this study. Serum vitamin D level was measured in the first 24 hours of life by liquid chromatography-spectrometry. Then, respiratory complications were compared between neonates with and without vitamin D insufficiency., Results: Among the 113 preterm newborns, 65 (58%) had a low and 48 (42%) had a normal level of vitamin D who were classified into two groups I and II, respectively. Respiratory distress syndrome (RDS) and requirement for surfactant administration was found in 40 cases (61.5%) in group I and in 20 cases (41.7%) in group II ( P =0.036). Also, 46 newborns (70.8%) in the first group and 22 (45.8%) in the second group needed non-invasive ventilation (NIV) ( P =0.007). Multiple logistic regression showed a significant association between vitamin D status and RDS (OR, 95% CI=2.840 (1.083-7.447), P =0.034), need for surfactant (OR, 95% CI=2.840 (1.083-7.447), P =0.034) and need for NIV (OR, 95% CI=3.929 (1.526-10.113), P =0.005)., Conclusion: The incidence of RDS, need for surfactants, and need for NIV in newborns with vitamin D insufficiency were higher than the neonates with normal levels., (2022 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Microbial growth confinement using liquid scaffolds based on an aqueous two-phase system (ATPS) is a promising technique to overcome the challenges in microbial-mammalian co-culture in vitro . To better understand the potential use of the ATPS in studying these complex interactions, the goal of this research was to characterize the effects of bacteria loading and biofilm maturation on the stability of a polyethylene glycol (PEG) and dextran (DEX) ATPS. Two ATPS formulations, consisting of 5% PEG/5% DEX and 10% PEG/10% DEX (w/v), were prepared. To test the containment limits of each ATPS formulation, Escherichia coli MG1655 overnight cultures were resuspended in DEX at optical densities (ODs) of 1, 0.3, 0.1, 0.03, and 0.01. Established E. coli colonies initially seeded at lower densities were contained within the DEX phase to a greater extent than E. coli colonies initially seeded at higher densities. Furthermore, the 10% PEG/10% DEX formulation demonstrated longer containment time of E. coli compared to the 5% PEG/5% DEX formulation. E. coli growth dynamics within the ATPS were found to be affected by the initial bacterial density, where colonies of lower initial seeding densities demonstrate more dynamic growth trends compared to colonies of higher initial seeding densities. However, the addition of DEX to the existing ATPS during the growth phase of the bacterial colony does not appear to disrupt the growth inertia of E. coli . We also observed that microbial growth can disrupt ATPS stability below the physical carrying capacity of the DEX droplets. In both E. coli and Streptococcus mutans UA159 colonies, the ATPS interfacial tensions are reduced, as suggested by the loss of fluorescein isothiocyanate (FITC)-DEX confinement and contact angel measurements, while the microbial colony remained well defined. In general, we observed that the stability of the ATPS microbial colony is proportional to polymer concentrations and inversely proportional to seeding density and culture time. These parameters can be combined as part of a toolset to control microbial growth in a heterotypic co-culture platform and should be considered in future work involving mammalian-microbial cell interactions.

Background: Evaluation of insulin-like growth factor-1 (IGF-1) association with retinopathy of prematurity (ROP) is our object., Materials and Methods: This study was conducted on IGF-1 levels of 40 neonates <34 weeks gestational age and 2000 g at 1 st week and 4-6 weeks after birth. All participants were evaluated for ROP after 31 weeks of gestation., Results: IGF-1 levels showed a significant difference between neonates ≤1500 and 1500-2000 g (1 and 4-6 weeks, P = 0.008, P = 0.039, respectively). No significant association was found between IGF-1 and ROP., Conclusion: Finding a meaningful association between IGF-1 and ROP requires consideration of factors affecting the IGF-1., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Research in Medical Sciences.)

Obesity and metabolic diseases, such as insulin resistance and type 2 diabetes (T2D), are associated with metastatic breast cancer in postmenopausal women. Here, we investigated the critical cellular and molecular factors behind this link. We found that primary human adipocytes shed extracellular vesicles, specifically exosomes, that induced the expression of genes associated with epithelial-to-mesenchymal transition (EMT) and cancer stem–like cell (CSC) traits in cocultured breast cancer cell lines. Transcription of these genes was further increased in cells exposed to exosomes shed from T2D patient–derived adipocytes or insulin-resistant adipocytes and required the epigenetic reader proteins BRD2 and BRD4 in recipient cells. The thrombospondin family protein TSP5, which is associated with cancer, was more abundant in exosomes from T2D or insulin-resistant adipocytes and partially contributed to EMT in recipient cells. Bioinformatic analysis of breast cancer patient tissue showed that greater coexpression of COMP (which encodes TSP5) and BRD2 or BRD3 correlated with poorer prognosis, specifically decreased distant metastasis–free survival. Our findings reveal a mechanism of exosome-mediated cross-talk between metabolically abnormal adipocytes and breast cancer cells that may promote tumor aggressiveness in patients with T2D.

Background: This study compared microleakage of Class II cavities restored using bonded-base and bulk-fill techniques with different bases., Materials and Methods: In this in vitro study, in 60 extracted human molars, standardized (4 mm × 2 mm × 8 mm) Class II cavities were prepared, such that the gingival floor was located 1 mm below the CEJ. The teeth were randomly divided into five groups and filled with: (1) Fuji II LC + x-tra fil, (2) Ionoseal + x-tra fil, (3) x-tra base + x-tra fil, (4) Grandio Flow + x-tra fil, and (5) x-tra fil only [control group]; in open-sandwich technique, the base thickness was 1 mm. The bases were coated all gingival floor. Except for the first group, where dentin conditioner was used, the Clearfil SE bond was applied before application of the bases and restorative materials as a bonding agent. After 500 thermocycles between 5°C and 55°C, the specimens were immersed in 0.5% basic fuchsine solution for 24 h. The restored teeth were sectioned, and the dye penetration in gingival floor was observed by a stereomicroscope at ×32. The data were analyzed using Kruskal-Wallis and Mann-Whitney tests in SPSS software. The significance was determined at 0.05 confidence interval., Results: The statistical analysis revealed a significant difference in microleakage among the study groups ( P < 0.001). The Ionoseal group followed by the control group (x-tra fil composite) had the greatest microleakage. Except for the Ionoseal group, all other groups had significantly less microleakage than the control group., Conclusion: The use of bonded-base techniques could reduce microleakage, including those in bulk-fill composite restorations., Competing Interests: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or nonfinancial in this article., (Copyright: © 2021 Dental Research Journal.)

Protein kinase A (PKA) is the main receptor for the universal cAMP second messenger. PKA is a tetramer with two catalytic (C) and two regulatory (R) subunits, each including two tandem cAMP-binding domains, i.e. CBD-A and -B. Activation of the complex occurs with cAMP binding first to CBD-B, followed by a second molecule of cAMP binding to CBD-A, which causes the release of the active C-subunit. Unlike previous constructs for eukaryotic cAMP-binding domains (CBDs), the 29.5 kDa construct analyzed here [i.e. RIα (119-379)] spans the CBDs in full and provides insight into inter-domain communication. In this note we report the 1 H, 13 C, and 15  N backbone assignments of cAMP-bound RIα (119-379) CBDs (BMRB No. 50920)., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

The interneurons ALA and RIS both regulate stress induced sleep in C. elegans but their roles in awake animal movement has been reported to differ. We describe the development of a motivated mobility-based assay that distinguishes between animals mutant for ALA function and those mutant for RIS function., (Copyright: © 2021 by the authors.)

Although the autologously transplanted cells are immunologically durable, allogeneic cell transplantation is inevitable in a series of cases. Mesenchymal stem cells (MSCs) are one of the suitable candidates for cardiac tissue regeneration that have been shown to acquire immunogenicity concurrent with cardiomyogenic differentiation. The present study aimed to exploit PD-L1, as a key immunomodulatory checkpoint ligand to protect the MSCs-derived cardiomyocyte-like cells (CLCs) against the detrimental alloimmunity. Mouse bone marrow-derived MSCs were stably transduced to overexpress PD-L1. MSCs were in vitro differentiated into CLCs and the expressions of immunologic molecules were compared between MSCs and CLCs. The in vitro and in vivo allogeneic immune responses were also examined. The differentiated CLCs had higher expressions of MHC-I and CD80. Upon in vitro coculture with allogeneic splenocytes, CLCs caused more CD4 + and CD8 + T cell activation, lymphocyte proliferation, and interferon-γ (IFN-γ) release in comparison to MSCs. PD-L1 overexpression on CLCs decreased the activation of CD8 + T cells, proliferation of lymphocytes, and release of IFN-γ. The PD-L1-overexpressing CLCs elicited lower in vivo CD4 + and CD8 + T cell activation and reduced the anti-donor antibody response accompanied by increased durability and reduced T cell infiltration. The present study verified the potential of PD-L1 overexpression as a preparative strategy for the protection of allogeneic MSCs-derived CLCs against the detrimental alloreaction., (© 2021 Wiley Periodicals LLC.)

Background: We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia and risk factors associated for mortality., Methods: In this study, we included inpatient with acute respiratory distress syndrome at Golestan Hospitals who had been discharged or had died in 2020. Epidemiological, and clinical data were extracted from electronic medical records and compared between recovered and died cases. We used multiple logistic regression methods to explore the risk factors associated with in-hospital death., Results: Overall 2,835 acute respiratory distress syndrome patients were included in this study, and 874 (30.83%) were positive for 2019-nCoV. Five hundred and sixty-three patients (19.86%) died, 1,687 patients (59.51%) were recovered. Of the total deaths, only 288 (10.15%) were attributed to COVID-19. The most common symptoms at onset of illness were respiratory distress [1,795 (63.32%)], fever [1,601 (56.47%)], dry cough [1,595 (56.26%)], sore throat [445 (15.70%)], and myalgia [342 (12.06%)]. One thousand and twelve (35.7%) had 1 or more coexisting medical conditions. In multiple logistic regression analysis, risk factors associated with the death included older age [OR (Odds Ratio) = 1.03; 95% CI; 1.02-1.04], blood oxygen level (SPO 2 < 93%) (OR = 2.44; 95% CI; 1.79-3.31), comorbidities (OR = 2.15; 95% CI; 1.62-2.84), respiratory distress (OR = 1.74; 95% CI; 1.28-2.37), and headache (OR = 0.44 95% CI; 0.21-0.92)., Conclusions: The 2019-nCoV infection caused collections of severe respiratory illness and was associated to a high ratio of hospitalization in ICU and high mortality. Older age and comorbidities were associated with more risk of death among patients with 2019-nCoV., Competing Interests: Conflict of interest statement The authors declare no conflict of interest., (©2021 Pacini Editore SRL, Pisa, Italy.)

Background: In chest computed tomography (CT) scan, bilateral peripheral multifocal ground-glass opacities, linear opacities, reversed halo sign, and crazy-paving pattern are suggestive for coronavirus disease 2019 (COVID-19) in clinically suspicious cases, but they are not specific for the diagnosis, as other viral pneumonias, like influenza and some viral pneumonia may show similar imaging findings., Aim: To find a specific imaging feature of the disease would be a welcome guide in diagnosis and management of challenging cases., Methods: Chest CT imaging findings of 650 patients admitted to a university Hospital in Tehran, Iran between January 2020 and July 2020 with confirmed COVID-19 infection by RT-PCR were reviewed by two expert radiologists. In addition to common non-specific imaging findings of COVID-19 pneumonia, radiologic characteristics of "pulmonary target sign" (PTS) were assessed. PTS is defined as a circular appearance of non-involved pulmonary parenchyma, which encompass a central hyperdense dot surrounded by ground-glass or alveolar opacities., Results: PTS were presented in 32 cases (frequency 4.9%). The location of the lesions in 31 of the 32 cases (96.8%) was peripheral, while 4 of the 31 cases had lesions both peripherally and centrally. In 25 cases, the lesions were located near the pleural surface and considered pleural based and half of the lesions (at least one lesion) were in the lower segments and lobes of the lungs. 22 cases had multiple lesions with a > 68% frequency. More than 87% of cases had an adjacent bronchovascular bundle. Ground-glass opacities were detectable adjacent or close to the lesions in 30 cases (93%) and only in 7 cases (21%) was consolidation adjacent to the lesions., Conclusion: Although it is not frequent in COVID-19, familiarity with this feature may help radiologists and physicians distinguish the disease from other viral and non-infectious pneumonias in challenging cases., Competing Interests: Conflict-of-interest statement: Schoepf UJ receives institutional research support and / or personal fees for consulting and speaking from Bayer, Bracco, ElucidBioImagingGuerbet, Heart Flow, Inc., Keya Medical, and Siemens Healthineers. Other authors declare no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Coronavirus infections, known as COVID-19, can induce a fatal respiratory system infection and also affect other organs, such as the kidney and heart. The mortality rate has been estimated between 1 and 5% in previous reports; however, the mortality and morbidity can be higher in patients with the immune-deficiency condition. Rheumatoid arthritis (RA) is one of the most rheumatoid disorders, and it is important to report their clinical and paraclinical data when affected with COVID-19. Evidence about their laboratory and radiologic findings is limited. In this case series, 10 cases of chronic and approved rheumatoid arthritis (RA) affected by COVID-19 are presented. Only 40% had dry cough, but myalgia and weakness as the general first presentation of infections was reported in most cases (80%). Gastrointestinal symptoms, including nausea/vomiting, diarrhea, anorexia, and abdominal pain, were reported in 50% of individuals. In blood cell count, 30% of cases had thrombocytopenia, and ESR in all cases was positive. Abnormal CRP and elevated LDH were seen in 90% of cases. In HRCT assessment, all cases had an abnormal parenchymal pattern, and 90% of cases presented the usual pattern of COVID-19 (bilateral multifocal GGO/consolidation). Although it is a limited report, these findings are helpful for comparison of clinical and paraclinical cases in RA cases with normal cases.

Objective: The main objective of this study was to review aspects of the current situation and structure of the integrated mental health care services for planning a reform. Aspects of the newly designed infrastructure, along with specification of duties of the various human resources, and its relation with Iran's Comprehensive Mental and Social Health Services (the SERAJ Program), will also be presented Method : This is a study on service design and three methods of literature review, deep interview with stakeholders, and focused group discussions. In the literature review, national and international official documents, including official reports of the World Health Organization (WHO) and consultant field visits, were reviewed. Deep semi-structured interviews with 9 stakeholders were performed and results were gathered and categorized into 3 main questions were analyzed using the responsibility and effectiveness matrix method. The Final results were discussed with experts, during which the main five-domain questions were asked and the experts' opinions were observed. Results: In this study, the main gaps of the public mental health care (PHC) services in Iran were identified, which included reduction of risk factors for mental disorders, training the general population, early recognition and treatment of patients with mental disorders, educating patients and their families, and rehabilitation services. The new model was then proposed to fill these gaps focusing on increasing access, continuity of care, coordination in service delivery, and comprehensiveness of care. A mental health worker was placed besides general healthcare workers and general practitioners (GPs). Services were prioritized and the master flowchart for mental health service delivery was designed. Conclusion: A reform was indeed necessary in the integrated mental health services in Iran, but regarding the infrastructure needed for this reform, including human and financial resources, support of the senior authorities of the Ministry of Health (MOH) is necessary for the continuity and enhancement of services. In this model, attention has been given to the principles of integrating mental health services into primary health care. Current experience shows that the primary health care system has been facing many executive challenges, and mental health services are not exclusion to this issue. Monitoring and evaluation of this model of service and efforts for maintaining sustainable financial resources is recommended to make a reform in this system and to stabilize it., (Copyright © 2021 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Familial mutations of the protein kinase A (PKA) R1α regulatory subunit lead to a generalized predisposition for a wide range of tumors, from pituitary adenomas to pancreatic and liver cancers, commonly referred to as Carney complex (CNC). CNC mutations are known to cause overactivation of PKA, but the molecular mechanisms underlying such kinase overactivity are not fully understood in the context of the canonical cAMP-dependent activation of PKA. Here, we show that oligomerization-induced sequestration of R1α from the catalytic subunit of PKA (C) is a viable mechanism of PKA activation that can explain the CNC phenotype. Our investigations focus on comparative analyses at the level of structure, unfolding, aggregation, and kinase inhibition profiles of wild-type (wt) PKA R1α, the A211D and G287W CNC mutants, as well as the cognate acrodysostosis type 1 (ACRDYS1) mutations A211T and G287E. The latter exhibit a phenotype opposite to CNC with suboptimal PKA activation compared with wt. Overall, our results show that CNC mutations not only perturb the classical cAMP-dependent allosteric activation pathway of PKA, but also amplify significantly more than the cognate ACRDYS1 mutations nonclassical and previously unappreciated activation pathways, such as oligomerization-induced losses of the PKA R1α inhibitory function., Competing Interests: The authors declare no competing interest.