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Tinea capities is the commonest dermatophytosis in children with diverse clinical presentations. The causative fungi of Tinea capitis vary with geographic area and time.This study was aimed to identify the etiologic agents and determine the related factors of Tinea capitis in Tehran, Iran. From clinically suspected cases of Tinea capitis, microscopy and culture were performed. Of 58patients 96% were children below 12 years of age with the male/ female ratio of 21, the common clinical manifestation was gray patch, followed by kerion, favus (scutula), black dot not seborrehic dermatitis- liker lesion, thrychophyton violaceum was the most common etiologic agent, responsible for 53.4% of infection, followed by T. shoepnleini (24.1%) Microsporum canis (5.5%) , T. mentagrophytes (3.4%) , T. tonsurans (1.7%) and M. gypseum (1.7%). T. violaceum was the predominat pathogen causing Tinea capitis in this region and gave rise to a varied clinical picture

Tinea corporis is a superficial fungal infection of the keratinized epithelial layer, presenting as erythematous scaling patches with central clearing. Sometimes it can resemble other skin disorders, so its misdiagnosis constitutes a problem of considerable practical importance. We describe a patient who presented with widespread Tinea corporis that morphology and distribution of the lesions mimicked lupus erythematosus and/or photodermatosis.

Human milk contains 2.2 ± 1.5×10 11 small extracellular vesicles (sEVs) per milliliter and human infants consume 1.7×10 14 milk sEVs (sMEVs) daily in 800 mL milk. Infant formula contains trace amounts of sMEVs. To date, eight adverse effects of milk depletion and five beneficial effects of sMEV supplementation have been reported including studies in infants and neonate mice. Formula-fed infants do not realize the benefits of sMEVs. Most of the phenotyping studies reported to date have the limitation that sMEV depletion and supplementation were initiated after mice were weaned. Here, we used a genetics approach for assessing effects of sMEV depletion on the development of suckling mice. Newborn C57BL/6J pups were fostered to Tumor Susceptibility Gene 101 (Tsg101) mammary-specific knockout (KO) dams or C57BL/6J dams (controls) in synchronized pregnancies. Tsg101 KO was associated with an 80% decrease of sMEVs. Postnatal weight gain and gut health (histology, morphology, and barrier function) were assessed until weaning at age three weeks. We observed a significant decrease in weight gain, length of small intestine, villi height, crypt depth, and intestinal barrier function in male and female pups fostered to Tsg101 dams compared to pups fostered to control dams. The effect size varied between 11 and 32 percent. Maternal Tsg101 KO did not affect the dams' health, content of macronutrients and dry mass of milk and had no effect on the amount of milk consumed by pups. We conclude that sMEVs are important for growth and gut health in neonate mice., Competing Interests: Declaration of competing interests The authors declare no conflict of interest. J. Zempleni serves as an editorial board member for the Journal of Nutritional Biochemistry and other scientific journals, and his research is currently funded by the National Institutes of Health, the National Institute of Food and Agriculture, and the Syngap Research Fund., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Regenerative medicine is revolutionizing oral and maxillofacial surgeries with stem cells, particularly mesenchymal stem cells, for tissue and bone regeneration. Despite promising in-vitro results, human trials are limited. A systematic review is needed to evaluate stem cell efficacy in maxillofacial issues, aiming to improve surgical outcomes and patient satisfaction., Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines, this review included peer-reviewed articles (2013-2023) on stem cells in oral surgery, excluding non-English publications, abstracts, reviews, and opinion pieces. Searches were conducted in PubMed, Web of Science, OVID, Cochrane, Dentistry & Oral Sciences Source-Ebscohost, and Scopus. Two authors independently screened titles and abstracts, resolving disagreements by consensus. Full-text analysis involved extracting key data, verified by a secondary reviewer and additional quality checks., Results: From 3540 initial articles, 2528 were screened after removing duplicates, and 7 met the inclusion criteria after excluding irrelevant studies. Key themes included the safety and efficacy of stem cell therapy, and bone regeneration and quality. Studies predominantly used mesenchymal stem cells. Findings showed positive outcomes in clinical safety and effectiveness and significant potential for bone regeneration., Conclusions: This systematic review highlights the potential of stem cell therapies in maxillofacial applications, supporting their safety, efficacy, and bone regeneration capabilities. Further research is needed to standardize protocols and confirm long-term benefits.

Immunotherapy has improved cancer treatment based on investigations of tumor immune escape. Manipulation of the immune system stimulates antitumor immune responses and blocks tumor immune escape routes. Genetically adoptive cell therapy, such as T cells, has yielded promising results for hematologic malignancies, but their application to solid tumors has been challenging. Macrophages have a wide broad of capabilities in regulating immune responses, homeostasis, and tissue development, as well as the ability to phagocyte, present antigens, and infiltrate the tumor microenvironment (TME). Given the importance of macrophages in cancer development, they could serve as novel tool for tumor treatment. Therefore, macrophages are used in different formats for direct and indirect targeting of tumor cells. This review summarized the available data on the various applications of macrophages in cancer immunotherapy., 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 © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Gastric cancer (GC) is a prominent cause of cancer-related mortality worldwide. Long noncoding RNA (lncRNA) maternal expression gene3 (MEG3) participates in numerous signaling pathways by targeting the miRNA-mRNA axis. Studies on human tumors have demonstrated that the antibiotic Ciprofloxacin induces cell cycle changes, programmed cell death, and growth suppression. In this study, we transfected MEG3 lncRNA and Ciprofloxacin into the MKN-45 GC cell line. qRT-PCR was employed to evaluate the effects on the specific microRNA and mRNA. The wound healing test, MTT assay, and flow cytometry were used to assess the impact of their administration on cell migration, viability, and apoptosis, respectively. Research showed that miR-147 expression fell even more after MEG3 lncRNA transfection, leading to an increase in B-cell lymphoma 2 (BCL-2) levels. Ciprofloxacin transfection did not significantly affect the axis, except for MEG3, which led to its slight upregulation. MEG3 lncRNA inhibited the migration of MKN-45 cells compared to the control group. When MEG3 lncRNA was coupled with Ciprofloxacin, there was a significant reduction in cell migration compared to untreated groups and controls. MTT assay and flow cytometry demonstrated that MEG3 lncRNA decreased cell viability and triggered apoptosis. Simultaneous administration of MEG3 lncRNA and Ciprofloxacin revealed a significant reduction in cell viability caused by increased apoptosis obtained from MTT or flow cytometry assays. Modulating the miR-147-BCL-2 axis decreases cell migration and survival while promoting cell death. In conclusion, combining MEG3 lncRNA with Ciprofloxacin may be an effective therapeutic approach for GC treatment by influencing the miR-14-BCl-2 axis, resulting in reduced cell viability, migration, and increased apoptosis., (© 2024 International Union of Biochemistry and Molecular Biology, Inc.)

Introduction: Most research examining vitamin D and dental caries focuses on children and younger adults. This study investigated the association between vitamin D levels and dental caries in older adults using data from the United States National Health and Nutrition Examination Survey from 2011 to 2016., Methods: Data were analyzed from 2723 participants aged 65 years and older who completed both dental examinations and serum 25(OH)D tests. Dental caries assessments included the decayed, missing, and filled teeth (DMFT) index and the presence of untreated dental caries. Vitamin D levels were measured as serum 25(OH)D concentrations and categorized as severely deficient (<25 nmol/L), deficient (25-49.9 nmol/L), insufficient (50-74.9 nmol/L), and normal (≥75 nmol/L). Logistic regression and Poisson regression models were used to assess the association between vitamin D levels and dental caries, adjusting for demographic factors., Results: The mean DMFT score was 17.73 ± 8.34, with 35.1% of participants having untreated dental caries. Vitamin D deficiency was associated with a 1.44 times higher likelihood of untreated caries (95% CI: 1.15, 1.81), which weakened after adjustment for demographic factors (adjusted OR: 1.23, 95% CI: 0.97, 1.55). Severe vitamin D deficiency correlated with a 1.13 times higher DMFT score (95% CI: 1.06, 1.20), with the association remaining similar after adjustment (adjusted RR: 1.12, 95% CI: 1.05, 1.20). Significant differences in vitamin D levels were observed across gender, race/ethnicity, and country of birth., Conclusions: This study suggests the potential importance of adequate vitamin D levels for maintaining dental health among older adults. Vitamin D deficiency is associated with a higher risk of poorer DMFT scores. Public health strategies that include vitamin D screening and supplementation, particularly for high-risk groups, may improve oral health outcomes in the older adult population. Further research is needed to elucidate the mechanisms by which vitamin D influences dental health and the potential for vitamin D supplementation to reduce the burden of dental caries in older adults.

Cancers of the kidney and renal pelvis are among the most prevalent types of urinary cancers. We aimed to outline the incidence trends of kidney and renal pelvis cancers by age, sex, race/ethnicity, and histology in the United States (US) from 2000 to 2020. The data was obtained from the Surveillance, Epidemiology, and End Results (SEER) 22 database. The identification of patients with kidney and renal pelvis cancers with morphologies of renal cell carcinoma, nephroblastoma, sarcoma, and neuroendocrine tumor was conducted utilizing the International Classification of Diseases for Oncology version 3. The average annual percent change (AAPC) were presented. All estimates were given in the form of counts and delayed age-standardized incidence rates (ASIRs) per 100,000 people. From 2000 to 2019, a total of 490,481 cases of kidney and renal pelvic cancer were recorded across all age groups in the US. The majority of them were among Non-Hispanic Whites (NHWs) (69.75%) and those aged 55-69 years (39.96%). The ASIRs per 100,000 for kidney and pelvis cancers were 22.03 for men and 11.14 for women. Non-Hispanic Black men had the highest ASIR (24.53 [24.24, 24.81]), and increase in ASIR over the 2000-2019 period (AAPC: 2.19% [1.84, 2.84]). There was a noticeable increase in incidence of kidney and renal pelvis cancers. Individuals aged 70-84 years had the highest ASIR for kidney and renal pelvis cancers. The COVID-19 era has resulted in a significant reduction in incidence rates across all demographics., (© 2024. The Author(s).)

Schwann cells (SCs) undergo phenotypic transformation and then orchestrate nerve repair following PNS injury. The ligands and receptors that activate and sustain SC transformation remain incompletely understood. Proteins released by injured axons represent important candidates for activating the SC Repair Program. The low-density lipoprotein receptor-related protein-1 (LRP1) is acutely up-regulated in SCs in response to injury, activating c-Jun, and promoting SC survival. To identify novel LRP1 ligands released in PNS injury, we applied a discovery-based approach in which extracellular proteins in the injured nerve were captured using Fc-fusion proteins containing the ligand-binding motifs of LRP1 (CCR2 and CCR4). An intracellular neuron-specific protein, Protein Kinase C and Casein Kinase Substrate in Neurons (PACSIN1) was identified and validated as an LRP1 ligand. Recombinant PACSIN1 activated c-Jun and ERK1/2 in cultured SCs. Silencing Lrp1 or inhibiting the LRP1 cell-signaling co-receptor, the NMDA-R, blocked the effects of PACSIN1 on c-Jun and ERK1/2 phosphorylation. Intraneural injection of PACSIN1 into crush-injured sciatic nerves activated c-Jun in wild-type mice, but not in mice in which Lrp1 is conditionally deleted in SCs. Transcriptome profiling of SCs revealed that PACSIN1 mediates gene expression events consistent with transformation to the repair phenotype. PACSIN1 promoted SC migration and viability following the TNFα challenge. When Src family kinases were pharmacologically inhibited or the receptor tyrosine kinase, TrkC, was genetically silenced or pharmacologically inhibited, PACSIN1 failed to induce cell signaling and prevent SC death. Collectively, these studies demonstrate that PACSIN1 is a novel axon-derived LRP1 ligand that activates SC repair signaling by transactivating TrkC., (© 2024 The Authors. GLIA published by Wiley Periodicals LLC.)

Purpose: The present study sets out to investigate the effect of cyclopentolate-induced cycloplegia on distance and near deviation and the accommodative convergence/accommodation (AC/A) ratio., Methods: This prospective study was performed on 30 subjects. The inclusion criteria included a lack of any active ocular pathology and systemic diseases, no history of ocular surgery, and nonuse of various medications. Refraction, near and distance deviation were measured for all subjects, and the same examinations were repeated after the administration of two drops of cyclopentolate 1% to both eyes., Results: The obtained data from 30 subjects, including 19 males, with a mean age of 22.53 ± 1.74 years were analyzed. The mean ± SD of near deviation in dry and cycloplegic conditions were -6.9 ± 8.1 and +6.4 ± 9.1 prism diopters, respectively, which were statistically significant ( P < 0.001). Distance deviation in cycloplegic conditions demonstrated an average difference of 0.8 prism diopters, compared to dry conditions ( P < 0.001). AC/A ratios were 4.7 ± 2.5 and 9.7 ± 3.9 (Δ/D) in non-cycloplegic and cycloplegic conditions, respectively, which was a statistically significant difference ( P < 0.001). The multiple regression indicated that among all under study variables, refraction (B coefficient: -2.4; P < 0.001) and near pre-cycloplegic deviation (B coefficient: 0.56; P < 0.001) were significantly associated with post-cycloplegic near deviation., Conclusion: The results of this study indicated that cycloplegia causes a considerable esophoric shift in near deviation and a negligible esophoric shift in distance deviation. As a result, the AC/A ratio demonstrated a significant increase due to unequal changes in near and distance deviation., Competing Interests: None., (Copyright © 2024 Asharlous et al.)

Background: Vaccination is a primary prevention approach to preventing disease by disconnecting the transmission chain. The current study utilized a BASNEF model framework to identify factors influencing subsequent doses of COVID-19 vaccination among older adults., Methods: This cross-sectional study was performed in the west of Iran in May 2022. The participants were selected via multi-stage sampling. Finally, 1120 participants contributed to the present study. The questionnaire consisted of three sections: a) Socio-demographic characteristics, b) cognitive impairments tests, and c) Questionnaire about the subsequent dose of COVID-19 vaccine uptake based on the BASNEF model. Data were analyzed using the software IBM AMOS-20 and SPSS-23 via one-way analysis of variance (ANOVA) and independent sample T-tests were used, too. The significance level of statistical tests was regarded as less than 0.05., Results: The presented results of analyzing 50% of the variance of vaccination intention as the dependent variable (R square = 0.497) and 10% of the behavior variance as the dependent variable (R square = 0.104) can be explained based on the BASNEF model. The enabling factors (β = 0.636, p < 0.001) and the intention (β = 0.322, p < 0.001) were important factors for subsequent doses of COVID-19 vaccine uptake in older adults., Conclusion: So, planning and implementing promotional intervention programs for older people (over 65; 80), females, illiterate, widows and divorced, good economic status, and urban areas is essential. It seems that enabling factors such as free vaccinations, vaccination inaccessible places such as public social security agencies, social supports such as involvement of the government and physicians, and improving information by the medium or knowledge-sharing experience, which can be further used to enhance the acceptance of subsequent doses of COVID-19 uptake in older adults., (© 2023. The Author(s).)

Objectives: The present study was conducted to examine the relationship between smartphone dependency and its effect on clinical tasks of nurses in educational and medical centers of Hamadan, in western Iran., Method: In this cross-sectional study, 248 nurses were selected via the proportional allocation sampling method. The required data were collected using a self-report, reliable and validated questionnaire, covering patterns of smartphone use, smartphone dependency, effects of smartphone dependency, and influence of smartphone on the clinical performance of nurses. The collected data were analyzed through descriptive statistics and logistic regression analysis., Results: The average age of the participants was 30.43 (± 5.68) years. The average smartphone dependency, effects of smartphone dependency, and clinical performance of the examined nurses were, respectively, 38.65 (20.93), 20.78 (13.90), and 29.48 (10.03). Clinical performance of nurses decreased with age ( P = 0.02) and increase of smartphone dependency ( P = 0.02), effects of smartphone dependency ( P ≤ 0.001), and smartphone use while working ( P ≤ 0.001). Higher work experience ( P = 0.02) and the application of smartphone multiple capabilities ( P = 0.02) had positive effects on the clinical performance of the examined nurses., Conclusions: The results of this study indicated that using smartphones affects the clinical performance of nurses, and if not well managed, it can lead to some physical, psychological, and social problems for the individual nurse, patients, and society. Thus, training nurses and developing regulations for the use of smartphones in the workplace must be considered by the relevant authorities., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Occupational and Environmental Medicine.)

Researchers have tried to find novel strategies for cancer treatment in the past decades. Among the utilized methods, administering oncolytic viruses (OVs) alone or combined with other anticancer therapeutic approaches has had promising outcomes, especially in solid tumors. Infecting the tumor cells by these viruses can lead to direct lysis or induction of immune responses. However, the immunosuppressive tumor microenvironment (TME) is considered a significant challenge for oncolytic virotherapy in treating cancer. Based on OV type, hypoxic conditions in the TME can accelerate or repress virus replication. Therefore, genetic manipulation of OVs or other molecular modifications to reduce hypoxia can induce antitumor responses. Moreover, using OVs with tumor lysis capability in the hypoxic TME may be an attractive strategy to overcome the limitations of the therapy. This review summarizes the latest information available in the field of cancer virotherapy and discusses the dual effect of hypoxia on different types of OVs to optimize available related therapeutic methods., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: The Arias-Stella reaction is a hormone-related atypical endometrial change characterized by cytomegaly, nuclear enlargement, and hyperchromasia of endometrial glands; typically associated with intrauterine or extrauterine pregnancies or with gestational trophoblastic disease. Although differentiating the Arias-Stella reaction (ASR) from clear cell carcinoma (CCC) of the endometrium is usually straightforward, but differentiating ASR might be difficult if it occurs outside the setting of pregnancy, in extra-uterine sites or in older patients. The aim of this study was to determine whether P504S/Alpha Methyacyl CoA racemase (AMACR) immunohistochemical (IHC) staining can be used to differentiate ASR from CCC., Methods: Fifty endometrial ASR and 57 CCC samples were assessed by IHC staining with antibody for AMACR. The immunoreactive score (IRS) was based on total intensity score (no staining to strong scored as 0-3) + percentage score (0-100% categorized as 0-3) ranged from 0 to 6. Positive expression was considered as a total IRS exceeding 2., Results: The mean age of the patients in the ASR was significantly lower than that of CCC (33.34 ± 6.36 and 57.81 ± 11.64 years old, respectively, p < 0.001). The overall AMACR staining score was significantly higher among CCC compared to ASR groups (p = 0.003). The positive and negative predictive values for AMACR expression in detecting CCC from ASR were 81.1% and 57%, respectively., Conclusion: IHC staining for AMACR can be helpful and a member of discriminatory IHC panel when clinical or histologic features cannot facilitate the differential diagnosis between ASR versus CCC., (© 2023. The Author(s).)

Research Question: What is the effect of vitamin D3 (1,25(OH) 2 D 3 ) on proliferation, cell cycle and apoptosis of endometrial stromal cells (ESC) in endometriotic patients?, Design: ESC isolated from 10 women with endometriosis and 10 healthy controls were treated with 1,25(OH) 2 D 3 . The proliferation of control endometrial stromal cells (CESC), eutopic endometrial stromal cells (EuESC) and ectopic endometrial stromal cells (EESC) was analysed 72 h after the treatment using methyl thiazolyl tetrazolium assay. Propidium iodide staining and flow cytometry were used to determine the cell cycle distribution in ESC. Annexin V/propidium iodide double staining was used to evaluate apoptosis in ESC., Results: In the presence of oestrogen, 1,25(OH) 2 D 3 treatment inhibited the proliferation of ESC from all three origins (P = 0.009 for CESC, P = 0.005 for EuESC and P < 0.001 for EESC). The percentage of S phase cells in EESC was higher than in EuESC and CESC (P = 0.002 and P = 0.001, respectively). The percentage of S phase cells in EuESC was higher than in CESC (P = 0.005). The percentage of G1 phase cells in EESC was lower than that of EuESC and CESC (P = 0.003 and P = 0.002, respectively) and the percentage of G1 phase cells in EuESC was lower than that of CESC (P = 0.007). Moreover, 1,25(OH) 2 D 3 inhibited cell cycle regardless of cell type (P = 0.002 in EESC, P = 0.001 in EuESC and P = 0.014 in CESC), but in the absence of oestrogen, inhibited cell cycle only in EuESC (P = 0.012)., Conclusions: Although 1,25(OH) 2 D 3 increased apoptotic and necrotic cells and decreased live cells in the EuESC and EESC, it did not affect apoptosis in CESC and only increased necrotic cells. These findings indicate that 1,25(OH) 2 D 3 potentially has a growth-inhibiting and pro-apoptotic effect on ESC from endometriotic patients., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: This study aimed to assess the effect of laser irradiation and Tooth Mousse on tooth hypersensitivity (TH) after office bleaching (OB)., Materials and Methods: This clinical trial, parallel-design split-mouth nonrandomized was conducted on 30 patients requiring OB. After scaling and fabrication of a custom tray, 35% hydrogen peroxide was applied on all teeth, and 940 nm diode laser (10 W, Class IV, 110-240 V) was irradiated to the upper and lower right quadrants. Laser in off mode was used for the left quadrants. Bleaching agent was then reapplied. After completion of bleaching, a custom tray containing tooth Mousse was placed on the maxillary arch while the tray was used without the paste for the mandibular arch. A visual analog scale was used to assess the degree of TH at 15 min and 24 h after OB. Data were compared using t -test, paired t -test, and analysis of variance. Significance level was set at α = 0.05., Results: Comparison of TH at 15 min and 24 h after OB showed a significantly lower TH score in the left upper quadrant (tooth Mousse alone) than right upper quadrant (both laser and Tooth Mousse) ( P < 0.05). The TH score in the right upper quadrant was significantly lower than that in the right lower quadrant (laser only) ( P < 0.05). The mean TH score in the left upper quadrant was insignificantly lower than that in the left lower quadrant (no intervention) ( P > 0.05)., Conclusion: The use of 940 nm diode laser for OB increases the postoperative TH. The application of Tooth Mousse can effectively decrease TH after OB with/without laser irradiation., 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.)

Background: Endothelin-1 (ET-1) is a peptide overexpressed in gastric cancer (GC) and linked to carcinogenesis and resistance to chemotherapy. Applying microRNAs (miRNAs/miRs) to downregulate ET-1 and reverse resistance to commonly used chemotherapy drugs such as 5-fluorouracil (5-FU) is practical., Methods: The current study sought to evaluate the miR-648 expression in GC and any plausibility of its replacement, either with or without the combination of chemo agents to downregulate ET-1 expression through interaction with its target gene. To this end, miR-648 and ET-1 expression levels were assessed in GC tissues and adjacent non-tumor tissues driven from 65 patients who had already undergone surgery, fifteen of which had received 5-FU before surgery. The impact of miR-648 and chemo agents on ET-1 expression was measured using qPCR and Western blotting. Further, an MTT assay was conducted to assess its association with cell viability. Ultimately, the association of miR-648 and ET-1 with clinicopathological characteristics was evaluated., Results: The current study revealed that miR-648 was considerably down-regulated, while ET-1 was substantially up-regulated in patients with GC. The 5-FU caused a significant increase in miR-648 and reduced ET-1 expression. It was also determined that overexpression of miR-648 suppressed ET-1 production, notably when combined with 5-FU, leading to survival reduction. These results further showed that miR-648 replacement could sensitize chemoresistant GC cells. Besides, a significant association between ET-1 and miR-648 with clinicopathological features was discovered CONCLUSIONS: miR-648 replacement may serve as a potential oncosuppressive therapeutic approach that warrants further investigation to translate into an effective GC treatment., Competing Interests: Competing interests None., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Tumor-infiltrating lymphocytes (TILs), frontline soldiers of the adaptive immune system, are recruited into the tumor site to fight against tumors. However, their small number and reduced activity limit their ability to overcome the tumor. Enhancement of TILs number and activity against tumors has been of interest for a long time. A lack of knowledge about the tumor microenvironment (TME) has limited success in primary TIL therapies. Although the advent of engineered T cells has revolutionized the immunotherapy methods of hematologic cancers, the heterogeneity of solid tumors warrants the application of TILs with a wide range of specificity. Recent advances in understanding TME, immune exhaustion, and immune checkpoints have paved the way for TIL therapy regimens. Nowadays, TIL therapy has regained attention as a safe personalized immunotherapy, and currently, several clinical trials are evaluating the efficacy of TIL therapy in patients who have failed conventional immunotherapies. Gaining favorable outcomes following TIL therapy of patients with metastatic melanoma, cervical cancer, ovarian cancer, and breast cancer has raised hope in patients with refractory solid tumors, too. Nevertheless, TIL therapy procedures face several challenges, such as high cost, timely expansion, and technical challenges in selecting and activating the cells. Herein, we reviewed the recent advances in the TIL therapy of solid tumors and discussed the challenges and perspectives., 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 Kazemi, Sadri, Najafi, Rahimi, Baghernejadan, Khorramdelazad and Falak.)

Background: This study aimed to identify the predictors of the intention to receive the COVID-19 vaccine among Iranian health care workers (HCWs) based on the Theory of Planned Behavior (TPB)., Methods: The study was a descriptive cross-sectional study that was conducted on 473 personnel working in hospitals of Hamadan, in May 2021 and before COVID-19 vaccination on hospital staff. The multi-stage sampling method was used for choosing participants. The survey included socio-demographic, questions related to TPB dimensions, and intention to receive a COVID-19 vaccine. Qualitative and quantitative data analyses were performed using the Chi-square test and T-test, respectively. Predictors of COVID-19 vaccination intention were determined using the logistic regression model., Results: Seventy percent of 361 eligible respondents stated their willingness to receive COVID-19 vaccine. The participants with the intention to receive COVID-19 vaccine had higher scores of attitude (7.25 ± 3.92 vs. 4.40 ± 5.14) and norm (3.04 ± 2.92 vs. -0.5 ± 3.18) ( P < 0.001). Having an underlying disease and being married were significantly associated with the intention to receive COVID-19 vaccine ( P < 0.05). Higher attitude and norm scores as a construct of the TPB were associated with an increase in intention to receive COVID-19 vaccine., Conclusions: The results of this study showed that the vaccination intention was affected by social, demographic, health, and behavioral features, such as age, marital status, underlying diseases, subjective norms, and attitude. Therefore, age groups below 50, single people, and those with no underlying diseases were eligible to be the target of interventional programs., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Occupational and Environmental Medicine.)

Hypoxia is a common characteristic of the tumor microenvironment. In response to hypoxia, expression of the hypoxia-inducible factor (HIF) can lead to activation of downstream molecular events such as epithelial-mesenchymal transition (EMT), invasion, and angiogenesis. In this study, CoCl2 was used to simulate hypoxia in SKBR3 and HEK293T cell lines to investigate whether this treatment can induce hypoxia-associated EMT and invasion in the studied cells. SKBR3 and HEK293T cells were treated with different concentrations of CoCl2 at different exposure times and their viability was analyzed. To confirm successful hypoxia induction, the expression levels of HIF1α and vascular endothelial growth factor A (VEGFA) mRNA were assessed. Additionally, the expression of EMT-associated markers including snail, E-cadherin, N-cadherin, and vimentin, as well as invasion-related genes including matrix metalloproteinase-2 (MMP2) and MMP9 was measured. We found that cell viability in CoCl2-treated cells was concentration-dependent and was not affected at low doses. While the expression of HIF and VEGFA genes was upregulated following hypoxia induction. E-cadherin expression was significantly downregulated in HEK293T cells; while, N-cadherin and snail were upregulated in both cell lines. Moreover, an increment of MMP expression was only observed in SKBR3 cells. Taken together, the findings indicated that CoCl2 can mimic hypoxia in both cell lines, but EMT was triggered in SKBR3 cells more effectively than in HEK293T cells, and invasion was only stimulated in SKBR3 cells. In conclusion, SKBR3 cancer cells can be used as an EMT model to better understand its control and manipulation mechanisms and to investigate new therapeutic targets for the suppression of tumor metastasis.

Objective: The goal of treatment in palindromic rheumatism (PR) is to control the attacks and prevent disease evolution to chronic arthritis. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) including antimalarial and methotrexate cannot control attacks in all patients., Methods: In this retrospective study, we assessed the efficacy of leflunomide in patients with PR who had an inadequate response to DMARDs. In this study, patients who had a diagnosis of PR and were treated with leflunomide because of active disease despite treatment with csDMARDs for at least 6 months were included. Remission was defined as no attacks for 3 months and prednisolone dose ≤5 mg/d. Leflunomide treatment failure was defined as failure to achieve remission, the need to add other DMARDs for controlling attacks and disease progression to chronic arthritis during treatment with leflunomide., Results: Ten cases with active disease despite treatment with hydroxychloroquine and methotrexate and low-dose prednisolone treated with leflunomide were included in the study. During the 12.6 ± 7.5 months of treatment with leflunomide, the frequency of attacks significantly decreased. Complete and partial remission were achieved in 90% of patients., Conclusion: Our results indicate that leflunomide controls PR attacks and it might be a new option for patients with PR., (© 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Holocarboxylase synthetase (HLCS) catalyzes the biotinylation of five distinct biotin-dependent carboxylases and perhaps chromatin proteins. HLCS deficiency causes multiple carboxylase deficiency which results in fatal consequences unless patients are diagnosed early and treated with pharmacological doses of biotin. The objective of this study was to develop an HLCS conditional knockout (KO) mouse and assess effects of HLCS knockout on embryo survival. In the mouse, exon 8 is flanked by LoxP sites, thereby removing a catalytically important region upon recombination by Cre. HLCS conditional KO mice were backcrossed for 14 generations with C57BL/6J mice to yield Hlcstm1Jze. Fertility and weight gain were normal and no frank disease phenotypes and abnormal feeding behavior were observed in the absence of Cre. HLCS knockout was embryonic lethal when dams homozygous for both the floxed Hlcs gene and tamoxifen-inducible Cre recombinase (denoted Hlcstm1.1Jze) were injected with tamoxifen on gestational days 2.5 and 10.5. This is the first report of an HLCS conditional KO mouse, which enables studies of the roles of HLCS and biotin in intermediary metabolism., Competing Interests: The authors have declared that no competing interests exist. J.Z. serves as consultant for PureTech Health, Inc. (Boston, MA) for work not related to this paper.

Schwann cells (SCs) are known to produce extracellular vesicles (EV) that participate in cell-cell communication by transferring cargo to target cells, including mRNAs, microRNAs, and biologically active proteins. Herein, we report a novel mechanism whereby SC EVs may regulate PNS physiology, especially in injury, by controlling the activity of TNFα. SCs actively sequester tumor necrosis factor receptor-1 (TNFR1) into EVs at high density, accounting for about 2% of the total protein in SC EVs (~1000 copies TNFR1/EV). Although TNFR2 was robustly expressed by SCs in culture, TNFR2 was excluded from SC EVs. SC EV TNFR1 bound TNFα, decreasing the concentration of free TNFα available to bind to cells and thus served as a TNFα decoy. SC EV TNFR1 significantly inhibited TNFα-induced p38 MAPK phosphorylation in cultured SCs. When TNFR1 was proteolytically removed from SC EVs using tumor necrosis factor-α converting enzyme (TACE) or neutralized with antibody, the ability of TNFα to activate p38 MAPK in the presence of these EVs was restored. As further evidence of its decoy activity, SC EV TNFR1 modified TNFα activities in vitro including: (1) regulation of expression of other cytokines; (2) effects on SC morphology; and (3) effects on SC viability. SC EVs also modified the effects of TNFα on sciatic nerve morphology and neuropathic pain-related behavior in vivo. By sequestering TNFR1 in EVs, SCs may buffer against the potentially toxic effects of TNFα. SC EVs provide a novel mechanism for the spatial and temporal regulation of neuro-inflammation., (© 2021 Wiley Periodicals LLC.)

The COVID-19 pandemic has accelerated neurological, mental health disorders, and neurocognitive issues. However, there is a lack of inexpensive and efficient brain evaluation and screening systems. As a result, a considerable fraction of patients with neurocognitive or psychobehavioral predicaments either do not get timely diagnosed or fail to receive personalized treatment plans. This is especially true in the elderly populations, wherein only 16% of seniors say they receive regular cognitive evaluations. Therefore, there is a great need for development of an optimized clinical brain screening workflow methodology like what is already in existence for prostate and breast exams. Such a methodology should be designed to facilitate objective early detection and cost-effective treatment of such disorders. In this paper we have reviewed the existing clinical protocols, recent technological advances and suggested reliable clinical workflows for brain screening. Such protocols range from questionnaires and smartphone apps to multi-modality brain mapping and advanced imaging where applicable. To that end, the Society for Brain Mapping and Therapeutics (SBMT) proposes the Brain, Spine and Mental Health Screening (NEUROSCREEN) as a multi-faceted approach. Beside other assessment tools, NEUROSCREEN employs smartphone guided cognitive assessments and quantitative electroencephalography (qEEG) as well as potential genetic testing for cognitive decline risk as inexpensive and effective screening tools to facilitate objective diagnosis, monitor disease progression, and guide personalized treatment interventions. Operationalizing NEUROSCREEN is expected to result in reduced healthcare costs and improving quality of life at national and later, global scales.

Endometriosis is a chronic inflammatory disease that has been reported to be associated with immune system dysfunction. On the other hand, the effect of Vitamin D as an immune modulator and its relation with several autoimmune and inflammatory diseases has been previously investigated. Moreover, several studies have reported the polymorphisms of VDR and VDBP genes can change the functions of these molecules. Therefore, these polymorphisms may be influential on endometriosis pathogenesis. In this study, we aimed at evaluating the association between VDR gene (FokI (F/f), BsmI (B/b), ApaI (A/a), TaqI (T/t)), and VDBP gene (GC*1S, GC*1F, and GC*2) polymorphisms with endometriosis in Iranian women population. This case-control study was performed on 120 women with endometriosis and 110 healthy women. ARMS-PCR and PCR-RFLP methods were used to inspect polymorphisms in VDR and VDBP genes, respectively. Based on the results, there was no statistically significant difference between the cases with endometriosis and control subjects in terms of genotypes and allele frequencies of VDR and VDBP gene polymorphisms. These data suggest that VDR and VDBP gene polymorphisms may have no role in endometriosis susceptibility in Iranian women., (© 2021. Society for Reproductive Investigation.)

Exosomes facilitate cell-to-cell communication by transferring regulatory molecules such as miRNA from donor to recipient cells, for example, miR-21-5p and miR-30d promote placentation. Exosomes and their miRNA cargos are not exclusively obtained from endogenous synthesis but may also be absorbed from dietary sources, such as milk. This study assessed the effects of milk exosomes and miRNA cargos on embryo development and fertility in C57BL/6 mice. Fluorophore-labeled milk exosomes, miR-21-5p and miR-30d accumulated in murine placenta and embryos following oral gavage. Seventeen mRNAs, miR-21-5p and miR-30d were differentially expressed in placentas of pregnant mice fed a milk exosome and RNA-depleted (ERD) diet or a milk exosome and RNA-sufficient (ERS) diet. Eight of these mRNAs encode proteins implicated in the synthesis of extracellular matrix components, cell adhesion and migration. Changes in mRNA expression were associated with corresponding changes in protein expression, for example, collagen type I. The size of litters born to dams fed ERD was 25-50% smaller than those born to ERS controls. This study implicates dietary exosomes and miRNA in placenta development and embryo survival.

Background: Leishmaniasis is the most important parasitic disease in Iran and is the third highest rate of rural cutaneous leishmaniasis in the world. Chitosan-polyethylene oxide nanocomposite fibers can be a suitable replacement for ordinary bandages. For the first time, in the absence of any published reports, the present in vitro study aimed to evaluate the anti-leishmanial effects of chitosan (CS)-polyethylene oxide (PEO)-berberine nanofibers on Leishmania major ., Methods: The present experimental study was conducted in 2018 in Tehran, Iran. The CS-PEO nanofibers containing berberine, as a natural anti-parasitic agent, were prepared using the electrospinning technique. Biocompatibility and fibroblast proliferation on nanofibers were investigated. In addition, the anti-leishmanial activity of CS-PEO nanofibers in both the promastigote and amastigote stages of Leishmania major was evaluated after parasite vital staining and MTT assay and compared to a control group. Statistical analysis was performed using SPSS software (version 18.0). Statistically significant differences were determined using the one-way ANOVA. The Duncan and Dunnett post hoc tests were used for within-group comparisons. P<0.05 was considered statistically significant., Results: The results showed that nanofiber scaffolds with a mean diameter of 77.5±19.5 nm were perfect, regular, bead-free, and non-toxic, on which fibroblast cells grew well and proliferated. In addition, the optical density indicated that berberine 20% (w/v) significantly prevented promastigotes growth (IC 50 =0.24 μg/mL) and amastigotes death (IC 50 =0.91 μg/mL) compared with other concentrations and the control group., Conclusion: The study on the cytotoxic effects showed that CS-PEO-berberine nanofibers had strong lethal effects on Leishmania major in promastigote and amastigote stages in vitro . Further studies are required to investigate the effects of this nanofiber on leishmanial ulcers in laboratory animals and clinical cases., (Copyright: © Iranian Journal of Medical Sciences.)

Purpose: To report clinical, histopathological, and treatment features of small cell carcinoma of (SmccB) bladder during 7 years in a referral center., Methods: The clinical, histopathological features, treatment modalities, and outcome of all patients with bladder SmccB treated between 2009 and 2016 who were managed in Hasheminejad Kidney Center (HKC) were retrospectively collected., Results: Thirteen patients were diagnosed and managed with SmccB. The average age of patients was 64.92 years. For each patient, 8 markers were used for IHC staining on average. Neuroendocrine markers such as CD 56, Neuron Specific Enolase, Synaptophysin, and Chromogranin were found in a significant percentage of patients (69%, 38%, 54%, and 31% respectively). Patients were managed with TURBT alone (N=3), chemotherapy after TURBT (N=4), chemotherapy plus radical surgery (N=4) and radical surgery alone (N=2). The best clinical result was seen in chemotherapy received patients with or without radical surgery. The mean(SE) of survival rate in patients who received only chemotherapy alone was 42.4 (10.0) months, while in those who were managed with chemotherapy plus radical surgery it was 47.7 (10.1) months., Conclusion: In our center immunohistochemistry was needed for definitive diagnosis in 17/19 samples. Misdiagnosis happened in two samples without IHC request. We think that use of immunohistochemistry should be mandatory for diagnosis of SmccB to exclude misdiagnosis. Chemotherapy is the most important part of treatment and the addition of radical surgery can slightly improve patients' survival.

Background: Hypoxia inducible factor-1 (HIF-1) is considered as the most activated transcriptional factor in response to low oxygen level or hypoxia. HIF-1 binds the hypoxia response element (HRE) sequence in the promoter of different genes, mainly through the bHLH domain and activates the transcription of genes, especially those involved in angiogenesis and EMT. Considering the critical role of bHLH in binding HIF-1 to the HRE sequence, we hypothesized that bHLH could be a promising candidate to be targeted in hypoxia condition., Methods: We inserted an inhibitory bHLH (ibHLH) domain in a pIRES2-EGFP vector and transfected HEK293T cells with either the control vector or the designed construct. The ibHLH domain consisted of bHLH domains of both HIF-1a and Arnt, capable of competing with HIF-1 in binding to HRE sequences. The transfected cells were then treated with 200 µM of cobalt chloride (CoCl 2 ) for 48 h to induce hypoxia. Real-time PCR and western blot were performed to evaluate the effect of ibHLH on the genes and proteins involved in angiogenesis and EMT., Results: Hypoxia was successfully induced in the HEK293T cell line as the gene expression of VEGF, vimentin, and β-catenin were significantly increased after treatment of untransfected HEK293T cells with 200 µM CoCl 2 . The gene expression of VEGF, vimentin, and β-catenin and protein level of β-catenin were significantly decreased in the cells transfected with either control or ibHLH vectors in hypoxia. However, ibHLH failed to be effective on these genes and the protein level of β-catenin, when compared to the control vector. We also observed that overexpression of ibHLH had more inhibitory effect on gene and protein expression of N-cadherin compared to the control vector. However, it was not statistically significant., Conclusion: bHLH has been reported to be an important domain involved in the DNA binding activity of HIF. However, we found that targeting this domain is not sufficient to inhibit the endogenous HIF-1 transcriptional activity. Further studies about the function of critical domains of HIF-1 are necessary for developing a specific HIF-1 inhibitor.

Objectives: Rapid healing of cutaneous leishmaniasis as one of the most important parasitic diseases leads to the decrease of scars and prevention of a great threat to the looks of the affected people. Today, the use of nano-scaffolds is rapidly increasing in tissue engineering and regenerative medicine with structures similar to the target tissue. Chitosan (CS) is a bioactive polymer with antimicrobial and accelerating features of healing wounds, which is commonly used in biomedicine. This study aimed to investigate the effects of CS/polyethylene oxide (PEO)/berberine (BBR) nanofibers on the experimental ulcers of Leishmania major in BALB/c mice., Materials and Methods: CS/PEO/BBR nanofibers were prepared by the electrospinning method, and their morphology was examined by SEM, TEM, and AFM. Then, water absorption, stability, biocompatibility, porosity, and drug release from nano-scaffolds were explored. Afterward, 28 BALB/c mice infected with the parasite were randomly divided into control and experimental groups, and their wounds were dressed with the produced nano-scaffolds. Finally, the effect of nanobandage on the animals was investigated by macroscopic, histopathologic, and in vivo imaging examinations., Results: The prepared nanofibers were completely uniform, cylindrical, bead-free, and biocompatible with an average diameter of 94±12 nm and had appropriate drug release. In addition, the reduced skin ulcer diameter ( P= 0.000), parasite burden ( P= 0.003), changes in the epidermis ( P= 0.023), and dermis ( P= 0.032) indicated significantly strong effectiveness of the produced nano-scaffolds against leishmania ulcers., Conclusion: Studies showed that CS/PEO/BBR nanofibers have a positive effect on the rapid healing of leishmania ulcers. Future studies should focus on other chronic ulcers treatment.

Exosomes and exosome-like vesicles participate in cell-to-cell communication in animals, plant, and bacteria. Dietary exosomes in bovine milk are bioavailable in nonbovine species, but a fraction of milk exosomes reaches the large intestine. We hypothesized that milk exosomes alter the composition of the gut microbiome in mice. C57BL/6 mice were fed AIN-93G diets, defined by their content of bovine milk exosomes and RNA cargos: exosome/RNA-depleted (ERD) versus exosome/RNA-sufficient (ERS) diets. Feeding was initiated at age 3 wk, and cecum content was collected at ages 7, 15, and 47 wk. Microbial communities were identified by 16S rRNA gene sequencing. Milk exosomes altered bacterial communities in the murine cecum. The abundance of three phyla, seven families, and 52 operational taxonomic units (OTUs) was different in the ceca from mice fed ERD and ERS ( P < 0.05). For example, at the phylum level, Tenericutes had more than threefold abundance in ERS mice at ages 15 and 47 wk compared with ERD mice ( P < 0.05). At the family level, Verrucomicrobiaceae were much less abundant in ERS mice compared with ERD mice age 47 wk ( P < 0.05). At the OTU level, four OTUs from the family of Lachnospiraceae were more than two times more abundant in ERS mice compared with ERD at age 7 and 47 wk ( P < 0.05). We conclude that exosomes in bovine milk alter microbial communities in nonbovine species, suggesting that exosomes and their cargos participate in the crosstalk between bacterial and animal kingdoms. NEW & NOTEWORTHY This is the first report that exosomes from bovine milk alter microbial communities in mice. This report suggests that the gut microbiome facilitates cell-to-cell communication by milk exosomes across species boundaries, and milk exosomes facilitate communication across animal and bacteria kingdoms.

Interleukin-10 (IL-10) is a pleiotropic cytokine, which has both regulatory and stimulatory effects on different immune cell types. Different studies have reported the importance of IL-10 and Transforming growth factor-beta (TGF-β) in the regulation of B cell class switching the production of immunoglobulin A (IgA); however, the underlying mechanisms remain to be fully elucidated. The objective of this study was to investigate the TGF-β response during B stimulation of human B cells by IL-10. Pan B cells of healthy donors were negatively purified by a magnetic cell separation technique. B cells were cultured with multimeric CD40 ligand (mCD40L) and IL-10 for two and seven days. After harvesting in specific days, TGF-β receptor II and surface IgA expression was determined by flow cytometry, while IgA and TGF-β secretion was assessed by enzyme-linked immunosorbent assay. B cells endogenously expressed TGF-β receptor II and after 48 hours cultivation with mCD40L or mCD40L plus IL-10, both the expression of this receptor and the production of TGF-β were significantly increased. Notably, TGF-β levels following stimulation with mCD40L and IL-10 were higher than those produced by B cells stimulated with mCD40L alone. Furthermore, at day 7 and following IL-10 stimulation, there was a significant rise in the amount of IgA secretion by class-switched plasma cells, which was higher than stimulation with mCD40L alone. Our findings suggest that IL-10 can modulate TGF-β production and TGF-β receptor expression in mCD40-activated human B lymphocytes.

Although recent studies have reported different aspects of autophagy, from pro-survival to pro-death roles of this process in malignant cells, the underlying mechanisms by which autophagy inhibitors contribute toward the induction of programmed cell death in cancerous cells are still unclear. In the present study, we have attempted to explore some of the molecular features of pharmacological inhibition of autophagy in TF-1 cells (an acute erythroid leukemia model). Our findings indicated that ara-C induces autophagy (with alteration of LC3B, p62, and Beclin-1) in the cells; however, targeting autophagy by 3-methyladenine and chloroquine significantly increased caspase-dependent apoptosis and the sub-G1 compartment in ara-C-treated cells. Moreover, cell cycle analysis showed that 3-MA, as an early-stage autophagy inhibitor, could elevate the cell population in the G0/G1 cell cycle phase, which was associated with upregulation of p21 and p27 expressions. Interestingly, autophagy inhibition was also accompanied by downregulation of c-Myc gene and protein expression levels and upregulated levels of Bax and Bak gene expressions. In addition, following inhibition of autophagy, the levels of tumor-suppressive miRNA (i.e. miR-204) increased, whereas the values of oncogenic miRNAs (including miR-21, miR-221, miR-30a, and miR-17) decreased. Overall, our experiments indicate that autophagy inhibitors (especially chloroquine) seem to be promising agents for combination therapy in acute erythroid leukemia.

Background: Evidence suggests that dietary microRNAs (miRs) are bioavailable and regulate gene expression across species boundaries. Concerns were raised that the detection of dietary miRs in plasma might have been due to sample contamination or lack of assay specificity. Objectives: The objectives of this study were to assess potential confounders of plasma miR analysis and to detect miRs from bovine milk in human plasma., Methods: Potential confounders of plasma miR analysis (circadian rhythm, sample collection and storage, calibration, and erythrocyte hemolysis) were assessed by quantitative reverse transcriptase polymerase chain reaction (PCR) by using blood from healthy adults (7 men, 6 women; aged 23-57 y). Bovine miRs were analyzed by RNase H2-dependent PCR (rhPCR) in plasma collected from a subcohort of 11 participants before and 6 h after consumption of 1.0 L of 1%-fat bovine milk., Results: The use of heparin tubes for blood collection resulted in a complete loss of miRs. Circadian variations did not affect the concentrations of 8 select miRs. Erythrocyte hemolysis caused artifacts for some miRs if plasma absorbance at 414 nm was >0.300. The stability of plasma miRs depended greatly on the matrix in which the miRs were stored and whether the plasma was frozen before analysis. Purified miR-16, miR-200c, and cel-miR-39 were stable for ≤24 h at room temperature, whereas losses equaled ≤80% if plasma was frozen, thawed, and stored at room temperature for as little as 4 h. rhPCR distinguished between bovine and human miRs with small variations in the nucleotide sequence; plasma concentrations of Bos taurus (bta)-miR-21-5p and bta-miR-30a-5p were >100% higher 6 h after milk consumption than before milk consumption., Conclusions: Confounders in plasma miR analysis include the use of heparin tubes, erythrocyte hemolysis, and storage of thawed plasma at room temperature. rhPCR is a useful tool to detect dietary miRs., (© 2018 American Society for Nutrition. All rights reserved.)

T-cell immunoglobulin and mucin domain (TIM)-3 have been shown to negatively regulate Th1 cell-mediated immunity. Activation of TIM-3 by galectin-9 induces Th1 cell apoptosis, which may contribute to skewing of immune response towards Th2-dominant immunity. The aim of this study was to determine whether certain genetic variations of TIM-3 influence predisposition to asthma in a sample of Iranian population. This case-control study was conducted on 209 patients with asthma and 200 healthy controls. The +4259 T>G and -574 G>T polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and amplification refractory mutation system-PCR(ARMS-PCR). Total serum IgE was further measured with ELISA. Notably, +4259T > G and-574G>T polymorphisms of TIM-3 were significantly associated with the susceptibility to asthma. In addition, the present study showed a significant difference between the distribution frequency of the GT + TT genotype and T allele on the +4259 T>G and -574 G>T locus between the groups.However, no correlation between the +4259 T > G and -574G > T polymorphisms and total serum IgE levels were observed. Together these results suggest that the TIM-3 +4259 T>G and -574 G>T polymorphisms are greatly associated with the susceptibility of Iranian population to asthma, which could open up new horizons for  better understanding of the pathophysiology, diagnostic, prognostic and therapeutic approaches of asthma.

This investigation is performed to evaluate the impact of static magnetic field on the Cell growth alignment, and differentiation potential in Human Mesenchymal Stem cells derived from human newborn cords. In vitro -cultured mesenchymal stem cells derived from human newborn cords were exposed to SMF up to 24 mT and compared with the control (unexposed) cultures. Viability was assessed via Trypan Blue staining and MTT assay. Cell cycle progression was studied after flow cytometry data analysis. Sox-2, Nanong, and Oct-4 Primers used for RT-PCR experiment. Morphological studies showed that the exposed cells were significantly aligned in parallel bundles in a correlation with the magnetic field lines. Viability measurements showed a significant reduction in cell viability which was noted after exposure to static magnetic field and initiated 36 h after the end of exposure time. Flow cytometric data analysis confirmed a decrease in G1 phase cell population within the treated and cultured groups compared with the corresponding control samples. However, the induced changes were recovered in the cell cultures after the post-exposure culture recovery time which may be attributed to the cellular repair mechanisms. Furthermore, the proliferation rate and Oct-4 gene expression were reduced due to the 18 mT static magnetic field exposure. The significant proliferation rate decrease accompanied by the Sox-2, Nanong, and Oct-4 gene expression decline, suggested the differentiation inducing effects of SMF exposure. Exposure to Static Magnetic fields up to 24 mT affects mesenchymal stem cell alignment and proliferation rate as well as mRNA expression of Sox-2, Nanong, and Oct-4 genes, therefore can be considered as a new differentiation inducer in addition to the other stimulators., (© Biomedical Engineering Society 2017.)

An ionic liquid-mediated multi-walled carbon nanotube (MWCNT)-polydimethylsiloxane (PDMS) sorbent was developed for headspace solid-phase microextraction (HS-SPME) of phenolic compounds from human urine samples. Sol-gel method was used to prepare this sorbent. For this purpose, MWCNTs were functionalized covalently and were attached chemically to the hydroxyl-terminated PDMS. Prepared fiber showed high thermal stability (over than 320°C) and good lifespan (>210 times). These good performances can be attributed to the performance of carbon nanotubes and sol-gel method. Affecting parameters on the efficiency of HS-SPME were investigated and optimized. Under the optimal conditions, linear dynamic ranges were observed over a range of 0.002-200 ng mL -1 with limits of detection from 0.0005 to 0.005 ng mL -1 and limits of quantitation between 0.002 and 0.02 ng mL -1 The relative standard deviations for one fiber (repeatability) (n = 5) at three different concentrations (0.05, 2 and 100 ng mL -1 ) were obtained from 4.6 up to 6.7% and between fibers or batch to batch (n = 3) (reproducibility) in the range of 5.7-7.8%. Urine samples were used as real samples. All real samples were spiked at 0.5 ng mL -1 of understudy analytes and the relative recovery percentages obtained from 90.7 to 102.1%., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Extracellular vesicles (EVs) in milk harbor a variety of compounds, including lipids, proteins, noncoding RNAs, and mRNAs. Among the various classes of EVs, exosomes are of particular interest, because cargo sorting in exosomes is a regulated, nonrandom process and exosomes play essential roles in cell-to-cell communication. Encapsulation in exosomes confers protection against enzymatic and nonenzymatic degradation of cargos and provides a pathway for cellular uptake of cargos by endocytosis of exosomes. Compelling evidence suggests that exosomes in bovine milk are transported by intestinal cells, vascular endothelial cells, and macrophages in human and rodent cell cultures, and bovine-milk exosomes are delivered to peripheral tissues in mice. Evidence also suggests that cargos in bovine-milk exosomes, in particular RNAs, are delivered to circulating immune cells in humans. Some microRNAs and mRNAs in bovine-milk exosomes may regulate the expression of human genes and be translated into protein, respectively. Some exosome cargos are quantitatively minor in the diet compared with endogenous synthesis. However, noncanonical pathways have been identified through which low concentrations of dietary microRNAs may alter gene expression, such as the accumulation of exosomes in the immune cell microenvironment and the binding of microRNAs to Toll-like receptors. Phenotypes observed in infant-feeding studies include higher Mental Developmental Index, Psychomotor Development Index, and Preschool Language Scale-3 scores in breastfed infants than in those fed various formulas. In mice, supplementation with plant-derived MIR-2911 improved the antiviral response compared with controls. Porcine-milk exosomes promote the proliferation of intestinal cells in mice. This article discusses the above-mentioned advances in research concerning milk exosomes and their cargos in human nutrition. Implications for infant nutrition are emphasized, where permitted, but data in infants are limited., Competing Interests: 2 Author disclosures: J Zempleni, A Aguilar-Lozano, M Sadri, S Sukreet, S Manca, D Wu, F Zhou, and E Mutai, no conflicts of interest., (© 2017 American Society for Nutrition.)

TIM (T-cell immunoglobulin (Ig) and mucin domain)-1, one of the members of TIM family, expresses on Th2 cells and promotes the production of Th2 signature cytokines. This can increase a series of responses in these cells which could be one of the causes of asthma or asthma-related phenotypes. The aim of this study was to investigate whether a TIM-1 promoter single nucleotide polymorphism (SNP), -416 G>C, is associated with asthma in Iranian population. In this case-control study, existence of the -416 G>C polymorphism was assessed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in 300 patients with asthma (97 atopic, 203 nonatopic) and 309 healthy volunteers. Additionally, the relationship between these polymorphism genotypes and total serum IgE levels in this Iranian population was evaluated. We discovered a significant association between the -416 G>C polymorphism and atopic asthma susceptibility in the population, but this SNP showed no connection with nonatopic asthma (P < 0.05). However, our results showed significant relation between this polymorphism and serum IgE level (P < 0.05). Our results suggest that -416 G>C polymorphism in TIM-1 gene could be a predisposing factor for atopic asthma in Iranian population, and CC genotype of this SNP can be associated with increased level of IgE in patients with asthma in the same population., (© 2015 John Wiley & Sons Ltd.)

Objectives: Hepatitis C is a major cause of liver failure worldwide. Current therapies applied for this disease are not fully effective and produce side effects in most cases. Non-structural protein 3 helicase (NS3) of HCV is one of the key enzymes in viral replication and infection. Therefore, this region is a promising target to design new drugs and therapies against HCV infection. The aim of this study was cloning and expression of HCV NS3 helicase fragment in Escherichia coli BL21 (DE3) using pET102/D-TOPO expression vector and studying immunoreactivity of the expressed antigen in Iranian infected with hepatitis C., Materials and Methods: The viral RNA was extracted from the serum of HCV infected patient. The NS3 helicase region was amplified by RT-PCR. The PCR product was directionally cloned into the expression vector pET102/D-TOPO and transformed into the BL21 strain of E. coli (DE3). The transformed bacteria were then induced by adding 1mM isopropyl-β-D-thiogalactopyranoside (IPTG) into the culture medium to enhance the protein expression. SDS-PAGE and western blotting were carried out to identify the protein under investigation, and finally purified recombinant fusion protein was used as the antigen for ELISA method., Results: The insertion of the DNA fragment of the NS3 region into the expression vector was further confirmed by PCR and sequencing. SDS-PAGE analysis showed the successful expression of the recombinant protein of interest. Furthermore, immunoreactivity of fusion NS3 helicase was confirmed by ELISA and western blotting., Conclusion: It seems that this recombinant protein could be a useful source of antigen for future studies on HCV diagnosis and therapy.

Corneal abrasion is the most common ophthalmologic complication that occurs during general anesthesia for nonocular surgery. Such abrasions can be caused by a variety of mechanisms and can lead to sight-threatening microbial keratitis and permanent scarring. There is no standard mode of protecting the cornea during general anesthesia for nonocular surgery. Methods described in the literature are not entirely effective and may be associated with unwanted side effects. Taping alone provides protection that is equivalent or superior to other interventions and has fewer side effects. Petroleum gel is flammable and is best avoided when electrocautery and open oxygen are to be used around the face. Preservative-free eye ointment is preferred, as preservative can cause corneal epithelial sloughing and conjunctival hyperemia. Recently, the application of Geliperm and bio-occlusive dressings has been advocated. Geliperm may be particularly useful during endonasal surgery when continuous perioperative observation of the eye is required. In this article, the literature on the etiology of perioperative corneal abrasions is reviewed and various protection strategies are compared in order to identify the best methods to prevent corneal abrasions during general anesthesia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Ophthalmologic complications are frequently encountered in intensive care unit (ICU) patients (Grixti et al. Ocul Surf 2012;10(1):26-42). However, eye care is often overlooked in the critical care setting or just limited to the ocular surface because treatment is focussed on the management of organ failures. Lack of awareness about other less common intraocular sight-threatening conditions may have a devastating effect on the patient's vision. To identify specific, frequently missed uncommon ocular disorders in ICU, a literature review using the keywords "Intensive Care," "Eye care," "ITU," "ICU," "Ophthalmological disorders," "Eye disorders" was performed. The databases of CINAHL, PuBMed, EMBASE, and Cochrane library were searched. The higher quality studies are summarized in the table with statements of methodology to clarify the level of evidence. The most prevalent ophthalmologic disorders identified in critically ill subjects include exposure keratopathy, chemosis, and microbial keratitis. In addition, uncommon eye disorders reported in ICU include metastatic endogenous endophthalmitis, acute primary angle closure, ischemic optic neuropathy, pupil abnormalities, vascular occlusions, and rhino-orbital cerebral mucormycosis. Early diagnosis and effective treatment will help to prevent visual loss., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background and Aims: The safety of donated blood is the most vital concern of a blood transfusion organization. Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) screening for blood transfusion products has gained more importance where knowing the prevalence rate will help health policy makers. In this paper, we will evaluate the prevalence of viral infection in donated blood in the province of Qazvin in 2009., Materials and Methods: This study has been conducted using a registration system of computerized records for donors in Qazvin in 2009 using the consensus mode on 20,591 blood donors. The results of their HBV, HCV, and HIV viral markers were evaluated and analyzed using the chi square statistical test., Results: The prevalence rate of HBV, HCV, and HIV viral markers using the ELISA primary test in the individuals studied has been 0.28%, 1.59% and 0.1%, respectively, and on the basis of their confirmatory tests, 0.23%, 0.17% and 0%, respectively. There was no significant statistical difference in their infection rate on the basis of sex and marital status. Regular donors (46.85%) had a smaller infection rate compared to others (P<0.005). There was a significant statistical difference in the rate of prevalence of infection for hepatitis B and C in the regular donors compared to first-time donors., Conclusion: Considering the lower prevalence of viral markers in regular donors it is recommended that more use be made of them for blood donation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Ocular surface disorders are frequently encountered in patients in Intensive Care Units (ICUs). Because of significant impairment of major organs, treatment is focused on the management of organ failures. Therefore, ophthalmological complications are frequently overlooked in this setting. To identify the types and frequencies of ocular surface disorders reported in patients in ICUs, a literature review using the keywords: Intensive Care; Eye care; ICU; ITU; Ophthalmological disorders; Eye disorders was performed. The databases of CINAHL, PUBMED, EMBASE and COCHRANE library were searched. The higher quality papers are summarized in tables with statements of methodology to clarify the level of evidence. The most prevalent ocular disorders identified in ICU patients were exposure keratopathy (3.6% to 60%), chemosis (9% to 80%), and microbial keratitis. Of the various eye care measures that have been advocated to prevent exposure keratopathy, the most effective is the application of moisture chambers or polyethylene covers. Early diagnosis and effective treatment will help to prevent microbial keratitis and visual loss., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: All blood transfusion services have various rules to insure that blood products are kept safe for transfusion. Donor selection is crucial in providing safe blood. We propose in our study to determine the influence of donor selection on blood safety., Methods: In this case-control study, donors who were referred to the Qazvin Blood Transfusion Organization during 2007-2009 were selected. Based on a special questionnaire, all blood donors were examined by physicians and every donor was categorized as one of two types of rejected donors (high risk and low risk) or as accepted donors. Data were analyzed by SPSS version 13.0, using chi-square and Fisher's exact tests, where P<0.05 was considered significant., Results: Single donors, the self-employed, the unemployed and students were banned from donation due to high-risk criteria (P<0.0001, 0.003). Female donors were banned from donation due to low-risk criteria. Hepatitis B was more prevalent among cases rejected for donation due to high-risk criteria than among healthy controls (P=0.014); but not so for hepatitis C (P=0.058). Hepatitis B was not significantly more prevalent among those cases rejected for donation due to low-risk criteria, than among healthy cases., Conclusion: Those having a history of unsafe sexual conduct and intravenous drug abusers and their spouses are at risk for hepatitis C. Cases rejected for donation due to low-risk criteria were banned from donation to maintain the donors' health, while other cases with low-risk criteria were banned to guarantee the blood recipients' health., (Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

We aimed to investigate the incidence of false alarms that occurred with the pass/fail criteria used in a published series of neonatal hearing screening programmes, as a function of age. We analysed the database of 19137 normally hearing babies (38274 ears) tested in the Wessex Universal Neonatal Hearing Screening Project. Otoacoustic emissions were recorded prior to discharge from maternity units, using IL088 equipment. We assessed the pass/fail rate using the Wessex criteria and 10 other pass/fail criteria published in the literature. Using Pearson's correlation coefficient, a statistically significant correlation between signal-to-noise ratio at each of the frequency bands 1, 2, 3, 4 and 5 kHz and babies' age in hours at the 0.01 level was identified. The correlation was also significant (0.01 level) between age and frequency reproducibility in each of the bands at 1, 2, 3, 4 and 5 kHz as well as the whole reproducibility. The number of false alarms reduced significantly after the first 24 h of life with all the criteria examined. We conclude that in the first hours after birth due to insufficient maturation of the otoacoustic emission, there is a high rate of false alarms. This increase in the false alarm rate, whilst dependent on the criteria used, occurs with all criteria. This leads to the consideration of whether the establishment of age-dependent pass/fail criteria could reduce the false alarm rate and the subsequent strain on diagnostic centres., (Copyright 2007 S. Karger AG, Basel.)

Laryngeal dysplasia is a common clinical concern. Despite major advancements in otolaryngology, a significant number of patients with the condition progress to invasive carcinoma. In the recent years, new diagnostic techniques such as autofluorescence and contact endoscopy have been applied to increase the accuracy of the laryngeal biopsies. Moreover, significant efforts have been made to correlate the histopathological appearance of the dysplastic samples to their clinical course. So far, a wide range of therapeutic strategies for different grades of dysplasia has been suggested by authors; however, there is a lack of outcome reviews. In the current review, the outcome of different therapeutic strategies for severe dysplasia and carcinoma in situ has been compared with statistical analysis. The paper also summarises the current knowledge of the alternative management methods as well as current areas of research in the chemoprevention of the condition. (1) Significant efforts have been made to develop new techniques to improve the accuracy of microlaryngoscopic assessment of laryngeal premalignancy. Comparative studies are required using microlaryngoscopy against the new techniques to evaluate their clinical utility. (2) The meta-analysis suggests a better local control rate with radiotherapy compared to other standard methods of management of dysplasia; however, functional impairment and complications associated with each of the standard treatments should be further evaluated.

To evaluate outcomes of intractable epistaxis managed with arterial embolisation. Fourteen sequential cases of intractable epistaxis that underwent embolisation in our centre were evaluated retrospectively and interviewed over the phone. All patients had several failed treatment modalities prior to embolisation. Patients' follow up ranged from 1 to 57 months with median of 26 months. All 14 cases underwent a single embolisation procedure with successful arrest of epistaxis. Four cases (29%) developed recurrent epistaxis at a later date. One (7%) required re-embolisation 19 months after his first procedure. One bled 17 days after embolisation, but this settled with hospital admission and Bismuth Iodoform Paraffin Paste packing. The other two developed minor episodes of epistaxis, which did not require hospital admission. Two patients developed local ischaemic complications following arterial embolisation. Of those, one developed necrosis of the left alar skin and cartilage that healed reasonably well after 5 months. The other case developed mucosal necrosis of the right side of the hard palate; this patient was the one who bled 17 days post-embolisation. The palatal necrosis healed in a satisfactory manner without causing any functional impairment of the oral cavity. Embolisation is a successful intervention in management of persistent epistaxis, when other interventions fail. The risks of major complications such as stroke are well known, and discussed with patients prior to the procedure. It is also important to discuss the risks of ischaemic damage to the face and oral cavity. In our experience, these complications have been minor and the benefits still outweigh the complications.