The evaluation of PD-1 and Tim-3 expression besides their related miRNAs in PBMCs of women with recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is a multifactorial disorder, associated with immunologic abnormalities. During pregnancy, the maternal immune system uses different tolerance mechanisms to deal with a semi-allogenic fetus. The expression of immune checkpoints and their related miRNAs in immune cells can ensure pregnancy at the feto-maternal interface by modulating immune responses. This study aims to evaluate the expression of the immune checkpoint molecules PD-1 and Tim-3 on circulating T cells by flow cytometry, that of mir-138 and mir-155 in PBMCs by Real-time PCR, and the concentrations of TGF-ß and IP-10 in the sera of women suffering from RPL as well as of gestational age-matched healthy pregnant women by ELISA. The percentage of PD-1 or Tim-3 expressing CD8+ T cells was significantly lower in RPL patients compared to the controls, while there was no significant difference in Tim-3 expression of CD4+ T cells between the two groups. The mRNA of both the PD-1 and Tim-3 genes were downregulated in PBMCs of RPL patients compared to controls, however, the difference was not statistically significant for Tim-3. The concentration of TGF-ß was significantly lower and that of IP-10 was significantly higher in the sera of RPL patients than in those of the controls. The relative expression of mir-138 and miR-155 were significantly lower, in PBMCs of RPL patients than in those of healthy pregnant women. These data confirm that by affecting cytokine production, immune checkpoints, and microRNAs play a role in establishing the appropriate local immune environment for successful pregnancy. The wider analysis of immune checkpoints may also yield new biomarkers for the diagnosis and prevention of RPL.

Comparison of the Effectiveness of Dexmedetomidine-Ketamine and Midazolam-Ketamine Regimens in Sedation of Children Treated with Extracorporeal Shock Wave Lithotripsy.

Background: Despite the high acceptability of the extracorporeal shock wave lithotripsy (ESWL) procedure in the treatment of urinary stones at all ages, it is necessary to use a variety of analgesic drugs during the procedure, especially among children. Objectives: We aimed to evaluate the effect of dexmedetomidine-ketamine (DK) and midazolam-ketamine (MK) compounds in the sedation of children (2-6 years old) undergoing ESWL. Methods: This randomized, double-blind clinical trial was performed on children aged 2 to 6 years with renal stones undergoing ESWL. The participants were randomly assigned to the DK and MK regimen groups (dexmedetomidine, 0.05 mcg/kg within 10 minutes infusion; midazolam, 0.05 mg/kg within 3 minutes infusion; ketamine, 0.5 mg/kg bolus injection). The patients were assessed with respect to sedation degree, post-procedure hemodynamic status, recovery time and awakening, and operator satisfaction. Results: Recovery time was significantly shorter in the DK group than in the MK group. Also, the DK regimen was more analgesic than the MK regimen; therefore, the need to repeat ketamine administration was less. There was no difference between the 2 methods in terms of cooperation at the time of separation of children from their parents, patient cooperation during the procedure, average verbal response time and average cooperation time after entering recovery, and operator satisfaction with the operation. No side effects were observed in the 2 groups. Conclusions: Ketamine with dexmedetomidine is associated with greater analgesia and shorter recovery time; however, sedation time was longer (insignificant) in ketamine with midazolam than in ketamine with dexmedetomidine. Thus, ketamine with dexmedetomidine is more preferred.

Long-Term Effects of ART on the Health of the Offspring.

Assisted reproductive technologies (ART) significantly increase the chance of successful pregnancy and live birth in infertile couples. The different procedures for ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), intrauterine insemination (IUI), and gamete intrafallopian tube transfer (GIFT), are widely used to overcome infertility-related problems. In spite of its inarguable usefulness, concerns about the health consequences of ART-conceived babies have been raised. There are reports about the association of ART with birth defects and health complications, e.g., malignancies, high blood pressure, generalized vascular functional disorders, asthma and metabolic disorders in later life. It has been suggested that hormonal treatment of the mother, and the artificial environment during the manipulation of gametes and embryos may cause genomic and epigenetic alterations and subsequent complications in the health status of ART-conceived babies. In the current study, we aimed to review the possible long-term consequences of different ART procedures on the subsequent health status of ART-conceived offspring, considering the confounding factors that might account for/contribute to the long-term consequences.

Autophagy-mediated immune system regulation in reproductive system and pregnancy-associated complications.

Autophagy lysosomal degradation is the main cell mechanism in cellular, tissue and organismal homeostasis and is controlled by autophagy-related genes (ATG). Autophagy has important effects in cellular physiology, including adaptation to metabolic stress, removal of dangerous cargo (such as protein aggregates, damaged organelles, and intracellular pathogens), regeneration during differentiation and development, and prevention of genomic damage in general. Also, it has been found that autophagy is essential for pre-implantation, development, and maintaining embryo survival in mammals. Under certain conditions, autophagy may be detrimental through pro-survival effects such as cancer progression or through possible cell death-promoting effects. Hormonal changes and environmental stress can initiate autophagy in reproductive physiology. The activity of autophagy can be upregulated under conditions like a lack of nutrients, inflammation, hypoxia, and infections. In this regard the dysregulation of autophagy involved in some pregnancy complications such as preeclampsia (PE) and pregnancy loss, and has a major impact on reproductive outcomes. Therefore, we aimed to discuss the relationship between autophagy and the female reproductive system, with a special focus on the immune system, and its role in fetal and maternal health.

Corrigendum to "Determination of metal(oids) in different traditional flat breads distributed in Isfahan city, Iran: Health risk assessment study by latin hypercube sampling" [Toxicol. Reports 10 (2023) 382-388].

[This corrects the article DOI: 10.1016/j.toxrep.2023.02.015.].

Self-Sensing Rubber for Bridge Bearing Monitoring.

Elastomeric bearings are widely used in bridges to support the superstructure, to transfer loads to substructures, and to accommodate movements induced by, for example, temperature changes. Bearing mechanical properties affect the bridge's performance and its response to permanent and variable loadings (e.g., traffic). This paper describes the research carried out at Strathclyde towards the development of smart elastomeric bearings that can be used as a low-cost sensing technology for bridge and/or weigh-in-motion monitoring. An experimental campaign was performed, under laboratory conditions, on various natural rubber (NR) specimens enhanced with different conductive fillers. Each specimen was characterized under loading conditions that replicated in-situ bearings to determine their mechanical and piezoresistive properties. Relatively simple models can be used to describe the relationship between rubber bearing resistivity and deformation changes. Gauge factors (GFs) in the range between 2 and 11 are obtained, depending on the compound and the applied loading. Experiments were also carried out to show that the developed model can be used to predict the state of deformation of the bearings under random loadings of different amplitudes that are characteristic of the passage of traffic over a bridge.

Optic disc drusen in patients diagnosed with normal tension glaucoma.

PURPOSE: To investigate the prevalence of optic disc drusen (ODD) and optic nerve head (ONH) morphology in patients diagnosed with normal tension glaucoma (NTG). METHODS: In this prospective cross-sectional study, we included patients diagnosed with NTG from two glaucoma units. In both eyes, dense enhanced depth imaging optical coherence tomography volume scans of the ONH by means of standardized scanning guidelines were performed to examine for presence of ODD, and radial ONH scans were used for investigating parameters such as scleral canal diameter, cup/disc ratio and cup depth. RESULTS: We found ODD in 7 (3.6%) of 195 eyes, in 6 (6.1%) out of 98 patients diagnosed with NTG. The ODD were not ophthalmoscopically visible in five out of six patients. Eyes with ODD had lower cup/disc ratio, 0.44 ± 0.4 (p = 0.040), and less-prominent cup depth, 236.6 ± 204.4 µm (p = 0.041) compared to eyes without ODD, 0.81 ± 0.2 and 437.8 ± 139.1 µm, respectively. We found no significant difference in scleral canal diameter between the eyes without (1602.8 ± 193 µm) and those with ODD (1492 ± 123.4 µm, p = 0.057). CONCLUSION: The prevalence of ODD in patients diagnosed with NTG is substantially higher than in the background population. A low cup/disc ratio correlates with ODD presence. Therefore, due to the challenges associated with NTG diagnosis, we recommend examining the deep layers of the ONH in NTG patients with a cup/disc ratio lower than 0.5 to avoid misdiagnosing ODD as NTG.

Study on the effect of medicinal leech therapy (Hirudo medicinalis) on full-thickness excisional wound healing in the animal model.

The possible impacts of alternative and conventional medicines on wound healing are now of growing interest. This study aimed to evaluate and elucidate the wound healing activity of medicinal leech therapy in wound excision of the rat model. After a round, full-thickness excision was made in the dorsal region of the body, the animals (n = 30) were randomly divided into three equal groups: I) the treatment group (MLT), where the wounds received leech treatment; II) the positive control group (PC), where the wounds received 1% sodium phenytoin treatment; and III) the negative control group (NC), where the wounds did not receive any treatment. On days 6 and 16, wound biopsy specimens were taken, and prepared sections were stained using various methods. The contraction rate differed significantly (P < 0.05) between the NC group and the other groups. The histopathological evaluation revealed that MLT group showed an accelerated healing process and lower inflammatory response compared to other groups. In ML-treated group maturation and remodeling of collagen had occurred, while in 1% sodium phenytoin treated group, proliferation was the prominent feature. Results showed that the fibroblast was significantly lower in the NC group in comparison to other groups. The number of MNC, s, and PMN, s was significantly higher in the NC group compared to other groups (P < 0.0001). In our study, medicinal leech therapy had a higher success rate in healing for the treatment of excisional wounds in animal models.

Composition and effects of seminal plasma in the female reproductive tracts on implantation of human embryos.

The function of seminal plasma involves acting as a transport medium for sperm and as a means of communication between the reproductive tissues of the male and female. It is also a vital factor to prime the reproductive tracts of the female for optimal pregnancy. When the reproductive tract of the female is exposed to seminal plasma, serious alterations take place, enhancing pathogen and debris clearance observed in the uterus throughout mating. It is also capable of supporting embryo growth, promoting the receptivity of the uterus, and establishing tolerance to the semi-allogenic embryo. Moreover, seminal plasma is capable of regulating the functions of several female reproductive organs and providing an ideal condition for effective embryo implantation and pregnancy. It is believed that the health state of the offspring is affected by exposure to seminal plasma. For the treatment of infertility, assisted reproductive technologies have been extensively employed. The application of seminal plasma as a therapeutic approach to enhance the development of embryo competency and rate of implantation, receptivity of endometrium, and establishment of maternal immune tolerance in cycles of ART appears possible. Herein, current knowledge on the composition of seminal plasma and the physiological roles it possesses on various parts of the female reproductive tract are summarized. Moreover, the role of seminal plasma in the development of embryos, implantation, and the following fetal growth and survival have been reviewed in this article.

Allogeneic lymphocytes immunotherapy in female infertility: Lessons learned and the road ahead.

The endometrium is an essential tissue in the normal immunologic dialogue between the mother and the conceptus, which is necessary for the proper establishment and maintenance of a successful pregnancy. It's become evident that the maternal immune system plays a key role in the normal pregnancy's initiation, maintenance, and termination. In this perspective, the immune system contributes to regulating all stages of pregnancy, thus immunological dysregulation is thought to be one of the major etiologies of implantation failures. Many researchers believe that immune therapies are useful tactics for improving the live births rate in certain situations. Lymphocyte immunotherapy (LIT) is an active form of immunotherapy that, when used on the relevant subgroups of patients, has been shown in multiple trials to dramatically enhance maternal immunological balance and pregnancy outcome. The primary goal of LIT is to regulate the immune system in order to create a favorable tolerogenic immune milieu and tolerance for embryo implantation. However, there are a plethora of influential factors influencing its therapeutic benefits that merit to be addressed. The objective of our study is to discuss the mechanisms and challenges of allogeneic LIT.

Enhanced depth imaging optical coherence tomography of the optic nerve head improves correct diagnosis in glaucoma suspects without glaucomatous optic disc morphology.

An 83-year-old woman with a long history of glaucoma and optic disc drusen (ODD) was referred for neuro-ophthalmological second opinion. The patient had been treated for decades with bilateral intraocular pressure (IOP)-lowering eye drops, laser trabeculoplasty and trabeculectomy and had severe, bilateral loss of visual fields and retinal nerve fibre layer (RNFL) thinning on optical coherence tomography (OCT) despite IOP that never exceeded 24 mm Hg. On ophthalmoscopy, only a single ODD was visible in the left eye and no optic disc cupping was apparent in either eye. Enhanced depth imaging OCT (EDI-OCT) of the optic nerve head revealed bilateral multiple, large, deep ODD, which in itself could easily explain the visual field loss and RNFL thinning of this patient. Optic nerve head examination using EDI-OCT is highly recommended for patients with a history of glaucoma but without optic nerve head cupping to avoid a potential misdiagnosis with consequent unnecessary treatment.

Oxidative Stress in Optic Neuropathies.

Increasing evidence indicates that changes in the redox system may contribute to the pathogenesis of multiple optic neuropathies. Optic neuropathies are characterized by the neurodegeneration of the inner-most retinal neurons, the retinal ganglion cells (RGCs), and their axons, which form the optic nerve. Often, optic neuropathies are asymptomatic until advanced stages, when visual impairment or blindness is unavoidable despite existing treatments. In this review, we describe systemic and, whenever possible, ocular redox dysregulations observed in patients with glaucoma, ischemic optic neuropathy, optic neuritis, hereditary optic neuropathies (i.e., Leber's hereditary optic neuropathy and autosomal dominant optic atrophy), nutritional and toxic optic neuropathies, and optic disc drusen. We discuss aspects related to anti/oxidative stress biomarkers that need further investigation and features related to study design that should be optimized to generate more valuable and comparable results. Understanding the role of oxidative stress in optic neuropathies can serve to develop therapeutic strategies directed at the redox system to arrest the neurodegenerative processes in the retina and RGCs and ultimately prevent vision loss.

The Liouville Formula for the Uncertain Homogeneous Linear System and Explicit Solutions of the System.

This paper presents some new definitions and results about a system of uncertain homogeneous linear differential equations. Introducing the uncertain fundamental system and uncertain fundamental matrix for the uncertain system, the Liouville formula will be proven for the system. Moreover, the explicit solutions of the system will be presented.

Effect of an inverted seated position with upper arm blood flow restriction on measures of elbow flexors neuromuscular performance.

PURPOSE: The objective of the investigation was to determine the concomitant effects of upper arm blood flow restriction (BFR) and inversion on elbow flexors neuromuscular responses. METHODS: Randomly allocated, 13 volunteers performed four conditions in a within-subject design: rest (control, 1-min upright position without BFR), control (1-min upright with BFR), 1-min inverted (without BFR), and 1-min inverted with BFR. Evoked and voluntary contractile properties, before, during and after a 30-s maximum voluntary contraction (MVC) exercise intervention were examined as well as pain scale. RESULTS: Inversion induced significant pre-exercise intervention decreases in elbow flexors MVC (21.1%, [Formula: see text] = 0.48, p = 0.02) and resting evoked twitch forces (29.4%, [Formula: see text] = 0.34, p = 0.03). The 30-s MVC induced significantly greater pre- to post-test decreases in potentiated twitch force ([Formula: see text] = 0.61, p = 0.0009) during inversion (↓75%) than upright (↓65.3%) conditions. Overall, BFR decreased MVC force 4.8% ([Formula: see text] = 0.37, p = 0.05). For upright position, BFR induced 21.0% reductions in M-wave amplitude ([Formula: see text] = 0.44, p = 0.04). There were no significant differences for electromyographic activity or voluntary activation as measured with the interpolated twitch technique. For all conditions, there was a significant increase in pain scale between the 40-60 s intervals and post-30-s MVC (upright

Cell therapy in female infertility-related diseases: Emphasis on recurrent miscarriage and repeated implantation failure.

About 17% of couples suffer from infertility conditions, worldwide. The most common reasons for female infertility are ovulation disorders, fallopian-related disorders, RM, RIF, endometriosis, and unexplained infertility. Despite advances in Assisted Reproductive Technologies, infertility has remained a serious problem. In recent years, a considerable progress in cell therapy as an emerging approach for the treatment infertility has been made. Cell therapy involves utilizing lymphocytes, platelet -rich plasma, PBMCs and different types of stem cells as therapeutic agents. Stem cells are usually multipotent cells existed in embryos, fetuses, and adults that proliferate and differentiate into different cell types under certain circumstances. The main types of stem cells are embryonic stem cells, decidual stromal cells, MSCs, human amniotic epithelial cells, and induced pluripotent-stem cells each functioning in a different way. The advantages of using stem cells as therapeutic agents are convenient sampling, abundant sources, and avoidable ethical issues. Lymphocyte immunotherapy, a simple and cost effective method, can be safe and useful approach if performed with proper dose of fresh lymphocytes intradermally before and during pregnancy. Overall, cell therapy mechanism of actions are inducing the production of cytokines, blocking antibodies and growth factors, proliferation of B10 cells, reducing the activity of NK cells, increasingTh2 and Treg cells and decreasing Th1 and Th17 cells. Cell therapy can be an effective strategy as it provides an interactive, dynamic, specific and individualized treatment. Although cell therapy is a promising approach, it still needs more investigation in order to improve and make it safer.

Implications for glycosylated compounds and their anti-cancer effects.

Glycosylated compounds are major secondary metabolites of plants, which have various therapeutic effects on human diseases, by acting as anti-cancer, antioxidant, and anti-inflammatory agents. Glycosylation increases stability, bioactivity, and solubility of compounds and improves their pharmacological properties. Two well-known examples of glycosylated compounds include cardiac and flavonoid, the anti-tumor activities of which have been emphasized by several studies. However, little is known about their role in the treatment or prevention of cancer. In this review, recent studies on anti-tumor properties of cardiac and flavonoid glycosides, and their mechanisms of action, have been investigated. More specifically, this review is aimed at focusing on the multifactorial properties of cardiac and flavonoid compounds as well as their correlation with signaling pathways in the treatment of cancer.

Altered TH1, TH2, TH17 balance in assisted reproductive technology conceived mice.

AIM AND PURPOSE: The higher prevalence rate of different diseases may accentuate the possible alteration of the immune system in individuals conceived through the assisted reproductive technologies (ART). The present study was conducted to evaluate the TH1, TH2, TH17 balance in intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) - conceived mice in comparison to naturally conceived offspring. METHODS: Mice (6-8 weeks) were divided into three groups (IVF- conceived, ICSI- conceived and naturally conceived). They were subjected to subcutaneous immunization witMycobacterium bovis Bacille Calmette-Guérin (BCG). The blood samples were taken and the sera were separated. Then the spleens were surgically removed at the time the mice were sacrificed. Serum levels of IFN-γ, IL-17A and IL-4 were detected by ELISA. Then the proportion of TCD4 cells possessing the T-bet+, GATA3+, and ROR-γt + were measured using FACS caliber flow cytometer. RESULTS: In comparison with naturally conceived mice, intracellular expression of T-bet and serum levels of IFN-γ were significantly decreased in ART- conceived mice. Moreover, ART- conceived offspring showed marked increase in IL-4 and IL-17A. CONCLUSION: It is concluded that compared to naturally conceived male mice, ART- conceived counterparts exhibit less efficient immune responses against BCG through further promotion of humoral and inflammatory related immune response characteristics.

Melanopsin-mediated pupillary light reflex and sleep quality in patients with normal tension glaucoma.

PURPOSE: The intrinsically photosensitive retinal ganglion cells (ipRGCs) and sleep quality are impaired in patients with primary open-angle glaucoma (POAG). In this study, we investigated whether ipRGCs and sleep quality were also impaired in patients with normal tension glaucoma (NTG). METHODS: We performed pupillometry and sleep quality assessment in 15 patients with NTG and 17 healthy age-matched controls. Pupillometry protocol consisted of monocular stimulation with high illuminance (100 lux) red (633 nm, 300 cd/m2 or 15.23 log quanta/cm2 /s) and blue light (463 nm, 332 cd/m2 or 15.27 log quanta/cm2 /s) and binocular pupil measurements. Prior to light stimulation, patients were dark-adapted for 5 min. The late postillumination pupillary response (PIPRL ate ) to blue light was used as marker of ipRGC activity. Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI) questionnaire. RESULTS: The PIPRL ate to blue light was significantly reduced in patients with NTG compared to healthy subjects (p < 0.001), indicating impairment of the melanopsin-mediated pupillary pathway. There was no significant difference in the response elicited by red light (p = 0.6). Baseline pupil diameter and pupillary constriction amplitude to both red and blue light were reduced in patients with NTG (p < 0.05). The global score in PSQI was not significantly different between healthy controls and patients with NTG, indicating normal sleep quality (p = 0.6). Furthermore, we found no correlation between sleep parameters and pupillary light reflex parameters. CONCLUSION: Patients with NTG exhibited reduced ipRGC activity compared to healthy subjects, while no differences were observed in sleep quality.

Microextraction on a screw.

For the first time, a rapid, efficient, simple, and inexpensive approach for solid phase microextraction on a screw (MES) was developed. MES is a miniaturized form of solid-phase extraction without any backpressure. In this system, analytes were adsorbed on the surface of micro channels of a screw that was coated by polypyrrole (PPy). Based on this procedure, the analytes are adsorbed on the solid phase and then eluted by a desorption solvent. The MES method followed by gas chromatography-mass spectrometry (MES-GC-MS) was applied for the rapid extraction and determination of six polycyclic aromatic hydrocarbons (PAHs) (as model analytes) in well water samples. Several parameters affecting the extraction procedure, including the sampling flow rate, the number of the loading/desorption cycles of the sample, and the volume of the desorption solvent, were evaluated and optimized. Under optimum conditions, the detection limits for the PAHs varied between 0.5 and 1 µg L-1 and linear ranges varied between 2 and 600 µg L-1. The results showed good correlation coefficients (R > 0.99) for all of the analytes in the studied calibration range. The relative recovery (RR%) of the desired MES-GC-MS method for the studied PAHs was between 83.0 and 104.0% and the interday and intraday precision (n = 5 days), expressed as relative standard deviation (RSD %), were between 3.9-6.2% and 6.2-8.9%, respectively. To evaluate the matrix effect, the developed method was also applied for preconcentration and determination of the selected PAHs in real water samples, and good results were obtained.

The effect of adding Rosmarinic and Ascorbic acids to vitrification media on fertilization rate of the mice oocyte: An experimental study.

BACKGROUND: Oocytes vitrification is a pivotal step for the widespread and safekeeping of animal genetic resources. Oocytes endure notable morphological and functional damage during cryopreservation. Oxidative stress is one of the adverse effects that vitrification imparts on oocytes. OBJECTIVE: In the present study, we investigated the antioxidant effect of Rosmarinic and Ascorbic acids on the quality and fertilizing ability of frozen-thawed mice oocyte. MATERIALS AND METHODS: In this experimental study, germinal vesicle oocytes obtained from two-months-old (30-40gr) NMRI mice were randomly divided into four groups. The basic cryoprotectants were 7.5% (v/v) ethylene glycol+7.5% (v/v) Propanediol as an equilibration media. Vitrification medium contained 15% (v/v) ethylene glycol+15% (v/v) propanediol, and 0.5 M sucrose. In the first group (Control), nothing was added to vitrification mediums, whereas, in the second and third groups, 0.5 mmol/L of Ascorbic acid and 105 µmol/L of Rosmarinic acid were added into vitrification medium, respectively. The cumulative concentration of Rosmarinic and Ascorbic acids were added to group 4. Mouse oocytes were vitrified and preserved for one month. The thawed oocytes were transferred into the α-MEM medium (Alpha Minimum Essential Medium) and maintained in this medium for 24 hr, to be matured and reach the metaphase II stage. RESULTS: The addition of Rosmarinic and Ascorbic acids to the vitrification solution improved the survival, maturation of Germinal vesicles, fertilization rate, and finally development to 4-cell stage. Maturation rates to 4-cell stage for Ascorbic acid, Rosmarinic acid, and both of them together were 80%, 80.76%, and 86.61%, respectively. CONCLUSION: These results indicate that the addition of a cumulative concentration of 0.5 mmol/L Ascorbic acid and 105 µmol/L of Rosmarinic acid to the cryopreservation solution for the mouse immature oocytes would be of significant value (p < 0.01).