The novel hepatoprotective effects of silibinin-loaded nanostructured lipid carriers against diazinon-induced liver injuries in male mice.

In the current study, silibinin-loaded nanostructured lipid carriers (Sili-NLCs) was synthesized, and the hepatoprotective effectiveness of Sili-NLCs against diazinon (DZN)-induced liver damage in male mice was evaluated. The emulsification-solvent evaporation technique was applied to prepare Sili-NLCs, and characterized by using particle size, zeta potential, entrapment efficacy (EE %), in vitro drug release behavior, and stability studies. In vivo, studies were done on male mice. Hepatotoxicity in male mice were induced by DZN (10 mg/kg/day, i.p.). Four groups treated with silibinin and Sili-NLCs with the same doses (100 and 200 mg/kg, p.o.). On 31th days, serum and liver tissue samples were collected. Alanine (ALT) and aspartate (AST) aminotransferase levels, oxidative stress biomarkers, inflammatory cytokines, and histopathological alterations were assessed. The Sili-NLCs particle size, zeta potential, polydispersity index (PDI), and EE % were obtained at 220.8 ± 0.86 nm, -18.7 ± 0.28 mV, 0.118 ± 0.03, and 71.83 ± 0.15%, respectively. The in vivo studies revealed that DZN significantly increased the serum levels of AST, ALT, hepatic levels of lipid peroxidation (LPO), and tumor necrosis factor-α (TNF-α), while decreased the antioxidant defense system in the mice's liver. However, Sili-NLCs was more effective than silibinin to return the aforementioned ratio toward the normal situation, and these results were well correlated with histopathological findings. Improvement of silibinin protective efficacy and oral bioavailability by using NLCs caused to Sili-NLCs can be superior to free silibinin in ameliorating DZN-induced hepatotoxicity in male mice.

Memory ability and retention performance relate differentially to sleep depth and spindle type.

Temporal interactions between non-rapid eye movement (NREM) sleep rhythms especially the coupling between cortical slow oscillations (SO, ∼1 Hz) and thalamic spindles (∼12 Hz) have been proposed to contribute to multi-regional interactions crucial for memory processing and cognitive ability. We investigated relationships between NREM sleep depth, sleep spindles and SO-spindle coupling regarding memory ability and memory consolidation in healthy humans. Findings underscore the functional relevance of spindle dynamics (slow versus fast), SO-phase, and most importantly NREM sleep depth for cognitive processing. Cross-frequency coupling analyses demonstrated stronger precise temporal coordination of slow spindles to SO down-state in N2 for subjects with higher general memory ability. A GLM model underscored this relationship, and furthermore that fast spindle properties were predictive of overnight memory consolidation. Our results suggest cognitive fingerprints dependent on conjoint fine-tuned SO-spindle temporal coupling, spindle properties, and brain sleep state.

The effect of foot posture on static balance, ankle and knee proprioception in 18-to-25-year-old female student: a cross-sectional study.

BACKGROUND & PURPOSE: Afferent input from the sole affects postural stability. Cutaneous reflexes from the foot are important to posture and gait. Lower-limb afferents alone provide enough information to maintain upright stance and are critical in perceiving postural sway. Altered feedback from propreoceptive receptors alters gait and patterns of muscle activation. The position and posture of the foot and ankle may also play an important role in proprioceptive input.Therefore, the current research aims to compare static balance and ankle and knee proprioception in people with and without flexible flatfeet. METHODOLOGY: 91 female students between the ages of 18 and 25 voluntarily participated in this study, of which 24 were in the flexible flatfoot group and 67 were in the regular foot group after evaluating the longitudinal arch of the foot. The position sense of ankle and knee joints were measured using the active reconstruction test of the ankle and knee angle; Static balance was measured using the Sharpened Romberg test. Data were non-normally distributed. Accordingly, non-parametric tests were applied. The Kruskal-Wallis test was applied to compare differences between groups in variables. RESULT: Kruskal-Wallis test showed a significant difference between two groups of flat feet and normal feet in the variables of static balance and position sense of ankle plantarflexion, ankle dorsiflexion, and knee flexion (p ≤ 0.05). A significant correlation was found between static balance and sense of ankle and knee position in the group with normal feet. The analysis of the regression line also showed that ankle and knee position sense could predict the static balance score in the regular foot group (ankle dorsiflexion position sense 17% (R2 = 0.17), ankle plantarflexion position sense 17% (R2 = 0.17) and knee flexion position sense 46% (R2 = 0.46) explain of changes in static balance). DISCUSSION & CONCLUSION: Flexible flatfoot soles can cause loss of balance and sense of joint position; therefore, according to this preliminary study, clinicians must be aware and should take into account this possible deficit in the management of these patients.

A supportive randomized clinical trial on Iranian infertile women with the history of infertility treatments dropout following unsuccessful ART cycle/s: A study protocol.

Introduction: Due to high dropout rate of infertility treatments and lack of any intervention for motivating infertile couples to continue treatments, the present study will be conducted with the aim of designing, implementing and determining the effectiveness of the proposed intervention in order to continue infertility treatments. Methods: & Analysis: We will conduct this study in two stages; a review of literature and past studies will be done to identify interventions that have been performed for infertile couples, and then an appropriate intervention with the aim of continuing infertility treatments for infertile women will be designed. After that a Delphi study will be designed in accordance with collected information of previous stages and will be approved by experts. In the second stage we will implement designed intervention of a randomized clinical trial on two groups of infertile women (control and intervention) with the history of infertility treatment dropout following unsuccessful cycle. We will use descriptive statistic in first and second stage. In second stage Chi square test and independent samples T test will be used to compare variables between groups and variables in study questionnaires before and after the intervention between two groups of study. Discussion: The present study will be the first study to be performed as a clinical trial on infertile women who have discontinued the treatments, with the aim of continuing treatments. Thereupon, it seems that the results of this study will be the basis for studies around the world to prevent premature cessation of infertility treatments.

Can different training methods reduce the kinematic risk factors of ACL injuries in children?

According to the research, a lack of neuromuscular control is a major cause of non-contact anterior cruciate ligament (ACL) injury during locomotion. This study aimed to determine the influence of various prescriptive and Constrained Led Approach (CLA) training approaches on lower extremity kinematics and stride length in children aged 3-5 years old while walking and running. Thirty-six children with a mean age of 4.79 years were separated into three groups: 1- prescriptive training group (n = 10), 2- CLA training group (n = 11), and 3- Control group (n = 10). The kinematics of the hip, knee and ankle joints in the sagittal plane at the moment of heel contact and toe-off were recorded before and after six weeks of intervention. According to the MANOVA, there was no statistically significant difference between the two training techniques in the joint angles at heel contact and toe-off during walking and running after intervention (p ≥ 0.05). However, there was a significant difference in the kinematic characteristics of walking and running between the training and the control groups (p ≤ 0.05). The two training techniques showed a statistically significant difference in stride length during running (p ≤ 0.05). The results indicated that prescriptive and CLA training are effective at altering the kinematics and distance factors underlying children's walking and running abilities.

Factors Associated with Infant Mortality Due to Congenital Anomalies: A Population-Based Case-Control Study.

Background: Congenital anomalies are one of the major public health problems and one of the leading cause of infant mortality and morbidity. We aimed to investigate some factors associated with infant mortality due to congenital anomalies in several provinces of Iran. Methods: This case-control study was conducted on 2199 women referring health centers of nine provinces of Iran 2015-2018. Cases were defined as mothers with infant death due to congenital anomalies, and control group comprised of mothers with live birth or infant deaths due to other causes (n=1986). The descriptive data were expressed as percentage and frequency. Factors associated with infant death due to congenital anomalies were evaluated and analyzed at 95% confidence level by logistic regression analysis. Results: The multiple logistic regression analysis reveal that history of cesarean delivery [OR:2.13 ;95%CI (1.58-2.87)], maternal age [OR:1.94 ;95%CI (1.31-2.86)])], area of living [OR: 1.69;95%CI (1.22-2.33)], maternal smoking during pregnancy [OR: 1.41; 95%CI (1.02-1.95)], consanguineous marriage [OR:1.53;95%CI (1.12-2.08)], also low birth weight [OR: 3.09; 95%CI (2.23-4.30)] were significantly associated with infant death due to congenital anomalies. Conclusion: Identification of factors associated with congenital anomalies has been shown to reduce treatment costs and medical complications of neonates. Therefore, genetic counseling and educational programs for high-risk women, and prenatal screening are essential to identify and prevent factors contributing to congenital abnormalities.

Enhancement of hippocampal-thalamocortical temporal coordination during slow-frequency long-duration anterior thalamic spindles.

Temporal nesting of cortical slow oscillations (SO), thalamic spindles and hippocampal ripples indicates multi-regional neuronal interactions required for memory consolidation. However how the thalamic activity during spindles organizes hippocampal dynamics remains largely undetermined. We analyzed simultaneous recordings of anterodorsal thalamus and CA1 in male mice to determine the contribution of thalamic spindles in cross-regional synchronization. Our results indicated that temporal hippocampo-thalamocortical coupling were more enhanced during slower and longer thalamic spindles. Additionally, spindles occurring closer to SO trough were more strongly coupled to ripples. We found that the temporal association between CA1 spiking/ripples and thalamic spindles was stronger following spatial exploration compared to baseline sleep. We further developed a hippocampal-thalamocortical model to explain the mechanism underlying the duration and frequency-dependent coupling of thalamic spindles to hippocampal activity. Our findings shed light on our understanding of the functional role of thalamic activity during spindles on multi-regional information transfer.Significance Statement:The contribution of thalamic spindles with differential properties to cross-regional synchronization and information transfer still remains poorly understood. Using simultaneous anterodorsal thalamic and hippocampal recordings from naturally sleeping mice before and after exploration, we found strong coupling of CA1 units to anterodorsal thalamic spindles and increase of this coupling following spatial experience. We further showed that the temporal coupling of CA1 units and hippocampal ripples with thalamic spindles and the spindle-associated modulation of CA1 units with ripples were stronger for spindles with slower frequency of oscillations. Our experimental as well as computational findings using a hippocampal-thalamocortical model provide the first demonstration that spindle frequency and duration can provide valuable information about the underlying multi-regional interactions essential for memory consolidation computations.

A systematic review and meta-analysis on dropout of infertility treatments and related reasons/factors.

Dropout of infertility treatments is a common phenomenon and many patients avoid continuing infertility treatments. Determining the total rate of treatment dropout, and related factors was the objective of the present systematic review and meta-analysis study. We performed an electronic literature search in Web of Science, Scopus, Embase, Cinhal, ProQuest and Medline databases and a manual search in Google scholar by using a set of Standard keywords. We included descriptive studies in English or Persian, from August 2000 to 2019. Finally, we extracted data of 25 papers for systematic review and 11 papers for meta-analysis. Data analysed by RevMan software. The results of the meta-analysis analysed by the random-effects model and studies heterogeneity analysed using the I2 calculation index. We tried to control high heterogeneity (because of the small amounts of p value and chi-square and large amount of I2) with statistical methods such as subgroup analysis and using random-effects model. The results showed that factors related to treatment, psychological and demographic/personal factors are the most common factors for dropout. It seems that educational and supportive programs on psychological, financial, therapeutic, demographic and personal factors can play an important role in reducing the incidence of infertility treatment's drop out before completing the course of treatment.

Investigation of crude oil properties impact on wettability alteration during low salinity water flooding using an improved geochemical model.

In low-salinity water flooding (LSWF), modifying the injected brine composition leads to greater oil recovery from carbonate reservoirs. The processes that control improved recovery during LSWF are not totally clear, which could lead to ambiguities in finding optimum brine composition regarding wettability alteration (WA) toward water wetness. One of the methods to determine WA is bound product sum (BPS) calculation using geochemical tools. In the case of wettability improvement, the BPS value of a crude oil-brine-rock (COBR) system should be at its minimum value. In this study, an improved geochemical model is developed, which includes the effects of oil composition (i.e., acid number, base number, and weight percent of nonhydrocarbon components) and physical properties of oil (i.e., density, viscosity, and solution gas-oil ratio) on COBR interactions. The proposed method generates BPS as a function of temperature, pressure, oil and brine composition, and pH for carbonate rocks. The model applicability was validated using several experimental data sets available in the literature. The results of the improved BPS model were in line with the results of contact angle and zeta potential measurements as the major indices of rock wettability. BPS calculations using the available geochemical tools sometimes failed to predict the correct WA trend since they overlooked the impact of oil properties on COBR interactions. The model predictability was also compared with the results of an available geochemical tool, PHREEQC, and the results demonstrate just how important the effect of oil properties and composition inclusion on wettability determination is. The improved BPS approach could be successfully utilized as an optimization tool to optimize the water composition during LSWF for a given COBR system.

The effects of learning with various noise on Gait Kinematics in 3-to-5-year-old children: a randomized controlled trial.

BACKGROUND: Lack of the neuromuscular control during locomotion in the knee joint leads to an increased risk of anterior cruciate ligament (ACL) injury in children. Hence, we aimed to explore the effects of a repetitive, model-oriented, and self-organized approach on lower limb kinematics during gait in children. METHODS: In randomized controlled trial, 36 children with 4 ± 0.79 years of age from the children gym were randomly (a lottery method) allocated into three groups, including (1) the model-oriented (n = 10), (2) Differential Learning (n = 11), and (3) control (n = 10) groups. Kinematic data of hip, knee, and ankle joints in the sagittal plane were recorded by a GoPro camera at the moments of heel-ground contact and toe-off the ground before and after a 6-week intervention (two sessions per week). RESULTS: The results indicate a 35% post-intervention increase of ankle dorsiflexion (95% CI: - 5.63 _ - 0.96) in the moment of heel-ground contact in the model-oriented group; however, knee flexion (95% CI: - 1.05 _ 8.34) and hip flexion (95% CI: 3.01 _ 11.78) were respectively decreased by 20% and 20%. After the intervention, moreover, ankle plantar flexion (95% CI: - 9.18 _ - 2.81) and hip extension (95% CI: - 12.87 _ - 3.72) have respectively increased by 37% and 37%, while knee flexion (95% CI: 3.49 _ 11.30) showed a %16 decrease in the moment of toe off the ground. As for the Differential Learning group, ankle dorsiflexion (95% CI: - 5.19 _ - 1.52) increased by 33%, and knee (95% CI: 0.60 _ 5.76) and hip flexion (95% CI: 2.15 _ 7.85) respectively decreased by 17% and 17% at the moment of the heel-ground contact following the intervention. At toe lifting off the ground, the plantar flexion (95% CI: - 7.77 _ - 2.77) increased by 35%, knee flexion (95% CI: 2.17 _ 7.27) decreased to 14%, and hip extension (95% CI: - 9.98 _ - 4.20) increased by %35 following the intervention for the Differential Learning group subjects. Based on the results obtained from the one-way ANOVA, there was a significant difference between these groups and the control group in all kinematic gait variables (p ≤ 0.05). However, no statistically significant differences were found between the two experimental groups. CONCLUSIONS: The results implied that the model-oriented repetitive and the self-organized Differential Learning approach were both appropriate to alter the kinematic gait pattern in the 3-5-year-old children. Previous research has almost exclusively recommended a model-oriented approach to change kinematic patterns and preventing non-contact motor injuries. However, the present study showed that the Differential Learning approach can help children to achieve the same goal by continuously changing environments and stimulating challenges. TRIAL REGISTRATION: Current Controlled Trials using the IRCT website with ID number of, IRCT20130109012078N5 "Prospectively registered" at 14/5/2021.

The essential role of hippocampo-cortical connections in temporal coordination of spindles and ripples.

The predominant activity of slow wave sleep is cortical slow oscillations (SOs), thalamic spindles and hippocampal sharp wave ripples. While the precise temporal nesting of these rhythms was shown to be essential for memory consolidation, the coordination mechanism is poorly understood. Here we develop a minimal hippocampo-cortico-thalamic network that can explain the mechanism underlying the SO-spindle-ripple coupling indicating of the succession of regional neuronal interactions. Further we verify the model predictions experimentally in naturally sleeping rodents showing our simple model provides a quantitative match to several experimental observations including the nesting of ripples in the spindle troughs and larger duration but lower amplitude of the ripples co-occurring with spindles or SOs compared to the isolated ripples. The model also predicts that the coupling of ripples to SOs and spindles monotonically enhances by increasing the strength of hippocampo-cortical connections while it is stronger at intermediate values of the cortico-hippocampal projections.

Spontaneous slow oscillation-slow spindle features predict induced overnight memory retention.

STUDY OBJECTIVES: Synchronization of neural activity within local networks and between brain regions is a major contributor to rhythmic field potentials such as the EEG. On the other hand, dynamic changes in microstructure and activity are reflected in the EEG, for instance slow oscillation (SO) slope can reflect synaptic strength. SO-spindle coupling is a measure for neural communication. It was previously associated with memory consolidation, but also shown to reveal strong interindividual differences. In studies, weak electric current stimulation has modulated brain rhythms and memory retention. Here, we investigate whether SO-spindle coupling and SO slope during baseline sleep are associated with (predictive of) stimulation efficacy on retention performance. METHODS: Twenty-five healthy subjects participated in three experimental sessions. Sleep-associated memory consolidation was measured in two sessions, in one anodal transcranial direct current stimulation oscillating at subjects individual SO frequency (so-tDCS) was applied during nocturnal sleep. The third session was without a learning task (baseline sleep). The dependence on SO-spindle coupling and SO-slope during baseline sleep of so-tDCS efficacy on retention performance were investigated. RESULTS: Stimulation efficacy on overnight retention of declarative memories was associated with nesting of slow spindles to SO trough in deep nonrapid eye movement baseline sleep. Steepness and direction of SO slope in baseline sleep were features indicative for stimulation efficacy. CONCLUSIONS: Findings underscore a functional relevance of activity during the SO up-to-down state transition for memory consolidation and provide support for distinct consolidation mechanisms for types of declarative memories.

Biological Aspects and Clinical Applications of Mesenchymal Stem Cells: Key Features You Need to be Aware of.

Mesenchymal Stem Cells (MSCs), a form of adult stem cells, are known to have a selfrenewing property and the potential to specialize into a multitude of cells and tissues such as adipocytes, cartilage cells, and fibroblasts. MSCs can migrate and home to the desired target zone where inflammation is present. The unique characteristics of MSCs in repairing, differentiation, regeneration, and the high capacity of immune modulation have attracted tremendous attention for exerting them in clinical purposes, as they contribute to the tissue regeneration process and anti-tumor activity. The MSCs-based treatment has demonstrated remarkable applicability towards various diseases such as heart and bone malignancies, and cancer cells. Importantly, genetically engineered MSCs, as a stateof- the-art therapeutic approach, could address some clinical hurdles by systemic secretion of cytokines and other agents with a short half-life and high toxicity. Therefore, understanding the biological aspects and the characteristics of MSCs is an imperative issue of concern. Herein, we provide an overview of the therapeutic application and the biological features of MSCs against different inflammatory diseases and cancer cells. We further shed light on MSCs' physiological interaction, such as migration, homing, and tissue repairing mechanisms in different healthy and inflamed tissues.

Dropout of infertility treatments and related factors among infertile couples.

BACKGROUND: Dropout of infertility treatments is a global issue and many factors play role in this phenomenon. It is one of the most challenges in life of infertile couples. The purpose of this study was to determine dropout rate and related factors/reasons in the world and in Iran. METHODS: We will conduct a mixed method study with sequential exploratory design (systematic review, qualitative and quantitative phase). In the first stage a systematic review on dropout rate of infertility treatments and related factors will be done. In second stage (quantitative-qualitative study), a retrospective cohort study will be conducted on infertile couples to determine dropout rate of infertility treatments. The follow-up period to assess the discontinuation of treatment in patients, who have discontinued the treatment, will be considered 6 months after the treatment cessation. Data would be analyzed by descriptive statistics. We want to determine proportion and percentage of discontinuation rate among different groups with different causes of infertility. Then, we also will use Chi-square test to compare discontinuation rates among these groups. In qualitative section of second stage, semi-structured interviews would be performed with infertile female who had the history of infertility treatments failure. In this stage, participants will be selected using purposeful sampling method with maximum variation in terms of age, education, occupation, type of infertility, type of treatments, number of unsuccessful treatment and infertility duration. Data would be analyzed using conventional content analysis. DISCUSSION: Determining dropout rate and its related factors/reasons would be helpful for future studies to plan suitable interventions for supporting infertile couples. It also helps politicians to have a better understanding of infertility and its consequences on infertile couple's life. In today's world, infertility is a common phenomenon due to postponement of childbearing following the older age of marriage, tendency to reach higher educational level, economical problems and etc. Infertility brings many challenges and stresses to the individuals by itself and it is very hard to cope with. The problem gets worse, when it is associated with failure in treatments. Many of infertile couples cannot tolerate this failure and may decide to discontinue treatments before achieving pregnancy for ending many stressors which are associated with treatments. As we know, childbearing and having at least one child has important position in some societies such as Iranian culture; so ending the treatment before achieving optimal result may have some adverse consequences in the families such as divorce, remarriage, family conflicts, et. Absolutely many factors play role in dropout of infertility treatments, and many studies around the world have suggested many factors/reasons in dropout of infertility treatments, but there are still many gaps about this subject, especially among Iranian society. This study would be conducted in three consecutive stages, in the first stage; we will do a complete review of existing studies of the world to find out related factors/reasons of dropout in detail. In second stage, dropout rate of infertile couples (380 couples) after at least one unsuccessful cycle of treatment would be achieved by assessing medical records and telephone interview. Data of the first and second stage will help us to have better vision about the issue of dropout and would be used to construct a semi structured interview for the last stage. And finally in the third stage, reasons of dropout would be asked by an in depth interview from infertile couples. We hope the information from this study will help politicians better understand and plan for dropout of treatment.

Early postkidney transplantation hypophosphatemia.

BACKGROUND: As hypophosphatemia is a common multifactorial problem of kidney transplantation (Tx), this research aimed at studying the frequency of posttransparent hypophosphatemia in the early postkidney Tx period and investigating the risk components associated with the situation. MATERIALS AND METHODS: In this study, 50 renal transplant recipients on the day before (-1) and on days 10 (+10) and 30 (+30) days after kidney Tx were examined for the levels of serum phosphate (Pi). Levels of serum creatinine (Cr), Pi, 25-hydroxyvitamin D (25[OH] D), intact parathyroid hormone (iPTH) and fibroblast growth factor 23 (FGF-23), the 24 h urinary excretion of Pi and Cr, estimated glomerular filtration rate (eGFR), and the ratio of transport maximum of Pi (TMP) to eGFR (TMP/GFR) were evaluated on the same days. RESULTS: Hypophosphatemia (serum Pi <2.5 mg/dl) was seen in 0%, 40%, and 42% of the patients on days -1, +10, and +30, respectively. The levels of 25(OH)D and iPTH were not significantly different in patients with and without hypophosphatemia on days +10 and +30. Compared to those with normophosphatemia, pre-Tx FGF-23 level was significantly higher in patients with hypophosphatemia on days +10 and +30, respectively. The regression coefficient of TMP/GFR and Cr was positive on days -1, +10, and +30. The coefficient of pre-Tx FGF-23 on post-Tx serum Pi was negative on days +10 (P < 0.03) and +30 (P < 0.003), and the coefficient of post-Tx FGF-23 was negative just on day +10 with serum Pi (P < 0.008). CONCLUSION: The main causes of post-Tx hypophosphatemia in the multivariate linear analysis were pre-Tx FGF-23 and post-Tx FGF-23 levels on days +10, post-Tx Cr, and TMP/GFR.