Effect of CYP3A5*1 expression on tacrolimus required dose after liver transplantation: A systematic review and meta‐analysis

We systematically collected eligible data to measure the effect of CYP3A5*1 expression on personalized tacrolimus therapy. Six databases were searched for studies on adult liver transplant recipients and donors of liver graft which reported tacrolimus dose requirement, trough blood concentration, and/or concentration/dose (C/D) ratio in expressers and nonexpressers of CYP3A5*1. Eligible data were pooled by meta‐analysis. Sixteen observational studies (1309 recipients, 1044 donors of liver graft) were included in the analyses. Tacrolimus C/D ratio was lower, and the dose was higher in recipient expressers of CYP3A5*1 and/or carriers of expresser liver graft at 1‐4 weeks and 2‐4, 6, and 12 months post‐transplantation. Tacrolimus blood concentration was lower at the first two weeks. Pair expressers were affected by about twofold, and the effect was different between ethnic groups. CYP3A5*1 expression in recipients increased tacrolimus required dose by 0.023 at first, 0.022 at third, and 0.012 mg/kg/day at sixth month. Its expression in graft tissue increased tacrolimus required dose by 0.024 at first, 0.035 at third, and 0.032 mg/kg/day at sixth month. Considering CYP3A5*1 polymorphism can be helpful in individualization of tacrolimus efficient dose prior to administration, and it can remove initial high‐risk lag time (over/underdose period before reaching target blood level) at first few days post‐transplantation.     

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population.

BACKGROUND: The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene has been variably associated with insulin resistance, obesity and type 2 diabetes in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that this variation might be associated with insulin resistance, type 2 diabetes and related metabolic traits in this population. METHODS: The Pro12Ala genotypes were determined by PCR-restriction fragment length polymorphism in 696 unrelated subjects including 412 non-diabetic controls and 284 type 2 diabetic patients. RESULTS: The frequency of the Ala allele was 9.4% and 5.9% in controls and type 2 diabetic subjects, respectively [adjusted odds ratio (OR) 0.457, p=0.005]. The Ala allele did not show a significant effect on anthropometric and biochemical parameters in the type 2 diabetic group, whereas in non-diabetic subjects, carriers of the Ala allele had significantly lower fasting insulin (p=0.007) and homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.009) levels compared to Pro/Pro subjects. Multivariate logistic regression analysis showed that Pro12Ala polymorphism was an independent determinant of type 2 diabetes in this population. CONCLUSIONS: Our results for a sample of Iranian type 2 diabetes cases and controls provide evidence that the Pro/Ala genotype of the PPARgamma-2 gene is associated with insulin sensitivity and may also have protective role against type 2 diabetes.     

Persian version of the Moorong Self-Efficacy Scale: psychometric study among subjects with physical disability

Purpose: Self-efficacy plays a key role in varying areas of human conditions which can be measured by different scales. The present study was aimed to evaluate the psychometric properties of Moorong Self-Efficacy Scale (MSES) in Iranian Subjects with Physical Disability (SWPD).

Method: Data were collected by face-to-face interviews and self-report surveys from 214 subjects. The face and content validity, and reliability were evaluated. Discriminates were evaluated between the sub-groups of disability levels, physical activity, and health condition levels. The concurrent, convergent, divergent, and construct validity were assessed by short form health survey scale (SF-36), general self-efficacy scale (GSES), hospital anxiety and depression scale (HADS), respectively. Replaceable exploratory factor analysis was evaluated. SPSS software was used for statistical analysis.

Results: There were acceptable face and content validity, and reliability. Furthermore, significant correlation was found between PSES and SF-36 (p?p?=?0.02), physical activity levels (p?p?=?0.001). The correlation of Persian Self-Efficacy Scale (PSES) scores with GSES (r?=?0.61, p?R?=??0.53, p?Conclusions: The PSES is a valid, reliable and sensitive tool to measure the self-efficacy among SWPD for planning and managing of disability problems.

• Implications for rehabilitation

• Psychometric properties of the Persian version of self-Efficacy scale (PSES) appear to be similar to original, English version.

• The PSES has been shown to have validity and reliability in Persian physical disables and can be used for patients with more different types of physical disability than individuals suffering from only Spinal Cord Injury (SCI).

• The PSES can be used in clinical practice and research work to evaluate the patients’ confidence in performing daily activities.

     

Developmental and cytogenetic assessments of preimplantation embryos derived from in-vivo or in-vitro matured human oocytes

Aneuploidy is of great relevance to embryo selection, as it represents one of the important causes of implantation failure. Furthermore, immature oocytes, retrieved during gonadotrophin-stimulated IVF cycles, are generally discarded in clinics; whereas, there was no detectable comprehensive evidence on higher rates of aneuploidy based on maturity status on the day of oocyte retrieval. As well, the correlation between embryo morphology on aneuploidy remains unclear. The aim was to evaluate the developmental and genetic integrity of human preimplantation embryos from rescue in-vitro matured MII stage oocytes as well as in vivo matured oocytes. 541 rescue in-vitro matured oocytes as case as well as 659 in-vivo matured oocytes as control were used for the developmental assay. Finally, 121 cleaved embryos with good quality were analyzed by FISH technique for the detection of chromosomes X, Y, 13, 15, 16, 18, 21 and 22. The fertilization rates were 61.62% and 61.76% in case and control groups, respectively. Also, embryo formation rates of 89.1% vs. 92.2% were recorded for case and control groups, respectively. Good quality embryos on day 3 were 62.54% in case and 68.36% in control groups. There were insignificant differences in fertilization, embryo formation and quality between the groups. Total abnormality in 35 of the 60 embryos was 58.5% in case and 62.3% in control (p < 0.05). There were significant differences between aneuploidy rates of embryos using only sex chromosome preimplantation genetic screening (PGS) and sex chromosome in combination with autosomal chromosomes PGS in case (58.5% vs 28.3%, p = 0.000) and control groups (62.3% vs 21.3%; p = 0.000). The results demonstrated that a high proportion of good quality embryos were aneuploid in both patient groups with no obvious increase in aneuploidies as a result of rescue IVM application. Furthermore, the morphological characteristics of embryos do not completely consistent with chromosomal content. Despite the Rescue IVM is currently not a routine procedure in association with IVF, our finding suggested a viable option for young infertile women facing cancellation of their IVF treatment due to ovarian over-response or resistance factors as well as patients with low functional ovarian reserve considering good quality of embryos from rescue IVM-MII oocytes.     

Calprotectin (S100A8/S100A9): a key protein between inflammation and cancer

Background

Calprotectin (S100A8/S100A9), a heterodimeric EF-hand Ca²⁺?binding protein, are abundant in cytosol of neutrophils and are involved in inflammatory processes and several cancerous pathogens.

Objective

The purpose of the present systematic review is to evaluate the pro- and anti-tumorigenic functions of calprotectin and its relation to inflammation.

Materials and methods

We conducted a review of studies published in the Medline (1966–2018), Scopus (2004–2018), ClinicalTrials.gov (2008–2018) and Google Scholar (2004–2018) databases, combined with studies found in the reference lists of the included studies.

Results

Elevated levels of S100A8/S100A9 were detected in inflammation, neoplastic tumor cells and various human cancers. Recent data have explained that many cancers arise from sites of infection, chronic irritation, and inflammation. The inflammatory microenvironment which largely includes calprotectin, has an essential role on high producing of inflammatory factors and then on neoplastic process and metastasis.

Conclusion

Scientists have shown different outcomes in inflammation, malignancy and apoptosis whether the source of the aforementioned protein is extracellular or intracellular. These findings are offering new insights that anti-inflammatory therapeutic agents and anti-tumorigenic functions of calprotectin can lead to control cancer development.

     

Evaluating the efficacy of extracted squalene from seed oil in the form of microemulsion for the treatment of COVID-19: A clinical study

This study investigates the effect of the nanostructure of squalene in the form of microemulsion on COVID-19 patients. In this blinded clinical trial, a comparison was made between the efficacy of squalene treatment and controls. A total of 30 COVID-19 patients admitted to the emergency department, and the infection ward was equally allocated to case (n = 15) and control (n = 15) groups according to their age and underlying diseases. The baseline characteristics of subjects, including age, gender, time of treatment onset, underlying condition, white blood cells count, and lymphocyte count were similar (p < 0.05). Baseline laboratory tests and computed tomography (CT) scans were performed for the study groups. The treatment group received 5 mg of intravenous squalene twice a day and standard treatment for 6 days, while controls received only standard treatment. After 6 days of treatment, clinical and CT scan changes were evaluated and compared in intervention and control groups. The need for oxygen therapy (p = 0.020), 2 days of no fever (p = 0.025), cough alleviation (p = 0.010), and lung high-resolution computed tomography improvement (p = 0.033) were significantly different between cases and controls within 7 days of admission. No adverse effects were observed in the treatment group. Our data suggest that squalene could be considered as a potential treatment for COVID-19, and further studies are required to confirm the results.     

Effect of eccentric and concentric contraction mode on myogenic regulatory factors expression in human vastus lateralis muscle

Skeletal muscle contractions are caused to release myokines by muscle fiber. This study investigated the myogenic regulatory factors, as MHC I, IIA, IIX, Myo-D, MRF4, Murf, Atrogin-1, Decorin, Myonection, and IL-15 mRNA expression in the response of eccentric vs concentric contraction. Eighteen healthy men were randomly divided into two eccentric and concentric groups, each of 9 persons. Isokinetic contraction protocols included maximal single-leg eccentric or concentric knee extension tasks at 60°/s with the dominant leg. Contractions consisted of a maximum of 12 sets of 10 reps, and the rest time between each set was 30 s. The baseline biopsy was performed 4 weeks before the study, and post-test biopsies were taken immediately after exercise protocols from the vastus lateralis muscle. The gene expression levels were evaluated using Real-Time PCR methods. The eccentric group showed a significantly lower RPE score than the concentric group (P?≤?0.05). A significant difference in MyoD, MRF4, Myonection, and Decorin mRNA, were observed following eccentric or concentric contractions (P?≤?0.05). The MHC I, MHC IIA, IL-15 mRNA has been changed significantly compared to the pre-exercise in the concentric group (P?≤?0.05). While only MHC IIX and Atrogin-1 mRNA changed significantly in the eccentric group (P?≤?0.05). Additionally, the results showed a significant difference in MyoD, MRF4, IL-15, and Decorin at the follow-up values between eccentric or concentric groups (P?≤?0.05). Our findings highlight the growing importance of elucidating the different responses of muscle growth factors associated with a myogenic activity such as MHC IIA, Decorin, IL-15, Myonectin, Decorin, MuRF1, and MHC IIX mRNA in following various types of exercise.

     

The relationship between general health and coping style with perceived stress in primigravida healthy pregnant women: Using the PATH model

The aim of this study was to analyze relationships among general health, coping style, and perceived stress in healthy primigravida pregnant women. A cross-sectional study was conducted at public health clinics in Hamadan city, Iran between July and December 2015. In total, 380 pregnant women were selected through stratified random sampling. Data were collected using the Revised Prenatal Coping Inventory and General Health Questionnaire. Perceived stress was assessed through an interview comprised of open-ended questions. The final PATH model fit well; general health (β = 0.02) as well as anxiety and sleep disorders (β = 0.03) were slightly directly associated with perceived stress, and only planning–preparation was related to perceived stress through general health (β = 0.09). The findings enhance the knowledge gained from previous perinatal stress research. General health status was directly related to stress, and coping style was indirectly related to stress. Coping styles may mediate the relationship between general health status and perceived stress, suggesting that midwives should attempt to improve the general health of women to reduce stress and its consequences during pregnancy by teaching patients appropriate coping styles. Further studies on the effect of coping style interventions on stress are warranted.