The association between fasting plasma glucose variability and incident eGFR decline: evidence from two cohort studies.

BACKGROUND: Glycemic variability (GV) is developing as a marker of glycemic control, which can be utilized as a promising predictor of complications. To determine whether long-term GV is associated with incident eGFR decline in two cohorts of Tehran Lipid and Glucose Study (TLGS) and Multi-Ethnic Study of Atherosclerosis (MESA) during a median follow-up of 12.2 years. METHODS: Study participants included 4422 Iranian adults (including 528 patients with T2D) aged ≥ 20 years from TLGS and 4290 American adults (including 521 patients with T2D) aged ≥ 45 years from MESA. The Multivariate Cox proportional hazard models were used to assess the risk of incident eGFR decline for each of the fasting plasma glucose (FPG) variability measures including standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) both as continuous and categorical variables. The time of start for eGFR decline and FPG variability assessment was the same, but the event cases were excluded during the exposure period. RESULTS: In TLGS participants without T2D, for each unit change in FPG variability measures, the hazards (HRs) and 95% confidence intervals (CI) for eGFR decline ≥ 40% of SD, CV, and VIM were 1.07(1.01-1.13), 1.06(1.01-1.11), and 1.07(1.01-1.13), respectively. Moreover, the third tertile of FPG-SD and FPG-VIM parameters was significantly associated with a 60 and 69% higher risk for eGFR decline ≥ 40%, respectively. In MESA participants with T2D, each unit change in FPG variability measures was significantly associated with a higher risk for eGFR decline ≥ 40%.Regarding eGFR decline ≥ 30% as the outcome, in the TLGS, regardless of diabetes status, no association was shown between FPG variability measures and risk of eGFR decline in any of the models; however, in the MESA the results were in line with those of GFR decline ≥ 40%.Using pooled data from the two cohorts we found that generally FPG variability were associated with higher risk of eGFR decline ≥ 40% only among non-T2D individuals. CONCLUSIONS: Higher FPG variability was associated with an increased risk of eGFR decline in the diabetic American population; however, this unfavorable impact was found only among the non-diabetic Iranian population.

Statins block mammalian target of rapamycin pathway: a possible novel therapeutic strategy for inflammatory, malignant and neurodegenerative diseases.

Inflammation plays a critical role in several diseases such as cancer, gastric, heart and nervous system diseases. Data suggest that the activation of mammalian target of rapamycin (mTOR) pathway in epithelial cells leads to inflammation. Statins, the inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), seem to be able to inhibit the mTOR. Statins are considered to have favorable effects on inflammatory diseases by reducing the complications caused by inflammation and by regulating the inflammatory process and cytokines secretion. This critical review collected data on this topic from clinical, in vivo and in vitro studies published between 1998 and June 2022 in English from databases including PubMed, Google Scholar, Scopus, and Cochrane libraries.

Neglected Adrenal Hypoplasia Congenita in Two Siblings with Novel Genetic Mutations in NR0B1 Gene and Notable Clinical Course: A Case Report.

BACKGROUND: Adrenal Hypoplasia Congenita (AHC) is a rare subtype of primary adrenal insufficiency (PAI) that can go undiagnosed easily. In this article, we report two brothers with hypogonadotropic hypogonadism and novel mutations in the NR0B1 gene who were misdiagnosed and mismanaged as having congenital adrenal hypoplasia (CAH) for several years. CASE PRESENTATION: Herein, we describe two brothers with similar histories; first, they were diagnosed with CAH and treated for that; however, after several years, they showed symptoms of lack of testosterone despite receiving CAH treatment. Low levels of testosterone and LH were detected in both, and a genetic test of CAH was negative for the first brother. Thereafter, DAX- 1 deficiency was suspected, and their genetic tests (the NR0B1 gene) confirmed the diagnosis of DAX-1. CONCLUSION: The diagnosis of CAH in case of low levels of 17- OHP, testosterone, and LH, as well as central hypogonadotropic hypogonadism, should be studied, and further investigations are mandatory to evaluate other subtypes of PAI, especially AHC.

Treatments for Olfactory Dysfunction in COVID-19: A Systematic Review.

Introduction Olfactory dysfunction (OD) has emerged as a notable symptom among coronavirus disease 2019 (COVID-19) patients, with its prevalence varying among different populations. Recognizing the need to provide therapeutic solutions for these individuals, the present study seeks to comprehensively review the current evidence on potential underlying mechanisms and treatment modalities to manage OD in COVID-19 patients. Objective To review the recent evidence on treatments for OD in COVID-19. From the beginning of the study until August 2nd, 2023, we conducted a systematic search on four electronic databases, PubMed, Scopus, Embase, and Web of Science, to find relevant publications. Data Synthesis In the present study, 37 articles were selected for data extraction and included in the final review. The total number of patients was of 3,560 (2,098 female and 1,462 male subjects). The predominant disorders reported were hyposmia, anosmia, and parosmia. In most of the studies, the pre and postintervention assessments were the same, except for one study, in which the pre-intervention assessment of the disorder was through the SST, Sniffin' Sticks Test (SST), and the post-intervention assessment was through the Visual Analog Scale (VAS) and the 22-item Sinonasal Outcome Test (SNOT-22). The findings suggest olfactory training (OT), ivermectin, palmitoylethanolamide, luteolin, and systemic corticosteroids, in combination with topical corticosteroids, are potential therapies for COVID-19 patients with olfactory impairment. Conclusion Although the review suggested several medications for OD treatment, further research must delve into the specific impact of OT, a non-pharmacological modality, regarding the mitigation of OD. By continuing to investigate and refine these therapeutic approaches, we can better support COVID-19 patients and improve their quality of life while navigating the challenges posed by OD.

MicroRNAs, long non-coding RNAs, and circular RNAs and gynecological cancers: focus on metastasis.

Gynecologic cancer is a significant cause of death in women worldwide, with cervical cancer, ovarian cancer, and endometrial cancer being among the most well-known types. The initiation and progression of gynecologic cancers involve a variety of biological functions, including angiogenesis and metastasis-given that death mostly occurs from metastatic tumors that have invaded the surrounding tissues. Therefore, understanding the molecular pathways underlying gynecologic cancer metastasis is critical for enhancing patient survival and outcomes. Recent research has revealed the contribution of numerous non-coding RNAs (ncRNAs) to metastasis and invasion of gynecologic cancer by affecting specific cellular pathways. This review focuses on three types of gynecologic cancer (ovarian, endometrial, and cervical) and three kinds of ncRNAs (long non-coding RNAs, microRNAs, and circular RNAs). We summarize the detailed role of non-coding RNAs in the different pathways and molecular interactions involved in the invasion and metastasis of these cancers.

Effect of family history of diabetes and obesity status on lifetime risk of type 2 diabetes in the Iranian population.

Background: Data are scarce for the lifetime risk of diabetes in the Middle East and North Africa region countries. We estimated the lifetime risk of type 2 diabetes among Iranian adults at age 20 and 40 years, and their variation by family history of diabetes and body mass index (BMI). Methods: The data from 8435 diabetes-free participants from the Tehran Lipid and Glucose study were used in this analysis. We estimated the lifetime risk of diabetes stratified by sex, and quantified the impact of family history of diabetes and BMI status on the lifetime risks, singly and jointly. Results: At age 20 years, the overall lifetime risk of diabetes was 57.8% (95% CI = 54.0%-61.8%) for men and 61.3% (57.2%-65.4%) for women. Having both family history of diabetes and increased level of BMI, alone, increased the lifetime risk of diabetes in both sexes. Moreover, the simultaneous presence of family history of diabetes and overweigh/obesity increased the lifetime risk of diabetes in both sexes. So that, at age 20 years the lifetime risk in obese men with positive family history of diabetes was about 54% higher, compared to normal weight men without family history of diabetes; the corresponding value for women was 42%. Also, normal weight men without family history of diabetes lived 24 years longer free of diabetes, compared with obese men with family history of diabetes. In women, the corresponding value was 20 years. Conclusion: Our study shows the alarming lifetime risk of diabetes across the strata of BMI, which emphasizes the need for more effective interventions to reduce incidence, particularly, among individuals with positive family history of diabetes.

Application of the 2017 American college of cardiology/American Heart Association Blood Pressure Guidelines for cardiovascular outcomes among Tehranian residents.

OBJECTIVES: To evaluate the associations of cardiovascular disease (CVD) outcomes with elevated blood pressure (BP), stage I of isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic diastolic hypertension (SDH), defined by 2017 ACC/AHA guidelines among the Tehranian adult population. METHOD: We enrolled 7068 residents of Tehran (district No. 13) aged at least 30 years, who were free of CVD and not taking antihypertensive medications at baseline. Participants were categorized into eight categories: normal BP (reference group), elevated BP, stage I IDH, stage I ISH, stage I SDH, and all stage II phenotypes. Significant interactions were found between age groups (<60 versus ≥60 years) and BP categories (P value: 0.017); hence, the analysis was performed in each age group, separately. We used multivariable Cox proportional regression analysis to evaluate the association of different BP categories with incident CVD. RESULTS: During 18years of follow-up, 1053 CVD events occurred. In the younger group, stage I of IDH and SDH were associated with increased CVD risk with hazard ratios (HRs) of 1.23 (95% confidence interval: 0.99-1.52) and 1.42 (1.04-1.94), respectively. In the older group, stage I of IDH had a lower risk for coronary heart disease (CHD) [HR 0.53 (0.29-0.96)]. As a sensitivity analysis, among high CVD risk individuals (10-year risk ≥10%), we found a higher risk for CVD among those with elevated BP and stage I of SDH. For individuals with 10-year risk less than 10%, all BP parameters, except stage I of IDH, were associated with increased CVD risk. Although there was no significant interaction between sex and BP categories, elevated BP and stage I of SDH significantly increased the risk of CVD only among men. CONCLUSION: Age is an important potential modifier in the association between stage I of hypertension and CVD/CHD risk. Stage I of IDH was not an alarming status for CVD development, whether the participants had a high CVD risk or not.

Comparative study of the outcomes of the second kidney transplantation from the young deceased donors versus living-unrelated donors.

PURPOSE: To compare the kidney graft function and survival in patients who had second kidney transplantation from living donors versus those who had a second transplant from young deceased donors. METHODS: In this retrospective cohort study, a total of 86 patients who underwent second kidney transplantation in Shariati hospital from 2001 until 2017 were enrolled. Baseline clinical data on the age, sex, type of kidney donor (living unrelated or deceased), duration of pretransplant dialysis, and the length of hospitalization were recorded. As the indicators of the graft function, we used the serum creatinine level and estimated glomerular filtration rate (eGFR) at time intervals during the study. The 1, 5, and 10-year graft survival rates were reported using life tables and the relative hazard ratios of the graft failure were calculated using the forward stepwise Cox proportional hazard model. RESULTS: Forty-six of our patients were men (53.5%), with a mean ± SD age of 44.3 ± 12.3 years at the time of transplantation. The majority of the enrolled patients received the kidney from living unrelated donors (50 vs. 36 patients). In terms of serum creatinine and eGFR, at time intervals, no significant difference was found between the two recipient groups. In the living donor group, the 1, 5, and 10-year graft survival rates of the second transplant were 91% (95%CI: 73-96%), 87% (95%CI: 69-95%), and 82% (95%CI: 59-92%), and for the deceased donor group were 95% (95% CI: 69-99%), 95% (95%CI: 69-99%), and 79% (95%CI: 31-95%), respectively. CONCLUSION: Considering the long-term outcomes of the second kidney transplantation, in our experience, the graft function and survival, either from the living or deceased donors, were favorable; and the type of organ donation had no significant effect on the risk of graft failure.

Lysophosphatidic Acid Signaling and microRNAs: New Roles in Various Cancers.

A wide range of microRNAs (miRNAs) are coded for in the human genome and contribute to the regulation of gene expression. MiRNAs are able to degrade mRNAs and/or prevent the RNA transcript from being translated through complementary binding of the miRNA seed region (nucleotide 2-8) to the 3'-untranslated regions of many mRNAs. Although miRNAs are involved in almost all processes of normal human cells, they are also involved in the abnormal functions of cancer cells. MiRNAs can play dual regulatory roles in cancer, acting either as tumor suppressors or as tumor promoters, depending on the target, tumor type, and stage. In the current review, we discuss the present status of miRNA modulation in the setting of lysophosphatidic acid (LPA) signaling. LPA is produced from lysophosphatidylcholine by the enzyme autotaxin and signals via a range of G protein-coupled receptors to affect cellular processes, which ultimately causes changes in cell morphology, survival, proliferation, differentiation, migration, and adhesion. Several studies have identified miRNAs that are over-expressed in response to stimulation by LPA, but their functional roles have not yet been fully clarified. Since RNA-based treatments hold tremendous promise in the area of personalized medicne, many efforts have been made to bring miRNAs into clinical trials, and this field is evolving at an increasing pace.

A meta-analysis of accuracy and sensitivity of chest CT and RT-PCR in COVID-19 diagnosis.

Nowadays there is an ongoing acute respiratory outbreak caused by the novel highly contagious coronavirus (COVID-19). The diagnostic protocol is based on quantitative reverse-transcription polymerase chain reaction (RT-PCR) and chests CT scan, with uncertain accuracy. This meta-analysis study determines the diagnostic value of an initial chest CT scan in patients with COVID-19 infection in comparison with RT-PCR. Three main databases; PubMed (MEDLINE), Scopus, and EMBASE were systematically searched for all published literature from January 1st, 2019, to the 21st May 2020 with the keywords "COVID19 virus", "2019 novel coronavirus", "Wuhan coronavirus", "2019-nCoV", "X-Ray Computed Tomography", "Polymerase Chain Reaction", "Reverse Transcriptase PCR", and "PCR Reverse Transcriptase". All relevant case-series, cross-sectional, and cohort studies were selected. Data extraction and analysis were performed using STATA v.14.0SE (College Station, TX, USA) and RevMan 5. Among 1022 articles, 60 studies were eligible for totalizing 5744 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value of chest CT scan compared to RT-PCR were 87% (95% CI 85-90%), 46% (95% CI 29-63%), 69% (95% CI 56-72%), and 89% (95% CI 82-96%), respectively. It is important to rely on the repeated RT-PCR three times to give 99% accuracy, especially in negative samples. Regarding the overall diagnostic sensitivity of 87% for chest CT, the RT-PCR testing is essential and should be repeated to escape misdiagnosis.