Are resting metabolic rate and clinical symptoms affected by variation of serum thyroid stimulating hormone levels within the normal range in healthy and women with hypothyroidism? A case-control study.

BACKGROUND: It is unclear whether variation in thyroid stimulating hormone (TSH) levels within the reference range affect energy expenditure and clinical symptoms and even within the normal range of TSH levels, resting energy expenditure may alter. The aim of the present study was to determine whether treated hypothyroid subjects and healthy subjects with a low-normal TSH range (0.3-2.3 mIU/L) have better clinical outcomes and increased energy expenditure than those with a high-normal TSH range (2.3-4.3 mIU/L). METHODS: This was a case-control study of 160 overweight/obese women with TSH levels across the reference range of 0.3-4.3 mU/l. Subjects were paired in four groups: healthy subjects with low-normal target TSH (n = 40), healthy subjects with high-normal target TSH (n = 40), subjects with treated hypothyroidism with low-normal target TSH (n = 40), and subjects with treated hypothyroidism with high-normal target TSH (n = 40). Resting energy expenditure (RMR), dietary intake, body composition, physical activity, and biochemical markers were assessed. RESULTS: Subjects with low-normal (≤2.3 mU/L) and high-normal (>2.3 mU/L) TSH levels did not differ in terms of RMR, serum T3 levels, and clinical symptoms except fatigue (P = 0.013). However, serum fT4 levels were found to be significantly different between the study groups (P = 0.002). Serum fT4 concentration was the highest in subjects with treated hypothyroidism with low-normal target TSH. CONCLUSION: Variation in serum TSH levels within the reference range did not significantly affect REE and clinical symptoms except fatigue in healthy and women with hypothyroidism.

The effect of conjugated linoleic acid supplementation in comparison with omega-6 and omega-9 on lipid profile: a graded, dose-response systematic review and meta-analysis of randomized controlled trials.

Conjugated linoleic acid (CLA) is a geometrical isomer of linoleic acid, which has anti-inflammatory, anti-diabetic, anti-cancer, and anti-obesity properties. However, the studies reported inconstant results about the CLA-related effects on lipid profiles. As a result, meta-analysis and systematic review were performed to survey the CLA supplementation-related effect on lipid profile including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG). To identify the relevant research, a systematic comprehensive search was initiated on the medical databases such as Scopus and PubMed/Medline until December 2022. The overall effect size was estimated by weighted mean difference (WMD) and 95% confidence interval (CI) in a random effect meta-analysis. In the final quantitative analysis, the meta-analysis considered 35 randomized controlled trials (RCTs) with 1,476 participants (707 controls and 769 cases). The pooled results demonstrated that CLA supplementation, compared with olive oil, significantly increased serum TG levels (WMD: 0.05 mmol/L; 95% CI: 0.01 to 0.1; p = 0.04; I2 = 0.0%, p = 0.91). With regard to TC level, CLA supplementation compared with placebo significantly reduced TC concentrations (WMD: -0.08 mmol/L; 95% CI: -0.14 to -0.02; p < 0.001; I2 = 82.4%). Moreover, the non-linear dose-response analysis indicated a decreasing trend of TC serum level from the 15th week of CLA supplementation compared with olive oil (Pnon-linearity = 0.01). The present meta-analysis and systematic review of 35 RCTs showed that the CLA intervention was able to raise the level of TG in comparison to olive oil; however, it can decrease TC level compared with placebo and olive oil.

Demographic and biological factors in interrelationships between physical, cognitive, psychological, and social frailty in community-dwelling older adults: Data from the Birjand Longitudinal Aging Study (BLAS).

Complex interrelationships may exist among different types of frailty. This study aimed to evaluate the demographic and biological factors that influence the different types of frailty in community-dwelling older adults in Iran through a cross-sectional analysis of data obtained from the Birjand Longitudinal Aging Study. This study is an ongoing cohort study of people aged 60 years and over and employed a multistage stratified cluster random sampling. Anthropometric measures were obtained by nurses. The "Fried frailty phenotype" was defined as physical frailty. Cognitive frailty was assessed using the Mini-Mental State Examination. Social frailty was evaluated by some questions, and psychological frailty was assessed using a patient health questionnaire. Blood samples were taken after overnight fasting. All statistical analyses were performed using Stata12 (Texas, USA) and Python. Some type of frailty had been experienced by 62.27 % of the older adults. Cognitive frailty was the dominant type of frailty (55.69 %). Based on multivariate regression analysis, age, sex, education, and marital status were the influencing factors in all types of frailty. Network analysis revealed that physical, cognitive, psychological, and social frailty had synergistic effects on each other, and age and sex had dominant interactions with frailty types. Cognitive frailty was dominant compared with other types of frailty, indicating the need to detect cognitive frailty at the earliest stage and to implement an appropriate program to manage cognitive frailty in older adults.

Prevalence of thyroid dysfunction among Iranian older adults: a cross-sectional study.

There is limited data on the prevalence of thyroid dysfunction in the older population. This study aimed to determine the prevalence of thyroid dysfunction among a sample of Iranian older adults. A cross-sectional analysis of older adults who aged 60 years and over was conducted. A total of 363 subjects were randomly selected from Birjand longitudinal aging study (BLAS) cohort study. Serum thyroid-stimulating hormone (TSH) level, total thyroxine (T4) and total triiodothyronine (T3) were measured by the enzyme-linked immunosorbent assay (ELISA). Based on thyroid function tests and history of taking medicines used to treat thyroid disorders, participants were classified into the following groups: euthyroid, overt/subclinical hypothyroidism, and overt/subclinical hyperthyroidism. Subsequently, the crude and World Health Organization (WHO) age-standardized prevalence were estimated for different thyroid function categories. A total of 171 men and 192 women, aged 60-94 years, were randomly selected. The crude prevalence of total hypothyroidism was 22.31% (subclinical [18.46%], overt [3.86%]), and that of hyperthyroidism was 1.66% (subclinical [1.38%], overt [0.28%]). The crude prevalence of total thyroid dysfunction was, therefore, 23.97%. A female preponderance was noticed in both total (P-value = 0.035) and overt (P-value = 0.035) hypothyroidism. An increasing trend with age was noticed in the prevalence of total hypothyroidism (P-value = 0.049). Age-standardized prevalence of total hypothyroidism and hyperthyroidism was 26.63% (95% confidence interval [CI] 20.58-33.69%) and 1.11% (95% CI 0.49-2.51%), respectively. A considerable proportion of our study population demonstrated evidence of thyroid dysfunction, particularly subclinical hypothyroidism. Our findings highlight the importance of further investigation of thyroid disorders among older Iranian adults.

Population pharmacokinetics of vancomycin in patients with diabetic foot infection: a comparison of five models.

Purpose: This study aimed to compare individual pharmacokinetic (PK) parameters of vancomycin with predicted values from five population PK models in patients with diabetic foot infections (DFIs). Methods: Patients with a diagnosis of DFI and an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min were included in the study. Individual PK data was carried on by collecting three vancomycin serum concentrations in a steady-state condition. Five published population-based nomograms were assumed to predict PK parameters. Optimal vancomycin exposure was considered as a trough level of 15-20 mg/L or the area under the curve over 24 h/minimum inhibitory concentration (AUC24/MIC) ≥ 400. Results: A total of 48 samples from 16 patients were analyzed. There was a statistically significant difference between the volume of distribution (Vd) obtained from population methods and the individual estimations (P ≤ 0.001 in Ambrose and Burton, P = 0.010 and 0.006 in Bauer and Burton revised models, respectively). AUC/MIC ≥ 400 was achieved in 68.7% of patients while 50% had a trough level of less than 15 mg/L. Conclusions: Vancomycin PK parameters, particularly individualized Vd, may not be predictable by population nomograms in patients with DFI and stable renal function. Moreover, the weak correlation between AUC24 values and trough concentrations underlines the starting practice of vancomycin AUC24-based monitoring and dosing in the clinical setting.

Diabetic stem cell therapy and nanomedicine: advancements in treating diabetes.

Objectives: In recent years, significant advancements have been made in the field of medical sciences, particularly in the treatment of diabetes using innovative methods. Diabetes, a chronic metabolic disorder considered by elevated blood glucose levels, disturbs millions of people worldwide. Methods: Conventional treatments for diabetes have shown limited success in providing long-term solutions, leading researchers to explore alternative therapies such as diabetic stem cell therapy and nanomedicine. In this article, we delve into the promising potential of these cutting-edge treatments and their impact on diabetes management. Results: Several achievements have been obtained to treat diabetes type I by merging nanomedicine and cell therapy such as insulin-loaded exosomes and nanoparticles loaded with different drugs. For instance, by engineering exosomes with specific nanocarriers, researchers can precisely deliver some molecules to target cells, promoting tissue repair and regeneration. Conclusions: It seems that using nanomedicine and cell therapy, we can explore the inventive way for a future somewhere diabetes is no longer a problem for millions, and people can hold a great quality life.

Bromelain- and Silver Nanoparticle-Loaded Polycaprolactone/Chitosan Nanofibrous Dressings for Skin Wound Healing.

A cutaneous wound is caused by various injuries in the skin, which can be wrapped with an efficient dressing. Electrospinning is a straightforward adjustable technique that quickly and continuously generates nanofibrous wound dressings containing antibacterial and anti-inflammatory agents to promote wound healing. The present study investigated the physicochemical and biological properties of bromelain (BRO)- and silver nanoparticle (Ag NPs)-loaded gel-based electrospun polycaprolactone/chitosan (PCL/CS) nanofibrous dressings for wound-healing applications. Electron microscopy results showed that the obtained nanofibers (NFs) had a uniform and homogeneous morphology without beads with an average diameter of 176 ± 63 nm. The FTIR (Fourier transform infrared) analysis exhibited the loading of the components. Moreover, adding BRO and Ag NPs increased the tensile strength of the NFs up to 4.59 MPa. BRO and Ag NPs did not significantly affect the hydrophilicity and toxicity of the obtained wound dressing; however, the antibacterial activity against E. coli and S. aureus bacteria was significantly improved. The in vivo study showed that the wound dressing containing BRO and Ag NPs improved the wound-healing process within one week compared to other groups. Therefore, gel-based PCL/CS nanofibrous dressings containing BRO and Ag NPs could be a promising solution for healing skin wounds.

Serum Vitamin D Status and Cognitive Function in Iranian Older Adults: Evidence from the Birjand Longitudinal Aging Study.

BACKGROUND: There is evidence of the role of vitamin D deficiency in cognitive decline. However, the results of studies regarding the relationship between the reduction of vitamin D concentrations and cognitive impairment are heterogeneous. OBJECTIVES: We aimed to answer the question of whether vitamin D deficiency is associated with cognitive decline in older adults. METHODS: In this cross-sectional study, the baseline data of the Birjand Longitudinal Aging Study (BLAS) were analyzed. Of 1420 participants in the BLAS, 1219 participants aged ≥60 y old were included in the present study. Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were measured by the enzyme-linked immunosorbent assay method. The 6-item Cognitive Impairment Test (6-CIT), Mini-Mental State Examination (MMSE), Category Fluency Test (CFT), and Abbreviated Mental Test Score (AMTS) were used to assess cognitive function. Multiple logistic regression analysis, adjusted for potential confounders, was employed to estimate the association between cognitive function and 25(OH)D concentrations. RESULTS: Among study participants, 905 (74.24%) had sufficient vitamin D concentrations (≥20 ng/ml), 209 (17.15%) had insufficient vitamin D concentrations (12-20 ng/ml), and 105 (8.61%) had vitamin D deficiency (<12 ng/ml). There was no significant correlation between serum 25(OH)D concentrations and scores of 6-CIT (P = 0.279), AMTS (P = 0.181), MMSE (P = 0.118), and CFT (P = 0.259). Also, the prevalence of cognitive impairment had no significant relationship with vitamin D status. Finally, in the multiple logistic regression analysis, there was no association between the insufficient or deficient concentrations of 25(OH)D and impaired cognitive function both before and after adjustment for various cofounders. CONCLUSIONS: The present study found no significant association between vitamin D status and cognitive impairment.

Risk factors for insulin resistance related to polycystic ovarian syndrome in Iranian population.

Polycystic ovary syndrome (PCOS) has significant metabolic sequelae linked to insulin resistance. This study aimed to compare clinical, metabolic, and hormonal characteristics of PCOS women with and without insulin resistance. The second aim was to compare the clinico-biochemical profiles of the various PCOS phenotypes. In this cross-sectional secondary analysis, we combined the baseline data from two separate randomized controlled trials (RCTs) in women diagnosed with PCOS. PCOS patients were categorized into the four Rotterdam PCOS phenotypes according to the presence of at least two criteria of oligomenorrhea/anovulation (O), hyperandrogenism (H), and polycystic ovary morphology (P): O-H-P, H-P, O-H, and O-P. Participants were categorized into two groups according to the homeostasis model assessment index of insulin resistance (HOMA-IR) levels: < 3.46, and ≥ 3.46. The correlation between the HOMA-IR and biometric, clinical, and biochemical variables was assessed in normal weight (BMI < 25) and overweight/obese (BMI ≥ 25) PCOS women. Then, the association between PCOS phenotypes and insulin resistance was investigated using logistic regression analysis. A total of 125 PCOS patients aged 18-40 years were included in the present study. Based on our results, the HOMA-IR index was positively correlated with diastolic blood pressure, free androgen index, and triglycerides levels; and negatively correlated with sex hormone-binding globulin in overweight/obese PCOS women. In addition, the HOMA-IR index was found to be positively correlated with alanine transaminase and negatively correlated with diastolic blood pressure in normal weight PCOS women. Moreover, individuals with O-H-P phenotype (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.02-6.24) had about two-fold increased risk of insulin resistance. In conclusion, the full-blown PCOS (O-H-P) phenotype has an increased risk of insulin resistance. Accordingly, phenotype division may help physicians to predict adverse metabolic outcomes.

Design, synthesis, and cytotoxic evaluation of quinazoline derivatives bearing triazole-acetamides.

A novel series of quinazoline-based agents bearing triazole-acetamides 8a-l were designed and synthesized. All the obtained compounds were tested for in vitro cytotoxic activities against three human cancer cell lines named HCT-116, MCF-7, and HepG2, as well as a normal cell line WRL-68 after 48 and 72 h. The results implied that quinazoline-oxymethyltriazole compounds exhibited moderate to good anticancer potential. The most potent derivative against HCT-116 was 8a (X = 4-OCH3 and R = H) with IC50 values of 10.72 and 5.33 µM after 48 and 72 h compared with doxorubicin with IC50 values of 1.66 and 1.21 µM, respectively. The same trend was seen in the HepG2 cancerous cell line in which 8a recorded the best results with IC50 values of 17.48 and 7.94 after 48 and 72 h, respectively. The cytotoxic analysis against MCF-7 showed that 8f with IC50 = 21.29 µM (48 h) exhibited the best activity, while compounds 8k (IC50 = 11.32 µM) and 8a (IC50 = 12.96 µM), known as the most effective cytotoxic agents after 72 h. Doxorubicin as positive control exhibited IC50 values of 1.15 and 0.82 µM after 48 and 72 h, respectively. Noteworthy, all derivatives showed limited toxicity against the normal cell line. Moreover, docking studies were also presented to understand the interactions between these novel derivatives and possible targets.

Factors related to hypermetabolism in individuals with type 2 diabetes mellitus and non-alcoholic fatty liver disease.

Considering the progressive prevalence and co-occurrence of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD), as well as the current evidence suggesting the elevated levels of basal metabolic rate (BMR) among these individuals, the present study aimed to identify factors determining hypermetabolism in such subjects. This cross sectional study was conducted in 30 to 53-year-old individuals with concurrent T2DM and NAFLD (controlled attenuation parameter score ≥ 260 dB/m). Resting energy expenditure (REE) was determined by an indirect calorimetry device. Hypermetabolism was defined as an elevated measured REE > 110% of the predicted REE. The multivariate logistic regression test was used for detecting factors associated with hypermetabolism. Between September, 2017, and March, 2018, a total of 95 eligible participants (64.40% male) with both T2DM and NAFLD were included, while 32.63% of them were classified as hypermetabolic. Overall, the mean recruitment age ± standard deviation and median (interquartile range) body mass index were 44.69 ± 5.47 years and 30.20 (27.80-33.30) kg/m2, respectively. Demographic, anthropometric and biochemical variables did not vary significantly across two groups except for total body water, low-density lipoprotein cholesterol and dipeptidyl peptidase 4 (DPP-4) inhibitors (p < 0.05). According to the results of multivariable logistic regression analyses, hypermetabolism had a positive association with adiponectin (odds ratio [OR] 1.167, 95% confidence interval [CI] 1.015-1.342, p = 0.030), physical activity (OR 1.134, 95% CI 1.002-1.284, p = 0.046), alanine transaminase (OR 1.062, 95% CI 1.006-1.122, p = 0.031) and diastolic blood pressure (OR 1.067, 95% CI 1.010-1.127, p = 0.021). However, fat free mass was inversely related to hypermetabolism (OR 0.935, 95% CI 0.883-0.991, p = 0.023). Adiponectin, alanine transaminase, physical activity, diastolic blood pressure and fat free mass were independently associated with hypermetabolism in subjects with NAFLD and T2DM.

Health-Related Quality of Life in Osteoporosis Patients with and without Fractures in Tehran, Iran.

BACKGROUND: This study aimed to measure the health-related quality of life (HRQOL) of patients with osteoporosis with and without fractures in Tehran, the capital city of Iran. METHODS: We surveyed a sample of 478 patients with osteoporosis aged over 50 years. Participants with fractures included patients referred to hospitals due to osteoporotic fractures which were alive 6 months after the fracture. Participants without fractures were randomly selected from patients with a definite diagnosis of osteoporosis admitted to 3 outpatient clinics in Tehran. Data were collected using the EuroQol 5-dimensional 5-level questionnaire. Statistical differences between patients with and without fracture were tested with Pearson's χ2 test, Student's t-test, and the Mann-Whitney U-test. The association between HRQOL and other variables was evaluated using a multiple linear regression model. RESULTS: The patients' mean age±standard deviation was 67.3±11.9 years, and 74.1% were women. One hundred and seventeen (23%) patients had hip fractures, 56 (11%) had vertebral fractures, 127 (25%) had forearm fractures, and 178 (40%) had no fractures. The median (interquartile range) values of HRQOL scores of those with hip, vertebral, and forearm fractures and those with no history of fracture were 0.53 (0.22), 0.60 (0.28), 0.64 (0.26), and 0.64 (0.27), respectively. The multiple regression model revealed a significant relationship between the HRQOL scores and sex, marital status, employment status, presence of any chronic illness in addition to osteoporosis, and type of fracture. CONCLUSIONS: Osteoporosis and its related fractures can reduce the HRQOL.

A systematic study of nano-based fibrous systems: Diagnostic and therapeutic approaches for dementia control.

Nano-based systems provide many advantages, including eluding gastrointestinal and first-pass metabolism of the drug and improving the potential advantage of reduced doses of drugs for an equal or better therapeutic effect compared to other parts of oral administration. Over the last few years, protein-based nanofibrous biomaterials have been used for better controlling dementia. PubMed, Scopus, and ISI Web of Science were consulted for available articles on nano-based fibrous systems for the treatment and diagnosis of dementia (up to October 2022). Of 725 articles that were identified and evaluated, only 19 were included. Eleven studies evaluated nanofibrous electrospun biomaterials for better dementia control. Among these, four investigated marker/biomarker detection for the early diagnosis of dementia. Two from four studies conducted hydrogel-based nanofibrous for Alzheimer's disease (AD) treatment. Additionally, four studies inspected stem cell (SC) transplantation on nano-based fibrous scaffolds for better treatment of dementia. Finally, two from the final four studies considered nano-based fibrous systems for the enhanced treatment of dementia. Our study concluded that nano-based fibrous platforms, exclusively peptide/protein-based nanofibrous scaffolds made from biomaterials, can be applied for dementia management by either diagnostic or therapeutic approaches specific in purpose-designed electrospun nanofibrous scaffolds.

Ovarian volume, not follicle count, is independently associated with androgens in patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is diagnosed based on chronic anovulation, androgen excess (clinical and/or biochemical), and polycystic ovaries in ultrasound. The aim of the present study was to evaluate which parameters in the transvaginal ultrasound (TVUS) of ovaries could be better associated with concurrent hormonal imbalance in the women with PCOS. METHODS: Using a cross-sectional design, this study focused on 61 subjects (18-40 years) with PCOS. Patients were recruited at three academic hospitals during the 2017-2019 period. PCOS was defined according to the Rotterdam criteria. The association of ovarian morphology with hormonal and metabolic feature was investigated using linear regression models, adjusted for a set of possible confounding variables including age, mensuration status and body mass index (BMI). RESULTS: The mean volume of both ovaries was positively associated with the total testosterone level (ß = 0.025, P value < 0.001), free androgen index (ß = 0.041, P value < 0.001) and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (ß = 0.032, P value = 0.004), even after adjustments made for age, mensuration status and BMI (fully-adjusted model). In contrast, in the fully-adjusted model, antral follicle count (AFC), follicle number per ovary (FNPO), ovarian area, stromal area, and ratio of stromal area to ovarian area (S/A) were not associated with androgen levels and LH/FSH ratio. In addition, after full adjustments, ovarian volume, AFC, FNPO, ovarian area, stromal area and S/A were not associated with insulin resistance, which was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). CONCLUSION: Increased ovarian volume is, thus, highly predictive of hyperandrogenemia and high LH/FSH ratio in PCOS patients.

Tryptophan and serotonin levels as potent biomarkers in diabetes mellitus complications: a new approach of diagnostic role.

Objective: Alterations in the serotonergic system were verified to act a role in the pathogenesis of altered neurological and psychiatric diseases. In recent years, Tryptophan (Trp) and serotonin (5-HT) levels have been considered potent biomarkers of diabetes mellitus (DM). Method: The different Trp metabolism may also play roles in the pathogenesis of DM and mounting risk of complications. The whole blood (WB) 5-HT level was mainly lower among diabetic patients compared to others. That is mostly derived from a lower platelet concentration of 5-HT in these patients. Results: Indeed, 5-HT level can be considered a potent biomarker for early detection of DM complications. Besides, it was proved that outside the digestive and central nervous systems, 5-HT was discovered in beta cells, and scientists have been attempting to realize its mechanism of action ever since. Towards to end, the determination methods, biomarker's role, and approaches of 5-HT and Trp levels were thoroughly investigated in both healthy and diabetic patients with or without complications. Moreover, the association between insulin and 5-HT has been specifically discussed. Conclusions: Our study concluded that Trp and 5-HT levels could be exclusively applied for early diagnosis of DM complications as well as many other complications.

The economic burden of osteoporosis in Iran in 2020.

Osteoporosis, the most common metabolic bone disease, leads to increased susceptibility to fractures. In 2020, about 150,000 osteoporotic fractures occurred in Iran. Osteoporosis and related fractures cost the community US$ 393 million. Introduction The present study aimed at estimating the economic burden of osteoporosis in Iran in 2020. METHODS: We estimated the annual economic burden of osteoporosis in the above 50 years old population using a prevalence-based approach and from a societal perspective. The incidence of osteoporosis and related fractures were estimated based on meta-analysis reports in Iran and international comparisons. The direct medical and non-medical costs as well as the monetary value of quality-adjusted life-years (QALYs) lost because of fractures were estimated. Cost data were extracted from patient records, medical services prices, and previous literature. RESULTS: A total of 154,530 osteoporotic fractures were estimated in Iran in 2020. The shares of the hip, vertebral, forearm, and other fractures were 14%, 15%, 17%, and 54%, respectively. There were also 3554 deaths from osteoporotic fractures. The economic burden of osteoporosis in Iran was estimated at US$ 393.24 million (US$ 2165 million purchasing power parity 2020). Direct medical and non-medical cost (47.44%), QALY loss (29.65%), and long-term care for prior hip fracture costs (9.4%) were the main component of the economic burden of osteoporosis. CONCLUSION: The economic burdens of osteoporosis are significant in Iran. Interventions to prevent osteoporosis and especially associated fractures, such as screening and prophylaxis, can reduce the cost of the disease and improve patients' quality of life. Further studies are needed to identify cost-effective and feasible interventions in Iran.

Design, synthesis, in vitro α-glucosidase inhibition, docking, and molecular dynamics of new phthalimide-benzenesulfonamide hybrids for targeting type 2 diabetes.

In the present work, a new series of 14 novel phthalimide-benzenesulfonamide derivatives 4a-n were synthesized, and their inhibitory activity against yeast α-glucosidase was screened. The obtained results indicated that most of the newly synthesized compounds showed prominent inhibitory activity against α-glucosidase. Among them, 4-phenylpiperazin derivative 4m exhibited the strongest inhibition with the IC50 value of 52.2 ± 0.1 µM. Enzyme kinetic study of compound 4m proved that its inhibition mode was competitive and Ki value of this compound was calculated to be 52.7 µM. In silico induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the target compounds over the active site of α-glucosidase. Obtained date of these studies demonstrated that our new compounds interacted as well with the α-glucosidase active site with the acceptable binding energies. Furthermore, in silico druglikeness/ADME/Toxicity studies of compound 4m were performed and predicted that this compound is druglikeness and has good ADME and toxicity profiles.

Annual incidence of osteoporotic hip fractures in Iran: a systematic review and meta-analysis.

BACKGROUND: Osteoporosis (OP) is progressively becoming a global concern with the aging of the world's populations. Osteoporotic fractures are associated with significantly increased mortality rates and a financial burden to health systems. This Meta-analysis aims to estimate the annual incidence of osteoporotic fractures in Iran. METHODS: A comprehensive systematic literature search was performed through Medline (PubMed), Embase, Scopus, Web of Science, and Google Scholar to identify studies which contain an investigation of the incidence of osteoporotic fractures in Iran up to December 3rd 2020, with no time and language restriction. For the risk of bias assessments of studies, the Joanna Briggs Institute (JBI) critical appraisal checklist for studies reporting prevalence data was used. The pooled estimation of the incidence of osteoporotic fractures in population aged≥50 years was calculated using random-effects meta-analysis, and the heterogeneity of included studies was quantified with the I2 statistic. RESULTS: In all, 6708 papers were initially retrieved from the electronic databases, among which seven studies were included in the meta-analysis. The pooled standardized annual cumulative incidence of hip fractures was estimated as 138.26 (95% CI: 98.71-193.65) per 100,000 population and 157.52 (95% CI: 124.29-199.64) per 100,000 population in men and women, respectively. CONCLUSION: This study showed a high incidence rate of osteoporotic hip fractures in Iran. Early detection and treatment of individuals with higher risks of primary fragility fractures at primary health care as well as implementing fracture liaison services to prevent secondary fractures are highly recommended. The results suffer from the following limitations: first, a low number of studies that were eligible for inclusion; second, the lack of population-based studies; and presence of highly heterogeneous studies despite the use of a random effect model.

DRESS Syndrome Induced by Sorafenib in a Patient With Medullary Thyroid Cancer: A Case Report.

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and life-threatening hypersensitivity reaction. It is characterized by fever, skin lesions, and internal organ involvement. Sorafenib is a tyrosine kinase inhibitor that is used for the treatment of certain cancers such as hepatocellular, renal cell, and thyroid cancer. Case Presentation: The case is a 40 years old man who presented with fever, generalized skin rash, and pruritus. The patient has received sorafenib for the treatment of medullary thyroid cancer (MTC) from 3 weeks ago. Following presentation, the drug was discontinued and causality was assessed by scoring system RegiSCAR and Naranjo scale that showed a probable DRESS. There was no internal organ involvement based on the laboratory evaluations. The considerable abnormality was eosinophilia among patient's laboratory tests. Antihistamines and topical and systemic corticosteroids were utilized for the management of the symptoms. Conclusion: To the best of our knowledge, this is the first case report of DRESS syndrome by sorafenib in the patients with MTC. Clinicians should be aware of sign and symptoms suggesting DRESS syndrome of sorafenib.