Protocol for preliminary, multicenteric validation of "PoCOsteo device": A point of care tool for proteomic and genomic study of osteoporosis.

One of the goals of the HORIZON 2020 project PoCOsteo was to develop a medical device, which would measure and/or quantify proteomic as well as genomic factors as present in whole blood samples collected through finger prick. After validating the tool in the clinical setting, the next step would be its clinical validation based on the existing guidelines. This article presents the protocol of a validation study to be carried out independently at two different centers (Division of Endocrinology and Diabetology at the Medical University of Graz as a clinic-based cohort, and the Endocrinology and Metabolism Research Institute at the Tehran University of Medical Sciences as a population-based cohort). It aims to assess the tool according to the Clinical & Laboratory Standards Institute guidelines, confirming if the proteomics and genomics measurements provided by the tool are accurate and reproducible compared with the existing state-of-the-art tests. This is the first time that such a detailed protocol for lab validation of a medical tool for proteomics and genomic measurement is designed based on the existing guidelines and thus could be used as a template for clinical validation of future point-of-care tools. Moreover, the multicentric cohort design will allow the study of a large number of diverse individuals, which will improve the validity and generalizability of the results for different settings.

New phenylthiosemicarbazide-phenoxy-1,2,3-triazole-N-phenylacetamides as dual inhibitors against α-glucosidase and PTP-1B for the treatment of type 2 diabetes.

This study describes the design, synthesis, and evaluation of a novel series of phenylthiosemicarbazide-phenoxy-1,2,3-triazole-N-phenylacetamide derivatives (7a-l) as dual inhibitors of α-glucosidase and protein tyrosine phosphatase 1-B (PTB-1B). The latter enzymes are two important targets in the treatment of type 2 diabetes. The in vitro obtained data demonstrated that all title compounds 7a-l were more potent than the standard inhibitor acarbose against α-glucosidase while only four derivatives (7a, 7g, 7h, and 7h) were more potent than the standard inhibitor suramin against PTP-1B. Furthermore, these data showed that the most potent α-glucosidase inhibitor was compound 7i, with sixfold higher inhibitory activity than acarbose, and the most potent PTP-1B inhibitor was compound 7a with 3.5-fold higher inhibitory activity than suramin. Kinetic studies of compounds 7i and 7a revealed that they inhibited their target enzymes in a competitive mode. The docking study demonstrated that compounds 7i and 7a well occupied the active site pockets of α-glucosidase and PTP-1B, respectively. In silico pharmacokinetic and toxicity assays of the most potent compounds were performed, and the obtained results were compared with those of the standard inhibitors.

Nitrophenylpiperazine derivatives as novel tyrosinase inhibitors: design, synthesis, and in silico evaluations.

A novel series of 4-nitrophenylpiperazine derivatives (4a-m) was designed and synthesized as potential tyrosinase inhibitors. Comprehensive characterization using 1H-NMR, 13C-NMR, CNH, and IR techniques was performed for all target compounds. Subsequently, the derivatives were evaluated for their inhibitory activity against tyrosinase. Among them, compound 4l, featuring an indole moiety at the N-1 position of the piperazine ring, exhibited a significant tyrosinase inhibitory effect with an IC50 value of 72.55 µM. Enzyme kinetics analysis revealed that 4l displayed mixed inhibition of the tyrosinase enzymatic reaction. Molecular docking was carried out in the enzyme's active site to further investigate the enzyme-inhibitor interactions. Based on the findings, compound 4l shows promise as a lead structure for the design of potent tyrosinase inhibitors. This study paves the way for the development of more effective tyrosinase inhibitors for potential applications in various fields.

Unveiling the lead exposure attributed burden in Iran from 1990 to 2019 through the lens of the Global Burden of Disease study 2019.

This study aimed to investigate the estimated burden attributed to lead exposure (LE), at the national and subnational levels from 1990 to 2019 in Iran. The burden attributed to LE was determined through the estimation of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs) and years lived with disability (YLDs) using the comparative risk assessment method of Global Burden of Disease (GBD) study presenting as age-standardized per 100,000 person year (PY) with 95% uncertainty intervals (95% UI). Furthermore, the burden of each disease were recorded independently. Eventually, the age-standardized YLLs, DALYs, deaths and YLDs rates attributed to LE demonstrated a decrease of 50.7%, 48.9%, 38.0%, and 36.4%, respectively, from 1990 to 2019. The most important causes of LE burden are divided into two acute and chronic categories: acute, mainly causes mental disorders (DALYs rate of 36.0 in 2019), and chronic, results in cardiovascular diseases (CVDs) (DALYs rate of 391.8) and chronic kidney diseases (CKDs) (DALYs rate of 26.6), with CVDs bearing the most significant burden. At the sub-national level, a decrease in burden was evident in most provinces; moreover, low and low-middle SDI provinces born the highest burden. The burden increased mainly by ageing and was higher in males than females. It was concluded that although the overall decrease in the burden; still it is high, especially in low and low-middle SDI provinces, in advanced ages and in males. Among IDID, CKDs and CVDs that are the most important causes of LE-attributed burden in Iran; CVDs bear the highest burden.

Adherence to the Mediterranean diet can beneficially affect the gut microbiota composition: a systematic review.

AIM: Dietary patterns could have a notable role in shaping gut microbiota composition. Evidence confirms the positive impact of the Mediterranean diet (MD), as one of the most studied healthy dietary patterns, on the gut microbiota profile. We conducted this systematic review to investigate the results of observational studies and clinical trials regarding the possible changes in the gut microbiota composition, metabolites, and clinical outcomes following adherence to MD in healthy cases or patients suffering from metabolic disorders. METHODS: A systematic literature search was conducted on PubMed, Web of Science, and Scopus databases until October 2023. Two researchers separately screened the titles, abstracts, and then full-text of the articles and selected the relevant studies. Quality assessment of observational and interventional studies was performed by Newcastle-Ottawa and Cochrane checklists, respectively. RESULTS: A total of 1637 articles were obtained during the initial search. Ultimately, 37 articles, including 17 observational and 20 interventional studies, were included in this systematic review. Ten observational and 14 interventional studies reported a correlation between MD adherence and microbiota diversity. Faecalibacterium and Prevotella were the most frequent bacterial genera with increased abundance in both observational and interventional studies; an Increment of Bacteroides genus was also reported in observational studies. Better glycemic control, lowering fat mass, better bowel movement, decreased bloating, inflammation, and hospitalization risk were the reported clinical outcomes. CONCLUSION: Adherence to the MD is associated with significant beneficial changes in the gut microbiota diversity, composition, and functions and major clinical improvements in most populations.

Overlap between Osteosarcopenia and Frailty and their association with poor health conditions: The Bushehr Elderly Health (BEH) Program.

Background: This study investigated the association of osteosarcopenia with frailty and poor health conditions among older Iranian adults. Methods: This cross-sectional study analyzed data from the Bushehr Elderly Health (BEH) Program. Osteosarcopenia was defined as the presence of osteopenia/osteoporosis and sarcopenia, while the Fried criteria were used to assess frailty. We assessed the history of falls and health-related quality of life (HRQoL), including physical and mental component summaries (PCS and MCS, respectively), history of fractures, activities of daily living (ADL), and instrumental activities of daily living (IADL), as indicators of poor health conditions. Results: This study included a total of 2371 older adults. The prevalence rates of osteosarcopenia-only, frailty-only, and osteosarcopenia with frailty were 17.4%, 3%, and 4.8%, respectively. The prevalence of a history of falls, poor ADL, and poor IADL was significantly higher in the frailty-only and osteosarcopenia with frailty groups. Osteosarcopenia with frailty was significantly associated with a history of falls [adjusted odds ratio (adjOR): 1.94, 95% confidence interval (CI) (1.20-3.15)], poor ADL [adjOR: 2.85, 95%CI (1.81-4.50)], and poor IADL [adjOR: 5.09, 95%CI (2.85-9.11)]. However, the frailty-only group also showed an association with falls and poor ADL and IADL. Only osteosarcopenia was associated with an increased OR for fracture. Frailty had the greatest effect on the MCS and PCS scores, whereas osteosarcopenia with frailty had a moderate impact. Conclusions: Osteosarcopenia with frailty significantly increased the odds of falls, poor ADL, poor IADL, and lower HRQoL compared with the robust group. Combined osteosarcopenia and frailty were not associated with poor health. These findings indicate the importance of diagnosing osteosarcopenia and frailty as separate entities to provide appropriate interventions and treatment.

NHC-Catalyzed Enantioselective Transformations Involving α-Bromoenals.

α-Haloenals, especially, α-bromoenals considered as one of the important building blocks in organic synthesis. They can participate in various (3+2)-, (3+3)-, (3+4)-, and (2+4)-annulation reactions with other organic molecules in the presence of an NHC catalyst to produce enantioenriched carbo-, and heterocyclic compounds. Herein, we have described NHC-catalyzed enantioselective transformations of α-bromoenals in the synthesis of various heterocycles, and carbocycles, as well as acyclic organic compounds.

Evaluation of novel 2-(quinoline-2-ylthio)acetamide derivatives linked to diphenyl-imidazole as α-glucosidase inhibitors: Insights from in silico, in vitro, and in vivo studies on their anti-diabetic properties.

The inhibition of the α-glucosidase enzyme is crucial for targeting type 2 diabetes mellitus (DM). This study introduces a series of synthetic analogs based on thiomethylacetamide-quinoline derivatives linked to diphenyl-imidazole as highly potential α-glucosidase inhibitors. Twenty derivatives were synthesized and screened in vitro against α-glucosidase, revealing IC50 values ranging from 0.18 ± 0.00 to 2.10 ± 0.07 µM, in comparison to the positive control, acarbose. Among these derivatives, compound 10c (IC50 = 0.180 µM) demonstrated the highest potency and revealed a competitive inhibitory mechanism in kinetic studies (Ki = 0.15 µM). Docking and molecular dynamic evaluations elucidated the binding mode of 10c with the active site residues of the α-glucosidase enzyme. Moreover, in vivo assessments on a rat model of DM affirmed the anti-diabetic efficacy of 10c, evidenced by reduced fasting and overall blood glucose levels. The histopathological evaluation enhanced pancreatic islet architecture and hepatocytes in liver sections. In conclusion, novel 2-(quinoline-2-ylthio)acetamide derivatives as potent α-glucosidase inhibitors were developed. Compound 10c emerged as a promising candidate for diabetes management, warranting further investigation for potential clinical applications and mechanistic insights.

Evaluation of the prevalence of cardiometabolic disorders (diabetes, hypertension, and hyperlipidemia) diagnosed, undiagnosed, treated, and treatment goal in the elderly: Bushehr Elderly Health Program (BEH).

As the population ages, the global burden of cardiometabolic disorders will increase. This study aimed to investigate the prevalence of cardiometabolic disorders (diabetes, hypertension, and hyperlipidemia) in elderly and to evaluate the effects of various variables including age, sex, education, marital status, smoking, income, physical activity, dementia and depressed mood on untreated cardiometabolic disorders. This was a cross sectional study conducted in Bushehr Elderly Health Program. A total 2381 participants were included. Medical data were collected by trained interviewers. The mean age of the study participants was 69.34 years. Proportions of diabetes, hypertension, hyperlipidemia and hypercholesterolemia were 43.25%, 75.71%, 64.74% and 35.31% respectively. Untreated diabetes prevalence was higher for males (OR = 1.60, 95%CI = 1.20-2.15), older adults (OR = 1.02, 95%CI = 1.00-1.05), and pre-frail status (OR = 0.69, 95%CI = 0.52-0.92). Males (OR = 2.16, 95%CI = 1.64-2.84) and current smokers (OR = 1.42, 95%CI = 1.05-1.93), in contrast to married participants (OR = 0.25, 95%CI = 0.08-0.78), people with higher education levels (OR = 0.51, 95%CI = 0.29-0.89) and dementia (OR = 0.78, 95%CI = 0.61-1.00) were more likely to have untreated HTN. Untreated dyslipidemia is more common in smokers (OR = 1.78, 95%CI = 1.19-2.66) and males (OR = 1.66, 95%CI = 1.21-2.27), while untreated hypercholesteremia is more common in males (OR = 3.20, 95%CI = 1.53-6.69) and is reported lower in people with dementia (OR = 0.53, 95%CI = 0.28-1.01).

Determinants of multimorbidity in older adults in Iran: a cross-sectional study using latent class analysis on the Bushehr Elderly Health (BEH) program.

BACKGROUND AND OBJECTIVES: Multimorbidity, defined as the presence of two or more long-term health conditions in an individual, is one of the most significant challenges facing health systems worldwide. This study aimed to identify determinants of classes of multimorbidity among older adults in Iran. RESEARCH DESIGN AND METHODS: In a cross-sectional sample of older adults (aged ≥ 60 years) from the second stage of the Bushehr Elderly Health (BEH) program in southern Iran, latent class analysis (LCA) was used to identify patterns of multimorbidity. Multinomial logistic regression was conducted to investigate factors associated with each multimorbidity class, including age, gender, education, household income, physical activity, smoking status, and polypharmacy. RESULTS: In 2,426 study participants (mean age 69 years, 52% female), the overall prevalence of multimorbidity was 80.2%. Among those with multimorbidity, 3 latent classes were identified. These comprised: class 1, individuals with a low burden of multisystem disease (56.9%); class 2, individuals with predominantly cardiovascular-metabolic disorders (25.8%) and class 3, individuals with predominantly cognitive and metabolic disorders (17.1%). Compared with men, women were more likely to belong to class 2 (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.52-2.54) and class 3 (OR 4.52, 95% CI 3.22-6.35). Polypharmacy was associated with membership class 2 (OR 3.52, 95% CI: 2.65-4.68) and class 3 (OR 1.84, 95% CI 1.28-2.63). Smoking was associated with membership in class 3 (OR 1.44, 95% CI 1.01-2.08). Individuals with higher education levels (59%) and higher levels of physical activity (39%) were less likely to belong to class 3 (OR 0.41; 95% CI: 0.28-0.62) and to class 2 (OR 0.61; 95% CI: 0.38-0.97), respectively. Those at older age were less likely to belong to class 2 (OR 0.95). DISCUSSION AND IMPLICATIONS: A large proportion of older adults in Iran have multimorbidity. Female sex, polypharmacy, sedentary lifestyle, and poor education levels were associated with cardiovascular-metabolic multimorbidity and cognitive and metabolic multimorbidity. A greater understanding of the determinants of multimorbidity may lead to strategies to prevent its development.

Decarboxylative 1,3-dipolar cycloadditions of l-proline.

1,3-Dipolar cycloaddition is one of the important chemical reactions between a 1,3-dipole and a dipolarophile to construct a five-membered heterocyclic compound. As an available α-amino acid reactant, l-proline is extensively used in 1,3-dipolar cycloaddition reactions. A diverse spectrum of bioactive spiro and fused N-heterocycles is obtained through this synthetic approach. In this review, we have described the use of l-proline in the synthesis of various spiro- and fused heterocyclic scaffolds.

The association between quality of life and diabetes: the Bushehr Elderly Health Program.

BACKGROUND AND OBJECTIVE: Considering the importance of diabetes and its increased prevalence with aging, this study aimed to evaluate the association between diabetes status and quality of life (QOL) and the determining factors in individuals over 60. METHODS: Two thousand three hundred seventy-five individuals including 819 (34.5%) with diabetes, aged 69.4 ± 6.4, from Bushehr Elderly Health Program (BEHP) were enrolled. We categorized the participants as non-diabetic, controlled diabetic, and poorly controlled diabetic. The QOL was assessed using the SF-12 questionnaire. The physical (PCS) and mental (MCS) component summaries of QOL were estimated. We compared the SF-12 domains and components between the categories using ANOVA. Further, the association of diabetes status with PCS and MCS was assessed after adjustment for possible confounders including age, sex, depression, cognitive impairment, physical activity, and other relevant factors using linear regression analysis. RESULTS: Individuals with diabetes had lower PCS (40.9 ± 8.8 vs. 42.7 ± 8.6, p-value < 0.001), and MCS scores (45.0 ± 10.2 vs. 46.4 ± 9.4, p-value < 0.001) compared to participants without diabetes. No significant differences were observed in PCS or MCS scores between controlled or poorly controlled individuals with diabetes. Diabetes status was associated with PCS and MCS scores in univariable analysis. Regarding physical component of QOL, after adjusting for other confounders, poorly controlled diabetes was significantly associated with PCS [beta: -1.27 (-2.02, -0.52)]; some other determinants include depression [-7.66 (-8.51, -6.80)], male sex [3.90 (3.24,4.57)], and good physical activity [1.87 (1.17,2.57)]. As for the mental component, controlled diabetes was significantly associated with MCS [-1.17 (-2.13, -0.22)]; other contributing factors include depression [-14.35 (-15.34, -13.37)], male sex [1.97 (1.20,2.73)], good physical activity [-1.55 (-2.35, -0.75)], and smoking [-1.42 (-2.24, -0.59)]. BMI had an inverse association with PCS [-0.19 (-0.26, -0.13)] and a direct association with MCS [0.14 (0.07,0.21)]. CONCLUSION: Individuals with diabetes exhibited reduced QOL scores. Upon adjusting for other variables, it was found that uncontrolled diabetes correlated with decreased PCS scores, whereas controlled diabetes was linked to lower MCS scores. Factors such as depression and being female were identified as contributors to diminished QOL in both physical and mental aspects. These results have the potential to guide healthcare decision-making, facilitating the creation of tailored interventions aimed at improving the QOL for individuals with diabetes, with a specific focus on women and depression.

Isolation and Phenotypic Characterization of Tumor-Infiltrating NK Cells in Skin Carcinoma.

In oncological research, the function of tumor-infiltrating natural killer (NK) cells in skin carcinoma presents a viable avenue for novel therapeutic methods. NK cells are essential to the body's defense against malignancies, including skin cancer, and are especially important in more sophisticated cancer immunotherapies such as vaccinations containing dendritic cells. The deadliest type of skin cancer, malignant melanoma, still has a poor prognosis even with advancements in early-stage therapies, which emphasizes the need for novel therapeutic strategies. NK cells from human melanoma metastases were subjected to single-cell RNA-seq analysis, which demonstrated notable variations in the transcriptional programs of tumor-infiltrating and circulating NK cells. Different transcriptional states are displayed by NK cells that have invaded tumors, indicating that they are functionally specialized in areas like chemokine production and cytotoxicity. These results emphasize the functions of NK cells in recruiting other significant immune cell types, such as cross-presenting dendritic cells, and in direct cytotoxicity against malignant cells. Investigating NK cells that infiltrate tumors in skin carcinomas presents a viable approach to comprehending and may be modifying the immune environment surrounding these cancers. It is essential to comprehend the distinct characteristics and roles of NK cells inside the tumor microenvironment in order to create more potent immunotherapeutic approaches to treat skin cancer. In order to perhaps open the door for new directions in cancer immunotherapy, the project intends to establish a thorough technique for the isolation and thorough phenotypic characterization of tumor-infiltrating NK cells in skin carcinoma.

Standardized GMP-Compliant Scalable 3D-Bioprocessing of Epidermal Stem Cells for Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) pose a significant threat to the health and well-being of individuals with diabetes, often leading to lower limb amputations. Fortunately, epidermal stem cell therapy offers hope for improving the treatment of DFUs. By leveraging 3D culture techniques, the scalability of stem cell manufacturing can be greatly enhanced. In particular, using bioactive materials and scaffolds can promote the healing potential of cells, enhance their proliferation, and facilitate their survival. Furthermore, 3D tissue-mimicking cultures can accurately replicate the complex interactions between cells and extracellular matrix, thereby ensuring that the stem cells are primed for therapeutic application. To ensure the safety and quality of these stem cells, it is essential to adhere to good manufacturing practice (GMP) principles during cultivation. This chapter provides a comprehensive overview of the step-by-step process for GMP-based 3D epidermal stem cell cultivation, thus laying the groundwork for developing reliable regenerative medicine therapies.

Pyrano[2,3-b]chromone derivatives as novel dual inhibitors of α-glucosidase and α-amylase: Design, synthesis, biological evaluation, and in silico studies.

Inhibition of α-glucosidase and α-amylase is an important target for treatment of type 2 diabetes. In this work, a novel series of pyrano[2,3-b]chromene derivatives 5a-m was designed based on potent α-glucosidase and α-amylase inhibitors and synthesized by simple chemical reactions. These compounds were evaluated against the latter enzymes. Most of the title compounds exhibited high inhibitory activity against α-glucosidase and α-amylase in comparison to standard inhibitor (acarbose). Representatively, the most potent compound, 4-methoxy derivative 5d, was 30.4 fold more potent than acarbose against α-glucosidase and 6.1 fold more potent than this drug against α-amylase. In silico molecular modeling demonstrated that compound 5d attached to the active sites of α-glucosidase and α-amylase with a favorable binding energies and established interactions with important amino acids. Dynamics of compound 5d also showed that this compound formed a stable complex with the α-glucosidase active site. In silicodrug-likeness as well as ADMET prediction of this compound was also performed and satisfactory results were obtained.

Epidemiological Insights into Diabetic Foot Amputation and its Correlates: A Provincial Study.

Background: Diabetic foot ulcer and potential subsequent lower extremity amputation are major complications of diabetes mellitus and are also prominent morbidity factors that could affect patients' quality of life. Objectives: This study aimed to assess the prevalence of diabetic foot amputation and explore correlates of amputation cause and type among subjects with diabetes mellitus in Tehran, Iran. Methods: A descriptive cross-sectional study was conducted to assess the demographic, sociological, and clinical characteristics of subjects who had undergone lower extremity amputation due to diabetic foot ulcers, from 2011 to 2020, in two educational medical centers in Tehran, Iran. We examined the medical records of 4676 individuals who were admitted to Shariati and Sina hospitals due to diabetic foot issues. Information related to patient demographics (age, gender, marital status), social factors (education level, insurance), and clinical data (medical history, laboratory results, and characteristics of diabetic foot ulcers) was collected for subjects who had undergone lower extremity amputation due to diabetic foot ulcer. The collected data was reported using average values, standard deviations and proportions and analyzed using statistical tests. Results: During one decade, 882 out of 4676 (18.8%) patients with diabetic foot ulcers underwent lower extremity amputations of various types in Sina and Shariati hospitals in Tehran, Iran. Of these, 692 (14.5%) were included for further analysis in the study and the rest were excluded due to lack of sufficient recorded data. About 75.9% of the study population was male, and the average age including both sexes was 60 years. About 92.7% were married, and on average, subjects had been afflicted with diabetes mellitus for 15.1 years. Statistical analysis using Pearson's chi-square test showed there was a significant association between the treatment regimen for diabetes mellitus and the type of amputation (P = .01), as well as between the duration of the disease and the cause of amputation (P = .01) and its type (P = .04). Conclusion: diabetes mellitus related treatment regimen and duration of disease are significantly associated with amputation cause and type.

Understanding Why and How Diabetic Patients Lose Their Feet: A Study from Tehran, Iran This study explored patients with diabetes in Tehran, Iran, experience foot problems leading to amputation. We looked at the records of 4676 patients over a decade, finding that 18.8% had lower limb amputations. Key factors included treatment methods for diabetes and the duration of the disease, significantly impacting the cause and type of amputation. These insights can guide better care to prevent such serious complications in patients with diabetes.

Global, regional, and national burden and quality of care index (QCI) of oral disorders: a systematic analysis of the global burden of disease study 1990-2017.

BACKGROUND: Oral disorders are still a major global public health challenge, considering their perpetuating and chronic nature. Currently, there is no direct index to measure the quality of care on a population scale. Hence, we aim to propose a new index to measure the quality of care for oral disorders worldwide. METHODS: We generated our database using the data from the Global Burden of Disease (GBD) study 2017. Among different variables such as prevalence, incidence, years lived with disability, and disability-adjusted life years, we utilised principal component analysis (PCA) to determine the component that bears the greatest proportion of information to generate the novel quality of care index (QCI) for oral disorders. RESULTS: Global QCI for oral disorders gradually increased from 1990 to 2017 (from 70.5 to 74.6). No significant gender disparity was observed during this period, and the gender disparity ratio (GDR) was considered optimal in 1990 and 2017. Between 1990 and 2017, the age-standardised QCI for all oral disorders increased in all the SDI regions. The highest QCI for all oral disorders in 2017 belonged to high-middle SDI countries (=80.24), and the lowest YLDs rate was seen in the low SDI quintile. In 1990, the quality of care in European, Central Asian, and Central and South American countries was in the lowest quintiles, whereas the North American, East Asian, Middle Eastern, and some African countries had the highest quality of dental care. Maynmar (=100), Uganda (=92.5), Taiwan (=92.0), China (=92.5), and the United States (=89.2) were the five countries with the highest age-standardised QCI. Nicaragua (=41.3), Belgium (=40.2), Venezuela (=38.4), Sierra Leone (=30.5), and the Gambia (=30.3) were the five countries with the least age-standardised QCI values. CONCLUSION: The quality of care for all oral disorders showed an increasing trend on a global scale from 1990 to 2017. However, the QCI distribution was not homogenous among various regions. To prevent the exacerbation of imminent disparities in this regard, better attention to total tooth loss in high-income countries and prioritising primary healthcare provision in low-income countries are recommended for oral disorders.

Human-Induced Pluripotent Stem Cell‒Derived Keratinocytes, as Therapeutic Option in Vitiligo.

Vitiligo is a skin condition affecting 1% of the global population, causing non-scaly, chalky-white macules on the skin and hair. It is caused by the pathologic destruction of melanocytes, which produce melanin. Research has focused on the abnormalities of melanocytes and their interaction with neighboring keratinocytes. Current treatments are mainly immunosuppressive drugs and UV radiation, which are scarce and ineffective. To treat vitiligo, regenerative medicine techniques, such as cell-based and cell-free methods, are recommended. Keratinocyte cell transplantation has shown promising results in treating vitiligo. Moreover, studies suggest individualized therapy for diseases can be provided by reprogramming somatic cells into induced pluripotent stem cells. On the other hand, differentiation into particular cell types is a key component of induced pluripotent stem cells-based treatment. In this chapter, the differentiation and validation of human induced pluripotent stem cells into a keratinocyte as a therapeutic option in vitiligo will be discussed.

Aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamides as potent α-glucosidase inhibitors; molecular dynamics, kinetic and structure-activity relationship studies.

Regarding the important role of α-glucosidase enzyme in the management of type 2 diabetes mellitus, the current study was established to design and synthesize aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamide (11a-o) and the structure of all derivatives was confirmed through various techniques including IR, 1H-NMR, 13C-NMR and elemental analysis. Next, the α-glucosidase inhibitory potentials of all derivatives were evaluated, and all compounds displayed potent inhibition with IC50 values in the range of 26.0 ± 0.8-459.8 ± 1.5 µM as compared to acarbose used as control, except 11f and 11l. Additionally, in silico-induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the newly synthesized compounds over the active site of α-glucosidase.

Burden of type 2 diabetes mellitus and its risk factors in North Africa and the Middle East, 1990-2019: findings from the Global Burden of Disease study 2019.

BACKGROUND: The prevalence of Type 2 Diabetes Mellitus (T2DM) in the North Africa and Middle East region is alarmingly high, prompting us to investigate the burden and factors contributing to it through the GBD study. Additionally, there is a lack of knowledge about the epidemiological status of T2DM in this region, so our aim is to provide a comprehensive overview of the burden of T2DM and its associated risk factors. METHODS: Using data from the 2019 Global Burden of Disease Study, we calculated the attributable burden of T2DM for each of the 21 countries in the region for the years 1990 and 2019. This included prevalence, mortality, disability-adjusted life years (DALYs), and risk factors. RESULTS: Between 1990 and 2019, there was a significant increase in the age-standardized incidence (79.6%; 95% Uncertainty Interval: 75.0 to 84.5) and prevalence (85.5%; [80.8 to 90.3]) rates of T2DM per 100,000 populations. The age-standardized mortality rate (1.7%; [-10.4 to 14.9]), DALYs (31.2%; [18.3 to 42.2]), and years lived with disability (YLDs) (82.6%; [77.2 to 88.1]) also increased during this period. Modifiable risk factors, such as high body mass index (56.4%; [42.8 to 69.8]), low physical activity (15.5%; [9.0 to 22.8]), and ambient particulate matter pollution (20.9%; [15.2 to 26.2]), were the main contributors to the number of deaths. CONCLUSION: The burden of T2DM, in terms of mortality, DALYs, and YLDs, continues to rise in the region. The incidence rate of T2DM has increased in many areas. The burden of T2DM attributed to modifiable risk factors continues to grow in most countries. Targeting these modifiable risk factors could effectively reduce the growth and disease burden of T2DM in the region.