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.

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.

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.

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.

Global, regional, and national quality of care index of cervical and ovarian cancer: a systematic analysis for the global burden of disease study 1990-2019.

BACKGROUND AND OBJECTIVE: Cervical cancer is the most preventable and ovarian cancer is the most lethal gynecological cancer. However, in the world, there are disparities in health care performances resulting in differences in the burden of these cancers. The objective of this study was to compare the health-system quality of care and inequities for these cancers using the Quality of Care Index (QCI). MATERIAL AND METHODS: The 1990-2019 data of the Global Burden of Disease (GBD) was analyzed to extract rates of incidence, prevalence, mortality, Disability-Adjusted Life Years (DALYs), Years of Life Lost (YLL), and Years of healthy life lost due to disability (YLD) of cervical and ovarian cancer. Four indices were developed as a proxy for the quality of care using the above-mentioned rates. Thereafter, a Principal Components Analysis (PCA) was applied to construct the Quality of Care Index (QCI) as a summary measure of the developed indices. RESULTS: The incidence of cervical cancer decreased from 1990 to 2019, whereas the incidence of ovarian cancer increased between these years. However, the mortality rate of both cancers decreased in this interval. The global age-standardized QCI for cervical cancer and ovarian cancer were 43.1 and 48.5 in 1990 and increased to 58.5 and 58.4 in 2019, respectively. QCI for cervical cancer and ovarian cancer generally decreased with aging, and different age groups had inequitable QCIs. Higher-income countries generally had higher QCIs for both cancers, but exceptions were also observed. CONCLUSIONS: Uncovering disparities in cervical and ovarian cancer care across locations, Socio-Demographic Index levels, and age groups necessitate urgent improvements in healthcare systems for equitable care. These findings underscore the need for targeted interventions and prompt future research to explore root causes and effective strategies for narrowing these gaps.

The global, regional, and national burden and quality of care index of kidney cancer; a global burden of disease systematic analysis 1990-2019.

Kidney cancer (KC) is a prevalent cancer worldwide. The incidence and mortality rates of KC have risen in recent decades. The quality of care provided to KC patients is a concern for public health. Considering the importance of KC, in this study, we aim to assess the burden of the disease, gender and age disparities globally, regionally, and nationally to evaluate the quality and inequities of KC care. The 2019 Global Burden of Disease study provides data on the burden of the KC. The secondary indices, including mortality-to-incidence ratio, disability-adjusted life years -to-prevalence ratio, prevalence-to-incidence ratio, and years of life lost-to-years lived with disability ratio, were utilized. These four newly merged indices were converted to the quality-of-care index (QCI) as a summary measure using principal component analysis. QCI ranged between 0 and 100, and higher amounts of QCI indicate higher quality of care. Gender disparity ratio was calculated by dividing QCI for females by males to show gender inequity. The global age-standardized incidence and mortality rates of KC increased by 29.1% (95% uncertainty interval 18.7-40.7) and 11.6% (4.6-20.0) between 1990 and 2019, respectively. Globally, the QCI score for KC increased by 14.6% during 30 years, from 71.3 to 81.6. From 1990 to 2019, the QCI score has increased in all socio-demographic index (SDI) quintiles. By 2019, the highest QCI score was in regions with a high SDI (93.0), and the lowest was in low SDI quintiles (38.2). Based on the World Health Organization regions, the QCI score was highest in the region of America, with Canada having the highest score (99.6) and the lowest in the African Region, where the Central African Republic scored the lowest (17.2). In 1990, the gender disparity ratio was 0.98, and in 2019, it was 0.97 showing an almost similar QCI score for females and males. Although the quality of care for KC has improved from 1990 to 2019, there is a significant gap between nations and different socioeconomic levels. This study provides clinicians and health authorities with a global perspective on the quality of care for KC and identifies the existing disparities.

Dietary fiber intake and all-cause and cause-specific mortality: An updated systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Accumulating evidence supports the effects of dietary fiber on the risk of non-communicable diseases (NCDs). However, there is no updated systematic review and meta-analysis that compares and pools the effect of different types of fiber on mortality. METHODS: In this systematic review and meta-analysis, all prospective cohort studies that evaluated the relationship between dietary fiber intake and all-cause or cause-specific mortality were included. The PubMed, SCOPUS, and Web of Science databases were searched up to October 2022. Data extraction and quality assessment were performed by two researchers independently. Heterogeneity between studies was assessed using Chi-square based test. Random/fixed effect meta-analysis was used to pool the hazard ratios (HR) or relative risks (RR) and 95 % confidence intervals (CI) for the association between different types of fiber and mortality. RESULTS: This systematic review included 64 eligible studies, with a total sample size of 3512828 subjects, that investigated the association between dietary fiber intake and mortality from all-cause, cardiovascular disease (CVD), and cancer. Random-effect meta-analysis shows that higher consumption of total dietary fiber, significantly decreased the risk of all-cause mortality, CVD-related mortality, and cancer-related mortality by 23, 26 and 22 % (HR:0.77; 95%CI (0.73,0.82), HR:0.74; 95%CI (0.71,0.77) and HR:0.78; 95%CI (0.68,0.87)), respectively. The consumption of insoluble fiber tended to be more effective than soluble fiber intake in reducing the risk of total mortality and mortality due to CVD and cancer. Additionally, dietary fiber from whole grains, cereals, and vegetables was associated with a reduced risk of all-cause mortality, while dietary fiber from nuts and seeds reduced the risk of CVD-related death by 43 % (HR:0.57; 95 % CI (0.38,0.77)). CONCLUSION: This comprehensive meta-analysis provides additional evidence supporting the protective association between fiber intake and all-cause and cause-specific mortality rates.

Development of CAR-NK Cells Targeting cSCC-Specific Antigens for Precision Immunotherapy.

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer that is frequently diagnosed, is distinguished by its propensity for aggressive behavior, frequent poor response to standard therapy, and capacity to metastasize to distant areas. Utilizing the body's natural immune defense mechanisms, particularly through the use of chimeric antigen receptor (CAR) technology, is receiving increasing attention in the dynamic field of oncological therapies. Although T cells have received most of the attention, this strategy has proven to be highly effective in battling some blood-related malignancies. However, there are considerable challenges when using this method in the context of solid tumors. The innate immune system's natural killer (NK) cells are essential parts because they have the ability to detect and destroy cancer cells. CAR-NK cells are a very promising approach because they combine the natural cytotoxic properties of natural killer (NK) cells with the precise targeting skills of chimeric antigen receptor (CAR) technology. With the use of this integrated strategy, the intrinsic diversity of cutaneous squamous cell carcinoma (cSCC) tumors may be successfully targeted, increasing treatment effectiveness and lowering the risk of tumor recurrence. This tactic is improved by the development of dual-specificity chimeric antigen receptors (CARs), which fully resolve the antigen presentation heterogeneity among tumor cells. In conclusion, the use of CAR-NK cells that precisely target cSCC-specific antigens has the potential to drastically transform therapy approaches for cSCC as well as other difficult solid tumors as oncological research advances. In order to create chimeric antigen receptor (CAR)-natural killer (NK) cells that particularly target antigens linked to cutaneous squamous cell carcinoma (cSCC), the goal of this protocol is to present a detailed method. The ultimate objective is to lay the groundwork for the development of precision immunotherapy.

Unraveling the link between insulin resistance and Non-alcoholic fatty liver disease (or metabolic dysfunction-associated steatotic liver disease): A Narrative Review.

Objective: Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming a significant global health concern, representing the leading cause of chronic liver disease and posing a substantial public health challenge. NAFLD is associated with higher insulin resistance (IR) levels, a key pathophysiological mechanism contributing to its development and progression. To counter this growing trend, it is crucial to raise awareness about NAFLD and promote healthy lifestyles to mitigate the impact of this disease. Methods: Relevant studies regarding IR and NAFLD published until May 30, 2023, were extracted from Google PubMed, Scopus, and Web Of Science web databases. The following keywords were used: IR, diabetes mellitus, Non-alcoholic fatty liver disease, and metabolic syndrome. Results: IR leads to an accumulation of fatty acids within liver cells, resulting from increased glycolysis and decreased apolipoprotein B-100. Furthermore, the manifestations of NAFLD extend beyond liver-related morbidity and mortality, affecting multiple organs and giving rise to various non-communicable disorders such as diabetes mellitus, metabolic syndrome, polycystic ovary syndrome, obstructive sleep apnea, and cardiovascular disease. Although lifestyle modification remains the primary treatment approach for NAFLD, alternative therapies, including pharmacological, herbal, and surgical interventions, may be considered. By implementing early and simple measures, cirrhosis, end-stage liver disease, and hepatocellular carcinoma can be prevented. Conclusions: There is a clear association between NAFLD and elevated levels of IR. Several metabolic conditions, such as obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome, are closely interrelated with NAFLD and IR. Raising awareness about NAFLD and promoting a healthy lifestyle are crucial steps to reverse the impact of this disease.

Pituitary tumor registry: a multidisciplinary program protocol.

Purpose: This registry aims to collect information to create an appropriate platform for the development of a basis for clinical research and basic sciences to carefully study pituitary adenomas. Methods: Demographic data, diagnosis, treatment, and outcome information of the patients with a confirmed diagnosis of pituitary adenomas will be collected by investigators of the registry. Analysis of registry data generates aggregate reports summarizing pituitary tumor epidemiology, treatment, and outcome. These reports include annual public data reports. In the future, the registry program may provide a wider network in Iran and ultimately support the expansion of international studies. Conclusion: For a long time, patients with pituitary adenomas should be observed. Implementing a registration system would greatly reduce the challenges of patients' follow-up so that their monitoring can be improved.

National and subnational burden of leukemia and its risk factors, 1990-2019: Results from the Global Burden of Disease study 2019.

BACKGROUND: Hematologic malignancies have a great essential role in cancer global burden. Leukemia which two major subtypes based on the onset, is one of the common subtypes of this malignancy. METHOD: For the GBD 2019 study, cancer registry data and vital registration system were used to estimate leukemia mortality. The Meta-Regression-Bayesian Regularized Trimmed (MR-BRT), Cause of Death Ensemble model (CODEm) and Spatiotemporal Gaussian Process Regression (ST-GPR) were used to model our data and estimate each quantity of interest. Mortality to incidence ratios (MIR) were used to generate incidence and survival from mortality rate. Prevalence and survival were used to generate years lived with disability (YLDs). Age-specific mortality and life expectancy at the same age were used to estimate years of life lost (YLLs). The sum of YLLs and YLDs generates DALYs. RESULTS: The total national incidence of leukemia increased from 6092 (UI 95%: 3803-8507) in 1990 to 6767 (4646-7890) new cases in 2019. However, leukemia age-standardized incidence ratio(ASIR) decreased from 11.6 (8-14.8) to 8.9 (6.2-10.3) new cases per 100,000 in this exact period. At the national level, deaths from leukemia increased 1.5-fold between 1990 and 2019, from 3287 (2284-4201) to 4424 (3137-5030), whereas the age-standardized death rate(ASDR) decreased from 8.3 (6.1-9.8) in 1990 to 6 (4.3-6.8) per 100,000 in 2019. In the study period, total leukemia DALYs decreased 12.2% and reached 162850 (110681-188806), in 2019. The age-standardized DALYs decreased 36.7% from 324.3 (224.8-413.4) in 1990 to 205.3 (140.3-237.8) in 2019. ASDR, DALYs, YLLs, and YLDs rate to high BMI was increasing while smoking and occupational exposure to benzene and formaldehyde were decreasing in the study period. CONCLUSION: This study provided a better understanding of leukemia burden and to reduce controversies of leukemia across Iran. The leukemia status alteration of the country, is trackable.

DNA Damage Responses, the Trump Card of Stem Cells in the Survival Game.

Stem cells, as a group of undifferentiated cells, are enriched with self-renewal and high proliferative capacity, which have attracted the attention of many researchers as a promising approach in the treatment of many diseases over the past years. However, from the cellular and molecular point of view, the DNA repair system is one of the biggest challenges in achieving therapeutic goals through stem cell technology. DNA repair mechanisms are an advantage for stem cells that are constantly multiplying to deal with various types of DNA damage. However, this mechanism can be considered a trump card in the game of cell survival and treatment resistance in cancer stem cells, which can hinder the curability of various types of cancer. Therefore, getting a deep insight into the DNA repair system can bring researchers one step closer to achieving major therapeutic goals. The remarkable thing about the DNA repair system is that this system is not only under the control of genetic factors, but also under the control of epigenetic factors. Therefore, it is necessary to investigate the role of the DNA repair system in maintaining the survival of cancer stem cells from both aspects.

Phenyl-quinoline derivatives as lead structure of cholinesterase inhibitors with potency to reduce the GSK-3ß level targeting Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that leads to cognitive decline and memory loss. Unfortunately, there is no effective treatment for this condition, so there is a growing interest in developing new anti-AD agents. In this research project, a series of phenyl-quinoline derivatives were designed as potential anti-AD agents. These derivatives were substituted at two different positions on benzyl and phenyl rings. The structures of the derivatives were characterized using techniques such as IR spectroscopy, 1H NMR, 13C NMR, and elemental analysis. During the in vitro screening, the derivatives were tested against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). It was observed that most of the derivatives showed higher selectivity against BChE compared to AChE. Among the derivatives, analog 7n (with a methoxy group at R1 and a 4-bromine substituent at R2 exhibited the highest potency, with a 75-fold improvement in the activity compared to the positive control. Importantly, this potent analog demonstrated no toxicity at the tested concentration on SH-SY5Y cells, indicating its potential as a safe anti-AD agent. The level of GSK-3ß was also reduced after treatments with 7n at 50 µM. Overall, this study highlights the design and evaluation of phenyl-quinoline derivatives as promising candidates for developing novel anti-AD agents.

The burden of rheumatoid arthritis and low back pain in North Africa and Middle East from 1990 to 2019: Results from the Global Burden of Disease Study 2019.

BACKGROUND: Rheumatoid arthritis (RA) and low back pain (LBP) are among the most prevalent musculoskeletal disorders (MSDs). The need for investigation of regional and local patterns of these two MSDs seems inevitable for better policy-making. The current study presents updated results of the Global Burden of Disease (GBD) Study 2019 and reports the burden of RA and LBP in North Africa and Middle East (NAME) countries from 1990 to 2019. METHODS: Incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and risk factors, including high body mass index, occupational ergonomic factors, and smoking, were extracted based on the GBD 2019 data. RESULTS: The age-standardized prevalence and mortality of RA were 120.6 (95% uncertainty interval [95% UI] 107.0-135.7) and 0.1 (95% UI 0.1-0.2) per 100 000 population in 2019 with 28.3% (95% UI 25.5%-30.9%) increase and 7.5% (95% UI -37.5% to 32.5%) decrease since 1990, respectively. Turkey had the highest age-standardized incidence, prevalence, and DALYs of RA in 2019. All RA burden measures were higher for women; however, the incidence was almost the same at ages greater than 65 years. The age-standardized prevalence and DALYs of LBP were 7668.2 (95% UI 6798.0-8636.3) and 862 (95% UI 605.5-1153.3) in 2019, which had decreased by 5.8% (95% UI -7.4% to -4.3%) and 6.0% (95% UI -7.7% to -4.2%) since 1990, respectively. Moreover, although Turkey had the highest incidence and prevalence in 1990, Iran was at the top in 2019. The regional age-standardized DALY rates due to RA and LBP attributed to smoking were 1.7 (95% UI 0.5-3.2) and 139.4 (95% UI 87.3-198.8) in 2019, respectively, which had decreased 2.2% (95% UI -19.2% to 13.7%) and 15.4% (95% UI -19.4% to -10.5%) since 1990, respectively. CONCLUSION: RA still imposes a significant burden in the NAME region as the burden measures have increased from 1990 to 2019. On the other hand, regarding LBP, a decreasing pattern was observed. Differences among the countries and between ages and genders can have implications, and the results of this study may be helpful for policy-makers in the NAME countries.

Burden of breast cancer and attributable risk factors in the North Africa and Middle East region, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: Breast cancer (BC) is the most common cancer in women globally. The North Africa and Middle East (NAME) region is coping hard with the burden of BC. We aimed to present the latest epidemiology of BC and its risk factors in this region. Methods: We retrieved the data on BC burden and risk factors from the Global Burden of Disease Study 2019 to describe BC status in the 21 countries of the NAME region from 1990 to 2019. We explored BC incidence, prevalence, deaths, disability-adjusted life years (DALYs), and attributable burden to seven risk factors of female BC, namely, alcohol use, diet high in red meat, low physical activity, smoking, secondhand smoke, high body mass index, and high fasting plasma glucose. Decomposition analysis on BC incidence trend was done to find out the contributing factors to this cancer's growth. Results: In 2019, there were 835,576 (95% uncertainty interval: 741,968 to 944,851) female and 10,938 (9,030 to 13,256) male prevalent cases of BC in the NAME region. This number leads to 35,405 (30,676 to 40,571) deaths among female patients and 809 (654 to 1,002) deaths in male patients this year. BC was responsible for 1,222,835 (1,053,073 to 1,411,009) DALYs among female patients in 2019, with a greater proportion (94.9%) of burden in years of life lost (YLLs). The major contributor to female BC incidence increase in the past three decades was found to be increase in age-specific incidence rates of BC (227.5%), compared to population growth (73.8%) and aging (81.8%). The behavioral risk factors were responsible for majority of attributable female BC burden (DALYs: 106,026 [66,614 to 144,247]). High fasting plasma glucose was found to be the risk factor with the largest effect (DALYs: 84,912 [17,377 to 192,838]) on female BC burden. Conclusion: The increasing incidence and burden of BC in the NAME region is remarkable, especially when considering limited resources in the developing countries of this region. Proper policies like expanding screening programs and careful resource management are needed to effectively manage BC burden.

Exploring the clinical benefit of ventilation therapy across various patient groups with COVID-19 using real-world data.

Scarcity of ventilators during COVID-19 pandemic has urged public health authorities to develop prioritization recommendations and guidelines with the real-time decision-making process based on the resources and contexts. Nevertheless, patients with COVID-19 who will benefit the most from ventilation therapy have not been well-defined yet. Thus, the objective of this study was to investigate the benefit of ventilation therapy among various patient groups with COVID-19 admitted to hospitals, based on the real-world data of hospitalized adult patients. Data used in the longitudinal study included 599,340 records of hospitalized patients who were admitted from February 2020 to June 2021. All participants were categorized based on sex, age, city of residence, the hospitals' affiliated university, and their date of hospitalization. Age groups were defined as 18-39, 40-64, and more than 65-year-old participants. Two models were used in this study: in the first model, participants were assessed by their probability of receiving ventilation therapy during hospitalization based on demographic and clinical factors using mixed-effects logistic regression. In the second model, the clinical benefit of receiving ventilation therapy among various patient groups was quantified while considering the probability of receiving ventilation therapy during hospital admission, as estimated in the first model. The interaction coefficient in the second model indicated the difference in the slope of the logit probability of recovery for a one-unit increase in the probability of receiving ventilation therapy between the patients who received ventilation compared to those who did not while considering other factors constant. The interaction coefficient was used as an indicator to quantify the benefit of ventilation reception and possibly be used as a criterion for comparison among various patient groups. Among participants, 60,113 (10.0%) cases received ventilation therapy, 85,158 (14.2%) passed away due to COVID-19, and 514,182 (85.8%) recovered. The mean (SD) age was 58.5 (18.3) [range = 18-114, being 58.3 (18.2) among women, and 58.6 (18.4) among men]. Among all groups with sufficient data for analysis, patients aged 40-64 years who had chronic respiratory diseases (CRD) and malignancy benefitted the most from ventilation therapy; followed by patients aged 65 + years who had malignancy, cardiovascular diseases (CVD), and diabetes (DM); and patients aged 18-39 years who had malignancy. Patients aged 65 + who had CRD and CVD gained the least benefit from ventilation therapy. Among patients with DM, patients aged 65 + years benefited from ventilation therapy, followed by 40-64 years. Among patients with CVD, patients aged 18-39 years benefited the most from ventilation therapy, followed by patients aged 40-64 years and 65 + years. Among patients with DM and CVD, patients aged 40-64 years benefited from ventilation therapy, followed by 65 + years. Among patients with no history of CRD, malignancy, CVD, or DM, patients aged 18-39 years benefited the most from ventilation therapy, followed by patients aged 40-64 years and 65 + years. This study promotes a new aspect of treating patients for ventilators as a scarce medical resource, considering whether ventilation therapy would improve the patient's clinical outcome. Should the prioritization guidelines for ventilators allocation take no notice of the real-world data, patients might end up being deprived of ventilation therapy, who could benefit the most from it. It could be suggested that rather than focusing on the scarcity of ventilators, guidelines focus on evidence-based decision-making algorithms to also take the usefulness of the intervention into account, whose beneficial effect is dependent on the selection of the right time in the right patient.

Design, synthesis, in vitro, and in silico evaluations of benzo[d]imidazole-amide-1,2,3-triazole-N-arylacetamide hybrids as new antidiabetic agents targeting α-glucosidase.

α-Glucosidase as a carbohydrate-hydrolase enzyme is a crucial therapeutic target for type 2 diabetes. In this work, benzo[d]imidazole-amide containing 1,2,3-triazole-N-arylacetamide derivatives 8a-n were synthesized and evaluated for their inhibitory activity against α-glucosidase. In vitro α-glucosidase inhibition assay demonstrated that more than half of the title compounds with IC50 values in the range of 49.0-668.5 µM were more potent than standard inhibitor acarbose (IC50 = 750.0 µM). The most promising inhibitor was N-2-methylphenylacetamid derivative 8c. Kinetic study revealed that compound 8c (Ki = 40.0 µM) is a competitive inhibitor against α-glucosidase. Significantly, molecular docking and molecular dynamics studies on the most potent compound showed that this compound with a proper binding energy interacted with important amino acids of the α-glucosidase active site. Study on cytotoxicity of the most potent compounds 8c, 8e, and 8g demonstrated that these compounds did not show cytotoxic activity against the cancer and normal cell lines MCF-7 and HDF, respectively. Furthermore, the ADMET study predicted that compound 8c is likely to be orally active and non-cytotoxic.

The prevalence and predictors of geriatric giants in community-dwelling older adults: a cross-sectional study from the Middle East.

The term "geriatric giants" refers to the chronic disabilities of senescence leading to adverse health outcomes. This study aimed to investigate the prevalence and predictors of geriatric giants in Southern Iran. The participants were selected from Bushehr city using a multistage cluster random sampling method. Demographic data were collected through interviews. Frailty, incontinence, immobility, depression, cognitive impairment, and malnutrition were measured by questionnaires and instruments. Finally, data from 2392 participants were analyzed. The prevalence of fecal incontinence was less than 1% among all participants and similar in men and women. In contrast, compared with men, women had higher prevalence of urinary incontinence (36.44% vs. 17.65%), depression (39.05% vs. 12.89%), anorexia and malnutrition (2.35% vs. 0.82%), immobility (8.00% vs. 2.5%), frailty (16.84 vs. 7.34), and pre-frailty (54.19 vs. 38.63%). The prevalence of dependence and cognitive impairment was also higher in women and considerably increased with the age of participants. In total, 12.07% of subjects were frail, and 46.76% were pre-frail. The prevalence of frailty exponentially increased in older age, ranging from 4.18% among those aged 60-64 years to 57.35% in those aged ≥ 80 years. Considering 95% confidence interval (CI), multivariate logistic regression revealed that low physical activity [odds ratio (OR) 31.73 (18.44-54.60)], cancer (OR 3.28 (1.27-8.44)), depression [OR 2.42 (1.97-2.98)], age [OR 1.11 (1.08-1.14)], waist circumference [OR 1.03 (1.01-1.06)], BMI [OR 1.07 (1.01-1.14)], MNA score [OR 0.85 (0.79-0.92)], polypharmacy [OR 2.26 (1.30-3.95)] and male gender [OR 0.63 (0.42-0.93)] were independently associated with frailty. White blood cell count (WBC), smoking, marital status, and number of comorbidities were not independently associated with frailty. Low physical activity was the strongest predictor of frailty, which may need more attention in geriatric care. Frailty, its predictors, and other components of geriatric giants were considerably more common among women and older ages.

Association of age-related declined renal function and osteoporosis based on trabecular bone score in Bushehr Elderly Health (BEH) program.

PURPOSE: Osteoporosis is a systemic disease characterized by decreased bone strength and an increased risk of fracture in old age. Age and pathologic renal failure are independent risk factors for osteoporosis. However, it is not determined whether age-related decreased renal function, in the context of senescence, can be considered as an independent risk factor for osteoporosis. Therefore, this study was conducted to evaluate the effect of senescence-induced renal failure on bone quality and trabecular bone score. METHODS: This study used a cross-sectional design and was carried out based on data collected during the Bushehr Elderly Health (BEH) program, Phase II. A total of 2,125 elderly participants aged over 60 years old entered the study after meeting the inclusion criteria and providing informed consent. They underwent examinations for weight, height, abdominal and hip circumference, as well as blood pressure measurement. All participants also underwent DXA to assess bone mass density (BMD). Trabecular bone score (TBS) was calculated using the DXA apparatus software output. Univariate and adjusted multivariate linear regression analyses were used to evaluate the associations. RESULTS: In the univariate linear regression analysis, there was a direct correlation between age-related renal failure and TBS (ß = 0.038, p < 0.0001), neck of femur BMD (ß = 0.047, p < 0.0001), and lumbar BMD (ß = 0.055, p < 0.0001). However, after adjusting for BMI, age, sex, smoking, and physical activity, no significant association was observed for these variables. CONCLUSION: It is hypothesized that age-related renal failure cannot be considered as an independent risk factor for osteoporosis in elderly individuals aged over 60 years old.