Molecular signaling directing neural plate border formation.

During embryonic development, the vertebrate embryonic epiblast is divided into two parts including neural and superficial ectoderm. The neural plate border (NPB) is a narrow transitional area which locates between these parts and contains multipotent progenitor cells. Despite its small size, the cellular heterogeneity in this region produces specific differentiated cells. Signaling pathways, transcription factors, and the expression/repression of certain genes are directly involved in these differentiation processes. Different factors such as the Wnt signaling cascade, fibroblast growth factor (FGF), bone morphogenetic protein (BMP) signaling, and Notch, which are involved in various stages of the growth, proliferation, and differentiation of embryonic cells, are also involved in the determination and differentiation of neural plate border stem cells. Therefore, it is essential to consider the interactions and temporospatial coordination related to cells, tissues, and adjacent structures. This review examines our present knowledge of the formation of the neural plate border and emphasizes the requirement for interaction between different signaling pathways, including the BMP and Wnt cascades, the expression of its special target genes and their regulations, and the precise tissue crosstalk which defines the neural crest fate in the ectoderm at the early human embryonic stages.

Optimizing the Steering of Driverless Personal Mobility Pods with a Novel Differential Harris Hawks Optimization Algorithm (DHHO) and Encoder Modeling.

This paper aims to improve the steering performance of the Ackermann personal mobility scooter based on a new meta-heuristic optimization algorithm named Differential Harris Hawks Optimization (DHHO) and the modeling of the steering encoder. The steering response in the Ackermann mechanism is crucial for automated driving systems (ADS), especially in localization and path-planning phases. Various methods presented in the literature are used to control the steering, and meta-heuristic optimization algorithms have achieved prominent results. Harris Hawks optimization (HHO) algorithm is a recent algorithm that outperforms state-of-the-art algorithms in various optimization applications. However, it has yet to be applied to the steering control application. The research in this paper was conducted in three stages. First, practical experiments were performed on the steering encoder sensor that measures the steering angle of the Landlex mobility scooter, and supervised learning was applied to model the results obtained for the steering control. Second, the DHHO algorithm is proposed by introducing mutation between hawks in the exploration phase instead of the Hawks perch technique, improving population diversity and reducing premature convergence. The simulation results on CEC2021 benchmark functions showed that the DHHO algorithm outperforms the HHO, PSO, BAS, and CMAES algorithms. The mean error of the DHHO is improved with a confidence level of 99.8047% and 91.6016% in the 10-dimension and 20-dimension problems, respectively, compared with the original HHO. Third, DHHO is implemented for interactive real-time PID tuning to control the steering of the Ackermann scooter. The practical transient response results showed that the settling time is improved by 89.31% compared to the original response with no overshoot and steady-state error, proving the superior performance of the DHHO algorithm compared to the traditional control methods.

Raha syrup attenuates the morphine withdrawal-induced locomotor sensitisation by increasing the cerebrospinal fluid serotonin in rats receiving the opium tincture maintenance treatment.

Morphine withdrawal increases locomotor sensitisation, relapse and impair regulation of serotonin system. We evaluated the effectiveness of Raha syrup on the cerebrospinal fluid (CSF) serotonin levels following locomotor sensitisation in morphine-withdrawn rats receiving the opium tincture (OT). Morphine withdrawal rats gavaged daily with OT and Raha syrup (for 30 days) and then challenged with morphine and evaluated for locomotor activity and CSF serotonin levels before morphine challenge and 2 weeks after cessation of treatment. Raha syrup attenuated locomotor activity, increased the CSF serotonin after morphine challenge, and continued 2 weeks after cessation of treatment in rats receiving OT. Whereas, rats receiving OT alone after morphine challenge exhibited a relative decrease in locomotor activity, without changing CSF serotonin. Raha syrup attenuated locomotor sensitisation in morphine-withdrawn rats receiving OT probably by increasing serotonin. Therefore, administration of Raha syrup along with OT may benefit to treatment relapse in addicts receiving OT maintenance treatment.

Evaluation of new bone formation in critical-sized rat calvarial defect using 3D printed polycaprolactone/tragacanth gum-bioactive glass composite scaffolds.

Critical-sized bone defects are a major challenge in reconstructive bone surgery and usually fail to be treated due to limited remaining bone quality and extensive healing time. The combination of 3D-printed scaffolds and bioactive materials is a promising approach for bone tissue regeneration. In this study, 3D-printed alkaline-treated polycaprolactone scaffolds (M-PCL) were fabricated and integrated with tragacanth gum- 45S5 bioactive glass (TG-BG) to treat critical-sized calvarial bone defects in female adult Wistar rats. After a healing period of four and eight weeks, the new bone of blank, M-PCL, and M-PCL/TG-BG groups were harvested and assessed. Micro-computed tomography, histological, biochemical, and biomechanical analyses, gene expression, and bone matrix formation were used to assess bone regeneration. The micro-computed tomography results showed that the M-PCL/TG-BG scaffolds not only induced bone tissue formation within the bone defect but also increased BMD and BV/TV compared to blank and M-PCL groups. According to the histological analysis, there was no evidence of bony union in the calvarial defect regions of blank groups, while in M-PCL/TG-BG groups bony integration and repair were observed. The M-PCL/TG-BG scaffolds promoted the Runx2 and collagen type I expression as compared with blank and M-PCL groups. Besides, the bone regeneration in M-PCL/TG-BG groups correlated with TG-BG incorporation. Moreover, the use of M-PCL/TG-BG scaffolds promoted the biomechanical properties in the bone remodeling process. These data demonstrated that the M-PCL/TG-BG scaffolds serve as a highly promising platform for the development of bone grafts, supporting bone regeneration with bone matrix formation, and osteogenic features. Our results exhibited that the 3D-printed M-PCL/TG-BG scaffolds are a promising strategy for successful bone regeneration.

Harmine exhibits anti-apoptotic properties and reduces diabetes-induced testicular damage caused by streptozotocin in rats.

Objective: Diabetes mellitus induces fertility problems in men, mainly because of increased free radicals. Natural resources are effective for male infertility treatment. This study investigated the effects of harmine, an alkaloid available in Peganum harmala L., on the male reproductive system of diabetic rats. Methods: We divided 32 rats into four groups, and eight were randomly placed in each group. For diabetes induction, the animals received 50 mg/kg of streptozotocin intraperitoneally. After 1 week, animals received 15 mg/kg of harmine (28 days; intraperitoneal). Histopathological examinations, serum levels of male hormones, levels of nitric oxide (NO) and malondialdehyde (MDA) in the testes, total antioxidant capacity (TAC), insulin serum levels, fasting blood glucose levels, the apoptotic index, and semen analysis were assessed. Results: The diabetes group exhibited morphological changes in testicular tissue, significant decreases in the diameter of the seminiferous tubule, the Johnsen score, testosterone, luteinizing hormone, follicle-stimulating hormone, insulin serum levels, and TAC in testicular tissue (p<0.01). Harmine treatment ameliorated the morphological changes in the testes and improved sperm parameters relative to the diabetes group (p<0.05). The NO and MDA levels in the testes, fasting blood glucose serum levels, and apoptotic index parameters were significantly elevated in the diabetes group, while in the diabetes+harmine group, these parameters were reduced (p<0.01). Conclusion: Harmine protects testicular tissue and sperm against diabetes-induced damage. This effect of harmine is associated with a rebalancing of the antioxidant capacity that subsequently decreases apoptosis in the testes.

Coadministration of doxorubicin with vitamin D3, Lactobacillus acidophilus, and Lactobacillus casei in the 4T1 mouse model of breast cancer: anticancer and enteroprotective effects.

The use of doxorubicin (Dox) in the treatment of breast cancer negatively affects the intestines and other tissues. Many studies have proven that probiotics and vitamin D3 have antitumor and intestinal tissue-protecting properties. To achieve effectiveness and minimize side effects, the current study aims to administer Dox together with probiotics (Lactobacillus acidophilus and Lactobacillus casei) and vitamin D3. Forty-two female BALB/c inbred mice were divided into six groups: Group 1 (Control), Group 2 (Dox), Group 3 (Dox and probiotics), Group 4 (Dox and vitamin D3), Group 5 (Dox, probiotics, and vitamin D3), and Group 6 (probiotics and vitamin D3). The 4T1 mouse carcinoma cell line was injected into the mammary fat pad of each mouse. Gene expression was examined using quantitative real-time PCR. The treated groups (except group 6) showed significantly reduced tumor volume and weight compared to the control group (P < 0.05, P < 0.01). Probiotics/vitamin D3 with Dox reduced chemotherapy toxicity and a combination of supplements had a significant protective effect against Dox (P < 0.05, 0.01, 0.001). The treated groups (except 6) had significantly higher expression of Bax/Caspase 3 genes and lower expression of Bcl-2 genes than the control group (P < 0.05, 0.01). Coadministration of Dox with probiotics and vitamin D3 showed promising results in reducing tumor size, protecting intestinal tissue and influencing gene expression, suggesting a strategy to enhance the effectiveness of breast cancer treatment while reducing side effects.

Bone marrow stromal cell-conditioned medium regenerates injured sciatic nerve by increasing expression of MPZ and NGF and decreasing apoptosis.

Objectives: Despite the many benefits of mesenchymal stem cell (MSC) transplantation for tissue regeneration, there are some limitations to using them, including the high costs, applying invasive procedures, the possibility of transplant rejection, and cell malignancy. This study aimed to investigate the effect of secretions of bone marrow stromal cells (BMSCs) with the cell-free strategy on damaged sciatic nerve with an emphasis on the role of apoptosis and the expression of myelin protein zero (MPZ) and nerve growth factor (NGF) proteins. Materials and Methods: BMSCs were cultured and a 25-fold concentrated conditioned medium (CM) from the cells was provided. After creating a crush injury in the left sciatic nerve of male rats, BMSCs or CM were injected into the injured site of the nerve. Four weeks later, the expression of MPZ, NGF, Bax, and Bcl-2 proteins in the sciatic nerve and histological parameters of the sciatic nerve and gastrocnemius muscle were assessed. Results: The results demonstrated that injection of CM decreased apoptosis and increased expression of MPZ and NGF proteins, improving remyelination and regeneration of the sciatic nerve almost as much as the transplantation of the BMSCs themselves compared to the control group. Conclusion: The results suggest that BMSC secretions may improve remyelination and regeneration of damaged sciatic nerve by increasing the expression of MPZ and NGF and decreasing apoptosis.

Effects of swimming exercise on neuropathic pain in a rat model: role of glutamate.

OBJECTIVE: The pain-reducing effects of the exercise were exerted through different mechanisms. Knowing more clear mechanisms helps to find more approach that is therapeutic. The objective of the present study is the evaluation of cerebrospinal fluid (CSF) glutamate level alteration in neuropathic pain rats and whether physical activity could modulate it. METHODS: In the present study 104 male Wistar rats weighing 180-220 g were randomly divided into 4 groups (Sham, Sham + Exe, Neuropathy, and Neuropathy + Exe) which in turn each group subdivided into 4 groups according to time points for behavioral testing and CSF sampling (Baseline, 2 weeks, 3 weeks, and 4 weeks). To induction of neuropathy (by chronic constriction injury,), after anesthetizing with a mixture of ketamine (80 mg/kg) and xylazine (10 mg/kg), the animal's right sciatic nerve was exposed and was ligated using four movable catgut chromic suture 4/0. The exercise protocol included 25 min of daily swimming, 5 days a week for 4 weeks. Thermal hyperalgesia and mechanical tactile threshold were detected using the plantar test and Von Frey filaments, respectively. CSF glutamate level was determined using high-performance liquid chromatography. RESULTS: Findings indicated that mechanical and thermal thresholds significantly (p < 0.01, p < 0.05 respectively) decreased in the neuropathy group against that in sham groups. On the other hand, exercise significantly increased mechanical tactile threshold (p < 0.0012) and thermal threshold (p < 0.05) compared to the neuropathy group. Moreover, CSF glutamate level prominently (p < 0.01) was increased in the neuropathy group compared to the sham group, and swimming exercise significantly (p < 0.001) reduced it. IN CONCLUSION: The present findings provide new evidence showing that medium-intensity swimming exercise attenuates pain-like behaviors in neuropathic pain animals, which is possibly due to decreasing CSF glutamate level and its neurotransmission.

Burden of Ischemic Heart Disease and Its Attributable Risk Factors in North Africa and the Middle East, 1990 to 2019: Results From the GBD Study 2019.

BACKGROUND: The North Africa and Middle East (NAME) region has one of the highest burdens of ischemic heart disease (IHD) worldwide. This study reports the contemporary epidemiology of IHD in NAME. METHODS AND RESULTS: We estimated the incidence, prevalence, deaths, years of life lost, years lived with disability, disability-adjusted life years (DALYs), and premature mortality of IHD, and its attributable risk factors in NAME from 1990 to 2019 using the results of the GBD (Global Burden of Disease study 2019). In 2019, 0.8 million lives and 18.0 million DALYs were lost due to IHD in NAME. From 1990 to 2019, the age-standardized DALY rate of IHD significantly decreased by 33.3%, mostly due to the reduction of years of life lost rather than years lived with disability. In 2019, the proportion of premature death attributable to IHD was higher in NAME compared with global measures: 26.8% versus 16.9% for women and 18.4% versus 14.8% for men, respectively. The age-standardized DALY rate of IHD attributed to metabolic risks, behavioral risks, and environmental/occupational risks significantly decreased by 28.7%, 37.8%, and 36.4%, respectively. Dietary risk factors, high systolic blood pressure, and high low-density lipoprotein cholesterol were the top 3 risks contributing to the IHD burden in most countries of NAME in 2019. CONCLUSIONS: In 2019, IHD was the leading cause of death and lost DALYs in NAME, where premature death due to IHD was greater than the global average. Despite the great reduction in the age-standardized DALYs of IHD in NAME from 1990 to 2019, this region still had the second-highest burden of IHD in 2019 globally.

Frequency -Specific Air- Conduction and Bone - Conduction Outcomes after Stapedotomy.

Introduction: The aim of this study was to investigate hearing outcome of stapes surgery, considering the post-operative air and bone conduction (AC&BC) changes, in a frequency specific approach. Materials and Methods: This was a retrospective cohort study. A total of 245 ears (231 patients), who underwent Stapedotomy at our tertiary referral center in a period of 5 years were enrolled in the study. Pure tone audiometry (PTA) was evaluated preoperatively and one month postoperatively. AC, BC, and Air-bone gap (ABG) were documented. Moreover, one-year post-op PTA was also recorded for more than a quarter of the cases. Results: Overall, significant improvements were observed in AC thresholds with a mean AC gain of 20.44±13.64 dB. At higher frequencies the results were poorer (AC gain of 27 dB at 250 Hz vs 7 dB at 8000 Hz). ABG significantly improved at all frequencies after one month. BC thresholds were typically better after surgery. However, there appears to be a worsening trend in BC thresholds at frequencies higher than 2000 Hz. In 68 patients with 1-year follow-up, BC thresholds were slightly worse (but not statistically significant) at most frequencies, in comparison to the one-month results. Conclusions: Stapes surgery significantly improves air and bone conduction hearing, particularly at lower frequencies. Nonetheless, there exists a potential for sensorineural hearing loss (SNHL) at high frequencies. However, the changes are insignificant and not within the speech frequencies. Therefore, patients are typically satisfied with the hearing outcome of the surgery.

Retinoic acid loaded with chitosan nanoparticles improves spermatogenesis in scrotal hyperthermia in mice.

OBJECTIVE: High temperatures can trigger cellular oxidative stress and disrupt spermatogenesis, potentially leading to male infertility. We investigated the effects of retinoic acid (RA), chitosan nanoparticles (CHNPs), and retinoic acid loaded with chitosan nanoparticles (RACHNPs) on spermatogenesis in mice induced by scrotal hyperthermia (Hyp). METHODS: Thirty mice (weighing 25 to 30 g) were divided into five experimental groups of six mice each. The groups were as follows: control, Hyp induced by a water bath (43 °C for 30 minutes/day for 5 weeks), Hyp+RA (2 mg/kg/day), Hyp+CHNPs (2 mg/kg/72 hours), and Hyp+RACHNPs (4 mg/kg/72 hours). The mice were treated for 35 days. After the experimental treatments, the animals were euthanized. Sperm samples were collected for analysis of sperm parameters, and blood serum was isolated for testosterone measurement. Testis samples were also collected for histopathology assessment, reactive oxygen species (ROS) evaluation, and RNA extraction, which was done to compare the expression levels of the bax, bcl2, p53, Fas, and FasL genes among groups. Additionally, immunohistochemical staining was performed. RESULTS: Treatment with RACHNPs significantly increased stereological parameters such as testicular volume, seminiferous tubule length, and testicular cell count. Additionally, it increased testosterone concentration and improved sperm parameters. We observed significant decreases in ROS production and caspase-3 immunostaining in the RACHNP group. Moreover, the expression levels of bax, p53, Fas, and FasL significantly decreased in the groups treated with RACHNPs and RA. CONCLUSION: RACHNPs can be considered a potent antioxidative and antiapoptotic agent for therapeutic strategies in reproductive and regenerative medicine.

The levels and trends of metabolic risk factors in the elderly population at the national and sub-national scale in Iran from 1990 to 2016.

Purpose: Describing the trends of metabolic risk factors (MRFs) in the elderly population. Methods: We used modeled data from previous comprehensive systematic reviews for MRFs among adults aged ≥ 60 years. Two stages of age-specific Spatio-temporal modeling and Gaussian process regression were used to estimate the mean of MRFs. We used crosswalk modeling to estimate the prevalence of elevated and raised Total cholesterol (TC), overweight/obesity and obesity, hypertension, and diabetes. Estimates were analyzed based on combinations of sex, age, year, and province from 1990 to 2016. Results: Comparing prevalence estimates from 2016 with those of 1990, in the elderly population, the age-standardized prevalence of overweight/obesity, obesity, diabetes, and hypertension increased, conversely, the prevalence of hypercholesteremia decreased. The prevalence of hypertension increased about 141.5% and 129.9% in men and women respectively. The age-standardized prevalence of diabetes increased about 109.5% in females, and 116.0% in males. Prevalence of elevated TC at the national level decreased to 67.4% (64.1-70.4) in women and to 51.1% (47.5-54.8) in men. These findings were almost shown across provinces. In general, the northern and western provinces had the highest prevalence of overweight/obesity in women in 2016. Conclusion: The rising prevalence of most MRFs, as well as the greater prevalence and mean of all MRFs in women, necessitate effective public health policies to reduce the burden of non-communicable diseases and run preventive programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01297-z.

The quality of care index for low back pain: a systematic analysis of the global burden of disease study 1990-2017.

BACKGROUND: . Low back pain is one of the major causes of morbidity worldwide. Studies on low back pain quality of care are limited. This study aimed to evaluate the quality of care of low back pain worldwide and compare gender, age, and socioeconomic groups. METHODS: . This study used GBD data from 1990 to 2017 from the Institute for Health Metrics and Evaluation (IHME) website. Extracted data included low back pain incidence, prevalence, disability-adjusted life years (DALYs), and years lived with disability (YLDs). DALYs to prevalence ratio and prevalence to incidence ratio were calculated and used in the principal component analysis (PCA) to make a proxy of the quality-of-care index (QCI). Age groups, genders, and countries with different socioeconomic statuses regarding low back pain care quality from 1990 to 2017 were compared. RESULTS: The proxy of QCI showed a slight decrease from 36.44 in 1990 to 35.20 in 2017. High- and upper-middle-income countries showed a decrease in the quality of care from 43.17 to 41.57 and from 36.37 to 36.00, respectively, from 1990 to 2017. On the other hand, low and low-middle-income countries improved, from a proxy of QCI of 20.99 to 27.89 and 27.74 to 29.36, respectively. CONCLUSION: . Despite improvements in the quality of care for low back pain in low and lower-middle-income countries between 1990 and 2017, there is still a large gap between these countries and higher-income countries. Continued steps must be taken to reduce healthcare barriers in these countries.

Falcaria vulgaris L. hydroalcoholic extract protects against harmful effects of mercuric chloride on the rat kidney.

Objective: Mercuric chloride (Merc; HgCl2) is toxic to humans and animals and contributes to environmental pollution, which usually results in nerve and systemic harm to different organs. Falcaria vulgaris (FV) is a medicinal plant rich in antioxidants. This research aimed to assess the FV hydroalcoholic extract effects on kidney toxicity induced by Merc. Materials and Methods: Forty-eight male rats were divided into eight groups: the control group: received saline; the Merc group: received 0.5 ml/day of 0.5 ppm aqueous Merc; FV1, 2, and 3 groups: received 50, 100, 150 mg/kg FV, respectively; and Merc + FV1, 2, and 3 groups: received Merc and FV at three doses. The administration period was 14-days. Subsequently, kidneys and sera were cumulated from each group for the analysis. Samples were analyzed via hematoxylin-eosin staining and biochemical tests. Results: The rats that received Merc displayed significant decrement in the kidney index, the diameter of renal corpuscles, total antioxidant capacity levels, superoxide dismutase activity (all, p<0.01), and 150 mg/kg FV mitigated these outcomes (all, p<0.05). Urea, creatinine, nitric oxide, and the level of apoptosis revealed a significant increment in the kidney of the rats that received Merc (all, p<0.01), and 150 mg/kg FV decreased these results. Furthermore, FV ameliorated histological changes induced by Merc (all, p<0.05). Conclusion: The FV hydroalcoholic extract protects the kidneys against Merc-induced nephrotoxicity. Antioxidant and anti-apoptotic FV hydroalcoholic extract properties were involved in this healing effect.

Diagnostic testing for hypertension, diabetes, and hypercholesterolaemia in low-income and middle-income countries: a cross-sectional study of data for 994 185 individuals from 57 nationally representative surveys.

BACKGROUND: Testing for the risk factors of cardiovascular disease, which include hypertension, diabetes, and hypercholesterolaemia, is important for timely and effective risk management. Yet few studies have quantified and analysed testing of cardiovascular risk factors in low-income and middle-income countries (LMICs) with respect to sociodemographic inequalities. We aimed to address this knowledge gap. METHODS: In this cross-sectional analysis, we pooled individual-level data for non-pregnant adults aged 18 years or older from nationally representative surveys done between Jan 1, 2010, and Dec 31, 2019 in LMICs that included a question about whether respondents had ever had their blood pressure, glucose, or cholesterol measured. We analysed diagnostic testing performance by quantifying the overall proportion of people who had ever been tested for these cardiovascular risk factors and the proportion of individuals who met the diagnostic testing criteria in the WHO package of essential noncommunicable disease interventions for primary care (PEN) guidelines (ie, a BMI >30 kg/m2 or a BMI >25 kg/m2 among people aged 40 years or older). We disaggregated and compared diagnostic testing performance by sex, wealth quintile, and education using two-sided t tests and multivariable logistic regression models. FINDINGS: Our sample included data for 994 185 people from 57 surveys. 19·1% (95% CI 18·5-19·8) of the 943 259 people in the hypertension sample met the WHO PEN criteria for diagnostic testing, of whom 78·6% (77·8-79·2) were tested. 23·8% (23·4-24·3) of the 225 707 people in the diabetes sample met the WHO PEN criteria for diagnostic testing, of whom 44·9% (43·7-46·2) were tested. Finally, 27·4% (26·3-28·6) of the 250 573 people in the hypercholesterolaemia sample met the WHO PEN criteria for diagnostic testing, of whom 39·7% (37·1-2·4) were tested. Women were more likely than men to be tested for hypertension and diabetes, and people in higher wealth quintiles compared with those in the lowest wealth quintile were more likely to be tested for all three risk factors, as were people with at least secondary education compared with those with less than primary education. INTERPRETATION: Our study shows opportunities for health systems in LMICs to improve the targeting of diagnostic testing for cardiovascular risk factors and adherence to diagnostic testing guidelines. Risk-factor-based testing recommendations rather than sociodemographic characteristics should determine which individuals are tested. FUNDING: Harvard McLennan Family Fund, the Alexander von Humboldt Foundation, and the National Heart, Lung, and Blood Institute of the US National Institutes of Health.

Risk of incident cardiovascular diseases at national and subnational levels in Iran from 2000 to 2016 and projection through 2030: Insights from Iran STEPS surveys.

BACKGROUND: Cardiovascular Disease (CVD) is the leading cause of death in developing countries. CVD risk stratification guides the health policy to make evidence-based decisions. AIM: To provide current picture and future trend of CVD risk in the adult Iranian population. METHODS: Nationally representative datasets of 2005, 2006, 2007, 2008, 2009, 2011, and 2016 STEPwise approach to non-communicable diseases risk factor surveillance (STEPS) studies were used to generate the 10-year and 30-year risks of CVD based on Framingham, Globorisk, and World Health Organization (WHO) risk estimation models. Trend of CVD risk was calculated from 2000 until 2016 and projected to 2030. RESULTS: In 2016, based on Framingham model, 14.0% of the Iranian, aged 30 to 74, were at great risk (≥20%) of CVD in the next 10 years (8.0% among females, 20.7% among males). Among those aged 25 to 59, 12.7% had ≥45% risk of CVD in the coming 30 years (9.2% among females, 16.6 among males). In 2016, CVD risk was higher among urban area inhabitants. Age-standardized Framingham 10-year CVD risk will increase 32.2% and 19%, from 2000 to 2030, in females and males, respectively. Eastern provinces had the lowest and northern provinces had the greatest risk. CONCLUSIONS: This study projected that CVD risk has increased from 2000 to 2016 in Iran. Without further risk factor modification, this trend will continue until 2030. We have identified populations at higher risks of CVD to guide future intervention.

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.

Burden of autism spectrum disorders in North Africa and Middle East from 1990 to 2019: A systematic analysis for the Global Burden of Disease Study 2019.

INTRODUCTION: Autism spectrum disorders (ASD) encompass a range of neurodevelopmental disorders that affect the patient's communication and behavior. There are some reports about the increasing prevalence of ASD in recent decades, mostly due to the improvement in diagnosis and screening status. Few studies suggested a lower prevalence of ASD in North Africa and Middle East compared to more developed regions. The aim of this study is to provide a comprehensive outlook of ASD in the region. METHODS: We used Global Burden of Disease (GBD) data from 1990 to 2019 in North Africa and Middle East, which is one of the seven super regions of the GBD categorization. In this study, we reported the epidemiologic indices, including prevalence, incidence, and years lived with disability (YLDs) for ASD in the 21 countries of the super region. We also compared these indices between the countries based on their sociodemographic index (SDI) which was calculated according to income per capita, mean education, and fertility rate. RESULTS: Age-standardized prevalence rate (ASPR) of ASD in the region is 304.4 (95% uncertainty interval 251.2-366.1) per 100,000 in 2019 with less than one percentage change since 1990. Age-standardized YLDs and incidence rates were 46.4 (30.4-67.5) and 7.7 (6.3-9.3) per 100,000 in 2019. The ASPR was 2.9 times greater in males compared to females in 2019. The highest age-standardized prevalence, incidence, and YLD rates among the countries were seen in Iran in 2019 (370.3, 9.3, and 56.4 per 100,000, respectively). High SDI countries had higher age-standardized YLDs rates compared to the other countries of the region. CONCLUSION: In conclusion, the trends of age-standardized epidemiologic indices remained approximately steady through the years 1990-2019 in the region. Though, there was a wide discrepancy between the countries of the region. The difference of YLDs among the countries of this region is related to the SDI of the countries. Monetary and public awareness status are the SDI factors that may affect the quality of life of ASD patients in the region. This study provides valuable information for governments and health systems to implement policies for maintaining the improving trend, achieving more timely diagnosis, and bettering the supportive actions in this region.

Global, Regional, and National Quality of Care Index (QCI) of Gastric Cancer: A Systematic Analysis for the Global Burden of Disease Study 1990-2017.

BACKGROUND: Gastric Cancer (GC)is the third leading cause of cancer death worldwide. We aimed to compare the quality of care of GC at global, regional, and national levels from 1990 to 2017 in different age, sex, and socio-demographic groups using the quality-of-care index. MATERIAL: METHOD: We used Mortality to Incidence Ratio, DALY to Prevalence Ratio, YLL to YLD Ratio, and Prevalence to Incidence Ratio, that all indicate the quality of care. Then, using Principal Component Analysis (PCA), these values are combined. A new index called QCI (Quality of Care Index), which indicates quality, is introduced to compare the quality of care in different countries in 1990 and 2017. Scores were calculated and scaled 0-100, with higher scores indicating better status. RESULTS: The global QCI of GC in 1990 and 2017 was 35.7 and 66.7, respectively. The QCI index is 89.6 and 16.4 in high and low SDI countries, respectively. In 2017, Japan had the highest QCI with a 100 score. Japan was followed by South Korea, Singapore, Australia, and the United States with 99.5, 98.4, 98.3, and 90.0. On the other hand, the Central African Republic, Eritrea, Papua New Guinea, Lesotho, and Afghanistan with 11.6, 13.0, 13.1, 13.5, and 13.7 had the worst QCI, respectively. CONCLUSION: The quality of care of GC has increased worldwide from 1990 to 2017. Also, higher SDI was associated with more quality of care. We recommend conducting more screening and therapeutic programs for early detection and to improve gastric cancer treatment in developing countries.

Global, regional, and national burden and quality of care index (QCI) of bipolar disorder: A systematic analysis of the Global Burden of Disease Study 1990 to 2019.

BACKGROUND: Bipolar disorders (BD) are significant debilitating mental problems. Here, we introduced a novel index as a representative of the quality of care delivered to BD patients worldwide. METHODS: The Global Burden of Disease (GBD) 2019 study was the primary data source on BD, including prevalence, incidence, and years lived with disability (YLDs). Secondary indices were created and transformed into a single component that accounted for most of the variation, using the Principal Component Analysis (PCA) method. This component, reported on a scale of 0 to 100, was presented as the quality of care index (QCI). The QCI was estimated in different age groups and areas within a 30-year time frame. Gender disparity ratio (GDR), as the female-to-male ratio of the QCI, was reported. RESULTS: The Global QCI slightly increased from 50.4 in 1990 to 53.1 in 2019. The GDR value was 0.95 in 2019. The high-middle SDI quintile had the highest QCI estimate of 63.0, and the lowest QCI value of 36.9 was regarding the low SDI quintile. Western-Pacific Region and South-East Asia had the highest and lowest QCI among WHO regions, with estimates of 70.7 and 31.2, respectively. The age group of 20 to 24 years old patients reported the lowest QCI estimate of 30.2, and the highest QCI of 59.8 was regarding 40 to 44 years old patients. CONCLUSION: The QCI in BD had only a subtle increase from 1990 to 2019 and is in need of further improvement. Inequalities between different regions and age groups are considerable and require proper attention.