The cross-talk between leptin and circadian rhythm signaling proteins in physiological processes: a systematic review.

BACKGROUND: Today, modern lifestyles and disrupted sleep patterns cause circadian clock rhythm impairments that are associated with altered leptin levels, which subsequently affect a wide range of physiological processes and have significant health burdens on societies. Nevertheless, there has been no systematic review of circadian clock genes and proteins, leptin, and related signaling pathways. METHODS: Accordingly, we systematically reviewed circadian clock proteins, leptin, and molecular mechanisms between them by searching Pubmed, Scopus, ProQuest, Web of Sciences, and Google Scholar until September 2022. After considering the inclusion and exclusion criteria, 20 animal studies were selected. The risk of bias was assessed in each study. RESULTS: The results clarified the reciprocal interconnected relationship between circadian clock genes and leptin. Circadian clock genes regulate leptin expression and signaling via different mechanisms, such as CLOCK-BMAL1 heterodimers, which increase the expression of PPARs. PPARs induce the expression of C/EBPα, a key factor in upregulating leptin expression. CLOCK-BMAL1 also induces the expression of Per1 and Rev-erb genes. PER1 activates mTORC1 and mTORC1 enhances the expression of C/EBPα. In addition, REV-ERBs activate the leptin signaling pathway. Also, leptin controls the expression of circadian clock genes by triggering the AMPK and ERK/MAPK signaling pathways, which regulate the activity of PPARs. Moreover, the roles of these molecular mechanisms are elucidated in different physiological processes and organs. CONCLUSIONS: Crosstalk between circadian clock genes and leptin and their affecting elements should be considered in the selection of new therapeutic targets for related disorders, especially obesity and metabolic impairments.

Unraveling the link between PTBP1 and severe asthma through machine learning and association rule mining method.

Severe asthma is a chronic inflammatory airway disease with great therapeutic challenges. Understanding the genetic and molecular mechanisms of severe asthma may help identify therapeutic strategies for this complex condition. RNA expression data were analyzed using a combination of artificial intelligence methods to identify novel genes related to severe asthma. Through the ANOVA feature selection approach, 100 candidate genes were selected among 54,715 mRNAs in blood samples of patients with severe asthmatic and healthy groups. A deep learning model was used to validate the significance of the candidate genes. The accuracy, F1-score, AUC-ROC, and precision of the 100 genes were 83%, 0.86, 0.89, and 0.9, respectively. To discover hidden associations among selected genes, association rule mining was applied. The top 20 genes including the PTBP1, RAB11FIP3, APH1A, and MYD88 were recognized as the most frequent items among severe asthma association rules. The PTBP1 was found to be the most frequent gene associated with severe asthma among those 20 genes. PTBP1 was the gene most frequently associated with severe asthma among candidate genes. Identification of master genes involved in the initiation and development of asthma can offer novel targets for its diagnosis, prognosis, and targeted-signaling therapy.

Carcinogenic and non-carcinogenic risk of exposure to metal fume in different types of welding processes.

The international agency for cancer research (IARC) has classified welding fumes as definitive carcinogens. The aim of the present study was to assess health risk due to exposure to welding fumes in different welding types. In this study, exposure to fumes of iron (Fe), chromium (Cr), and nickel (Ni) in the breathing zone air of 31 welder engaged in arc, argon and CO2 welding was assessed. Carcinogenic and non-carcinogenic risk assessments due to exposure to fumes were performed using the method proposed by the Environmental Protection Agency (EPA) by Monte Carlo simulation. The results showed that in the CO2 welding, concentration of Ni, Cr, and Fe was lower than the 8-h Time-Weighted Average Threshold Limit Value (TWA-TLV), recommended by the American Conference of Governmental Industrial Hygienists (ACGIH). In argon welding, Cr and Fe concentrations were higher than the TWA-TLV. In arc welding, concentrations of Ni and Fe were more than the TWA-TLV. In addition, the risk of non-carcinogenicity due to exposure to Ni and Fe in all three types of welding was more than standard level (HQ>1). The results indicated that the welders are at health risk due to exposure to metal fumes. Preventive exposure control measures such as local ventilation need to be implemented in welding workplaces.

Micronucleus assay of DNA damage among welders: Effects of welding processes.

Metal fumes, gases, noise, and radiation are hazardous occupational exposures that may be encountered by welders. We have evaluated DNA damage among welders; the buccal micronucleus cytome (BMCyt) assay was used. Thirty-four exposed welders (cases) and an equal number of non-welders (controls) participated in this study. Cell types including basal, early and late differentiated cells with micronucleus (MN), dense chromatin, karyorrhectic, pyknotic, karyolitic, and binucleated cells (NBUD) were measured. Damage levels among, arc, argon, and CO2 welders were statistically significantly higher, compared to the control group. Results showed that mean of MN and NBUDs as indicators of DNA damages among arc, argon and CO2 welding's were significantly higher compared to control group. Also, the mean of DNA damage levels were statistically higher among the arc welders than among the argon or CO2 welders; and levels were higher among the argon welders than the CO2 welders. Preventative measures need to be implemented to reduce exposure to harmful agents during welding.

Male-biased association of endothelial nitric oxide synthase Asp298Glu substitution (NOS3-c.894G/T) with asthma risk and severity.

OBJECTIVE: The nitric-oxide pathway plays a crucial role in the pathogeneses of asthma and NOS3-encoded endothelial nitric oxide synthase is one of the main components of the pathway. Variants of NOS3 are known to contribute to asthma development and pathophysiology. METHODS: We investigated the association of NOS3-c.894G/T (rs1799983) with asthma risk and severity by studying frequencies of its genotypes and alleles in 555 asthmatics (93 intermittent, 240 mild, 158 moderate, and 64 severe asthma cases) and 351 control participants using the PCR-FRLP method, logistic regression analysis and generalized ordered logit estimates. RESULTS: GT genotype (ORadj: 1.39; CI: 1.04-1.85; p = 0.026), dominant model GT + TT (ORadj: 1.41; CI: 1.07-1.87; p = 0.015), and T allele (ORadj: 1.32; CI: 1.05-1.67; p = 0.018) was associated with increased ORs in asthmatics. Also, the frequency of GT + TT (ORadj: 1.55; CI: 1.01-2.38; p = 0.044) was significantly higher in males. Furthermore, GT genotype (ORadj: 1.39; CI: 1.04-1.85; p = 0.024), GT + TT (ORadj: 1.42; CI: 1.07-1.87; p = 0.014), and T allele (ORadj: 1.32; CI: 1.05-1.66; p = 0.018) in total population and GT + TT (ORadj: 1.56; CI: 1.02-2.37; p = 0.04) in males were significantly associated with increased risk of severe, moderate, mild, intermittent asthma vs. controls. Also, GT genotype (ORadj: 1.39; CI: 1.02-1.91; p = 0.039) was significantly more frequent in severe, moderate grades vs. lower severity grades in the total population. Frequencies of GT genotype (ORadj: 1.77; CI: 1.05-3.00; p = 0.032) and GT + TT (ORadj: 1.74; CI: 1.04-2.90; p = 0.036) in total population and GT genotype (ORadj: 2.40; CI: 1.16-4.97; p = 0.018) and GT + TT (ORadj: 2.30; CI: 1.12-4.74; p = 0.023) in male subpopulation were significantly higher in severe cases compared to lower grades. CONCLUSIONS: NOS3-c.894G/T may be associated with asthma risk and its severer grades, with greater effects in men.

Sex-specific association of exposure to air pollutants and Nrf2 gene expression and inflammatory biomarkers in exhaled breath of healthy adolescents.

Studies investigating the nuclear factor erythroid 2-related factor 2 (Nrf2) expression levels in the respiratory system of healthy subjects are scarce. Moreover, separate studies on the health-related outcomes of air pollution for each sex are limited. The current panel study investigated sex-specific Nrf2 expression levels and related oxidative stress and inflammatory responses among healthy adolescents exposed to PM2.5, PM10, O3, and PM2.5-bounded metals in a high traffic region. Forty-nine healthy nonsmoking subjects participated in the study for five consecutive months (Nov. 2019 to Feb. 2020). Each subject was asked to provide 1 mL of exhaled breath condensate (EBC). Data were analyzed using linear mixed-effects models. The results showed that PM10, PM2.5, O3, and PM2.5-bounded metals were negatively linked to Nrf2 expression level in EBC of females with -58.3% (95% CI: 79.5, -15.4), -32.1% (95% CI: -50.3, -7.1), -76.2% (95% CI: -92.6, -23.9), and -1.9 (95% CI: -3.4, -0.4), respectively. While our results presented no significant association between the studied pollutants and Nrf2 gene expression in males, significant associations were observed between the pollutants and total nitric oxide (NOx), interleukins 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in the EBC of females. In the case of males, only EBC cytokines showed a significant association with air pollutants. Overall, this study suggests that exposure to ambient air pollutants may affect the respiratory system with biologically different mechanisms in males and females. PM2.5 concentration had a positive correlation with exhaled TNF-α and IL6 values in females while positive correlation with TNF-α and negative correlation with IL6 values in males. O3 had a negative correlation with TNF-α in males.

Economic Burden of Asthma in Northwest Iran.

Background: The economic burden of asthma is a major public health concern. This study estimates the economic burden of asthma in Northwest of Iran. Methods: A longitudinal study was conducted between 2017 and 2018 in Tabriz (Iran) using the Persian version of the Work Productivity and Activity Impairment (WPAI) questionnaire. Direct and indirect costs associated with asthma were estimated based on the societal perspective, prevalence-based approach, and bottom-up method. Annual indirect costs were estimated using the human capital (HC) method. The structural equation model was used to evaluate the relationship between costs, sex, and asthma severity. Results: A total of 621 patients with asthma were enrolled in the study. Significant differences were found between female and male patients for the mean cost of radiology (P=0.006), laboratory (P=0.028), and diagnostic (P=0.017) tests at baseline, and for laboratory (P=0.012), and diagnostic (P=0.027) tests at one-year follow-up. The more severe asthma, the more significant the costs for annual physician office visits (P=0.040) and medications (P=0.013). As asthma severity increased, significantly higher expenditures were observed in women for days lost from work at baseline (P=0.009) and one-year follow-up (P=0.001), and in men for productivity loss at work due to impairment at baseline (P=0.045). A significant association between indirect costs and the cost of impairment-related lost productivity at work (ß=3.29, P<0.001), and between severe asthma and indirect costs (ß=32.36, P<0.001) was observed. Conclusion: High costs are incurred by Iranian asthma patients, especially because of impairment-related productivity loss at work associated with asthma exacerbation.

Single-Center Experience of Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension: The Results from the Tabriz University Medical Sciences (TUMS) CTEPH Program.

INTRODUCTION: Pulmonary endarterectomy (PEA) remains the preferred and potentially curative option for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to report the results of PEA for CTEPH in a tertiary center in Tabriz, Iran. METHODS: We analyzed the results of 42 CTEPH patients undergoing PEA, who were enrolled in the Tabriz University of Medical Sciences (TUMS-CTEPH) from January 2016 to October 2020. The main outcome measures included the New York Heart Association (NYHA) functional classification, the 6-Minute Walk Distance, hemodynamic measures in right heart catheterization, morbidity, and mortality. RESULTS: There was a significant improvement in the NYHA function class (2.6 ± 0.5 vs 1.1 ± 0.34), mean pulmonary arterial pressure (47.1 ± 13 vs 27.9 ± 8 mm Hg), cardiac output (4.3 ± 1.06 vs 5.9 ± 1.2 L/min), and pulmonary vascular resistance (709.4 ± 297.5 vs 214 ± 77 dyn s/cm5). Fifteen patients (35%) developed complications. The most common complication (10 [23%]) was reperfusion injury. Also, postsurgical mortality was 4% during hospital admission and 1-year follow-up. CONCLUSION: This is the first single-center report of PEA from Iran. Post-PEA and 1-year survival were acceptable as a referral center. PEA can be performed safe with low mortality. Greater awareness of PEA and patients' access to experienced CTEPH centers are important issues.

Female-biased association of NOS2-c.1823C>T (rs2297518) with co-susceptibility to metabolic syndrome and asthma.

The nitric oxide (NO) pathway contributes to the pathogeneses of metabolic syndrome (MetS) and asthma. NOS2 encodes inducible-NO synthase, which is an important enzyme of the pathway, and its variations could affect the risk of asthma and MetS and thereby co-susceptibility to them. This study aims to estimate the association of NOS2-c.1823C>T with risk of asthma, MetS, and asthma with MetS condition (ASMetS), and with asthma stages: intermittent, mild, moderate, and severe asthma. The study included asthmatics (n = 555), MetS (n = 334), and ASMetS cases (n = 232) and 351 controls, which were genotyped by the PCR-RFLP method. The T allele was significantly associated with an increased risk of asthma and MetS in the sample population and females. CT genotype and CT+TT model were significantly associated with increased risk of ASMetS in females. A significant association between CT genotype and increased risk of ASMetS in the sample population and females was found in ASMetS versus MetS. In the sample population and among females, the T allele was significantly associated with severe asthma. The rs2297518 single nucleotide polymorphism of NOS2 contributes to the risk of MetS, asthma, and co-susceptibility to them, and this contribution may be stronger in females compared to males.

The effect of Fingolimod on patients with moderate to severe COVID-19.

Hyper-inflammation, cytokine storm, and recruitment of immune cells lead to uncontrollable endothelial cell damage in patients with coronavirus disease 2019 (COVID-19). Sphingosine 1-phosphate (S1P) signaling is needed for endothelial integrity and its decreased serum level is a predictor of clinical severity in COVID-19. In this clinical trial, the effect of Fingolimod, an agonist of S1P, was evaluated on patients with COVID-19. Forty patients with moderate to severe COVID-19 were enrolled and divided into two groups including (1) the control group (n = 21) receiving the national standard regimen for COVID-19 patients and (2) the intervention group (n = 19) that prescribed daily Fingolimod (0.5 mg) for 3 days besides receiving the standard national regimen for COVID-19. The hospitalization period, re-admission rate, intensive care unit (ICU) administration, need for mechanical ventilation, and mortality rate were assessed as primary outcomes in both groups. The results showed that re-admission was significantly decreased in COVID-19 patients who received Fingolimod compared to the controls (p = .04). In addition, the hemoglobin levels of the COVID-19 patients in the intervention group were increased compared to the controls (p = .018). However, no significant differences were found regarding the intubation or mortality rate between the groups (p > .05). Fingolimod could significantly reduce the re-admission rate after hospitalization with COVID-19. Fingolimod may not enhance patients' outcomes with moderate COVID-19. It is necessary to examine these findings in a larger cohort of patients with severe to critical COVID-19.

Burden of chronic obstructive pulmonary disease and its attributable risk factors in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019.

OBJECTIVE: To report the global, regional, and national burden of chronic obstructive pulmonary disease (COPD) and its attributable risk factors between 1990 and 2019, by age, sex, and sociodemographic index. DESIGN: Systematic analysis. DATA SOURCE: Global Burden of Disease Study 2019. MAIN OUTCOME MEASURES: Data on the prevalence, deaths, and disability adjusted life years (DALYs) of COPD, and its attributable risk factors, were retrieved from the Global Burden of Disease 2019 project for 204 countries and territories, between 1990 and 2019. The counts and rates per 100 000 population, along with 95% uncertainty intervals, were presented for each estimate. RESULTS: In 2019, 212.3 million prevalent cases of COPD were reported globally, with COPD accounting for 3.3 million deaths and 74.4 million DALYs. The global age standardised point prevalence, death, and DALY rates for COPD were 2638.2 (95% uncertainty intervals 2492.2 to 2796.1), 42.5 (37.6 to 46.3), and 926.1 (848.8 to 997.7) per 100 000 population, which were 8.7%, 41.7%, and 39.8% lower than in 1990, respectively. In 2019, Denmark (4299.5), Myanmar (3963.7), and Belgium (3927.7) had the highest age standardised point prevalence of COPD. Egypt (62.0%), Georgia (54.9%), and Nicaragua (51.6%) showed the largest increases in age standardised point prevalence across the study period. In 2019, Nepal (182.5) and Japan (7.4) had the highest and lowest age standardised death rates per 100 000, respectively, and Nepal (3318.4) and Barbados (177.7) had the highest and lowest age standardised DALY rates per 100 000, respectively. In men, the global DALY rate of COPD increased up to age 85-89 years and then decreased with advancing age, whereas for women the rate increased up to the oldest age group (≥95 years). Regionally, an overall reversed V shaped association was found between sociodemographic index and the age standardised DALY rate of COPD. Factors contributing most to the DALYs rates for COPD were smoking (46.0%), pollution from ambient particulate matter (20.7%), and occupational exposure to particulate matter, gases, and fumes (15.6%). CONCLUSIONS: Despite the decreasing burden of COPD, this disease remains a major public health problem, especially in countries with a low sociodemographic index. Preventive programmes should focus on smoking cessation, improving air quality, and reducing occupational exposures to further reduce the burden of COPD.

Status of TNF-α and IL-6 as pro-inflammatory cytokines in exhaled breath condensate of late adolescents with asthma and healthy in the dust storm and non-dust storm conditions.

Exposure to airborne particulate matter (PM) can be considered as an important risk factor for human health. Some cytokines have been recognized as the biomarkers of exposure to air pollution. Experimental studies indicate that PM exposure could be associated with inflammation. Thus, the purpose of this study was to evaluate whether the exposure to air PM is associated with biomarkers of inflammation. The specific aim of this study was to determine the correlation between airborne PM levels and IL-6 and TNF-α as airway inflammation biomarkers among two groups of late adolescents in northwest of Iran. This study included 46 subjects, comprising 23 asthmatic subjects and 23 non-asthmatic persons. Environmental PM (PM10, PM2.5 and PM1) levels were measured in dust storm and non-dust storm days during both cold and warm seasons. Following the sampling of PM, Two pro-inflammatory cytokines of IL-6 and TNF-α in exhaled breath condensate (EBC) were also determined in the EBC samples via commercial ELISA kits. Daily mean ambient air PM10, PM2.5 and PM1 concentrations during the dust storm days was 221.79, 93.13 and 25.52 µg m-3 and in non-dusty days 48.37, 18.54 and 6.1 µg m-3, respectively. Biomarkers levels were significantly (p < 0.001) higher in asthmatic students compared to the non-asthmatic subjects. EBC cytokines levels were increased in dust storm days compared to the non-dusty days (p < 0.001) and were positively correlated with different size of ambient PM concentration. Dust storm conditions can increase the pro-inflammatory cytokines and cause adverse effects on pulmonary health and lung tissue damage.

Global burden of lower respiratory infections during the last three decades.

Background: Lower respiratory infections (LRIs) cause a substantial mortality, morbidity and economic burden. The present study reported the global, regional and national burden of LRIs and their attributable risk factors in 204 countries and territories, between 1990 and 2019, by age, sex, etiology, and Socio-demographic Index (SDI). Methods: Using publicly available data from the Global Burden of Disease (GBD) study 2019, we reported the incidence, deaths and disability-adjusted life-years (DALYs), due to LRIs. Estimates were presented as counts and age-standardized rates per 100,000 population with their associated uncertainty intervals (UIs). Results: Globally, in 2019 there were 488.9 million (95% UI: 457.6 to 522.6) incident cases and 2.4 million (2.3-2.7) deaths due to LRIs. The global age-standardized incidence and death rates for LRIs were 6,295 (5,887.4-6,737.3) and 34.3 (31.1-37.9) per 100,000 in 2019, which represents a 23.9% (22.5-25.4) and 48.5% (42.9-54.0) decrease, respectively since 1990. In 2019, Guinea [12,390.4 (11,495.5-13,332.8)], Chad [12,208.1 (11,289.3-13,202.5)] and India [11,862.1 (11,087.0-12,749.0)] had the three highest age-standardized incidence rates of LRI. Equatorial Guinea [-52.7% (95% UI: -55.8 to -49.3)], Chile [-50.2% (95% UI: -53.4 to -47.0)] and Albania [-48.6% (95% UI: -51.7 to -45.3)] showed the largest decreases from 1990 to 2019. In 2019, a decrease in the incidence rate of LRI was observed at the global level up to the 25-29 age group, then the incidence rates increased with age. The burden of LRIs decreased with increasing SDI at both the regional and national levels. Globally, child wasting (33.1%), household air pollution from solid fuels (24.9%) and a lack of access to handwashing facilities (14.4%) made the largest contributions to the LRI burden in 2019. Conclusions: Although the burden of LRIs decreased over the period 1990-2019, LRIs still contribute to a large number of incident cases, deaths and DALYs. Preventative programs with a focus on reducing exposure to attributable risk factors should be implemented, especially in less developed countries.

Pattern of drug resistant Mycobacterium tuberculosis in the west and northwest of Iran: a meta-analysis.

Background and Objectives: Drug-resistant tuberculosis (Tb) is a major public health issue across the world. Therefore, it is crucial to determine its pattern in different regions of the world. The aim of this study was to review the prevalence of drug resistant TB in the west and northwest of Iran. Materials and Methods: A systematic literature search was performed to identify studies (2010 to 2021) in Google Scholar, PubMed, Thomson Reuters, Scientific Information Database (SID), Cochrane Library, and Medical Library (MedLib) databases. The patterns of any drug-resistant Mycobacterium tuberculosis (MTB); resistance to isoniazid (INH), rifampicin (RMP), streptomycin (SMP), ethambutol (EMB), and multiple drug resistance (MDR) were reviewed in tuberculosis in the west and northwest of Iran. Results: In this review, 7 studies met the eligibility criteria for a meta-analysis. The pooled proportion of any drug resistant TB was 13% (CI 95%: 9.0, 17.0) (43.0% in re-treatment group). The pooled prevalence of any drug resistant TB was more than 1.5 times higher in men compared to women (15% vs. 9.0%). The pooled prevalence (%) of resistance to INH, RMP, SMP, EMB and MDR-TB was 11.0%, 12.0%, 13.0%, 6.0%, and 6.0%, respectively. Kermanshah Province (a province in the west of Iran) showed a high prevalence of any type of drug resistance and MDR-TB (15.9% and 20.0%, respectively). Conclusion: It seems that the western provinces of Iran have a different pattern of drug resistance compared to the northwestern provinces. Considering the extent of Iran and the neighboring countries, it is recommended that the pattern of tuberculosis drug resistance be reviewed separately in different provinces or regions of Iran. Drug resistance in the re-treatment group was more than three times that of all patients with TB drug resistance. The burden of drug resistance reduces significantly with better control and management of TB drug treatment and preventing re-infection.

The early start of hemoperfusion decreases the mortality rate among severe COVID-19 patients: A preliminary study.

BACKGROUND: Coronavirus disease-2019 (COVID-19)-related organ failure is partly related to a sepsis-like syndrome and extreme pro-inflammatory cytokine release, named cytokine storm. Therapeutic strategies that prevent the production of or remove the pro-inflammatory cytokines could potentially be an effective therapy in critically afflicted COVID-19 patients. METHODS: In this clinical trial study, from April until June 2020, 68 COVID-19 patients (35 vs. 33 controls) with severe critical symptoms, and PaO2 /FiO2 (P/F) ratio less than 200 mmHg either received a single standard therapy or a combination of standard treatment for COVID-19 combined with hemoperfusion (hemofilter, HA330 D Javfron) for 4 h, in 3 consecutive days. The length of hospital stay and mechanical ventilation, the resolution of radiologic abnormalities, and the mortality rate were defined as the primary outcomes. RESULTS: Demographic characteristics, the acute physiology, and chronic health evaluation score of both groups were similar (p > 0.05). Importantly, we noticed a significant mortality rate reduction in the perfused group compared with controls (37.1% vs. 63.6%, p = 0.02), this positive effect was stronger among those with a P/F ratio higher than 75 (mortality rate of 84.7% for P/F ratio < 75 vs. 15.4% for P/F ratio ≥ 75, p = 0.02). CONCLUSIONS: The results imply that early start of hemoperfusion could be more effective and significantly reduce the mortality rate among COVID-19 patients with critical diseases.

Prevalence, Deaths, and Disability-Adjusted Life-Years Due to Asthma and Its Attributable Risk Factors in 204 Countries and Territories, 1990-2019.

BACKGROUND: Understanding global trends in the point prevalence, deaths, and disability-adjusted life-years (DALYs) for asthma will facilitate evidence-based decision-making. RESEARCH QUESTION: What are the global, regional, and national burdens of asthma in 204 countries and territories between 1990 and 2019 by age, sex, and sociodemographic index (SDI)? STUDY DESIGN AND METHODS: Publicly available data from the Global Burden of Disease study from 1990 through 2019 were used. All estimates were presented as counts and age-standardized rates per 100,000, along with their associated uncertainty intervals. RESULTS: In 2019, the global age-standardized point prevalence and death rates for asthma were 3,415.5 and 5.8 per 100,000, which represent a 24% and 51.3% decrease since 1990, respectively. Moreover, in 2019, the global age-standardized DALY rate was 273.6 and the global point prevalence of asthma was highest in the group 5 to 9 years of age. Also in 2019, the United States (10,399.3) showed the highest age-standardized point prevalence rate of asthma. Generally, the burden of asthma decreased with increasing SDI. Globally, high BMI (16.9%), smoking (9.9%), and occupational asthmagens (8.8%) contributed to the 2019 asthma DALYs. INTERPRETATION: Asthma remains an important public health issue, particularly in regions with low socioeconomic development. Future research is needed to examine thoroughly the associations asthma has with its risk factors and the factors impeding optimal self-management. Further research also is needed to understand and implement better the interventions that have reduced the burden of asthma.

Potency of BNT162b2 and mRNA-1273 vaccine-induced neutralizing antibodies against severe acute respiratory syndrome-CoV-2 variants of concern: A systematic review of in vitro studies.

BNT162b2 and mRNA-1273 are two types of mRNA-based vaccine platforms that have received emergency use authorization. The emergence of novel severe acute respiratory syndrome (SARS-CoV-2) variants has raised concerns of reduced sensitivity to neutralization by their elicited antibodies. We aimed to systematically review the most recent in vitro studies evaluating the effectiveness of BNT162b2 and mRNA-1273 induced neutralizing antibodies against SARS-CoV-2 variants of concern. We searched PubMed, Scopus, and Web of Science in addition to bioRxiv and medRxiv with terms including 'SARS-CoV-2', 'BNT162b2', 'mRNA-1273', and 'neutralizing antibody' up to June 29, 2021. A modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist was used for assessing included study quality. A total 36 in vitro studies meeting the eligibility criteria were included in this systematic review. B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) are four SARS-CoV-2 variants that have recently been identified as variants of concern. Included studies implemented different methods regarding pseudovirus or live virus neutralization assays for measuring neutralization titres against utilized viruses. After two dose vaccination by BNT162b2 or mRNA-1273, the B.1.351 variant had the least sensitivity to neutralizing antibodies, while B.1.1.7 variant had the most sensitivity; that is, it was better neutralized relative to the comparator strain. P.1 and B.1.617.2 variants had an intermediate level of impaired naturalization activity of antibodies elicited by prior vaccination. Our review suggests that immune sera derived from vaccinated individuals might show reduced protection of individuals immunized with mRNA vaccines against more recent SARS-CoV-2 variants of concern.