HPV16 E7-CT (gp96) fusion protein: Molecular cloning, expression and purification of a recombinant 6xHis-tagged protein in E. coli

The development of a therapeutic vaccine against human papillomavirus (HPV) is important for the control of cervical cancer. E7 is the major transforming protein produced in cervical cancers, and therefore represents potential tumor-specific antigen that could be the target of immunotherapy for cervical cancer. Among different vaccine strategies, protein-based vaccines are capable of generating CD8+ T cell responses in vaccinated animals and humans. Recently, development of novel strategies that enhance protein vaccine potency is important for generation of effective cancer vaccines and immunotherapies. Heat shock proteins (HSPs) including Gp96 have been shown to act as potent immuno-adjuvant to enhance antigen-specific tumor immunity. Therefore, the HSP-based protein vaccines can be administered by fusing antigens to HSPs, in vitro. It has been known that the HSP fragments (e.g., N-/or C-terminal regions) as mini-chaperones are better choice for immunization. The most straightforward method to produce large amounts of recombinant protein suitable for a vaccine is to clone the gene into a prokaryotic expression vector and produce the protein in Escherichia coli. In current study, we describe cloning of the HPV16 E7 gene linked to C-terminal fragment of gp96, identification and purification of the resultant E7-CT (gp96) fusion protein for next usage as a potential vaccine candidate protein against HPV in a pre-clinical trial. The recombinant E7-CT (gp96) migrated as a 51 kDa protein in SDS-PAGE. In Western blot experiment, the existence of a 51 kDa band for rE7-CT (gp96) was confirmed by rabbit anti-His as well as mouse anti-HPV16 E7 monoclonal antibodies. The protein of interest was both in the insoluble and the soluble fraction; therefore, purification was performed under denaturating and native conditions by affinity chromatography on Ni-NTA resin using 6xHis-tag

Spatial-time analysis of cardiovascular emergency medical requests: enlightening policy and practice

Background: Response time to cardiovascular emergency medical requests is an important indicator in reducing cardiovascular disease (CVD) -related mortality. This study aimed to visualize the spatial-time distribution of response time, scene time, and call-to-hospital time of these emergency requests. We also identified patterns of clusters of CVD-related calls. Methods: This cross-sectional study was conducted in Mashhad, north-eastern Iran, between August 2017 and December 2019. The response time to every CVD-related emergency medical request call was computed using spatial and classical statistical analyses. The Anselin Local Moran's I was performed to identify potential clusters in the patterns of CVD-related calls, response time, call-to-hospital arrival time, and scene-to-hospital arrival time at small area level (neighborhood level) in Mashhad, Iran. Results: There were 84,239 CVD-related emergency request calls, 61.64% of which resulted in the transport of patients to clinical centers by EMS, while 2.62% of callers (a total of 2218 persons) died before EMS arrival. The number of CVD-related emergency calls increased by almost 7% between 2017 and 2018, and by 19% between 2017 and 2019. The peak time for calls was between 9 p.m. and 1 a.m., and the lowest number of calls were recorded between 3 a.m. and 9 a.m. Saturday was the busiest day of the week in terms of call volume. There were statistically significant clusters in the pattern of CVD-related calls in the south-eastern region of Mashhad. Further, we found a large spatial variation in scene-to-hospital arrival time and call-to-hospital arrival time in the area under study. Conclusion: The use of geographical information systems and spatial analyses in modelling and quantifying EMS response time provides a new vein of knowledge for decision makers in emergency services management. Spatial as well as temporal clustering of EMS calls were present in the study area. The reasons for clustering of unfavorable time indices for EMS response requires further exploration. This approach enables policymakers to design tailored interventions to improve response time and reduce CVD-related mortality.This study was financially sponsored by Mashhad University of Medical Sciences (Project grant: 980861)

Association between heavy metals and colon cancer: an ecological study based on geographical information systems in North-Eastern Iran

Background: Colorectal cancer has increased in Middle Eastern countries and exposure to environmental pollutants such as heavy metals has been implicated. However, data linking them to this disease are generally lacking. This study aimed to explore the spatial pattern of age-standardized incidence rate (ASR) of colon cancer and its potential association with the exposure level of the amount of heavy metals existing in rice produced in north-eastern Iran. Methods: Cancer data were drawn from the Iranian population-based cancer registry of Golestan Province, northeastern Iran. Samples of 69 rice milling factories were analysed for the concentration levels of cadmium, nickel, cobalt, copper, selenium, lead and zinc. The inverse distance weighting (IDW) algorithm was used to interpolate the concentration of this kind of heavy metals on the surface of the study area. Exploratory regression analysis was conducted to build ordinary least squares (OLS) models including every possible combination of the candidate explanatory variables and chose the most useful ones to show the association between heavy metals and the ASR of colon cancer. Results: The highest concentrations of heavy metals were found in the central part of the province and particularly counties with higher amount of cobalt were shown to be associated with higher ASR of men with colon cancer. In contrast, selenium concentrations were higher in areas with lower ASR of colon cancer in men. A significant regression equation for men with colon cancer was found (F(4,137) = 38.304, P < .000) with an adjusted R2 of 0.77. The predicted ASR of men colon cancer was − 58.36 with the coefficients for cobalt = 120.33; cadmium = 80.60; selenium = − 6.07; nickel = − 3.09; and zinc = − 0.41. The association of copper and lead with colon cancer in men was not significant. We did not find a significant outcome for colon cancer in women. Conclusion: Increased amounts of heavy metals in consumed rice may impact colon cancer incidence, both positively and negatively. While there were indications of an association between high cobalt concentrations and an increased risk for colon cancer, we found that high selenium concentrations might instead decrease the risk. Further investigations are needed to clarify if there are ecological or other reasons for these discrepancies. Regular monitoring of the amount of heavy metals in consumed rice is recommended.This study was supported by Golestan University of Medical Sciences (grant number of 90–10–1-30209)

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

The relationship of resilience and social support with post-traumatic growth: The mediating role of emotion regulation strategies

The current research design was descriptive-correlation research. The statistical population of the research includes all the children of the witness families living in the border provinces of Iraq, which was selected based on Morgan's table, a sample of 250 people was available. The data were collected using the social support scale, flexibility of emotion regulation strategies and post-traumatic growth scale and were tested and analyzed using the Pearson correlation method and structural equation model in SPSS24 and AMOS24 software. The results showed, there was a direct and significant relationship between social support and resilience with post-traumatic growth. Also, emotion regulation strategies indirectly mediated the effects of resilience and social support on post-traumatic growth. It is suggested to pay attention to resilience training, emotion regulation and support for people who have experienced trauma

The relationship of resilience and social support with post-traumatic growth: The mediating role of emotion regulation strategies

The current research design was descriptive-correlation research. The statistical population of the research includes all the children of the witness families living in the border provinces of Iraq, which was selected based on Morgan's table, a sample of 250 people was available. The data were collected using the social support scale, flexibility of emotion regulation strategies and post-traumatic growth scale and were tested and analyzed using the Pearson correlation method and structural equation model in SPSS24 and AMOS24 software. The results showed, there was a direct and significant relationship between social support and resilience with post-traumatic growth. Also, emotion regulation strategies indirectly mediated the effects of resilience and social support on post-traumatic growth. It is suggested to pay attention to resilience training, emotion regulation and support for people who have experienced trauma

Application of montmorillonite/octadecylamine nanoparticles in the removal of textile dye from aqueous solutions: Modeling, kinetic, and equilibrium studies

In the study, the proliferation of industries has been associated with an increase in the production of industrial wastewater and subsequent environmental pollution, wherein dyes emerge as prominent pollutants. The characteristics of nanoclay modified with octadecylamine, were elucidated throughvarious techniques, including Field Emission Scanning Electron Microscopy/Energy Dispersive Spectroscopy (FE-SEM/EDS), Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), X-ray Diffraction (XRD), and Brunauer-Emmett-Teller Surface Area Analysis (BET). The research delved into the impact of variables such as pH, initial dye concentration, adsorbent dose, temperature, and ultrasonication time on the removal of Acid Black 1 (AB1) through an ultrasonic process, employing a central composite design (CCD). Optimal conditions for the adsorption process were determined: pH at 5.46, adsorbent mass at 4 mg/30 mL, initial dye concentration at 20 mg/L, ultrasound time at 20 min, and temperature at 50 °C, resulting in a remarkable 96.49% adsorption efficiency. The fitting of experimental equilibrium data to different isotherm models, including Langmuir, Freundlich, and Temkin, indicated thatthe Freundlich model was the most suitable. Analysis of the adsorption data with various kinetic models such as pseudo-first and second-order models, and intraparticle diffusion models, revealed the applicability of the second-order equation model. A thermodynamic study unveiled that the adsorption process was spontaneous and endothermic. In conclusion, the study highlights the significant capability ofmontmorillonite nanoclay modified with octadecylamine in removing AB1 dye, rendering it a viable option for wastewater treatment

The association between the preservative agents in foods and the risk of breast cancer

In the etiology of breast malignancy, dietary habits and lifestyle-related risk factors in the coherence of cancer prevention guidelines, e.g., WCRF/AICR is well documented. In addition, the consumption of staple food products rich in carbohydrate as major calorie resources such as potato, bread, and ready-to-eat cereals are partly object to having roles in breast tumorigenesis. In this review, the possible associations of preservatives and nutritive risk factors of staple foods in dietary patterns with breast cancer development based on the experimental and observational cohort-based studies were discussed. In this regard, the influence kinetics of insulin, insulin-like growth factor-1, and insulin-activated AMPK/Akt pathway on sorts of starch and protein is a concerning biologic concept in promoting the risk of tumorigenesis. Hence, Akt-dependent controlled proliferation, induced apoptosis, and controlled oxidative stress in specific condition could be concentrated as the preventive strategies. Although preservatives such as sorbate, benzoate, and nitrate are considered Generally Recognized as Safe, there are some issues concerning the safety of their applications, including the possibility of allergies and immunosuppressive effects from benzoate, the formation of carcinogenic nitrosamines from nitrites, and interaction sorbate with nitrite in the stomach which consequently can be resulted in the production of a series of genotoxic compounds7181229124