Izražajnost kalretinina kao biomarkera rizika za metastatski karcinom mliječne žlijezde u pasa

Malignant breast tumors are the most common tumors in humans and are associated with a poor prognosis. An accurate animal model of human mammary gland tumorigenesis is needed to test novel diagnosis and treatment strategies. Dogs represent a promising model since they develop such tumors spontaneously. In the present study, three immunomarkers, including calretinin, c-Kit (CD117) and placental alkaline phosphatase (Plap), were used and compared with each other, in relation to estrogen and progesterone receptors and HER2 (triple markers), with the intention of malignancy grading. Enhanced expression of calretinin and placental alkaline phosphatase, without immunoreaction to c-Kit in neoplastic cells, is related to high-grade malignancy. Out of 50 tumors, 31 were metastasized, 29 of which (93.5%) were moderately to strongly calretinin positive (P<0.05). However, the results for c-Kit - and Plap+ in metastatic tumors were not reproducible. It may be concluded that calretinin could be introduced as a determinant biomarker in the diagnosis of breast cancer metastasis.Maligni tumori dojke najčešći su tumori u ljudi i povezani su s lošom prognozom. Da bi se testirali novi dijagnostički postupci i terapijske procedure u ljudi, potreban je prikladan životinjski model tumorogeneze mliječne žlijezde. Psi su potencijalno dobar model zbog spontanog razvoja ovakvih tumora. U ovom su istraživanju, s ciljem stupnjevanja malignosti, međusobno uspoređena tri imunomarkera, kalretinin, c-Kit (CD117) i placentalna alkalna fosfataza (Plap), a zatim su isti uspoređeni i s estrogenskim, progesteronskim te HER2 (trostrukim) markerima. Povećanje izražajnosti kalretinina i placentalne alkalne fosfataze, bez imunoreakcije na c-Kit u neoplastičnim stanicama povezano je s visokim stupnjem malignosti. Od 50 tumora, 31 je metastazirao, od kojih je 29 (93,5 %) bilo umjereno do izrazito pozitivno na kalretinin (P < 0,05). Doduše, rezultati za c-Ki ti Plap+ nisu bili ponovljivi. Zaključujemo da bi kalretinin mogao poslužiti kao biomarker u dijagnostici metatstatskog raka dojke

Analysis of Factors Affecting Management Behavior of Rural Wheat Producers towards Pesticide Waste in Qorveh County

Unhygienic disposal of pesticide waste after use on the farm has very dangerous consequences for the environment and agriculture. The purpose of the study was to analysis of factors affecting management behavior of rural wheat producers towards pesticide waste in Qorveh County. Statistical population of the research consisted of irrigated wheat producers (N= 1700). Sample size was determined 170 using the Cochran formula. Cases were selected through random proportional stratified sampling. The main research tool was a researcher-made questionnaire whose validity was confirmed by experts and its reliability was confirmed by citing Cronbach's alpha, CR and AVE coefficients. The findings of the structural equation model showed that there was a positive and significant relationship between farmers' knowledge and information resources and their attitudes toward the use of chemical pesticides. Besides, knowledge and attitude variables were able to explain 71% of the changes in wheat farmers' managerial behavior towards pesticide wastes

Expression, purification and DNA-binding properties of zinc finger domains of DOF proteins from Arabidopsis thaliana

Introduction: DOF proteins are a family of plant-specific transcription factors with a conserved zinc finger (ZF) DNA-binding domain. Although several studies have demonstrated their specific DNA binding, quantitative affinity data is not available for the binding of DOF domains to their binding sites. Methods: ZF domains of DOF2.1, DOF3.4, and DOF5.8 from Arabidopsis thaliana were expressed and purified. Their DNA binding affinities were assessed using gel retardation assays and microscale thermophoresis with two different oligonucleotide probes containing one and two copies of recognition sequence AAAG. Results: DOF zinc finger domains (DOF-ZFs) were shown to form independently folded structures. Assessments using microscale thermophoresis demonstrated that DOF-ZFs interact more tightly (~ 100 fold) with double-motif probe than the single-motif probe. The overall Kd values for the DOF3.4-ZF and DOF5.8-ZF to the double-motif probe were ~2.3±1 and 2.5±1 µM, respectively. Conclusion: Studied DOF-ZF domains formed stable complexes with the double-motif probe. Although DOF3.4-ZF and DOF5.8-ZF do not dimerize with an appreciable affinity in the absence of DNA (judging from size-exclusion and multiangle laser light scattering data), it is possible that these ZFs form protein-protein contacts when bound to this oligonucleotide, consistent with previous reports that DOF proteins can homo- and hetero-dimerize

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

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

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

Factors Affecting Attitude of the Greenhouse Owner towards Sustainable Agriculture in Alborz province

The attitude of greenhouse owner as the basis of agricultural production towards sustainable agriculture could be grounds for increasing the sustainability of this type of cultivation system. Therefore, the main purpose of this study is to investigate the factors affecting the attitude of greenhouse owners towards sustainability in the Alborz province. The target population for this study consisted of all active greenhouse owners in the Alborz province (N=366). The sample size was determined by using Cochran’s formula (n=155) and using the proportional stratified random sampling method. The validity was confirmed by a panel of experts and its reliability was established by Cronbach's Alpha coefficient (0.85). The results showed that the attitude of 41 percent of the respondents towards sustainability was positive. Also, there were significant differences between the attitudes of the respondents in the group with related education and unrelated education group. Correlation analysis showed that the there is a positive relation between attitude towards searching behavior and the use of communication channels. In addition, the results of multiple regression analysis indicated that about 40 percent of the attitudes of greenhouse owner towards sustainable agriculture are explained by 4 variables. The result of this study indicate that by using different means of providing information and training, we can change the attitudes of greenhouse owners and lead them to produce more sustainable and healthy product

Determinants of Safety and Health Behaviors of Wheat Farmers towards the Use of Chemical Pesticides in Qorveh County

The poisoning of farm workers with pesticides is a common job hazard caused by the application of pesticides, especially in developing countries. Agriculture is directly related to the environment including water resources, and farming behaviors can entail a plethora of positive or negative effects on these vital resources. So, the present study aimed to explore the safety and health behaviors of wheat farmers towards the use of chemical pesticides in Qorveh County in Kurdistan province, Iran. The statistical population of this applied research consisted of all irrigated wheat farmers in the 2019‐2020 crop year (N = 1700) in Qorveh County. The sample size was determined to be 170 people by Cochran’s formula, and the random multistage technique was adopted for data collection. The main research instrument was a questionnaire whose content validity was checked by a panel of experts and the average variance extracted (AVE) index. Also, its reliability was estimated by Cronbach’s alpha and the Cumulative Reliability (CR) coefficient. The results of the structural equation modeling (SEM) showed that the variables of the information source, attitude, and knowledge of chemical pesticide application accounted for 79 percent of the variance in the factors affecting the safety and health behaviors of wheat farmers as to the application of these pesticides. Considering the significant relationship that information source, attitude, and knowledge have with safety and health behaviors, it is recommended to hold training courses to familiarize wheat farmers with the hazards of conventional farming practices and the benefits of IPM practices by the organizations in charge, e.g. Agricultural Jihad Organization. This will foster a positive attitude among the farmers to adopt safety and healthy behaviors

Circulating Thyroid Hormones and Indices of Energy and Lipid Metabolism in Normal and Hormonally Induced Oestrus Cows

In a field study, circulating thyroid hormones, their free forms and indices of energy and lipid metabolism were measured in blood samples of 16 dairy cows expressing detectable oestrus signs. The cows were divided into two equal groups according to their days in milk (DIM=53-90 and DIM=100-150). In each group, 4 cows expressed the oestrus signs normally and the others were induced by hormone injection. Serum thyroxin (T4), free thyroxin (fT4), triiodothyronine (T3), free triiodothyronine (fT3), glucose, beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), triglyceride (TAG), cholesterol, very low density lipoproteins (VLDL-cholesterol), low density lipoproteins (LDL-cholesterol) and high density lipoproteins (HDL-cholesterol) were investigated. Comparison of all oestrus cows (normal or induced) between DIM groups (n=8 each) revealed lower levels of T4 (P=0.027) and T3 (P=0.022), but higher concentrations of fT4 (P=0.031) and fT3 (P=0.006) in the cows with lower DIM. Higher concentrations of TAG and VLDL (P=0.021) and cholesterol (P=0.046) as well as a tendency (P=0.074) for lower levels of BHB were other remarkable findings in cows with lower DIM. In cows with DIM=53-90, the normal oestrus cows had higher levels of T3 (P=0.044) as well as tendencies (P=0.083) for higher T4 and lower fT4 compared with induced cows. In cows with DIM=100-150, however, no significant difference was observed between the normal and induced oestrus cows. In conclusion, the cows that express oestrus signs normally may have better metabolic and thyroid hormone conditions compared to those that express heat by hormone injection. With progress in DIM, however, such differences may become less evident