Cyclooxygenase inhibitors combined with deuterium-enriched water augment cytotoxicity in A549 lung cancer cell line via activation of apoptosis and MAPK pathways

Objective(s): Combination chemotherapy is a rational strategy to increase patient response and tolerability and to decrease adverse effects and drug resistance. Recently, the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been reported to be associated with reduction in occurrence of a variety of cancers including lung cancer. On the other hand, growing evidences suggest that deuterium-enriched water (DEW, D2O) and deuterium-depleted water (DDW) play a role both in treatment and prevention of cancers. In the present study, we examined the effects of DEW and DDW in combination with two NSAIDs, celecoxib and indomethacin, on A549 human non-small lung cancer cell to identify novel treatment options. Materials and Methods: The cytotoxicity of celecoxib or indomethacin, alone and in combination with DDW and DEW was determined. The COX-2, MAPK pathway proteins, the anti-apoptotic Bcl2 and pro-apoptotic Bax proteins and caspase-3 activity were studied for cytotoxic combinations.Results: Co-administration of selective and non-selective COX-2 inhibitors with DEW led to a remarkable increase in cytotoxicity and apoptosis of A549 cells. These events were associated with activation of p38 and JNK MAPKs and decreasing pro-survival proteins Bcl-2, COX-2 and ERK1/2. Furthermore, the combination therapy activated caspase-3, and the apoptosis mediator, and disabled poly ADP-ribose polymerase (PARP), the key DNA repair enzyme, by cleaving it.  Conclusion: The combination of DEW with NSAIDs might be effective against lung cancer cells by influence on principal cell signalling pathways, and this has a potential to become a candidate for chemotherapy

Opium use and risk of mortality from digestive diseases: A prospective cohort study

Objectives:Opium use, particularly in low doses, is a common practice among adults in northeastern Iran. We aimed to investigate the association between opium use and subsequent mortality from disorders of the digestive tract.Methods:We used data from the Golestan Cohort Study, a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50,045 adults were enrolled during a 4-year period (2004-2008) and followed annually until December 2012, with a follow-up success rate of 99. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest.Results:In all, 8,487 (17) participants reported opium use, with a mean duration of 12.7 years. During the follow-up period 474 deaths from digestive diseases were reported (387 due to gastrointestinal cancers and 87 due to nonmalignant etiologies). Opium use was associated with an increased risk of death from any digestive disease (adjusted hazard ratio (HR)=1.55, 95 confidence interval (CI)=1.24-1.93). The association was dose dependent, with a HR of 2.21 (1.57-3.31) for the highest quintile of cumulative opium use vs. no use (P trend =0.037). The HRs (95 CI) for the associations between opium use and malignant and nonmalignant causes of digestive mortality were 1.38 (1.07-1.76) and 2.60 (1.57-4.31), respectively. Increased risks were seen both for smoking opium and for ingestion of opium.Conclusions:Long-term opium use, even in low doses, is associated with increased risk of death from both malignant and nonmalignant digestive diseases

Molecular identification of Palearctic members of Anopheles maculipennis in northern Iran

BACKGROUND: Members of Anopheles maculipennis complex are effective malaria vectors in Europe and the Caspian Sea region in northern Iran, where malaria has been re-introduced since 1994. The current study has been designed in order to provide further evidence on the status of species composition and to identify more accurately the members of the maculipennis complex in northern Iran. METHODS: The second internal transcribed spacer of ribosomal DNA (rDNA-ITS2) was sequenced in 28 out of 235 specimens that were collected in the five provinces of East Azerbayjan, Ardebil, Guilan, Mazandaran and Khorassan in Iran. RESULTS: The length of the ITS2 ranged from 283 to 302 bp with a GC content of 49.33 – 54.76%. No intra-specific variations were observed. Construction of phylogenetic tree based on the ITS2 sequence revealed that the six Iranian members of the maculipennis complex could be easily clustered into three groups: the An. atroparvus – Anopheles labranchiae group; the paraphyletic group of An. maculipennis, An. messeae, An. persiensis; and An. sacharovi as the third group. CONCLUSION: Detection of three species of the An. maculipennis complex including An. atroparvus, An. messae and An. labranchiae, as shown as new records in northern Iran, is somehow alarming. A better understanding of the epidemiology of malaria on both sides of the Caspian Sea may be provided by applying the molecular techniques to the correct identification of species complexes, to the detection of Plasmodium composition in Anopheles vectors and to the status of insecticide resistance by looking to related genes

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 injury morbidity and mortality from 1990 to 2017 : results from the Global Burden of Disease Study 2017

Correction:Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.Peer reviewe

Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050

Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached$8. 8 trillion (95% uncertainty interval UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total,$40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this,$13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and$1.4 billion was repurposed from existing health projects. $3.1 billion (22.4$2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7$1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Prevalence of Musculoskeletal Disorders in Rural Women in Qazvin Province

Objective: In a fast-paced world of technology that is changing people’s lifestyles and reducing mobility, rural women who were once a model of mobility have not been spared. This study aimed to investigate the prevalence of musculoskeletal abnormalities of the upper and lower limbs in rural women in Qazvin province. Methods: The present study was a descriptive-comparative study. The statistical population of this study was rural women in Qazvin province with an age range of 15-65 years and an average age (41.88±15.70). In this research, 3023 people participated and were divided into four groups with different age ranges. Subjects were selected by snowball sampling method and participated in the study voluntarily. The collection tools included consent form, musculoskeletal abnormalities registration form, caliper, vertical line, checkerboard, and New York test. Descriptive statistics were used to show the prevalence of anomalies, and the Kruskal-Wallis test was used for group comparison in SPSS software v. 24. Results: Kruskal-Wallis test showed that in the variables head forward (P=0.001), torticollis (P=0.001), shoulder forward (P=0.008), uneven shoulder (P=0.001), kyphosis (P=0.001), lordosis (P=0.001), flat back (P=0.003), scoliosis (P=0.001), anterior pelvic rotation (P=0.001), genu Varum (P=0.001), genu valgum (P=0.001), genu recurvatum (P=0.001), flat foot (P=0.008), Pes cavus (P=0.004) and hallux valgus (P=0.001). There was a significant difference between groups. Also, the highest prevalence of upper limb deformities was related to uneven shoulder, head forward, and lordosis. The highest prevalence of lower limb deformities was related to anterior pelvic rotation, genu valgum, and flat foot. Conclusion: The results show that the prevalence of musculoskeletal abnormalities of the upper and lower limbs in rural women in Qazvin province is highly prevalent in the age range of 35-31 years and 50-36 years. Therefore, researchers believe that providing information about the prevalence of postural disorders can effectively design preventive programs and emphasize the need to develop corrective exercise and rehabilitation programs for this segment of society

Considering Causes of Death in the Emergency Department of Firoozgar Hospital: A 5-Year Cross Sectional Study

مقدمه: مطالعاتی که در زمینه مرگ‌ومیر انسان‌ها و بیماری‌ها و صدماتی که موجب از دست رفتن زندگی افراد می‌گردد، یکی از مهم‌ترین نقش‌ها را در تعیین و ارزیابی اثربخشی نظام سلامت دارند. لذا مطالعه حاضر باهدف تعيين ميزان مرگ‌ومیر بيمارستاني و علل و عوامل دخيل در آن در بيمارستان آموزشي درماني فیروزگر صورت ‌گرفت. روش كار: این مطالعه مقطعی و گذشته‌نگر از اول فروردین سال 1392 تا اسفند سال 1396 در بیمارستان فیروزگر تهران انجام شد. به همین منظور پرونده بالینی کلیه بیماران فوت‌شده در اورژانس، در فاصله زمانی مذکور موردمطالعه قرار گرفت. اطلاعات دموگرافیک و علل فوت استخراج و داده‌های به‌دست‌آمده با استفاده از نرم‌افزار 25 SPSS  مورد تجزیه‌وتحلیل آماری قرار گرفت. یافته‌ها: تعداد 1065 مورد فوت شده در دوره 92 تا 96 مورد قرار گرفتند. سپسيس (02/24%)، ايست قلبي- ريوي خارج بيمارستان (46/20%)، سندرم كرونري حاد (48/19%)، تروما (تصادف و سقوط) (78/17%)، نارسايي چند ارگاني (08/7%)، خونريزي مغزي (8/6%) و آمبولي ريه (38/4%) علل اصلی مرگ‌ومیر بیمارستانی بودند. نتیجه‌گیری: شیوع بالای عللی همچون سپسیس و تروما به عنوان علت مرگ در بخش اورژانس، اهمیت کنترل و پیشگیری این مشکلات را نشان می‌دهد که با تجهیز اورژانس بیمارستان فیروزگر و برنامه‌ریزی مناسب بتوان امید به زندگی بیماران مراجعه‌کننده به این بیمارستان را افزایش داد.Introduction: Studying the causes of mortality plays the most important role in determining and evaluating the health system's effectiveness. Accordingly, this study aimed to identify the causes of death in the emergency department for planning and providing appropriate facilities to reduce mortality rate in patients. Methods: This cross-sectional observational study was conducted in the Firoozgar Hospital, Tehran from April 2013 to March 2017. The clinical records of all patients who died in the emergency department through the study period were studied. The extracted demographic characteristics and causes of death were analyzed using SPSS-25 software. Results: In the last 5 years, sepsis (24.02%), out-of-hospital cardiac arrest (20.46%), acute coronary syndrome (19.48%), trauma (accidents and falls from a height) (17.78%), multi organ dysfunction (7.08%), intracranial hemorrhage (6.8%) and pulmonary embolism (4.38%) were the main causes of mortality in hospitals. Conclusion: Sepsis, out-of-hospital cardiac arrest, ACS, trauma, multi organ dysfunction, intracranial hemorrhage and pulmonary embolism are the main causes of mortality in hospitals. The high prevalence of death causes, such as sepsis and trauma indicate that such causes should be controlled and prevented, so that by equipping the emergency departments and proper planning, life expectancy can be increase

Efficacy of long-term outcomes and prosthesis satisfaction in war related above knee amputees of Tehran

Background and purpose: Amputation is one of the most deleterious events that one may experience throughout his/her life. Gait patterns adopted by Amputees with prosthesis can cause such various types of pain as back pain, hip joint pain and contralateral pain. Knowledge about existing problems associated with amputated limb can be useful in making decisions about appropriate treatment plans and rehabilitation programs for these patients. The aim of this study was to evaluate long-term outcomes and prosthesis satisfaction in persons with war-related above-knee amputations. Material and methods: Sixty-one Iranian subjects with above knee amputation were requested to fill out the Persian version of Prosthesis Evaluation Questionnaire (PEQ) and to judge whether they were satisfied with their current prosthesis. Results: Phantom sensation, phantom pain, residual limb pain, lateral limb pain and back pain was respectively reported in 88.5%, 77%, 36.1%, 33% and 72.1% of the subjects. Moreover, it became evident that 19.67% of the subjects were truly satisfied with their current prosthesis. Conclusion: According to study results, phantom sensation, phantom pain, back pain, residual limb pain and pain in the lateral limb are the most prevalent outcomes of war related amputations. Satisfaction rates were higher than moderate in more than half of the patients studied. Key words: limb loss, phantom pain, phantom sensation, satisfactio