Standardised mortality ratios in people exposed to sulphur mustard during the Iran-Iraq war: a retrospective study with 39-year follow-up.

OBJECTIVES: Sulphur mustard (SM) is a chemical weapon agent that was extensively used by Iraqi troops during the Iran-Iraq war (1980-1988), resulting in exposure among Iranian military personnel and civilians. However, there is limited and conflicting information about the long-term mortality effects of SM exposure. This study aimed to determine the standardised mortality ratios (SMRs) in individuals exposed to SM gas during the Iran-Iraq war. STUDY DESIGN: This was a retrospective follow-up study. METHODS: Data were obtained from the Veterans and Martyr Affair Foundation of Iran (VMAF) regarding all confirmed individuals who were exposed to SM during the Iran-Iraq war (1980-1988) up to 30 March 2019. The mortality rate, cumulative mortality and SMR with 95 % confidence intervals (CIs) were calculated to assess mortality in chemical warfare survivors (CWS), and results were compared with the general Iranian population. Overall survival was analysed using the Kaplan-Meier curve, and the log-rank test was employed to compare survival probability across different categories. RESULTS: Among the 48,067 confirmed CWS, a total of 4358 (9.1 %) individuals had died by the end of the study period (30 March 2019), with a mean age of 55.5 ± 14.4 years at the time of death. Overall, at the 39-year follow-up, the mortality rate due to all causes of death for people who were exposed to SM was lower than the general Iranian population (SMR: 0.70, 95 % CI: 0.68-0.72). However, cause-specific SMR analysis showed that the mortality rate due to liver cancer (SMR: 1.98, 95 % CI: 1.59-2.45), poisonings (SMR: 1.92, 95 % CI: 1.52-2.38), respiratory disorders (SMR: 1.59, 95 % CI: 1.46-1.73) and multiple myeloma (SMR: 1.72, 95 % CI: 1.06-2.62) were approximately twofold higher in CWS than the general population. CONCLUSIONS: This study provides valuable insights into the mortality effects of SM exposure among the Iranian population affected by the Iran-Iraq war. The results emphasise the importance of continued monitoring and support for individuals exposed to SM, particularly in the context of managing and addressing the heightened risks associated with liver cancer, poisonings, respiratory disorders and multiple myeloma. Further research and interventions may be necessary to mitigate these specific health challenges in the affected population.

Procedural pain in routine dental care for children: a part of the Swedish BITA study.

AIM: To investigate the frequency and reported intensity levels of dental treatment pain and discomfort in children, in conjunction with regular dental visits. METHODS: The study included 2363 children in four different age cohorts. Data was collected from structured interviews by dental personnel regarding pain experiences or discomfort after treatments, including analgesia, extractions, operative treatments and radiographic examinations. RESULTS: One-third of all treatment occasions were experienced as painful and/or causing discomfort. Treatment sessions including analgesia were assessed as painful in 49.7% of occasions, with injection being the most common given reason for pain. Extraction was painful in 62.4% of occasions, with injection as the main reason for pain. Operative treatments were assessed as painful in 38.8% of occasions, with drilling as the most common reason for pain and discomfort. Pain was reported in approximately 19% of all radiographic examinations. CONCLUSIONS: Injection was the major reason for pain during treatment, including injection and extraction, while drilling was the most common cause of pain during restorative treatment. Dentists should try to minimise the experience of pain and discomfort by using all available measures to perform pain-free and effective dental injections.

Two lung development-related microRNAs, miR-134 and miR-187, are differentially expressed in lung tumors.

INTRODUCTION: MicroRNAs (miRNAs) are involved in various cellular events needed for embryonic development and tumorigenesis. As some of the development-specific gene expression patterns could be observed in cancers, we speculated that the expression pattern of lung development-specific miRNAs miR-134 and miR-187 might be altered in lung tumor samples. Lung cancer is the first cause of cancer related deaths worldwide, mostly due to its late diagnosis. Therefore, finding a reliable diagnostic tumor marker, based on molecular profile of tumorigenesis, would be critical in lowering lung cancer mortality. METHODS: We employed a real-time RT-PCR approach to evaluate the expression alteration of two lung development-related miRNAs in lung tumor tissues. The suitability of miRs expression alterations as lung tumor biomarkers was tested by receiver operating characteristic (ROC) curve analysis. The effect of miR-187 overexpression on a lung carcinoma cell cycle was assessed using flow cytometry analysis. RESULTS: Our data revealed a significant upregulation (7.8 times, p<0.02) of miR-134 in lung tumors. However, its expression level failed to discriminate different tumor types and grades of malignancies from each other. Moreover, the ROC curves analysis did not give it a good score as a reliable biomarker (AUC=0.522, P=0.729). In contrast, miR-187 showed a significant down-regulation (P=0.008) in lung tumors. Similarly, its expression level failed to differentiate different tumor types or grades of malignancies. Nevertheless, ROC curve analysis gave it an AUC score of 0.669 (P=0.012), which suggests its suitability as a potential biomarker for lung cancer. Furthermore, ectopic expression of miR-187 in A549 cells caused a cell cycle arrest in G1 phase (P=0.013). CONCLUSION: Altogether, our data demonstrated an altered expression of two development-related miRNAs namely miR-134 and miR-187 in lung tumors for the first time. Moreover we have shown that miR-134 and miR-187 expression alternation were in accordance with their approved regulatory roles, therefore these miRNAs could serve as new biomarkers with potential usefulness in lung cancer diagnosis and treatments. In addition, miR-187 expression in tumor cells could perturb cell cycle which supported its possible role as tumor suppressor.

Short-term Curcuminoid Supplementation for Chronic Pulmonary Complications due to Sulfur Mustard Intoxication: Positive Results of a Randomized Double-blind Placebo-controlled Trial.

Pulmonary problems are among the most frequent chronic complications of sulfur mustard (SM) intoxication and are often accompanied by deregulated production of pro-inflammatory cytokines. Curcuminoids, comprising curcumin, demethoxycurcumin and bisdemethoxycurcumin, are phytochemicals with remarkable anti-inflammatory properties that are derived from dried rhizomes of the plant Curcuma longa L. (turmeric). The present pilot study aimed to investigate the clinical effects of supplementation with curcuminoids on markers of pulmonary function and systemic inflammation in SM-intoxicated subjects. In a randomized double-blind placebo-controlled trial, 89 male subjects who were suffering from chronic SM-induced pulmonary complications were recruited and assigned to either curcuminoids (500 mg TID per oral; n=45) or placebo (n=44) for a period of 4 weeks. Efficacy measures were changes in the spirometric parameters (FVC, FEV1, FEV1/FVC) and serum levels of inflammatory mediators including interleukins 6 (IL-6) and 8 (IL-8), tumor necrosis factor-α (TNFα), transforming growth factor-ß (TGFß), high-sensitivity C-reactive protein (hs-CRP), calcitonin gene related peptide (CGRP), substance P and monocyte chemotactic protein-1 (MCP-1). 78 subjects completed the trial. Although FEV1 and FVC remained comparable between the groups, there was a greater effect of curcuminoids vs. placebo in improving FEV1/FVC (p=0.002). Curcuminoids were also significantly more efficacious compared to placebo in modulating all assessed inflammatory mediators: IL-6 (p<0.001), IL-8 (p=0.035), TNFα (p<0.001), TGFß (p<0.001), substance P (p=0.016), hs-CRP (p<0.001), CGRP (p<0.001) and MCP-1 (p<0.001). Curcuminoids were safe and well-tolerated throughout the trial. Short-term adjunctive therapy with curcuminoids can suppress systemic inflammation in patients suffering from SM-induced chronic pulmonary complications.

Trend of knowledge production of research centers in the field of medical sciences in iran.

Establishment of medical research centers at universities and health-related organizations and annually evaluation of their research activities was one of the strategic policies which followed by governmental organization in last decade in order to strengthening the connections between health research system and health system. The aim of this study is to scrutinize the role of medical research centers in medical science production in Iran. This study is a cross sectional which has been performed based on existing reports on national scientometrics and evaluation results of research performance of medical research centers between years 2001 to 2010. During last decade number of medical research centers increased from 53 in 2001 to 359 in 2010. Simultaneous scientific output of medical research centers has been increased especially articles indexed in ISI (web of science). Proper policy implementation in the field of health research system during last decades led to improving capacity building and growth knowledge production of medical science in recent years in Iran. The process embedding research into the health systems requires planning up until research products improves health outcomes and health equity in country.

The analysis of health research system evaluation in medical sciences universities.

BACKGROUND: Based on Iran by 2025 defined vision, we must to receive the first grade of science position in south western Asian region. Thus we need to have a comprehensive evaluation program. METHODS: A comprehensive WHO Health Research System Analysis (HRSA)- based evaluation system was developed to evaluate the HRS in Iran. This article has explored the results of the five-year evaluation (2003-2008) and aims to introduce this method to other developing countries. Here we explore the results of research performance evaluation from 2002 to 2010 and by comparing the results with previous available information, we reveal the probable role of this method in research promotion and proposed approach to facilitate and expedite achieving the prospects for goals of health research based on the visions of Iran by 2025. RESULTS: All of the indicators of stewardship and capacity building axes are received to their predefined levels. Moreover all of the medical science university research policies are based on their strategic plannings which are extracted from national visions of Iran by 2025. Most of the predefined goals in knowledge production domain had a significant grow trend but for more growth for commitments they should be closely follow. CONCLUSION: We developed an HRS-based comprehensive evaluation program to our national vision as well as our regional and international research competition.

The evaluation of international relationship role in promotion of health system research.

BACKGROUND: Regarding the need for scientific development and achievement our national goals, it is clear that international cooperation has the main role in this way. Here is a report on what we have done during past almost 10 years (2001-2011) in the field of international medical research activities in Deputy Ministry for Research & Technology, Ministry of Health, Iran. Our effort was focused to identify and contact with the prominent scientific centers among the world where could make a connection between our researchers in medical science universities with those centers.

Health research evaluation and its role on knowledge production.

BACKGROUND: Knowledge production and evaluation are two important functions of health research system (HRS). In this article, we aimed to reveal the correlation between evaluation of health research organizations and health knowledge production promotion. METHODS: A comprehensive evaluation system was developed to evaluate the academic performance of national medical science universities on an annual basis. It assess following domains; stewardship, capacity building and knowledge production. Measurable indicators for each domain were assigned, a 'research profile' for each department was provided. In this study, we compared the results of annually national Health Research System evaluation findings during 2005-2008. RESULTS: The number of scientific articles has been increased from 4672 to 8816 during 2005 to 2008. It is mentionable that, the number of articles which has been published in indexed data bases has risen too. This fact could be related to directed policy for more international publication of scientific articles from Iran. The proportion of total articles to the number of academic members was 1.14 in 2008, comparing to 0.84 in 2005. It means that this proportion have increased about twice (0.7 Vs 0.45) during mentioned time. Moreover, other scientific products such as authored books based on domestic researches and cited articles in textbooks have increased according to special attention to knowledge production by policy makers. CONCLUSION: We conclude that Health System Research evaluation could be used as a mean for implementing policies and promoting knowledge production.

Developing data elements for research information system in health; a starting point for systems integration.

BACKGROUND: This study defines necessary data elements required for the research information system in the domain of health, and its level of accountability to national health research indicators from the experts' perspective is being explored. METHODS: This qualitative study was conducted based on comparative approach using the focus group method. Data were collected through 6 semi-structured group discussions held at the Undersecretary for Research and Technology, Ministry of Health and Medical Education, Tehran, Iran. For this study, 48 researchers were selected for the group discussions. All interviews and group discussions were recorded and transcribed. The Data analysis was performed simultaneously using Strauss and Corbin method. RESULTS: BASED ON CONTENT ANALYSIS, THE NECESSARY DATA ELEMENTS IDENTIFIED FOR THE NATIONAL HEALTH RESEARCH INFORMATION SYSTEM DESIGNED FOR ALL DATABASES WERE THE FOLLOWING: organizations, researchers, journals, articles, research projects and dissertations. Also, extracted from the focus group discussion were three main themes regarding data elements of these databases for the National Health Research Information System: 1) essential elements for each database 2) the system's data elements accountability to the national indicators in the domain of health research and 3) recommendations in the direction of optimizing the data. CONCLUSIONS: The results obtained from this study can serve as a valuable source in designing research information system in the domain of health within the country and in the region as well.

Dynamics of Leishmania infection rates in Rhombomys opimus (Rodentia: Gerbillinae) population of an endemic focus of zoonotic cutaneous leishmaniasis in Iran.

Zoonotic cutaneous leishmaniasis (ZCL) due to Leishmania major is a great public health problem in the Old World. Leishmania major is widely distributed in populations of rodents in arid and savannah regions. In this study, seasonal variation of natural infection with Leishmania parasites in Rhombomys opimus (Rodentia: Gerbillinae) population of an endemic focus of ZCL in Iran was monitored. The study was conducted from October 2007 to October 2008 in the central part of the country. Nested polymerase chain reaction (PCR) assay was used for the detection and identification of Leishmania parasites, and the results were confirmed by PCR-restriction fragment length polymorphism (RFLP). The results showed that Leishmania infection rate was 55.8% (29 out of 52 gerbils) using nested PCR. The highest and lowest Leishmania infection rates were observed in fall and summer, respectively. Gerbils that were found to be infected only with L. major were 5.8%, and that with Leishmania turanica were 23.1%. A mixed natural infection was seen in the rodents with L. major and L. turanica (21.2%), with L. major and L. gerbilli (1.9%), and with all the three species (3.9%). Leishmania major infection alone was seen in fall and winter whereas mixed infection of L. major and L. turanica was observed in all seasons except in summer. Leishmania turanica infection was observed throughout the year. It is concluded that L. major, L. gerbilli, and L. turanica circulate in the population of R. opimus in central part of Iran. Leishmania major infection is usually accompanied by L. turanica in naturally infected gerbils with the highest rate in fall. It is recommended that the role of L. turanica in the epidemiology and transmission of ZCL should be reconsidered.

Noninvasive diagnosis of bronchiolitis obliterans due to sulfur mustard exposure: could high-resolution computed tomography give us a clue?

PURPOSE: Previous pathological investigations have reported bronchiolitis obliterans (BO) as the major long-term sequela of exposure to sulfur mustard. In this study, we investigated whether high-resolution computed tomography (HRCT) could be used as a noninvasive imaging modality to differentiate between mustard lung (as a subtype of BO) and other respiratory disorders. MATERIALS AND METHODS: Three groups of patients with sulfur-mustard-induced lung injury (BO), severe chronic asthma (resistant asthma) and smoking habit, respectively, were recruited. Also 30 nonsmoking participants were recruited randomly as the control group. Pulmonary function tests (PFT) and HRCT were performed. Images were viewed with a window level of -450 and window width of 1,400 HU. All images were evaluated by an expert radiologist who was blinded regarding the patients' diagnoses and clinical situations. RESULTS: Airway involvement was higher and more frequent than parenchymal involvement in the groups with chemical-induced injury and asthma in comparison with smokers. On the other hand, parenchymal involvement was more frequent than airway involvement in the smokers' group in comparison with the other groups. CONCLUSIONS: HRCT can be a very useful method for differentiating between mustard lung, resistant asthma and lung injuries due to cigarette smoking.

Molecular epizootiology of rodent leishmaniasis in a hyperendemic area of iran.

BACKGROUND: Zoonotic cutaneous leishmaniasis (ZCL) is an expanding disease and public health problem in Iran. In the current study, natural Leishmania infection rate and seasonal fluctuation of the infection in Rhombomys opimus population of a hyperendemic focus of ZCL in Iran was investigated. METHODS: The study was conducted from October 2006 to October 2008 in Esfahan Province, central part of Iran. An extensive sampling of rodents using Sherman traps was done in different seasons. Nested PCR assay was used for detection and identification of Leishmania species and the results were confirmed using PCR-RFLP. RESULTS: Leishmania infection rate was 58.6% (34 of 58) using nested PCR. 44.8% of the gerbils were infected only with L. turanica and 1.7% with L. gerbilli alone. A mixed natural infection with L. major and L. turanica was seen in 12.1% of the rodents. L. major infection alone was not seen in R. opimus population in the study area. The highest and lowest Leishmania infection rates were observed in fall and spring respectively. L. turanica infection was observed throughout the year whereas mixed infections with L. major and L. turanica was not seen in spring. CONCLUSION: It is concluded that in the study area, L. major, L. gerbilli and L. turanica circulate in the population of R. opimus. Leishmania major infection usually accompanied by L. turanica in naturally infected gerbils with the highest rate in fall. It is recommended that the role of L. turanica in the epidemiology and transmission of ZCL be revisited.

Karyosystematic and morphometric characterization of the rodents as reservoir hosts of zoonotic cutaneous leishmaniasis in an endemic focus of Isfahan Province, Iran.

BACKGROUND & OBJECTIVES: Rodents belonging to Gerbillinae subfamily are the main reservoir hosts of zoonotic cutaneous leishmaniasis (ZCL) in Iran. Regarding the important role of these rodents in the maintenance of Leishmania major in the nature, their identification with morphometric, cytogenetic and molecular methods seems to be essential. The karyotype study of these species, captured from a new focus of zoonotic cutaneous leishmaniasis located in the south of Isfahan Province was carried out in 2007. METHODS: Twenty specimens containing seventeen Meriones persicus and three Nesokia indica were captured from Mobarakeh rural district south of Isfahan. Giemsa-stained karyotypes of these two species were prepared from bone marrow chromosome preparations. Systematic important characters of the body and cranium (incisors, molars, occipitonasal, condylobasal, zygomatic, tympanic bullae, etc.) of these rodents were studied. Cranium size was measured using a Vernier calipers. RESULTS: Specimens of M. persicus and N. indica had 2n = 42. The karyotype study of these species included metacentric, sub-metacentric and acrocentric chromosomes. Morphological studies were completely matched with the reported characters of these species and further confirmed the diagnoses. INTERPRETATION & CONCLUSION: Based on the results of this study, M. persicus and N. indica are two completely differentiated rodents species that were collected from a new focus and they can also be differentiated morphologically.

Late respiratory effects of sulfur mustard: how is the early symptoms severity involved?

The association between severity of exposure to sulfur mustard (SM) and late respiratory complications is not clear. The aim of this study was to determine the presence of late pulmonary complications in patients with mild, moderate, and severe initial symptoms of sulfur mustard exposure. This was a retrospective cohort study on patients with mild, moderate, and severe initial symptoms of sulfur mustard exposure (during 1983-1988) in Baqyatallah University of medical sciences (2004-2005). The 'mild' group (n = 115) had no early symptom at the time of exposure. The 'moderate' group (n = 273) had early symptoms after exposure and were not hospitalized for that reason. The 'severe' group (n = 215) had early symptoms and had been hospitalized accordingly. Pulmonary function tests and high-resolution computed tomography of the chest were performed. The chi-square test was used for data analysis. The severe and moderate groups had a similar frequency of obstructive pattern (21%), whereas only one patient in the mild group showed this pattern. Air trapping did not significantly differ between groups. In the mild group, 74.8% (n = 86) showed significant air trapping, whereas it was 62.3% (n = 170) in moderate and 67.0% (n = 144) in severe groups (P = 0.057). Moderate and severe exposure to sulfur mustard causes an equal risk of late pulmonary complications, while mild exposure has lesser risk. Bronchiolitis obliterans is the main underlying respiratory consequence of sulfur mustard exposures and may relate to host factors rather than to severity of early symptoms.

Population-based platelet reference values for an Iranian population.

There are a few reports regarding the reference range for platelet indices in the populations of Iran and its neighbouring countries, but these studies were of small sample size. This study aimed at defining platelet reference values for medical research and practice. A cross-sectional survey was performed on 19,993 young adult Iranians who participated in a compulsory pre-marriage screening programme over a 6-month period. Platelet indices were measured using an automated Technicon H2 cell counter. The platelet count [given as 95% reference interval (2.5 percentile-97.5 percentile) and mean +/- standard deviation] were 145-356 x 10(9)/l (237 +/- 55.2); the platelet distribution width was 40.2-57.4% (46.9 +/- 5.7) the Plateletocrit was, 0.13-0.32% (0.22 +/- 0.05) and the mean platelet volume was 7.4-10.7 fl (9.2 +/- 2.9). The first three indices showed significant differences between males and females. The reference values of platelet indices in Iranians were found to be different from international data; they were a little lower than those in Caucasians but higher than the indices found for Africans.

Distal esophagitis in patients with mustard-gas induced chronic cough.

Although confounded by some factors such as medications or surgical complications, the relationship between esophageal pathology and pulmonary disorders has been the subject of many studies. The present study sought to investigate the said relationship in patients inflicted by respiratory disorders induced by mustard gas (MG). A case group of patients complaining of respiratory complications and chronic coughs following MG exposure, and a control group of patients with chronic coughs but without a history of MG exposure were studied. All the case and control subjects had symptoms of gastro-esophageal reflux disease. Chest high resolution tomography (HRCT) was performed to evaluate the existence of pulmonary disorders. Endoscopy and histological studies were carried out to determine the severity of esophagitis in both groups presenting with gastroesophageal reflux. Ninety male patients, who had met our criteria, along with 40 male control cases underwent the diagnostic procedures. The frequency of endoscopic esophagitis findings in the chemically exposed group was significantly higher than that in the control group (70.0%vs. 42.5%). A pathological evaluation revealed that the frequency of esophagitis in the cases was more than that in the controls (32.3%vs. 14.2%). Chest HRCT evaluation demonstrated that half the case group had more than 25% air trapping in expiratory films, mostly compatible with bronchiolitis obliterans (BO). In addition, they were suffering from asthma, chronic bronchitis and bronchiectasis. Bronchiolitis obliterans, along with other lung disorders, can be considered as contributors in the pathogenesis of esophagitis in MG exposed patients.

Pre-marriage prevention of thalassaemia: report of a 100,000 case experience in Isfahan.

BACKGROUND: Iran like other middle east countries has a large number of major thalassaemics. Due to religious restrictions on abortion, the routine prevention of the birth of thalassaemic children by this means is not possible. The aim of this study is to describe an alternative means to prevent the birth of thalassaemic children. METHODS: From January 1993 to January 1996, 10,000 people preparing for marriage were screened for the thalassaemia trait, using CBC and HbA2 level measurement. High risk couples were referred for further consultation regarding the disease and the means of its prevention. The proposed actions of the couples regarding thalassaemia prevention were evaluated immediately after consultation and then re-evaluated three months later. RESULT: After the project had been running for three years the average of high risk couple initially deciding not to marry was 90% and no new cases of thalassemia were detected in the children of the screened population. CONCLUSION: Where both members of the couple were trait-positive their preferred choice was not to marry, rather than to marry and use other or no methods of preventing a thalassemia affected child being born to them. Cultural and religious ideas can affect such decisions and in some Islamic countries the establishment and use of a genetic counselling centre can help prevent most of new thalassaemia cases.