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Background: Since the COVID-19 pandemic, several cases of cerebral venous sinus thrombosis (CVST) have been reported in SARS-CoV-2 infected individuals. This study provides a series of patients with CVST and SARS-CoV-2 infection.Methods: Consecutive patients with documented SARS-CoV-2 infection, as well as clinical and radiological characteristics of CVST, were reported from three teaching hospitals in the South West, North West, and the center of Iran from June to July 2020. We also searched the abstract archives until the end of August 2020 and gathered 28 reported cases. The diagnostic criteria for SARS-CoV-2 infection were determined according to SARS-CoV-2 detection in oropharyngeal or nasopharyngeal samples in clinically suspected patients. Demographics, main COVID-19 symptoms, confirmatory tests for SARS-CoV-2 infection diagnosis, the interval between the diagnosis of SARS-CoV-2 infection and CVST, clinical and radiological features of CVST, therapeutic strategies, CVST outcomes, rate of hemorrhagic transformation, and mortality rate were investigated.Results: Six patients (aged 31 to 62 years old) with confirmed CVST and SARS-CoV-2 infection were admitted to our centers. Four patients had no respiratory symptoms of SARS-CoV-2 infection. Five out of six patients developed the clinical manifestations of CVST and SARS-CoV-2 infection simultaneously. Three patients had known predisposing factors for CVST. Despite receiving CVST and SARS-CoV-2 infection treatments, four out of six patients passed away.Conclusions: The role of SARS-CoV-2 as a “cause” versus an “additive contributor” remains to be elucidated. Practitioners should be aware of the possibility of CVST in SARS-CoV-2 infection.

This longitudinal study was designed to evaluate the association between acute prestroke stress and the severity stroke and its outcomes including mortality, recurrence, disability and functional dependency. Patients with first-ever stroke (FES) were recruited from the Mashhad Stroke Incidence Study. Patients were asked about any acute severe prestroke stress in the two weeks prior to index stroke. Disability and functional disability were defined using modified the Rankin Scale and Barthel Index, respectively. We used logistic and ordinal regression tests to assess the association between acute prestroke stress and study outcomes. Among 624 patients with FES, 169 reported acute prestroke stress. Patients with acute prestroke stress were younger than those without stress (60.7 ± 14.4 vs. 66.2 ± 14.7; p

Background: Little is known about the association between socioeconomic status and long-term stroke outcomes, particularly in low- and middle-income countries. Methods: Patients were recruited from the Mashhad Stroke Incidence Study in Iran. We identified different socioeconomic variables including the level of education, occupation, household size, and family income. Residential location according to patient’s neighbourhood was classified into less privileged area (LPA), middle privileged area and high privileged area (HPA). Using Cox regression, competing risk analysis and logistic regression models, we determined the association between socioeconomic status and 1- and 5-year stroke outcomes. Generalized linear model was used for adjusting associated variables for stroke severity. Results: Six hundred twenty-four patients with first-ever stroke were recruited in this study. Unemployment prior to stroke was associated with an increased risk of 1- and 5-year post-stroke mortality (1 year: adjusted hazard ratio [aHR] 3.3; 95% CI 1.6–7.06: p = 0.001; 5 years: aHR 2.1; 95% CI 1.2–3.6: p = 0.007). The 5-year mortality rate was higher in less educated patients (p = 0.03). Patients living in LPA compared to those living in HPAs experienced a more severe stroke at admission (aB 3.84; 95% CI 0.97–6.71, p = 0.009) and disabling stroke at 1 year follow-up (OR 6.1; 95% CI 1.3–28.4; p = 0.02). Conclusion: A comprehensive stroke strategy should also address socioeconomic disadvantages.

Background: Rituximab is a monoclonal antibody against CD20 antigen present on mature B lymphocytes. It is commonly used in some hematologic, rheumatologic as well as neurologic disorders, including multiple sclerosis (MS) and neuromyelitis optica (NMO). Although there are some data about the safety of rituximab in patients with MS and NMO, there are few experiences regarding its safety in the Iranian population with MS, and known complications are often related to the studies conducted on the patients in other countries or with other autoimmune diseases and malignancies that are different from the population of patients with MS in terms of the underlying disease status and the concomitant medications or previous medications used. Objectives: The aim of this study was to investigate the infusion related, short-term and delayed side effects of rituximab on patients with MS and NMO in the population of the south of Iran. Methods: This was a longitudinal study on patients with MS and neuromyelitis optica who were referred to the health centers affiliated to Shiraz University of Medical Sciences from September 2018 to February 2019 and received Rituximab. They were observed for side effects from the first infusion of the drug to at least 6 months later. A checklist prepared by the researcher was used to collect the data. Independent t-test and chi-square test were used for data analysis. The significance level was considered 0.05 in this study. Results: In this study, 37% of the patients had at least one side effect during the first infusion. The most common side effect was chills (shivering). Short-term side effects occurred in 15.5% of the patients. The most common type was skin manifestations. These side effects led to hospitalization in two patients. Delayed side effect was developed in 20.7% of the patients. The most common delayed side effect was skin manifestations. Conclusions: Overall, there was no unexpected side effect in patients under the study and the side effects developed were comparable to previous studies as well as those conducted on patients other than patients with MS and neuromyelitis optica. Side effects were often mild, with only two cases leading to hospitalization, both of which were self-limiting as well, and there were no serious life-threatening side effects, except for one case with bradycardia.

Objective: Few data are available on the associations between the level of pre-stroke physical activity and long-term outcomes in patients with stroke. This study is designed to assess the associations between pre-stroke physical activity and age of first-ever stroke occurrence and long-term outcomes. Methods: Six hundred twenty-four cases with first-ever stroke were recruited from the Mashhad Stroke Incidence Study a prospective population-based cohort in Iran. Data on Physical Activity Level (PAL) were collected retrospectively and were available in 395 cases. According to the PAL values, subjects were classified as inactive (PAL < 1.70) and active (PAL ≥ 1.70). Age at onset of stroke was compared between active and inactive groups. Using logistic model, we assessed association between pre-stroke physical activity and long-term (5-year) mortality, recurrence, disability, and functional dependency rates. We used multiple imputation to analyze missing data. Results: Inactive patients (PAL < 1.70) were more than 6 years younger at their age of first-ever-stroke occurrence (60.7 ± 15.5) than active patients (67.0 ± 13.2; p < 0.001). Patients with PAL< 1.7 also had a greater risk of mortality at 1 year [adjusted odds ratio (aOR) = 2.31; 95%CI: 1.14–4.67, p = 0.02] and 5 years after stroke (aOR = 1.81; 95%CI: 1.05–3.14, p = 0.03) than patients who were more physically active. Recurrence rate, disability, and functional dependency were not statistically different between two groups. Missing data analysis also showed a higher odds of death at one and 5 years for inactive patients. Conclusions: In our cohort, we observed a younger age of stroke and a higher odds of 1- and 5-year mortality among those with less physical activity. This is an important health promotion strategy to encourage people to remain physically active.

Despite recent declines in stroke mortality in high-income countries, the incidence and mortality of stroke have increased in many low- and middle-income countries. Population-based information on stroke in such countries is a research priority to address this rising trend. This study was designed to evaluate 5-year stroke mortality and its associated factors.During a 12-month period beginning from November 2006, 624 patients with first-ever stroke (FES) living in Mashhad, Iran, were recruited and followed longitudinally. Kaplan-Meier analyses were used to determine the cumulative risk of death. Prognostic variables associated with death were assessed using a Cox proportional hazard, backward logistic regression model.The 5-year cumulative risk of death was 53.8% for women and 60.5% for men (log rank = .1). The most frequent causes of death were stroke (41.2%), myocardial infarction/vascular diseases (16.4%), and pneumonia (14.2%). In multivariable Cox proportional hazard analysis, male gender (hazard ratio [HR]: 1.29, 95% confidence interval [CI]: 1.01-1.64), age (HR: 1.04, 95% CI: 1.03-1.05, per 1-year increase), National Institute of Health Stroke Scale score at admission (HR: 1.11, 95% CI: 1.09-1.12, per 1-point increase), atrial fibrillation (HR: 1.78, CI: 1.24-2.54), and education 12 years (HR: 1.61, 95% CI: 1.08-2.4) were associated with greater 5-year case fatality.Long-term case fatality following stroke in Iran is greater than that observed in many high-income countries. Targeting strategies to reduce the poor outcome following stroke, such as treating AF, is likely to reduce this disparate outcome.

Background: Little is known about the risk of recurrent stroke in low- and middle-income countries. This study was designed to identify the long-term risk of stroke recurrence and its associated factors. Methods: From November 21, 2006 for a period of 1 year, 624 patients with first-ever stroke (FES) were registered from the residents of 3 neighborhoods in Mashhad, Iran. Patients were followed up for the next 5 years after the index event for any stroke recurrence or death. We used competing risk analysis and cause-specific Cox proportional hazard models to estimate the cumulative incidence of stroke recurrence and its associated variables. Results: The cumulative incidence of stroke recurrence was 14.5% by the end of 5 years, with the largest rate during the first year after FES (5.6%). Only advanced age (adjusted hazard ratio [HR] 1.02; 95% CI 1.01–1.04) and severe stroke (National Institutes of Health Stroke Scale score >20; HR 2.23; 95% CI 1.05–4.74) were independently associated with an increased risk of 5-year recurrence. Case fatality at 30 days after first recurrent stroke was 43.2%, which was significantly greater than the case fatality at 30 days after FES of 24.7% (p = 0.001). Conclusion: A substantial number of our patients either died or had stroke recurrences during the study period. Advanced age and the severity of the index stroke significantly increased the risk of recurrence. This is an important finding for health policy makers and for designing preventive strategies in people surviving their stroke.

Cervical cancer is the second most common malignancy worldwide and the third leading cause of death in women. It accounts for 1% of all cancers and is the third neoplasm ever diagnosed. Several viruses can cause cancer so that viruses are connected to almost 15–20% of human malignancies and nearly 80% of cervical and liver. MicroRNAs can be used as a tumor oncogene by controlling related genes of tumors. In addition, they can be applied as biomarkers in the diagnosis, prognosis, and even treatment of cancer tissues. The current study aimed to investigate the changes in the expression of miR-21, miR-16, miR-143, and miR-34a related to the severity of the disease in women with low or high grades of squamous intraepithelial lesion or carcinoma infected by HPV-16. In this case-control study, the expression of four microRNAs in formalin-fixed paraffin-embedded tissues of 36 patients with cervical cancer and 36 samples of healthy women are studied by real-time-PCR. For all four miRNAs, enhanced expression was observed in low-grade SIL patients, compared to controls. Also, increased expression of miR-21 in high-grade SIL patients and decreased expression of miR-143 in this grade were found. MicroRNAs can play important roles as biomarkers in the diagnosis of different stages of cervical carcinoma.

Background and Purpose: Little is known about the short- and long-term outcomes of ischemic stroke of undetermined mechanism (ISUM). Methods: Subjects were recruited from the Mashhad Stroke Incidence Study. Ischemic stroke (IS) was classified on the basis of the TOAST criteria. We further categorized patients with ISUM into ISUMneg (negative clinical/test results for large artery, small artery) and ISUMinc (incomplete investigations). Cox proportional hazard models and the competing-risk regression model were used to compare 1 and 5 years mortality (all-causes) and recurrent rate among IS subtypes. Results: Overall, 1-year mortality was higher in those with ISUMinc than in ISUMneg (adjusted hazard ratio [aHR] 1.6, 95% CI 1.01–2.8; p = 0.04) and in other stroke subtypes. Cardioembolic stroke was associated with the greatest risk of stroke recurrence at one year (aHR 4.9, 95% CI 1.8–12.9; p = 0.001) and 5 years (HR 2.1, 95% CI 1.1–3.7; p = 0.01) as compared to ISUMneg. Conclusions: The classification of ISUM as a single group may lead to over- or underestimation of mortality and recurrence in this major category of IS. A better definition of ISUM is necessary to predict death and recurrence accurately.

Background There is controversial evidence about the effect of cerebellar low-frequency stimulation in patients with essential tremor (ET). Objectives In this study we assessed safety and effectiveness of 1 Hz (low-frequency) cerebellar repetitive transcranial magnetic stimulation (rTMS) on tremor severity in patients with essential tremor in a sham-controlled crossover trial. Methods A total of 23 patients assigned into two groups to receive either sham (n = 10) or rTMS (n = 13) treatment, with crossing over after a two-month washout period. Intervention consisted of 900 pulses of 1 Hz rTMS at 90% resting motor threshold or the same protocol of sham stimulation over each cerebellar hemisphere for 5 consecutive days. Tremor severity was assessed by Fahn-Tolosa-Marin (FTM) scale at baseline and at days 5, 12 and 30 after intervention. The FTM consists of 3 subscales including tremor severity rating, performance of motor tasks, and functional disability. Carry-over and treatment effects were analyzed using independent samples t-test. Results There was no significant improvement in the total FTM scores in rTMS compared to the sham stimulation on day 5 (p = 0.132), day 12 (p = 0.574), or day 30 (p = 0.382). Similarly, FTM subscales, including tremor severity rating, motor tasks, and functional disability did not improve significantly after rTMS treatment. Mild headache and local pain were the most frequent adverse events. Conclusion Although cerebellar rTMS seems to have acceptable safety when used in ET patients, this study could not prove any efficacy for it in reduction of tremor in these patients. Larger studies are needed to evaluate efficacy of this therapeutic intervention and to provide evidence about the optimal stimulation parameters.

Background Accurate information about disability rate after stroke remains largely unclear in many countries. Population-based studies are necessary to estimate the rate and determinants of disability after stroke. Methods Patients were recruited from the Mashhad Stroke Incidence Study and followed for five years after their index event. Disability was measured using the modified Rankin scale and functional dependency was measured using the Barthel index. Results Among 684 patients registered in this study, 624 were first-ever strokes. In total, 69.0% (n = 409) of patients either died or remained disabled at five-year follow-up. Among the first-ever stroke survivors, 18.5% (n = 69) at one year and 15.9% (n = 31) at five years required major assistance in their daily activities. Patients with a history of stroke (before the study period) compared with first-ever strokes were more likely to be disabled at one year (modified Rankin scale>2 in 40.0% vs. 19.1%; P Conclusion We found that significant disability and functional dependency after stroke in Northeast Iran were largely attributable to the effects of stroke severity and prior dependency.

Introduction: Constipation and distension are dominant gastrointestinal problems after stroke in the elderly. Always they are treated by the use of laxatives and fibers. Abdominal massage along with a healthy lifestyle can be a solution. Purpose: This study aimed to investigate the effect of abdominal massage and lifestyle training on constipation and distention of the elderly with stroke. Method: This study was a randomized clinical trial that was conducted on elderly patients with stroke at Qaem hospital of Mashhad, Iran. 68 patients were randomly allocated into control (n = 34) and intervention (n = 34) groups in 2017−2018. Finally 29 elderly in the intervention and 34 in the control group completed the study. Intervention included the abdominal massage by using ''I LOV U'' method along with lifestyle education. Each abdominal massage lasted for 15 min, twice daily for ten days that was performed at first session by the researcher and then continued by the key care giver. Data were collected by the demographic form, constipation assessment score (CAS), distension measurement tool (meter), and food tolerance evaluation checklist. Results: The results indicated that both groups were homogeneous in demographic variables (P > 0.05). The repeated ANOVA showed a more significant decrease in abdominal circumference of the intervention group during the 10- days study (P = 0.029).The Friedman test showed a significant difference in frequency of defecation in two groups in 10- day study (P < 0.0001). Therefore the CAS Score was significantly decreased in intervention group more than the control group (0.30 < 0.98 < 1.59, P = 0.001, EF = 0.44). The food tolerance frequencies through Gavage (P = 0.20), and also orally (P < 0.001) were significantly improved in the intervention group. Conclusion: According to results, the abdominal massage along with lifestyle training could improve constipation and distension and also increase food intake tolerance in the elderly patients with stroke.

Ethnopharmacological relevance Complementary and alternative medicine has been increasingly used to treat chronic illnesses, such as diabetes mellitus. However, various limitations in terms of their application and efficacies exist. Furthermore, there is still much to be done to discover the right herbal medicine for diabetes. Aim of the study This paper aims to evaluate previous herbal studies on the management of diabetes mellitus, to address their strengths and weaknesses and propose a general framework for future studies. Approach and methods Data sources such as PubMed, ScienceDirect, Scopus, SpringerLink, and Wiley were searched, limited to Iran, using 36 search terms such as herbal, traditional, medicine, and phytopharmacy in combination with diabetes and related complications. Reviewed articles were evaluated regarding the use of botanical nomenclature and included information on (1) identity of plants and plant parts used, (2) the processing procedure, and (3) the extraction process. The main outcomes were extracted and then surveyed in terms of the efficacies of herbs in the management of diabetes mellitus. Then a comparative study was performed between Iranian and non-Iranian studies with respect to herbs best studied in Iran. Results Of the 82 herbs studied in Iran, only six herbs were endemic and 19 were studied in detail. Although most of the reviewed herbs were found to decrease the level of blood glucose (BG) and/or glycated hemoglobin (HbA1C) in both Iranian and non-Iranian studies, information on their pharmacological mechanisms is scarce. However, the level of HbA1C was measured in a limited number of clinical trials or animal studies. Available information on both short- and long-term use of studied herbs on diabetes related complications and functions of involved organs as well as comorbid depression and/or simultaneous changes in lifesyle is also insufficient. Furthermore, little or no information on their phytochemical, toxicological, and herb–drug interaction properties is available. It is worth noting that the efficacy of the reviewed herbs has been studied scarcely in both humans and animals regarding both Iranian and non-Iranian studies. A significant number of reviewed articles failed to cite the scientific name of herbs and include information on the processing procedure and the extraction process. Conclusions Treatment of diabetes mellitus as a multifactorial disease using herbal medicines requires a comprehensive approach. In order to discover the right herbal medicine for the management of diabetes many other important factors than the levels of BG, HbA1C and insulin should be considered. According to our criteria, all the reviewed herbs suffered from inadequate investigation in human, animal and in vitro models in this respect, whereas they are worth investigating further. However, more research on endemic plants and the traditional history of herbal medicine is warranted. In our opinion, the pharmacological, toxicological, and phytochemical information should be obtained before clinical trials. Furthermore, information such as botanical scientific nomenclature, side effects, and toxicity will improve the quality and validity of publications in herbal research. In particular, designing a database covering all valid information about herbs and/or diseases will decrease unnecessary costs and increase the efficiency of research.

Background: Little is known about the association between inflammatory markers in the acute stroke phase and long-term stroke outcomes. Methods: In a population-based study of stroke with 5 years follow-up, we measured the level of serum heat shock protein 27 immunoglobulin G antibody (anti-HSP27), C-reactive protein (CRP), and pro-oxidant antioxidant balance (PAB) in the acute stroke phase. We analyzed the association between these inflammatory biomarkers and stroke outcomes (recurrence, death and disability/functional dependency) with using multivariable Cox proportional hazard models. Results: Two hundred sixty-five patients with first-ever stroke were included in this study. The severity of stroke at admission, measured by National Institute of Health Score Scale was associated with serum concentration of CRP (Spearman’s rank correlation coefficient rs = 0.2; p = 0.004). CRP also was associated with 1-year combined death and recurrence rate ([adjusted hazard ratio 1.06, 95% CI 1.01–1.12; p = 0.02]). However, we did not find any association between the concentrations of CRP, anti-HSP27, PAB, and 5-year death and stroke recurrence rates. None of 3 biomarkers was associated with the long-term disability rate (defined as modified Rankin Scale >2) and functional dependency (defined as Barthel Index Conclusion: CRP has a significant direct, yet weak, correlation to the severity of stroke. In addition, the level of CRP at admission may have a clinical implication to identify those at a higher risk of death or recurrence.

Computing and memory in living cells are central to encoding next-generation therapies and studying in situ biology, but existing strategies have limited encoding capacity and are challenging to scale. To overcome this bottleneck, we developed a highly scalable, robust and compact platform for encoding logic and memory operations in living bacterial and human cells. This platform, named DOMINO for DNA-based Ordered Memory and Iteration Network Operator, converts DNA in living cells into an addressable, readable, and writable computation and storage medium via a single-nucleotide resolution read-write head that enables dynamic and highly efficient DNA manipulation. We demonstrate that the order and combination of DNA writing events can be programmed by biological cues and multiple molecular recorders can be coordinated to encode a wide range of order-independent, sequential, and temporal logic and memory operations. Furthermore, we show that these operators can be used to perform both digital and analog computation, and record signaling dynamics and cellular states in a long-term, autonomous, and minimally disruptive fashion. Finally, we show that the platform can be functionalized with gene regulatory modules and interfaced with cellular circuits to continuously monitor cellular phenotypes and engineer gene circuits with artificial learning capacities. We envision that highly scalable, compact, and modular DOMINO operators will lay the foundation for building robust and sophisticated synthetic gene circuits for numerous biotechnological and biomedical applications.One Sentence SummaryA programmable read-write head with single-nucleotide-resolution for genomic DNA enables robust and scalable computing and memory operations in living cells.

Introduction: Cerebral venous-sinus thrombosis (CVST) is a life threatening condition that needs rapid diagnosis and treatment. It appears comparatively more common in Middle East and South Asia. Objectives: To determine the demographic, clinical patterns, etiologies and prognostic factors of CVST in the North East of Iran. Materials and Methods: All adult patients admitted with a documented diagnosis of CVST from January 2011 to March 2012 in an academic hospital in the North East of Iran, entered this prospective descriptive study. The patients' demographic characteristics, clinical presentations, laboratory and brain imaging findings, treatment options were also studied. Follow-up visits were performed at month 1, 6, and then at month 12 using modified Rankin Scale (mRS). Findings were analyzed using descriptive tests and Chi square test in SPSS software version 21. Results: Sixty patients (13.3% men, 86.7% women) with mean age of 38.11±11.30 years were identified. Fifty one cases (85%) had a clinical picture of increased intracranial pressure. Causes included positive antiphospholipid antibodies in 3.3%, protein C, S and anti thrombin III deficiency in 5%, 1.7% and 3.3%, polycythemia in 1.7%, infections in 1.7%, postpartum in 9.6% of women, and using Oral Contraceptive Pills (OCPs) in 65.38%. We found 10% mortality rate on discharge and 11.9% within 30 days and 42.7% rate of death or dependency at month 12. Conclusion: The findings of the study indicate that the use of OCPs was a main factor associated with CVST especially in association with inherited hypercoagulable state.

Background: Intracranial large-artery disease (LAD) is a predominant vascular lesion found in patients with stroke of Asian, African, and Hispanic origin, whereas extracranial LAD is more prevalent among Caucasians. These patterns are not well-established in the Middle East. We aimed to characterize the incidence, risk factors, and long-term outcome of LAD strokes in a Middle-Eastern population. Methods: The Mashhad Stroke Incidence Study is a community-based study that prospectively ascertained all cases of stroke among the 450,229 inhabitants of Mashhad, Iran between 2006 and 2007. Ischemic strokes were classified according to the TOAST criteria. Duplex-ultrasonography (98.6%), MR-angiography (8.3%), CT-angiography (11%), and digital-subtraction angiography (9.7%) were performed to identify involvements. Vessels were considered stenotic when the lumen was occluded by >50%. Results: We identified 72 cases (15.99 per 100,000) of incident LAD strokes (mean age 67.6 ± 11.7). Overall, 77% had extracranial LAD (58% male, mean age 69.8 ± 10.3; 50 [89%] carotid vs. 6 [11%] vertebral artery), and the remaining 23% (56% male, mean age 60.2 ± 13.4; 69% anterior-circulation stenosis) had intracranial LAD strokes. We were unable to detect differences in case-fatality between extracranial (1-year: 28.6%; 5-year: 59.8%) and intracranial diseases (1-year: 18.8%; 5-year: 36.8%; log-rank; p = 0.1). Conclusion: Extracranial carotid stenosis represents the majority of LAD strokes in this population. Thus, public health strategies may best be developed in such a way that they are targeted toward the risk factors that contribute to extracranial stenosis.

Background Population-based data regarding stroke among women are scarce in developing countries. This study was designed to determine whether sex differences exist in stroke incidence, mortality, and recurrence. Methods The Mashhad Stroke Incidence Study is a population-based cohort study in Iran. For a period of 1 year, all patients with stroke in 3 geographical regions in Mashhad were recruited and then followed up for 5 years. Age- and sex-specific crude incidence rates were standardized to the World Health Organization New World Population. Male-to-female incidence rate ratios were assessed for all age groups and all subtypes of first-ever stroke (FES). Results The annual crude incidence rate of FES (per 100,000 population) was similar in men (144; 95% confidence interval [CI]: 129-160) and women (133; 95% CI: 119-149). Standardized FES annual incidence rates were 239 (95% CI: 213-267) for men and 225 (95% CI 200-253) for women, both greater than in most western countries. There were no significant differences in stroke recurrence or case-fatality between women and men during early and long-term follow-up. Conclusion The similar incidence of stroke between men and women highlights the importance of equally prioritizing adequate preventive strategies for both sexes. The greater relative incidence of stroke in women in Mashhad compared with other countries warrants improvement of primary and secondary stroke prevention.

Background Incidence, risk factors, case fatality and survival rates of ischemic stroke subtypes are unknown in the Middle East due to the lack of community-based incidence stroke studies in this region. Aim To characterize ischemic stroke subtypes in a Middle Eastern population. Methods The Mashad Stroke Incidence Study is a community-based study that prospectively ascertained all cases of stroke among the 450,229 inhabitants of Mashhad, Iran between 2006 and 2007. We identified 512 cases of first-ever ischemic stroke [264 men (mean age 65.5 ± 14.4) and 248 women (mean age 64.14 ± 14.5)]. Subtypes of ischemic stroke were classified according to the TOAST criteria. Incidence rates were age standardized to the WHO and European populations. Results The proportion of stroke subtypes was distributed as follows: 14.1% large artery disease, 15% cardioembolic, 22.5% small artery disease, 43.9% undetermined and 4.5% other. The greatest overall incidence rates were attributed to undetermined infarction (49.97/100,000) followed by small artery disease (25.54/100,000). Prevalence of hypertension, diabetes and atrial fibrillation differed among ischemic stroke subtypes. Overall, there were 268 (52.34%) deaths and 73 (14.25%) recurrent strokes at five years after incident ischemic stroke, with the greatest risk of recurrence seen in the large artery disease (35.6%) and cardioembolic (35.5%) subgroups. Survival was similar in men and women for each stroke subtype. Conclusions We observed markedly greater incidence rates of ischemic stroke subtypes than in other countries within the Mashad Stroke Incidence Study after age standardization. Our findings should be considered when planning prevention and stroke care services in this region.

The use of herbal medicine has been faced with a huge welcome by patients and scientists, as well as drug industries. It seems that reducing the time of research, economizing investments with better safety, and conducting high-quality botanical research are essential and indispensable. This study aimed to introduce the first reciprocal herb-disease encyclopedia and to recount some of the salient points of herbal research based on Iranian studies. A search limited to Iran was conducted using 36 search terms in the data banks Pubmed, Scopus, ScienceDirect, Wiley, and SpringerLink up to the end of 2012. Data including the investigated disease(s) and common and scientific names of the investigated herbs were extracted from the titles and abstracts of 1310 articles. Investigated subjects and diseases have been categorized in 18 groups: cancer, cardiovascular, cellular-molecular, embryology, endocrinology, genito-urology, gastrointestinal, gynecology, immunology, infectious, metabolism, mucocutaneous, musculoskeletal, neuroscience, ophthalmology, renal, reproductive, and respiratory topics. Herbs including Crocus sativus L., Allium sativum L., and Zataria multiflora Boiss from totally 560 studied herbs were the most studied ones. Only 69 of 560 studied (12.5%) herbs were endemic to Iran. Due to the vast majority of information available for herbs and diseases, an herb-disease encyclopedia comes to the help of herbal researchers and enthusiasts to find that which herb is useful or recommended for which kind(s) of health problems, and/or for the management, pretreatment or treatment of a specific disease or disorders.

Purpose: To investigate whether microRNA (MIR)-184 mutations make a substantial contribution to keratoconus (KCN) among affected Iranian patients. Methods: A total of 47 Iranian KCN patients, diagnosed based on family history, clinical examinations using slit lamp biomicroscopy, refraction and corneal topography were enrolled in this study. The pri-miR-184 encoding gene obtained from the DNAs of all participants was amplified using polymerase chain reaction and subsequently sequenced by the Sanger dideoxynucleotide protocol. The sequences were compared to MIR184 reference sequence in order to identify sequence variations. The potential effects of a single variation observed on RNA structure was predicted. Results: Only one sequence variation, +39G >T, was observed within the pri-miR-184 encoding sequence in one proband. The patient's KCN-affected sister harbored the same variation. The variation was not novel and was recently shown to be present at similar frequencies among large cohorts of KCN patients and control individuals. Conclusion: Mutations in MIR-184 are not a major cause of keratoconus among Iranian patients. The pri-miR-184 sequence needs to be screened in larger cohorts in order to establish whether mutations in the gene are present at low frequencies among Iranian patients.

Background In developing countries, there are few comprehensive studies of mortality following stroke. Aims and/or hypothesis We aimed to determine the one-year case fatality rate following stroke and to identify factors associated with death in a population-based stroke incidence study in Iran. Methods Six hundred eighty-four patients who had suffered a stroke between November 21, 2006, and November 20, 2007, and were recruited to the Mashhad Stroke Incidence Study were followed up at one-year. Most patients were seen in an outpatient visit. When patients had died, a verbal autopsy was conducted by telephone with the next of kin. Results A total of 226 (34.3%) patients died during the first year following stroke. The cumulative one-year case fatality rate was 30.6% following ischemic stroke and 53.0% following hemorrhagic stroke (55.8% after intracerebral hemorrhage and 35.7% after subarachnoid hemorrhage). The majority of these deaths occurred in the first 28 days after stroke (17.7% with ischemic and 43.0% with hemorrhagic stroke). Factors associated with greater mortality at one-year (excluding those who died during the first week) were hemorrhagic stroke [hazard ratio (HR) 3.99; 95% confidence interval 1.90-8.37], age (HR 1.05; 95% confidence interval 1.03-1.08), previous transient ischemic attack (HR 2.45; 95% confidence interval 1.00-5.99), and National Institutes of Health Stroke Scale on admission (HR 1.14; 95% confidence interval 1.10-1.17). Conclusion Despite the younger age of stroke occurrence in Iran, the one-year case fatality rate following stroke is similar to that reported in developed countries.

Background Insufficient information is available on the barriers that explain low rates of thrombolytic therapy for acute ischemic stroke (AIS) in developing countries compared with rates in developed societies. By the present study, we aimed to assess the implementation of thrombolytic therapy in the northeast of Iran to explore the gaps and hurdles against thrombolysis as the generally accepted treatment for AIS. Methods In a 1-year cohort study among AIS patients admitted to the second largest tertiary neurologic referral center in Iran, those who met the prespecified selection criteria were treated with intravenous recombinant tissue plasminogen activator (rtPA). Results Among 1,144 patients admitted with AIS, only 14 (1.2%) were treated with rtPA. The mean onset-to-needle and door-to-needle times were 172 and 58 minutes, respectively; 980 (85.6%) patients were initially excluded from the study because of late arrival. Additionally, 60 patients in total were omitted because of either their high age (3.7%) or passing the gold standard time limit for rtPA therapy after preliminary evaluations (1.6%), and 90 more patients (7.9%) were considered not suitable for thrombolysis because of the severity of the symptoms or the higher risk of bleeding on rtPA. Conclusions Access to thrombolytic therapy for AIS in Iran is less than in most developed countries but comparable with other developing countries. Awareness campaigns are needed to minimize barriers and improve access to thrombolysis and specialized stroke care in Iran.

The past decade has witnessed tremendous advances in the design and implementation of synthetic gene circuits that program living cells to perform specific user-defined tasks. Synthetic circuits have been implemented in bacteria, yeast, and mammalian cells, using a variety of transcriptional and post-transcriptional regulatory mechanisms. These devices, which lie at the intersection of biology and engineering, have provided insights into the function of naturally occurring gene regulatory networks. Furthermore, they hold the potential for transformative future applications in medicine, bioremediation, manufacturing, and more. In this review, some examples are presented of commonly used synthetic circuits, including oscillators, switches, memory devices, and circuits that perform digital and analog computation. The building blocks of synthetic gene circuits, as well as the challenges and considerations of circuit design, are also discussed. Finally, an overview is provided of the potential practical applications of this dynamic field of research. Keywords: analog circuit; digital circuit; logic gate; orthogonality; oscillator; synthetic transcription factor (sTF); toggle switch; transfer function; tunability

Headache is the most frequent presenting symptom of cerebral venous thrombosis (CVT), most commonly associated with other manifestations.

Background Migraine is one of the most common types of headache, with significant socioeconomic effects. Prophylactic drugs are used to prevent migraine headaches but are unpromising. Objective To assess the effects of adding acupuncture to conventional migraine prophylaxis. Methods One hundred patients with migraine (41 male, 59 female), in whom prophylactic drugs had not produced a fall of at least 50% in the number of attacks, entered the study. The patients were randomised into two groups, sham and true acupuncture. The patients in both groups continued their prophylactic treatment and received 12 sessions of either true or sham acupuncture. Each session was 30 min and was repeated three times a week. The number of headaches in the two groups was compared at baseline, and at the end of four successive months. Results There was no significant difference in the frequency of attacks between the two groups before intervention. After 1 month, the frequency of attacks each month decreased from 5.1 (0.8) to 3.4 (1.2) in the true acupuncture group, and from 5.0 (0.8) to 4.4 (1.1) in the sham acupuncture group (a significant difference, pConclusions Acupuncture is applicable as an adjunct to prophylactic drugs in migraineurs in whom the number of attacks does not fall with prophylactic medication.

Background and Purpose— The epidemiology of stroke and its subtypes in the Middle East is unclear. Most previous studies have been performed in Western countries, and incidence rates are unlikely to apply in the Middle East. We aimed to determine the incidence of stroke in Mashhad, northeastern Iran. Methods— During a 12-month period (2006–2007), we prospectively ascertained all strokes occurring in a population of 450 229. Multiple overlapping sources were used to identify people with stroke. A large number of volunteers assisted in finding stroke patients not admitted to hospital. Potential cases were reviewed by a group of stroke experts before inclusion. Results— A total of 624 first-ever strokes occurred during the study period, 98.4% undergoing imaging. Despite a relatively low crude annual incidence rate of first-ever stroke FES (139; 95% CI, 128 to 149) per 100 000 residents, rates adjusted to the European population aged 45 to 84 years were higher than in most other countries: 616 (95% CI, 567 to 664) for ischemic stroke, 94 (95% CI, 75 to 113) for intracerebral hemorrhage, and 12 (95% CI, 5 to 19) for subarachnoid hemorrhage. Age-specific stroke incidence was higher in younger patients than is typically seen in Western countries. Comparison of age-specific incidence rates between regions revealed that stroke in Mashhad occurs approximately 1 decade earlier than in Western countries. Conclusions— The results of this study provide evidence that the incidence of stroke in Iran is considerably greater than in most Western countries, with stroke occurring at younger ages. Ischemic stroke incidence was also considerably greater than reported in other regions.

Background The Hajj Ceremony, the largest annual gathering in the world, is the most important life event for any Muslim. This study was designed to evaluate the incidence of stroke among Iranian pilgrims during the Hajj ceremony. Methods We ascertained all cases of stroke occurring in a population of 92,974 Iranian pilgrims between November 27, 2007 and January 12, 2008. Incidence and risk factors of the first ever stroke in Hajj pilgrims were compared, within the same time frame, to those of the Mashhad residents, the second largest city in Iran. Data for the latter group were extracted from the Mashhad Stroke Incidence Study (MSIS) database. Results During the study period, 17 first-ever strokes occurred in the Hajj pilgrims and 40 first-ever stroke strokes occurred in the MSIS group. Overall, the adjusted incidence rate of first ever stroke in the Hajj cohort was lower than that of the MSIS population (9 vs. 16 per 100,000). For age- and gender-specific subgroups, the Hajj stroke crude rates were in general similar to or lower than the general population of Mashhad, Iran, with the exception of women aged 35 to 44 years and aged >75 years who were at greater risk of having first-ever stroke than the non-pilgrims of the same age. Conclusion The first ever stroke rate among Iranian Hajj pilgrims was lower than that of the general population in Mashhad, Iran, except for females 35–44 or more than 75 years old. The number of events occurring during the Hajj suggests that Islamic countries should consider designing preventive and screening programs for pilgrims.