Injectable Multi-Drug Formulation for the Postoperative Management of Ocular Surgery

In this dissertation, the interaction between particles or particles and polymers were examined. In addition, outcomes of such studies were used to develop drug delivery formulations. Initially, by carrying out Brownian dynamics (BD) simulations binding kinetics between two spheres in the dilute limit under shear flow for the entire Pe values (measure of flow strength) was studied. Effects of Pe, hydrodynamic interactions, inter-particle potential and surface anisotropy were studied. Results were in agreement with previous literature that had limited range of applicability including zero and infinite shear rate Smoluchowski limits, as well as high Pe perturbation results of Feke and Schowalter [J. Fluid Mech. 133, 17-35 (1983)]. Next, developing a drug delivery system for the postoperative management of ocular surgery was considered. In routine care after cataract surgery, patients are required to receive antibiotics for a week and steroids for at least a month. Later during postoperative treatment period, ocular pressure increases and could be managed by administration of ocular hypotensives, which adds to postoperative treatment burden. Currently, the required drug molecules in the postoperative treatment are delivered mainly by eye drops, which have significant shortcomings, such as poor patient compliance, low drug bioavailability and allergic reactions. Hence, different routes were pursued to make a formulation that reduces reliance on the patients to use eye drops. Initially, layer-by-layer (LbL) assembly of nanoparticles (NPs) and polyelectrolytes was considered as a viable strategy. The goal was to layer different sheets of LbL films with different drug loaded NPs in order to fine-tune the drug release profile. The effect of different parameters on the growth of LbL films was studied and the optimal conditions to grow thick LbL films with inexpensive blank NPs were attained. Unfortunately, by switching from blank polystyrene NPs to biodegradable poly(D,L-lactide-co-glycolide) (PLGA) NPs, the growth of LbL films was interrupted. Therefore, we were faced with the challenge of modifying our research to find a more robust solution for postoperative management following cataract surgery. In a subsequent attempt, the multidrug release system was developed utilizing thermoresponsive polymer solutions. The invented drug release system is composed of microparticles incorporated into a bulk hydrogel that was engineered to be in liquid form at room temperature for simple delivery into the eye and form a hydrogel network at physiological body temperatures to act as a depot release platform. The delivery platform was designed to mimic current topical application of postoperative ocular formulations, releasing the antibiotic for up to a week, and the corticosteroid and the ocular hypotensive agents for at least a month. Different means to finely tune drug release was demonstrated. To ensure the most linear drug release, more hydrophobic blocks such as PLCL should be used in the triblock copolymer. Increasing the hydrophobicity of the polymer encapsulating the drug molecules, it was possible to prolong the release duration of drugs substantially. Finally, preliminary results on overcoming the poor bioavailability of free drug molecules to be used for the treatment of ocular diseases and cancer were examined. Two anti-hypoxia inducible factors (anti-HIFs) were successfully loaded in PLGA NPs with small particle size and considerable drug loading. Next, drug release from NPs was evaluated, in vitro. Finally, the effect of NPs on inhibiting HIF expression and blocking angiogenesis were examined in vivo. Results demonstrate significant improvements using NPs compared to free drug.PHDMechanical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/140939/1/maziar_1.pd

Association between generation gap in interest, familiarity and application of information and communication technology

Given the introduction of information and communication technology and its rapid progress in every society, its use and application is different between various social institutions in that it demonstrates the difference between previous and present generation. Hence, the research was conducted in the school year 2012-2013 with the aim of applying information technology among female high school students and their mothers in Gorgan Province. The research method is a descriptive-analytical method; using a cluster sampling, of 34 female schools 8 schools were randomly chosen and 260 students were included in the study out of 1625 students. Using collected questionnaires and information obtained from independent t-test the results indicated that there was a significant difference between the mean of familiarity, interest and mothers' and their children's use of information technology. © Medwell Journals, 2016

Static and dynamic source identification of trace elements in river and soil environments under anthropogenic activities in the Haraz plain, Northern Iran

Unsustainable human activities have disrupted the natural cycle of trace elements, causing the accumulation of chemical pollutants and making it challenging to determine their sources due to interwoven natural and human-induced processes. A novel approach was introduced for identifying the sources and for quantifying the contribution of trace elements discharge from rivers to soils. We integrated fingerprinting techniques, soil and sediment geochemical data, geographically weighted regression model (GWR) and soil quality indices. The FingerPro package and the state-of-the-art tracer selection techniques including the conservative index (CI) and consensus ranking (CR) were used to quantify the relative contribution of different upland sub-watersheds in trace element discharge soil. Our analysis revealed that off-site sources (upland watersheds) and in-site sources (land use) both play an important role in transferring trace elements to the Haraz plain (northern Iran). The unmixing model's results suggest that the Haraz sub-watersheds exhibit a higher contribution to trace elements transfer in the Haraz plain, and therefore, require greater attention in terms of implementing soil and water conservation strategies. However, it is noteworthy that the Babolroud (adjacent to Haraz) exhibited a better performance of the model. A spatial correlation between certain heavy metals, such as As and Cu, and rice cultivation existed. Additionally, we found a significant spatial correlation between Pb and residential areas, particularly in the Amol region. Our result highlights the importance of using advanced spatial statistical techniques, such as GWR, to identify subtle but critical associations between environmental variables and sources of pollution. The methodology used comprehensively identifies dynamic trace element sourcing at the watershed scale, allowing for pollutant source identification and practical strategies for soil and water quality control. Tracer selection techniques (CI and CR) based on conservatives and consensus improve unmixing model accuracy and flexibility for precise fingerprinting

Coronary Artery Bypass Grafting: Simultaneous Head and Neck Mass Surgery

Background: Coronary artery disease (CAD) and cancer have common risk factors. According to the necessity of mass resection in patients with CAD at the same time, we decided to do neck and head mass resection and coronary artery bypass grafting (CABG) simultaneously and assess the results.Methods: The current study was done on patients who were candidates for simultaneous head and neck mass resection and CABG. The patients’ files were extracted, the information and complications were recorded in a questionnaire, and then necessary data were extracted.Results: Totally 9 patients (3 females and 6 males) with a mean age of 69.11 ± 6.67 standard deviation years were studied. The most common site of squamous cell carcinoma in this study was tongue. Infection occurred in three patients, two of which (66.66%) died. Side effects occurred in four patients.Conclusions: It seems that, according to the anatomical position of neck mass, proximity to the airways and large blood supply in that area, and also because of inappropriate access to the anatomical zones, the survival rate and complications in this surgical setting (simultaneous surgeries) are different from that of other studies. It seems that further studies are needed to be done with the subject of concomitant head and neck mass surgery and CABG this time with a larger number of patients

Nomenclature

ABSTRACT — Bouncing, balancing and swinging the leg forward can be considered as three basic control tasks for bipedal locomotion. Defining the trunk by an unstable inverted pendulum, balancing as being translated to trunk stabilization is the main focus of this paper. The control strategy is to generate a hip torque to have upright trunk to achieve robust hopping and running. It relies on the Virtual Pendulum (VP) concept which is recently proposed for trunk stabilization, based on human/animal locomotion analysis. Based on this concept, a control approach, named Virtual Pendulum Posture control (VPPC) is presented, in which the trunk is stabilized by redirecting the ground reaction force to a virtual support point. The required torques patterns generated by the controller, could partially be exerted by elastic structures like hip springs. Hybrid Zero Dynamics (HZD) control approach is also applied as an exact method of keeping the trunk upright. Stability of the motion which is investigated by Poincare ´ map analysis could be achieved by hip springs, VPPC and HZD. The results show that hip springs, revealing muscle properties, could facilitate trunk stabilization. Compliance in hip produces acceptable performance and robustness compared with VPPC and HZD, while it is a passive structure

Measuring Iran’s success in achieving Millennium Development Goal 4: a systematic analysis of under-5 mortality at national and subnational levels from 1990 to 2015

Background Child mortality as one of the key Millennium Development Goals (MDG 4—to reduce child mortality by two-thirds from 1990 to 2015), is included in the Sustainable Development Goals (SDG 3, target 2—to reduce child mortality to fewer than 25 deaths per 1000 livebirths for all countries by 2030), and is a key indicator of the health system in every country. In this study, we aimed to estimate the level and trend of child mortality from 1990 to 2015 in Iran, to assess the progress of the country and its provinces toward these goals. Methods We used three different data sources: three censuses, a Demographic and Health Survey (DHS), and 5-year data from the death registration system. We used the summary birth history data from four data sources (the three censuses and DHS) and used maternal age cohort and maternal age period methods to estimate the trends in child mortality rates, combining the estimates of these two indirect methods using Loess regression. We also used the complete birth history method to estimate child mortality rate directly from DHS data. Finally, to synthesise different trends into a single trend and calculate uncertainty intervals (UI), we used Gaussian process regression. Findings Under-5 mortality rates (deaths per 1000 livebirths) at the national level in Iran in 1990, 2000, 2010, and 2015 were 63·6 (95% UI 63·1–64·0), 38·8 (38·5–39·2), 24·9 (24·3–25·4), and 19·4 (18·6–20·2), respectively. Between 1990 and 2015, the median annual reduction and total overall reduction in these rates were 4·9% and 70%, respectively. At the provincial level, the difference between the highest and lowest child mortality rates in 1990, 2000, and 2015 were 65·6, 40·4, and 38·1 per 1000 livebirths, respectively. Based on the MDG 4 goal, five provinces had not decreased child mortality by two-thirds by 2015. Furthermore, six provinces had not reached SDG 3 (target 2). Interpretation Iran and most of its provinces achieved MDG 4 and SDG 3 (target 2) goals by 2015. However, at the subnational level in some provinces, there is substantial inequity. Local policy makers should use effective strategies to accelerate the reduction of child mortality for these provinces by 2030. Possible recommendations for such strategies include enhancing the level of education and health literacy among women, tackling sex discrimination, and improving incomes for families

Growth Kinetics in Layer‐by‐Layer Assemblies of Organic Nanoparticles and Polyelectrolytes

The growth rates of layer‐by‐layer (LbL) assemblies of polyelectrolytes (PEs) with oppositely charged polystyrene (PS) nanoparticles (NPs) as a function of molecular weight (MW) of the PEs, ionic strength of the media, and NP size and charge are systematically investigated. To optimize LbL growth, the effects of suspension concentration, pH of the media, and deposition time on the growth rate of multilayers are assessed. Both linear and exponential growth behaviors are observed and, under optimal conditions, films of up to around 1 μm thick can readily be assembled after 10 or so bilayers have been deposited. For many of the cases studied, an intermediate MW of PE leads to the fastest film buildup, for both cationic poly(ethyleneimine) deposited alternately with anionic PS NPs and for anionic poly(acrylic acid) deposited alternately with cationic PS NPs. The existence of an optimal MW suggests that growth rate is determined by a balance of thermodynamic factors, including density of polymer bridges between particles, and kinetic factors, specifically the diffusivity of polymer in the film. The optimal MW, however, is very sensitive to the materials used. Moreover, depending on the MW of the PE, increasing salinity could increase or decrease the growth kinetics. Finally, the surface morphology of the films is characterized with AFM and SEM to reveal that the roughness increases less than linearly with film thickness.Growth factors: The growth rates of layer‐by‐layer (LbL) assemblies of polyelectrolytes (PEs) with oppositely charged polystyrene nanoparticles are systematically investigated. The molecular weight of a PE has a considerable effect on LbL film growth and its surface morphology (see figure).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135666/1/cphc201600789_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135666/2/cphc201600789-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135666/3/cphc201600789.pd

Disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE) in Iran and its neighboring countries, 1990–2015

BACKGROUND: Summary measures of health are essential in making estimates of health status that are comparable across time and place. They can be used for assessing the performance of health systems, informing effective policy making, and monitoring the progress of nations toward achievement of sustainable development goals. The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) as main summary measures of health. We assessed the trends of health status in Iran and 15 neighboring countries using these summary measures. METHODS: We used the results of GBD 2015 to present the levels and trends of DALYs, life expectancy (LE), and HALE in Iran and its 15 neighboring countries from 1990 to 2015. For each country, we assessed the ratio of observed levels of DALYs and HALE to those expected based on socio-demographic index (SDI), an indicator composed of measures of total fertility rate, income per capita, and average years of schooling. RESULTS: All-age numbers of DALYs reached over 19 million years in Iran in 2015. The all-age number of DALYs has remained stable during the past two decades in Iran, despite the decreasing trends in all-age and age-standardized rates. The all-cause DALY rates decreased from 47,200 in 1990 to 28,400 per 100,000 in 2015. The share of non-communicable diseases in DALYs increased in Iran (from 42% to 74%) and all of its neighbors between 1990 and 2015; the pattern of change is similar in almost all 16 countries. The DALY rates for NCDs and injuries in Iran were higher than global rates and the average rate in High Middle SDI countries, while those for communicable, maternal, neonatal, and nutritional disorders were much lower in Iran. Among men, cardiovascular diseases ranked first in all countries of the region except for Bahrain. Among women, they ranked first in 13 countries. Life expectancy and HALE show a consistent increase in all countries. Still, there are dissimilarities indicating a generally low LE and HALE in Afghanistan and Pakistan and high expectancy in Qatar, Kuwait, and Saudi Arabia. Iran ranked 11th in terms of LE at birth and 12th in terms of HALE at birth in 1990 which improved to 9th for both metrics in 2015. Turkey and Iran had the highest increase in LE and HALE from 1990 to 2015 while the lowest increase was observed in Armenia, Pakistan, Kuwait, Kazakhstan, Russia, and Iraq. CONCLUSIONS: The levels and trends in causes of DALYs, life expectancy, and HALE generally show similarities between the 16 countries, although differences exist. The differences observed between countries can be attributed to a myriad of determinants, including social, cultural, ethnic, religious, political, economic, and environmental factors as well as the performance of the health system. Investigating the differences between countries can inform more effective health policy and resource allocation. Concerted efforts at national and regional levels are required to tackle the emerging burden of non-communicable diseases and injuries in Iran and its neighbors

The burden of disease and injury in Iran 2003

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to estimate the burden of disease and injury in Iran for the year 2003, using Disability-Adjusted Life Years (DALYs) at the national level and for six selected provinces.</p> <p>Methods</p> <p>Methods developed by the World Health Organization for National Burden of Disease (NBD) studies were applied to estimate disease and injury incidence for the calculation of Years of Life Lost due to premature mortality (YLL), Years Lived with Disability (YLD), and DALYs. The following adjustments of the NBD methodology were made in this study: a revised list with 213 disease and injury causes, development of new and more specific disease modeling templates for cancers and injuries, and adjustment for dependent comorbidity. We compared the results with World Health Organization (WHO) estimates for Eastern Mediterranean Region, sub-region B in 2002.</p> <p>Results</p> <p>We estimated that in the year 2003, there were 21,572 DALYs due to all diseases and injuries per 100,000 Iranian people of all ages and both sexes. From this total number of DALYs, 62% were due to disability premature deaths (YLD) and 38% were due to premature deaths (YLL); 58% were due to noncommunicable diseases, 28% – to injuries, and 14% – to communicable, maternal, perinatal, and nutritional conditions. Fifty-three percent of the total number of 14.349 million DALYs in Iran were in males, with 36.5% of the total due to intentional and unintentional injuries, 15% due to mental and behavioral disorders, and 10% due to circulatory system diseases; and 47% of DALYs were in females, with 18% of the total due to mental and behavioral disorders, 18% due to intentional and unintentional injuries, and 12% due to circulatory system diseases. The disease and injury causes leading to the highest number of DALYs in males were road traffic accidents (1.071 million), natural disasters (548 thousand), opioid use (510 thousand), and ischemic heart disease (434 thousand). The leading causes of DALYs in females were ischemic heart disease (438 thousand), major depressive disorder (420 thousand), natural disasters (419 thousand), and road traffic accidents (235 thousand). The burden of disease at the province level showed marked variability. DALY estimates by Iran's NBD study were higher than those for EMR-B by WHO.</p> <p>Conclusion</p> <p>The health and disease profile in Iran has made the transition from the dominance of communicable diseases to that of noncommunicable diseases and road traffic injuries. NBD results are to be used in health program planning, research, and resource allocation and generation policies and practices.</p

Maternal mortality and morbidity burden in the Eastern Mediterranean region : findings from the Global Burden of Disease 2015 study

Assessing the burden of maternal mortality is important for tracking progress and identifying public health gaps. This paper provides an overview of the burden of maternal mortality in the Eastern Mediterranean Region (EMR) by underlying cause and age from 1990 to 2015. We used the results of the Global Burden of Disease 2015 study to explore maternal mortality in the EMR countries. The maternal mortality ratio in the EMR decreased 16.3% from 283 (241-328) maternal deaths per 100,000 live births in 1990 to 237 (188-293) in 2015. Maternal mortality ratio was strongly correlated with socio-demographic status, where the lowest-income countries contributed the most to the burden of maternal mortality in the region. Progress in reducing maternal mortality in the EMR has accelerated in the past 15 years, but the burden remains high. Coordinated and rigorous efforts are needed to make sure that adequate and timely services and interventions are available for women at each stage of reproductive life