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Introduction: Early ICH expansion is associated with a higher rate of poor outcomes and death in aSAH patients, especially in limited-resource settings. This study aimed to investigate the impact of ICH expansion on the outcomes and the factors related to an ICH expansion in aSAH patients in an LMIC. Hypothesis: Understanding factors related to ICH after an aneurysmal rupture in different countries, particularly in limited-resource regions, is crucial for reducing poor outcomes and mortality. Methods: We performed a multicenter prospective cohort study of patients (≥18 years) presenting with aSAH at three central hospitals in Hanoi, Vietnam, from August 2019 to June 2021. We collected data on the demographics, baseline characteristics, management, and outcomes and compared these data between patients who had an ICH expansion (defined as ICH detected on an admission CT scan) and patients who did not. We assessed factors associated with ICH expansion on admission using logistic regression. Results: Of 415 patients, 198 (47.7%) were men, and the median age was 57.0 years (IQR: 48.0-67.0). ICH expansion accounted for 20.5% (85/415) of aSAH patients. There was a significant difference in the 90-day poor outcomes (43.5%; 37/85 and 29.1%; 96/330; p=0.011) and 90-day mortality (36.5%; 31/85 and 20.0%; 66/330; p=0.001) between patients who had ICH and patients who did not have ICH expansion. The multivariate analysis showed that systolic BP of 140 mmHg or more (OR: 2.674; 95% CI: 1.372-5.214), WFNS grades II (OR: 3.683; 95% CI: 1.250-10.858) to V (OR: 6.912; 95% CI: 2.553-18.709), and a ruptured MCA aneurysm (OR: 3.717; 95% CI: 1.848-7.477) were independent predictors of ICH expansion. Conclusions: In our study, ICH accounted for a substantial proportion of aSAH patients and contributed significantly to a high rate of poor outcomes and death. On admission, a higher systolic BP, a worse neurological status, and a ruptured MCA aneurysm were independent predictors of ICH expansion. This study indicates independent predictors of an early ICH expansion, such as a higher admission systolic BP and a worse initial neurological status, after aneurysmal ruptures that require only a clinical examination and, therefore, may be particularly valuable in resource-limited settings.

In this study, we developed a method for the production of androsta-9(11)-diene-3,17-dione (Δ9(11)-AD), which is a combination of phytosterol side-chain microbial oxidation with simultaneous 9α‑hydroxylation and subsequent chemical regio-selective dehydration of 9α-hydroxy-3,17-diketo-intermediate without isolation and purification. Phytosterol was converted into 9α-hydroxyandrost-4-ene-3,17-dione (9-OH-AD) with the use of the wild-type Mycobacterium sp. VKM Ac-1817D strain. The product was extracted from the culture medium with the use of an organic solvent and dehydrated in the extract with mineral acid. The resulting Δ9(11)-AD was purified with the selective crystallization method. Minor products were isolated and identified. It has been shown that this strain is capable of sterol transformation with the formation of methyl ester of 9α-hydroxypregn-4-ene-3-one-20-carboxylic acid. Our approach makes it possible to simplify the flow chart for production of the target compound. It not only eliminates 9-OH-AD loss but also minimizes the amount of production waste.

Background: Halogenated corticosteroids are widely used in medicine, and the global need of these steroidal APIs is estimated to be 40 – 70 tons, annually. Vietnam currently imports the pharmaceutical compounds up to 90%, in particular 100% of steroidal drugs. Currently, industrial production is based on the chemical syntheses of corticosteroids from either 16- dehydropregnenolone acetate (obtained from diosgenin) or androstenedione (obtained from phytosterol). The development of shorter synthetic schemes and more economically feasible technologies is of great significance. Introduction of 1(2)-double bond at the final stages of the corticosteroids synthesis results inpoor yield. 21-Acetoxypregna-1,4,9(11),16-tetraene-3,20-dione (tetraene acetate) is a key intermediate in the synthesis of highly active halogenated corticosteroids such as dexamethasone and other halogenated corticosteroids. 21-acetoxypregna-1,4,9(11),16- tetraene-3,20-dione is a key intermediate in the synthesis of dexamethasone from the readily available and cheap 9α-hydroxyandrost-4-ene-3,17-dione. Objective: The purpose of this study was the development of an efficient and shorter procedure for the synthesis of 21-acetoxypregna-1,4,9(11),16-tetraene-3,20-dione from 9α-hydroxyandrostenedione, which is a product of a bio-oxidative degradation of the side chain of phytosterols. Methods: Pregnane side chain was constructed using cyanohydrin method. For 1(2)- dehydrogenation, selene dioxide was applied for the introduction of Δ1(2)-double bond. Other stages of the synthesis were epimerization, Stork’s iodination procedure and dehydration. Result: 21-Acetoxypregna-1,4,9(11),16-tetraene-3,20-dione was prepared from 9α- hydroxyandrostenedione in yield more than 46%. Conclusion: An efficient and practically feasible procedure for the synthesis of 21-acetoxypregna- 1,4,9(11),16-tetraene-3,20-dione from 9α-hydroxyandrostenedione, a key intermediate for the synthesis of 9-haloidated corticoids, has been developed. The procedure can be applied for the production of value-added 9-haloidated corticoids.

T he chemical composition of volatiles from the stem barks of three different Kadsura species has been studied. The essential oils were obtained by hydrodistillation and analyzed by GC and GC-MS. The components were identified by MS libraries and their LRIs. The essential oils content varied between 0.15% and 0.20% (v/w), calculated on a dry weight basis. Sesquiterpene hydrocarbons (25.2% - 57.9%) and oxygenated sesquiterpenes (27.1%- 64.4%) are the main oil fractions . Kadsura coccinea(Lemaire) A. C. Smith., afforded oil whose major compounds were b -caryophylene (23.6%), d -cadinene (8.6%), caryophyllene oxide (7.8%) , epi- a -bisabolol (7.5%) and a -copaene (6.6%) . On the other hand, a -muurolol (43.5%) was the most singly abundant constituent of Kadsura longipeduculata Finet & Gagnepain. , with minor amounts of a -cadinol (5.4%), b -caryophylene (5.4%) and d -cadinene (5.0%). However, we have identified a -acorenol (10.1%), d -cadinene (9.6%), g -cadinene (8.1%) and d -elemene (6.8%) as the major constituents of Kadsura induta A. C. Smith.

This thesis presents the design and the implementation of Oulu Traffic Simulation System (OTSS), a traffic simulation system for the City of Oulu, Finland. Following agent-based approach, the simulation generates artificial agents that represent the population synthesis of the City of Oulu. Data from several sources, including official statistics, government-organized open data and crowdsourced information were collected and used as input for the simulation. Two traffic demand models are presented in this thesis: (1) the random model which generates traffic trips as random, discrete events; and (2) the activity-based model which defines traffic trips as sequential events in the agents’ day plan. The software development of the system follows the spiral model of software development and enhancement. During the implementation, several development cycles were conducted before the UML software design. The system was executed on two computation systems to test its real-time performance. To evaluate the traffic models, data extracted from the simulation was compared with aggregated survey data from Finnish Transport Agency and traffic count stations around the city. The results showed that a typical server is capable of running the simulation, and even though there were differences in the duration and distance of individual trips, the simulation reflects real-life traffic count significantly well.