Production Levels Research Articles

Fine-Regulating the Carbon Flux of l-Isoleucine Producing Corynebacterium glutamicum WM001 for Efficient l-Threonine Production.

l-Threonine, an essential amino acid, is widely used in various industries, with an annually growing demand. However, the present Corynebacterium glutamicum strains are difficult to achieve industrialization of l-threonine due to low yield and purity. In this study, we engineered an l-isoleucine-producing C. glutamicum WM001 to efficiently produce l-threonine by finely regulating the carbon flux. First, the threonine dehydratase in WM001 was mutated to lower the level of l-isoleucine production, then the homoserine dehydrogenase and aspartate kinase were mutated to release the feedback inhibition of l-threonine, and the resulting strain TWZ006 produced 14.2 g/L l-threonine. Subsequently, aspartate ammonia-lyase and aspartate transaminase were overexpressed to accumulate the precursor l-aspartate. Next, phosphoenolpyruvate carboxylase, pyruvate carboxylase and pyruvate kinase were overexpressed, and phosphoenolpyruvate carboxykinase, oxaloacetate decarboxylase were inactivated to fine-regulate the carbon flux among oxaloacetate, pyruvate and phosphoenolpyruvate. The resulting strain TWZ017 produced 21.5 g/L l-threonine. Finally, dihydrodipicolinate synthase was mutated with strong allosteric inhibition from l-lysine to significantly decrease byproducts accumulation, l-threonine export was optimized, and the final engineered strain TWZ024/pXTuf-thrE produced 78.3 g/L of l-threonine with the yield of 0.33 g/g glucose and the productivity of 0.82 g/L/h in a 7 L bioreactor. To the best of our knowledge, this represents the highest l-threonine production in C. glutamicum, providing possibilities for industrial-scale production.

The Role of Advanced Glycation End Products in Saphenous Vein Graft Failure.

We aimed to investigate the relationship between Advanced glycation end products (AGE) levels in patients with saphenous vein graft (SVG) failure and in patients without SVG failure. In our study, 55 patients with a history of previous coronary artery bypass grafting (CABG) surgery, who subsequently underwent coronary angiography for any reason and were found to have either SVG occlusion or significant lesions, were included as study patients. Additionally, 55 patients who have had CABG surgery without SVG failure for at least 1 year served as the control group. AGE values of the patients were measured using the skin autofluorescence method. In our study results, we observed a significant difference in AGE levels between the two groups of patients with similar demographic characteristics (SVG failure groups AGE 3.2 (2.8-3.6) vs control groups AGE 2.4 (2.1-2.7) p <0.001). In the ROC-curve analysis, we determined the ability of AGE levels to detect SVG failure with an area under the curve of 0.869. We found that in patients with AGE >3, it could detect SVG failure with a sensitivity of 70.9% and a specificity of 87.3%. Our results demonstrate that AGE levels can predict SVG failure risk inexpensively, easily, and quickly.

Cross-Over Application of Algerian Dairy Lactic Acid Bacteria for the Design of Plant-Based Products: Characterization of Weissella cibaria and Lactiplantibacillus plantarum for the Formulation of Quinoa-Based Beverage

The food industry constantly seeks new starter cultures with superior characteristics to enhance the sensory and overall quality of final products. Starting from a collection of Algerian dairy (goat and camel) lactic acid bacteria, this work focused on the exploration of the technological and probiotic potential of Weissella cibaria (VR81 and LVT1) and Lactiplantibacillus plantarum R12 strains isolated from raw camel milk and fermented milk, respectively. These bioactive strains were selected for their high performance among ten other LAB strains and were used as starter cultures to develop a novel and nutritionally enhanced dairy-like plant-based yogurt using quinoa (Chenopodium quinoa Willd) as a raw matrix. The strains were evaluated for their antagonistic effects against Listeria innocua, Listeria ivanovii, Staphylococcus aureus, Escherichia coli, Salmonella enterica, and Pseudomonas aeruginosa, resilience to acidic and osmotic challenges, and tolerance to gastrointestinal mimicking conditions (i.e., pepsin and bile salt). Their aggregation and adhesion profiles were also analyzed. Furthermore, L. plantarum and W. cibaria were tested in single and co-culture for the fermentation and biocontrol of quinoa. The strains exhibited probiotic properties, including a high potential for biocontrol applications, specifically against L. innocua and P. aeruginosa (20 mm diameter zone with the neutralized cell-free supernatant), which disappeared after protease treatment, suggesting that bioactive peptides might be responsible for the observed antimicrobial effect. Additionally, they demonstrated resilience to acidic (pH 2) and osmotic challenges (1M sucrose), tolerance to gastro-intestinal conditions, as well as good aggregation and adhesion profile. Furthermore, the strains were able to produce metabolites of interest, such as exopolysaccharide (yielding up to 4.7 mg/mL) and riboflavin, reaching considerable production levels of 2.5 mg/L upon roseoflavin selection. The application of W. cibaria and L. plantarum as primary starters (both in single and co-culture) for fermenting quinoa resulted in effective acidification of the matrix (ΔpH of 2.03 units) and high-quality beverage production. in vivo challenge tests against L. innocua showed the complete inhibition of this pathogen when L. plantarum was included in the starter, either alone or in combination with W. cibaria. Both species also inhibited Staphylococcus and filamentous fungi. Moreover, the co-culture of mutant strains of L. plantarum R12d and W. cibaria VR81d produced riboflavin levels of 175.41 µg/100 g in fermented quinoa, underscoring their potential as starters for the fermentation, biopreservation, and biofortification of quinoa while also displaying promising probiotic characteristics.

Market Evolution and Consumer Trends in Poland's Confectionery Industry

The Polish confectionery market is considered to be one of the most developed and dynamic markets in the world. But in recent years, the Polish food industry has faced a sharp increase in production and marketing costs, disruptions in the supply chains of raw materials, consumables and packaging, as well as the loss of traditional sales markets due to the war in Ukraine. The study of the peculiarities of the Polish confectionery market made it possible to assess the main indicators of the Polish market of confectionery goods of all categories, as well as its volume and trends. The article analyzes the situation on the Polish confectionery market, including production, export, import, consumption, geographic location of the market, levels of competition and development of the market's production and transport infrastructure. It was concluded that during 2022 there was a 12% increase in the volume of production of confectionery goods of all categories. At the same time the manufacture of Polish flour confectionery products increased by 19.3%. The growth rates of production of cocoa–rich and sugar sweets were 3.8% and 6.8%, respectively. About 50–70% of manufactured products are exported by Polish manufacturers. It is necessary to mention that during 2022 a record number of products were exported from Poland, exceeding the similar figures of the previous year by 13.8%. Meanwhile, despite the presence of developed domestic production of confectionery goods in Poland, the volume of imported supplies traditionally remains high and increased by 7.8% in 2022. At the same time, the level of competition in the Polish domestic market for flour, cocoa–rich/chocolate and sugar confectionery products is estimated as high. The level of the market's production and transport infrastructure is rated as developed.

WORKERS JOB SATISFACTION IN TEXTILE FACTORY: BIBLIOMETRIC ANALYSIS

Textile industry represents one of the most competitive industries. Consequently, the management tend to create pressures to their workers to pace with the high productivity level. This constant pressure given to the workers may possibly affect their job satisfaction. Hence, this study focuses on the bibliometric analysis in mapping the trend, conceptual structure, and characteristic of job satisfaction of textile factory workers. The data collection process results in 147 papers out of the total of 241 extracted papers. According to the bibliometric analysis, research in this field is mainly led by the USA and France. The co-occurrence analysis shows Four major theme: Study on job satisfaction, worker’s health assessment, cultural influence on textile factory workers, and review on absenteeism. The results indicate that workers were more concerned about the security of their current position rather than overall employment security, and this factor affected their job satisfaction and well-being.

Synthesis of β-ionone from xylose and lignocellulosic hydrolysate in genetically engineered oleaginous yeast Yarrowia lipolytica.

β-ionone, an apocarotenoid derived from a C40 terpenoid has an intense, woody smell and a low odor threshold that has been widely used in as an ingredient in food and cosmetics. Yarrowia lipolytica is a promising host for β-ionone production because of its oleaginous nature, its ability to produce high levels of acetyl-CoA (an important precursor for terpenoids), and the availability of synthetic biology tools to engineer the organism. In this study, β-carotene-producing Y. lipolytica strain XK17 was employed for β-ionone biosynthesis. First, we explored the effect of different sources of carotenoid cleavage dioxygenase (CCD) genes on β-ionone production. A high-yielding strain rUinO-D14 with 122mg/L of β-ionone was obtained by screening promoters combined with rDNA mediated multi-round iterative transformations to optimize the expression of the CCD gene of Osmanthus fragrans. Second, to further develop a high-level production strain for β-ionone, we optimized key genes in the mevalonate pathway by multi-round iterative transformations mediated by non-homologous end joining, combined with a protein tagging strategy. Finally, the introduction of a heterologous oxidoreductase pathway enabled the engineered Y. lipolytica strain to use xylose as a sole carbon source and produce β-ionone. In addition, the potential for use of lignocellulosic hydrolysate as the carbon source for β-ionone production showed that the NHA-A31 strain had a high β-ionone productivity level. This study demonstrates that engineered Y. lipolytica can be used for the efficient, green and sustainable production of β-ionone.

Assessing the impact of structural change in sustainable consumption and lifestyles research

Scientific evidence highlights the pivotal role for structural change in pursuit of the sustainability transformation. A particular challenge for research on structural aspects of sustainable consumption and lifestyles, however, is the assessment of their impact. Especially quantifying the impact of structural change remains a serious problem. While some forms of structural change can be quantified, like the rate of building renovations, changes in the energy mix at the production level, or trends in access to health care or education, the impact of other changes such as societal narratives about wellbeing, political campaigns on energy technologies or policies, or the abandonment of the growth paradigm defy easy quantification. This article aims to shed light on potential avenues for quantitatively assessing the impact of structural change drawing on insights gained by a group of international and interdisciplinary research consortia funded by the European Union in the area of sustainable consumption, citizenship, and lifestyles research. It delineates strengths and weaknesses of different approaches, foci and blindspots of associated data types. Thereby, it highlights fundamental decisions that need to be made in research designs, but also important aspects to consider in the interpretation of results. Finally, the article highlights the particular challenges related to assessing the impact of deep political and ideational structures.

Minor Modification in Asbestos Roof of Cow Shed for Reduction of Heat Stress in Dairy Cows during Summer Season

Thermo neutral zone (TNZ) is the range of ambient temperature & humidity in which animals feel comfortable and their production level is optimum. When temperature humidity index (THI) goes above 72, the dairy cows begin to show symptoms of mild heat stress, which affects the milk production in dairy animals during summer season in India. Asbestos and GI sheet are commonly used as roofing material in many cattle farms throughout the world. This experiment was carried out on apparently healthy cross bred jersey cows receiving balanced ration during the month of May in the livestock farm of OUAT, Bhubaneswar for one week. The existing cattle shed was partitioned into three compartments by raising brick walls, each having the dimension of 30 x 25 ft size. The asbestos roof of first one was covered with 90 % grade green shed-net. Over the asbestos roof of second compartment, heat reflective white colour was painted and asbestos roof of third one was left as such. From 8.00 AM to 5.00PM, the THI of the normal asbestos roof shed varied from mild to moderate heat stress range. But THI of both shed-net covered shed and heat reflective colour painted shed was found to be within the mild heat stress range i.e. 72-79 during noon indicating a comfortable ambient condition for the animals in summer season when the outside ambient temperature went up to 40 0C during noon. No significant (P>0.05) change in the milk production was observed among the groups during the week. However, a decrease (P<0.05) of 0.43, 0.25 and 0.38 L in milk yield of the cows was observed when they were kept under normal asbestos shed, heat reflective colour painted shed and shed-net covered shed, respectively. From the study, this can be concluded that the impact of heat stress on milk production can be reduced by painting the rood of the shed with heat reflective colour paint.

Effectiveness of the Application of the Six Sigma Model for the Productivity of an Organic Banana Exporting Company

The highly competitive landscape of current markets forces companies to adopt effective models to improve their processes and increase their production levels. This study was carried out in an organic banana exporting company, to determine the impact on productivity when applying the Six Sigma methodology. The study had a quantitative approach, applied modality, with a pre-experimental design and an explanatory level. The techniques for collecting information were observation and documentary analysis. After implementing the five phases of the model, an increase of 24.7% in productivity was obtained; Likewise, it was observed that the process capacity would have gone from 0.60 to 1.16, and the Sigma level would have increased from 2.9 to 3.8, causing a lower number of defects per million opportunities in production.

СОЦІАЛЬНО-ЕКОНОМІЧНІ ЦИКЛИ: ТЕОРЕТИЧНА ІНТЕРПРЕТАЦІЯ ТА СТАТИСТИЧНЕ ОЦІНЮВАННЯ

Sustainable national economic development requires a balance of aggregate demand and aggregate supply. The country's government is working out economic and legal mechanisms to achieve macroeconomic balance against factors that can disrupt it. The preconditions of macroeconomic instability include exogenous (natural and military-political) and endogenous (macroeconomic cyclical development). Due to the combination of these factors, achieving national macroeconomic balance is an urgent scientific and practical task for economists, scientists who study macroeconomics, as well as politicians and government officials. The key questions that need to be answered are the length of the cycle, the pace of the recession, and most importantly, the development of effective mechanisms for restoring macroeconomic balance and its long-term maintenance. The study of sustainable national economic development assumes cyclicality. It can be considered an independent process from the point of view of the manifestation of self-regulation of the market economy, when the equilibrium will be restored after a certain period of time by the action of market mechanisms, and also as a process of decline in business activity, which can be scientifically and practically studied as a phenomenon and, accordingly, an effective macroeconomic strategy of government policy can be identified. With the aim of accelerated and controlled passage of the economic cycle and development of effective government instruments, scientists study the essence and causes of macroeconomic instability, manifestations of unemployment and inflation. Cyclicality should be considered as a movement of the national economy, a form of its development and improvement. The socio-economic cycle involves fluctuations in the macroeconomic situation (level of employment, production and prices) from recession to upswing against the background of the general trend of the dynamics of the gross domestic product. The success of the government's macroeconomic policy is determined by the cause of the crisis, the degree of state regulation of the economy, opportunities to use the results of scientific and technical development, and the ratio of the shares of the real and non-productive sectors of the economy. This approach involves theoretical interpretation and statistical evaluation of socio-economic cycles. The article considers the main aspects of the theoretical interpretation of socio-economic cycles. A review of the scientific works of leading macroeconomists regarding the study of the essence and manifestations of cyclicality in the economy, social life of society was carried out, and attention was also paid to the issues of the interrelationship of the development of the economies of different countries in the conditions of globalization. The main factors of cyclical fluctuations and their periodicity are highlighted, the main theoretical provisions of economic cyclicality are given. The article provides a methodology for statistical evaluation of socio-economic cycles and the selection of its individual phases (recession, boom) based on the application of the method of statistical equations of dependencies and the method of complex statistical coefficients. Using the method of statistical equations of dependence, the existence of a relationship between the result indicator (GDP, billion US dollars, y) and two factors: "External debt, billion US dollars, x", "Number of registered unemployed, thousands of people, z" was established . It was determined that the factor "External debt, billion US dollars, x" plays the main role in the formation of the output indicator (GDP). It is substantiated that when the value of "GDP, billion US dollars" increases by 1 billion dollars. In the USA, the factor "External debt, billion US dollars" is expected to increase by 0.63 billion US dollars, and with an increase in the value of "GDP, billion US dollars" by 1 billion dollars. In the USA, the value of the factor "Number of registered unemployed, thousands of persons" is expected to decrease. for 5.43 thousand persons. Cyclicality was studied on the basis of the two mentioned methods and two phases of the economic development cycle of Ukraine were identified: 2008-2009 and 2013-2015. A generalization was obtained regarding the existence of a phase of the seven-year economic cycle.

Methyl jasmonate mitigates biochemical and phytochemical changes in salt stressed Stevia rebaudiana plants

This study explored the effects of salt stress on growth, oxidative stress, and steviol glycoside content in Stevia rebaudiana Bertoni plants cultivated in soil supplemented with methyl jasmonate (MeJA). Stevia plants were cultivated under normal and salt stress conditions, with and without MeJA supplements of 30 ?M, 60 ?M, and 120 ?M. Samples were harvested after the 1st, 3rd, 5th, 10th, and 15th day of treatment. The levels of chlorophyll (p<0.0001), carotenoids (p<0.0001), and antioxidant enzymes such as catalase (p<0.0001), superoxide dismutase (p<0.0001), APX (p<0.0001), and glutathione reductase (p<0.0001) were observed. The quantification of steviol glycosides, including stevioside (p<0.0001) and rebaudioside-A (p<0.0001), was studied by the most advanced hyphenated technique, LC-MS/MS. The study revealed that the oxidative stress responses were significantly improved in MeJA-treated plants compared to salt-stress control plants. The level of production of phenols (p<0.0001), flavonoids, total sugar, reducing sugar, and steviol glucosides was significantly altered in salt-stress plants. MeJA showed a dose- and time-dependent significant effect on the improvement of these factors over salt stress. In conclusion, MeJA not only improves the growth of plants but also reduces oxidative stress and enhances the level of phytochemicals under saline stress.

Localization of Genetic Factors that Determine the Economically-Useful Traits of the PEAR (<i>Pyrus</i>) and Methods of Marker-Assisted Selection

DNA markers are an alternative method for accelerated identification of interested genes and loci at the early stages of ontogenesis, and, consequently, DNA markers are able to intensify the breeding process. This article represents overview of research on the localization of economically useful traits in the pear genome and the development and use of marker-assisted selection (MAS) techniques. At the moment, several traits have been localized in the pear genome, i.e.: resistance to scab European (V. pirina Aderh) and Asian (V. nashicola), black spot (Alternaria alternata (Fr.) Keissler), brown spot (Stemphylium vesicarium), fire blight (Erwinia amylovora), pear psylla (Cacopsylla pyri), pear sawfly (Caliroa cerasi), pear blister mite (Eriophyes pyri), self-incompatibility, dwarf trait. Major genes and loci of quantitative traits (QTLs) of fruits characteristics have also been identified, namely: skin color and rustiness of the fruit, size and weight of the fruit, taste, level of ethylene production, harvest time etc. It should be noted that currently Russian research is limited to the validation and use of MAS methods developed abroad. According to the experience of Japanese scientists, the use of MAS for several key traits has made it possible to triple the efficiency of the breeding process. Despite the currently limited list of MBC methods for pears, the high speed of genomic technologies development promises rapid development of new MAS methods in the future. In combination with new breeding technologies (New Breeding Techniques) based on accelerated flowering, the use of MAS for pears is a promising direction of breeding.

The Critical Role of Soft Skills in Engineering: Enhancing Performance and Career Advancement

Today’s engineering graduates seeking jobs require a combination of technical abilities and the right soft skills, as organizations prefer a professional individual who has developed an overall personality that encompasses both professionalism and alignment with society, rather than relying solely on qualifications and academic scores. The 21st-century workforce has changed the way they define job skills, with managers prioritizing non-technical (soft) skills in addition to technical skills, as having these alone is no longer enough in today's competitive market place. This article aims to analyze the significance of soft skills in the engineering sector, as highlighted in the literature review. An understanding of these soft skills is crucial for organizations to optimize the levels of productivity amongst their employees and for individuals desiring to advance their futures within a competitive job landscape. This article attempts to shed light on these soft skills in the hopes of investing in training program designs that can maximize engineers professional efficacy and career successes within their industry, engineering.

25-hydroxycholesterol promotes brain cytokine production and leukocyte infiltration in a mouse model of lipopolysaccharide-induced neuroinflammation

Neuroinflammation has been implicated in the pathogenesis of several neurologic and psychiatric disorders. Microglia are key drivers of neuroinflammation and, in response to different inflammatory stimuli, overexpress a proinflammatory signature of genes. Among these, Ch25h is a gene overexpressed in brain tissue from Alzheimer’s disease as well as various mouse models of neuroinflammation. Ch25h encodes cholesterol 25-hydroxylase, an enzyme upregulated in activated microglia under conditions of neuroinflammation, that hydroxylates cholesterol to form 25-hydroxycholesterol (25HC). 25HC can be further metabolized to 7α,25-dihydroxycholesterol, which is a potent chemoattractant of leukocytes. We have previously shown that 25HC increases the production and secretion of the proinflammatory cytokine, IL-1β, by primary mouse microglia treated with lipopolysaccharide (LPS). In the present study, wildtype (WT) and Ch25h-knockout (KO) mice were peripherally administered LPS to induce an inflammatory state in the brain. In LPS-treated WT mice, Ch25h expression and 25HC levels increased in the brain relative to vehicle-treated WT mice. Among LPS-treated WT mice, females produced significantly higher levels of 25HC and showed transcriptomic changes reflecting higher levels of cytokine production and leukocyte migration than WT male mice. However, females were similar to males among LPS-treated KO mice. Ch25h-deficiency coincided with decreased microglial activation in response to systemic LPS. Proinflammatory cytokine production and intra-parenchymal infiltration of leukocytes were significantly lower in KO compared to WT mice. Amounts of IL-1β and IL-6 in the brain strongly correlated with 25HC levels. Our results suggest a proinflammatory role for 25HC in the brain following peripheral administration of LPS.

8015 Growth Hormone Axis Dysfunction in PMM2-CDG: Exploring the Role of Dynamic Tests for the Management of Short Stature in Two Pediatric Cases

Abstract Disclosure: G. Del Medico: None. E. Procopio: None. L. Ferri: None. A. Barbato: None. A. Morrone: None. S. Stagi: None. PMM2-CDG is the most prevalent congenital disorder of glycosylation (CDG) and is caused by defective phosphomannomutase2 (PMM2) activity. According to the 2019 guidelines, approximately half of PMM2-CDG patients exhibit short stature and low serum levels of insulin-like growth factor-1 (IGF-1), IGF binding protein 3 (IGFBP3), and acid-labile subunit (ALS). Despite this, there is no expert consensus on the endocrinological management of this condition. We investigated the growth hormone (GH) axis in two 12-year-old female patients with PMM2-CDG. The first patient was compound heterozygote for the most common PMM2 gene variants in Italy, p.(Leu32Arg) and p.(Arg141His). She presented with short stature (< 2 Standard Deviation Score, SDS) and low serum levels of IGF-1 and IGF-BP3 (< 2.5° for age and sex). Bone age was significantly delayed. Tanner stage was prepubertal. Somatotropic response to GH stimulation testing (Levodopa) was normal. After the IGF-1 generation test with recombinant GH, serum IGF-1 increased by 115%. The second patient was compound heterozygote for the known PMM2 pathogenetic variant p.(Ala108Val) and the novel p.(Thr171Asnfs*11) variant (only case described in literature). She presented short stature (< 2 SDS) with near-to-normal IGF-1 and IGF-BP3 serum levels (2.5° for age and sex). Bone age was slightly delayed. Tanner stage was prepubertal. She also exhibited severe obesity, hypertriglyceridemia, and hepatic steatosis. Her somatotropic response to two GH stimulation tests (Levodopa and Arginine) was deficient, probably because of her significant overweight. IGF-1 serum levels didn’t increase after the IGF-1 generation test. Hypoglycosylation in PMM2-CDG impairs the IGF1 system on multiple levels. It destabilizes the ternary complex formed by IGF-1 and glycoproteins IGFBP3 and ALS, therefore reducing the half-life of circulating IGF-1. Hypoglycosylation also reduces IGF1 production by impairing its precursor proIGF-1Ea and its cellular secretion. As a result, PMM2-CDG patients have GH insensitivity, with normal GH production but low levels of IGF-1. However, there is a lack of information in the literature on the use of dynamic tests and hormonal therapies (GH and rhIGF-1) in CDG. The IGF-1 generation test in our patients showed partial GH sensitivity in the first patient and GH insensitivity in the second patient. These observations suggest variability. Some PMM2-CDG patients may benefit from an extended trial with GH therapy, while for GH-insensitive patients a trial with recombinant IGF-1 might be considered. This is one of the first reports that explores the potential role of dynamic tests in PMM2-CDG. As the biochemical effects of hypoglycosylation on the GH-IGF1 pathway are becoming clearer more clinical research is needed to reach a consensus on the management and treatment of short stature in these patients. Presentation: 6/3/2024

9396 Deciphering The Enigma: A Case Report On New-onset Graves Disease Presenting As Thyroid Storm In The First Trimester Of Pregnancy, Managed In The Intensive Care Setting

Abstract Disclosure: M. Zeb: None. S.W. Salari: None. A. Tiwari: None. A. Vadher: None. A. Dabaja: None. S. Kambhatla: None. Graves' disease, an autoimmune disorder characterized by hyperthyroidism, presents unique challenges when manifesting as thyroid storm during pregnancy. We report a case of a 27-year-old African American woman at 9 weeks gestation who presented with palpitations, agitation, and fever. On examination, she exhibited fever, tachycardia, tremors in hands, and mild bilateral exophthalmos. Thyroid function tests revealed markedly elevated free thyroxine and suppressed thyroid-stimulating hormone levels. Thyroid ultrasound confirmed diffuse thyroid enlargement with increased vascularity, consistent with Graves' disease. Pelvic ultrasound estimated the gestational age at 9 weeks and 2 days, with a serum β-hCG level of 135,037 mIU/mL. An electrocardiogram revealed sinus tachycardia, and a complete metabolic panel indicated mild hypokalemia. The Thyroid Stimulation Immunoglobulin (TSI) and Thyrotropin receptor antibodies were tested positive. The Burch-Warsofsky point score of 45, supported the diagnosis of thyroid storm. The patient received intensive care treatment including intravenous fluids, hydrocortisone, beta-blockers, Lugol’s iodine, propylthiouracil, and potassium replacement. Following treatment, thyroid function stabilized within 48 hours, and her hyperthyroid symptoms resolved. The patient was discharged on oral labetalol and propylthiouracil. Thyroid storm, characterized by severe manifestations of hyperthyroidism, is a rare but potentially life-threatening condition, especially during pregnancy. Prompt recognition and intervention are crucial due to associated maternal and fetal morbidity and mortality. A multidisciplinary approach, involving endocrinology, obstetrics, and critical care, is essential to optimize outcomes. The unique physiologic changes of pregnancy, such as increased thyroid hormone production and altered thyroid hormone-binding globulin levels, can complicate the diagnosis and management of hyperthyroidism. Our case underscores the importance of vigilance for thyroid dysfunction in pregnant women, even in the absence of prior thyroid disease. Additionally, the potential impact of hyperthyroidism and thyroid storm on pregnancy outcomes highlights the need for early recognition and intervention. Long-term management of Graves' disease during pregnancy may also require adjustment of antithyroid medication dosage and monitoring of thyroid function to maintain euthyroidism while minimizing fetal exposure to medication. Further research is warranted to refine diagnostic criteria, treatment protocols, and long-term management strategies for thyroid storm in pregnancy. Increased awareness among healthcare providers about the risks and management strategies for this rare but serious complication is also necessary. Presentation: 6/3/2024

Analysis of the Variation in Salaries of Employees of Government Ministries in Iraq by Using of The Lorenz Curve and The Gini Coefficient*H.

The disparity in the distribution of income is one of the main reasons for the failure to achieve social justice among members of society, which creates an unhealthy environment for workers in government sectors and institutions and also works to reduce the quality of work and lower the level of productivity. Conversely, reducing disparity leads to increased productivity and creates a suitable environment. It contributes to increasing productivity rates and improving the quality of institutional performance. The research discussed an important topic related to the extent of the discrepancy between the salaries of employees in Iraqi government institutions using the Lorenz curve and the Gini coefficient through a presentation of the research problem, which is the extent of the discrepancy in the salaries of state employees according to the approved salary scale, and what impact this has on social justice in the distribution of income, assuming that the adoption of A salary scale set by the authorities is based on reducing financial disparities between state employees with equal qualifications, such as educational attainment and work tasks, and reduces disparities of discrimination between workers in various government sectors and achieves social justice in income distribution. The research concluded that the actual distribution curve was very close to the symmetry line curve, in addition to the presence of a very small gap between the two lines, which indicates fairness in the distribution of monthly salaries among workers in government ministries who are in the fourth degree/first stage of the approved salary scale. The value of the Gini coefficient complementary to the work of the Lorenz curve was about (0.4), which means that the value of the Gini coefficient is close to zero. This indicates that the distribution of salaries of employees of government ministries is close to equitable distribution.

Versatile filamentous fungal host highly-producing heterologous natural products developed by genome editing-mediated engineering of multiple metabolic pathways

Natural secondary metabolites are medically, agriculturally, and industrially beneficial to humans. For mass production, a heterologous production system is required, and various metabolic engineering trials have been reported in Escherichia coli and Saccharomyces cerevisiae to increase their production levels. Recently, filamentous fungi, especially Aspergillus oryzae, have been expected to be excellent hosts for the heterologous production of natural products; however, large-scale metabolic engineering has hardly been reported. Here, we elucidated candidate metabolic pathways to be modified for increased model terpene production by RNA-seq and metabolome analyses in A. oryzae and selected pathways such as ethanol fermentation, cytosolic acetyl-CoA production from citrate, and the mevalonate pathway. We performed metabolic modifications targeting these pathways using CRISPR/Cas9 genome editing and demonstrated their effectiveness in heterologous terpene production. Finally, a strain containing 13 metabolic modifications was generated, which showed enhanced heterologous production of pleuromutilin (8.5-fold), aphidicolin (65.6-fold), and ophiobolin C (28.5-fold) compared to the unmodified A. oryzae strain. Therefore, the strain generated by engineering multiple metabolic pathways can be employed as a versatile highly-producing host for a wide variety of terpenes.

Isolation and characterization of a degradation product of mexiletine hydrochloride using FT-IR, LC-MS and NMR: method development and validation of stability indicating RP-HPLC method for quantification of characterized impurity

Mexiletine Hydrochloride is an antiarrhythmic drug used to treat acute and chronic ventricular arrhythmias. Significant degradation of unknown impurity was observed while evaluating the impurity profile of the Mexiletine Hydrochloride stability studies. The levels of the unknown impurity are more than the regulatory identification/qualification threshold level (0.08%). Mexiletine was forcefully subjected to various stress conditions, such as acidic, basic, oxidation, photolysis, and thermal. Among these stress conditions, we identified an unknown degradation impurity in the thermal stress (105°C for 15 days) of Mexiletine, the same as that of an unknown impurity observed in the stability studies. The present research reports the isolation of unknown impurity in thermal stress by preparative HPLC and the characterization of isolated unknown degradation impurity using LC-MS, FT-IR, and NMR techniques. The spectral data elucidated the structure of the degradation product, and it was identified as “(E)-2-(((1-(2,6-dimethylphenoxy)propan-2-yl)imino)methyl)-6-methylphenol”. A stability-indicating HPLC method was developed and validated to determine and quantify the degradation product in Mexiletine Hydrochloride. The levels of the unknown degradation product reduced to below the limit of detection (<0.007%) from 0.10% after applying its relative response factor “16.5” and complying with the regulatory threshold limits. It helps to extend the shelf life of Mexiletine.

Study of indoor and outdoor noise in primary schools in the city of São Paulo - Brazil

Noise pollution has been treated by the World Health Organization as the cause of several diseases, in addition to being the second largest environmental polluter, being surpassed only by air pollution. For schools, excessive noise, in addition to causing illness, is responsible for low levels of cognition and low productivity for both students and teachers. In general, Brazilian public schools are built on land provided by the government, in places that are not suitable for their siting. Thus, in Brazilian schools, students are exposed to noise from the surroundings, as well as noise generated indoors, which is not negligible, reaching levels that can be harmful to health and incompatible with educational activities. This study shows the evaluation of the level of indoor and outdoor noise in classrooms of five primary schools in the city of São Paulo, in the pre-pandemic period of COVID-19, comparing the results with those established by legislation, in addition to evaluating other descriptors such as LAeq, L10, L90, and SIL. The results show that classroom users are exposed to noise levels that complicate the communication of the teacher's message to the student, disrupt concentration and can even be affecting their health