Production Levels Research Articles

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.

Ursolic Acid Restores Redox Homeostasis and Pro-inflammatory Cytokine Production in Denervation-Induced Skeletal Muscle Atrophy.

Skeletal muscle (SkM) atrophy results from metabolic disorders causing body and muscle mass loss, affecting morbidity and mortality. Increased oxidative stress, inflammation, and poor prognosis are the leading causes of involuntary weight loss. Ursolic acid (UA), known for its antioxidant and anti-inflammatory properties, can potentially reduce oxidative stress and inflammation in muscles, but its effects on muscle mass regulation are still unknown. Therefore, the present study investigated the medicinal efficacy of UA and its mode of action against the murine model of SkM atrophy over 7days of UA supplementation. Denervation-induced SkM atrophy significantly impacts overall body weight and the weight of individual muscles (p < 0.05). However, supplementation with UA can effectively counteract these effects by promoting the synthesis of the slow-myosin heavy chain, thereby restoring body weight and myotube diameter. Moreover, UA also plays a crucial role in reducing the production levels of reactive oxygen species (ROS), lipid peroxidation (LPO), and caspase-3-like activity in atrophied muscles. UA also prevents the leakage of creatine kinase (CK) through the upregulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) expression. Furthermore, the results obtained from qRT-PCR demonstrated a significant decrease in the levels of pro-inflammatory markers, namely IL-1β, IL-6, TNF-α, and TWEAK, up to four-fold after the third day of the UA intervention. UA also upregulated PGC-1α, Bcl2, and p-Aktser473 expression towards the regulation of redox homeostasis.

When products speak differently: Designing new languages for established products

Innovating product language has been proven to be an effective measure to change what products mean to customers and create new product categories. However, how to embed a new language into a product characterized by an established design has not been addressed in the past. Thus, we discuss a single case study of Videndum, a company producing premium branded tools and accessories for content creation (i.e., photography supports and accessories) that is redefining their product language and seeking to incorporate new narratives into their existing line‐up of products. Our case study is based on 18 interviews across all levels of the organization, analysis of archival data and observations to explore the actions the company is taking to change product language for their established products. Our findings show that designers can work at the level of the design principles to inform how new meanings can be embedded into signs at the product level, to build a new coherent product language. We identify two layers of design principles, value‐principles and solution‐principles, and show their different impact on product language. By doing so, we contribute to understand how companies design new product languages for established products in practice, providing managers with practical knowledge on how to perform the translation from abstract values to product features.

Eco-efficiency of coffee production and consumption in the UK at the product and sectoral levels

Coffee is one of the most consumed products globally, and yet its eco-efficiency is still unknown. To address this knowledge gap, this paper examines for the first time the life cycle eco-efficiency of different coffee drinks to identify the most sustainable options and opportunities for improvements in the coffee industry. Nine types of coffee are considered: espresso, latte, cappuccino, Americano, drip-filter, coffee pods, spray-dried and freeze-dried instant, and instant coffee mix. Taking a cradle-to-grave approach, the following life stages are included: coffee cultivation, production and consumption, and end-of-life valorisation of spent coffee grounds. The methodology follows the eco-efficiency ISO 14045 standard to measure the environmental efficiency of a system relative to the economic value it generates. The eco-efficiency is estimated at both the product (one serving) and sectoral (annual consumption) levels based on life cycle assessment (LCA), life cycle costing (LCC) and economic value added (VA). The results show that latte has the highest environmental impacts and LCC but it also has the highest VA at both the product and sectoral levels. Spray-dried instant coffee, on the other hand, has the lowest impacts but also the lowest VA, which makes it the least eco-efficient option. Espresso emerges as the most eco-efficient drink because it has moderate environmental impacts and high VA. Latte and coffee pods are the second most eco-efficient drinks, followed by cappuccino, Americano, and instant coffee mix. Valorising spent coffee grounds could reduce the environmental impacts, LCC and increase the VA at the sectoral level. For example, the climate change impact would be reduced by 80.5-132.1 kt CO2 eq./yr and primary energy demand by 0.9-2.3 PJ/yr while also increasing the VA by £50.2-95 M/yr. When compared to some other food sectors, coffee is 6.4 times more eco-efficient than cheddar cheese and 5.4 times than ice cream and biscuits, respectively. The findings of this study can be used to guide businesses, consumers and policy makers in identifying more eco-efficient coffee products and improving the environmental and economic sustainability of the coffee industry.

Variability in addictive and carcinogenic potential of smokeless tobacco products marketed in Mumbai, India: a surveillance study

India has the highest incidence worldwide of smokeless tobacco (SLT)-associated oral cancer, accounting for nearly 70% of all SLT users globally. Nicotine and tobacco-specific N-nitrosamines (TSNA) play critical roles in the addictive and carcinogenic potential, respectively, of SLT products. Our group has previously reported substantial variability in nicotine and TSNA levels across a small SLT product sample in India, calling for systematic surveillance. However, there is no information available on the current levels of these constituents in Indian SLT. We analysed 321 samples representing 57 brands of eight popular types of manufactured SLT products purchased from five local markets in Mumbai, India between August, and September 2019. The sampling locations were Mumbai Central, Kurla, Thane, Vashi, and Airoli. Product pH, moisture content, total and unprotonated (biologically available) nicotine, and TSNA levels were measured at the Advanced Centre for Treatment, Research, and Education in Cancer (ACTREC) in Mumbai. Total nicotine content ranged from 0.45 to 35.1mg/g across products. The unprotonated nicotine fraction contributed 0.1-100% of the total nicotine content. The carcinogenic TSNA levels ranged 0.06-76 ug/g for N'-nitrosonornicotine (NNN), 0.02-19.2 ug/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 0.01-6.51 ug/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). Consistent with our previous study, we observed substantial variations across different brands of the same product type. This is the most extensive and the first within-country study to report brand-specific nicotine and TSNA levels in SLT products marketed in Mumbai, India. Our results show that levels of these constituents remain extremely variable across Indian SLT and are strikingly high in many products. Enhanced public education and continued efforts to reduce SLT use prevalence in India are critical for reducing the global burden of SLT-associated morbidity and mortality. Regulation of nicotine and TSNA levels in SLT products should be considered. This work was supported by the National Institutes of Health (USA) grant R01-TW010651 and, in part, by grants R01-CA180880 and R50-CA211256. The LC-MS/MS analysis was supported in part by XII Plan project funding from the Department of Atomic Energy, Government of India.

Prevalence of coronary artery calcification in patients with end-stage renal disease undergoing dialysis and the association of various risk factors with the development of coronary artery calcification in this patient population

Background: Patients with end-stage renal disease (ESRD) on dialysis exhibit a significantly higher risk of coronary artery calcification (CAC) than age-matched normal individuals, contributing to elevated cardiovascular morbidity and mortality. Aims and Objectives: This study designed to assess the prevalence of CAC in ESRD patients on dialysis and identify associated risk factors. Materials and Methods: Fifty ESRD patients undergoing maintenance dialysis and twenty normal subjects were included in this cross-sectional observational study. Serum calcium, phosphate, and parathyroid hormone were measured in all ESRD patients and normal controls. Multi Row Spiral Computed Tomography was performed to determine CAC scoring (CACS). Results: CACS was significantly higher in ESRD patients compared to normal subjects (mean CACS: 91.4±32.7 vs. 7.75±9.5 Agatston units, P&lt;0.05). Elevated levels of calcium phosphate products, serum leptin, intact parathyroid hormone (iPTH), presence of diabetes mellitus, and longer duration of dialysis were correlated with increased incidence of CACS in ESRD patients, as indicated by higher odd’s ratios ranged from 1.10 to 6.93. Conclusion: CAC is highly prevalent in ESRD patients on dialysis, emphasizing the need for stringent risk factor management. Our findings suggest that controlling calcium phosphate product, serum leptin, age, iPTH levels, and duration of dialysis may reduce CAC burden in this population, potentially mitigating cardiovascular risk and improving outcomes.

A cell-free system for functional studies of small membrane proteins

Numerous small proteins have been discovered across all domains of life, among which many are hydrophobic and predicted to localize to the cell membrane. Based on a few that are well-studied, small membrane proteins are regulators involved in various biological processes, such as cell signaling, nutrient transport, drug resistance, and stress response. However, the function of most identified small membrane proteins remains elusive. Their small size and hydrophobicity make protein production challenging, hindering function discovery. Here, we combined a cell-free system with lipid sponge droplets and synthesized small membrane proteins in vitro. Lipid sponge droplets contain a dense network of lipid bilayers, which accommodates and extracts newly synthesized small membrane proteins from the aqueous surroundings. Using small bacterial membrane proteins MgrB, SafA, and AcrZ as proof of principle, we showed that the in vitro produced membrane proteins were functionally active, for example, modulating the activity of their target kinase as expected. The cell-free system produced small membrane proteins, including one from human, up to micromolar concentrations, indicating its high level of versatility and productivity. Furthermore, AcrZ produced in this system was used successfully for in vitro co-immunoprecipitations to identify interaction partners. This work presents a robust alternative approach for producing small membrane proteins, which opens a door to their function discovery in different domains of life.

Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis.

Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism. We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes. Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, - 3.72 to - 0.15) and etelcalcetide (- 7.80, - 11.80 to - 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, - 9.73 to - 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, - 6.72 to - 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, - 8.91 to - 2.37), calcitriol (- 9.36, - 14.81 to - 3.92), and paricalcitol (- 9.30, - 13.78 to - 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions. The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet.

Производительность труда в российской Арктике: структурная динамика и регионально-отраслевые тенденции

Labor productivity is a key indicator of economic development and public well-being. This study assesses the structural shifts, regional dynamics, and sectoral trends in the domain of labor productivity in the Russian Arctic from 2011 to 2021, identifying aggregated economic sectors. The findings reveal that labor productivity levels in the Russian Arctic exceed the national average, primarily due to the resource-based nature of regional economies. However, a major issue is the persistently high level of interregional differentiation in labor productivity within the Arctic. The study demonstrates that an initially high level of labor productivity does not necessarily ensure long-term growth. An analysis of structural shifts in labor productivity over the past decade indicates a shift towards the market sector of the Arctic economy, evidenced by an increased share in gross regional product (GRP) and a decrease in time worked. Within the market sector, several trends are observed: the leading role of the extractive industry is maintained due to its expanding share in GRP; the role of agriculture is growing, reflected in a decreased share of hours worked; and the importance of other market sector branches, particularly transport, communication, and electric power, is diminishing as their share of total hours worked increases. The observed decline in labor productivity within the non-market sector suggests the potential for negative social consequences for the Arctic population. An analysis of labor productivity growth rates indicates that the leading sectors in terms of growth are mining, finance and business services, construction, and trade. These sectors can be considered sources of economic growth in the Arctic. Interregional differences in labor productivity growth rates within the same sector of the Arctic economy suggest the influence of regional factors, highlighting the potential for discovering unique reserves of productivity growth in each region.

Most important performance evaluation methods of production lines: A comprehensive review on historical perspective and emerging trends

Production is one of the most significant building blocks that strengthen the sustainable economy of companies and thus contribute to the countries’ welfare. Performance indicators of the production line affect planning operations and the efficiency of the supply chain to which the factory is connected. The key indicators to monitor and improve for production line designers and performance analysts include production rate, resource utilization rate, and average inventory level. The production rate is considered the most important indicator that closely affects an industrial plant’s productivity and efficiency levels. From this perspective, accurate and fast estimation of this indicator is very critical. Production rate can be calculated by simulation, analytical technique, or artificial intelligence methods according to the production line characteristics. In this comprehensive review, the most important performance evaluation methods are discussed historically and systematically about the buffer allocation problem using the snowball sampling method. With this explicit motivation, 145 papers were reviewed and classified according to production line topology, hypothetical/real-case line, machine reliability, previous method on which the method is based, and originality and/or line characteristics. To present a comprehensive comparison, the methods considered were analyzed according to different criteria. This review provides general/in-depth qualitative and quantitative discussions and highlights insights to practitioners and scholars. In addition, the impact of recent key work on production line analysis in the field is assessed along with emerging trends, evolving manufacturing paradigms are discussed, and the challenges associated with performance analysis are addressed.

Acute Pain Management Following Mandibular Third Molar Exodontia: A Bibliometric Analysis of Randomized Controlled Trials

Introduction and aimsTo reveal the evolution of pain management strategies following mandibular third molar (M3M) exodontia, examine the geographic contribution of research, and explore future developments through a bibliometric analysis. MethodsA comprehensive search was conducted in various leading databases. Data on bibliometrics, participant demographics, and agent regimens were extracted for eligible studies. Descriptive bibliometrics, citation analysis, and keyword bursts were performed to assess the research outputs, distribution, and emerging hotspots. ResultsA total of 173 randomized control trials from 2004 to 2024 were included. The number of publications showed a consistent upward trend since 2007. Brazil exhibited the most publications and citations. Germany presented the highest mean citations per publication. Brazil, Spain, and Italy showed the closest collaboration. Appropriately 14,391participants with 14,710 extracted M3M were enrolled. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most extensively studied analgesics, followed by glucocorticoids, opioids, and paracetamol. NSAIDs and paracetamol were predominantly administered orally, whereas glucocorticoids and opioids were primarily applied topically (P < .001). Studies on opioids significantly predated the studies using other agents. Adverse events were found in 50.87% of the included studies, where nausea and vomiting were the most frequently reported. Tramadol and piroxicam have drawn increasing interest in recent years. ConclusionsThis study revealed information on the research outputs, distribution, and future developments of analgesic agents following M3M exodontia. Brazil exhibited the highest level of productivity and recorded the most citations. NSAIDs generated the largest amount of research and are emerging as a benchmark for comparative studies. Oral administration is the most frequently used approach for agent delivery. Nausea and vomiting are the most commonly reported adverse effects. Clinical relevanceThe bibliometric analysis offers insights into the field of pain management following mandibular 3rd molar exodontia and how it has evolved. Tramadol and piroxicam have become research hotspots in recent years.

Стохастично моделиране при маслодайните култури в България в условията на Зелената сделка

This study is designated to elaborate and propose a model for estimation of outcomes and effects at the level of production of oilseed crops in Bulgaria. The projections are manifested through scenarios based on the stochastic error, which is yielded as a difference between real and modelling results on the projected variables. It is deemed to provide a good basis for modelling of scenarios driven by specific parameters from the Green Deal of EU. The applied stochastic model gives a very good basis to elaborate and simulate further sensitive scenarios generated by the factors and variables of the Green Deal. It is thought to carried out through incorporation of the variables covering the world price of oilseeds and the use of nitrogen mineral fertilizers. The applied and evolved model for projecting the development and future outlook of the production of oilseed crops in Bulgaria provides a system of model equations, which is created as a interdependencies between different variables. This model is considered to achieve and reveal specific quantitative results, facilitating the scenario comparisons. The presented model results are made as an estimation of the stochastic error, standing for the difference between the model over the real historical data in the period of 15 years, between 2007 – 2021. It is assumed that production and market risks in the oilseeds sector will increase crucially if the full-scale implementation of the intended restrictions and bans connected to Green Deal measures are adopted. Those restrictions are seen in purported reduction in the use of plant protection chemicals and fertilizers application. Production risks are mainly highlighted in the cut of production yield, market volatility of the oilseed commodity and the affected efficiency due to cost increment. Market risks will mainly be related to securing a market stability and appropriate cost level of the production. The results from the model show that up to the time of this study work covering the historical real data up to 2021, specific signals and turbulences in the production, supply and market performance of the sector are not yet noticed and the supposed stagnation effects from the Green Deal measures are not displayed. Therefore, putting aside the expected strong impact of the Green Deal on the sector by 2030, the production and consumption of oilseeds is projected to remain strong and to gravitate in the high levels achieved in the best years reached recently, indicating that the sector is on the upward trend and the constraints and bans of the Green Deal may have a greater affect eventually in future.

Correlation between Farmers' Activeness in Farmer Groups with Productivity and Income of Cocoa Farming in Trenggalek Regency

The cocoa plantation in Suruh Village, Trenggalek Regency is the main supplier of cocoa beans to UPH Rumah Coklat owned by the Department of Agriculture and Food of Trenggalek Regency. For example, in cocoa farmers' participation in the "Tunggal Jaya" Farmers Group, farmers are taught to make rorak and worm palaces to deal with climate change which helps maintain soil moisture and increase fertility. The objectives of this study are to determine 1) the level of farmer activeness, 2) the level of productivity, 3) the level of income, and 4) the correlation between farmer activeness in farmer groups with productivity and income of cocoa farming in Suruh Village, Trenggalek Regency. The number of samples used was 111 respondents. Data analysis used the Likert scale, productivity analysis, income analysis, and Pearson correlation. The results of the study showed: 1) cocoa farmer activeness in farmer groups in Suruh Village, Trenggalek Regency is in the active category with an overall average score of 3.56; 2) the average productivity of cocoa farming is in the medium category at 0.54 tons/ha/year; 3) the average income of cocoa farming is Rp6,016,562/year; 4) the correlation between farmer activeness with productivity is 0.865, farmer activeness with income is 0.760, and productivity with income is 0.868. The direction of the three correlations is positive and significant.

The Effect of Activities-Based Teaching in The English Context on EFL University Students

This study presents a pragmatic approach focusing on the meaning of speech and knowledge regarding the undergraduate students' understanding and utilization of speech act ‘request’ within the Department of English Language at the College of Arts. Quantitative approach has been employed to analyze request strategies by using an open-ended questionnaire comprising sixteen diverse scenarios to gather data on various request speech acts. The study investigates the effectiveness of instructional interventions in developing students' proficiency in this speech act. The findings from the pre-tests revealed that students exhibited comparable performance across all three strategies: direct requests, conventionally indirect requests, and non-conventionally indirect requests have been assessed in terms of both awareness and production levels. Despite the initial similarity in performance among learners, substantial improvements have been observed after the instructional phase. Specifically, individuals within the experimental group demonstrated notable enhancements in their awareness and production of requests, coupled with a decreased reliance on direct request strategies. These findings underscore the potential for pragmatics instruction rich in input to enhance learners' identification and utilization of suitable pragmatic elements within diverse social contexts. Overall, the study highlights the importance of pragmatic education in foreign language learning, suggesting its efficacy in fostering learners' pragmatic competence.

Из истории развития табаководства как важнейшей отрасли торгового земледелия в губер-ниях Южного Кавказа во второй половине XIX – начале XX века

The article focuses on the evolution of tobacco cultivation in the South Caucasus over the research period. The author investigates the spread of this technological culture throughout all provinces in the specified region. Information is provided on the quantity of land occupied for tobacco cultiva-tion, tobacco types, industrial firms and their owners, tobacco products produced, and tobacco sales locations. The author examines the many causes of the shift in demand for tobacco products over this historical time, as well as the unequal level of tobacco production. The essay discusses the excellent conditions for the growth of tobacco production in the South Caucasus, which eventually became commodities. The report also underlined the Russian government’s interest in spreading this crop, which was the primary raw material for the tobacco sector. The government, which contributed to the region’s colonial exploitation by the Russian and foreign bourgeoisie, benefited financially from the expansion of the cultivation of technologi-cal and precious crops. The author finds that the tobacco business in the South Caucasus evolved, improved, and gradually adopted the characteristics of commercial agriculture, which included commodity rela-tions. It is emphasized that the quick expansion of commercial agriculture is closely tied to the emergence of capitalist relationships in agriculture.

Low Frequency Ventilation During Cardiopulmonary Bypass to Protect Postoperative Lung Function in Cardiac Valvular Surgery: The PROTECTION Phase II Randomized Trial.

Cardiac surgery with cardiopulmonary bypass (CPB) triggers pulmonary injury. In this trial we assessed the feasibility, safety, and efficacy of low frequency ventilation (LFV) during CPB in patients undergoing valvular surgery. Patients with severe mitral or aortic valve disease were randomized to either LFV or usual care. Primary outcomes included release of generic inflammatory and vascular biomarkers and the lung-specific biomarker sRAGE (soluble receptor for advance glycation end products) up to 24 hours postsurgery. Secondary outcomes included pulmonary function tests and 6-minute walking test up to 8 weeks postdischarge. Sixty-three patients were randomized (33 LFV versus 30 usual care). Mean age was 66.8 years and 30% were female. LFV was associated with changes of sRAGE (soluble receptor for advance glycation end products) levels (geometric mean ratio, 3.05; [95% CI, 1.13-8.24] 10 minutes post CPB, and 1.07 [95% CI, 0.64-1.79], 0.84 [95% CI, 0.55-1.27], 0.67 [95% CI, 0.42-1.07], and 0.62 [95% CI, 0.45-0.85] at 2, 6, 12, and 24 hours post CPB respectively). No changes were observed for any of the generic biomarkers. Respiratory index soon after surgery (mean difference, -0.61 [95% CI, -1.24 to 0.015] 10 minutes post end of CPB), forced expiratory volume after 1 second/forced vital capacity ratio (0.050 [95% CI, 0.007-0.093] at 6 to 8 weeks pos-surgery), Forced vital capacity alone (95% CI, -0.191 L [-0.394 to 0.012]) and 6-minute walking test score at discharge (63.2 m [95% CI, 12.9-113.6]) were better preserved in the LFV group. No other differences were noted. The use of LFV during CPB in patients undergoing valvular surgery was feasible and safe and was associated with changes in sRAGE levels along with better preserved lung function and walking performance. These observations warrant further investigation in larger future studies. URL: https://www.isrctn.com; Unique Identifier: ISRCTN75795633.

Lithophysical characteristics of productive strata of cupriferous sandstone within Zhezkazgan ore district in the Central Kazakhstan

Purpose. The paper concerns additional geological appraisal and identification of extra localization criteria of cupriferous mineralization of a stratiform type. The research is intended to define physical and geological factors influencing sandstone distribution within the north-end of Zhezkazgan synclinal in the Central Kazakhstan. Methods. A complex analysis of geological and mineralogical, geophysical, and geochemical data was carried out relying upon the information obtained from deep-hole wells. Modern methods to process and interpret the field data were applied. The analysis involved lithological dismemberment of the productive Taskuduk suite as well as determination of sulfide mine-ralization zone boundaries. Findings. The research has shown that the productive levels reach down to 1500-m depth. The data interpretation has helped specify the geological structure and develop a model of ore-promising bodies of cupriferous sandstones at great depth. The applied complex data analysis has increased potential to prospect new loci of productive cupriferous sandstone deposits of Zhezkazgan type. Originality. The research has contributed significantly to understanding of the physical and geological factors influencing the copper ore distribution in deep layers. New physical and geological criteria, determining deep copper mineralization localization, have been identified which were not considered by earlier similar studies. Practical implications. The obtained new data as well as the developed methods are important while deep drilling planning and implementing to identify promising copper mineralization sites. The findings may be used to optimize exploration within the north-end of Zhezkazgan synclinal, and other districts having analogous geological conditions.

Development of a Maturity Model for the Digital transformation of companies in the context of Construction Industry 4.0

The construction industry is characterized by a low level of productivity and digitalization, as well as the critical perceived instability of costs, deadlines and quality. One way to address these challenges is to increase the use of digital methods and technologies in the future. Optimal use of these can help to improve the quality of planning and execution and optimize the operation of existing buildings. The challenge is the implementation and integration of these methods and technologies into existing company structures. In many cases, companies do not have a unified understanding of the current state of digitization in their organization. This article closes this research gap and presents the development of a novel maturity model for construction companies in the context of Construction Industry 4.0, the Digital Construction Company Maturity Model (DCCMM). Based on a literature review, the appropriate technologies used in the construction industry are identified and the basic requirements for the maturity model are defined. Once implemented, the model comprises five dimensions and 28 assessment parameters that describe digital transformation across six maturity levels. The conceptual model is tested and validated in eight construction companies. This is done in the context of qualitative interviews. The DCCMM serves as a holistic framework for the individual classification of companies in terms of digital transformation. This provides construction companies with a transparent and comprehensible indication of the degree of digitalization of their own structures. The result will make a significant contribution to further digitalization in the construction industry.

PRODUCTIVITY OF PURSE SEINE FISHING TOOLS OPERATING IN THE WATERS OF OUTER AMBON BAY, MALUKU.

The decline in fish populations can negatively impact the livelihoods of fishermen and local food security. Therefore, maintaining the sustainability of fisheries is an urgent necessity. Evaluating the productivity of purse seine catches in the outer waters of Ambon Bay is crucial in this context. This study aims to measure the productivity level of purse seine fishing gear and identify the factors that influence it. The research was conducted from June 2023 to May 2024 in Laha Village, Outer Ambon Bay, Ambon Island. The research method used is a quantitative descriptive method, which aims to describe the productivity of purse seine fishing gear in detail based on data obtained in the form of graphs and tables. Data collection was carried out through field surveys and direct observations during fishing activities. The data analysis results showed that the highest volume and number of trips were in November, with 18 trips and a production volume of 644 kg/trip, while the lowest was in May, with 12 trips and a production volume of 184 kg/trip.

Sodium octanoate mediates GPR84-dependent and independent protection against sepsis-induced myocardial dysfunction

IntroductionThis study aims to evaluate the therapeutic effects of sodium octanoate (SO), a medium-chain fatty acid salt, on SIMD in a murine model and to explore its underlying mechanisms. MethodsMale mice were subjected to sepsis models through two methods: intraperitoneal injection of lipopolysaccharide (LPS) and cecal ligation and punction (CLP). Mice received interval doses of SO every 2hours or 4hours for a total of six times or three times after LPS treatment. The relationship between SO and G protein-coupled receptor 84 (GPR84) was evaluated through GEO data analysis and molecular docking studies. DBA/2 mice were used to study the role of the GPR84 protein in the SO-mediated protection. Energy metabolomics was utilized to comprehensively assess the impact of SO on the levels of cardiac energy metabolic products in septic mice. histone modification identification techniques were used to further identify the specific sites of histone modification in the hearts of SO-treated septic mice. ResultsSO treatment significantly improved myocardial contractile function, restored the oxidative stress imbalance and enhanced the myocardium's resistance to oxidative injury. SO significantly promotes the expression of GPR84. The loss of GPR84 function markedly attenuates the protective effects of SO. SO enhanced myocardial energy metabolism by promoting the synthesis of acetyl-CoA and upregulating genes involved in fatty acid β-oxidation which were abolished by medium-chain acyl-CoA dehydrogenase (MCAD) knockdown. SO induced histone acetylation, particularly at H3K123 and H3K80. ConclusionOur study demonstrates that SO exerts protective effects against SIMD through both GPR84-mediated anti-inflammatory and antioxidant actions and GPR84-independent enhancement of myocardial energy metabolism, possibly mediated by MCAD.