Rapid Emergence Research Articles

Blockchain’s Role in Finance beyond Cryptocurrency

The rapid emergence of blockchain technology outside of cryptocurrency in financial applications. Blockchain, mostly known as the underlying technology backing decentralized currencies such as Bitcoin, is today being tapped for a range of other financial services by its underlying features: decentralization, transparency, and security. The research explores blockchain's role in advancing transaction processing, auditability, andinnovations such as decentralized finance and smart contracts that are changing traditional financial systems. The paper elaborates on how this technology benefits from efficiency relating to points of asset management, trade finance, and financing in the supply chain. It further goes into blockchain security and privacy challenges associated with these new technologies being adopted in areas such as these. This survey synthesizes recent insights to identify crucial opportunities and challenges for blockchains in the financial sector in bringing systemic change across global markets

Studying Target-Engagement of Anti-Infectives by Solvent-Induced Protein Precipitation and Quantitative Mass Spectrometry.

Antimicrobial resistance (AMR) poses a serious threat to global health. The rapid emergence of resistance contrasts with the slow pace of antimicrobial development, emphasizing the urgent need for innovative drug discovery approaches. This study addresses a critical bottleneck in early drug development by introducing integral solvent-induced protein precipitation (iSPP) to rapidly assess the target-engagement of lead compounds in extracts of pathogenic microorganisms under close-to-physiological conditions. iSPP measures the change in protein stability against solvent-induced precipitation in the presence of ligands. The iSPP method for bacteria builds upon established SPP procedures and features optimized denaturation gradients and minimized sample input amounts. The effectiveness of the iSPP workflow was initially demonstrated through a multidrug target-engagement study. Using quantitative mass spectrometry (LC-MS/MS), we successfully identified known drug targets of seven different antibiotics in cell extracts of four AMR-related pathogens: the three Gram-negative bacteria Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and the Gram-positive bacterium Staphylococcus aureus. The iSPP method was ultimately applied to demonstrate target-engagement of compounds derived from target-based drug discovery. We employed five small molecules targeting three enzymes in the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway─a promising focus for anti-infective drug development. The study showcases iSPP adaptability and efficiency in identifying anti-infective drug targets, advancing early-stage drug discovery against AMR.

Oral Intake of Collagen and Collagen Hydrolysate From Takifugu bimaculatus Attenuates Ultraviolet‐Induced Skin Photoaging in Mice

ABSTRACTWith the rapid emergence of pufferfish aquaculture and processing industries, fish skin is underutilized as a byproduct of processing, leading to resource waste. In this study, Takifugu bimaculatus skin collagen (TBSC) was extracted by acetic acid solubilization and its physicochemical properties were analyzed. The effects of TBSC and the TBSC hydrolysate (TBSCH) on ultraviolet (UV) irradiation‐induced photoaging were investigated using a mouse model. The purity of TBSC was 90.02%. Electrophoresis and Fourier infrared spectroscopy characterization of TBSC showed that the type of collagen in TBSC was typical standard type I. The degree of hydrolysis was selected to optimize the hydrolysis conditions for TBSC. The papain enzyme dosage, temperature, pH, and hydrolysis duration of 51,000 U/g, 48.03°C, 5.35, and 4 h have been demonstrated to be the optimum hydrolysis conditions for TBSCH. Oral administration of either TBSC or TBSCH ameliorated UV‐induced skin erythema and hyperkeratosis. TBSC and TBSCH treatment increased collagen content and had an inhibitory effect on matrix metalloproteinase (MMP)‐2 and MMP‐3 expression, whereas MMP‐9 expression was significantly reversed only in the TBSCH‐treated groups. The expression of the c‐Jun protein was much lower in these groups, suggesting that TBSCH had a greater alleviating effect on collagen degradation and extracellular matrix breakdown. Therefore, it is proposed that TBSCH has the potential to be used as a nutricosmetic agent with protective attributes against UV‐induced skin damage and concurrent collagen depletion.

Complete genome sequencing of SARS-CoV-2 strains that were circulating in Uzbekistan over the course of four pandemic waves.

Since the rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a global COVID-19 pandemic affecting millions of people globally, it has become one of the most urgent research topics worldwide to better understand the pathogenesis of COVID-19 and the impact of the harmful variants. In the present study, we conducted whole genome sequencing (WGS) analysis of 110 SARS-CoV-2 genomes, to give more data about the circulation of SARS-CoV-2 variants during the four waves of pandemic in Uzbekistan. The whole genome sequencing of SARS-CoV-2 samples isolated from PCR-positive patients from Tashkent, Uzbekistan, in the period of 2021 and 2022 were generated using next-generation sequencing approaches and subjected to further genomic analysis. According to our previous studies and the current genome-wide annotations of clinical samples, we have identified four waves of SARS-CoV-2 in Uzbekistan between 2020 and 2022. The dominant variants observed in each wave were Wuhan, Alpha, Delta, and Omicron, respectively. A total of 347 amino acid level variants were identified and of these changes, the most frequent mutations were identified in the ORF1ab region (n = 159), followed by the S gene (n = 115). There were several mutations in all parts of the SAR-CoV-2 genomes but S: D614G, E: T9I, M: A63T, N: G204 R and R203K, NSP12: P323L, and ORF3a(NS3): T223I were the most frequent mutations in these studied viruses. In our previous study, no mutation was found in the envelope (E) protein. In contrast, in our present study, we identified 3 (T9I, T11A and V58F) mutations that made changes to the structure and function of the E protein of SARS-CoV-2. In conclusion, our findings showed that with the emergence of each new variant in our country, the COVID-19 pandemic has also progressed. This may be due to the considerable increase in the number of mutations (Alpha-46, Delta- 146, and Omicron-200 mutations were observed in our samples) in each emerged variant that shows the SARS-CoV-2 evolution.

Niche-specific metabolic phenotypes can be used to identify antimicrobial targets in pathogens.

Bacterial pathogens pose a major risk to human health, leading to tens of millions of deaths annually and significant global economic losses. While bacterial infections are typically treated with antibiotic regimens, there has been a rapid emergence of antimicrobial resistant (AMR) bacterial strains due to antibiotic overuse. Because of this, treatment of infections with traditional antimicrobials has become increasingly difficult, necessitating the development of innovative approaches for deeply understanding pathogen function. To combat issues presented by broad- spectrum antibiotics, the idea of narrow-spectrum antibiotics has been previously proposed and explored. Rather than interrupting universal bacterial cellular processes, narrow-spectrum antibiotics work by targeting specific functions or essential genes in certain species or subgroups of bacteria. Here, we generate a collection of genome-scale metabolic network reconstructions (GENREs) of pathogens through an automated computational pipeline. We used these GENREs to identify subgroups of pathogens that share unique metabolic phenotypes and determined that pathogen physiological niche plays a role in the development of unique metabolic function. For example, we identified several unique metabolic phenotypes specific to stomach pathogens. We identified essential genes unique to stomach pathogens in silico and a corresponding inhibitory compound for a uniquely essential gene. We then validated our in silico predictions with an in vitro microbial growth assay. We demonstrated that the inhibition of a uniquely essential gene, thyX, inhibited growth of stomach-specific pathogens exclusively, indicating possible physiological location-specific targeting. This pioneering computational approach could lead to the identification of unique metabolic signatures to inform future targeted, physiological location-specific, antimicrobial therapies, reducing the need for broad-spectrum antibiotics.

BRD4 Degradation Enhanced Glioma Sensitivity to Temozolomide by Regulating Notch1 via Glu-Modified GSH-Responsive Nanoparticles.

Temozolomide (TMZ) serves as the principal chemotherapeutic agent for glioma; nonetheless, its therapeutic efficacy is compromised by the rapid emergence of drug resistance, the inadequate targeting of glioma cells, and significant systemic toxicity. ARV-825 may play a role in modulating drug resistance by degrading the BRD4 protein, thereby exerting anti-glioma effects. Therefore, to surmount TMZ resistance and achieve efficient and specific drug delivery, a dual-targeted glutathione (GSH)-responsive nanoparticle system (T+A@Glu-NP) is designed and synthesized for the co-delivery of ARV-825 and TMZ. As anticipated, T+A@Glu-NPs significantly enhanced penetration of the blood-brain barrier (BBB), facilitated drug uptake by glioma cells, and exhibited efficient accumulation in brain tissue. Additionally, T+A@Glu-NPs exhibited augmented efficacy against glioma both in vitro and in vivo through the induction of apoptosis, inhibition of proliferation, and cell cycle arrest. Furthermore, mechanistic exploration revealed that T+A@Glu-NPs degraded the BRD4 protein, leading to the downregulation of Notch1 gene transcription and the inhibition of the Notch1 signaling pathway, thereby augmenting the therapeutic efficacy of glioma chemotherapy. Taken together, the findings suggest that T+A@Glu-NPs represents a novel and promising therapeutic strategy for glioma chemotherapy.

Unveiling key factors in solar eruptions leading to the solar superstorm in 2024 May

NOAA active region (AR) 13664/8 produced the most intense geomagnetic effects since the Halloween event of 2003. The resulting extreme solar storm is thought to be the consequence of multiple interacting coronal mass ejections (CMEs). Notably, this AR exhibits exceptionally rapid magnetic flux emergence. The eruptions on which we focus all occurred along collisional polarity inversion lines (PILs) through collisional shearing during a three-day period of extraordinarily high flux emergence (sim 1021 Mx hr$^ $). Our key findings reveal how photospheric magnetic configurations in eruption sources influence solar superstorm formation and geomagnetic responses, and link exceptionally strong flux emergence to sequential homologous eruptions: (1) We identified the source regions of seven halo CMEs that were distributed primarily along two distinct PILs. This distribution suggests two groups of homologous CMEs. (2) The variations in the magnetic flux emergence rates in the source regions are correlated with the CME intensities. This might explain the two contrasting cases of complex ejecta that are observed at Earth. (3) Our calculations of the magnetic field gradients around the CME source regions show strong correlations with eruptions. This provides crucial insights into solar eruption mechanisms and enhances our prediction capabilities for future events.

Harnessing Oxidative Stress to Obtain Natural Riboflavin Secreting Lactic Acid Bacteria for Use in Biofortification.

Lactococcus lactis suffers from oxidative stress and riboflavin starvation at elevated temperatures due to dissolved oxygen, which can be relieved partially by exogenously supplied riboflavin. Here we explore whether this phenomenon can be harnessed to obtain riboflavin overproducing mutants. Using a riboflavin auxotrophic L. lactis strain as a riboflavin biosensor, we screened L. lactis cultures that had been exposed to temperature induced oxidative stress for up to one year. Riboflavin secreting mutants could readily be identified, some of which had arisen after just two weeks of exposure to oxidative stress. Whole genome sequencing revealed mutations in the riboswitch, which regulate riboflavin biosynthesis. Riboflavin secretion conferred a significant increase in tolerance to oxidative stress and enabled growth at high temperatures in the presence of dissolved oxygen. It was subsequently demonstrated that vigorous aeration at high temperature (37 °C) could prompt rapid emergence of riboflavin secreting mutants. The protective effect provided by riboflavin against oxidative stress may explain the natural occurrence of lactic acid bacteria (LAB) secreting riboflavin. By optimizing fermentation conditions and eliminating lactate formation, we achieved 64 mg/L riboflavin, the highest reported titer so far for LAB, which indicates great potential for use as a riboflavin fortification agent in food.

Inhibition mechanism of potential antituberculosis compound lansoprazole sulfide

Tuberculosis is one of the most common causes of death worldwide, with a rapid emergence of multi-drug-resistant strains underscoring the need for new antituberculosis drugs. Recent studies indicate that lansoprazole-a known gastric proton pump inhibitor and its intracellular metabolite, lansoprazole sulfide (LPZS)-are potential antituberculosis compounds. Yet, their inhibitory mechanism and site of action still remain unknown. Here, we combine biochemical, computational, and structural approaches to probe the interaction of LPZS with the respiratory chain supercomplex III2IV2 of Mycobacterium smegmatis, a close homolog of Mycobacterium tuberculosis supercomplex. We show that LPZS binds to the Qo cavity of the mycobacterial supercomplex, inhibiting the quinol substrate oxidation process and the activity of the enzyme. We solve high-resolution (2.6 Å) cryo-electron microscopy (cryo-EM) structures of the supercomplex with bound LPZS that together with microsecond molecular dynamics simulations, directed mutagenesis, and functional assays reveal key interactions that stabilize the inhibitor, but also how mutations can lead to the emergence of drug resistance. Our combined findings reveal an inhibitory mechanism of LPZS and provide a structural basis for drug development against tuberculosis.

Repurposing Plant-Based Histone Acetyltransferase Inhibitors: A Review of Novel Therapeutic Strategies Against Drug-Resistant Fungal Biofilms.

The rapid emergence of drug-resistant fungal strains necessitates the development of novel therapeutic approaches for battling biofilm-related infections. Biofilms, efflux pumps, and suppression of virulence traits in pathogenic yeasts are governed by epigenetic enzymes, namely, histone acetyltransferases (HATs) and histone deacetylases (HDACs). The review article is focused on the use of histone acetyltransferase inhibitors (HATi), a mechanism-based epidrug that inactivates the regular function of HATs. With an emphasis on specific plant-based HATi and their Structure-Activity Relationship (SAR), the review enumerates the extensive list of anticancer HATi that can be screened for antifungal activities. By repurposing these anticancer HATi, this approach may help generate broad-spectrum antifungal medications that highlight common biological pathways between fungus and cancer, possibly revolutionizing both treatment domains.

Preventive behaviors for COVID-19 in Chile: Lessons from a population follow-up for 2021 and 2022.

The rapid emergence of COVID-19 urged policy responses worldwide, focusing on vaccination and mobility restrictions. Chile represents a unique scenario for analyzing personal preventive measures amid intensive communication and vaccination campaigns. This study aims to explore changes in population adherence to non-pharmacological preventive measures during the pandemic and the factors that explain this adherence each year. 386 individuals who participated in two population-based studies (2021 and 2022) were considered. An interview was conducted to measure adherence to self-care practices, and case and contact tracing by the health authorities. The Wilcoxon signed-rank test was performed to measure change between 2021 and 2022, bivariate analysis, and a linear regression model for each year were performed. Mask-wearing in public places was the most commonly used measure (95.9% in 2021, 89.9% in 2022). Follow-up of cases and cases contacts by the health authority had high coverage in 2021 (94.3% and 83% respectively). A greater decrease was observed in contact tracing in 2022 totaling 33.3%. An increase in the score of adherence to preventive practices was observed in 2022 (p < 0.00). The regression model showed in 2021 that women were more likely to adopt preventive behaviors (95% confidence interval: 0.27 to 1.13) and the overweight/obese had higher adherence compared to normal body mass index (95% confidence interval: 0.06 to 0.98). In 2022 being a young adult (30 to 49 years) predicted the adoption of behavioral precautions (95% confidence interval: 0.00 to 1.32). Adherence to preventive measures increased even with high vaccination coverage, likely due to the epidemiological situation with the Omicron variant circulating in 2022.

ACTINOBACTERIAL DIVERSITY DETERMINATION IN MALAYSIAN BRIS (BEACH RIDGES INTERSPERSED WITH SWALES) SOIL BY CULTURE-DEPENDENT APPROACH

Globally, the rapid emergence of antibiotic-resistant bacteria poses a major threat to public health, threatening the effectiveness of antibiotics. Addressing the crisis of antimicrobial resistance requires urgency in new drug discovery and the effort in finding novel compounds is dramatically evolving. However, one of the main obstacles is the rediscovery of known compounds from natural resources. To overcome this challenge, exploring underexploited location for new resource of actinomycetes, such as Beach Ridges Interspersed with Swales (BRIS) soil in Malaysia, was selected. Soil samples from Jambu Series and Rudua Series in Setiu, Terengganu were collected and analysed. A total of 87 actinomycetes strains were isolated on yeast malt agar (ISP2), Actinomyces agar and Zobell marine agar, with the highest number from the Jambu series using serial dilution and spread plate method. Antimicrobial screening revealed that 31 isolates exhibited activity against ESKAPE pathogens, with 28 and 12 isolates showing activity against Gram-positive and Gram-negative bacteria, respectively. These isolates showed strong inhibiting response towards one or more ESKAPE pathogens. This study highlights the potential of BRIS soil as an underexploited habitat for discovering actinobacterial communities which could lead to the discovery of a new potential antimicrobial producer to serve as novel drug leads.

Both chebulagic acid and punicalagin inhibit respiratory syncytial virus entry via multi-targeting glycoprotein and fusion protein.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections, with no currently available small-molecule drugs that are both safe and effective. A major obstacle in antiviral drug development is the rapid emergence of drug-resistant viral strains. Targeting multiple viral compounds may help mitigate the development of resistance. Herein, we conducted a drug screening using the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to identify compounds that simultaneously target the RSV fusion (F) protein, glycoprotein (G), and the host heparan sulfate proteoglycans (HSPGs). From this screening, 10 candidate compounds were identified for their ability to interact with all three targets. Among these 10 candidates, chebulagic acid (CHLA) and punicalagin (PUG) demonstrated the most potent inhibition of RSV replication. In vitro dose-response assays confirmed the antiviral efficacy of CHLA (IC50: 0.07864 µM) and PUG (IC50: 0.08065 µM). Further experiments revealed both CHLA and PUG disrupt RSV attachment and membrane fusion by targeting the RSV-F and G proteins, rather than HSPG. Notably, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with docking assays predicting their binding sites at cysteines 176 and 182. Additionally, CHLA enhanced the conformational stability of the RSV-F protein before fusion. In an in vivo study, both CHLA and PUG were shown to alleviate RSV-induced pulmonary pathology by reducing viral titers, mitigating lung injury, and suppressing the inflammatory responses in the lungs. Our findings suggest that CHLA and PUG hold potential as therapeutic agents for RSV infection.IMPORTANCEA significant challenge in developing anti-respiratory syncytial virus (RSV) agents is the rapid emergence of resistant viral strains. Designing drugs that target multiple viral components can effectively reduce the likelihood of developing resistant strains. In this study, we screened compounds from the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to simultaneously targe the RSV fusion (F) protein, glycoprotein (G), and host heparan sulfate proteoglycans (HSPGs). Our findings revealed that chebulagic acid (CHLA) and punicalagin (PUG) significantly inhibited RSV replication both in vitro and in vivo and interacted with all three targets. Both CHLA and PUG were able to disrupt RSV attachment and membrane fusion. Mechanistically, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with CHLA also enhancing the conformational stability of the RSV-F protein before fusion. In conclusion, our study suggests that CHLA and PUG hold promise as therapeutic agents against RSV infection.

Fighting Mutations with Mutations: Evolutionarily Adapting a DNA Aptamer for High‐Affinity Recognition of Mutated Spike Proteins of SARS‐CoV‐2

AbstractAn on‐going challenge with COVID‐19, which has huge implications for future pandemics, is the rapid emergence of viral variants that makes diagnostic tools less accurate, calling for rapid identification of recognition elements for detecting new variants caused by mutations. We hypothesize that we can fight mutations of the viruses with mutations of existing recognition elements. We demonstrate this concept via rapidly evolving an existing DNA aptamer originally selected for the spike protein (S‐protein) of wildtype SARS‐CoV‐2 to enhance the interaction with the same protein of the Omicron variants. The new aptamer, MBA5SA1, has acquired 22 mutations within its 40‐nucleotide core sequence and improved its binding affinity for the S‐proteins of diverse Omicron subvariants by &gt;100‐fold compared to its parental aptamer (improved from nanomolar to picomolar affinity). Deep sequencing analysis reveals dynamic competitions among several MBA5SA1 variants in response to increasing selection pressure imposed during in vitro selection, with MBA5SA1 being the final winner of the competition. Additionally, MBA5SA1 was implemented into an enzyme‐linked aptamer binding assay (ELABA), which was applied for detecting Omicron variants in the saliva of infected patients. The assay produced a sensitivity of 86.5 % and a specificity of 100 %, which were established with 83 clinical samples.

Harnessing the microbiome: probiotics, antibiotics and their role in canine and feline gastrointestinal disease.

Unfavourable alterations of the host microbial environment, known as dysbiosis, have been identified in many canine and feline gastrointestinal (GI) diseases. As a result, normalisation of microbial composition and function has become an important therapeutic target. Given the complex and individualistic interplay between the resident microbiota, host and environment, a multimodal approach is often necessary when addressing dysbiosis in dogs and cats with GI disease. Systemic antibiotics are often empirically used to treat acute and chronic GI diseases. However, with modern genomic techniques demonstrating the profound negative effect antibiotics can have on the GI microbiota and the rapid emergence of resistant bacteria globally, there has been an increased focus on identifying antibiotic alternatives for use in small animal practice. Biotics, such as prebiotics, probiotics and synbiotics, are of growing interest due to their potential supportive effect on the microbiota. This article reviews the evidence for the use of biotics in canine and feline GI disease, highlighting how judicious use of antibiotics and targeted probiotic supplementation can enhance patient outcomes by promoting a balanced gut microbial environment.

Reflecting on the Impact of Generative AI for Sustainability Accounting Scholarship

ABSTRACT Our yearly editorial is dedicated to reflections concerning two recent digitalisation-based developments, both of which are currently radically transforming the publishing arena. We begin by considering the rapid emergence of generative Artificial Intelligence (AI) models known as Large Language Models (LLMs), which have already had tremendous effects on academic knowledge production. In this context, we clarify our stance on the use of AI in articles submitted to Social & Environmental Accountability Journal (SEAJ) and reviews conducted for the journal. We then continue by taking a closer look at the proliferation of systematic literature reviews, in their multiple versions, e.g. bibliometric-based reviews, which are submitted to the journal in increasing numbers. We use this editorial to revisit our editorial policy and outline the kind of submissions welcomed at SEAJ.

Understanding the clinical and environmental drivers of antifungal resistance in the One Health context.

Antifungal drugs have had a tremendous impact on human health and the yields of crops. However, in recent years, due to usage both in a health setting and in agriculture, there has been a rapid emergence of antifungal drug resistance that has outpaced novel compound discovery. It is now globally recognized that new strategies to tackle fungal infection are urgently needed, with such approaches requiring the cooperation of both sectors and the development of robust antifungal stewardship rationales. In this review, we examine the current antifungal regimes in clinical and agricultural settings, focusing on two pathogens of importance, Candida auris and Aspergillus fumigatus, examining their drivers of antifungal resistance, the impact of dual-use azoles and the impact agricultural practices have on driving the emergence of resistance. Finally, we postulate that a One Health approach could offer a viable alternative to prolonging the efficacy of current antifungal agents.

Engineered Hybrid Lantibiotic that Selectively Combats Infections Caused by Staphylococcus aureus.

The rapid emergence of antibiotic-resistant strains of Staphylococcus aureus presents a substantial challenge to global public health, underscoring the urgent need for novel antibiotics with diverse mechanisms of action. In this study, we conducted mutagenesis on the C-terminal region of the lantibiotic ripcin C to enhance its antimicrobial efficacy against S. aureus. The resulting optimized variant, ripcin CP23A, demonstrated potent and selective antimicrobial activity, with a minimal inhibitory concentration of 2-4 mg/L against S. aureus. Beyond its strong antimicrobial properties, ripcin CP23A exhibited significant antibiofilm activity against methicillin-resistant S. aureus (MRSA). Mechanistic studies revealed that, in addition to targeting lipid II, ripcin CP23A disrupts bacterial membranes, a capability absent in ripcin C, which may contribute to its superior antimicrobial and antibiofilm effects. Moreover, ripcin CP23A displayed favorable biosafety and plasma stability profiles. Notably, in a mouse model of MRSA-induced mastitis, ripcin CP23A effectively reduced bacterial load, alleviated inflammation, and preserved the normal histomorphology of mammary glands. This study introduces ripcin CP23A as a promising antibiotic candidate for the treatment of MRSA-related infections.

Effect of Propofol and Isoflurane on Hemodynamic changes during Spinal Surgery Under General Anesthesia

Background: Hemodynamic stability are vital requirements of up-to-date anesthesia. Both propofol and isoflurane meet these criteria though the clinical effects like postoperative nausea vomiting after administering propofol and isoflurane have been studied in various surgeries but have not been much evaluated or studied in patients undergoing major surgical procedures like spine surgeries, There’ is definite advantage of one technique over the other. Isoflurane has a low blood gas partition coefficient, which contributes to rapid induction and emergence from anaesthesia than with other volatile anesthetics in current clinical use. Propofol has been established as the intravenous agent that provides faster and smoother recovery &amp; peri operative hemodynamic stability. Objective: To compare the effects of isoflurane and propofol regarding hemodynamic status in spinal surgery under general anaesthesia. Methods: After getting ethical approval, a randomized controlled trial study design was performed where patients were selected in the pre-anesthetic checkup room based on inclusion and exclusion criteria for those who were scheduled for spine surgeries under general anesthesia is admitted in the Department of Neurosurgery in East West Medical College from January 2023 – December 2024. A total number of 40 patients were selected. 20 patients were enrolled each in group A and group B by lottery method in a sealed envelope. They were divided into two groups by randomization; Group A and Group B. A written informed consent was taken from all selected patients. Patients were advised to fast for at least 8 hours before intervention. In Group A, anesthesia is maintained with propofol infusion, nitrous oxide (66%), and oxygen (33%) while in Group B, anesthesia is maintained with Isoflurane, nitrous oxide (66%), and oxygen (33%). All patients were given N2O in oxygen and 1.25% inspired concentration of Isoflurane (MAC -1.15). In Group A propofol infusion at rate of 80 μg/kg/min (fixed from the beginning). All data was collected at –Just after starting, 15 minutes, 30-minute, 1 hour, and &gt;1 hour interval per operatively. Data was compiled, edited and plotted in tabular and figure form. P value was determined as significant when it was &lt;0.05. Results: 40 patients yielded the following results. The mean age of Group A and B were 32.56±12.55 years and 34.6±12.5 years. Mean difference of heart rate was lower in Group A than that of Group B. Other parameters in both groups were confined to good and acceptable categories. But interestingly, there was a statistically significant difference found between Group A and Group B in Systolic Blood Pressure (SBP) &amp; Diastolic Blood Pressure (DBP). The scoring was far better in Group A than Group B. Mean SBP was higher in Group B than Group A (p= &gt;0.05). Similarly, mean DBP was also higher in Group B than Group A (p = &gt;0.05). Conclusion: Propofol is better for maintaining hemodynamic status than Isoflurane for Spine surgery under General anaesthesia. EWMCJ Vol. 12, No. 1&amp;2, January-July 2024: 21-26

Omiganan-Based Synthetic Antimicrobial Peptides for the Healthcare of Infectious Endophthalmitis.

Bacterial endophthalmitis is a severe infection of the aqueous or vitreous humor of the eye that can lead to permanent vision loss. Due to the rapid emergence of antibiotic resistance and dose-limiting toxicities, the standard treatment of bacterial endophthalmitis via the intravitreal injection of broad-spectrum antibiotics remains inadequate. Membrane active cationic antimicrobial peptides (AMPs) have emerged as a promising class of effective and broad-spectrum antimicrobial agents with potential to overcome antibiotic resistance. In this work, we investigate, for the first time, the use of omiganan (IK-12), a 12-amino acid indolicidin derivative for the treatment of bacterial endophthalmitis. Additionally, IK-12 was used as a template to perform amino acid rearrangements, without altering the length or type of amino acids, to yield a series of new derivative AMPs with varying extents of secondary structure formation under membrane mimicking conditions. IK-12 and its derivatives demonstrated strong and broad-spectrum antibacterial activities against a panel of clinically isolated Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus commonly implicated in bacterial endophthalmitis. Interestingly, two of the new IK-12 derivatives, IP-12 and WP-12, showed lower geometric mean minimum inhibitory concentration and higher 50% hemolysis concentration values, which effectively translated into 2- to 3.4-fold higher bacterial selectivity than the parent IK-12. Furthermore, the intravitreal injection of IK-12, IP-12, and WP-12 in a rabbit model of MRSA-induced endophthalmitis led to considerably improved clinical presentation and reduced recruitment of inflammatory cells. In all, these results demonstrate the potential of IK-12 and its derivatives, IP-12 and WP-12, as promising candidates for the treatment of bacterial endophthalmitis.