Effects of environmental relevant concentrations of acetochlor on growth, hematology, serum biochemistry and histopathology of Japanese quail.

Acetochlor is frequently applied to various food crops in agriculture sector, and long-term exposure can cause significant endocrine-disrupting effects in exposed animals including impacts on human health. This study aimed to evaluate the effects of acetochlor on the growth, hematology, serum biochemistry, and histopathological alterations in Japanese quail. Eighty male quail were obtained and divided into four groups (A-D) and given acetochlor orally for the period of 45 days. Group A was served as the control, while groups B, C, and D received 20mg/kg, 30mg/kg, and 40mg/kg acetochlor, respectively. The study found that Japanese quail administered higher doses of acetochlor exhibited reduced frequency of crowing and foam production. The results showed that increased concentrations of acetochlor led to adverse effects on the growth parameters of Japanese quail. Hematology analysis indicated that birds exposed to higher concentrations of acetochlor experienced a significant decrease in red blood cell count, hemoglobin concentration, hematocrit (HCT), mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC), along with a significant increase in white blood cell count compared to the control group. Additionally, higher concentrations of acetochlor led to a significant increase in various serological indices including urea, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), while the values of total proteins, albumin, and plasma proteins declined. The histopathology results of treated Japanese quail exposed to higher concentrations of acetochlor showed a range of pathological lesions in the testes, heart, and brain. The study concluded that even low concentrations of acetochlor can cause slight to significant changes in Japanese quail, affecting their physical, hematological, histopathological and serum biochemical parameters.

Effects of drought and moisture stress on the growth and ecophysiological traits of Schima superba seedlings.

Changes in rainfall patterns are important environmental factors affecting plant growth, especially when larger precipitation events and prolonged drought periods occur in subtropical regions. There are many studies on how drought reduces plant biomass through drought-sensitive functional traits, but how excess water affects plant growth and ecophysiology is still poorly understood. Therefore, a greenhouse experiment was conducted on Schima superba (Theaceae), a dominant tree species in subtropical forests and commonly used in forestry, in a closed chamber under control (25% soil water content (SWC) as in local forests), drought stress (D, 15% SWC) and moisture stress (W, 35% SWC). Plant growth and ecophysiological traits related to morphology, leaf gas exchange, water potential and structural traits were measured. Compared to control, S. suberba under dry conditions significantly decreased its aboveground biomass, photosynthetic rate (A), leaf water potential and nitrogen use efficiency, but increased intrinsic water use efficiency, root to shoot ratio and specific root length. S. superba under wet conditions also significantly decreased its total biomass, aboveground biomass and specific root length, while W had no effect on A and leaf water potential. Our results indicate that S. superba shows a decrease in carbon gain under drought stress, but less response under wet conditions. This emphasizes the need to consider the strength and frequency of rainfall pattern changes in future studies because rainfall may either alleviate or intensify the effects of drought stress depending on the moisture level, thus suitable water conditions is important for better management of this tree species in subtropical China.

2D Materials in Advanced Electronic Biosensors for Point-of-Care Devices.

Since two-dimensionalal (2D) materials have distinct chemical and physical properties, they are widely used in various sectors of modern technologies. In the domain of diagnostic biodevices, particularly for point-of-care (PoC) biomedical diagnostics, 2D-based field-effect transistor biosensors (bio-FETs) demonstrate substantial potential. Here, in this review article, the operational mechanisms and detection capabilities of biosensing devices utilizing graphene, transition metal dichalcogenides (TMDCs), black phosphorus, and other 2D materials are addressed in detail. The incorporation of these materials into FET-based biosensors offers significant advantages, including low detection limits (LOD), real-time monitoring, label-free diagnosis, and exceptional selectivity. The review also highlights the diverse applications of these biosensors, ranging from conventional to wearable devices, underscoring the versatility of 2D material-based FET devices. Additionally, the review provides a comprehensive assessment of the limitations and challenges faced by these devices, along with insights into future prospects and advancements. Notably, a detailed comparison of FET-based biosensors is tabulated along with various other biosensing platforms and their working mechanisms. Ultimately, this review aims to stimulate further research and innovation in this field while educating the scientific community about the latest advancements in 2D materials-based biosensors.

Defect-engineered dual Z-scheme core-shell MoS2/WO3-x/AgBiS2 for antibiotic and dyes degradation in photo and night catalysis: Mechanism and pathways.

Water pollution caused by antibiotics and synthetic dyes and imminent energy crises due to limited fossil fuel resources are issues of contemporary decades. Herein, we address them by enabling the multifunctionality in dual Z-scheme MoS2/WO3-x/AgBiS2 across photolysis, photo Fenton-like, and night catalysis. Defect, basal, and facet-engineered WO3-x is modified with MoS2 and AgBiS2, which extended its photoresponse from the UV-NIR region, inhibited carrier recombination, and reduced carrier transfer resistance. The electric field rearrangement leads to a flow of electrons from MoS2 and AgBiS2 to WO3-x and intensifies the electron population, which is crucial for night catalysis. When MoS2/WO3-x/AgBiS2 was employed against doxycycline hydrochloride (DOXH), it removed 95.65, 81.11, and 77.92 % of DOXH in 100 min during photo-Fenton (PFR), night-Fenton (NFR), and photocatalytic (PCR) reactions, respectively. It also effectively removed 91.91, 98.17, 99.01, and 98.99 % of rhodamine B (RhB), Congo red (CR), methylene blue (MB), and methylene orange (MO) in Fenton reactions, respectively. ESR analysis consolidates the ROS generation feature of MoS2/WO3-x/AgBiS2 using H2O2 with and without irradiation. This work provides a strategy to eliminate the deficiencies of WO3-x and is conducive to the evolution of applications seeking to combat environmental and energy crises.

Predictors for poor daily weight gain in preterm neonates exposed to different dose regimens of caffeine in ICU- a retrospective cohort study.

BACKGROUND: With a wide therapeutic index, efficacy, ease of use, and other neuroprotective and respiratory benefits, caffeine citrate(CC) is currently the drug of choice for preterm neonates (PTNs). Caffeine-induced excessive energy expenditure, diuresis, natriuresis, and other CC-associated potential side-effects (CC-APSEs) result in lower daily-weight gain (WG) in premature neonates. This study aimed to evaluate the risk factors for daily-WG in neonates exposed to different dose regimens of caffeine in ICU. METHOD: This retrospective cohort study included neonates of ≤ 36weeks gestational age (GA) and received CC-therapy. The same participants were followed for data analysis in two postnatal phases: 15-28 and 29-42 days of life (DOL). Based on daily CC-dose, formed group-I (received; standard-doses = 5 mg/kg/day), group-II (received;>5-7 mg/kg/day), and group-III (received;>7 mg/kg/day). Prenatal and postnatal clinical characteristics, CC-regimen, daily-WG, CC-APSEs, and concomitant risk-factors, including daily-caloric intake, Parenteral-Nutrition duration, steroids, diuretics, and ibuprofen exposure, were analyzed separately for group-II and group-III using group-I as standard. Regression analysis was performed to evaluate the risk factors for daily-WG. RESULTS: Included 314 PTNs. During 15-28 DOL, the mean-daily-WG(MD-WG) was significantly higher in group-I than group-II [19.9 ± 0.70 g/kg/d vs. 17.7 ± 0.52 p = 0.036] and group-III [19.9 ± 0.70 g/kg/d vs. 16.8 ± 0.73 p < 0.001]. During 29-42 DOL the MD-WG of group-I was only significantly higher than group-III [21.7 ± 0.44 g/kg/d vs. 18.3 ± 0.41 g/kg/d p = 0.003] and comparable with group-II. During 15-28 DOL, observed CC-APSEs was significantly higher in group-II and III but during 29-42 DOL it was only significant in group-III. In the adjusted regression analysis for daily-WG during 15-28DOL, with respect to standard-dose, 5-7 mg/kg/day (ß=-1.04; 95%CI:-1.62,-0.93) and > 7-10 mg/kg/day (ß=-1.36; 95%CI:-1.56,-1.02) were associated with a lower daily-WG. However, during 29-42DOL, this association was present only for > 7-10 mg/kg/day (ß=-1.54; 95%CI:-1.66,-1.42). The GA ≤ 27weeks (ß=-1.03 95%CI:-1.24, -0.88) was associated with lower daily-WG only during 15-28DOL. During both periods of therapy, higher cumulative-caffeine dose and presence of culture proven sepsis, tachypnea, hyponatremia, and feeding intolerance were significantly associated with lower daily-WG. Conversely, daily kcal intake was found to be linked with an increase in daily-WG in both periods. CONCLUSION: In this study cohort exposure to higher caffeine daily and cumulative doses is associated with lower postnatal daily-WG in PTNs than standard-daily doses, which may be due to its catabolic effects and CC-APSEs.

The effect of water in THF/water mixtures on CMC, aggregation sizes, and fluorescence quenching of a new calix[4]resorcinarene macrocycle.

This study explores how water content modulates the self-assembly and fluorescence behavior of a novel calixarene, C1. C1 forms large, flattened structures in pure THF, but water addition triggers a transition to smaller, unimodal clusters. A critical micellar concentration (CMC) is identified, decreasing with increasing water content. Fluorescence quenching is observed upon water addition, attributed to nonradiative deactivation. These findings highlight water as a key regulator of C1's assembly and fluorescence, paving the way for further development of water-responsive calixarene systems.

Smartphone-assimilated colorimetric sensor for sub-nanomolar emamectin detection via KA30 capped silver nanoparticles in food, bio-fluids and water samples.

In this report, we firstly synthesized nitro calix [4] resorcinarene compound (referred as KA30) and characterized it though proton (1H) nuclear magnetic resonance (NMR) spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and Fourier Transform Infra-red (FTIR) spectroscopy. KA30 was applied as functionalizing agent for the formation of silver nanoparticles (KA30-AgNPs). These NPs were confirmed as highly selective and extremely sensitive colorimetric sensor for ultra-low level detection of emamectin (EMA) as a novel report. Significant aspect of the sensor is its unique detection range between 0.0005 and 29.5 µM via color change from yellow to colorless with hypochromic-bathochromic shift exhibiting limit of detection (LOD) and limit of quantification (LOQ) as 0.12 nM and 0.4 nM respectively. The sensor was applied to colorimetrically and optically detect EMA in real samples of serum, urine and food. The sensor was further allied with smartphone for real-time, and on-site detection of EMA and results were validated through UPLC.

Dose-Response Study of Caffeine on Postnatal Weight Gain in Premature Neonates-A Retrospective Cohort Study.

Background: Caffeine citrate (CC)-induced excessive energy expenditure, diuresis, natriuresis, and other CC-associated potential side effects (CC-APSEs) result in lower daily weight gain (WG) in premature neonates. This study aimed to assess higher CC-doses' effect on the mean daily-WG (MD-WG) and CC-APSE development, considering 5 mg/kg/day as the standard regimen. Method: This retrospective cohort study included neonates of ≤36 weeks gestational age and received CC-therapy. The same participants were followed for data analysis in two postnatal phases: 15-28 and 29-42 days of life (DOL). Based on daily CC-dose, formed group-I=(5 mg/kg/day), group-II=(>5-7 mg/kg/day), and group-III=(>7 mg/kg/day). Data was analyzed separately for group-II and group-III using group-I as the standard. Results: The study included 284 neonates. During phase-I, the MD-WG was significantly higher in group-I than group-II (19.9 ± .88 g/kg/d vs 17.5 ± .49, P = .031) and group-III (19.9 ± .88 g/kg/d vs 16.7 ± .71, P < .001). During 29-42 DOL, the MD-WG of group-I was only significantly higher than group-III (21.5 ± .42 g/kg/d vs 18.1 ± .39 g/kg/d, P = .003) and comparable with group-II. During 15-28 DOL, CC-APSEs were significantly higher in group-II and group-III but during 29-42 DOL was significant only in group-III. Conclusion: Exposure to higher caffeine doses in this study cohort is associated with lower postnatal WG in preterm neonates than standard daily doses may be due to its catabolic effects and CC-APSEs.

Association of Caffeine Daily Dose With Respiratory Outcomes in Preterm Neonates: A Retrospective Cohort Study.

Apnea and poor respiratory drive increase the risk of extubation failure (EF) and prolonged invasive mechanical ventilation (IMV) in preterm neonates (pre-nates) with respiratory distress. Caffeine citrate (CC) is often prescribed for pre-nates in doses of 5-10 mg/kg in 24 h. This study aimed to evaluate the most effective dosage regimen (5 mg/kg/day vs >5-10 mg/kg/day) to prevent apnea and EF with minimal caffeine-associated potential side effects (CC-APSEs) in pre-nates. This one-year retrospective cohort study included all the eligible neonates admitted to NICU and received CC-therapy till 28 days of life (DOL) or discharge. Based on CC-daily dose formed LD-caffeine-group (5 mg/kg/day) and HD-caffeine-group (>5-10 mg/kg/day). Antenatal, prenatal, and postnatal characteristics, CC-regimen, comorbidities, and CC-APSEs were compared between the groups. Predictors of apnea and EF were analyzed through logistic regression. There were 181 and 72 neonates in the LD and HD-caffeine-groups respectively. In HD-caffeine-group daily CC-dose was 7 to 7.5 mg/kg/day in 93% of neonates and >7.5 to 10 mg/kg/day in only 7%. Significantly fewer neonates experienced apnea and EF in the HD-caffeine-group till 28DOL or discharge. This difference was even greater in the subgroup of ≤28 weeks GA (15.6% vs 40.0%; P < .01). In HD-caffeine-group the incidence of severe/moderate-BPD was significantly lower and the frequency of CC-APSEs was higher. Multivariate analysis showed that; the smaller the GA higher the risk of apnea (AOR = 0.510, 95% CI 0.483-0.999) and EF (AOR = 0.787, 95% CI 0.411-0.997). The HD-caffeine was inversely associated with developing apnea (AOR = 0.244, 95% CI 0.053-0.291) and EF (AOR = 0.103, 95% CI 0.098-2.976). IMV-duration before extubation (AOR = 2.229, 95% CI 1.672-2.498) and severe/moderate-BPD (AOR = 2.410, 95%CI 1.104-2.952) had a high risk of EF. Initiating early HD-caffeine may prevent apnea and extubation failure in preterm neonates. Optimization of caffeine initiation time and dosages can be a safe and feasible approach to decrease the burden of neonatal respiratory morbidities.

Accurate multilevel thresholding image segmentation via oppositional Snake Optimization algorithm: Real cases with liver disease.

Liver-related diseases significantly contribute to global mortality rates. Accurate segmentation of liver disease from CT scans is essential for early diagnosis and treatment selection, particularly in computer-aided diagnosis (CAD) systems. To address challenges posed by inconsistent liver presence and unclear boundaries, an enhanced Snake Optimization (SO) algorithm is proposed that integrates with opposition-based learning (OBL) called (SO-OBL), proving effective in global optimization and multilevel image segmentation. Experiments using CEC'2022 test functions compare SO-OBL with eleven recent and state-of-the-art metaheuristic algorithms, demonstrating its superior performance. Additionally, an advanced liver disease segmentation model based on SO-OBL incorporates an optimized multilevel thresholding technique, leveraging Otsu's function. Notable segmentation metric results, including FSIM = 0.947, SSIM = 0.941, PSNR = 24.876, MSE = 236.88, and execution time = 0.281, underscore the model's efficiency and potential for accurate diagnosis in CAD systems.

Mutational and expressional association of the PIK3CA gene with the risk of breast cancer in the Pakistani population.

PI3K pathway is a very important pathway that is reported to be involved in breast cancer. Mutation of PI3K and p110 alpha-catalytic subunit of phosphatidylinositol 3-kinase (PIK3CA) is of high predictive and prognostic values in breast cancer. The purpose of the current study was to screen the hotspot mutations of the PIK3CA gene i.e. rs2677760, rs3806685, rs121913273 & rs121913279 along with expressional analysis of PI3K and PIK3CA genes in breast cancer female patients. For mutational analysis, TaqMan assay & Sanger sequencing were performed while for expressional analysis real-time PCR was carried out. Mutant allele C of rs2677760 was observed to be high in postmenopausal patients. The frequency of mutant allele G of rs3806685 was significantly high in breast cancer patients. All diseased and control samples were of wild type for the hotspot rs121913273 and rs121913279 with allele G for rs121913273 and A for rs121913279. Expression of the PI3K was high in breast cancer tissue samples as compared to the adjacent controls. While the expression of the thePIK3CA gene was significantly high in premenopausal breast cancer patients. It was concluded that the mutant allele C of rs2677760 might have some sort of association with the menopausal status and it could be used as a diagnostic marker in post-menopausal women if studied further. Mutant allele G of rs3806685 was also found to be associated with breast cancer. While multiallelic rs121913273 and rs121913279 showed a different trend for the studied population. For expressional analysis, PI3K showed over-expression in the cases while PIK3CA gene expression was observed to be significantly associated with pre-menopausal status.

Enhanced Photocatalytic Degradation of Malachite Green Dye Using Silver-Manganese Oxide Nanoparticles.

Efficient and excellent nanoparticles are required for the degradation of organic dyes in photocatalysis. In this study, silver-manganese oxide nanoparticles (Ag-Mn-NPs) were synthesized through a wet chemical precipitation method and characterized as an advanced catalyst that has enhanced photocatalytic activity under sunlight irradiation. The nanoparticles were characterized using scanning electron microscopy (SEM), XRD, UV-vis light spectra, and energy-dispersive X-ray (EDX) spectroscopy, revealing their spherical and agglomerated form. The EDX spectra confirmed the composition of the nanoparticles, indicating their presence in oxide form. These bimetallic oxide nanoparticles were employed as photocatalysts for the degradation of malachite green (MG) dye under sunlight irradiation in an aqueous medium. The study investigated the effects of various parameters, such as irradiation time, catalyst dosage, recovered catalyst dosage, dye concentration, and pH, on the dye's photodegradation. The results showed that Ag-Mn oxide nanoparticles exhibited high photocatalytic activity, degrading 92% of the dye in 100 min. A longer irradiation time led to increased dye degradation. Moreover, a higher catalyst dosage resulted in a higher dye degradation percentage, with 91% degradation achieved using 0.0017 g of the photocatalyst in 60 min. Increasing the pH of the medium also enhanced the dye degradation, with 99% degradation achieved at pH 10 in 60 min. However, the photodegradation rate decreased with increasing dye concentration. The Ag-Mn oxide nanoparticles demonstrate excellent potential as a reliable visible-light-responsive photocatalyst for the efficient degradation of organic pollutants in wastewater treatment.

Molecular Insights into the In Vivo Analgesic and Anti-Inflammatory Activity of Indomethacin Analogues.

The primary objective of this research was to identify and explore the most potent and efficacious cyclooxygenase inhibitors, utilizing indole acetic acid drugs as a lead molecule. To achieve this objective, various derivatives (2a-2c and 2e-2g) of the selected lead molecule, indomethacin, were synthesized using a reflux condensation process, targeting the hydroxyl group. The synthesized analogues were subjected to different spectroscopic procedures to determine their structure and confirm their analogues. These derivatives were further screened for acute toxicity and anti-nociceptive and anti-inflammatory activity using established protocols. Docking analysis was performed to evaluate the possible protein-ligand interaction. The test compounds were found to be safe at doses of 50, 75, 100, and 200 mg/kg, i.p. The pharmacological screening revealed that test compounds 2a-2f had a superior peripheral analgesic effect at a dose of 10 mg/kg, in comparison to the parent drug indomethacin, while compound 2g exhibited slightly lower activity at the same dose. The hot plate results showed lower central analgesic activity of the test compounds compared to the standard Tramal, but it was still significant. Anti-inflammatory results were significant, comparable to Diclofenac sodium and indomethacin, except for compounds 2b, 2c, and 2e at a dose of 10 mg/kg body weight. Molecular docking analysis demonstrated that the derived compounds had augmented negative binding energies (-149.39, -146.72, -160.85, -159.34, -140.03, and -150.91 KJ/mol) compared to the parent drugs (-141.07), which supported the research's theme of producing stronger derivatives of standard drugs with significant anti-nociceptive and anti-inflammatory potential. The derived compounds exhibited significant analgesic and anti-inflammatory activities and, therefore, have the potential to be studied further as new drug candidates for pain and inflammation.

Dynamic Coati Optimization Algorithm for Biomedical Classification Tasks.

Medical datasets are primarily made up of numerous pointless and redundant elements in a collection of patient records. None of these characteristics are necessary for a medical decision-making process. Conversely, a large amount of data leads to increased dimensionality and decreased classifier performance in terms of machine learning. Numerous approaches have recently been put out to address this issue, and the results indicate that feature selection can be a successful remedy. To meet the various needs of input patterns, medical diagnostic tasks typically involve learning a suitable categorization model. The k-Nearest Neighbors algorithm (kNN) classifier's classification performance is typically decreased by the input variables' abundance of irrelevant features. To simplify the kNN classifier, essential attributes of the input variables have been searched using the feature selection approach. This paper presents the Coati Optimization Algorithm (DCOA) in a dynamic form as a feature selection technique where each iteration of the optimization process involves the introduction of a different feature. We enhance the exploration and exploitation capability of DCOA by employing dynamic opposing candidate solutions. The most impressive feature of DCOA is that it does not require any preparatory parameter fine-tuning to the most popular metaheuristic algorithms. The CEC'22 test suite and nine medical datasets with various dimension sizes were used to evaluate the performance of the original COA and the proposed dynamic version. The statistical results were validated using the Bonferroni-Dunn test and Kendall's W test and showed the superiority of DCOA over seven well-known metaheuristic algorithms with an overall accuracy of 89.7%, a feature selection of 24%, a sensitivity of 93.35% a specificity of 96.81%, and a precision of 93.90%.

Characterization and outlook of climatic hazards in an agricultural area of Pakistan.

Many dimensions of human life and the environment are vulnerable to anthropogenic climate change and the hazards associated with it. There are several indices and metrics to quantify climate hazards that can inform preparedness and planning at different levels e.g., global, regional, national, and local. This study uses biased corrected climate projections of temperature and precipitation to compute characteristics of potential climate hazards that are pronounced in the Gomal Zam Dam Command Area (GZDCA)- an irrigated agricultural area in Khyber Pakhtunkhwa province of Pakistan. The results answer the question of what the future holds in the GZDCA regarding climate hazards of heatwaves, heavy precipitation, and agricultural drought. The results of heatwaves and agricultural drought present an alarming future and call for immediate actions for preparedness and adaptation. The magnitude of drought indices for the future is correlated with the crop yield response based on AquaCrop model simulations with observed climate data being used as input. This correlation provides insight into the suitability of various drought indices for agricultural drought characterization. The results elaborate on how the yield of wheat crop grown in a typical setting common in the South Asian region respond to the magnitude of drought indices. The findings of this study inform the planning process for changing climate and expected climate hazards in the GZDCA. Analyzing climate hazards for the future at the local level (administrative districts or contiguous agricultural areas) might be a more efficient approach for climate resilience due to its specificity and enhanced focus on the context.

Evaluation of haematological, serum biochemical and oxidative stress parameters in cattle naturally infected with lumpy skin disease virus.

Lumpy skin disease (LSD) is a vector-borne viral transboundary disease of cattle caused by the LSD virus (LSDV). Despite investigations on clinical and outbreak features of LSDV, information on disease pathogenesis and alternative changes in blood parameters are scarce. Keeping this in view, the current study was designed to determine haematological, serum biochemical, and oxidative stress parameters in naturally infected cattle with LSDV during the recent surge of outbreaks in Punjab, Pakistan. A total of 35 blood samples was collected from polymerase chain reaction-confirmed LSDV-infected cattle for assessment of all parameters. The haematological examination of blood samples showed a significant reduction (p < 0.05) in different variables of erythrogram and leucogram. On the other hand, differences between levels of various serum biochemical parameters with the significant increase in levels of alkaline phosphatase, serum alanine aminotransferase, aspartate aminotransferase, and blood urea nitrogen were observed in LSDV naturally infected cattle. Moreover, malondialdehyde levels for lipid peroxidation and nitrate concentration were markedly elevated whereas glutathione S-transferase fluorescent and serum superoxide dismutase enzymes showed a decrease in levels. The current study suggests that alternations in haematological and serum biochemical parameters following LSDV infection stimulate oxidative stress and such findings may be useful for early and rapid diagnosis and improvement in the treatment strategy of the disease.

Azole and 5-nitroimidazole based nanoformulations are potential antiamoebic drug candidates against brain-eating amoebae.

AIM: Herein, the anti-parasitic activity of azoles (fluconazole and itraconazole) and 5-nitroimdazole (metronidazole) against the brain-eating amoebae: Naegleria fowleri and Balamuthia mandrillaris was elucidated. METHODS AND RESULTS: Azoles and 5-nitroimidazole based nanoformulations were synthesized and characterized using a UV-visible spectrophotometer, atomic force microscopy, and fourier transform infrared spectroscopy. H1-NMR, EI-MS, and ESI-MS were performed to determine their molecular mass and elucidate their structures. Their size, zeta potential, size distribution, and polydispersity index (PDI) were assessed. Amoebicidal assays revealed that all the drugs and their nanoformulations, (except itraconazole) presented significant anti-amoebic effects against B. mandrillaris, while all the treatments indicated notable amoebicidal properties against N. fowleri. Amoebicidal effects were radically enhanced upon conjugating the drugs with nanoparticles. The IC50 values for KM-38-AgNPs-F, KM-20-AgNPs-M, and KM-IF were 65.09, 91.27, and 72.19 µg.mL-1, respectively, against B. mandrillaris. Whereas against N. fowleri, the IC50 values were: 71.85, 73.95, and 63.01 µg.mL-1, respectively. Additionally, nanoformulations significantly reduced N. fowleri-mediated host cell death, while nanoformulations along with fluconazole and metronidazole considerably reduced Balamuthia-mediated human cell damage. Finally, all the tested drugs and their nanoformulations revealed limited cytotoxic activity against human cerebral microvascular endothelial cell (HBEC-5i) cells. CONCLUSION: These compounds should be developed into novel chemotherapeutic options for use against these distressing infections due to free-living amoebae, as currently there are no effective treatments.

Investigating the self-assembling of nicotinic hydrazide-based amphiphile into nano-range vesicles and its amphotericin B loading applications.

Most of the drugs are hydrophobic and have low water solubility, therefore posing issues in their absorption and bioavailability. Nonionic surfactants improve the solubility of hydrophobic drugs by entrapping them in their lipid bilayers. Two nonionic surfactants NODNH-16 and NODNH-18 are synthesized and characterized using different techniques i.e. EI-MS, 1H NMR, and FTIR. These newly synthesized surfactants were screened for blood hemolysis assay and cell toxicity studies using the NIH/3T3 cell line to assess their biocompatibility. Then amphotericin B was loaded into niosomal vesicles, and the drug entrapment efficiency of these surfactants was measured using UV-visible spectroscopy. The morphology of drug-loaded niosomes of synthesized surfactants was investigated using AFM, and their size, polydispersity, and zeta potential were measured with the Zetasizer instrument. Finally, a simulation study was performed to determine the pattern of self-assembly of the synthesized amphiphiles. Both synthesized nonionic surfactants showed good entrapment efficiency of 60.65 ± 2.12% and 68.45 ± 2.12%, respectively. It was also confirmed that both these synthesized nonionic surfactants were safe and biocompatible and showed less blood hemolysis (i.e. 21.13 ± 2.11% and 23.32 ± 2.45%) and higher 3T3 cells' viability at 150 µg/mL concentration as compared to Tween®-80. The antifungal potential of amphotericin B-loaded niosomes has been evaluated against unicellular multi-fungal species, which showed a promising potential for fungicidal activity. These results are substantiated by constructing a safe vehicle system for drug delivery.

Evaluation of MONOFER-induced hypersensitive reactions: A retrospective cohort study.

Iron deficiency is the most common cause of anaemia. Over the years, various IV preparations of iron have been developed, including Monofer® (Iron isomaltoside 1000), that showed a remarkable reduction in the occurance of hypersensitivity reactions. The main aim of the study was to evaluate the severity and extent to which hypersensitivity reactions occur after the administration of IV iron isomaltoside 1000 in an Asian population. Multistage sampling was adopted for this study. The overall sample size was 864. The mean age of the participants was 55.29 ±18.44 years. The results depicted that 63 (7.29%) of the entire participants faced hypersensitivity reactions after IV administration. A total of 43 (68.25%) participants who experienced hypersensitivity reactions showed clinical symptoms within one hour, 11(17.46%) showed reaction in 1-3 hours and 9 (14.29%) showed in > 3 Hours. The majority of the studied population showed significant improvement only after the administration of Pheniramine maleate, while only a few of them received Hydrocortisone.