Experimental Trials Research Articles

Influence of drug induced nausea and euphoria/ dysphoria on Pain Scores in non-painful cats, a prospective, randomised, experimental trial

Influence of drug induced nausea and euphoria/ dysphoria on Pain Scores in non-painful cats, a prospective, randomised, experimental trial

The Effect of Pre-Exercise Caffeine and Glucose Ingestion on Endurance Capacity in Hypoxia: A Double-Blind Crossover Trial

The impact of caffeine and glucose supplementation in a hypoxic environment on endurance exercise performance remains inconclusive. The current study examined the effect of pre-exercise carbohydrate and caffeine supplementation on endurance exercise performance in an acute hypoxic environment. Eight healthy active young males participated in this double-blind, within-subjects crossover study. Participants ingested the test drink 60 min before exercising at 50% Wmax for 90 min on a cycle ergometer (fatiguing preload); there followed an endurance performance test at 85% Wmax until exhaustion in a hypoxic chamber (~15%O2). Participants completed four experimental trials in a randomized order: caffeine (6 mg·kg−1; Caff), glucose (1 g·kg−1; CHO), caffeine (6 mg·kg−1) + glucose (1 g·kg−1; Caff−CHO), and taste- and color-matched placebo with no caffeine or CHO (PLA). Blood samples were collected during fasting, pre-exercise, every 30 min throughout the exercise, and immediately after exhaustion. The caffeine and glucose trials significantly enhanced endurance capacity in hypoxic conditions by Caff, 44% (68.8–31.5%, 95% confidence interval), CHO, 31% (44.7–15.6%), and Caff−CHO, 46% (79.1–13.2%). Plasma-free fatty-acid and glycerol concentrations were higher in Caff and PLA than in CHO and Caff−CHO (p < 0.05). The estimated rate of fat oxidation was higher in Caff and PLA than in CHO and Caff−CHO (p < 0.05). There were no significant differences in ratings of perceived exertion between trials. In conclusion, the ingestion of caffeine, glucose, or caffeine + glucose one hour before exercising in hypoxic conditions significantly improved 85% Wmax endurance performance after prolonged exercise.

Myocardial contractile function in the post-traumatic period of cardiac contusion in rats with different stress resistance: A preclinical experimental randomized trial

Background. Pathogenesis of cardiac contusion involves primary traumatic and secondary hypoxic mechanisms of myocardial contractile function depression as well as body reactions aimed at adapting to altered environment. A significant part of these reactions is realized in the context of stress. The intensity of the stress component in myocardial dysfunction is largely determined by the individual stress reactivity of the body. Objectives. To assess the contractile function and functional reserves of the myocardium of rats with a high and low level of stress resistance in the post-traumatic period of cardiac contusion. Methods. A preclinical experimental randomized trial involved 134 white mature nonlinear male rats weighing about 270 g. The animals were divided by sequentially performed Open Field and Porsolt Forced Swim tests into 2 groups: group 1 — animals with low stress resistance, group 2 — animals with high stress resistance. Within each group, the animals were randomized into control and experimental subgroups. In the experimental subgroups, 6, 12 and 24 hours after simulating cardiac contusion, the force and rate indicators of myocardial contractility were evaluated using the Fallen isolated heart model. The summary measures of the study included assessing the contractile force and rate of isolated hearts of rats with low and high stress resistance, particularly under conditions of high-frequency rhythm load (ranging from 4.0 to 8.3 Hz) during the post-traumatic period of cardiac contusion. Data analysis was performed using software packages MS Office 2013 (Microsoft Corporation, USA) and Statistica, v. 10 (StatSoft, USA). The differences were considered to be statistically significant at p < 0.05. Results. 6, 12 and 24 hours after simulating a cardiac contusion, contractile force and rate of isolated hearts decreased in group 1 and group 2. In low stress-resistant animals, immediately following the stabilization period and during high-frequency rhythm test, the contractility force and rate in isolated hearts were statistically significantly lower (p = 0.0008) compared to those recorded in highly stress-resistant individuals. During the stimulation of a high-frequency rhythm, isolated hearts in the experimental group revealed diastolic dysfunction at all time points. In highly stress-resistant animals, diastolic dysfunction occurred at a heart rate of 300 min-1 and above, whereas in low stress-resistant animals, it manifested at a heart rate of 240 min-1 and above. At the same heart rate, diastolic dysfunction in low stress-resistant animals was statistically significantly greater (p = 0.0008) compared to that of highly resistant animals. Conclusion. The post-traumatic period following experimental myocardial contusion is characterized by a reduction in the force and rate of myocardial contractility, as well as a decrease in functional reserves of the myocardium, regardless of stress resistance. High stress resistance is associated with better preservation of cardiac contractile function and contractility reserves, whereas low stress resistance correlates with a more pronounced degree of myocardial dysfunction and a significant reduction in functional reserves of the contused heart. Differences in the severity of contractile dysfunction under conditions of high and low body resistance to stress can be attributed to varying degrees of secondary myocardial damage in the contused area, resulting from the misbalance between stress-activating and stress-limiting mechanisms involved in the development of secondary damage.

Mechanical properties of aramid and UHMWPE thermoplastic composites: numerical and experimental trials

The out-of-plane behaviour of 8 different composites exposed to very high deformation rates and non-standard conditions was investigated in our previous studies. The mechanical properties of these composites have been evaluated through tests conducted at deformation rates comparable to those experienced during explosions. Based on the relevant test results, this study conducted a numerical analysis of 3 best-performing Aramid UD GS3000, Artec Aramid/Woven Aramid CT736, and H62 UD-UHMWPE-reinforced composites. In this regard, LS-DYNA's MAT54 model was compared with other failure mechanics-based models and preferred because it requires less experimental data and can simulate damage progression in dynamic failures. Since the samples used in the study were non-standard, quasi-static tensile and shear tests were performed based on the loads to which the composites would be exposed to create an accurate numerical analysis. Both tensile and shear strength values of the Artec Aramid/Woven Aramid CT736 composite are higher than those of the Aramid UD GS3000 and H62 UD-UHMWPE composites. When the numerical analysis results were compared with the tensile test data, compliance rates of 99.84% for Aramid UD GS3000 reinforced composite, 99.34% for Artec Aramid/Woven Aramid CT736 reinforced composite, and 96.42% for H62 UD-UHMWPE reinforced composite were determined. The analysis showed that the shear stress-strain curves provided 100% agreement at the maximum stress value.

Sprouting and Growth of Garlic (Allium sativum L.) At Green Stage Under Various Nutrients.

Garlic (Allium sativum L.) is a vital crop, yet its growth and sprouting at the green stage can be significantly influenced by nutrient availability, which poses a challenge for optimizing yield and quality. The present research was carried out in 2022–2023 at the Nursery Department of Horticulture, Sindh Agriculture University Tandojam, to assess the sprouting and growth of garlic (Allium sativum L.) at green stage under various nutrients. The experimental trial was carried out in complete randomization (CRD) with three replications. Two varieties, a Chinese and a local (Desi) (Desi) variety, were grown in the pots. Macronutrients used as treatments included N1 (control). N2 = NPK+TE (trace elements) 2 g, L-1. N3 = Calcium Nitrate 0.5g, L-1 and N4 = NPK+TE 2g, L-1 + Calcium Nitrate 0.5g, L-1. The results of the present studies showed a statistically significant difference for treatments and nutrient combinations. Best results for all observations were noted in plants supplied with NPK+TE 2g L-1 that had maximum plant height 55.83 cm, leaves plant-1 6.83, leaf length 47.66 cm, leaf weight 8.96g, plant weight 13.20g, neck thickness 6.55mm, root weight 2.68g, and root depth 19.83cm. Fallow control plant height 41.00cm leaves plant-1 5.00, leaf length 31.00cm, leaves weight 4.73g, plant weight 7.61g, neck thickness 3.51mm, root weight 1.46g and root depth 12.00cm. In between varieties the Chinese had maximum plant height 54.66cm, leaves plant-1 7.00, leaf length 45.00cm, leaves weight 10.04g, plant weight 10.99g, neck thickness 8.26mm, root weight 2.81g and root depth 22.00cm. Based on nutrients, the Chinese variety of garlic performed better growth at the green stage than the local (Desi) variety of garlic. The findings of this study show that nutrient N2 = NPK+TE (Trace Elements) 2g L-1had better results for all parameters, and all results were statistically significant.

Anesthetic Gas Scavenging System for Gas Evacuation in the ICU.

Inhaled sedation is increasing in ICUs, with active carbon filters (ACFs) commonly used for evacuating halogenated gases. However, the potential benefits of a waste anesthetic gas system (WAGS) similar to the ones used in operating rooms should be explored. To limit the suction over the flow sensor where the WAGS is connected on ICU ventilators, an anesthetic gas receiving system (AGRS) is required, constituting with the WAGS an active gas receiving and scavenging system (AGRSS). Ensuring that this whole device does not compromise the flow sensor reliability is crucial. The aim of this study was to compare various gas evacuation devices and assess the reliability of AGRSS on ICU ventilators. In this experimental study, pressures and flows were recorded during the ventilation of a test lung using various ventilator settings and gas evacuation methods: no device (reference condition), ACF, the WAGS alone, AGRSS (WAGS and AGRS together), and the expiratory valve connected to the medical vacuum system with the AGRS in between. Visual comparisons of the pressure and flow curves followed by a statistical analysis comparing median pressures and flows of each device to the reference were performed. The test lung model demonstrated consistent comparability in pressures and flows among all devices, except for the WAGS alone, which exhibited discordance through significant overestimation or underestimation. These findings indicate that using a WAGS with the AGRS system appeared to be reliable for managing gas evacuation in ICUs without compromising pressure or flow delivery. The data from this experimental trial should be confirmed with clinical studies involving human subjects. Given the increasing use of inhaled sedation in ICUs, these results support the daily application of the WAGS with the AGRS for gas evacuation, similar to its established use in anesthesiology.

Are caffeine effects equivalent between different modes of administration: the acute effects of 3 mg.kg-1 caffeine on the muscular strength and power of male university Rugby Union players.

There is growing interest in the potential of alternative modes of caffeine administration for enhancing sports performance. Given that alternative modes may evoke improved physical performance via distinct mechanisms, effects may not be comparable and studies directly comparing the erogenicity of alternative modes of caffeine administration are lacking. To address this knowledge gap, the present study evaluated the effect of 3 mg·kg-1 caffeine delivered in anhydrous form via capsule ingestion, chewing gum or mouth rinsing on measures of muscular strength, power, and strength endurance in male Rugby Union players. Twenty-seven participants completed the study (Mean ± SD: Age 20 ± 2 yrs; daily caffeine consumption 188 ± 88 mg). Following assessments and reassessment of chest press (CP), shoulder press (SP), Deadlift (DL), and Squat (SQ) 1-repetition maximum (1RM) and familiarization to the experimental procedures, participants completed six experimental trials where they were administered 3 mg.kg-1 caffeine (Caff) or placebo (Plac) capsule(CAP), chewing gum(GUM) or mouth rinse(RINSE) in a randomized, double-blind and counterbalanced fashion prior to force platform assessment of countermovement jump, drop jump and isometric mid-thigh pull performance. Strength endurance was measured across two sets of CP, SP, DL, and SQ at 70% 1RM until failure. Pre-exercise perceptions of motivation and arousal were also determined. Caffeine increased perceived readiness to invest mental effort (p = .038; ηp2=.156), countermovement jump height (p = .035; ηp2=.160) and SQ repetitions until failure in the first set (p < .001; d = .481), but there was no effect of delivery mode (p > .687; ηp2<.015). Readiness to invest physical effort, felt arousal, drop jump height, countermovement jump, drop jump and isometric mid-thigh pull ground reaction force-time characteristics and repetitions until failure in CP, SP and DL were not affected by caffeine administration or mode of caffeine delivery (p > .0.052; ηp2< .136). 3 mg.kg-1 caffeine administered via capsule, gum or mouth rinse had limited effects on muscular strength, power, and strength endurance. Small effects of caffeine on CMJ height could not be explained by changes in specific ground reaction force-time characteristics and were not transferable to DJ performance, and effects specific to the SQ RTP exercise underpin the complexity in understanding effects of caffeine on muscular function. Novel modes of caffeine administration proposed to evoke benefits via distinct mechanisms did not offer unique effects, and the small number of effects demonstrated may have little translation to a single performance trial when data examining direct comparison of each caffeine vehicle compared against a mode matched placebo is considered.

Evaluating the efficacy of Lactobacillus acidophilus derived postbiotics on growth metrics, Health, and Gut Integrity in broiler chickens.

Continuous use of antibiotics in poultry feed as growth promoters poses a grave threat to humanity through the emergence of antibiotic resistance, necessitating the exploration of novel and sustainable alternatives. The present study was carried out to evaluate the performance of postbiotics derived from Lactobacillus acidophilus in broiler birds. The postbiotics were harvested by culturing probiotic bacteria from the stock cultures at the required temperature and duration under laboratory conditions and supplemented to broilers via feed. For experimentation, 480-day-old CARI-Bro Dhanraja (slow-growing broiler) straight-run chicks were randomly split up into six groups. Treatment groups diets are as follows: T1- Basal diet (BD)+0.2%(v/w) MRS Broth/ uninoculated media; T2 - BD + Antibiotic (CTC); T3- BD + Probiotic; T4, T5 & T6 - BD + postbiotics supplementation of 0.2%, 0.4% and 0.6%(v/w) respectively. The chicks were raised under an intensive, deep litter system with standard protocol for 6 weeks. Results showed that 0.2% of postbiotics (T4) had significantly (P < 0.001) higher body weight (1677.52g) with better FCR (1.75) and immune response. Postbiotic supplementation altered various serum attributes positively, in this study. Significant (P < 0.001) reductions in total plate counts (TPC), coliform counts, and maximum Lactobacillus counts were recorded in all postbiotic-supplemented groups. The villus height (1379.25μm), width (216.06μm) and crept depth (179.25μm) showed significant (P < 0.001) improvement among the treatment groups on the 21st and 42nd day of the experimental trial, with the highest value in the T4 group (0.2% postbiotic supplementation). Jejunal antioxidant values also noted significantly (P < 0.001) higher values in T4 group. The study concludes that 0.2% postbiotic supplementation can act as a substitute to antibiotic growth promoters and also combat the disfavour activity of probiotics in broilers.

The effect of aged simulation suit on nursing students’ empathy, attitudes, and willingness to care for older adults: Experimental trial mixed-method study

ABSTRACT This study investigates the impact of age simulation suits on nursing students’ empathy, attitudes, and willingness to care for older adults. An experimental trial with a mixed-method design was conducted during the spring semester of the 2023–2024 academic year, involving 43 third-year nursing students. The intervention group (n = 23) wore age simulation suits, while the control group (n = 20) wore placebo clothing. Pre- and post-testt assessments measured empathy, attitudes toward older adults, and willingness to work with them. Content analysis was performed on the intervention group’s experiences. Results indicated a significant increase in the intervention group’s willingness to work with older adults after the simulation (Z = –3.232, p < .001; Hedges’ g: 0.819). However, no significant changes were observed in empathy or attitude scores (p > .05), and the control group showed no significant changes in any measured variables (p > .05). Content analysis revealed four key themes related to students’ feelings: (i) isolation and dependency, (ii) physical challenges and limitations, (iii) emotional responses and empathy, and (iv) changes in behavior and perception. Additionally, four main themes regarding new learnings were identified: (i) understanding and empathy, (ii) patience and communication, (iii) practical challenges and adaptation, and (iv) long-term impact and reflection. Two themes emerged on how nursing students can best approach older adults in their future practice: (i) enhancing care through empathy and training and (ii) promoting safety and well-being through preventive measures.

Latrophilin-2 Deletion in Cardiomyocyte Disrupts Cell Junction, Leading to D-CMP.

Latrophilin-2 (Lphn2), an adhesive GPCR (G protein-coupled receptor), was found to be a specific marker of cardiac progenitors during the differentiation of pluripotent stem cells into cardiomyocytes or during embryonic heart development in our previous studies. Its role in adult heart physiology, however, remains unclear. The embryonic lethality resulting from Lphn2 deletion necessitates the establishment of cardiomyocyte-specific, tamoxifen-inducible Lphn2 knockout mice, which was achieved by crossing Lphn2flox/flox mice with mice having MerCreMer (tamoxifen-inducible Cre recombinase) under the α-myosin heavy chain promoter. Tamoxifen treatment for several days completely suppressed Lphn2 expression, specifically in the myocardium, and induced the dilated cardiomyopathy (D-CMP) phenotype with serious arrhythmia and sudden death in a short period of time. Transmission electron microscopy showed mitochondrial abnormalities, blurred Z-discs, and dehiscent myofibrils. The D-CMP phenotype, or heart failure, worsened during myocardial infarction. In a mechanistic study of D-CMP, Lphn2 knockout suppressed PGC-1α and mitochondrial dysfunction, leading to the accumulation of reactive oxygen species and the global suppression of junctional molecules, such as N-cadherin (adherens junction), DSC-2 (desmocollin-2; desmosome), and connexin-43 (gap junction), leading to the dehiscence of cardiac myofibers and serious arrhythmia. In an experimental therapeutic trial, activators of p38-MAPK, which is a downstream signaling molecule of Lphn2, remarkably rescued the D-CMP phenotype of Lphn2 knockout in the heart by restoring PGC-1α and mitochondrial function and recovering global junctional proteins. Lphn2 is a critical regulator of heart integrity by controlling mitochondrial functions and cell-to-cell junctions in cardiomyocytes. Its deficiency leads to D-CMP, which can be rescued by activators of the p38-MAPK pathway.

Gender differences in the use of an upper-extremity exoskeleton during physically and cognitively demanding tasks- a study protocol for a randomized experimental trial

BackgroundUpper limb exoskeletons are recommended to alleviate muscle fatigue, particularly in working conditions inducing musculoskeletal discomfort like overhead work. However, wearing an exoskeleton might introduce cognitive-motor interference, affecting performance. Understanding its neural impact and potential gender differences in design effects is crucial. Therefore, the aim of this study is to examine exoskeleton effects addressing cross-gender comparisons, and exploring the impact on cognitive and physical workload in real-world scenarios. The research questions address the impact of exoskeleton use on muscle synergies, upper body posture, cognitive resources, comfort/discomfort, acceptance and usability.MethodsThe cross-sectional study integrates a multifactorial mixed-measure design. Participants are grouped by gender (female vs. male) and working condition (with vs. without exoskeleton). Motor performance and underlying neuronal correlates (fNIRS) will be analyzed. Based on an a priori sample size calculation, 80 participants (40 female/40 male) will be recruited. Working performance will be assessed by 1. Physical Performance Task (PILE task) and 2. Precision Task (following the Fitts paradigm), while body postures will be monitored with an Xsens motion capture system. Brain activation will be captured with an fNIRS system comprising 32 active optodes. Postural comfort/discomfort, acceptance, and usability will be reported via standardized questionnaires.DiscussionThe study will gain insights into potential gender differences in exoskeleton use and will contribute to designing and optimizing the implementation of exoskeletons by considering muscle synergies, movement variability and cognitive resource allocation. Additionally, the study also highlights user discomfort, a crucial factor that could impede widespread adoption, particularly among females, in real-world scenarios.

Investigating the use of a mobile portfolio app to develop pre-service teachers’ reflective abilities and orientations to learning to teach

ABSTRACT Mobile technologies are expected to provide many benefits for teacher reflection during teaching practice. However, empirical studies on these outcomes are still scarce. In an experimental field trial, we tested the effects of different variants of a mobile portfolio app on the development of pre-service teachers’ self-reported reflective ability, their orientations to learning to teach (e.g. developing ideas through discussion), and the interaction between their use of the mobile portfolio and orientation with regard to the development of reflective ability. Although there were only small direct effects of using the mobile app to foster reflective ability, the use of the app seemed to enhance the willingness to develop ideas for teaching practice through discussion and communication with mentors. These orientations were positively correlated with reflective ability; however, they showed no moderating effect on reflective ability when using the app.

Alteplase vs. Tenecteplase: An In-depth Analysis of Their Relative Effectiveness in Treating Acute Ischemic Stroke

Dear Editor, Stroke stands as the second-leading cause of death worldwide [1, 2]. Each year, over 12 million individuals are impacted by stroke, resulting in approximately 6.5 million fatalities [1]. Stroke globally ranks as the third-leading factor causing a combination of death and disability [2]. Every year, around seven hundred thousand individuals in the United States undergo an Acute Ischemic Stroke (AIS), making up 85% of all stroke cases [2]. New treatments like intravenous thrombolysis and mechanical thrombectomy have cut mortality by 10% compared to older methods, enhancing long-term disability prevention rates following Acute Ischemic Stroke [2]. Alteplase is the sole FDA-approved thrombolytic drug in AIS within the first 4.5 hours. Despite its potential for disability-free recovery, its usage is constrained by a brief time window and adverse effects, notably a 6% risk of symptomatic bleeding. In addition, its fibrinolytic efficacy is limited, achieving vascular reopening in less than half of the patients, and can cause cytotoxicity to the already hypoxic brain with resultant cerebral edema [2]. Tenecteplase (TNK), a modified variant of alteplase, has improved features including greater fibrin selectivity and longer half-life and is given as a single bolus instead of an infusion, thanks to genetic recombinant technology [3]. Numerous studies have supported TNK's efficacy over alteplase in treating AIS. In 2016, Bruce C.V. Campbell and colleagues demonstrated that, according to the analysis of modified Rankin scale scores, tenecteplase exhibited a more favorable overall functional outcome compared to alteplase [4]. A dosage of 0.25 mg/kg of tenecteplase emerges as a promising alternative to replace alteplase as the preferred treatment for patients with AIS occurring within 4.5 hours due to TNK's superior early neurological recovery rates and comparable safety outcomes [3]. Despite gathering evidence from experimental trials indicating TNK's advantages over alteplase for AIS, the use of TNK at a dosage of 0.4 mg/kg appears to pose safety concerns when compared to alteplase [3]. Bruce C.V. Campbell and his fellow researchers revealed in their study that in spite of the beneficial effects of TNK relative to alteplase, there was no significant variation in the speed of recovery to independent function. Notably, they found no discernible distinction in the occurrence of intracranial hemorrhage [4]. ---Continue

The non-inferiority of piperonyl-butoxide Yorkool® G3 insecticide-treated nets compared to Olyset®Plus measured by Anopheles arabiensis mortality in experimental huts in Tanzania

BackgroundNon-inferiority trials are recommended by the World Health Organization (WHO) to demonstrate that health products show comparable efficacy to that of existing standard of care. As part of the WHO Global Malaria Programme (GMP) process of assessment of malaria vector control products, a second-in-class insecticide-treated net (ITN) must be shown to be non-inferior to a first-in-class product based on mosquito mortality. The public health impact of the first-in-class pyrethroid-piperonyl butoxide (PBO) ITN, Olyset® Plus, has been demonstrated in epidemiological trials in areas with insecticide-resistant mosquitoes, but there is a need to determine the efficacy of other pyrethroid-PBO nets to ensure timely market availability of nets in order to increase access to ITNs. The non-inferiority of a deltamethrin-PBO ITN Yorkool® G3 was evaluated entomologically against Olyset® Plus in experimental huts in Tanzania, following WHO guidelines for non-inferiority trials.MethodsThe trial of the two pyrethroid-PBO ITNs was conducted in experimental huts in Lupiro, Tanzania, using a randomized 7 × 7 Latin square block design. The study ran for 49 nights in 14 huts assessing the mosquito mortality and blood-feeding of wild, free-flying, pyrethroid-resistant Anopheles arabiensis. Using the non-inferiority approach, the comparative efficacy (primary endpoint was mosquito mortality at 24 h and secondary endpoint was blood-feeding) of unwashed and 20 times field-washed pyrethroid-PBO Yorkool® G3 ITNs, were compared with the first-in-class product Olyset® Plus and against a pyrethroid-only ITN, PermaNet® 2.0 ITNs, as a standard comparator.ResultsThe experimental hut trial demonstrated non-inferiority and superiority of Yorkool® G3 to Olyset® Plus based on mosquito mortality [51% vs. 39%, OR 1.68 (95% CI 1.50–1.88)], given that lower 95% CI exceeded 0.74 (delta of 39%) and the margin of no difference (1). Blood-feeding inhibition was high for all treated ITNs (> 90%) and Yorkool® G3 was non-inferior to Olyset® Plus [4% vs. 2%, OR 1.81 (95% CI 1.46–2.39)], given that upper 95% CI was less than 4.85 (delta of 4%). The pyrethroid-PBO ITNs were superior to the pyrethroid-only net, PermaNet® 2.0, as determined by both the proportion of mortality and blood-feeding of mosquitoes (p-value < 0.05).ConclusionYorkool® G3 ITNs demonstrated non-inferiority to the first-in-class Olyset® Plus and superiority over the standard pyrethroid-only ITN, PermaNet® 2.0 as measured by mortality and blood-feeding inhibition of wild pyrethroid-resistant An. arabiensis mosquitoes. Yorkool® G3 ITNs are potential tools for the control of metabolic insecticide-resistant malaria vectors, and their market availability will contribute to the cost-effective selection of ITNs by malaria control programmes to improve population access to ITNs.

Modulating Microbial Resistance: Transcription Factor Regulation of Antibiotic Resistance in Escherichia coli

Abstract Introduction/Objective Antibiotic resistance is a global health emergency, with resistance detected to all antibiotics currently in clinical use and only a few novel drugs in the development pipeline. Antibiotics target key biological processes in bacteria, such as protein synthesis, cell wall synthesis, DNA replication and protein translation. Cells tightly control their internal states in different environments by regulating their transcriptional program through the activity of transcription factors (TFs) that control the expression of multiple downstream effector genes. We hypothesized that efficacy of specific antibiotics can be adjusted by altering the transcriptional states of bacteria prior to treatment, using TF knockout (KO) and over- expression (O-E) strains. Methods/Case Report Aim: Calculate the IC50 of 9 TF KO strains and 9 TF O-E strains across across a panel of representative antibiotics. A previous barcode screen study had identified TF KOs which were associated with antibiotic resistance/susceptibility. A serial antibiotic dilution was prepared in M9 media. E. coli TF KO and O-E strains were cultured for 24 hours in M9 media+Antibiotic (37°C, shaking). Each strain/antibiotic combination contained a technical replicate. Growth was measured by OD, allowing for calculation of growth curves, drug response curves, IC50, and EC50. Strain-specific IC50 and EC50 were compared to wild-type (WT) IC50 and EC50 as a measure of drug resistance/susceptibility. Results (if a Case Study enter NA) Experiments demonstrated consistent, TF-specific patterns of drug susceptibility. Compared to WT, TF KO strains demonstrated altered antibiotic IC50s (drug susceptibility). Compared to WT, TF O-E strains also demonstrated altered antibiotic IC50s (drug susceptibility). Conclusion Hypothesis Weakly Supported – TF states affect IC50s (Abx resistance). The relationships outlined in initial screen were consistently represented in experimental trials. Strain resistance/susceptibility is directly related to TF system and drug mechanism of action. For example, drugs that inhibited ribosomal function demonstrated greater effectiveness against KO/O-E strains that relied more heavily on protein synthesis pathways. Drug resistance is not binary but is shaped by a number of internal cellular factors, including gene regulation by TFs.

Phytochemicals of Swertia chirayita Roxb. ex Fleming against malarial dihydroorotate dehydrogenase: an in silico study

The global economic burden of malaria is rising and lack of effective drugs against it have imposed an insurmountable challenge in designing it that is both affordable and resistanceless. The plants with ethnobotanical values are relatively safer and its use is a viable option as therapeutics for various demographic locations. In this regard, the chemical components of a plant, Swertia chirayita Roxb. ex Fleming (traditionally used as an antimalarial agent) were explored by multiple computational tools against dihydroorotate dehydrogenase (DHODH) protein of Plasmodium falciparum (PDB ID: 6GJG), a causative agent of the disease. The docking scores were calculated to be − 10.220, − 10.131, − 10.071, − 10.024, and − 9.905 kcal/mol for the top five molecules (decussatin, swerchirin, 1-hydroxy-3,5,8-trimethoxyxanthen-9-one, swertinin, and chiratol), respectively with the native ligand possessing a higher value of − 9.873 kcal/mol. The adducts were geometrically and thermodynamically stable as revealed by several parameters extracted from 200 ns molecular dynamics simulations (MDS) and verified by a single run of 600 ns. The smooth RMSD profiles from a cumulative MDS of 2.0 μs, pointed towards a sturdy nature of the receptor geometry with limited translational or rotational motion of the ligands. The involvement of LEU11, CYS14, LEU15, CYS23, PHE27, ILE102, ARG104, TYR337, LEU340, and VAL341 amino acid residues with mainly hydrophobic interactions at the orthosteric site were observed for most of the adducts. The binding free energy changes (up to − 30.18 ± 4.38 kcal/mol) hinted at the feasibility and sustained thermodynamical spontaneity of the forward reaction of the complex formation. The hit molecules could possibly disrupt or inhibit the normal functioning of the DHODH receptor leading to the likely prevention and cure of the disease and are recommended for experimental trials.

Landmark-aware autonomous odometry correction and map pruning for planetary rovers

Planetary rover autonomous localization is paramount for a planetary surface exploration mission. However, existing methods demonstrate limited localization accuracy, mostly due to the unstructured texture characterization of planetary surface. In response, this study presents a novel Neural Radiance Field (NeRF) driven visual odometry correction method that allows for high-precision 6-DoF rover pose estimation and local map pruning. First, an innovative image saliency evaluation approach, combining binarization and feature detection, is introduced to meticulously select landmarks that are conducive to rover re-localization. Subsequently, we conduct 3D reconstruction and rendering of the chosen landmarks based on a-priori knowledge of planetary surface images and their Neural Radiance Field (NeRF) models. High-precision odometry correction is achieved through the optimization of photometric loss between NeRF rending images and real images. Simultaneously, the odometry correction mechanism is employed in an autonomous manner to refine the NeRF model of the corresponding landmark, leading to an improved local map and gradually enhanced rover localization accuracy. Numerical simulation and experiment trials are carried out to evaluate the performance of the proposed method, results of which demonstrate state-of-the-art rover re-localization accuracy and local map pruning.

Predictive Gaze Analytics: A Comparative Case Study of the Foretelling Signs of User Performance during Interaction with Visualizations of Ontology Class Hierarchies

The current research landscape in ontology visualization has largely focused on tool development, yielding an extensive array of visualization tools. Although many existing solutions provide multiple ontology visualization layouts, there is limited research in adapting to an individual user’s performance, despite successful applications of adaptive technologies in related fields, including information visualization. In an effort to innovate beyond traditional one-size-fits-all visualizations, this paper contributes one step towards realizing user adaptive visualization by recognizing timely moments when users may potentially need intervention, as real-time adaptation can only occur if it is possible to correctly predict user success and failure during an interaction in the first place. In addition, an open-source, reusable, and extensible software: Beach Environment for the Analytics of Human Gaze (BEACH-Gaze) is made available to the broader scientific community interested in descriptive and predictive gaze analytics. Building on a wealth of research in eye tracking, this paper compares four approaches to predictive gaze analytics through a series of experiments that utilize scheduled gaze digests, irregular gaze events, the last known gaze status, as well as all gaze captured for a user at a given moment in time. The results from a set of experimental trials suggest that irregular gaze events are most informative of early predictions of user performance, whereas cognitive workload appears to be most indicative of overall user performance in the task scenario presented in this paper. These empirical findings highlight the importance of an analytical approach to gaze on user predictions and indicate careful consideration when applying.

Blood-spinal cord barrier in spinal cord injury: a scientific review based on own experimental trial

Objective. To analyze the mechanisms of the blood-spinal cord barrier permeability violation after spinal cord injury and to assess its impact on the development of secondary injuries, including those in the areas significantly remote from the epicenter of injury.Material and Methods. The article is an analysis of 45 publications supplemented by our own experimental data. The search for articles was conducted in databases such as PubMed, Scopus and Web of Science on the topic under study. Experimental data were obtained using confocal microscopy and bioluminescence detection on a rat spinal cord contusion injury model.Results. The problem of barrier disintegration in a region remote from the injury epicenter is considered. It is shown that spinal cord injury significantly increases the permeability of the blood-spinal cord barrier, which promotes enhanced transmigration of immune cells and release of cytotoxic molecules. The results of our own studies on a model of dosed contusion injury in the thoracic spinal cord of a rat show that the permeability of the barrier increases not only in the injury epicenter, but also along the entire length of the organ. This circumstance is especially significant for the lumbar spinal cord, where neural networks that are critical for the maintenance and restoration of motor function are localized.Conclusion. Potential causes of remote barrier disruption have been discussed, including the possible influence of damage biomarker molecules that travel from the injury epicenter to remote regions of the spinal cord via the bloodstream or cerebrospinal fluid. The promising clinical application of effective experimental approaches to contain barrier disruption and restore the blood-spinal cord barrier and the lack of translational research in this direction are highlighted.

Molecular hydrogen as a biological marker and a drug

The aim of the review was to examine the main characteristics of hydrogen ion metabolism and its hemostatic function in the human body. For diagnostic purposes, molecular hydrogen (H2) is considered a biological marker. The results of the analysis of therapeutic programs for the clinical use of hydrogen are presented. The use of H2 as a drug in the treatment of more than 170 diseases is also discussed.Conclusion. The use of H2 in various fields of medicine, including oncological diseases, is actively studied based on experimental biological experiments and clinical trials.