Perspectives on label-free microscopy of heterogeneous and dynamic biological systems.

Significance: Advancements in label-free microscopy could provide real-time, non-invasive imaging with unique sources of contrast and automated standardized analysis to characterize heterogeneous and dynamic biological processes. These tools would overcome challenges with widely used methods that are destructive (e.g., histology, flow cytometry) or lack cellular resolution (e.g., plate-based assays, whole animal bioluminescence imaging). Aim: This perspective aims to (1) justify the need for label-free microscopy to track heterogeneous cellular functions over time and space within unperturbed systems and (2) recommend improvements regarding instrumentation, image analysis, and image interpretation to address these needs. Approach: Three key research areas (cancer research, autoimmune disease, and tissue and cell engineering) are considered to support the need for label-free microscopy to characterize heterogeneity and dynamics within biological systems. Based on the strengths (e.g., multiple sources of molecular contrast, non-invasive monitoring) and weaknesses (e.g., imaging depth, image interpretation) of several label-free microscopy modalities, improvements for future imaging systems are recommended. Conclusion: Improvements in instrumentation including strategies that increase resolution and imaging speed, standardization and centralization of image analysis tools, and robust data validation and interpretation will expand the applications of label-free microscopy to study heterogeneous and dynamic biological systems.

Transcriptomic changes in the posterior pallium of male zebra finches associated with social niche conformance.

Animals plastically adjust their physiological and behavioural phenotypes to conform to their social environment-social niche conformance. The degree of sexual competition is a critical part of the social environment to which animals adjust their phenotypes, but the underlying genetic mechanisms are poorly understood. We conducted a study to investigate how differences in sperm competition risk affect the gene expression profiles of the testes and two brain areas (posterior pallium and optic tectum) in breeding male zebra finches (Taeniopygia castanotis). In this pre-registered study, we investigated a large sample of 59 individual transcriptomes. We compared two experimental groups: males held in single breeding pairs (low sexual competition) versus those held in two pairs (elevated sexual competition) per breeding cage. Using weighted gene co-expression network analysis (WGCNA), we observed significant effects of the social treatment in all three tissues. However, only the treatment effects found in the pallium were confirmed by an additional randomisation test for statistical robustness. Likewise, the differential gene expression analysis revealed treatment effects only in the posterior pallium (ten genes) and optic tectum (six genes). No treatment effects were found in the testis at the single gene level. Thus, our experiments do not provide strong evidence for transcriptomic adjustment specific to manipulated sperm competition risk. However, we did observe transcriptomic adjustments to the manipulated social environment in the posterior pallium. These effects were polygenic rather than based on few individual genes with strong effects. Our findings are discussed in relation to an accompanying paper using the same animals, which reports behavioural results consistent with the results presented here.

Translational regulation enhances distinction of cell types in the nervous system.

Multicellular organisms are composed of specialized cell types with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains underinvestigated. By performing RNA-seq and Ribo-seq in genetically defined cells in the Drosophila brain, we here revealed substantial post-transcriptional regulations that augment the cell-type distinctions at the level of protein expression. Specifically, we found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low in glia, leading to their preferential translation in neurons. Notably, distribution of ribosome footprints on these mRNAs exhibited a remarkable bias toward the 5' leaders in glia. Using transgenic reporter strains, we provide evidence that the small upstream open-reading frames in the 5' leader confer selective translational suppression in glia. Overall, these findings underscore the profound impact of translational regulation in shaping the proteomics for cell-type distinction and provide new insights into the molecular mechanisms driving cell-type diversity.

Accelerating the continuous community sharing of digital neuromorphology data.

The tree-like morphology of neurons and glia is a key cellular determinant of circuit connectivity and metabolic function in the nervous system of essentially all animals. To elucidate the contribution of specific cell types to both physiological and pathological brain states, it is important to access detailed neuroanatomy data for quantitative analysis and computational modeling. NeuroMorpho.Org is the largest online collection of freely available digital neural reconstructions and related metadata and is continuously updated with new uploads. Earlier in the project, we released multiple datasets together yearly, but this process caused an average delay of several months in making the data public. Moreover, in the past 5 years, >80% of invited authors agreed to share their data with the community via NeuroMorpho.Org, up from <20% in the first 5 years of the project. In the same period, the average number of reconstructions per publication increased 600%, creating the need for automatic processing to release more reconstructions in less time. The progressive automation of our pipeline enabled the transition to agile releases of individual datasets as soon as they are ready. The overall time from data identification to public sharing decreased by 63.7%; 78% of the datasets are now released in less than 3 months with an average workflow duration below 40 days. Furthermore, the mean processing time per reconstruction dropped from 3 h to 2 min. With these continuous improvements, NeuroMorpho.Org strives to forge a positive culture of open data. Most importantly, the new, original research enabled through reuse of datasets across the world has a multiplicative effect on science discovery, benefiting both authors and users.

Exploiting multivariate network meta-analysis: A calibrated Bayesian composite likelihood inference.

Multivariate network meta-analysis has emerged as a powerful tool in evidence synthesis by incorporating multiple outcomes and treatments. Despite its advantages, this method comes with methodological challenges, such as the issue of unreported within-study correlations among treatments and outcomes, which potentially lead to misleading conclusions. In this paper, we proposed a calibrated Bayesian composite likelihood approach to overcome this limitation. The proposed method eliminated the need to specify a full likelihood function while allowing for the unavailability of within-study correlations among treatments and outcomes. Additionally, we developed a hybrid Gibbs sampler algorithm along with the Open-Faced Sandwich post-sampling adjustment to enable robust posterior inference. Through comprehensive simulation studies, we demonstrated that the proposed approach yielded unbiased estimates while maintaining coverage probabilities close to the nominal level. Furthermore, we implemented the proposed method on two real-world network meta-analysis datasets; one comparing treatment procedures for the root coverage and another comparing treatments for anaemia in chronic kidney disease patients.

Impacts of wildfire-season air quality on park and playground visitation in the Northwest United States.

A significant cost of wildfires is the exposure of local and regional populations to air pollution from smoke, which can travel hundreds of miles from the source fire and is associated with significant negative health consequences. Wildfires are increasing in frequency and intensity in the United States, driven by historic fire management approaches and global climate change. These influences will take many decades or longer to reverse, so the main opportunities for mitigating health effects involve minimizing human exposure through changes in behavior or infrastructure. One key recommendation for reducing pollution exposures during wildfire smoke events is to limit time and physical activity outdoors, but there is limited evidence on the extent to which people make this change. We estimate how use of parks and playgrounds changes with air quality during wildfire season in the northwest United States. We find small reductions in park and playground visits on moderately polluted days, and large reductions, to 50-60% of baseline visits, when pollution levels are high. Disaggregating results by neighborhood characteristics, we find a significantly greater behavioral response to moderate levels of air pollution in neighborhoods with higher socio-economic status, although responses to high levels of pollution are similar across neighborhood types.

Comparative Analysis of Gender-Based Differences in Behavioral Mastery, Goals, and Characteristics in Autistic Individuals: An Applied Behavior Analysis Study.

Introduction  It is widely recognized that the prevalence and diagnosis of autism spectrum disorder (ASD) are more common in males than in females. Despite this, there is a significant gap in the body of autism research that investigates gender differences for treatment effects of applied behavior analysis (ABA) across a variety of measured variables. This research aims to comprehensively evaluate gender distinctions concerning target behavioral objectives, goals, and deficit variables. Materials and methods This study analyzed retrospective data from 100 participants, including 89 juveniles and four adults, with seven cases lacking age documentation, who underwent a three-month ABA program from March 19 to June 11, 2023. The ABA program included various methodologies such as functional analysis, discrete trial training, mass trials, and naturalistic training. Data on outcome measures, including target behavioral proficiency, age, average trials to proficiency, average teaching days to proficiency, open behavioral objectives, and target trends, were collected using the "Catalyst" software (Catalyst Software Corporation, New York, NY). Participant demographics were summarized using statistical analyses for categorical (gender and race/ethnicity) and continuous variables (percentage of mastered behavioral objectives, age, average trials, average teaching days, open objectives, percentage of failed objectives during maintenance, percentage of objectives with upward, downward, and flat trends). These statistics included mean, standard deviation, median, and range and were analyzed inferentially using nine separate two-sample independent t-tests and corresponding effect sizes using Cohen's d. Results There were no statistically significant disparities based on gender (p > 0.05) across all nine variables examined: Percentage of Targets Mastered, Age, Average Trials to Mastery, Average Teaching Days to Mastery, Open Targets, Percentage of Targets Failed in Maintenance, Percentage of Targets Trending Up, Percentage of Targets Trending Down, and Percentage of Targets Trending Flat, and wide confidence intervals were detected. Conclusions  Non-significant gender differences in response to ABA treatments regarding these nine behavioral goals, mastery, and deficit variables may be relevant. They suggest that ABA treatments could be equally beneficial for both male and female autistic individuals. These results should be interpreted cautiously. The general pattern observed, characterized by broad confidence intervals, carries a degree of statistical uncertainty, which may suggest substantial gender differences. These results might question the prevailing beliefs about the variation in treatment response based on gender. This could profoundly impact clinical practices, implying that healthcare professionals should not favor one gender over another when suggesting ABA therapies. Instead, the treatment advice should be tailored to each child's unique requirements and traits, regardless of gender. The investigators expect these results to encourage additional research in this field. Comprehending the elements that affect treatment response is vital for improving treatment results and customizing care.

Psychometric Properties of the Persian Version of the Intensive Care Experience Questionnaire (ICE-Q).

Background and Purpose: It is important to assess the experience of patients who have been admitted to an intensive care unit to provide the best treatment and nursing care possible. Therefore, a valid and reliable tool is necessary for measurement. This study aimed to determine the psychometric properties of the Persian version of the Intensive Care Experience Questionnaire (ICEQ) for open-heart surgery patients. Methods: The study was conducted in four steps: translation, face and content validity, confirmatory factor analysis, and reliability assessment. The adapted questionnaire was administered to 200 Iranian cardiac surgery patients who had received treatment in an intensive care unit within the past month. Results: In the final Persian version of ICEQ, there are 4 factors and 21 items. Following the translation and cultural adaptation process, the content validity was evaluated. Three items had content validity ratio < 0.6, so they were deleted. Scale-level content validity index/Average was 0.81 and more than 0.7 for each item on the scale. This scale was validated through confirmatory factor analysis using fit indicators (comparative fit index, normalized fit index, root mean square error of approximation, and chi-square). There was Cronbach's alpha of 0.71-0.85, and intraclass correlation coefficients were 0.82-0.93 for subscales. Conclusions: The Persian version of ICEQ showed appropriate psychometric properties. This scale may be useful to inform the development of effective interventions to improve subsequent outcomes for Iranian open-heart surgery patients.

Robotic versus open mini-incision living donor nephrectomy: Single centre experience.

BACKGROUND: Robotic surgery is associated with less tissue manipulation and earlier recovery with minimal incision. The aim of this study was to compare the short-term clinical outcomes between robotic-assisted donor nephrectomy (RDN) and open mini-incision donor nephrectomy (ODN). METHODS: From 2016 to 2019, 141 cases involving RDN were analysed. Patient outcomes were compared with those of 191 patients who underwent ODN from 2010 to 2015. Demographics, operation factors, perioperative outcomes, and complications were retrospectively reviewed. RESULTS: The RDN group presented with less blood loss than the ODN group (p = 0.023). The length of hospital stay was significantly shorter in the RDN group than in the ODN group (p < 0.005). The overall rate of complications was low and there was no significant difference in complication rates between the groups. CONCLUSION: The robotic approach has benefits over the traditional open approach, including shorter length of hospital stay and reduced intraoperative blood loss.

Open-fitting hearing aids: a comparative analysis between open behind-the-ear and open completely-in-the-canal instant-fit devices.

PURPOSE: Our study aims to assess the open-fitting capabilities and vent properties of traditional open-fitting behind-the-ear (open BTE) hearing aids to instant-fit open-fitting completely-in-the-canal (open CIC) systems. METHODS: The study analysed data from 40 patients grouped in two groups based on the used hearing aids. Free field pure tone and speech audiometry were performed to obtain the free-field pure tone average and free-field word recognition score (WRS). The matrix sentence test was employed to evaluate the auditory performance and functional outcomes of patients. The Satisfaction with Amplification in Daily Life (SADL) and the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire were used to assess the personal satisfaction and benefit provided by the hearing aid. Real ear measurements were conducted to objectively evaluate the Real-Ear Unaided Gain (REUG) and Real-Ear Occluded Gain (REOG) of the two groups. For this purpose, six frequency bands (band 1 from 125 to 200 Hz, band 2 from 250 to 400 Hz, band 3 from 500 to 800 Hz, band 4 from 1000 to 1600 Hz, band 5 from 2000 to 3150 Hz, and band 6 from 4000 to 6300 Hz) were defined and compared. RESULTS: Free-field WRS exhibited a significant difference (p-value = 0.004) between open BTE and open CIC, with better results for the open BTE. Matrix test speech reception threshold scores did not differ significantly between groups. No statistical significant difference were observed between APHAB and SADL total scores. Correlation tests revealed a negative correlation between SRT and APHAB scores in the open BTE group, not seen in the open CIC. No statistically significant difference was observed for all bands of REUG values, demonstrating comparability in terms of acoustic resonance of the external auditory canal. Comparing the REOG recorded in the two groups a significant difference was observed for bands 2 through 6. While the average REOG values for bands 5 and 6 were higher in patients with traditional open BTE aids, in contrast, for bands 2, 3, and 4, the REOG values for the open CIC group were higher and statistically significant compared to patients wearing traditional open-fitting BTE hearing aids. CONCLUSION: Patients with open CIC seem to perform worse in quiet environments compared to noisy ones, as indicated by the free field WRS score. However, the absence of differences in functional performance assessed with the matrix sentence test, and in the psychosocial aspects, makes these devices a good solution for individuals who reject hearing aids due to aesthetic concerns. The differences in terms of real ear measurements, while statistically significant, do not negatively impact overall performance.

Analysis of high-risk factors and mortality prediction of ruptured abdominal aortic aneurysm.

INTRODUCTION: Ruptured abdominal aortic aneurysms (RAAAs) are among the most dangerous emergencies in vascular surgery, with a high death rate and numerous risk factors influencing perioperative death. Therefore, identifying the critical risk factors for RAAAs is crucial to increasing their survival rate. Our aim was to identify those risk factors from a wide range of parameters. METHODS: Retrospective analysis of hospitalised RAAA patients treated at this center between May 2004 and January 2023. After comparing the preoperative data of patients who survived and those who died, high-risk characteristics influencing the perioperative care of RAAA patients were identified, and logistic regression analysis was carried out. The mean follow-up time was 45.34 months. RESULTS: During the study period, a total of 155 patients (average age 67.4±71.93 years, 123 (78.85%)males, 32 (20.51%)females) were enrolled. The patients participating in the group were divided into survival group (n = 123) and death group (n = 27). The main differences included hemodynamic instability (51.9% vs 28.5%; P=0.019), sudden cardiac arrest (14.8% vs 1.6%; P=0.010), deterioration of consciousness (40.7% vs 17.1%; P=0.007), renal impairment (22.2% vs 2.4%; P=0.001), chronic kidney disease (18.5% vs3.2%; P=0.010). There is also a history of cancer (Ca) (18.5% vs 4.1%; P=0.021). Risk factors for Endovascular aneurysm repair (EVAR) include diastolic blood pressure ≤ 50 mmHg (36.4% vs 8.0%; P=0.025), renal function impairment (18.2% vs 0; P=0.015), and chronic kidney disease (27.3% vs 4.0%; P=0.028). Risk factors for open surgical repair (OSR) include diastolic blood pressure ≤ 50 mmHg (40.0% vs 6.3%; P=0.014). Finally, the above statistically significant factors were analyzed by Logistic regression analysis, and it was found that diastolic blood pressure ≤ 50mmHg, cardiac arrest, renal function damage and Ca history were independent risk factors. We followed 123 individuals and 14 were lost to follow-up, with an overall survival rate of 43.8%. CONCLUSION: Hemodynamics, which includes shock, blood pressure, cardiac arrest, deterioration of consciousness, and other conditions, are the primary risk factors for the perioperative death of a ruptured abdominal aortic aneurysm. Simultaneously, diastolic blood pressure ≤50mmHg was found to be associated with risk factors for OSR, whereas renal function impairment, chronic renal illness, and diastolic blood pressure ≤50mmHg were associated with risk for EVAR.

The diagnostic ability of peripapillary vessel density in primary open-angle glaucoma suspects.

OBJECTIVE: To assess the diagnostic ability of peripapillary vessel density (pVD) in primary open-angle glaucoma suspect (GS) patients. METHODS: Sixteen primary open-angle GS patients (22 eyes) and 20 normal controls (22 eyes) were included. In the GS group, OCTA measurements of pVD (superior, inferior, nasal, temporal, and global), OCT measurements of retinal nerve fiber layer (RNFL) thickness, disc area, rim area and ganglion cell complex (GCC) thickness were examined. In the control group, pVD measurements were performed. The vessel density between the two groups was compared. The correlation between OCTA and OCT parameters was evaluated. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of OCTA measurements. RESULTS: The global (P<0.001), nasal (P=0.003), and inferior (P=0.002) quadrant pVD in GS group was considerably lower than the control group. The global pVD was positively correlated with the inferior RNFL thickness (r=0.492, P=0.023) and rim area (r=0.483, P=0.027). The inferior pVD was positively correlated with the inferior RNFL thickness (r=0.648, P=0.001), the nasal RNFL thickness (r=0.441, P=0.045), the rim area (r=0.439, P=0.046) and the GCC thickness (r=0.472, P=0.048). The global pVD had the best diagnostic value (AUC=0.825, sensitivity 86.36%, specificity 72.73%, cutoff value 45%), followed by the inferior (AUC=0.749) and nasal (AUC=0.748) quadrant pVD. CONCLUSION: In primary open-angle GS patients, the global and inferior quadrant pVD was lower than that of normal people, and it was positively correlated with the inferior RNFL thickness and rim area. The diagnostic value of pVD for discriminating GS from normal people was excellent with high sensitivity and specificity.

High-Precision Optical Fiber-Based Lickometer.

Quantifying and analyzing licking behavior can offer valuable insights into fundamental neurobiological mechanisms controlling animal consummatory behaviors. Lickometers are typically based on electrical properties, a strategy that comes with limitations, including susceptibility to electrical interference and generation of electrical disturbances in electrophysiological measurements. While optical lickometers offer an alternative method to measure licks and quantify fluid intake in animals, they are prone to false readings and susceptibility to outside light sources. To overcome this problem, we propose a low-cost open-source lickometer that combines a restricted infrared beam defined by optical fibers, with a poke design that allows easy access to the tongue while limiting access of other body parts and external light sources. This device also includes features for detecting nose pokes and presenting visual cues during behavioral tasks. We provide validation experiments that demonstrate the optical lickometer's reliability, high-sensitivity and precision, and its application in a behavioral task, showcasing the potential of this tool to study lick microstructure in combination with other techniques, such as imaging of neural activity, in freely moving mice.

Long-term outcomes of surgical or endovascular treatment of adult with midaortic syndrome: A single-center retrospective study over a 14-year period.

Objective: Midaortic syndrome is a rare clinical condition that has been mainly studied in juveniles through case reports and series. This study aims to report the anatomic characteristics and long-term outcomes of 41 adult patients with midaortic syndrome who received open surgical treatment or endovascular treatment over a 14-year period. Methods: A consecutive cohort of 41 adult patients diagnosed with midaortic syndrome at our center between January 2008 and November 2021 were enrolled in the study. Patients' baseline and anatomic characteristics were collected and analyzed. Primary follow-up outcomes included death and reintervention. Other follow-up outcomes included hypertension and complications. Results: The study enrolled 41 adult patients with midaortic syndrome with a mean age of 37.5 ± 13.4 years. Twenty-five patients received open surgical treatment, and 16 patients received endovascular treatment. Isolated infrarenal lesions were more likely to be found in the endovascular treatment group (P = .005), whereas patients with multiple (P = .002) or intravisceral involvement (P = .001) were more likely to be found in the open surgical treatment group. The open surgical treatment group was more likely to have a lower postoperative peak systolic pressure gradient (P = .020). The 5- and 10-year reintervention-free survivals were 87.7% and 71.7% in the open surgical treatment group and 92.3% and 79.1% in the endovascular treatment group, respectively. Conclusions: Both open surgical treatment and endovascular treatment showed satisfactory long-term efficacy outcomes for adult patients with midaortic syndrome. Given the patients' relatively young age and long life expectancy, strict and regular lifelong follow-up is necessary.

Open-ended versus bounded evolution: Mineral evolution as a case study.

To what extent are naturally evolving systems limited in their potential diversity (i.e. "bounded") versus unrestricted ("open-ended")? Minerals provide a quantitative model evolving system, with well-documented increases in mineral diversity through multiple stages of planetary evolution over billions of years. A recent framework that unifies behaviors of both biotic and abiotic evolving systems posits that all such systems are characterized by combinatorial richness subject to selection. In the case of minerals, combinatorial richness derives from the possible combinations of chemical elements coupled with permutations of their formulas' coefficients. Observed mineral species, which are selected for persistence through deep time, represent a miniscule fraction of all possible element configurations. Furthermore, this model predicts that as planetary systems evolve, stable minerals become an ever-smaller fraction of the "possibility space." A postulate is that "functional information," defined as the negative log2 of that fraction, must increase as a system evolves. We have tested this hypothesis for minerals by estimating the fraction of all possible chemical formulas observed from one stage of mineral evolution to the next, based on numbers of different essential elements and the maximum chemical formula complexity at each of nine chronological stages of mineral evolution. We find a monotonic increase in mineral functional information through these nine stages-a result consistent with the hypothesis. Furthermore, analysis of the chemical formulas of minerals demonstrates that the modern Earth may be approaching the maximum limit of functional information for natural mineral systems-a result demonstrating that mineral evolution is not open-ended.

Value of negative pressure sealing drainage on wound healing of Gustilo IIIB and IIIC open fractures.

BACKGROUND: Gustilo III fractures have a high incidence and are difficult to treat. Patients often experience difficulty in wound healing. Negative pressure drainage technology can help shorten wound healing time and has positive value in improving patient prognosis. AIM: To explore the clinical value of the negative pressure sealing drainage technique in wound healing of Gustilo IIIB and IIIC open fractures. METHODS: Eighty patients with Gustilo IIIB and IIIC open fractures with skin and soft tissue injuries who were treated in the Second People's Hospital of Dalian from March 2019 to December 2021 were selected as the research subjects. They were divided into a study group (n = 40, healed with negative pressure closed drainage) and a control group (n = 40, healed with conventional dressing changes) according to the variation in the healing they received. The efficacy of the clinical interventions, the variations in the regression indicators (time to wound healing, time to fracture healing, time to hospitalization), and the conversion and healing of bacterial wounds were compared 1-3 mo after the intervention. RESULTS: The total effective rate of patients among the study group was 95.00% (38/40), which was notably higher than 75.00% (30/40) among the control group (P < 0.05). The wound healing time, fracture healing time, and hospital stay of the patients in the study group was shorter than the control group (P < 0.05). After the intervention, the negative bacterial culture at the wound site rate and wound healing rate of the patients among the study group increased compared to the control group (P < 0.05). CONCLUSION: Negative pressure sealing and drainage technology has a good therapeutic effect on patients with Gustilo IIIB and IIIC open fracture wounds with skin and soft tissue injury. It can notably enhance the wound healing rate and the negative rate of bacteria on the wound surface and help to speed up the recovery process of patients.

Behavioral neuroscience in zebrafish: unravelling the complexity of brain-behavior relationships.

This paper reviews the utility of zebrafish (Danio rerio) as a model system for exploring neurobehavioral phenomena in preclinical research, focusing on physiological processes, disorders, and neurotoxicity biomarkers. A comprehensive review of the current literature was conducted to summarize the various behavioral characteristics of zebrafish. The study examined the etiological agents used to induce neurotoxicity and the biomarkers involved, including Aß42, tau, MMP-13, MAO, NF-Кß, and GFAP. Additionally, the different zebrafish study models and their responses to neurobehavioral analysis were discussed. The review identified several key biomarkers of neurotoxicity in zebrafish, each impacting different aspects of neurogenesis, inflammation, and neurodegeneration. Aß42 was found to alter neuronal growth and stem cell function. Tau's interaction with tubulin affected microtubule stability and led to tauopathies under pathological conditions. MMP-13 was linked to oxidative assault and sensory neuron degeneration. MAO plays a role in neurotransmitter metabolism and neurotoxicity conversion. NF-Ðšß was involved in pro-inflammatory pathways, and GFAP was indicative of neuroinflammation and astroglial activation. Zebrafish provide a valuable model for neurobehavioral research, adhering to the "3Rs" philosophy. Their neurotoxicity biomarkers offer insights into the mechanisms of neurogenesis, inflammation, and neurodegeneration. This model system aids in evaluating physiological and pathological conditions, enhancing our understanding of neurobehavioral phenomena and potential therapeutic interventions.

Binding of steroid substrates reveals the key to the productive transition of the cytochrome P450 OleP.

OleP is a bacterial cytochrome P450 involved in oleandomycin biosynthesis as it catalyzes regioselective epoxidation on macrolide intermediates. OleP has recently been reported to convert lithocholic acid (LCA) into murideoxycholic acid through a highly regioselective reaction and to unspecifically hydroxylate testosterone (TES). Since LCA and TES mainly differ by the substituent group at the C17, here we used X-ray crystallography, equilibrium binding assays, and molecular dynamics simulations to investigate the molecular basis of the diverse reactivity observed with the two steroids. We found that the differences in the structure of TES and LCA affect the capability of these molecules to directly form hydrogen bonds with N-terminal residues of OleP internal helix I. The establishment of these contacts, by promoting the bending of helix I, fosters an efficient trigger of the open-to-closed structural transition that occurs upon substrate binding to OleP and contributes to the selectivity of the subsequent monooxygenation reaction.

Treatment outcomes and prognostic factors of the apical barrier technique with premixed calcium silicate-based putty in necrotic permanent teeth with open apices: a retrospective cohort study with up to six years follow-up.

OBJECTIVES: To evaluate treatment outcomes of the apical barrier technique with premixed calcium silicate-based putty for treating necrotic permanent teeth with open apices and to identify prognostic factors. MATERIALS AND METHODS: Permanent teeth with necrotic pulps and open apices treated by the apical barrier technique with premixed calcium silicate-based putty, with a minimum follow-up of 12 months, were included. Treatment outcomes were based on clinical signs, symptoms, and radiographic evaluation. The treatment outcome was dichotomized into success or failure according to strict and loose criteria. The chi-square test (or Fisher's exact test) and multiple logistic regression analysis were used to evaluate possible prognostic factors associated with treatment outcomes. RESULTS: Seventy-four teeth with a follow-up time of 12-72 months (mean, 25.74 ± 14.36 months) were included in the final evaluation. The success rate was 97.30% using the loose criteria and 66.22% using the strict criteria. Multiple logistic regression analysis indicated that the size of pre-operative periapical lesion (≥ 5 mm) (odds ratio [OR]: 18.96; P = 0.0153) and root canal underfilling (OR: 8.341; P = 0.0448) were significant predictors for treatment failure under the strict criteria. CONCLUSION: The apical barrier technique with premixed calcium silicate-based putty is a highly successful procedure for treating necrotic permanent teeth with open apices after an observation period of up to 6 years. Treatment success under the strict criteria is primarily affected by the size of the pre-operative periapical lesion and the apical extent of root-filling. CLINICAL RELEVANCE: Careful case selection and ensuring adequate root filling quality are essential to the successful outcome of the apical barrier technique with premixed calcium silicate-based putty.