Early Stages Of Development Research Articles

Biochemical basis and therapeutic potential of mitochondrial uncoupling in cardiometabolic syndrome.

Mild uncoupling of oxidative phosphorylation is an intrinsic property of all mitochondria, allowing for adjustments in cellular energy metabolism to maintain metabolic homeostasis. Small molecule uncouplers have been extensively studied for their potential to increase metabolic rate, and recent research has focused on developing safe and effective mitochondrial uncoupling agents for the treatment of obesity and cardiometabolic syndrome (CMS). Here, we provide a brief overview of CMS and cover the recent mechanisms by which chemical uncouplers regulate CMS-associated risk-factors and comorbidities, including dyslipidemia, insulin resistance, steatotic liver disease, type 2 diabetes, and atherosclerosis. Additionally, we review the current landscape of uncoupling agents, focusing on repurposed FDA-approved drugs and compounds in advanced preclinical or early-stage clinical development. Lastly, we discuss recent molecular insights by which chemical uncouplers enhance cellular energy expenditure, highlighting their potential as a new addition to the current CMS drug landscape, and outline several limitations that need to be addressed before these agents can successfully be introduced into clinical practice.

A Review on the Water Invasion Mechanism and Enhanced Gas Recovery Methods in Carbonate Bottom-Water Gas Reservoirs

Carbonate gas reservoirs are crucial in gas field development, with carbonate bottom-water gas reservoirs being a significant subset. However, the development of these reservoirs often faces challenges such as water invasion, leading to a low gas recovery rate. Enhancing gas recovery is a primary goal for researchers in this field. This study provides a systematic review of the mechanisms, identification, and dynamic prediction of water invasion in these gas reservoirs. The technical adaptability and application range of different enhanced recovery methods are summarized, and their application effects are evaluated. The results indicate that carbonate gas reservoirs have diverse types of storage and permeability spaces, with a wide distribution of pore size scales, leading to various types of enclosed gas caused by water invasion. The prediction accuracy of water invasion models for bottom-water gas reservoirs with fractures and vugs is relatively low. Therefore, numerical simulation research on the basis of fine reservoir characterization is the key technology. The control of bottom-water invasion and the rescue measures after the bottom-water invasion are the keys to improving gas recovery, which can be divided into four types: drainage gas recovery, water control production, active drainage, and injection medium. Gas production by drainage is the main technology for improving gas recovery, among which foam drainage is the most widespread. The optimization of development parameters in production by water control has a good effect in the early stages of development. The active drainage technology on the water invasion channel is the bottom-up technology for the effective development of strong water-flooded gas reservoirs. CO2 injection may have great potential to improve the recovery of bottom-water gas reservoirs, which is one of the important research directions under the background of “carbon peaking and carbon neutrality”. The research provides theoretical and technical reference significance for enhanced recovery of carbonate bottom-water gas reservoirs.

Numerical simulation–based optimization of an integrated framework for the efficient development and sustainable utilization of geothermal resources: Application to the Bedugul geothermal field

Geothermal energy is a crucial renewable resource that can generate large power continuously but requires integrated and accurate assessments of its development and utilization for long-term and sustainable exploitation. Accordingly, this study develops an assessment framework considering all the influential factors for power generation: the potential capacity; silica scaling; type of power generation system; and temporal changes in the pressure, temperature, and fluid saturation in the reservoir. The applicability and effectiveness of the proposed method are demonstrated via a case study of the Bedugul geothermal two-phase system on Bali Island, Indonesia, using a calibrated numerical model and a stochastic resource assessment. The numerical model is a combination of wellbore, silica scaling, and thermodynamic power generation models. On the basis of the wellbore model by the Hagedorn and Brown pressure drop correlation, the calculated means of the production capacity and enthalpy from the liquid reservoir are 39.0 kg/s and 1340 kJ/kg, respectively. Using double-flash and flash-binary power generation systems over an exploitation period with a two-phase reservoir temperature of 260 °C, a reinjection temperature of 130 °C, and a silica scaling model, the predicted production from the liquid reservoir can sustain a power generation of 60 MWe, which is equivalent to 70 % of the power potential, according to a stochastic resource assessment using the Plackett–Burman design. The double-flash system is found to generate 1.0 MWe more power (a 1.6 % increase relative to the baseline capacity) than the flash-binary system using pentane as working fluid and to extend the lifetime of the make-up wells by 2.5 years. Consequently, it is vital, at an early stage of development, to understand the nature and properties of reservoirs and the thermodynamics of power generation systems via comprehensive research and reliable and accurate assessments of the power production capacity.

Impact of β-Carotene Enrichment on Carotenoid Composition and Gene Expression in Artemia Metanauplii

Background: Carotenoids play essential nutritional and physiological roles in aquatic animals. Since aquatic species cannot synthesize carotenoids de novo, they must obtain these compounds from their diet to meet the physiological and adaptive requirements needed in specific aquaculture stages and conditions. Carotenoid supplementation in Artemia represents a promising strategy to enhance pigmentation, health, and growth in aquaculture species, particularly in larvae and other early developmental stages. Methods: In this study, a β-carotene enrichment process was applied to Artemia metanauplii to investigate the biological fate and potential effects of β-carotene. Results: The results indicated significant β-carotene uptake by Artemia, with peak levels observed at 12 h. Alongside β-carotene, two xanthophylls—canthaxanthin and echinenone—were detected in Artemia, each exhibiting distinct patterns during the enrichment and subsequent depletion phases. The transcriptome analysis identified 2705 differentially expressed genes (DEGs), offering valuable insights into gene functions associated with carotenoid absorption, metabolism, and antioxidant mechanisms. The findings suggest that β-carotene enrichment enhances metabolic activity and energy pathways, supporting the physiological functions of Artemia. Notably, unlike other crustaceans, Artemia lack certain enzymes necessary for converting β-carotene into astaxanthin, restricting them to producing keto-carotenoids like canthaxanthin. Furthermore, the study highlights the upregulation of genes encoding lipid transport proteins, such as CD36 and ABC transporters, which may contribute to carotenoid absorption in Artemia. Additional functional insights are provided by the gene BCO2, which regulates pigmentation by preventing excessive carotenoid accumulation, along with ketolase and hydroxylase enzymes in carotenoid metabolic pathways. Conclusions: This research advances our understanding of carotenoid metabolism in crustaceans, with potential implications for aquaculture nutrition and feed formulation.

Dynamic O-GlcNAcylation governs long-range chromatin interactions in V(D)J recombination during early B-cell development.

V(D)J recombination secures the production of functional immunoglobulin (Ig) genes and antibody diversity during the early stages of B-cell development through long-distance interactions mediated by cis-regulatory elements and trans-acting factors. O-GlcNAcylation is a dynamic and reversible posttranslational modification of nuclear and cytoplasmic proteins that regulates various protein functions, including DNA-binding affinity and protein-protein interactions. However, the effects of O-GlcNAcylation on proteins involved in V(D)J recombination remain largely unknown. To elucidate this relationship, we downregulated O-GlcNAcylation in a mouse model by administering an O-GlcNAc inhibitor or restricting the consumption of a regular diet. Interestingly, the inhibition of O-GlcNAcylation in mice severely impaired Ig heavy-chain (IgH) gene rearrangement. We identified several factors crucial for V(D)J recombination, including YY1, CTCF, SMC1, and SMC3, as direct targets of O-GlcNAc modification. Importantly, O-GlcNAcylation regulates the physical interaction between SMC1 and SMC3 and the DNA-binding patterns of YY1 at the IgH gene locus. Moreover, O-GlcNAc inhibition downregulated DDX5 protein expression, affecting the functional association of CTCF with its DNA-binding sites at the IgH locus. Our results showed that locus contraction and long-range interactions throughout the IgH locus are disrupted in a manner dependent on the cellular O-GlcNAc level. In this study, we established that V(D)J recombination relies on the O-GlcNAc status of stage-specific proteins during early B-cell development and identified O-GlcNAc-dependent mechanisms as new regulatory components for the development of a diverse antibody repertoire.

A zebrafish-based in vivo model of Zika virus infection unveils alterations of the glutamatergic neuronal development and NS4A as a key viral determinant of neuropathogenesis.

Infection of pregnant women by Zika virus (ZIKV) is associated with severe neurodevelopmental defects in newborns through poorly defined mechanisms. Here, we established a zebrafish in vivo model of ZIKV infection to circumvent limitations of existing mammalian models. Leveraging the unique tractability of this system, we gained unprecedented access to the ZIKV-infected brain at early developmental stages. The infection of zebrafish larvae with ZIKV phenocopied the disease in mammals including a reduced head area and neural progenitor cells (NPC) infection and depletion. Moreover, transcriptomic analyses of NPCs isolated from ZIKV-infected embryos revealed a distinct dysregulation of genes involved in survival and neuronal differentiation, including downregulation of the expression of the glutamate transporter vglut1, resulting in an altered glutamatergic network in the brain. Mechanistically, ectopic expression of ZIKV protein NS4A in the larvae recapitulated the morphological defects observed in infected animals, identifying NS4A as a key determinant of neurovirulence and a promising antiviral target for developing therapies.

Effect of Phlorethol from the Brown Alga Costaria costata (Turn.) Saund. (Order Laminariales) on Gametes and Embryogenesis of the Sea Urchin Strongylocentrotus intermedius (A. Agassiz, 1864)

The effect of a fraction of phlorethol (CcPh), one of the polyphenolic compounds isolated from the brown alga Costaria costata (Turn.) Saund (Laminariales), on gametes and embryogenesis of the sea urchin Strongylocentrotus intermedius (A. Agassiz, 1864) was studied. Using a model of developing sea urchin embryos, it was shown that phlorethol at concentrations ≤700 µg/mL did not exert cytotoxic effect on early developmental stages (from zygote to 16-celled stage blastomere). The embryotoxic effect of phlorethol, causing death of 50% of embryos, was expressed in a concentration (I) range of 50 I ≤ 100 µg/mL only after 24 h of incubation, in the blastula stage. When exposed to concentrations of ≥100 µg/mL, embryos that survived to the blastula stage did not develop further and died after 36 h of incubation. Under the effect of phlorethol, the fertilizing capacity of sea urchin spermatozoa and oocytes reduced. The concentration of phlorethol inhibiting fertilization by 50% (IC50) when acting on sperm was 1.28±0.38 µg/mL and when acting on oocytes was 3.83±0.82 µg/mL. Thus, phlorethol reduces the fertilizing capacity of sea urchin gametes at concentrations much lower than embryotoxic concentrations and can potentially find practical application as part of new contraceptive drugs for mammals and humans.

Environmental pollution by plasticizers and the relationship to vector dengue mosquito Aedes aegypti: Bisphenol A (BPA) affect the development and viral immune pathway response

Bisphenol A (BPA) is a widely used industrial chemical found in various products, leading to human exposure through dietary and non-dietary sources. It acts as an endocrine disruptor, affecting reproductive processes in vertebrates by binding to estrogen receptors. While its effects on vertebrates have been extensively studied, much less is known about its impact on invertebrates. This study investigates the effects of BPA on the development and immune response of Aedes aegypti mosquitoes, which are important vectors for arboviral diseases, such as dengue, an emergent viral disease worldwide. Artificial aquatic niches (AAN) were sampled, and BPA concentrations were quantified. Ae. aegypti larvae were exposed to varying BPA concentrations, and their development, fecundity, fertility, and immune response were assessed. Results show delayed development and decreased emergence of mosquitoes exposed to BPA. Females exposed to BPA exhibited reduced oviposition while hatching rates remained unaffected. Furthermore, BPA exposure altered the expression of immune response genes in adult mosquitoes, with differential effects observed between sexes. This suggests that BPA exposure during early developmental stages can modulate the antiviral immune response in adult mosquitoes, possibly through the 20-hydroxyecdysone (20E) signaling pathway. Overall, this study highlights the potential impact of BPA on the development and immune function of mosquito vectors, with implications for vector competence and disease transmission.

Fruit characters in early divergent Arecaceae-Arecoideae: comparative carpology of Hyophorbe Gaertn. (Chamaedoreeae)

ABSTRACT The phylogenetic relationships of two early divergent tribes of Arecoideae (Chamaedoreeae and Iriarteeae) remain poorly resolved. Nevertheless, in some phylogenetic reconstructions the genus Hyophorbe is recognized as the earliest divergent genus of the subfamily. Hence, the fruit anatomy, histogenesis and organogenesis of Hyophorbe species is studied here, with the aim of revealing the key carpological characters of early divergent taxa of Arecaceae – Arecoideae. The multilayered pericarp consists mostly of the mesocarp (parenchymatous cells with different inclusions) and differentiates into outer and inner zones from its early developmental stages (in H. lagenicaulis an additional 1–3 layered inner subdermal zone develops in the inner mesocarp). The one-layered endocarp is represented either by palisade sclereids, lignification of which begins at late developmental stages, or by almost unspecialized thin-walled epidermal cells. The fruits of Hyophorbe species are referred to two different morphogenetic types: the pyrenariums of the Ilex type with a one-layered lignified endocarp (H. lagenicaulis, H. verschaffeltii, H. indica) and berries of the Nuphar type without a continuous lignified zone in the pericarp (H. vaughanii and H. amaricaulis). It is shown that the lignified palisade endocarp could be interpreted as a plesiomorphic character state of Ceroxyloideae – Arecoideae clade, whereas a non-lignified endocarp could be treated as an apomorphy of this clade or a plesiomorphic character state of the family Arecaceae.

Microseismicity Around Loki's Castle Hydrothermal Vent Field Reveals the Early Stages of Detachment Faulting at the Mohns‐Knipovich Ridge Intersection

AbstractAt slow to ultraslow spreading ridges, the limited melt supply results in tectonic accretion and the exhumation of mantle rocks. Melt supply is focused toward volcanic centers where magmatic accretion dominates. In areas where the ridges reorientate, both types of accretion can occur across the ridge axis with detachment faults developing on the inside corners and hydrothermal vent fields located in close proximity. Microseismicity studies improve the understanding of the tectonic processes at detachment faults and their interplay with hydrothermal vent systems, but are mostly limited to mature detachment faults or short deployment times. This study presents results from a ∼11 months ocean bottom seismometer deployment around the Loki's Castle hydrothermal vent field at the intersection of the slow to ultraslow spreading Mohns and Knipovich Ridge. We observe seismicity to be highly asymmetric with the majority of the plate divergence being accommodated by an emerging detachment fault at the inside corner of the intersection west of Loki's Castle. Seismic activity related to the detachment fault displays a distinct contrast, with continuous low‐magnitude events occurring at depth and episodic large‐magnitude events concentrated in clusters within the footwall. The detachment fault shows no significant roll‐over at shallow depths and the locus of spreading is located east of the detachment. These results suggest that the detachment fault west of Loki’s Castle is at an early development stage.

Assessment of the relative cardiotoxicity and behavioral effects of butylated hydroxytoluene and its metabolites in developing zebrafish (Danio rerio)

Butylated hydroxytoluene (BHT) and its transformation products are ubiquitously detected in aquatic environments. Despite studies reporting on the adverse effects of BHT exposure in early-staged zebrafish, the comparative toxicity of its metabolites is not known. To address this, zebrafish embryos were exposed continuously to 0.01–1 μM BHTs (BHT, BHT-Q, BHT-OH, BHT-CHO, and BHT-COOH) for up to 6 days. Each chemical altered the heart rates of developing zebrafish at 72 hpf. When assessing cardiac morphology at 48 and 72 hpf, BHT-COOH showed stronger effects compared to BHT in inducing pericardial edema and myocardial hypertrophy. This effect is hypothesized to be attributed to differences in transcriptional regulation of key genes during cardiac development. BHT predominantly affected transcript expression in the early (15 hpf) or late stages (48–72 hpf) of heart development, but did not impact the transcription during the middle stage (24–36 hpf). Conversely, BHT-COOH altered the expression of early transcription factors (i.e. tbx5, nkx2.5, gata4, hand2) and functional genes (i.e. myh6, nppa, cacna1ab, and atp2a2) at all stages of cardiac development. The effects on the heart may also be related to behavioral changes observed in larval fish. Behavior was most sensitive with low chemical exposures (0.01 μM), while at higher concentrations, heart rate was a more sensitive indicator of BHT-induced toxicity. Taken together, our results indicate that BHTs induce adverse effects on cardiovascular function and BHT metabolites may pose higher risk than the parent compound.

Elucidation of molecular mechanisms involved in tadpole toxicity employing QSTR and q-RASAR approach

Tadpoles, as early developmental stages of frogs, are vital indicators of toxicity and environmental health in ecosystems exposed to harmful organic compounds from industrial and runoff sources. Evaluating each compound individually is challenging, necessitating the use of in-silico methods like Quantitative Structure Toxicity Relationship (QSTR) and Quantitative Read-Across Structure Activity Relationship (q-RASAR). Utilizing the comprehensive US EPA's ECOTOX database, which includes acute LC50 toxicity and chronic endpoints, we extracted crucial data such as study types, exposure routes, and chemical categories. Regression-based QSTR and q-RASAR models were developed from this dataset, emphasizing key chemical descriptors. Lipophilicity and unsaturation were significant for predicting acute toxicity, while electrophilicity, nucleophilicity, and molecular branching were crucial for chronic toxicity predictions. Additionally, q-RASAR models integrated with the "intelligent consensus" algorithm were employed to enhance predictive accuracy. The performance of these models was rigorously compared across various approaches. These refined models not only predict the toxicity of untested compounds but also reveal underlying structural influences. Validation through comparison with existing literature affirmed the relevance and robustness of our approach in ecotoxicology.

Automation of Biochemical Assays Using an Open-sourced, Inexpensive Robotic Liquid Handler.

High Throughput Screening is crucial in pharmaceutical companies for efficient testing in drug discovery and development. Our Vaccines Analytical Research and Development Department (V-AR&D) extensively uses Robotic Liquid Handlers in their High Throughput Analytics (HTA) group for assay development and sample screening. However, these instruments are expensive and require extensive training. Opentrons' OT-2 liquid handler offers a more affordable option (< $10,000) with Python programming language and open-source flexibility, reducing training requirements. OT-2 allows broadening of testing capabilities and method transfer without significant capital investments. Two biochemical assays were conducted to assess OT-2′s performance, and it demonstrated accurate pipetting with low covariance compared to Tecan-EVO liquid handlers. Though OT-2 has some limitations such as lack of a crash detection system and limited deck space, it is a cost-effective, medium-throughput, and accurate liquid handling tool suitable for early-stage development and method transfer.

Immunolocalization of Extensin and Pectin Epitopes in Liparis loeselii Protocorm and Protocorm-like Bodies

Liparis loeselii (L.) Rich, an endangered member of the Orchidaceae family, is found in alkaline fens. With the declining populations of L. loeselii, there is a pressing need to reintroduce this species in Central Europe. As in vitro germination is a crucial tool for obtaining plants for introduction into the environment, we looked at the morphological changes occurring during the early stages of L. loeselii development in vitro. As the early stages of orchid development, especially the protocorm stage, are thought to be responsible for SAM formation and the initiation of symbiotic association, we focused on cell wall elements whose epitopes have been found in similar processes in other species: the extensin and pectin rhamnogalacturonan I (RG-I) side chain epitopes. We addressed the following questions: Does the cell wall of L. loeselii change its composition during the early stages of development, as noted in other species? Are there noticeable similarities in the cell wall to organs of different species whose function is to contact microorganisms? Are there regularities that allow the recognition of individual structures on this basis? Immunolocalization revealed changes in the distribution of certain extensins (JIM11 and JIM20) and RG-I (LM5 and LM6) side chain epitopes. Extensins, a type of cell wall protein, were observed during the initial stages of the formation of PLB and the shoot apical meristem of protocorms and PLBs. RG-I, on the other hand, was found to play a significant role in the development of the protocorm and PLB. In pseudobulbs, which appeared on the protocorms, extensins occurred in their storage part. However, RG-I side chains (1→4)-β-galactans (LM5), and (1→5)-α-L-arabinans (LM6) were not found in pseudobulbs. We revealed that a common feature of protocorms and PLBs was an increased amount of extensins, which were detected with the JIM11 antibody, and pectins, which were detected with the LM5 antibody, that were present together, which may prove helpful in determining the identity of the induced structures and distinguishing them from pseudobulbs. Thus, our study unveiled the role of extensins and RG-I during the growth of protocorms and PLBs. We suggest that PLBs may mimic the wall remodelling that occurs in protocorms, which indicates that using cell wall components is an invitation to be colonised by a fungal partner. However, this needs to be tested in future research. The findings of this research can help interpret future studies on the propagation, acclimatisation, and introduction of L. loeselii into the natural environment.

Why Coaching Needs Real Intelligence, Not Artificial Intelligence

The movement of AI into the coaching arena continues to be steady and confident, meeting only rare and timid resistance. The progress of this movement can be explained by decades of technological advances, the entrepreneurial attitude of AI developers, and the inherent peculiarities of the coaching business. The voices of caution are too quiet in ‘the noise of progress’. However, there are important reasons for coaching communities to be apprehensive about the ways this movement could change coaching as a service and what this means for all involved. In this paper, I address potential problematic issues with the AI revolution in the context of a multitude of conceptual holes in coaching as a profession. I argue that dehumanising coaching under the guise of ‘enhancement by AI’ undermines human intelligence, which is desperately needed while the discipline of organisational coaching remains in its early stages of development.

Barriers and enablers to the implementation of person-centred care in an Indonesian hospital: a qualitative study

Introduction: Person-centred care (PCC) is increasingly considered as one of the criteria standards for delivering healthcare in hospitals. Registered nurses are increasingly expected to provide PCC in daily practice. However, although the hospital commits to enhancing and improving PCC, implementing this approach into practice has faced barriers and enablers. As the implementation of PCC is still at an early stage of development, it is well-recognised that the need to identify barriers and enablers is essential. This study aims to explore these barriers and enablers to implementing PCC in Indonesian hospitals. Methods: This study employed a qualitative exploratory study conducted from July 2023 to September 2023 at a public hospital in Pekanbaru, Riau Province. It applied semi-structured interviews to collect data on barriers and enablers to implement PCC from 2 managers and 12 nurses from the medical ward. All participants were selected using a purposive sampling technique. Data collected from interviews were transcribed and then thematically analysed. Results: Three barriers-related themes emerged, namely time constraints and workload, lack of resources, and communication challenges. Furthermore, three enablers themes also emerged, including leadership, commitment, and sufficient monitoring and supervision. Conclusions: The study results lead hospital managers and policymakers to overcome existing barriers using adaptive planning and strategies and to improve enablers with well-trained professionals and strong leadership to deliver a PCC approach into practice. The implications to practice are that healthcare organisations must continue their support to decrease the barriers and optimise professional care in healthcare facilities to improve healthcare services.

Root Growth and Apical Foramen Closure Velocity of Maxillary Permanent Central Incisor in Korean Children

This study aimed to evaluate the growth velocity of root elongation and the timing of apical foramen closure in maxillary permanent central incisors using panoramic radiographs. The study also examined the timing of alveolar eruption and its relationship with root development while considering potential sex-specific differences. The study included 176 patients (94 males, 82 females) from the Seoul National University Dental Hospital, each with three or more panoramic radiographs taken between 2014 and 2023 and analyzed to measure the crown length, total tooth length, root length, and mesiodistal width of the apical foramen. Root lengths were expressed as percentages of the fully developed stage. Scatter plots and polynomial trend lines were used to evaluate the relationship between age and tooth development, with intraobserver reliability assessed using Cohen’ s kappa. Root growth velocity peaked during the early stages of development, with females generally exhibiting earlier and faster apical foramen closure than males. Significant correlations were found between the root length and apical foramen width (Pearson correlation coefficients, males, -0.907; females, -0.887, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001). The mean age for alveolar eruption was 7.27 years for males (N = 16) and 7.10 for females (N = 17), predominantly at Demirjian stage F. The study presents the critical periods of rapid root elongation and apical foramen closure in the maxillary central incisors, underscoring their importance for clinical dental practice. Future research is warranted to provide a more comprehensive understanding of human dental development.

Potential anti-schistosomal effect of Daflon, a repurposed drug targeting different stages of Schistosome maturity.

Despite the long history of experimental trials to combat schistosomiasis, it remains a significant burden due to drug resistance and the effectiveness of the standard treatment only against the mature stage, while skipping other early developmental stages thus leading to severe permanent pathological sequelae. Therefore, repurposing a commonly used well-known safe drug would be a wise alternative. We investigated the potential anti-schistosomal drug activity of Daflon® (DAF) against different schistosomal developmental stages. DAF was administrated at a dose of 100 mg/kg/mouse on days zero, 21, and 42 post-infection towards the invasive, immature, and mature stages of Schistosoma mansoni respectively in comparison to the standard anti-schistosomal drug (Praziquantel). All mice were sacrificed on day 49 post-infection. DAF induced a significant reduction in the total and female worm count, hepatic granuloma size, and number, the extent of liver parenchymal injury and fibrosis as well as intestinal and hepatic egg count compared to the infected untreated control. Liver malondialdehyde (MDA) levels significantly decreased in all DAF-treated groups. Scanning electron microscope findings revealed edema, tegumental blebs, cracks, and fissures in male tegument in all DAF-treated groups with distortion of the ventral suckers and disarrangement of the spines of the oral sucker. The female worm from DAF-treated groups showed tegumental edema with loss of the spines at the posterior end. Compared to the documented reduction of testosterone levels and distortion of testicular architecture in the S. mansoni-infected untreated group, DAF significantly restored testosterone levels and testicular architecture.

Reimagining professional development for school leaders in Brazil, Chile, and Colombia: an examination of current approaches and future directions

ABSTRACT This study examines current approaches to professional development (PD) for school leaders in Brazil, Chile, and Colombia. While PD programs indicate significant progress, school leadership remains in an early stage of development. The findings highlight the need for national policy commitments to ensure long-term sustainability. The challenge is not only in offering accessible programs for new principals but also in ensuring quality and promoting continuous professionalisation. The analysis underscores the need for individual-centred PD approaches that prioritise the personal growth of school leaders, recognising the multifaceted dimensions of their roles. Additionally, it emphasises the importance of embedding professional development within a learning system that fosters partnerships between academia, government, and wider society. Addressing the need for a more context-sensitive approach to professional preparation, the study also highlights the political dimension of school leadership, advocating for programs that equip leaders with the political awareness necessary to navigate complex policy contexts effectively. Recognising the influence of the Global North, this study advocates for reimagining PD approaches to integrate and prioritise contextualised practices and knowledge, considering the diverse realities and challenges faced by educators in the region.

Unveiling Swelling and Erosion Dynamics: Early Development Screening of Mirabegron Extended Release Tablets

Although the development of extended release (ER) matrices has been extensively investigated, understanding the most appropriate mechanism of drug release to achieve the desired release remains a cost- and time-consuming challenge in the early stages of formulation development. This study aimed to investigate the early stage of developing ER hydrophilic matrix tablets containing mirabegron as a model drug, focusing on the effects of polymer type, diluent type, and polymer amount on critical quality attributes (CQAs), namely, tablet swelling and erosion behavior. A full factorial design was employed to explore the interactions of control factors through multivariate regression analysis, emphasizing the application of quality by design (QbD) principles. The swelling and erosion performances of 72 formulations were evaluated. The swelling data were fitted to the Vergnaud model. Finally, in vitro drug release profiles were investigated for four of the formulations studied. The polymer type, diluent type, and polymer amount had distinct effects on the swelling and erosion behavior of the ER matrix tablets. Compared with those with isomalt (G720) or dextrate (DXT), formulations with polyethylene glycol 8000 (P8000) consistently exhibited greater swelling. Additionally, higher molecular weight was correlated with increased swelling within the same polymer type. Hydroxypropylmethylcellulose (HPMC) and polyethylene oxide (PEO)-based formulations showed higher swelling rates, while polyvinyl alcohol (PVA-80) displayed the highest erosion percentage. The findings highlight the significance of incorporating early-stage screening designs to maximize efficiency and optimize time and resource. This approach enables the development of a comprehensive understanding of drug release mechanisms from ER matrix tablets.Graphical abstract