-
American Journal of Human Genetics Jun 2024Extra-axial cavernous hemangiomas (ECHs) are complex vascular lesions mainly found in the spine and cavernous sinus. Their removal poses significant risk due to their...
Extra-axial cavernous hemangiomas (ECHs) are complex vascular lesions mainly found in the spine and cavernous sinus. Their removal poses significant risk due to their vascularity and diffuse nature, and their genetic underpinnings remain incompletely understood. Our approach involved genetic analyses on 31 tissue samples of ECHs employing whole-exome sequencing and targeted deep sequencing. We explored downstream signaling pathways, gene expression changes, and resultant phenotypic shifts induced by these mutations, both in vitro and in vivo. In our cohort, 77.4% of samples had somatic missense variants in GNA14, GNAQ, or GJA4. Transcriptomic analysis highlighted significant pathway upregulation, with the GNAQ c.626A>G (p.Gln209Arg) mutation elevating PI3K-AKT-mTOR and angiogenesis-related pathways, while GNA14 c.614A>T (p.Gln205Leu) mutation led to MAPK and angiogenesis-related pathway upregulation. Using a mouse xenograft model, we observed enlarged vessels from these mutations. Additionally, we initiated rapamycin treatment in a 14-year-old individual harboring the GNAQ c.626A>G (p.Gln209Arg) variant, resulting in gradual regression of cutaneous cavernous hemangiomas and improved motor strength, with minimal side effects. Understanding these mutations and their pathways provides a foundation for developing therapies for ECHs resistant to current therapies. Indeed, the administration of rapamycin in an individual within this study highlights the promise of targeted treatments in treating these complex lesions.
PubMed: 38917801
DOI: 10.1016/j.ajhg.2024.05.020 -
Animal : An International Journal of... Jun 2024Alternatives to hormonal treatments (HTs) in dairy sheep reproduction management are being explored in response to increasing societal concerns regarding animal welfare...
Alternatives to hormonal treatments (HTs) in dairy sheep reproduction management are being explored in response to increasing societal concerns regarding animal welfare and food safety. However, hormone-free reproduction implies higher variability in flock performances and additional constraints for timely synchronised artificial insemination (AI) in the flock, impacting the diffusion of genetic progress. The use of the male effect, a well-known practice to induce synchronised oestrus, combined with precision tools (e.g., heat detector), is a plausible way to implement AI without HT in dairy sheep farms. To date, the consequences of such alternative reproduction management on the whole farm sustainability remain unknown. To anticipate these potential impacts, a multiagent model (REPRIN'OV) was used to simulate dairy sheep farms' sustainability indicators (biotechnical, economic, environmental and workload). A reproduction management scenario, including the use of the male effect followed by AI on the adult ewes (HFAI), was simulated and compared to the current reproduction management of four case study farms (Early_conv, Late_conv, Early_org and Late_org). They were selected to represent the different agricultural models (Conventional or Organic) and reproduction seasons (Early - during spring, out of ewes' natural reproduction season - or Late -from early summer to the end of autumn) of the Roquefort Basin's farms in Southern France. Simulation results showed that the HFAI scenario had different consequences depending on the farm's production system type. A negative effect on most key sustainability indicators of the Conv farms was observed, as a significant reduction in the fertility rate, in the proportion of young ewes born from AI (-54% in both farms; P < 0.05) and in the flock's milk production were observed; while the workload and greenhouse gas (GHG) emissions were increased compared to the initial scenario. In the Org farms, HFAI had neutral to positive effects on most indicators as the fertility, milk production of the flock, workload during milking and GHG emissions were barely affected by this scenario, while an increase in the proportion of young ewes born from AI was observed (+39% and + 43% in each farm, respectively; P < 0.05), allowing a better farm gross margin. Still, the workload during lambing was increased in Early_org (+18%; P < 0.05), as Early farms, tended to be more negatively impacted by HFAI than Late ones. Overall, our simulation approach provides interesting elements to exchange with stakeholders on how to progress towards a socially acceptable reproduction management system, for the dairy sheep sector.
PubMed: 38917727
DOI: 10.1016/j.animal.2024.101210 -
Advances in Colloid and Interface... Jun 2024Diffuse soft matter interfaces take many forms, from end-tethered polymer brushes or adsorbed surfactants to self-assembled layers of lipids. These interfaces play...
Diffuse soft matter interfaces take many forms, from end-tethered polymer brushes or adsorbed surfactants to self-assembled layers of lipids. These interfaces play crucial roles across a multitude of fields, including materials science, biophysics, and nanotechnology. Understanding the nanostructure and properties of these interfaces is fundamental for optimising their performance and designing novel functional materials. In recent years, reflectometry techniques, in particular neutron reflectometry, have emerged as powerful tools for elucidating the intricate nanostructure of soft matter interfaces with remarkable precision and depth. This review provides an overview of selected recent developments in reflectometry and their applications for illuminating the nanostructure of diffuse interfaces. We explore various principles and methods of neutron and X-ray reflectometry, as well as ellipsometry, and discuss advances in their experimental setups and data analysis approaches. Improvements to experimental neutron reflectometry methods have enabled greater time resolution in kinetic measurements and elucidation of diffuse structure under shear or confinement, while innovation in analysis protocols has significantly reduced data processing times, facilitated co-refinement of reflectometry data from multiple instruments and provided greater-than-ever confidence in proposed structural models. Furthermore, we highlight some significant research findings enabled by these techniques, revealing the organisation, dynamics, and interfacial phenomena at the nanoscale. We also discuss future directions and potential advancements in reflectometry techniques. By shedding light on the nanostructure of diffuse interfaces, reflectometry techniques enable the rational design and tailoring of interfaces with enhanced properties and functionalities.
PubMed: 38917595
DOI: 10.1016/j.cis.2024.103238 -
Asian Pacific Journal of Cancer... Jun 2024The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector...
Evaluation of the Expression EGFR, HER2/NEU and the End Effector ERK of the RAS/RAF/MAP Kinase Pathway in Prostatic Adenocarcinoma for a Possible Role as New Target Therapy.
UNLABELLED
The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector molecule (ERK) are important in the carcinogenesis of many tumors. The activation of these protooncogenes in prostate cancer is still under investigation. The aim of this work was to study EGFR, HER2- neu, inactive (non-phosphorylated) and active (phosphorylated) ERK expression in prostatic adenocarcinomas in correlation to the clinical and pathological parameters.
METHODS
Immunohistochemistry- using tissue microarrays- for EGFR, HER2/neu, non-phosphorylated, and phosphor-ERK, was performed on tissues from 166 patients- with primary prostatic adenocarcinoma with no prior treatment-. The results of different markers expression were correlated with the clinical and pathological parameters and were analyzed statistically.
RESULTS
The prostatic tissue showed EGFR, HER2 neu, phosphorylated and non-phosphorylated ERK expression in 8.4%, 1.4%, 78.2%, and 83.4% respectively whether low (patchy) or high expression (diffuse). There were no significant correlations found between patient characteristics and expression of the tested markers. The negative immune reactivity for non-phosphorylated ERK and EGFR- was significantly correlated with high tumor stage (p values 0.03 and 0.01, respectively).
CONCLUSION
EGFR and HER2/neu may play a limited role in prostatic adenocarcinoma as they showed positive expression in a limited number of the examined tissues specifically HER2neu. The expression of non-phosphorylated ERK (mostly weak to moderate) and phosphorylated ERK (mostly moderate to strong)- was appreciated in most cases. Thus, we suggest that anti-EGFR drugs may have a limited role in the treatment of castrate-resistant prostate cancer, but anti-MEK/ERK drugs may have more promising role as a target therapy. It is recommended to perform further molecular testing to elucidate the exact mechanism and significance of these markers.
PubMed: 38918683
DOI: 10.31557/APJCP.2024.25.6.2193 -
Scientific Reports Jun 2024This study compares the adsorption behavior of both Methylene Blue (MB) and Congo Red (CR) dyes on the surfaces of cement kiln dust (CKD) powder from the experimentally...
This study compares the adsorption behavior of both Methylene Blue (MB) and Congo Red (CR) dyes on the surfaces of cement kiln dust (CKD) powder from the experimentally simulated wastewater solution. The cement kiln dust powder was characterized using X-ray Fluorescence (XRF), X-ray diffraction (XRD), N adsorption-desorption Brunauer-Emmett-Teller (BET), Fourier Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM) tests. The adsorption for such dyes was studied under varying mixing contact times, temperatures, and pH as well as various initial concentrations of both dyes and adsorbent using the batch mode experiments. Pseudo-first-order, pseudo-second-order, and intraparticle diffusion models were applied, and the results revealed that the pseudo-second-order fitted well to the kinetic data. Thermodynamic parameters stated that the adsorption process was endothermic. Studying Linear and nonlinear forms of Langmuir and Freundlich's adsorption isotherms revealed that the adsorption process was followed by both homogeneous mono-layer and heterogeneous multilayer coverage on the active sites of cement kiln dust particles. The data showed that the adsorption capacities of the methylene blue and Congo red dyes were 58.43 and 123.42 mg/g, respectively and cement kiln dust is an adsorbent with little cost for the treatment of wastewater.
PubMed: 38918519
DOI: 10.1038/s41598-024-64191-5 -
Scientific Reports Jun 2024Hypodense volumes (HDV) in mediastinal masses can be visualized in a computed tomography scan in Hodgkin lymphoma. We analyzed staging CT scans of 1178 patients with...
Hypodense volumes (HDV) in mediastinal masses can be visualized in a computed tomography scan in Hodgkin lymphoma. We analyzed staging CT scans of 1178 patients with mediastinal involvement from the EuroNet-PHL-C1 trial and explored correlations of HDV with patient characteristics, mediastinal tumor volume and progression-free survival. HDV occurred in 350 of 1178 patients (29.7%), typically in larger mediastinal volumes. There were different patterns in appearance with single lesions found in 243 patients (69.4%), multiple lesions in 107 patients (30.6%). Well delineated lesions were found in 248 cases (70.1%), diffuse lesions were seen in 102 cases (29.1%). Clinically, B symptoms occurred more often in patients with HDV (47.7% compared to 35.0% without HDV (p = 0.039)) and patients with HDV tended to be in higher risk groups. Inadequate overall early-F-FDG-PET-response was strongly correlated with the occurrence of hypodense lesions (p < 0.001). Patients with total HDV > 40 ml (n = 80) had a 5 year PFS of 79.6% compared to 89.7% (p = 0.01) in patients with HDV < 40 ml or no HDV. This difference in PFS is not caused by treatment group alone. HDV is a common phenomenon in HL with mediastinal involvement.
Topics: Humans; Male; Female; Hodgkin Disease; Adult; Mediastinal Neoplasms; Middle Aged; Tomography, X-Ray Computed; Young Adult; Aged; Adolescent; Mediastinum; Fluorodeoxyglucose F18; Positron-Emission Tomography; Progression-Free Survival
PubMed: 38918503
DOI: 10.1038/s41598-024-64253-8 -
Advances in Experimental Medicine and... 2024Extracting temporal regularities and relations from experience/observation is critical for organisms' adaptiveness (communication, foraging, predation, prediction) in... (Review)
Review
Extracting temporal regularities and relations from experience/observation is critical for organisms' adaptiveness (communication, foraging, predation, prediction) in their ecological niches. Therefore, it is not surprising that the internal clock that enables the perception of seconds-to-minutes-long intervals (interval timing) is evolutionarily well-preserved across many species of animals. This comparative claim is primarily supported by the fact that the timing behavior of many vertebrates exhibits common statistical signatures (e.g., on-average accuracy, scalar variability, positive skew). These ubiquitous statistical features of timing behaviors serve as empirical benchmarks for modelers in their efforts to unravel the processing dynamics of the internal clock (namely answering how internal clock "ticks"). In this chapter, we introduce prominent (neuro)computational approaches to modeling interval timing at a level that can be understood by general audience. These models include Treisman's pacemaker accumulator model, the information processing variant of scalar expectancy theory, the striatal beat frequency model, behavioral expectancy theory, the learning to time model, the time-adaptive opponent Poisson drift-diffusion model, time cell models, and neural trajectory models. Crucially, we discuss these models within an overarching conceptual framework that categorizes different models as threshold vs. clock-adaptive models and as dedicated clock/ramping vs. emergent time/population code models.
Topics: Animals; Time Perception; Models, Neurological; Humans; Biological Clocks; Computer Simulation; Neurons
PubMed: 38918346
DOI: 10.1007/978-3-031-60183-5_4 -
La Radiologia Medica Jun 2024Radical prostatectomy (RP) is recommended in case of localized or locally advanced prostate cancer (PCa), but it can lead to side effects, including urinary incontinence... (Review)
Review
BACKGROUND
Radical prostatectomy (RP) is recommended in case of localized or locally advanced prostate cancer (PCa), but it can lead to side effects, including urinary incontinence (UI) and erectile dysfunction (ED). Magnetic resonance imaging (MRI) is recommended for PCa diagnosis and staging, but it can also improve preoperative risk-stratification.
PURPOSE
This nonsystematic review aims to provide an overview on factors involved in RP side effects, highlighting anatomical and pathological aspects that could be included in a structured report.
EVIDENCE SYNTHESIS
Considering UI evaluation, MR can investigate membranous urethra length (MUL), prostate volume, the urethral sphincter complex, and the presence of prostate median lobe. Longer MUL measurement based on MRI is linked to a higher likelihood of achieving continence restoration. For ED assessment, MRI and diffusion tensor imaging identify the neurovascular bundle and they can aid in surgery planning. Finally, MRI can precisely describe extra-prostatic extension, prostate apex characteristics and lymph-node involvement, providing valuable preoperative information for PCa treatment.
CONCLUSIONS
Anatomical principals structures involved in RP side effects can be assessed with MR. A standardized MR report detailing these structures could assist urologists in planning optimal and tailored surgical techniques, reducing complications, and improving patients' care.
PubMed: 38918291
DOI: 10.1007/s11547-024-01831-w -
Clinical Neuroradiology Jun 2024After vertical parasagittal hemispherotomy a restricted diffusion is often seen ipsilaterally and even distant from the adjacent resection margin. This retrospective...
PURPOSE
After vertical parasagittal hemispherotomy a restricted diffusion is often seen ipsilaterally and even distant from the adjacent resection margin. This retrospective cohort study analyses the anatomic site and the time course of the diffusion restriction after vertical parasagittal hemispherotomy.
METHODS
Fifty-nine patients were included into this study, all of them having had one pre-operative and at least one post-operative MRI, including diffusion imaging at b‑values of 0 and 1000 s/mm with a calculated ADC.
RESULTS
Diffusion restriction occurred exclusively on the operated site in all patients. In the basal ganglia, diffusion restriction was present in 37 of 38 patients at the first postoperative day with a duration of 38 days. In the midbrain, the posterior limb of the internal capsule and the thalamus, a restricted diffusion became postoperatively prominent at day 9 in all three localizations, with a duration of 36, 34 and 36 days, respectively. The incidence of thalamic lesions was lower if a preoperative damage had occurred.
CONCLUSION
The restricted diffusion in the basal ganglia resembles direct effects of the operation at its edges, whereas the later appearing diffusion restriction in the midbrain and the posterior limb of the internal capsule rather belong to a degeneration of the descending fibers being transected by the hemispherotomy in the sense of a Wallerian degeneration. The presence of preoperative hemispheric lesions influences the development of diffusion restriction at subacute fiber degeneration.
PubMed: 38918242
DOI: 10.1007/s00062-024-01427-x -
Burns : Journal of the International... Jun 2024Superoxide dismutase (SOD), a natural enzyme with high antioxidant activity, reduces injury and accelerates wound healing by scavenging superoxide radicals. This enzyme...
INTRODUCTION
Superoxide dismutase (SOD), a natural enzyme with high antioxidant activity, reduces injury and accelerates wound healing by scavenging superoxide radicals. This enzyme plays an important role in cellular defense against oxidative stress such as burn injury. The aim of this study was to load SOD into solid lipid nanoparticles for the treatment of rat burn wounds.
METHODS
Solid lipid nanoparticles were prepared by Solvent Emulsification Diffusion method and evaluated for particle size, enzyme activity and enzyme entrapment efficiency. Twenty-seven rats in 3 different groups were induced with deep second-degree burns and then treated with SOD-loaded solid lipid nanoparticles, solid lipid nanoparticles without enzyme, or SOD solution. After the treatment period, the wounds were evaluated macroscopically for the area of healing and microscopically for indices of re-epithelialization, granulation tissue and angiogenesis.
RESULTS
The optimized SOD-loaded solid lipid nanoparticles showed a particle size of 35-85 ± 2.41 nm, 78.4 ± 4.31 % entrapment efficiency and 90 % initial enzyme activity. Macroscopic examination showed that the best recovery rate belonged to the solid lipid nanoparticle group. Pathological studies also showed that angiogenesis and granulation tissue were significantly better in this group. Compared to the other two groups, SOD-loaded solid lipid nanoparticles showed a significant improvement in pathological factors, particularly angiogenesis and granulation tissue, as well as a faster reduction in the number of inflammatory cells.
CONCLUSION
Based on this study, solid lipid nanoparticles could be used as an effective delivery system for SOD in the treatment of second-degree burns.
PubMed: 38918152
DOI: 10.1016/j.burns.2024.05.017