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he objective of this work is to study the effects of contact parameters on the cracking parameters of a specimen and a pad assembly. These parameters have been studied and evaluated by the finite element method analysis in two dimensions fretting fatigue model through the Abaqus calculation code. Different values of the coefficient of friction of 0.1, 0.3 and 0.6 were applied on the various lengths in contact for a = 0.1, 0.5 and 1mm. Thus, on the various values of angle of orientation of the crack equal to 15 �, 30 � and 45 �. In addition, elements of the type (CPE4R) and the criterion of maximum tangential stress were applied. The curves of the crack parameters such as the SIF coefficients and the integral J were obtained and discussed.

Hadi Khoshmohabat,1 Shahram Paydar,2 Alireza Makarem,1,3 Mohammad Yasin Karami,2 Niloofar Dastgheib,4 Seyed Ali Hossein Zahraei,4 Rohallah Rezaei,2 Golnoush Sadat Mahmoudi Nezhad21Trauma Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran; 2Trauma Research Center, Rajaee (Emtiaz) Trauma Hospital, Shiraz University of Medical Sciences, Shiraz, Iran; 3Department of Urology, Shiraz University of Medical Sciences, Shiraz, Iran; 4Student Research Committee, Shiraz University of Medical Sciences, Shiraz, IranIntroduction: Planning for management of bleeding in trauma injuries is very important. The initial purpose in emergency situations should be immediate establishment of an efficient hemostasis, principally in its topical application. In this study, we aimed to review the major relevant articles in the case of application of cellulose hemostatic agent on trauma injuries.Methods: We searched the online databases such as PubMed, MEDLINE, Wiley, EMBASE, ISI Web of Knowledge, and Scopus. Two reviewers independently searched and assessed the titles and abstracts of all articles.Results: Upon screening the titles and abstracts, 24 studies were identified for full-text review. The oxidized cellulose had the best clotting times, while it demonstrated low absorption ability. Surgical and thermosensitive chitosan hemostatic could be valuable for managing hemorrhage from liver injuries in trauma patients.Conclusion: Recently, the application of cellulose hemostatic agents has been one of the main improvements obtained for controlling bleeding in trauma injuries. However, generally according to the literature review, the decision about using each agent should be made on a case-by-case basis. However, it can be mentioned that the perfect hemostatic agent has not been still identified.Keywords: cellulose hemostatic agent, trauma, injury

The effects of dietary nucleotide (NT) were evaluated on some serum biochemical parameters and acute stress responses of the catfish (Pangasianodon hypophthalmus). Five experimental diets including 0, 0.25, 0.5, 0.75, and 1% NT were supplied to catfish fry for 10 weeks. At the end of the experiment, fish fed the control and 1% NT diets were subjected to handling and crowding stress. The results showed that the fish supplied with 0.25-0.75% NT had a lower level of lactate dehydrogenase (LDH) (P<0.05) while other serum enzymes including alkaline phosphatase (ALP), asparate transaminase (ASP), and alanine transaminase (ALT) were not significantly reduced by NT inclusion in the diet (P>0.05). The fish which received the highest doses (0.75 and 1%) of NT exhibited higher levels of triglyceride than the other groups (P<0.05) while they showed no significant differences in other biochemical parameters including total protein, albumin, globulin, cholesterol, and glucose (P>0.05). To investigate stress responses, cortisol (primary response), serum glucose, and serum ion concentrations including sodium, potassium and calcium (secondary responses) were measured. The results showed significant fluctuations in all the tested components during the sampling intervals for up to 48 h post-stress; the exceptions, however, were glucose in the group on the 1% NT diet as well as serum cortisol and calcium levels in those supplied with the control diet. Based on the results obtained, it may be concluded that dietary NT can improve liver function in iridescent catfish, but it has no obvious positive effects on other serum biochemical parameters and stress responses. [ABSTRACT FROM AUTHOR]

Statement of the problem: Presently, various imaging methods are available for the disclosure of proximal caries. Some recent studies have attempted to determine the diagnostic accuracy of available modalities, but they have shown variable results. Aim: This study was carried out to recognize and examine the correctness of cone-beam computed tomography (CBCT), regular radiographs and the nondirect digital system in the disclosure of interproximal caries. Materials and Method: In this observational tryout study, forty-two extracted non-cavitated, unrestored person molar and premolar teeth were placed in the blocks with proximal surfaces in touch. Then they were appraised by CBCT, formal radiographs and the nondirect digital system for the disclosure of interproximal caries. Four oral and maxillofacial radiologists used a 4-point scale to assess the pictures for the existence or absence of proximal caries. Caries depth was specified by histological examination. The gathered data were assessed by SPSS software using Weighted Kappa and Friedman test. Results: Statistics demonstrated that the accuracy of the indirect digital system was somewhat better than conventional systems. The accuracy of the indirect digital system was better than cone beam system, and this difference was statistically significant. Conclusion: The digital system was better than CBCT in the disclosure of proximal caries. The formal radiography fell in between the two other systems without a statistically significant deviation in detecting caries. Thus, CBCT is not advised to detect proximalcaries because of the higher radiation dose. [ABSTRACT FROM AUTHOR]

The present study was conducted to evaluate the effects of dietary nucleotides ( NT) on growth performance, immune responses, and intestinal morphology of striped catfish, Pangasianodon hypophthalmus. Different levels of NT (0, 0.25. 0.5, 0.75, and 1% weight per weight, WW−1) were used in the basal diet and then randomly allocated to triplicate groups of fish with an average initial weight of 1.52 ± 0.11 g for 10 weeks. Nucleotide supplementation did not improve growth parameters significantly (P > 0.05). Feeding fish with a NT-containing diet significantly improved ACH50 activity and Ig M levels in comparison to the control group (P < 0.05). The dietary NT (P < 0.05) affected the intestinal morphology, whereby the folds and enterocyte heights in the mid-intestine were significantly increased compared to the control group (P < 0.05), while the microvilli length was not affected. The results indicate that feeding striped catfish with commercial NT have significant effects on the immune parameters and intestinal morphology of catfish and that the best NT levels are 0.25 and 0.5%. [ABSTRACT FROM AUTHOR]

Strength properties of reservoir rocks play an important role in oil drilling and production. Meanwhile, uniaxial compressive strength is a decisive parameter in the gas and oil drilling. Considering that the uniaxial compressive strength is affected by many parameters, such as fracture and porosity, it can indicate the mechanical properties of the rock. Hence, uniaxial compressive strength is effective in selecting the bit, the ability to drill, wellbore stability analysis, sand production, and determining the in-situ stress field. There are several ways to estimate these parameters, one of which is the use of petrophysical information. Since uniaxial compressive strength estimation is affected by many different parameters, it is always faced with uncertainty. On the other hand, geostatistics can help a lot to analyze and process the data. In this article, the uniaxial compressive strength data in one of the oil fields of southwestern Iran has been examined and processed by using geostatistical methods. Thus, the spatial structure of the uniaxial compressive strength was determined by the best variogram model. Then by using the Kriging interpolation method, uniaxial compressive strength is estimated along the wall of the well with the lowest error. [ABSTRACT FROM PUBLISHER]

Chronic wounds, defined by their prolonged healing process, significantly impair patient quality of life and impose a hefty financial burden on healthcare systems worldwide. Sex/gender-specific mechanisms regulate inflammation and infection, angiogenesis, matrix synthesis, and cell recruitment contribute to cutaneous wound healing, but remain largely understudied. This review is aimed to spotlight the innovative realm of bioengineering and nanomedicine, which is at the helm of revolutionizing complex chronic wound care. It underscores the significance of integrating patient sex into the development and (pre)clinical testing of these avant-garde treatment modalities, in order to enhance healing prospects for both women and men. Moreover, we explore the representation of both sexes in clinical trials of bioengineered and nanomedicine products. Finally, we examine the primary reasons for the historical neglect in translating sex-specific wound healing research into clinical practice and propose strategic solutions. By tackling these issues, the article advocates for advanced treatment frameworks that could significantly improve healing outcomes for individuals of all sexes, thereby optimizing both efficacy and inclusivity in chronic wound management., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Importance: Progressive multifocal leukoencephalopathy (PML) is a life-threatening viral infection with no approved antiviral treatment., Objective: To determine whether restoring the compromised immune system of patients with PML with directly isolated allogeneic virus-specific (DIAVIS) T cells is a promising therapeutic strategy, especially if other curative options are absent., Design, Setting, and Participants: A retrospective case series of patients with PML who were treated with DIAVIS T cells was conducted between March 2020 and February 2022. T cells were isolated from healthy donors within 24 hours and targeted against the BK polyomavirus. Patients with PML were treated monocentrically. Eligibility for treatment with DIAVIS T cells was assessed for patients with confirmed PML, and exclusion criteria included stable PML disease and previous treatment with natalizumab., Exposure: Fresh DIAVIS T cells were administered with a maximum dose of 2 × 104 CD3+ cells/kg body weight. Remaining T cells were cryopreserved in divided doses and administered in additional treatments approximately 2 and 6 weeks later., Main Outcomes and Measures: Primary outcome measures were clinical response and survival of patients, compared with the outcomes of a historical reference group of PML cases receiving best supportive treatment (BST) and with recently published real-world data of patients with PML who were treated with immune checkpoint inhibition., Results: The study cohort consisted of 28 patients (median [IQR] age, 60 [51-72] years; 20 male [71.4%]). Twenty-two patients (79%) treated with DIAVIS T cells showed response, resulting in significant clinical stabilization or improvement and a reduction in viral load. Six individuals (21%) were classified as nonresponders, deteriorated rapidly, and died, as did 2 other patients during a 12-month follow-up. Older age was the only predictor of a poor treatment response. Survival analysis revealed better 12-month survival rates (hazard ratio, 0.42; 95% CI, 0.24-0.73; P =.02) from diagnosis for patients treated with DIAVIS T cells (18 of 26 [69%]; 12-mo survival rate, 69%) compared with historical controls with BST (57 of 113 [50%]; 12-mo survival rate, including censored data, 45%)., Conclusion and Relevance: This case series of DIAVIS T-cell therapy in PML provides first class IV evidence suggesting efficacy to reduce mortality and improve functional outcome. Further prospective studies are required to confirm these results.

Background: Diagnostic criteria for progressive supranuclear palsy (PSP) include midbrain atrophy in MRI and hypometabolism in [ 18 F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) as supportive features. Due to limited data regarding their relative and sequential value, there is no recommendation for an algorithm to combine both modalities to increase diagnostic accuracy. This study evaluated the added value of sequential imaging using state-of-the-art methods to analyse the images regarding PSP features., Methods: The retrospective study included 41 PSP patients, 21 with Richardson's syndrome (PSP-RS), 20 with variant PSP phenotypes (vPSP) and 46 sex- and age-matched healthy controls. A pretrained support vector machine (SVM) for the classification of atrophy profiles from automatic MRI volumetry was used to analyse T1w-MRI (output: MRI-SVM-PSP score). Covariance pattern analysis was applied to compute the expression of a predefined PSP-related pattern in FDG-PET (output: PET-PSPRP expression score)., Results: The area under the receiver operating characteristic curve for the detection of PSP did not differ between MRI-SVM-PSP and PET-PSPRP expression score (p≥0.63): about 0.90, 0.95 and 0.85 for detection of all PSP, PSP-RS and vPSP. The MRI-SVM-PSP score achieved about 13% higher specificity and about 15% lower sensitivity than the PET-PSPRP expression score. Decision tree models selected the MRI-SVM-PSP score for the first branching and the PET-PSPRP expression score for a second split of the subgroup with normal MRI-SVM-PSP score, both in the whole sample and when restricted to PSP-RS or vPSP., Conclusions: FDG-PET provides added value for PSP-suspected patients with normal/inconclusive T1w-MRI, regardless of PSP phenotype and the methods to analyse the images for PSP-typical features., Competing Interests: Competing interests: H-JH has used atlas-based volumetric MRI analysis in industry-sponsored research projects. CB received a grant from the Hilde-Ulrichs-Stiftung, served as a consultant for Bial, Hormosan Pharma, Merz Pharmaceuticals and Zambon and received honoraria for scientific presentations from Abbvie, Bial, Stada Pharma, TAD Pharma, UCB Pharma and Zambon. MP-N received lecture fees from Abbott, Abbvie, Boston Scientific and served as consultant for Medtronic, Boston Scientific, Abbott, Zambon and Abbvie. SK was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy–ID 390857198), the Ehrmann Foundation and the Lüneburg Heritage. SK receives research funding from CurePSP and reports travel support from Life Molecular Imaging outside the submitted work. MK received honoraria for scientific presentations from Abbvie and Ever Pharma. JL reports speaker fees from Bayer Vital, Biogen, EISAI, TEVA and Roche, consulting fees from Axon Neuroscience and Biogen, author fees from Thieme medical publishers and W. Kohlhammer medical publishers and is inventor in a patent 'Oral Phenylbutyrate for Treatment of Human 4-Repeat Tauopathies' (EP 23 156 122.6) filed by LMU Munich. In addition, he reports compensation for serving as chief medical officer for MODAG, is beneficiary of the phantom share program of MODAG and is inventor in a patent 'Pharmaceutical Composition and Methods of Use' (EP 22 159 408.8) filed by MODAG, all activities outside the submitted work. J-JR received speaker honoraria from GE Healthcare. OS received research support from Life Molecular Imaging. HB received reader honoraria from Life Molecular Imaging and speaker honoraria from Novartis/AAA. MPW received speaker or consultancy honoraria from Alexion, Bayer Healthcare, Biogen, Biologix, Bristol Myers Squibb, Celgene, Genilac, Imcyse, IXICO, Icometrix, Medison, Merck-Serono, Novartis, Roche, Sanofi-Genzyme. Publication royalties from Springer and Elsevier. GH was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy–ID 390857198) and within the Hannover Cluster RESIST (EXC 2155–project number 39087428), the EU/EFPIA/Innovative Medicines Initiative (2) Joint Undertaking (IMPRIND grant no 116060), the European Joint Programme on Rare Diseases (Improve-PSP), Deutsche Forschungsgemeinschaft (DFG, HO2402/6-2 Heisenberg Program, HO2402/18-1 MSAomics), the VolkswagenStiftung (Niedersächsisches Vorab), the Petermax-Müller Foundation (Etiology and Therapy of Synucleinopathies and Tauopathies); participated in indurtry-sponsored research projects from Abbvie, Biogen, Biohaven, Novartis, Roche, Sanofi, UCB; served as a consultant for Abbvie, Alzprotect, Aprineua, Asceneuron, Bial, Biogen, Biohaven, Kyowa Kirin, Lundbeck, Novartis, Retrotope, Roche, Sanofi, UCB; received honoraria for scientific presentations from Abbvie, Bayer Vital, Bial, Biogen, Bristol Myers Squibb, Kyowa Kirin, Roche, Teva, UCB, Zambon; received publication royalties from Academic Press, Kohlhammer and Thieme. All other authors declare that they have no potential conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Magnetic resonance imaging is the most sensitive method for detecting inflammatory activity in multiple sclerosis, particularly in the brain where it reveals subclinical inflammation. Established MRI markers include contrast-enhancing lesions and active T2 lesions. Recent promising markers like slowly expanding lesions and phase rim lesions are being explored for monitoring chronic inflammation, but require further validation for clinical use. Volumetric and quantitative MRI techniques are currently limited to clinical trials and are not yet recommended for routine clinical use. Additionally, MRI is crucial for detecting complications from disease-modifying treatments and for implementing MRI-based pharmacovigilance strategies, such as in patients treated with natalizumab., Competing Interests: Disclosure N. Mahmoudi has nothing to disclose. M.P. Wattjes received speaker or consultancy honoraria from Alexion, Bayer Healthcare, Biogen, Biologix, Celgene, Genilac, Imcyse, IXICO, Icometrix, Medison, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, Springer Healthcare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Despite progress in bone tissue engineering, reconstruction of large bone defects remains an important clinical challenge. Here, a biomaterial designed to recruit bone cells, endothelial cells, and neuronal fibers within the same matrix is developed, enabling bone tissue regeneration. The bioactive matrix is based on modified elastin-like polypeptides (ELPs) grafted with laminin-derived adhesion peptides IKVAV and YIGSR, and the SNA15 peptide for retention of hydroxyapatite (HA) particles. The composite matrix shows suitable porosity, interconnectivity, biocompatibility for endothelial cells, and the ability to support neurites outgrowth by sensory neurons. Subcutaneous implantation leads to the formation of osteoid tissue, characterized by the presence of bone cells, vascular networks, and neuronal structures, while minimizing inflammation. Using a rat femoral condyle defect model, longitudinal micro-CT analysis is performed, which demonstrates a significant increase in the volume of mineralized tissue when using the ELP-based matrix compared to empty defects and a commercially available control (Collapat). Furthermore, visible blood vessel networks and nerve fibers are observed within the lesions after a period of two weeks. By incorporating multiple key components that support cell growth, mineralization, and tissue integration, this ELP-based composite matrix provides a holistic and versatile solution to enhance bone tissue regeneration., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

The non-invasive nature and potential for sustained release make transdermal drug administration an appealing treatment option for cancer therapy. However, the strong barrier of the stratum corneum (SC) poses a challenge for the penetration of hydrophilic chemotherapy drugs such as 5-fluorouracil (5-FU). Due to its biocompatibility and capacity to increase drug solubility and permeability, especially when paired with chemical enhancers, such as oleic acid (OA), which is used in this work, choline glycinate ([Cho][Gly]) has emerged as a potential substance for transdermal drug delivery. In this work, we examined the possibility of transdermal delivery of 5-FU for the treatment of breast cancer using an ionic hydrogel formulation consisting of [Cho][Gly] with OA. Small angle neutron scattering, rheological analysis, field emission scanning electron microscopy, and dynamic light scattering analysis were used to characterize the ionic hydrogel. The non-covalent interactions present between [Cho][Gly] and OA were investigated by computational simulations and FTIR spectroscopy methods. When subjected to in vitro drug permeation using goat skin in a Franz diffusion cell, the hydrogel demonstrated sustained release of 5-FU and effective permeability in the order: [Cho][Gly]-OA gel > [Cho][Gly] > PBS (control). The hydrogel also demonstrated 92% cell viability after 48 hours for the human keratinocyte cell line (HaCaT cells) as well as the normal human cell line L-132. The breast cancer cell line MCF-7 and the cervical cancer cell line HeLa were used to study in vitro cytotoxicity that was considerably affected by the 5-FU-loaded hydrogel. These results indicate the potential of the hydrogel as a transdermal drug delivery vehicle for the treatment of breast cancer.

Self-assembled hyaluronic acid-based nanogels are versatile drug carriers due to their biodegradable nature and gentle preparation conditions, making them particularly interesting for delivery of peptide therapeutics. This study aims to elucidate the relation between peptide structure and encapsulation in a nanogel. Key peptide properties that affect encapsulation in octenyl succinic anhydride-modified hyaluronic acid nanogels were identified as we explored the effect on nanogel characteristics using 12 peptides with varying charge and hydrophobicity. The size and surface properties of the microfluidics-assembled peptide-loaded nanogels were evaluated using dynamic light scattering, laser Doppler electrophoresis, and small angle neutron scattering. Additionally, the change in peptide secondary structure upon encapsulation in nanogels, their release from the nanogels, and the in vitro antimicrobial activity were assessed. In conclusion, the more hydrophobic peptides showed stronger binding to the nanogel carrier and localized internally rather than on the surface of the nanogel, resulting in more spherical nanogels with smoother surfaces and slower release profiles. In contrast, cationic and hydrophilic peptides localized at the nanogel surface resulting in fluffier nanogel structures and quick and more complete release in biorelevant medium. These findings emphasize that the advantages of nanogel delivery systems for different applications depend on the therapeutic peptide properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The development of lipid nanoparticle (LNP) based therapeutics for delivery of RNA has triggered the advance of new strategies for formulation, such as high throughput microfluidics for precise mixing of components into well-defined particles. In this study, we have characterised the structure of LNPs throughout the formulation process using in situ small angle x-ray scattering in the microfluidic chip, then by sampling in the subsequent dialysis process. The final formulation was investigated with small angle x-ray (SAXS) and neutron (SANS) scattering, dynamic light scattering (DLS) and cryo-TEM. The effect on structure was investigated for LNPs with a benchmark lipid composition and containing different cargos: calf thymus DNA (DNA) and two model mRNAs, polyadenylic acid (polyA) and polyuridylic acid (polyU). The LNP structure evolved during mixing in the microfluidic channel, however was only fully developed during the dialysis. The colloidal stability of the final formulation was affected by the type of incorporated nucleic acids (NAs) and decreased with the degree of base-pairing, as polyU induced extensive particle aggregation. The main NA LNP peak in the SAXS data for the final formulation were similar, with the repeat distance increasing from polyU

We investigate the structure and interactions of a model anionic/amphoteric mixed surfactant micellar system, namely, sodium dodecyl sulfate (SDS) and N , N -dimethyldodecylamine N -oxide (DDAO), employing SANS, FTIR, DLS, and pH measurements, in the range 0.1-100 mM total surfactant concentration and 0-100% DDAO. Increasing surfactant concentration is found to elongate the prolate ellipsoid micelles ( R Polar ∼ 25-40 Å), accompanied by up to a 6-fold increase in micellar charge. The surfactant synergy, in terms of micellar charge and size, diffusion coefficient, solution pH, and headgroup interactions, was found to vary with concentration. At lower concentrations (≤50 mM), the SDS-DDAO ratio of maximum synergy is found to be asymmetric (at 65-85% DDAO), which is rationalized using regular solution theory, suggesting an equilibrium between Na + dissociation, DDAO protonation, and counterion concentration. At higher concentrations, maximum synergy shifts toward the equimolar ratio. Overall, our study expands and unifies previous reports, providing a comprehensive understanding for this model, synergetic mixed micellar system.