Your browser doesn't support javascript.
loading
Montrer: 20 | 50 | 100
Résultats 1 - 20 de 5.214
Filtrer
1.
Biomaterials ; 313: 122748, 2025 Feb.
Article de Anglais | MEDLINE | ID: mdl-39180918

RÉSUMÉ

Extracellular vesicles (EVs) are future promising therapeutics, but their instability in vivo after administration remains an important barrier to their further development. Many groups evaluated EV surface modification strategies to add a targeting group with the aim of controlling EV biodistribution. Conversely, fewer groups focused on their stabilization to obtain "stealth" allogenic EVs. Modulating their stabilization and biodistribution is an essential prerequisite for their development as nano-therapeutics. Here, we explored polyoxazolines with lipid anchors association to the EV membrane (POxylation as an alternative to PEGylation) to stabilize EVs in plasma and control their biodistribution, while preserving their native properties. We found that this modification maintained and seemed to potentiate the immunomodulatory properties of EVs derived from mesenchymal stem/stromal cells (MSC). Using a radiolabeling protocol to track EVs at a therapeutically relevant concentration in vivo, we demonstrated that POxylation is a promising option to stabilize EVs in plasma because it increased EV half-life by 6 fold at 6 h post-injection. Moreover, EV accumulation in tumors was higher after POxylation than after PEGylation.


Sujet(s)
Vésicules extracellulaires , Cellules souches mésenchymateuses , Vésicules extracellulaires/métabolisme , Vésicules extracellulaires/composition chimique , Animaux , Humains , Distribution tissulaire , Cellules souches mésenchymateuses/métabolisme , Cellules souches mésenchymateuses/cytologie , Oxazoles/composition chimique , Souris , Propriétés de surface , Lignée cellulaire tumorale , Souris de lignée C57BL , Femelle
2.
J Mech Behav Biomed Mater ; 160: 106735, 2024 Sep 10.
Article de Anglais | MEDLINE | ID: mdl-39288664

RÉSUMÉ

Tendon-bone fibrocartilaginous insertion, or enthesis, is a specialized interfacial region that connects tendon and bone, effectively transferring forces while minimizing stress concentrations. Previous studies have shown that insertion features gradient mineralization and branching fiber structure, which are believed to play critical roles in its excellent function. However, the specific structure-function relationship, particularly the effects of mineralization and structure at the mesoscale fiber level on the properties and function of insertion, remains poorly understood. In this study, we develop mesoscale computational models of the distinct fiber organization at tendon-bone insertions, capturing the branching network from tendon to interface fibers and the different mineralization scales. We specifically analyze three key descriptors: the mineralization scale of interface fibers, the mean, and relative standard deviation of the local branching angles of interface fibers. Tensile test simulations on insertion models with varying mineralization scales of interface fibers and structures are performed to mimic the primary loading condition applied to the insertion. We measure and analyze five representative mechanical properties: Young's modulus, strength, toughness, resilience, and failure strain. Our results reveal that mechanical properties are significantly influenced by the three key descriptors, with tradeoffs observed between mutually exclusive properties. For instance, strength and resilience plateau beyond a certain mineralization scale, while failure strain and Young's modulus exhibit monotonic decreasing and increasing trends, respectively. Consequently, there exists an optimal mineralization scale for toughness due to these tradeoffs. By analyzing the mesoscale deformation and failure mechanisms from simulation trajectories, we identify three fracture regimes closely related to the trends in mechanical properties, supporting the observed tradeoffs. Additionally, we examine in detail the effects of the mean and relative standard deviation of local branching angles on mechanical properties and deformation mechanisms. Overall, our study enhances the fundamental understanding of the composition-structure-function relationships at the tendon-bone insertion, complementing recent experimental studies. The mechanical insights from our work have the potential to guide the future biomimetic design of fibrillar adhesives and interfaces for joining soft and hard materials.

3.
Article de Anglais | MEDLINE | ID: mdl-39309372

RÉSUMÉ

Future multichip packages require Die-to-Die (D2D) interconnects operating at frequencies above 10 GHz; however, the extension of copper interconnects and epoxy dielectrics presents a trade-off between performance and reliability. This paper explores insertion losses and adhesion as a function of interface roughness at frequencies up to 18 GHz. We probe epoxy surface chemistry as a function of curing time and use wet etching to modulate surface roughness. The morphology is quantified by atomic force microscopy (AFM) and two-dimensional fast Fourier transform (2D FFT). Peel test and vector network analysis are used to examine the impacts of both type and level of roughness. The trade-offs between power efficiency and reliability are presented and discussed.

4.
Ultrasound J ; 16(1): 43, 2024 Sep 19.
Article de Anglais | MEDLINE | ID: mdl-39297921

RÉSUMÉ

BACKGROUND: The use of peripherally inserted central venous catheters (PICCs) has increased worldwide in the last decade. However, PICCs are associated to catheter-related thrombosis (CRT) and central line-associated bloodstream infections (CLABSIs). We describe the characteristics of patients requiring a PICC, estimate the incidence rate, and identify potential risk factors of PICC-related complications. METHODS: All adult patients requiring a PICC at our institution (Fundación Santa Fe de Bogotá, Bogota, Colombia) from September 2022 to May 2024 were included in the analysis. The database from active PICC monitoring collected demographic and PICC-related information. The incidence rate of CLABSI and CRT, and crude odds ratios (cORs) were estimated. RESULTS: Overall, 1936 individuals were included in the study. The median age was 67 years (IQR: 50-78 years), and 51.5% were females. The median duration of PICC lines was 10 days (IQR: 4-17). Seventy-nine patients had catheter-related complications, mostly in the Intensive Care Unit (ICU). The CLABSI and CRT institutional incidence rates per 1000 catheter-days were 2.03 (2.96 in the ICU) and 0.58 (0.61 in the ICU), respectively. Prolonged catheter use (≥ 6 days), PICC insertion in the intensive care unit, and postoperative care after cardiac surgery were identified as potential risk factors for CLABSI, while a catheter insertion into the brachial vein was associated with CRT. CONCLUSION: Daily PICC assessment, particularly in patients with prolonged catheter use, PICC insertion into the brachial vein, or in postoperative care after cardiac surgery may significantly reduce CLABSI and CRT cases. Implementing Vascular Access Teams, venous catheter care bundles, and institutional insertion protocols optimize clinical outcomes.

5.
Trends Pharmacol Sci ; 2024 Sep 19.
Article de Anglais | MEDLINE | ID: mdl-39304474

RÉSUMÉ

Extracellular vesicle (EV)-based therapeutics have gained substantial interest in the areas of drug delivery, immunotherapy, and regenerative medicine. However, the clinical translation of EVs has been slowed due to limited yields and functional heterogeneity, as well as inadequate targeting. Engineering EVs to modify their inherent function and endow them with additional functions has the potential to advance the clinical translation of EV applications. Bio-orthogonal click chemistry is an engineering approach that modifies EVs in a controlled, specific, and targeted way without compromising their intrinsic structure. Here, we provide an overview of bio-orthogonal labeling approaches involved in EV engineering. We also present the isolation methods of bio-orthogonally labeled vesicles using magnetic beads, microfluidics, and microarray chip technologies. We highlight the in vivo applications of bio-orthogonal labeling EVs for diagnosis and therapy, especially the exciting potential of bio-orthogonal glycometabolic engineered EVs for targeted therapies.

6.
J Vasc Access ; : 11297298241282369, 2024 Sep 21.
Article de Anglais | MEDLINE | ID: mdl-39305185

RÉSUMÉ

BACKGROUND: The clinical use of ultrasound has increased the chances of successful insertion of all venous access devices, including short peripheral cannulas (SPC) and long peripheral catheters (LPC). The aim of the study was to compare the clinical performance of peripheral cannulas inserted using the traditional "blind" technique versus those inserted with ultrasound guidance (US). METHODS: In this retrospective study we compared 135 peripheral intravenous cannulations (PIVCs) with ultrasound guidance and 135 PIVCs with blind technique, inserted in children (0-18 years) in the emergency department. All devices were inserted using the catheter-over-needle technique. With the blind technique, superficial arm veins were cannulated using SPCs (1.9 cm, 24G; 2.5 cm, 22G; 3.2 cm, 20G), while with US, deeper non-palpable veins were accessed using SPCs of 3.2 cm, 24G; and LPCs of 6.4 cm, 22G; 6.4 cm, 20G. RESULTS: The accesses were removed electively in 66% of US-PIVCs, with an average duration of the device of 5.3 ± 4.0 days, but only in 30% of Blind-PIVCs, which presented an average duration of 2.5 ± 1.8 days. The longest dwelling time (8.7 ± 5.1 days) was observed in 20G LPCs inserted with US into the basilic vein of the arm; among Blind-PIVCs, the longest duration (3.0 ± 2.1 days) was observed in 22G SPCs inserted into the cephalic vein at the forearm. The most commonly encountered complication in both groups was accidental dislodgment. CONCLUSIONS: PIVCs with ultrasound guidance were apparently more effective than the blind ones, reducing the number of successive cannulations. Additionally, LPCs, with their greater length compared to SPCs, have proven to be more durable and may be recommended as emergency venous access in children requiring peripheral access for 4-15 days. Dislodgement should be reduced by improving the securement of the device.

7.
Cureus ; 16(8): e67355, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39310615

RÉSUMÉ

Introduction  As a medical condition, obesity is a global public health concern that still has no satisfactory solution. Endoscopic sleeve gastroplasty (ESG) and intragastric balloon (IGB) are proven to be safe and efficient in producing weight loss. Endoscopic sleeve gastroplasty has achieved significant success; therefore, it is timely to compare it to intragastric balloon therapy. Methods  We retrospectively reviewed prospectively collected data for patients undergoing ESG or IGB. Weight was recorded at one week, one month, and three months post-procedure, and the percentage of total body weight loss (%TBWL) was calculated. Severe adverse events requiring hospital admission/procedure reversal were also recorded. We aim to see if one procedure is more efficient in providing weight loss in a short-term period.  Results A total of 20 patients underwent ESG and 31 patients underwent IGB insertion. ESG patients showed a superior mean %TBWL at one-week post-procedure (%TBWL±SD = 4.87±1.88 vs 3.76±1.95). IGB patients showed a higher mean of %TBWL at one-month post-procedure (%TBWL±SD = 8.00±3.60 vs 7.25±3.29). Both procedures show similar %TBWL at three months post-procedure (%TBWL±SD ESG = 10.857±3.83 vs %TBWL ± SD IGB = 10.852±5.78). Conclusions  We found that both the IGB insertion and ESG procedures result in clinically significant weight loss. However, the short-term weight loss between these two procedures is similar. Although similar, the number of adverse events in the IGB group is significantly higher than in the ESG group.

8.
Pol J Microbiol ; 73(3): 363-375, 2024 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-39268958

RÉSUMÉ

Escherichia coli, a rod-shaped Gram-negative bacterium, is a significant causative agent of severe clinical bacterial infections. This study aimed to analyze the epidemiology of extended-spectrum ß-lactamase (ESBL)-producing mcr-1 -positive E. coli in Shandong, China. We collected 668 non-duplicate ESBL-producing E. coli strains from clinical samples at Shandong Provincial Hospital between January and December 2018, and estimated their minimum inhibitory concentrations (MICs) using a VITEK® 2 compact system and broth microdilution. Next-generation sequencing and bioinformatic analyses identified the mcr-1 gene and other resistance genes in the polymyxin B-resistant strains. The conjugation experiment assessed the horizontal transfer capacity of the mcr-1 gene. Of the strains collected, 24 polymyxin B-resistant strains were isolated with a positivity rate of 3.59% and among the 668 strains, 19 clinical strains carried the mobile colistin resistance gene mcr-1, with a positivity rate of approximately 2.8%. All 19 clinical strains were resistant to ampicillin, cefazolin, ceftriaxone, ciprofloxacin, levofloxacin, and polymyxin B. Seventeen strains successfully transferred the mcr-1 gene into E. coli J53. All transconjugants were resistant to polymyxin B, and carried the drug resistance gene mcr-1. The 19 clinical strains had 14 sequence types (STs), with ST155 (n = 4) being the most common. The whole-genome sequencing results of pECO-POL-29_mcr1 revealed that no ISApl1 insertion sequences were found on either side of the mcr-1 gene. Our study uncovered the molecular epidemiology of mcr-1-carrying ESBL-producing E. coli in the region and suggested horizontal transmission mediated by plasmids as the main mode of mcr-1 transmission.


Sujet(s)
Antibactériens , Infections à Escherichia coli , Protéines Escherichia coli , Escherichia coli , Tests de sensibilité microbienne , Épidémiologie moléculaire , Polymyxine B , Centres de soins tertiaires , bêta-Lactamases , Escherichia coli/génétique , Escherichia coli/effets des médicaments et des substances chimiques , Polymyxine B/pharmacologie , Humains , Chine/épidémiologie , bêta-Lactamases/génétique , Protéines Escherichia coli/génétique , Protéines Escherichia coli/métabolisme , Antibactériens/pharmacologie , Infections à Escherichia coli/microbiologie , Infections à Escherichia coli/épidémiologie , Résistance bactérienne aux médicaments/génétique , Plasmides/génétique , Multirésistance bactérienne aux médicaments/génétique
9.
Angew Chem Int Ed Engl ; : e202413115, 2024 Sep 24.
Article de Anglais | MEDLINE | ID: mdl-39317992

RÉSUMÉ

Two-dimensional conjugated metal-organic frameworks (2D c-MOFs) have shown great promise in various electrochemical applications due to their intrinsic electrical conductivity. A large pore aperture is a favorable feature of this type of material because it facilitates the mass transport of chemical species and electrolytes. In this work, we propose a ligand insertion strategy in which a linear ligand is inserted into the linkage between multitopic ligands, extending the metal ion into a linear unit of -M-ligand-M-, for the construction of 2D c-MOFs with large pore apertures, utilizing only small ligands. As a proof-of-concept trial of this strategy, a 2D c-MOF with mesopores of 3.2 nm was synthesized using commercially available ligands hexahydrotriphenylene and 2,5-dihydroxybenzoquinone. The facilitation of the diffusion of redox species by the large pore size of this MOF was demonstrated through a series of probes. With this feature, it showed superior performance in the electrochemical analysis of a variety of biological species.

10.
Zhongguo Fei Ai Za Zhi ; 27(8): 579-592, 2024 Aug 20.
Article de Chinois | MEDLINE | ID: mdl-39318251

RÉSUMÉ

In non-small cell lung cancer (NSCLC), as an improtant oncogenic driver gene, epidermal growth factor receptor exon 20 insertion (EGFR ex20ins) has a unique protein structure and is primarily drug-resistant to traditional EGFR-tyrosine kinase inhibitors (EGFR-TKIs). In recent years, exploration of targeted therapy for EGFR ex20ins has never stopped. Firstly Mobocertinib and Amivantamab obtained approval from U.S. Food and Drug Administration (FDA) for EGFR ex20ins mutant NSCLC patients, then other drugs, such as Sunvozertinib, made breakthroughs and combination therapies also obtained gains. Multi-pronged measures are hopeful to overcome EGFR ex20ins drug resistance. As mentioned above, it's definitely important to gain deeper understanding of molecular mechanism of EGFR ex20ins and assess effect and difference between novel drugs. This review is devoted to make a summary about newest achievement so to provide valuable reference about precise therapy for patients with EGFR ex20ins.
.


Sujet(s)
Récepteurs ErbB , Exons , Tumeurs du poumon , Humains , Récepteurs ErbB/génétique , Récepteurs ErbB/antagonistes et inhibiteurs , Tumeurs du poumon/génétique , Tumeurs du poumon/traitement médicamenteux , Carcinome pulmonaire non à petites cellules/génétique , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Mutagenèse par insertion , Mutation , Animaux , Inhibiteurs de protéines kinases/usage thérapeutique
11.
Zhongguo Zhen Jiu ; 44(9): 1017-22, 2024 Sep 12.
Article de Chinois | MEDLINE | ID: mdl-39318292

RÉSUMÉ

OBJECTIVE: To compare the improvement of joint function in female patients with early-middle-stage knee osteoarthritis (KOA) treated by oblique insertion at ashi point with long needle and oral celecoxib capsule. METHODS: A total of 105 female patients with early-middle-stage KOA were randomly divided into an observation group (65 cases, 6 cases dropped out, 3 cases were discontinued) and a control group (40 cases, 6 cases dropped out, 2 cases were discontinued). Patients in the observation group were treated with oblique insertion at ashi point (hard knots of quadriceps femoris, hamstring muscle, popliteal muscle, etc.) with long needle, once every other 3 days, twice a week, for a total of 2 weeks. Patients in the control group were treated with oral celecoxib capsules, 0.2 g each time, once a day for 2 weeks. Both groups started functional exercise after 2 weeks of treatment. The joint function score of Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and pain visual analogue scale (VAS) score of the two groups were observed before and after treatment and after 6 weeks of treatment completion (follow-up), the 12-item short-form health survey (SF-12) score was compared between the two groups before treatment and in follow-up, and the safety of the two groups was evaluated. RESULTS: After treatment and during the follow-up, the joint function scores of WOMAC and VAS scores of the two groups were lower than those before treatment (P<0.05). During the follow-up, the joint function scores of WOMAC and VAS scores were lower than those after treatment (P<0.05), and the SF-12 scores were higher than those before treatment (P<0.05) in the two groups. After treatment, the joint function score of WOMAC of the observation group was lower and the VAS score was higher than those of the control group (P<0.001, P<0.01). During the follow-up, the SF-12 score of the observation group was higher than that of the control group (P<0.05). No serious adverse reactions occurred in both groups. CONCLUSION: The treatment of oblique insertion at ashi point with long needle can improve the knee joint function and quality of life of female patients with early-middle-staqe KOA, which is better than oral celecoxib capsule.


Sujet(s)
Points d'acupuncture , Thérapie par acupuncture , Gonarthrose , Humains , Femelle , Gonarthrose/physiopathologie , Gonarthrose/traitement médicamenteux , Gonarthrose/thérapie , Adulte d'âge moyen , Sujet âgé , Articulation du genou/physiopathologie , Résultat thérapeutique , Adulte , Aiguilles
12.
Plants (Basel) ; 13(17)2024 Sep 09.
Article de Anglais | MEDLINE | ID: mdl-39274014

RÉSUMÉ

Enhancing the marker repository and the development of breeder-friendly markers in chickpeas is important in relation to chickpea genomics-assisted breeding applications. Insertion-deletion (InDel) markers are widely distributed across genomes and easily observed with specifically designed primers, leading to less time, cost, and labor requirements. In light of this, the present study focused on the identification and development of InDel markers through the use of double-digest restriction site-associated DNA sequencing (ddRADSeq) data from 20 chickpea accessions. Bioinformatic analysis identified 20,700 InDel sites, including 15,031 (72.61%) deletions and 5669 (27.39%) insertions, among the chickpea accessions. The InDel markers ranged from 1 to 25 bp in length, while single-nucleotide-length InDel markers were found to represent the majority of the InDel sites and account for 79% of the total InDel markers. However, we focused on InDel markers wherein the length was greater than a single nucleotide to avoid any read or alignment errors. Among all of the InDel markers, 96.1% were less than 10 bp, 3.6% were between 10 and 20 bp, and 0.3% were more than 20 bp in length. We examined the InDel markers that were 10 bp and longer for the development of InDel markers based on a consideration of the genomic distribution and low-cost genotyping with agarose gels. A total of 29 InDel regions were selected, and primers were successfully designed to evaluate their efficiency. Annotation analysis of the InDel markers revealed them to be found with the highest frequency in the intergenic regions (82.76%), followed by the introns (6.90%), coding sequences (6.90%), and exons (3.45%). Genetic diversity analysis demonstrated that the polymorphic information content of the markers varied from 0.09 to 0.37, with an average of 0.20. Taken together, these results showed the efficiency of InDel marker development for chickpea genetic and genomic studies using the ddRADSeq method. The identified markers might prove valuable for chickpea breeders.

13.
Virulence ; 15(1): 2397512, 2024 Dec.
Article de Anglais | MEDLINE | ID: mdl-39282989

RÉSUMÉ

Porcine epidemic diarrhea virus (PEDV) causes diarrhea and vomiting in piglets, leading to a mortality rate of 100%. Due to the high frequency of mutation, it is important to monitor the evolution of PEDV and develop potential vaccine candidates. In this study, two PEDV strains (ZJ2022 and ZQ2022) were identified by PCR. These strains were subsequently isolated, and their genome sequences, growth characteristics, and pathogenicity were compared. Phylogenetic and recombination analyses revealed that both strains belonged to GIIa-subgroup, and ZQ2022 was identified as a recombinant strain derived from ZJ2022. Further sequence analysis showed that the ZJ2022 strain had a modified top region of the S1 protein due to a three amino acid insertion (T380_Y380insGGE) in the S1 gene. According to the virus growth curve, ZJ2022 exhibited better cellular adaptation than ZQ2022, with higher viral titers from 8 hpi to 24 hpi. Additionally, ZQ2022 exhibited a high level of pathogenicity, causing severe diarrhea in piglets at 36 hpi and a 100% mortality rate by 96 hpi. In contrast, ZJ2022 showed lower pathogenicity, inducing severe diarrhea in piglets at 60 hpi, with a mortality rate of 60% at 96 hpi and 100% at 120 hpi. In summary, our findings provided evidence of the undergoing mutations in Chinese PEDV strains. Furthermore, the S gene insertion strain ZJ2022 exhibited strong cellular adaptability and low pathogenicity, making it a potential candidate strain for vaccine development.


Sujet(s)
Animaux nouveau-nés , Infections à coronavirus , Diarrhée , Phylogenèse , Virus de la diarrhée porcine épidémique , Maladies des porcs , Animaux , Virus de la diarrhée porcine épidémique/génétique , Virus de la diarrhée porcine épidémique/pathogénicité , Virus de la diarrhée porcine épidémique/isolement et purification , Virus de la diarrhée porcine épidémique/classification , Suidae , Maladies des porcs/virologie , Infections à coronavirus/médecine vétérinaire , Infections à coronavirus/virologie , Virulence , Diarrhée/virologie , Diarrhée/médecine vétérinaire , Glycoprotéine de spicule des coronavirus/génétique , Génome viral , Mutagenèse par insertion , Chine , Cellules Vero
14.
BMC Genomics ; 25(1): 864, 2024 Sep 16.
Article de Anglais | MEDLINE | ID: mdl-39285286

RÉSUMÉ

BACKGROUND: Greater yam is a key staple crop grown in tropical and subtropical regions, while its asexual propagation mode had led to non-flowering mutations. How transposable elements contribute to its genetic variations is rarely analyzed. We used transcriptome and whole genome sequencing data to identify active transposable elements (TEs) and genetic variation caused by these active TEs. Our aim was to shed light on which TEs would lead to its intraspecies variation. RESULTS: Annotation of de novo assembly transcripts indicated that 0.8 - 0.9% of transcripts were TE related, with LTR retrotransposons (LTR-RTs) accounted for 65% TE transcripts. A large portion of these transcripts were non-autonomous TEs, which had incomplete functional domains. The majority of mapped transcripts were distributed in genic deficient regions, with 9% of TEs overlapping with genic regions. Moreover, over 90% TE transcripts exhibited low expression levels and insufficient reads coverage to support full-length structure assembly. Subfamily analysis of Copia and Gypsy, the two LTR-RTs revealed that a small number of subfamilies contained a significantly larger number of members, which play a key role in generating TE transcript. Based on resequencing data, 15,002 L-RT insertion loci were detected for active LTR-RT members. The insertion loci of LTR-RTs were highly divergent among greater yam accessions. CONCLUSIONS: This study showed the ongoing transcription and transpositions of TEs in greater yam, despite low transcription levels and incomplete proteins insufficient for autonomous transposition. While our research did not directly link these TEs to specific yam traits such as tuber yield and propagation mode, it lays a crucial foundation for further research on how these TE insertion polymorphisms (TIPs) might be related to variations in greater yam traits and its tuber propagation mode. Future research may explore the potential roles of TEs in trait variations, such as tuber yield and stress resistance, in greater yam.


Sujet(s)
Éléments transposables d'ADN , Dioscorea , Dioscorea/génétique , Dioscorea/croissance et développement , Éléments transposables d'ADN/génétique , Rétroéléments , Tubercules/génétique , Tubercules/croissance et développement , Génome végétal , Transcriptome , Variation génétique , Séquences répétées terminales/génétique
15.
Mol Ther Methods Clin Dev ; 32(3): 101319, 2024 Sep 12.
Article de Anglais | MEDLINE | ID: mdl-39282078

RÉSUMÉ

We developed an in vivo hematopoietic stem cell (HSC) gene therapy approach that does not require cell transplantation. To achieve therapeutically relevant numbers of corrected cells, we constructed HSC-tropic HDAd5/35++ vectors expressing a 3' UTR truncated HMGA2 gene and a GFP reporter gene. A SB100x transposase vector mediated random integration of the tHMGA2/GFP transgene cassette. HSCs in mice were mobilized by subcutaneous injections of G-CSF and AMD3100/Plerixafor and intravenously injected with the integrating tHMGA2/GFP vector. This resulted in a slow but progressive, competitive expansion of GFP+ PBMCs, reaching about 50% by week 44 with further expansion in secondary recipients. Expansion occurred at the level of HSCs as well as at the levels of myeloid, lymphoid, and erythroid progenitors within the bone marrow and spleen. Importantly, based on genome-wide integration site analyses, expansion was polyclonal, without any signs of clonal dominance. Whole-exome sequencing did not show significant differences in the genomic instability indices between tHGMGA2/GFP mice and untreated control mice. Auto-expansion by tHMGA2 was validated in humanized mice. This is the first demonstration that simple injections of mobilization drugs and HDAd vectors can trigger auto-expansion of in vivo transduced HSCs resulting in transgene-marking rates that, theoretically, are curative for hemoglobinopathies.

16.
Cureus ; 16(8): e67831, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39323674

RÉSUMÉ

Introduction In emergency situations, airway management is often given priority over other treatment methods. The preferred technique for airway management of unconscious patients is endotracheal intubation, which has become the standard of care. Intubation of the trachea not only enables controlled ventilation even for extended periods and in any position but also allows for the removal of tracheal secretions. Supraglottic airways have several advantages over endotracheal intubation, including faster insertion, less need for neuromuscular blockade, and less hemodynamic instability. They can also be used as a bridge to intubation or as a rescue device when intubation fails or is contraindicated. The aim of this randomized controlled clinical study is to simulate a prehospital emergency/disaster scenario to evaluate and study the feasibility and effectiveness of the use of intubating laryngeal mask airway (ILMA) for onsite airway management from 360 degrees around the patient's head as in such situations, there may be limited or no access behind the head of the victim. Such a scenario can be extrapolated to disaster conditions where the victims may be trapped under the rubble following a building collapse /earthquake or are trapped in a vehicular road traffic/ train accident. It may take substantial time for extrication and evacuation of such patients to a hospital and hence it may be life-saving to provide prompt and early onsite airway management from wherever access is possible around the victim. We believe that the provision of a steel handle integrated with the airway tube may provide an opportunity for successful insertion of the device from 360 degrees around the patient merely by suitably changing the way the handle is gripped, so as to allow a single-handed smooth arc-like movement of the device for insertion, irrespective of the position of the rescuer relative to the patient's head. Objectives Our objective is to study the ease and time of insertion of ILMA, the number of attempts for successful ILMA insertion, and oropharyngeal leak pressure attained from unconventional positions in a supine patient.  Materials and methods This prospective, randomized, observer-blinded controlled trial included 90 patients undergoing elective surgery under general anesthesia. Patients were randomized using a chit and box system for group allocation. Groups were as follows: Group 1 (n=30) - Investigator standing on the back of the head of the patient (0°); Group 2 (n=30) - Investigator standing on the left side facing the patient (120°); Group 3 (n=30) - Investigator standing on the right side facing the patient (240°). Then ease and time of insertion of ILMA, number of attempts for successful ILMA insertion and oropharyngeal leak pressure were noted, and intergroup comparison was done. Conclusion ILMA has proved to be an effective ventilatory device and a suitable conduit for intubation in patients lying in the supine position from a conventional standard position standing behind the head of the patient, as well as non-conventional position, facing the patient at 120° or 240° from the standard position.

17.
Heliyon ; 10(17): e37094, 2024 Sep 15.
Article de Anglais | MEDLINE | ID: mdl-39319143

RÉSUMÉ

Proton-based aqueous electrolytes can be used to achieve high performance electrochromic nanocrystal thin films due to their small ion size. However, acidic aqueous electrolyte systems have not yet been explored in near-infrared (NIR) absorbing plasmonic tungsten oxide nanocrystal films. Here, we demonstrate tungsten suboxide nanorod films with excellent visible and NIR modulation performance in the H+-based aqueous electrolytes, thanks to their mesoporous structure, nanosized domains, and open tunnel structure. Colloidally synthesized WO2.83 nanorods with an average width of 6 nm and length of 48 nm were converted to WO2.90 nanorod film via annealing in air, while still preserving open tunnels. These films exhibit fast switching speed (tc = 0.9 s, tb = 2.1 s), excellent cycling stability over 2500 cycles, wide optical modulation up to ΔT = 53.8 % in the NIR region, and a high coloration efficiency (CE) of 167 cm2 C⁻1 at 1300 nm. Additionally, introducing a thin spacer (25 µm) reduced intrinsic NIR absorption from water, thereby enhancing the NIR modulation properties. These highly performing aqueous proton-electrolytes-based electrochromic devices open new possibilities for implementing visible and NIR electrochromism.

18.
J Plast Reconstr Aesthet Surg ; 98: 112-121, 2024 Aug 16.
Article de Anglais | MEDLINE | ID: mdl-39243713

RÉSUMÉ

Peripheral nerve repair is daily activity for several microsurgeons. Numerous nerve repair techniques are applied, including neurorrhaphy, nerve grafting and nerve transfer, depending on the nature and extent of the injury. However, these techniques become unfeasible when the distal nerve end is not preserved during the peripheral nerve injury or a segment of the muscle is transferred without the nerve supplying it. However, direct muscle neurotization (DMN) achieves muscle reinnervation by suturing the nerve directly into the muscle tissue, without requiring a distal nerve end for coaptation. Despite promising results in the literature, DMN is not widely adopted in clinical practice. Animal models may help in advancing novel therapeutic approaches, due to their anatomic and physiologic similarities to humans. This review highlights the current scientific understanding and recent advancements in DMN as well as the animal models and target muscle that have been used in the past to investigate the basic principles behind this surgical technique. The presented information should aid in establishing the clinical importance of DMN in peripheral nerve injury.

19.
Small ; : e2405586, 2024 Sep 05.
Article de Anglais | MEDLINE | ID: mdl-39235375

RÉSUMÉ

Direct laser writing has gained remarkable popularity by offering architectural control of 3D objects at submicron scales. However, it faces limitations when the fabrication of microstructures comprising multiple materials is desired. The generation processes of multi-material microstructures are often very complex, requiring meticulous alignment, as well as a series of step-and-repeat writing and development of the materials. Here, a novel material system based on multilayers of chemically tailored polymers containing anthraquinone crosslinker units is demonstrated. Upon two-photon excitation, the crosslinkers only require nearby aliphatic C,H units as reaction partners to form a crosslinked network. The desired structure can be written into a solid multi-layered material system, wherein the properties of each material can be designed at the molecular level. In this way, C,H insertion crosslinking (CHic) of the polymers within each layer, along with simultaneous reaction at their interfaces, is performed, leading to the one-step fabrication of multi-material microstructures. A multi-material 3D scaffold with a sixfold symmetry is produced to precisely control the adhesion of cells both concerning surface chemistry and topology. The demonstrated material system shows great promise for the fabrication of 3D microstructures with high precision, intricate geometries and customized functionalities.

20.
Orthop Traumatol Surg Res ; : 103989, 2024 Sep 06.
Article de Anglais | MEDLINE | ID: mdl-39245265

RÉSUMÉ

BACKGROUND: The wedge effect is known to be influenced by the insertion of the proximal femoral intramedullary nail through the fracture line and the large proximal diameter of the nail. However, the impact of the nail insertion angle (NIA) on the wedge effect remains unclear. This study aimed to investigate: (1) how to evaluate the NIA intraoperatively, (2) whether the NIA is associated with the wedge effect, (3) whether the NIA can serve as a reliable predictor of the wedge effect, (4) which factors affect the NIA, and (5) which surgical techniques can prevent the occurrence of the wedge effect associated with the NIA. HYPOTHESIS: We hypothesized that an excessive NIA is related to the wedge effect and that lateral deviation of the entry point is associated with an excessive NIA. PATIENTS AND METHODS: Intraoperative fluoroscopy images of patients who underwent intramedullary nail fixation for intertrochanteric hip fractures between 2013 and 2023 were analyzed. NIA and insertion point distance (IPD) were measured on hip anteroposterior radiographs with the guidewire inserted. Femoral shaft lateralization (FSL) and neck-shaft angle (NSA) were measured on hip anteroposterior radiographs before and after nail insertion; differences in FSL and NSA were calculated. A negative difference in FSL combined with a positive difference in NSA indicated the occurrence of the wedge effect. Pearson's correlation test was used to determine relationships between continuous variables (NIA, FSL, NSA, and IPD). Binary logistic regression analyzed the association between NIA and the wedge effect. Receiver operating characteristic (ROC) curve analysis was used to determine the threshold value of NIA, with predictive performance assessed using the area under the ROC curve (AUC). Other potential factors influencing the wedge effect were also examined. RESULTS: A total of 408 patients were included. The mean NIA was 15.61 ± 4.49 °. Post-nail insertion, the average increase in FSL was 3.20 mm, and the average decrease in NSA was 1.90 °. Pearson's correlation test revealed that NIA was negatively correlated with the difference in FSL (R = 0.565, P < 0.001) and positively correlated with the difference in NSA (R = 0.509, P < 0.001). Binary logistic regression showed a significant correlation between NIA and the wedge effect (P < 0.001). ROC analysis indicated that the AUC for NIA was 0.813, with an optimal cutoff point of 14.85 °. IPD was positively correlated with NIA (R = 0.519, P < 0.001). Unstable fractures were associated with increased lateralization of the femoral shaft after nail insertion (P = 0.003). DISCUSSION: The NIA is positively correlated with the wedge effect in intramedullary nail fixation of intertrochanteric hip fractures. The wedge effect tends to occur when the NIA is >14.85 °, particularly in unstable fractures. Lateral deviation of the entry point is associated with an excessive NIA. Adducting the affected limb, moving the entry point slightly medial and using a medial pusher may help control the NIA to less than 14.85 ° to reduce the wedge effect. LEVEL OF EVIDENCE: III.

SÉLECTION CITATIONS
DÉTAIL DE RECHERCHE