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1.
Mol Cell ; 83(18): 3236-3252.e7, 2023 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-37683647

RESUMO

Nucleosome chains fold and self-associate to form higher-order structures whose internal organization is unknown. Here, cryoelectron tomography (cryo-ET) of native human chromatin reveals intrinsic folding motifs such as (1) non-uniform nucleosome stacking, (2) intermittent parallel and perpendicular orientations of adjacent nucleosome planes, and (3) a regressive nucleosome chain path, which deviates from the direct zigzag topology seen in reconstituted nucleosomal arrays. By examining the self-associated structures, we observed prominent nucleosome stacking in cis and anti-parallel nucleosome interactions, which are consistent with partial nucleosome interdigitation in trans. Histone citrullination strongly inhibits nucleosome stacking and self-association with a modest effect on chromatin folding, whereas the reconstituted arrays undergo a dramatic unfolding into open zigzag chains induced by histone citrullination. This study sheds light on the internal structure of compact chromatin nanoparticles and suggests a mechanism for how epigenetic changes in chromatin folding are retained across both open and condensed forms.


Assuntos
Histonas , Nucleossomos , Humanos , Nucleossomos/genética , Histonas/genética , Citrulinação , Heterocromatina , Cromatina/genética
2.
Trends Biochem Sci ; 49(7): 559-563, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38670884

RESUMO

In January 2024, a targeted conference, 'CellVis2', was held at Scripps Research in La Jolla, USA, the second in a series designed to explore the promise, practices, roadblocks, and prospects of creating, visualizing, sharing, and communicating physical representations of entire biological cells at scales down to the atom.

3.
Biochem Biophys Res Commun ; 717: 150057, 2024 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-38718568

RESUMO

Leptospirosis is a widespread zoonotic infectious disease of human and veterinary concern caused by pathogenic spirochetes of the genus Leptospira. To date, little progress towards understanding leptospiral pathogenesis and identification of virulence factors has been made, which is the main bottleneck for developing effective measures against the disease. Some leptospiral proteins, including LipL32, Lig proteins, LipL45, and LipL21, are being considered as potential virulence factors or vaccine candidates. However, their function remains to be established. LipL45 is the most expressed membrane lipoprotein in leptospires, upregulated when the bacteria are transferred to temperatures resembling the host, expressed during infection, suppressed after culture attenuation, and known to suffer processing in vivo and in vitro, generating fragments. Based on body of evidence, we hypothesized that the LipL45 processing might occur by an auto-cleavage event, deriving two fragments. The results presented here, based on bioinformatics, structure modeling analysis, and experimental data, corroborate that LipL45 processing probably includes a self-catalyzed non-proteolytic event and suggest the participation of LipL45 in cell-surface signaling pathways, as the protein shares structural similarities with bacterial sigma regulators. Our data indicate that LipL45 might play an important role in response to environmental conditions, with possible function in the adaptation to the host.


Assuntos
Leptospira , Lipoproteínas , Lipoproteínas/metabolismo , Lipoproteínas/química , Lipoproteínas/genética , Leptospira/metabolismo , Leptospira/química , Fator sigma/metabolismo , Fator sigma/química , Fator sigma/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Modelos Moleculares , Leptospirose/metabolismo , Leptospirose/microbiologia
4.
Pediatr Blood Cancer ; 71(5): e30933, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38430473

RESUMO

INTRODUCTION: In complex pediatric surgical oncology, surgical planning is contingent upon data gathered from preoperative imaging. Three-dimensional (3D) modeling and printing has been shown to be beneficial for adult presurgical planning, though pediatric literature is less robust. The study reviews our institutional experience with the use of 3D image segmentation and printed models in approaching resection of extracranial solid tumors in children. METHODS: This is a single institutional series from 2021 to 2023. Models were based on computed tomography and magnetic resonance imaging studies, optimized for 3D imaging. The feasibility and creation of the models is reviewed, including specific techniques, software, and printing materials from our institution. Clinical implications for surgical planning are also described, along with detailed preoperative and intraoperative images. RESULTS: 3D modeling and printing was performed for four pediatric patients diagnosed with extracranial solid tumors. Diagnoses included Ewing sarcoma, hepatoblastoma, synovial sarcoma, and osteosarcoma. No intraoperative complications or discrepancies with the preoperative 3D-printed model were noted. No evidence of local recurrence was identified in any patient thus far. CONCLUSION: Our institutional series demonstrates a wide spectrum of clinical application for 3D modeling and printing technology within pediatric surgical oncology. This technology may aid in surgical planning for both resection and reconstruction, can be applied to a diverse breadth of diagnoses, and may potentially augment patient and/or family education about their condition.


Assuntos
Sarcoma de Ewing , Sarcoma Sinovial , Criança , Humanos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/cirurgia , Tomografia Computadorizada por Raios X
5.
Neuroradiology ; 66(3): 443-455, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38183426

RESUMO

BACKGROUND: Optimal lumbar puncture segment selection remains controversial. This study aims to analyze anatomical differences among L3-4, L4-5, and L5-S1 segments across age groups and provide quantitative evidence for optimized selection. METHODS: 80 cases of CT images were collected with patients aged 10-80 years old. Threedimensional models containing L3-S1 vertebrae, dural sac, and nerve roots were reconstructed. Computer simulation determined the optimal puncture angles for the L3-4, L4-5, and L5-S1 segments. The effective dural sac area (ALDS), traversing nerve root area (ATNR), and area of the lumbar inter-laminar space (ALILS) were measured. Puncture efficacy ratio (ALDS/ALILS) and nerve injury risk ratio (ATNR/ALILS) were calculated. Cases were divided into four groups: A (10-20 years), B (21-40 years), C (41-60 years), and D (61-80 years). Statistical analysis was performed using SPSS. RESULTS: 1) ALDS was similar among segments; 2) ATNR was greatest at L5-S1; 3) ALILS was greatest at L5-S1; 4) Puncture efficacy ratio was highest at L3-4 and lowest at L5-S1; 5) Nerve injury risk was highest at L5-S1. In group D, L5-S1 ALDS was larger than L3-4 and L4-5. ALDS decreased after age 40. Age variations were minimal across parameters. CONCLUSION: The comprehensive analysis demonstrated L3-4 as the optimal first-choice segment for ages 10-60 years, conferring maximal efficacy and safety. L5-S1 can serve as an alternative option for ages 61-80 years when upper interspaces narrow. This study provides quantitative imaging evidence supporting age-specific, optimized lumbar puncture segment selection.


Assuntos
Vértebras Lombares , Punção Espinal , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Vértebras Lombares/diagnóstico por imagem , Região Lombossacral , Tomografia Computadorizada por Raios X
6.
Curr Urol Rep ; 26(1): 3, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39305366

RESUMO

PURPOSE OF REVIEW: The application of artificial intelligence (AI) to enhance clinical decision-making in Peyronie's disease (PD) has generated significant interest. This review explores the current landscape of AI in PD evaluation. RECENT FINDINGS: Recent advances in 3D modeling offer a more sophisticated approach to assessing PD deformities; however, the implementation of 3D modeling in clinical practice faces challenges, including the need for specialized equipment and time-consuming data processing, sometimes taking several hours of labor. AI holds promise for overcoming these hurdles through its ability to efficiently process large volumes of data and to perform accurate predictions based on such data. Future integration of AI with 3D modeling techniques could revolutionize PD evaluation by improving patient counseling, surgical planning, and clinical decision-making. Significant gaps in the literature have yet to be addressed, including the absence of robust evidence that incorporating such technology is superior to standard diagnostics.


Assuntos
Inteligência Artificial , Induração Peniana , Induração Peniana/diagnóstico , Humanos , Masculino , Imageamento Tridimensional , Tomada de Decisão Clínica/métodos
7.
Proc Natl Acad Sci U S A ; 118(42)2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34645712

RESUMO

Chromosomes are segmented into domains and compartments, but how these structures are spatially related in three dimensions (3D) is unclear. Here, we developed tools that directly extract 3D information from Hi-C experiments and integrate the data across time. With our "4DHiC" method, we use X chromosome inactivation (XCI) as a model to examine the time evolution of 3D chromosome architecture during large-scale changes in gene expression. Our modeling resulted in several insights. Both A/B and S1/S2 compartments divide the X chromosome into hemisphere-like structures suggestive of a spatial phase-separation. During the XCI, the X chromosome transits through A/B, S1/S2, and megadomain structures by undergoing only partial mixing to assume new structures. Interestingly, when an active X chromosome (Xa) is reorganized into an inactive X chromosome (Xi), original underlying compartment structures are not fully eliminated within the Xi superstructure. Our study affirms slow mixing dynamics in the inner chromosome core and faster dynamics near the surface where escapees reside. Once established, the Xa and Xi resemble glassy polymers where mixing no longer occurs. Finally, Xist RNA molecules initially reside within the A compartment but transition to the interface between the A and B hemispheres and then spread between hemispheres via both surface and core to establish the Xi.


Assuntos
Mamíferos/genética , Cromossomo X , Animais , Inativação do Cromossomo X
8.
Sensors (Basel) ; 24(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38732778

RESUMO

The selection of the optimal methodology for the 3D geometric documentation of cultural heritage is a subject of high concern in contemporary scientific research. As a matter of fact, it requires a multi-source data acquisition process and the fusion of datasets from different sensors. This paper aims to demonstrate the workflow for the proper implementation and integration of geodetic, photogrammetric and laser scanning techniques so that high-quality photorealistic 3D models and other documentation products can be generated for a complicated, large-dimensional architectural monument and its surroundings. As a case study, we present the monitoring of the Mehmet Bey Mosque, which is a landmark in the city of Serres and a significant remaining sample of the Ottoman architecture in Greece. The surveying campaign was conducted in the context of the 2022-2023 annual workshop of the Interdepartmental Program of Postgraduate Studies "Protection Conservation and Restoration of Cultural Monuments" of the Aristotle University of Thessaloniki, and it served as a geometric background for interdisciplinary cooperation and decision-making on the monument restoration process. The results of our study encourage the fusion of terrestrial laser scanning and photogrammetric datasets for the 3D modeling of the mosque, as they supplement each other as regards geometry and texture.

9.
Sensors (Basel) ; 24(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38544257

RESUMO

Dental 3D modeling plays a pivotal role in digital dentistry, offering precise tools for treatment planning, implant placement, and prosthesis customization. Traditional methods rely on physical plaster casts, which pose challenges in storage, accessibility, and accuracy, fueling interest in digitization using 3D computed tomography (CT) imaging. We introduce a method that can reduce both artifacts simultaneously. To validate the proposed method, we carried out CT scan experiments using plaster dental casts created from dental impressions. After the artifact correction, the CT image quality was greatly improved in terms of image uniformity, contrast-to-noise ratio (CNR), and edge sharpness. We examined the correction effects on the accuracy of the 3D models generated from the CT images. As referenced to the 3D models derived from the optical scan data, the root mean square (RMS) errors were reduced by 8.8~71.7% for three dental casts of different sizes and shapes. Our method offers a solution to challenges posed by artifacts in CT scanning of plaster dental casts, leading to enhanced 3D model accuracy. This advancement holds promise for dental professionals seeking precise digital modeling for diverse applications in dentistry.


Assuntos
Artefatos , Tomografia Computadorizada por Raios X , Tomografia Computadorizada de Feixe Cônico/métodos
10.
Int Orthop ; 48(9): 2403-2410, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38767711

RESUMO

PURPOSE: Concurrent use of minus heads with tapered stems in total hip arthroplasty (THA) decreases the prosthetic range of motion (pROM). Three-dimensional preoperative templating can simulate the location of the impingement by taking the hip through a virtual pROM. This enables surgeons to simulate how modifying the type of implant, orientation, and position influences impingement. We hypothesized that CT-based modeling would result in a decrease in the pROM, thereby increasing the risk of impingement when minus heads are used. METHODS: Forty-three patients who underwent robotic-assisted primary THAs were included. Prosthetic head diameter (32/36-mm) and head length (minus/zero/plus) were the predictors. Maximum external rotation at full hip extension and internal rotation at 90° and 100° of flexion prior to prosthetic impingement were the outcome variables. A CT-based preoperative planning software was used for pROM estimation and impingement detection. RESULTS: Significant decreases in pROM were found for both head diameters as the head length decreased and was more pronounced in external rotation during full hip extension (changes of 2.8-3.4° for the 32-mm head and 1.6-2.8° for the 36-mm head (p = 0.00011)). The magnitude of loss in pROM when using a minus head was larger than the gain provided by a plus head in tapered stems (p < 0.0001). CONCLUSION: Head length affects the offset and pROM. When the use of minus heads or smaller heads is indicated, 3D preoperative templating for assessing postoperative pROM and impingement provides surgeons with options to consider alternate surgical plans offering additional assurance and protection from dislocation.


Assuntos
Artroplastia de Quadril , Articulação do Quadril , Prótese de Quadril , Imageamento Tridimensional , Desenho de Prótese , Amplitude de Movimento Articular , Software , Tomografia Computadorizada por Raios X , Humanos , Artroplastia de Quadril/métodos , Masculino , Feminino , Amplitude de Movimento Articular/fisiologia , Pessoa de Meia-Idade , Idoso , Imageamento Tridimensional/métodos , Articulação do Quadril/cirurgia , Articulação do Quadril/fisiopatologia , Articulação do Quadril/diagnóstico por imagem , Procedimentos Cirúrgicos Robóticos/métodos , Cuidados Pré-Operatórios/métodos
11.
J Environ Manage ; 354: 120278, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38354616

RESUMO

The blue carbon ecosystem, including the salt marsh ecosystem, possesses a significant carbon sequestration potential. Therefore, accurately quantifying the carbon storage within such ecosystems is crucial for the adequate accounting of carbon sequestration. The present work chose a Spartina alterniflora ecosystem in the Xiaogan Island (China) as the study area (approximately 11 ha), and employed the Bayesian maximum entropy (BME) approach to assimilate both hard organic carbon (OC) data and soft OC data measured from 2 cm and 10 cm stratified samples. A 3-dimensional model was developed for space-time OC estimation purposes based on the sediment chronology results. The 10-fold BME cross validation results demonstrated a high estimation accuracy, with the R2, RMSE and MAE values equal to 0.8564, 0.1026 % and 0.0748 %, respectively. A noteworthy outcome was the BME-generated carbon storage density maps with 1 m spatial resolution. These maps revealed that the carbon storage density at the top 30 cm sediment depth in the stable zone (with elder stand age of S. alterniflora) was higher than that in the rapid expansion zone, i.e., 71.79 t/ha vs. 69.82 t/ha, respectively. Additionally, the study found that the averaged carbon burial rate and the total carbon storage at the top 30 cm sediment depth across the study area were 266 g C/m2/yr and 781.50 t, respectively. Lastly, the proposed BME-based framework of carbon storage estimation was found to be versatile and applicable to other blue carbon ecosystems. This approach can foster the development of a standardized carbon sink metrological methodology for diverse blue carbon ecosystems.


Assuntos
Ecossistema , Áreas Alagadas , Carbono/análise , Teorema de Bayes , Entropia , Poaceae , China , Sequestro de Carbono
12.
Surg Radiol Anat ; 46(6): 859-869, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38630269

RESUMO

PURPOSE: The purpose of this study is to investigate the morphometric properties of the internal carotid artery (ICA) by measuring the diameters and angles of its segments and exploring variations related to sex and the presence of aneurysms. METHODS: Digital subtraction angiography (DSA) images were utilized from 130 aneurysm patients and 75 non-aneurysm individuals to create 3D ICA models using 3D Slicer software. Segment diameters were measured via Autodesk Meshmixer 3.5.474 and angles were evaluated using ImageJ software. RESULTS: In total, DSA images of 130 aneurysm patients and 75 individuals with normally reported carotid systems were evaluated. It was found that the intracranial aneurysms (IAs) were predominantly formed on the anterior cerebral artery (ACA) in males (%43), whereas in females IAs were frequently localized in the C6 segment (31.7%) and middle cerebral artery (MCA) (30.2%). In the control group, the evaluation of gender differences in segment diameters and angles revealed that males had significantly larger C4 and C5 segment diameters (4.62 vs. 4.32 mm and 4.41 vs. 4.09 mm, respectively) and a greater C6 angle (146.9° vs. 139.7°) compared to females. Comparisons between patients with an aneurysm at the anterior cerebral artery (ACA) and the control group revealed that the ACA group had wider diameters in the C1 (4.88 vs. 4.53 mm), C3 (4.65 vs. 4.4 mm), C5 (4.51 vs. 4.25 mm), and ACA (2.36 vs. 2.06 mm) segments. Additionally, the ACA group had wider angles in the ACA (104.1° vs. 94.1°) and C6 segments (147.7° vs. 143.3°), whereas the control group exhibited wider angles in the middle cerebral artery (MCA) segment (141.5° vs. 135.5°) compared to the ACA aneurysm group. Patients with anterior cerebral artery (ACA) aneurysms exhibited larger diameters in C1, C3, C5, C6, and ACA segments compared to the control group. Additionally, while the control group had larger MCA angle, patients with ACA aneurysms had larger angles in C6 segment and ACA. CONCLUSION: Our results demonstrated that formation of aneurysms is affected by anatomical configuration of the ICA as well as sex characteristics, particularly regarding the ACA and MCA bifurcation angles, which showed associations with aneurysms in the respective branches.


Assuntos
Angiografia Digital , Artéria Carótida Interna , Imageamento Tridimensional , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Feminino , Masculino , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/anatomia & histologia , Pessoa de Meia-Idade , Adulto , Fatores Sexuais , Idoso , Artéria Cerebral Anterior/diagnóstico por imagem , Estudos de Casos e Controles , Variação Anatômica , Angiografia Cerebral
13.
Artigo em Russo | MEDLINE | ID: mdl-38549407

RESUMO

OBJECTIVE: To evaluate mechanical strength of three methods of polymethyl methacrylate skull implant fixation in two experimental models. MATERIAL AND METHODS: The first experiment was performed on a plastic model that was as close as possible to bone in structural characteristics. The second experiment was performed on a biological specimen (a ram's head). We assessed the quality of implant fixation to bone window edges by craniofixes, ties and microscrews and lateral intercortical screws. RESULTS: Craniofixes are feasible for small flat flaps, but not advisable for wide highly curved implants. They are also the most expensive method of fixation. Implant fixation by ties and microscrews is a universal method comparable in price to craniofix. Lateral intercortical fixation is effective both for small flat implants and wide implants with large curvature. However, this method is not always applicable. CONCLUSION: Combined fixation by lateral intercortical screws and ties allows for the most effective fixation while reducing the overall price of consumables.


Assuntos
Polimetil Metacrilato , Titânio , Masculino , Animais , Ovinos , Polimetil Metacrilato/química , Crânio/cirurgia , Próteses e Implantes , Craniotomia/métodos
14.
Proteins ; 91(12): 1871-1878, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37314190

RESUMO

In CASP15, there was a greater emphasis on multimeric modeling than in previous experiments, with assembly structures nearly doubling in number (41 up from 22) since the previous round. CASP15 also included a new estimation of model accuracy (EMA) category in recognition of the importance of objective quality assessment (QA) for quaternary structure models. ModFOLDdock is a multimeric model QA server developed by the McGuffin group at the University of Reading, which brings together a range of single-model, clustering, and deep learning methods to form a consensus of approaches. For CASP15, three variants of ModFOLDdock were developed to optimize for the different facets of the quality estimation problem. The standard ModFOLDdock variant produced predicted scores optimized for positive linear correlations with the observed scores. The ModFOLDdockR variant produced predicted scores optimized for ranking, that is, the top-ranked models have the highest accuracy. In addition, the ModFOLDdockS variant used a quasi-single model approach to score each model on an individual basis. The scores from all three variants achieved strongly positive Pearson correlation coefficients with the CASP observed scores (oligo-lDDT) in excess of 0.70, which were maintained across both homomeric and heteromeric model populations. In addition, at least one of the ModFOLDdock variants was consistently ranked in the top two methods across all three EMA categories. Specifically, for overall global fold prediction accuracy, ModFOLDdock placed second and ModFOLDdockR placed third; for overall interface quality prediction accuracy, ModFOLDdockR, ModFOLDdock, and ModFOLDdockS were placed above all other predictor methods, and ModFOLDdockR and ModFOLDdockS were placed second and third respectively for individual residue confidence scores. The ModFOLDdock server is available at: https://www.reading.ac.uk/bioinf/ModFOLDdock/. ModFOLDdock is also available as part of the MultiFOLD docker package: https://hub.docker.com/r/mcguffin/multifold.


Assuntos
Proteínas , Software , Conformação Proteica , Proteínas/genética , Proteínas/química , Modelos Moleculares , Biologia Computacional
15.
Proteins ; 91(5): 619-633, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36511838

RESUMO

Riboflavin is an essential water-soluble vitamin that needs to be provided through the diet because of the conversion into flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), important cofactors in hundreds of flavoenzymes. The adsorption and distribution of riboflavin is mediated by transmembrane transporters of the SLC52 family, namely RFVT1-3, whose mutations are mainly associated with two diseases, MADD and the Brown-Vialetto-Van Laere syndrome. Interest in RFVTs as pharmacological targets has increased in the last few years due to their overexpression in several cancer cells, which can be exploited both by blocking the uptake of riboflavin into the cancerous cells, and by performing cancer targeted delivery of drugs with a high affinity for RFVTs. In this work, we propose three-dimensional structural models for all three human riboflavin transporters obtained by state-of-the-art artificial intelligence-based methods, which were then further refined with molecular dynamics simulations. Furthermore, two of the most notable mutations concerning RFVT2 and RFVT3 (W31S and N21S, respectively) were investigated studying the interactions between the wild-type and mutated transporters with riboflavin.


Assuntos
Inteligência Artificial , Perda Auditiva Neurossensorial , Humanos , Riboflavina/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Perda Auditiva Neurossensorial/genética , Relação Estrutura-Atividade , Mononucleotídeo de Flavina , Flavina-Adenina Dinucleotídeo/metabolismo
16.
Neurourol Urodyn ; 42(1): 297-302, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36321797

RESUMO

INTRODUCTION: Sacral neuromodulation (SNM) is an effective treatment of urinary and bowel dysfunction, including secondary to neurological disorders. The learning curve for the optimal electrode placement for SNM is steep, expensive, and limited by patient factors such as obesity and previous injuries. We aim to create a patient specific 3-dimensional (3D) model for successful SNM training. MATERIALS AND METHODS: A total of 26 urology residents who had different level of knowledge and experience were enrolled to the 3D SNM training program. The creation of 3D sacrum model has been started with evaluation of real patient computerized tomography images and creation of Digital Imaging and Communications in Medicine files. The segmented anatomic structures from the files then edited and stereolithographic files were generated for 3D-model prints via Mimics© software. The 3D-printed models were used for training and evaluation of participants during the SNM intervention was performed. The evaluation of 3D SNM model training was led by one mentor who is expert on SNM. RESULTS: On the preprinted 3D sacrum model all 26 participants were requested to perform the essential steps to complete a SNM procedure and individual procedure time was recorded. The mean and median scores were 18.8 and 19, respectively according to Likert scores (min 11 max 28). CONCLUSIONS: SNM is increasing in popularity as a treatment option with physicians and patients with refractory symptoms. Few experienced specialists exist, and more effective training methods are needed to tackle the increasing demand, and individual patient anatomy.


Assuntos
Terapia por Estimulação Elétrica , Humanos , Terapia por Estimulação Elétrica/métodos , Sacro/diagnóstico por imagem , Resultado do Tratamento , Tecnologia , Impressão Tridimensional , Tomografia
17.
Arch Insect Biochem Physiol ; 112(1): e21977, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36254855

RESUMO

Juvenile hormone epoxide hydrolase (JHEH) plays an important role in the metabolism of juvenile hormone III (JH III) in insects. To study the role that JHEH plays in female Aedes aegypti JHEH 1, 2, and 3 complementary DNA (cDNAs) were cloned and sequenced. Northern blot analyses show that the three transcripts are expressed in the head thorax, the gut, the ovaries, and the fat body of females. Molecular modeling shows that the enzyme is a homodimer that binds JH III acid (JH IIIA) at the catalytic groove better than JH III. The cDNA of JHEH 1 and 2 are very similar indicating close relationship. Knocking down of jheh 1, 2, and 3 in adult female and larval Ae. aegypti using double-stranded RNA (dsRNA) did not affect egg development or caused adult mortality. Larvae that were fed bacterial cells expressing dsRNA against jheh 1, 2, and 3 grew normally. Treating blood-fed female Ae. aegypti with [12-3 H](10R) JH III and analyzing the metabolites by C18 reversed phase chromatography showed that JHEH preferred substrate is not JH III but JH IIIA. Genomic analysis of jheh 1, 2, and 3 indicate that jheh 1 and 2 are transcribed from a 1.53 kb DNA whereas jheh 3 is transcribed from a 10.9 kb DNA. All three genes are found on chromosome two at distinct locations. JHEH 2 was expressed in bacterial cells and purified by Ni affinity chromatography. Sequencing of the recombinant protein by MS/MS identified JHEH 2 as the expressed recombinant protein.


Assuntos
Aedes , Feminino , Animais , Aedes/genética , Aedes/metabolismo , Espectrometria de Massas em Tandem , Epóxido Hidrolases/genética , Epóxido Hidrolases/química , Epóxido Hidrolases/metabolismo , Larva , Proteínas Recombinantes/metabolismo , DNA Complementar/genética , Clonagem Molecular , Hormônios Juvenis/metabolismo
18.
Arch Insect Biochem Physiol ; 114(2): 1-24, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37526204

RESUMO

Heliothis virescens larval chymotrypsin (GenBank accession number AF43709) was cloned, sequenced and its three dimensional (3D) conformation modeled. The enzyme's transcript was first detected 6 days after larval emergence and the transcript level was shown to fall between larval ecdysis periods. Comparisons between the activities of larval gut chymotrypsin and trypsin shows that chymotrypsin activity is only 16% of the total trypsin activity and the pH optimum of the larval chymotrypsin is between pH 9-10, however the enzyme also exhibited a broad activity between pH 4-6. Injections of AeaTMOF and several shorter analogues into 3rd instar larvae followed by Northern blot analyses showed that although the chymotrypsins activities were inhibited by 60%-80% the transcript level of the sequenced chymotrypsin was not reduced and was similar to controls in which the chymotrypsin activity was not inhibited, indicating that AeaTMOF and its analogues exert a translational control. Based on these observations a putative AeaTMOF receptor (ABCC4) homologous to the Ae. aegypti ABC receptor sequence was found in the H. virescens genome. 3D molecular modeling and docking of the AeaTMOF and several of its analogues to the ABCC4 receptor showed that it can bind AeaTMOF and its analogues as was shown before for the Ae. aegypti receptor.


Assuntos
Quimotripsina , Mariposas , Animais , Quimotripsina/genética , Tripsina/metabolismo , Mariposas/metabolismo , Larva/metabolismo
19.
Arch Insect Biochem Physiol ; 113(3): e22018, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37106507

RESUMO

Aedes aegypti adult and larval blood downregulated chymotrypsin II was cloned, sequenced and its 3D conformation modeled. Cloning of the enzymes from adult and larval guts indicated that both genes sit at the same location on Chromosome 2. Genomic analyses showed that larval and adult genes are the same and both have four exons and three introns that are located on an 8.32 Kb DNA in direction with the Ae. aegypti genome. The adult and larval transcript synthesis is controlled by alternative splicing explaining small difference in the amino acids sequences. Chymotrypsin II that was extracted from guts of sugar-fed and at 48 after blood feeding showed a pH optimum of 4-5 with a broad shoulder of activity from pH 6 to 10. Dot blot analyses show that the enzyme's transcript is downregulated after females take a blood meal and upregulated at 48 h after the blood meal. A Chymotrypsin II transcript was also detected in the larval gut during different times of larval developmental stages, indication that Ae. aegypti chymotrypsin II is synthesized by adults and larval guts. The possibility that JH III and 20HE play an active role in the regulation is discussed.


Assuntos
Aedes , Quimotripsina , Feminino , Animais , Quimotripsina/genética , Aedes/metabolismo , Íntrons , Éxons , Clonagem Molecular , Larva/metabolismo
20.
Childs Nerv Syst ; 39(9): 2449-2457, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37272936

RESUMO

INTRODUCTION: Pediatric cerebrovascular lesions are very rare and include aneurysms, arteriovenous malformations (AVM), and vein of Galen malformations (VOGM). OBJECTIVE: To describe and disseminate a validated, reproducible set of 3D models for optimization of neurosurgical training with respect to pediatric cerebrovascular diseases METHODS: All pediatric cerebrovascular lesions treated at our institution with adequate imaging studies during the study period 2015-2020 were reviewed by the study team. Three major diagnostic groups were identified: aneurysm, AVM, and VOGM. For each group, a case deemed highly illustrative of the core diagnostic and therapeutic principles was selected by the lead and senior investigators for printing (CSG/JM). Files for model reproduction and free distribution were prepared for inclusion as Supplemental Materials. RESULTS: Representative cases included a 7-month-old female with a giant left MCA aneurysm; a 3-day-old male with a large, complex, high-flow, choroidal-type VOGM, supplied from bilateral thalamic, choroidal, and pericallosal perforators, with drainage into a large prosencephalic vein; and a 7-year-old male with a left frontal AVM with one feeding arterial vessel from the anterior cerebral artery and one single draining vein into the superior sagittal sinus CONCLUSION: Pediatric cerebrovascular lesions are representative of rare but important neurosurgical diseases that require creative approaches for training optimization. As these lesions are quite rare, 3D-printed models and open source educational materials may provide a meaningful avenue for impactful clinical teaching with respect to a wide swath of uncommon or unusual neurosurgical diseases.


Assuntos
Malformações Arteriovenosas , Aneurisma Intracraniano , Malformações Arteriovenosas Intracranianas , Malformações da Veia de Galeno , Humanos , Criança , Masculino , Feminino , Lactente , Malformações da Veia de Galeno/cirurgia , Artéria Cerebral Anterior , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Impressão Tridimensional , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/cirurgia
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