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1.
Pediatr Emerg Care ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950383

RESUMO

OBJECTIVES: The aim of this study was to create and validate a 3-dimensional (3D) ultrasound model with normal and abnormal pediatric hip joint anatomy that is comparable to a pediatric hip joint in appearance and anatomy and replicates sonographic characteristics of a pediatric hip joint. METHODS: A 3D rendering of the bone and soft tissue was created from a computed tomography pelvic scan of a pediatric patient. This rendering was modified to include a unilateral joint effusion. The bone was 3D printed with a photopolymer plastic, whereas the soft tissue was cast with a silicone mixture in a 3D-printed mold. The effusion was simulated by injecting saline into the soft tissue cavity surrounding the bone. The ultrasound model was validated by pediatric point-of-care ultrasonographers at an international pediatric ultrasound conference. RESULTS: A pediatric hip ultrasound model was developed that simulates both normal and abnormal pediatric hip joint anatomy, each with an appropriately sized, measurable joint effusion. Validation by pediatric point-of-care ultrasonographers showed that the key aspects of a normal pediatric hip joint (femoral physis, sloped femoral neck, and adequate soft tissue) with an identifiable and measurable effusion were included in the ultrasound model. CONCLUSIONS: In this study, we successfully created a cost-effective, reusable, and reproducible 3D pediatric hip ultrasound model. The majority of pediatric point-of-care ultrasonographers who evaluated the model agreed that this model is comparable to a pediatric patient for the purpose of teaching ultrasound skills and joint space measurement.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39002850

RESUMO

BACKGROUND: Minibeam radiation therapy (MBRT) is characterized by the delivery of submillimeter wide regions of high "peak" and low "valley" doses throughout a tumor. Preclinical studies have long shown the promise of this technique, and we report here the first clinical implementation of MBRT. METHODS: A clinical orthovoltage unit was commissioned for MBRT patient treatments using 3, 4, 5, 8, and 10 cm diameter cones. The 180 kVp output was spatially separated into minibeams using a tungsten collimator with 0.5 mm wide slits spaced 1.1 mm on center. Percentage depth dose (PDD) measurements were obtained using film dosimetry and plastic water for both peak and valley doses. PDDs were measured on central axis for offsets of 0, 0.5, and 1 cm. The peak-to-valley ratio (PVR) was calculated at each depth for all cones and offsets. To mitigate the effects of patient motion on delivered dose, patient-specific 3D printed collimator holders were created. These conformed to the unique anatomy of each patient and affixed the tungsten collimator directly to the body. Two patients were treated with MBRT, both received 2 fractions. RESULTS: Peak PDDs decreased gradually with depth. Valley PDDs initially increased slightly with depth, then decreased gradually beyond 2 cm. PVRs were highest at the surface for smaller cone sizes and offsets. In vivo film dosimetry confirmed a distinct delineation of peak and valley doses on both patients treated with MBRT with no dose blurring. Both patients experienced prompt improvement in symptoms and tumor response. CONCLUSIONS: We report commissioning results, treatment processes, and the first two patients treated with MBRT using a clinical orthovoltage unit. While demonstrating feasibility of this approach is a crucial first step toward wider translation, clinical trials are needed to further establish safety and efficacy.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38981580

RESUMO

BACKGROUND: Virtual surgical planning (VSP) for composite microvascular free flaps has become standard of care for oncologic head and neck reconstruction. Controversy remains as to the use of three-dimensional (3D)-printed patient-specific titanium implants (PSIs) versus hand-bent stock reconstruction plates. Proponents of PSIs cite improved surgical accuracy, reduced operative times, and improved clinical outcomes. Detractors purport increased cost associated with PSIs and presumed equivalent accuracy with less expensive stock plates. PURPOSE: The study purpose was to measure and compare the 3D-volumetric accuracy of PSI versus stock reconstruction plates among subjects undergoing VSP-guided mandibular fibular free flap reconstruction. STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study of subjects undergoing VSP-guided fibular free flap reconstructions at Mayo Clinic between 2016 and 2023 was performed. Subjects were excluded for non-VSP guidance, midfacial reconstruction, nonfibular free flaps, and lack of requisite study variables. PREDICTOR VARIABLE: The primary predictor was the type of reconstruction plate utilized (PSI vs stock plate). MAIN OUTCOME VARIABLE: The main outcome was volumetric surgical accuracy of the final reconstruction compared to the preoperative surgical plan by root mean square error (RMSE) calculation. Lower RMSE values indicated a higher surgical accuracy. COVARIATES: Covariates included age, sex, race, smoking status, American Society of Anesthesiologists (ASA) Physical Status Classification System, Charlson Comorbidity Index, preoperative diagnosis, and number of fibular segments. ANALYSES: Differences in surgical accuracy were assessed between preoperative and postoperative segmented scans using volumetric overlays from which RMSE values were calculated. Univariate and multivariate modeling of plate type to RMSE calculation was performed. Statistical significance set to P < .05. RESULTS: Total of 130 subjects were identified, 105 PSI and 25 stock plates. Calculated mean RMSE in millimeters (mm) for stock plates was 1.46 (standard deviation: 0.33) and 1.15 (standard deviation: 0.36) for PSIs. Univariate modeling demonstrated a statistically significant difference in RMSE of 0.31 (95% confidence interval: 0.16-0.47) (P < .001) equating to a 21.2% (P < .001) improved volumetric surgical accuracy for PSIs. The association of improved volumetric accuracy with PSIs has been maintained in all multivariate models controlling for confounding. CONCLUSION AND RELEVANCE: In modern era VSP-guided head and neck fibular free flap reconstruction, patient-specific 3D-printed titanium implants confer a statistically significant improvement in volumetric surgical accuracy over stock reconstruction plates.

4.
Neuroinformatics ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38867116

RESUMO

Photogrammetry scans has directed attention to the development of advanced camera systems to improve the creation of three-dimensional (3D) models, especially for educational and medical-related purposes. This could be a potential cost-effective method for neuroanatomy education, especially when access to laboratory-based learning is limited. The aim of this study was to describe a new photogrammetry system based on a 5 Digital Single-Lens Reflex (DSLR) cameras setup to optimize accuracy of neuroanatomical 3D models. One formalin-fixed brain and specimen and one dry skull were used for dissections and scanning using the photogrammetry technique. After each dissection, the specimens were placed inside a new MedCreator® scanner (MedReality, Thyng, Chicago, IL) to be scanned with the final 3D model being displayed on SketchFab® (Epic, Cary, NC) and MedReality® platforms. The scanner consisted of 5 cameras arranged vertically facing the specimen, which was positioned on a platform in the center of the scanner. The new multi-camera system contains automated software packages, which allowed for quick rendering and creation of a high-quality 3D models. Following uploading the 3D models to the SketchFab® and MedReality® platforms for display, the models can be freely manipulated in various angles and magnifications in any devices free of charge for users. Therefore, photogrammetry scans with this new multi-camera system have the potential to enhance the accuracy and resolution of the 3D models, along with shortening creation time of the models. This system can serve as an important tool to optimize neuroanatomy education and ultimately, improve patient outcomes.

7.
J Neurosurg ; : 1-12, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579353

RESUMO

OBJECTIVE: The objective of this study was to describe the quantitative features of intraoperative electromyographic recordings obtained from cranial nerve III, IV, and VI neuromonitoring using 25-mm intraorbital electrodes, in the larger context of demonstrating the practicality of this technique during neurosurgical cases. METHODS: A 25-mm-long shaft-insulated intraorbital needle electrode is routinely used at the authors' institution for extraocular muscle (EOM) electromyographic monitoring of the inferior rectus, superior oblique, and/or lateral rectus muscles when their function is at risk. Cases monitored between January 1, 2021, and December 31, 2022, were reviewed for patient demographics, tumor location and pathology, EOMs monitored, pre- and postoperative examination, and complications from electrode placement. Compound muscle action potentials on triggered electromyography, as well as neurotonic discharges on free-run electromyography, were described quantitatively. RESULTS: There were 141 cases in 139 patients reviewed during the 24-month time span, with 278 EOMs monitored (inferior rectus/superior oblique/lateral rectus muscles 68/68/142). Triggered electromyography yielded biphasic or triphasic compound muscle action potentials from EOMs with a mean onset latency of 1.51 msec (range 0.94-3.22 msec), mean maximal peak-to-trough amplitude of 1073.93 µV (range 76.75-7796.29 µV), and high specificity for the channel in nearly all cases. Neurotonic discharges were recorded in 30 of the 278 EOMs (with all 3 muscles represented) and associated with a greater incidence of new or worsened ophthalmoparesis (OR 4.62, 95% CI 1.3-16.4). There were 2 cases of small periorbital ecchymosis attributed to needle placement; additionally, 1 case of needle-related intraorbital hematoma occurred after the review period. CONCLUSIONS: The 25-mm shaft-insulated intraorbital electrode facilitates robust and consistent electromyographic recordings of EOMs that are advantageous over existing techniques. Combined with the relative ease of needle placement and low rate of complications, the technique is practical for neuromonitoring during craniotomies.

8.
Radiother Oncol ; 195: 110260, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38548114

RESUMO

OBJECTIVES: Metastasis-directed stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). We assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. METHODS: Spine SBRT treatments with imaging follow-up were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, delivering 20-24 Gy in 1 fraction to the gross tumor volume (GTV) and 16 Gy to the low dose volume (or 27-36 Gy and 21-24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. RESULTS: 522 eligible spine SBRT treatments (68 % single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95 % confidence interval: 34.3-54.4). The cumulative incidence of local failure was 10.5 % (7.4-13.4) at 1 year and 16.3 % (12.6-19.9) at 2 years. Local control was maximized at 15.3 Gy minimum dose for single-fraction treatment (HR = 0.31, 95 % CI: 0.17 - 0.56, p < 0.0001) and confirmed via multivariable analyses. Cumulative incidence of local failure was 6.1 % (2.6-9.4) vs. 14.2 % (8.3-19.8) at 1 year using this cut-off, with comparable findings for minimum 14 Gy. Additionally, epidural and soft tissue involvement were predictive of local failure (HR = 1.77 and 2.30). CONCLUSIONS: Spine SBRT offers favorable local control; however, minimum dose to the GTV has a strong association with local control. Achieving GTV minimum dose of 14-15.3 Gy with single fraction SBRT is recommended whenever possible.


Assuntos
Radiocirurgia , Dosagem Radioterapêutica , Neoplasias da Coluna Vertebral , Humanos , Radiocirurgia/métodos , Radiocirurgia/efeitos adversos , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/cirurgia , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Idoso de 80 Anos ou mais , Adulto , Falha de Tratamento , Estudos Retrospectivos , Carga Tumoral
9.
Elife ; 122024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506902

RESUMO

Age-related muscle wasting and dysfunction render the elderly population vulnerable and incapacitated, while underlying mechanisms are poorly understood. Here, we implicate the CERS1 enzyme of the de novo sphingolipid synthesis pathway in the pathogenesis of age-related skeletal muscle impairment. In humans, CERS1 abundance declines with aging in skeletal muscle cells and, correlates with biological pathways involved in muscle function and myogenesis. Furthermore, CERS1 is upregulated during myogenic differentiation. Pharmacological or genetic inhibition of CERS1 in aged mice blunts myogenesis and deteriorates aged skeletal muscle mass and function, which is associated with the occurrence of morphological features typical of inflammation and fibrosis. Ablation of the CERS1 orthologue lagr-1 in Caenorhabditis elegans similarly exacerbates the age-associated decline in muscle function and integrity. We discover genetic variants reducing CERS1 expression in human skeletal muscle and Mendelian randomization analysis in the UK biobank cohort shows that these variants reduce muscle grip strength and overall health. In summary, our findings link age-related impairments in muscle function to a reduction in CERS1, thereby underlining the importance of the sphingolipid biosynthesis pathway in age-related muscle homeostasis.


Assuntos
Fibras Musculares Esqueléticas , Músculo Esquelético , Idoso , Humanos , Animais , Camundongos , Envelhecimento , Caenorhabditis elegans/genética , Esfingolipídeos
11.
Radiographics ; 44(2): e230075, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38271257

RESUMO

Lymphatic flow and anatomy can be challenging to study, owing to variable lymphatic anatomy in patients with diverse primary or secondary lymphatic pathologic conditions and the fact that lymphatic imaging is rarely performed in healthy individuals. The primary components of the lymphatic system outside the head and neck are the peripheral, retroperitoneal, mesenteric, hepatic, and pulmonary lymphatic systems and the thoracic duct. Multiple techniques have been developed for imaging components of the lymphatic system over the past century, with trade-offs in spatial, temporal, and contrast resolution; invasiveness; exposure to ionizing radiation; and the ability to obtain information on dynamic lymphatic flow. More recently, dynamic contrast-enhanced (DCE) MR lymphangiography (MRL) has emerged as a valuable tool for imaging both lymphatic flow and anatomy in a variety of congenital and acquired primary or secondary lymphatic disorders. The authors provide a brief overview of lymphatic physiology, anatomy, and imaging techniques. Next, an overview of DCE MRL and the development of an MRL practice and workflow in a hybrid interventional MRI suite incorporating cart-based in-room US is provided, with an emphasis on multidisciplinary collaboration. The spectrum of congenital and acquired lymphatic disorders encountered early in an MRL practice is provided, with emphasis on the diversity of imaging findings and how DCE MRL can aid in diagnosis and treatment of these patients. Methods such as DCE MRL for assessing the hepatic and mesenteric lymphatic systems and emerging technologies that may further expand DCE MRL use such as three-dimensional printing are introduced. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.


Assuntos
Doenças Linfáticas , Linfografia , Humanos , Linfografia/métodos , Meios de Contraste , Imageamento por Ressonância Magnética/métodos , Doenças Linfáticas/diagnóstico por imagem , Doenças Linfáticas/patologia , Sistema Linfático/patologia
12.
Neuroradiology ; 66(3): 417-425, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38197949

RESUMO

PURPOSE: Although CT-guided biopsies of the calvarium, skull base, and orbit are commonly performed, the best approaches, efficacy, and safety of such procedures remain scantly described in the literature. This retrospective review of percutaneous biopsies illustrates several approaches to challenging biopsy targets and provides a review of procedural planning considerations and histopathologic yield. METHODS: A retrospective review of CT-guided biopsies of the skull base, calvarium, and orbit between 1/1/2010 and 10/30/2020 was conducted. Patient demographics and procedural factors were recorded, including lesion size and location, biopsy approach, and needle gauge. Outcomes were also noted, including CT dose length product, complications, and histopathologic yield. RESULTS: Sixty-one CT-guided biopsies were included in the final analysis: 34 skull base, 23 calvarial, and 4 orbital lesions. The initial diagnostic yield was 32/34 (94%) for skull base lesions, with one false-negative and one non-diagnostic sample. Twenty-one of twenty-three (91%) biopsies in the calvarium were initially diagnostic, with one false-negative and one non-diagnostic sample. In the orbit, 4/4 biopsies were diagnostic. The total complication rate for the cohort was 4/61 (6.6%). Three complications were reported in skull base procedures (2 immediate and 1 delayed). A single complication was reported in a calvarial biopsy, and no complications were reported in orbital biopsies. CONCLUSION: Percutaneous CT-guided core needle biopsies can be performed safely and with a high diagnostic yield for lesions in the skull base, calvarium, and orbit.


Assuntos
Cabeça , Órbita , Humanos , Órbita/diagnóstico por imagem , Base do Crânio/diagnóstico por imagem , Biópsia Guiada por Imagem/métodos , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos
13.
Anat Sci Educ ; 17(1): 39-46, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37622671

RESUMO

The 3D stereoscopic technique consists in providing the illusional perception of depth of a given object using two different images mimicking how the right and left eyes capture the object. Both images are slightly different and when overlapped gives a three-dimensional (3D) experience. Considering the limitations for establishing surgical laboratories and dissections courses in some educational institutions, techniques such as stereoscopy and photogrammetry seem to play an important role in neuroanatomy and neurosurgical education. The aim of this study was to describe how to combine and set up realistic models acquired with photogrammetry scans in 3D stereoscopic projections. Three donors, one dry skull, embalmed brain and head, were scanned using photogrammetry. The software used for displaying the final realistic 3D models (Blender, Amsterdam, the Netherlands) is a free software and allows stereoscopic projection without compromising the interactivity of each model. By default, the model was exported and immediately displayed as a red cyan 3D mode. The 3D projector used in the manuscript required a side-by-side 3D mode which was set up with simple commands on the software. The final stereoscopy projection offered depth perception and a visualization in 360° of each donor; this perception was noted especially when visualizing donors with different cavities and fossae. The combination of 3D techniques is of paramount importance for neuroanatomy education. Stereoscopic projections could provide a valuable tool for neuroanatomy instruction directed at clinical trainees and could be especially useful when access to laboratory-based learning is limited.


Assuntos
Anatomia , Imageamento Tridimensional , Anatomia/educação , Software , Fotogrametria , Neuroanatomia/educação
14.
Aust N Z J Obstet Gynaecol ; 64(1): 77-79, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37702257

RESUMO

Monitoring the fetal heartbeat underpins assessment of fetal wellbeing in labour. Although commonly employed in clinical practice, shortcomings remain. A recent review of clinical practice guidelines highlights the variation in definitions of the fetal heart rate that will lead to differences in interpretation. Will intrapartum care be improved by greater consensus around clinical practice guidelines through rationalisation or refinement of guidelines, or will the future see this technique replaced by more accurate forms of fetal monitoring?


Assuntos
Cardiotocografia , Trabalho de Parto , Gravidez , Feminino , Humanos , Cardiotocografia/métodos , Determinação da Frequência Cardíaca , Monitorização Fetal/métodos , Previsões , Frequência Cardíaca Fetal
15.
BMC Psychiatry ; 23(1): 919, 2023 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062406

RESUMO

BACKGROUND: Individual placement and support (IPS) is an evidence-based practice (EBP) designed to help people with severe mental illness re-enter the labour market. Implementing an IPS program within a new context (e.g., primary health care setting) to support populations that are complex and multi-barriered presents a set of unique challenges and considerations. This paper provides community-based perspectives that identify implementation strengths and challenges and highlights potential strategies aimed at addressing emergent barriers. METHODS: A case study was conducted across three community health centres in British Columbia (BC), Canada, where a novel IPS program was embedded within primary care services. Data collection consisted of open-ended surveys and focus groups with service providers directly involved in program implementation and their associated clinical and managerial support teams (n = 15). Using the updated Consolidated Framework for Implementation Research (CFIR) as a guide, we performed deductive thematic analysis to identify key areas impacting IPS implementation. RESULTS: Integration with existing health care systems and primary health care teams and support from leadership across all levels were identified as both key facilitators and barriers to implementation. Facilitators and barriers were identified across all domains, with those within innovation and process most easily addressed. Four cross-cutting themes emerged for promoting more integrated and sustainable program implementation: investing in pre-implementation activities, supporting a dynamic and flexible program, building from community experiences, and developing a system for shared knowledge. CONCLUSIONS: Implementing an IPS program embedded within primary health care settings is complex and requires extensive planning and consultation with community-based service providers and decision-makers to achieve full integration. Future practice and policy decisions aimed at supporting employment and well-being should be made in collaboration with communities.


Assuntos
Atenção à Saúde , Emprego , Adulto , Humanos , Colúmbia Britânica , Grupos Focais , Atenção Primária à Saúde
16.
J Clin Med ; 12(24)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38137599

RESUMO

Hepatocellular carcinoma (HCC), constituting the predominant manifestation of liver cancer, stands as a formidable medical challenge. The prognosis subsequent to surgical intervention, particularly for individuals presenting with a solitary tumor, relies heavily on the degree of invasiveness. The decision-making process surrounding therapeutic modalities in such cases assumes paramount importance. This case report illuminates a rather unusual clinical scenario. Here, we encounter a patient who, following a disease-free interval, manifested an atypical presentation of HCC, specifically, a solitary cardiac metastasis. The temporal interval of remission adds an additional layer of complexity to the case. Through a multidisciplinary planning process, the decision was made for surgical removal of the metastatic tumor.

17.
Elife ; 122023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38149844

RESUMO

Insulin resistance (IR) is a complex metabolic disorder that underlies several human diseases, including type 2 diabetes and cardiovascular disease. Despite extensive research, the precise mechanisms underlying IR development remain poorly understood. Previously we showed that deficiency of coenzyme Q (CoQ) is necessary and sufficient for IR in adipocytes and skeletal muscle (Fazakerley et al., 2018). Here, we provide new insights into the mechanistic connections between cellular alterations associated with IR, including increased ceramides, CoQ deficiency, mitochondrial dysfunction, and oxidative stress. We demonstrate that elevated levels of ceramide in the mitochondria of skeletal muscle cells result in CoQ depletion and loss of mitochondrial respiratory chain components, leading to mitochondrial dysfunction and IR. Further, decreasing mitochondrial ceramide levels in vitro and in animal models (mice, C57BL/6J) (under chow and high-fat diet) increased CoQ levels and was protective against IR. CoQ supplementation also rescued ceramide-associated IR. Examination of the mitochondrial proteome from human muscle biopsies revealed a strong correlation between the respirasome system and mitochondrial ceramide as key determinants of insulin sensitivity. Our findings highlight the mitochondrial ceramide-CoQ-respiratory chain nexus as a potential foundation of an IR pathway that may also play a critical role in other conditions associated with ceramide accumulation and mitochondrial dysfunction, such as heart failure, cancer, and aging. These insights may have important clinical implications for the development of novel therapeutic strategies for the treatment of IR and related metabolic disorders.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Doenças Mitocondriais , Humanos , Camundongos , Animais , Ubiquinona , Transporte de Elétrons , Diabetes Mellitus Tipo 2/metabolismo , Ceramidas/metabolismo , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Doenças Mitocondriais/patologia
18.
Cancer Immunol Immunother ; 72(12): 4001-4014, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37973660

RESUMO

BACKGROUND: Regulation of alternative splicing is a new therapeutic approach in cancer. The programmed cell death receptor 1 (PD-1) is an immunoinhibitory receptor expressed on immune cells that binds to its ligands, PD-L1 and PD-L2 expressed by cancer cells forming a dominant immune checkpoint pathway in the tumour microenvironment. Targeting this pathway using blocking antibodies (nivolumab and pembrolizumab) is the mainstay of anti-cancer immunotherapies, restoring the function of exhausted T cells. PD-1 is alternatively spliced to form isoforms that are either transmembrane signalling receptors (flPD1) that mediate T cell death by binding to the ligand, PD-L1 or an alternatively spliced, soluble, variant that lacks the transmembrane domain. METHODS: We used PCR and western blotting on primary peripheral blood mononuclear cells (PBMCs) and Jurkat T cells, IL-2 ELISA, flow cytometry, co-culture of melanoma and cholangiocarcinoma cells, and bioinformatics analysis and molecular cloning to examine the mechanism of splicing of PD1 and its consequence. RESULTS: The soluble form of PD-1, generated by skipping exon 3 (∆Ex3PD1), was endogenously expressed in PBMCs and T cells and prevents cancer cell-mediated T cell repression. Multiple binding sites of SRSF1 are adjacent to PD-1 exon 3 splicing sites. Overexpression of phosphomimic SRSF1 resulted in preferential expression of flPD1. Inhibition of SRSF1 phosphorylation both by SRPK1 shRNA knockdown and by a selective inhibitor, SPHINX31, resulted in a switch in splicing to ∆Ex3PD1. Cholangiocarcinoma cell-mediated repression of T cell IL-2 expression was reversed by SPHINX31 (equivalent to pembrolizumab). CONCLUSIONS: These results indicate that switching of the splicing decision from flPD1 to ∆Ex3PD1 by targeting SRPK1 could represent a potential novel mechanism of immune checkpoint inhibition in cancer.


Assuntos
Processamento Alternativo , Colangiocarcinoma , Humanos , Fosforilação , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Proteínas Serina-Treonina Quinases/genética , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Arginina/genética , Arginina/metabolismo , Serina/química , Serina/genética , Serina/metabolismo , Exaustão das Células T , Interleucina-2/genética , Leucócitos Mononucleares/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Imunoterapia
19.
Insects ; 14(11)2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37999068

RESUMO

Vegetation connectivity is an essential aspect of the habitat complexity that impacts species interactions at local scales. However, agricultural intensification reduces connectivity in agroforestry systems, including coffee agroecosystems, which may hinder the movement of natural enemies and reduce the ecosystem services that they provide. Ants play an important role in regulating the coffee berry borer (CBB), which is the most damaging coffee pest. For arboreal ant communities, the connections between trees are important structures that facilitate ant mobility, resource recruitment, foraging success, and pest control ability. To better understand how connectivity impacts arboreal ants in coffee agroecosystems, we conducted an experiment to assess the impact of artificial (string) and naturally occurring vegetation (vines, leaves, branches) connectivity on Azteca sericeasur behavior on coffee plants. We compared ant activity, resource recruitment, and CBB removal rates across three connectivity treatments connecting coffee plants to A. sericeasur nest trees: vegetation connectivity, string, and control (not connected) treatments. We found higher rates of ant activity, resource recruitment, and CBB removal on plants with naturally occurring vegetation connections to A. sericeasur nest trees. Artificial connectivity (string) increased the rates of resource recruitment and CBB removal but to a lesser extent than vegetation connectivity. Moreover, vegetation connectivity buffered reductions in ant activity with distance from the ant nest tree. These results reinforce how habitat complexity in the form of vegetation connectivity impacts interspecific interactions at the local scale. Our results also suggest that leaving some degree of vegetation connectivity between coffee plants and shade trees can promote ant-mediated biological pest control in coffee systems.

20.
3D Print Med ; 9(1): 33, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38008795

RESUMO

BACKGROUND: Medical three dimensional (3D) printing is performed for neurosurgical and otolaryngologic conditions, but without evidence-based guidance on clinical appropriateness. A writing group composed of the Radiological Society of North America (RSNA) Special Interest Group on 3D Printing (SIG) provides appropriateness recommendations for neurologic 3D printing conditions. METHODS: A structured literature search was conducted to identify all relevant articles using 3D printing technology associated with neurologic and otolaryngologic conditions. Each study was vetted by the authors and strength of evidence was assessed according to published guidelines. RESULTS: Evidence-based recommendations for when 3D printing is appropriate are provided for diseases of the calvaria and skull base, brain tumors and cerebrovascular disease. Recommendations are provided in accordance with strength of evidence of publications corresponding to each neurologic condition combined with expert opinion from members of the 3D printing SIG. CONCLUSIONS: This consensus guidance document, created by the members of the 3D printing SIG, provides a reference for clinical standards of 3D printing for neurologic conditions.

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