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1.
Bone Joint J ; 106-B(6): 632-638, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38821510

RESUMO

Aims: Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods: A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 105 colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results: The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log10 (95%) and 1.5-log10 (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 103 vs 7.0 × 104; p = 0.022; 3.6 × 103 vs 1.0 × 105; p = 0.007, respectively) at POD 21. There was a significant 1.6-log10 (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 100 vs 4.7 × 101, respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion: In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections.


Assuntos
Antibacterianos , Sulfato de Cálcio , Modelos Animais de Doenças , Infecções Relacionadas à Prótese , Infecções Estafilocócicas , Vancomicina , Animais , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Relacionadas à Prótese/microbiologia , Camundongos , Vancomicina/administração & dosagem , Antibacterianos/administração & dosagem , Infecções Estafilocócicas/prevenção & controle , Carga Bacteriana/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Distribuição Aleatória , Prótese do Joelho/efeitos adversos , Feminino
3.
Expert Rev Anticancer Ther ; 24(5): 253-261, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38594892

RESUMO

INTRODUCTION: The use of immune checkpoint inhibitors (ICI) targeting the PD-1/PD-L1 pathway has changed the landscape in the treatment of triple negative breast cancer (TNBC). The ICI pembrolizumab in combination with chemotherapy now forms a standard of care for the treatment of advanced PD-L1 positive TNBC and as part of neoadjuvant therapy for high-risk early-stage disease. Evidence in this space is rapidly advancing. AREAS COVERED: This review aims to highlight the evolving role of immunotherapy in TNBC management and to discuss current challenges. The studies in this review were searched from PubMed and ClinicalTrials.gov. EXPERT OPINION: The KEYNOTE-522 trial demonstrated that the addition of peri-operative pembrolizumab to neoadjuvant chemotherapy improves patient outcomes in early-stage TNBC. However, critical questions remain including how to select which patients truly gain benefit from the addition of pembrolizumab; the optimal duration of therapy, and the optimal adjuvant therapy depending on pathologic response.


Assuntos
Anticorpos Monoclonais Humanizados , Inibidores de Checkpoint Imunológico , Terapia Neoadjuvante , Receptor de Morte Celular Programada 1 , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Feminino , Terapia Neoadjuvante/métodos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Estadiamento de Neoplasias , Imunoterapia/métodos , Antígeno B7-H1/antagonistas & inibidores , Seleção de Pacientes , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/farmacologia , Quimioterapia Adjuvante/métodos
4.
Genetics ; 227(2)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38626297

RESUMO

Giardia is a prevalent single-celled microaerophilic intestinal parasite causing diarrheal disease and significantly impacting global health. Double diploid (essentially tetraploid) Giardia trophozoites have presented a formidable challenge to the development of molecular genetic tools to interrogate gene function. High sequence divergence and the high percentage of hypothetical proteins lacking homology to proteins in other eukaryotes have limited our understanding of Giardia protein function, slowing drug target validation and development. For more than 25 years, Giardia A and B assemblages have been readily amenable to transfection with plasmids or linear DNA templates. Here, we highlight the utility and power of genetic approaches developed to assess protein function in Giardia, with particular emphasis on the more recent clustered regularly interspaced palindromic repeats/Cas9-based methods for knockdowns and knockouts. Robust and reliable molecular genetic approaches are fundamental toward the interrogation of Giardia protein function and evaluation of druggable targets. New genetic approaches tailored for the double diploid Giardia are imperative for understanding Giardia's unique biology and pathogenesis.


Assuntos
Giardia , Giardíase , Giardia/genética , Giardia/patogenicidade , Giardíase/parasitologia , Giardíase/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Humanos , Sistemas CRISPR-Cas , Animais
5.
Cancers (Basel) ; 16(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38610956

RESUMO

A multidisciplinary approach to the management of tongue cancer is vital for achieving optimal patient outcomes. Nursing and allied health professionals play essential roles within the team. We developed symposia comprising a series of online lectures offering a detailed perspective on the role each discipline and consumer perspective has in the management of patients with tongue cancer. The topics, including epidemiology and prevention, diagnosis, treatment planning, surgery, adjuvant care, and the management of recurrent or metastatic disease, were thoroughly examined. The symposia highlighted the significance of fostering collaboration and continuous learning through a multidisciplinary approach. This initiative should be relevant to healthcare professionals, researchers, and policymakers striving to enhance patient outcomes in tongue cancer care through innovative collaboration.

6.
Radiol Cardiothorac Imaging ; 6(2): e230182, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38602469

RESUMO

Fetal cardiac MRI using Doppler US gating is an emerging technique to support prenatal diagnosis of congenital heart disease and other cardiovascular abnormalities. Analogous to postnatal electrocardiographically gated cardiac MRI, this technique enables directly gated MRI of the fetal heart throughout the cardiac cycle, allowing for immediate data reconstruction and review of image quality. This review outlines the technical principles and challenges of cardiac MRI with Doppler US gating, such as loss of gating signal due to fetal movement. A practical workflow of patient preparation for the use of Doppler US-gated fetal cardiac MRI in clinical routine is provided. Currently applied MRI sequences (ie, cine or four-dimensional flow imaging), with special consideration of technical adaptations to the fetal heart, are summarized. The authors provide a literature review on the clinical benefits of Doppler US-gated fetal cardiac MRI for gaining additional diagnostic information on cardiovascular malformations and fetal hemodynamics. Finally, future perspectives of Doppler US-gated fetal cardiac MRI and further technical developments to reduce acquisition times and eliminate sources of artifacts are discussed. Keywords: MR Fetal, Ultrasound Doppler, Cardiac, Heart, Congenital, Obstetrics, Fetus Supplemental material is available for this article. © RSNA, 2024.


Assuntos
Imageamento por Ressonância Magnética , Cuidado Pré-Natal , Feminino , Gravidez , Humanos , Radiografia , Coração Fetal/diagnóstico por imagem , Tecnologia
7.
Front Cardiovasc Med ; 11: 1323443, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38410246

RESUMO

Purpose: This study aims to evaluate deep learning (DL) denoising reconstructions for image quality improvement of Doppler ultrasound (DUS)-gated fetal cardiac MRI in congenital heart disease (CHD). Methods: Twenty-five fetuses with CHD (mean gestational age: 35 ± 1 weeks) underwent fetal cardiac MRI at 3T. Cine imaging was acquired using a balanced steady-state free precession (bSSFP) sequence with Doppler ultrasound gating. Images were reconstructed using both compressed sensing (bSSFP CS) and a pre-trained convolutional neural network trained for DL denoising (bSSFP DL). Images were compared qualitatively based on a 5-point Likert scale (from 1 = non-diagnostic to 5 = excellent) and quantitatively by calculating the apparent signal-to-noise ratio (aSNR) and contrast-to-noise ratio (aCNR). Diagnostic confidence was assessed for the atria, ventricles, foramen ovale, valves, great vessels, aortic arch, and pulmonary veins. Results: Fetal cardiac cine MRI was successful in 23 fetuses (92%), with two studies excluded due to extensive fetal motion. The image quality of bSSFP DL cine reconstructions was rated superior to standard bSSFP CS cine images in terms of contrast [3 (interquartile range: 2-4) vs. 5 (4-5), P < 0.001] and endocardial edge definition [3 (2-4) vs. 4 (4-5), P < 0.001], while the extent of artifacts was found to be comparable [4 (3-4.75) vs. 4 (3-4), P = 0.40]. bSSFP DL images had higher aSNR and aCNR compared with the bSSFP CS images (aSNR: 13.4 ± 6.9 vs. 8.3 ± 3.6, P < 0.001; aCNR: 26.6 ± 15.8 vs. 14.4 ± 6.8, P < 0.001). Diagnostic confidence of the bSSFP DL images was superior for the evaluation of cardiovascular structures (e.g., atria and ventricles: P = 0.003). Conclusion: DL image denoising provides superior quality for DUS-gated fetal cardiac cine imaging of CHD compared to standard CS image reconstruction.

8.
Obes Surg ; 34(4): 1122-1130, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38366263

RESUMO

A global shift is occurring as hospital procedures move to ambulatory surgical settings. Surgeons have performed outpatient sleeve gastrectomy (SG) in bariatric surgery since 2010. However, prospective trials are needed to ensure its safety before widespread adoption. PURPOSE: The study aimed to present a comprehensive report on the prospective data collection of 30-day outcomes of outpatient primary laparoscopic SG (LSG). This trial seeks to assess whether outpatient LSG is non-inferior to hospital-based surgery in selected patients who meet the outpatient surgery criteria set by the American Society for Metabolic and Bariatric Surgery. MATERIALS AND METHODS: This study is funded by the Society of American Gastrointestinal and Endoscopic Surgeons and has been approved by the Advarra Institutional Review Board (Pro00055990). Cognizant of the necessity for a prospective approach, data collection commenced after patients underwent primary LSG procedures, spanning from August 2021 to September 2022, at six medical centers across the USA. Data centralization was facilitated through ArborMetrix. Each center has its own enhanced recovery protocols, and no attempt was made to standardize the protocols. RESULTS: The analysis included 365 patients with a mean preoperative BMI of 43.7 ± 5.7 kg/m2. Rates for 30-day complications, reoperations, readmissions, emergency department visits, and urgent care visits were low: 1.6%, .5%, .2%, .2%, and 0%, respectively. Two patients (0.5%) experienced grade IIIb complications. There were no mortalities or leaks reported. CONCLUSION: The prospective cohort study suggests that same-day discharge following LSG seems safe in highly selected patients at experienced US centers.


Assuntos
Cirurgia Bariátrica , Laparoscopia , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Estudos Prospectivos , Pacientes Ambulatoriais , Padrão de Cuidado , Laparoscopia/métodos , Cirurgia Bariátrica/métodos , Gastrectomia/métodos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
9.
Artigo em Inglês | MEDLINE | ID: mdl-38216538

RESUMO

OBJECTIVES: Spontaneous breathing has an important effect on pulmonary arterial blood flow in patients with Glenn/Fontan circulation. Unilateral diaphragmatic paralysis (DP) is a frequent complication after heart surgery in congenital heart disease. The aim of this study was to investigate the influence of unilateral DP on blood flow distribution in the pulmonary arteries with Glenn/Fontan circulation. METHODS: Magnetic resonance phase-contrast imaging was used to evaluate stroke volume index (SVI) in the left and right pulmonary arteries in patients with Glenn/Fontan circulation with unilateral DP. Data for 18 patients with univentricular heart and unilateral DP were analysed, 8 in the Glenn stage and 10 in the Fontan stage. Ten patients had right-sided DP, and 8 had left-sided DP. A diaphragmatic plication was performed in 7 patients. The control group consisted of 36 patients with Glenn (n = 16)/Fontan (n = 20) circulation without DP. RESULTS: In both left- and right-sided DP, the SVI to the ipsilateral side was significantly lower than in controls [2.81 (1.45-4.50) ml/m2 left vs 11.97 (7.36-16.37) ml/m2 in controls, P < 0.0002; 8.2 (4.49-12.64) ml/m2 with right vs 12.64 (9.66-16.61) ml/m2 in controls; P = 0.0284]. The SVI to the contralateral side showed a slight but non-significant increase in the presence of unilateral DP. CONCLUSIONS: Unilateral DP in patients with Glenn/Fontan circulation has a negative impact on pulmonary arterial SVI on the side of the paralysis.

10.
JACC Case Rep ; 29(2): 102158, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38264310

RESUMO

A male preterm infant with total anomalous pulmonary venous connection developed progressive respiratory distress but was considered too high risk for surgical repair because of his critical condition. We demonstrated that percutaneous transhepatic stent implantation for portosystemic shunt creation is a feasible bridging procedure when surgery is not possible.

11.
Antibiotics (Basel) ; 12(10)2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37887191

RESUMO

Bacterial biofilms on orthopedic implants are resistant to the host immune response and to traditional systemic antibiotics. Novel therapies are needed to improve patient outcomes. TRL1068 is a human monoclonal antibody (mAb) against a biofilm anchoring protein. For assessment of this agent in an orthopedic implant infection model, efficacy was measured by reduction in bacterial burden of Staphylococcus aureus, the most common pathogen for prosthetic joint infections (PJI). Systemic treatment with the biofilm disrupting mAb TRL1068 in conjunction with vancomycin eradicated S. aureus from steel pins implanted in the spine for 26 of 27 mice, significantly more than for vancomycin alone. The mechanism of action was elucidated by two microscopy studies. First, TRL1068 was localized to biofilm using a fluorescent antibody tag. Second, a qualitative effect on biofilm structure was observed using scanning electron microscopy (SEM) to examine steel pins that had been treated in vivo. SEM images of implants retrieved from control mice showed abundant three-dimensional biofilms, whereas those from mice treated with TRL1068 did not. Clinical Significance: TRL1068 binds at high affinity to S. aureus biofilms, thereby disrupting the three-dimensional structure and significantly reducing implant CFUs in a well-characterized orthopedic model for which prior tested agents have shown only partial efficacy. TRL1068 represents a promising systemic treatment for orthopedic implant infection.

12.
OTA Int ; 6(4): e289, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37901451

RESUMO

Objective: We aimed to evaluate the difference in 30-day outcomes after surgical management of proximal humerus fractures (PHFs) between patients with and without chronic liver disease as defined by a MELD score greater than 10. Design: This was a retrospective database review. Setting: All centers participating in the American College of Surgeons National Surgical Quality Improvement Program database were included. Patients/Participants: Patients with proximal humerus fractures who (1) underwent ORIF, HA, or SA and (2) had calculable MELD scores were included. Intervention: Open reduction and internal fixation, hemiarthroplasty, or shoulder arthroplasty was used for treatment. Main outcome measurements: Thirty-day complications, mortality, readmission, and reoperation rates were measured. Results: Of the total 1732 PHF patients identified, 300 had a MELD score higher than 10. After propensity matching by significant covariates, MELD score higher than 10 was found to be significantly associated with higher rates of 30-day mortality, 30-day readmission, transfusion within 72 hours, and systemic complications. Among patients with a MELD score higher than 10, treatment with SA or HA instead of ORIF was associated with a higher rate of transfusion and longer operative time. There were no significant differences between treatment cohorts regarding mortality, reoperation, readmission, or complications. Conclusions: A MELD score higher than 10 is associated with higher risk of surgical complications, transfusion, and death in patients undergoing surgery for proximal humerus fractures. Among patients with a MELD score higher than 10, ORIF was associated with a lower transfusion rate and shorter operative time than arthroplasty or hemiarthroplasty. Level of Evidence: Prognostic Level III.

13.
Artigo em Inglês | MEDLINE | ID: mdl-37776606

RESUMO

Giardia duodenalis is the causative agent of the neglected diarrhoeal disease giardiasis. While often self-limiting, giardiasis is ubiquitous and impacts hundreds of millions of people annually. It is also a common gastro-intestinal disease of domestic pets, wildlife, and livestock animals. However, despite this impact, there is no vaccine for Giardia currently available. In addition, treatment relies on chemotherapies that are associated with increasing failure rates. To identify new treatment options for giardiasis we recently screened the Compounds Australia Scaffold Library for new chemotypes with selective anti-Giardia activity, identifying three compounds with sub-µM activity and promising selectivity. Here we extended these studies by examining the anti-Giardia activity of series CL9569 compounds. This compound series was of interest given the promising activity (IC50 1.2 µM) and selectivity demonstrated by representative compound, SN00798525 (1). Data from this work has identified an additional three thieno [3,2-b]pyrrole 5-carboxamides with anti-Giardia activity, including 2 which displayed potent cytocidal (IC50 ≤ 10 nM) and selective activity against multiple Giardia strains, including representatives from both human-infecting assemblages and metronidazole resistant parasites. Preclinical studies in mice also demonstrated that 2 is well-tolerated, does not impact the normal gut microbiota and can reduce Giardia parasite burden in these animals.


Assuntos
Giardia lamblia , Giardíase , Parasitos , Humanos , Animais , Camundongos , Giardíase/tratamento farmacológico , Giardíase/veterinária , Giardíase/parasitologia , Giardia , Metronidazol/uso terapêutico , Fezes/parasitologia
14.
J Inherit Metab Dis ; 46(6): 1147-1158, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37467014

RESUMO

Glycogen storage disease type-Ia (GSD-Ia), characterized by impaired blood glucose homeostasis, is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC). Using the G6pc-R83C mouse model of GSD-Ia, we explored a CRISPR/Cas9-based double-strand DNA oligonucleotide (dsODN) insertional strategy that uses the nonhomologous end-joining repair mechanism to correct the pathogenic p.R83C variant in G6pc exon-2. The strategy is based on the insertion of a short dsODN into G6pc exon-2 to disrupt the native exon and to introduce an additional splice acceptor site and the correcting sequence. When transcribed and spliced, the edited gene would generate a wild-type mRNA encoding the native G6Pase-α protein. The editing reagents formulated in lipid nanoparticles (LNPs) were delivered to the liver. Mice were treated either with one dose of LNP-dsODN at age 4 weeks or with two doses of LNP-dsODN at age 2 and 4 weeks. The G6pc-R83C mice receiving successful editing expressed ~4% of normal hepatic G6Pase-α activity, maintained glucose homeostasis, lacked hypoglycemic seizures, and displayed normalized blood metabolite profile. The outcomes are consistent with preclinical studies supporting previous gene augmentation therapy which is currently in clinical trials. This editing strategy may offer the basis for a therapeutic approach with an earlier clinical intervention than gene augmentation, with the additional benefit of a potentially permanent correction of the GSD-Ia phenotype.


Assuntos
Doença de Depósito de Glicogênio Tipo I , Oligonucleotídeos , Camundongos , Animais , Oligonucleotídeos/metabolismo , Sistemas CRISPR-Cas , Doença de Depósito de Glicogênio Tipo I/genética , Doença de Depósito de Glicogênio Tipo I/terapia , Doença de Depósito de Glicogênio Tipo I/metabolismo , Fígado/metabolismo , Glucose-6-Fosfatase/genética , Glucose-6-Fosfatase/metabolismo
16.
Eur J Radiol ; 163: 110831, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37059004

RESUMO

PURPOSE: To compare standard breath-hold (BH) cine imaging to a radial pseudo-golden-angle free-breathing (FB) technique in congenital heart disease (CHD). METHODS: In this prospective study, short-axis and 4-chamber BH and FB cardiac MRI sequences of 25 participants with CHD acquired at 1.5 Tesla, were quantitatively compared regarding ventricular volumes, function, interventricular septum thickness (IVSD), apparent signal to noise ratio (aSNR), and estimated contrast to noise ratio (eCNR). For qualitative comparison, three image quality criteria (contrast, endocardial edge definition, and artefacts) were rated on a 5-point Likert scale (5: excellent, 1: non-diagnostic). Paired t-Test was used for group comparisons, Bland-Altman analysis for agreement between techniques. Inter-reader agreement was compared using intraclass correlation coefficient. RESULTS: IVSD (BH 7.4 ± 2.1 mm vs FB 7.4 ± 1.9 mm, p =.71), biventricular ejection fraction (left ventricle [LV]: 56.4 ± 10.8% vs 56.1 ± 9.3%, p =.83; right ventricle [RV]: 49.5 ± 8.6% vs 49.7 ± 10.1%, p =.83), and biventricular end diastolic volume (LV: 176.3 ± 63.9 ml vs 173.9 ± 64.9 ml, p =.90; RV: 185.4 ± 63.8 ml vs 189.6 ± 66.6 ml, p =.34) were comparable. Mean measurement time for FB short-axis sequences was 8.1 ± 1.3 compared to 4.4 ± 1.3 min for BH (p <.001). Subjective image quality between sequences was deemed comparable, (4.6 ± 0.6 vs 4.5 ± 0.6, p =.26, for 4-chamber views) with a significant difference regarding short-axis views (4.9 ± 0.3 vs 4.5 ± 0.6, p =.008). aSNR was similar (BH 25.8 ± 11.2 vs FB 22.2 ± 9.5, p =.24), while eCNR was higher for BH (89.1 ± 36.1 vs 68.5 ± 32.1, p =.03). CONCLUSION: FB sequences yielded comparable results to BH regarding image quality, biventricular volumetry, and function, though measurement times were longer. The FB sequence described might be clinically valuable when BHs are insufficiently performed.


Assuntos
Cardiopatias Congênitas , Respiração , Humanos , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodos , Cardiopatias Congênitas/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Suspensão da Respiração , Reprodutibilidade dos Testes
17.
Mol Ther Nucleic Acids ; 32: 289-301, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37096163

RESUMO

Antisense oligonucleotides (ASOs) are short synthetic nucleic acids that recognize and bind to complementary RNA to modulate gene expression. It is well established that single-stranded, phosphorothioate-modified ASOs enter cells independent of carrier molecules, primarily via endocytic pathways, but that only a small portion of internalized ASO is released into the cytosol and/or nucleus, rendering the majority of ASO inaccessible to the targeted RNA. Identifying pathways that can increase the available ASO pool is valuable as a research tool and therapeutically. Here, we conducted a functional genomic screen for ASO activity by engineering GFP splice reporter cells and applying genome-wide CRISPR gene activation. The screen can identify factors that enhance ASO splice modulation activity. Characterization of hit genes uncovered GOLGA8, a largely uncharacterized protein, as a novel positive regulator enhancing ASO activity by ∼2-fold. Bulk ASO uptake is 2- to 5-fold higher in GOLGA8-overexpressing cells where GOLGA8 and ASOs are observed in the same intracellular compartments. We find GOLGA8 is highly localized to the trans-Golgi and readily detectable at the plasma membrane. Interestingly, overexpression of GOLGA8 increased activity for both splice modulation and RNase H1-dependent ASOs. Taken together, these results support a novel role for GOLGA8 in productive ASO uptake.

18.
Radiol Cardiothorac Imaging ; 5(1): e220129, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36860838

RESUMO

Purpose: To apply Doppler US (DUS)-gated fetal cardiac cine MRI in clinical routine and investigate diagnostic performance in complex congenital heart disease (CHD) compared with that of fetal echocardiography. Materials and Methods: In this prospective study (May 2021 to March 2022), women with fetuses with CHD underwent fetal echocardiography and DUS-gated fetal cardiac MRI on the same day. For MRI, balanced steady-state free precession cine images were acquired in the axial and optional sagittal and/or coronal orientations. Overall image quality was assessed on a four-point Likert scale (from 1 = nondiagnostic to 4 = good image quality). The presence of abnormalities in 20 fetal cardiovascular features was independently assessed by using both modalities. The reference standard was postnatal examination results. Differences in sensitivities and specificities were determined by using a random-effects model. Results: The study included 23 participants (mean age, 32 years ± 5 [SD]; mean gestational age, 36 weeks ± 1). Fetal cardiac MRI was completed in all participants. The median overall image quality of DUS-gated cine images was 3 (IQR, 2.5-4). In 21 of 23 participants (91%), underlying CHD was correctly assessed by using fetal cardiac MRI. In one case, the correct diagnosis was made by using MRI only (situs inversus and congenitally corrected transposition of the great arteries). Sensitivities (91.8% [95% CI: 85.7, 95.1] vs 93.6% [95% CI: 88.8, 96.2]; P = .53) and specificities (99.9% [95% CI: 99.2, 100] vs 99.9% [95% CI: 99.5, 100]; P > .99) for the detection of abnormal cardiovascular features were comparable between MRI and echocardiography, respectively. Conclusion: Using DUS-gated fetal cine cardiac MRI resulted in performance comparable with that of using fetal echocardiography for diagnosing complex fetal CHD.Keywords: Pediatrics, MR-Fetal (Fetal MRI), Cardiac, Heart, Congenital, Fetal Imaging, Cardiac MRI, Prenatal, Congenital Heart DiseaseClinical trial registration no. NCT05066399 Supplemental material is available for this article. © RSNA, 2023See also the commentary by Biko and Fogel in this issue.

19.
JBJS Case Connect ; 13(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36821418

RESUMO

CASE: A 16-year-old, right-hand-dominant, Asian male, elite tennis player presented to the clinic with a 1-month history of left shoulder pain. Originally, the pathology was believed to be shoulder-based, but lack of improvement after several weeks of therapy warranted further imaging, which ultimately revealed a nondisplaced fracture of the posterior left first rib. CONCLUSION: Stress injuries are not uncommon in the sport of tennis, but atraumatic rib fractures are rare. Given the increase in youth sports specialization and overtraining and other risk factors such as adolescent age and race, it is important to keep rib stress fracture on the differential.


Assuntos
Fraturas de Estresse , Fraturas das Costelas , Tênis , Humanos , Masculino , Adolescente , Fraturas de Estresse/etiologia , Tênis/lesões , Costelas/lesões , Fraturas das Costelas/complicações , Dor de Ombro/etiologia
20.
Oral Maxillofac Surg ; 27(1): 69-78, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35119553

RESUMO

The aim of this cohort case series is to present a new subperiosteal implant device that uses CAD-CAM technologies together with 3D metal printing capabilities to produce direct bone-anchored dental prosthetic solutions for the management of atrophic edentulous alveolus and jaws. The clinical experience of 21 subperiosteal devices implanted over a 4-year period is presented. The results of this study showed 14 of the 21 cases were successful (66.7%), while 7 cases had complications including exposure of the metal frame (5 cases), mobility of the device (1 case) and 1 case failed for reasons unrelated to the device. Four of the 7 cases were successfully salvaged resulting in an overall success rate of 85.7% (18 /21 cases). This study supports the use of fully customized subperiosteal jaw implants as a simple and reliable alternative for dental rehabilitation of atrophic edentulous cases which would otherwise require bone grafts for conventional fixed dental implant solutions. With more research, the clinical potential for this device is significant as it not only avoids the need for complex and lengthy reconstructive jaw surgery but also allows for the placement of immediate prosthetic teeth at the time of implantation.


Assuntos
Implantes Dentários , Arcada Edêntula , Boca Edêntula , Humanos , Arcada Edêntula/reabilitação , Arcada Edêntula/cirurgia , Boca Edêntula/cirurgia , Maxila/cirurgia , Prótese Dentária Fixada por Implante , Implantação Dentária Endóssea/métodos , Resultado do Tratamento , Seguimentos , Falha de Restauração Dentária
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