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1.
FASEB J ; 38(13): e23780, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38948938

RESUMO

Aerobic training (AT), an effective form of cardiac rehabilitation, has been shown to be beneficial for cardiac repair and remodeling after myocardial infarction (MI). The p300/CBP-associated factor (PCAF) is one of the most important lysine acetyltransferases and is involved in various biological processes. However, the role of PCAF in AT and AT-mediated cardiac remodeling post-MI has not been determined. Here, we found that the PCAF protein level was significantly increased after MI, while AT blocked the increase in PCAF. AT markedly improved cardiac remodeling in mice after MI by reducing endoplasmic reticulum stress (ERS). In vivo, similar to AT, pharmacological inhibition of PCAF by Embelin improved cardiac recovery and attenuated ERS in MI mice. Furthermore, we observed that both IGF-1, a simulated exercise environment, and Embelin protected from H2O2-induced cardiomyocyte injury, while PCAF overexpression by viruses or the sirtuin inhibitor nicotinamide eliminated the protective effect of IGF-1 in H9C2 cells. Thus, our data indicate that maintaining low PCAF levels plays an essential role in AT-mediated cardiac protection, and PCAF inhibition represents a promising therapeutic target for attenuating cardiac remodeling after MI.


Assuntos
Infarto do Miocárdio , Condicionamento Físico Animal , Remodelação Ventricular , Fatores de Transcrição de p300-CBP , Animais , Fatores de Transcrição de p300-CBP/metabolismo , Fatores de Transcrição de p300-CBP/antagonistas & inibidores , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Camundongos , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38949261

RESUMO

STUDY DESIGN: A retrospective, single-center, observational study. OBJECTIVE: This study investigated the risk factors associated with the failure of conservative treatment for adjacent vertebral fractures (AVFs). SUMMARY OF BACKGROUND DATA: Adjacent vertebral fractures following vertebroplasty for osteoporotic vertebral compression fractures are not uncommon. Presently, there is a lack of consensus regarding the management of adjacent vertebral fractures. METHODS: We included patients who developed adjacent vertebral fractures within two years post single-level vertebroplasty between January 2013 and December 2020. All patients initially underwent six weeks of conservative treatment, including pain medications, bracing, and physical therapy. Surgical intervention was offered to those with intractable back pain due to AVFs. Baseline demographics, AVF characteristics, and radiological measurements were systematically collected, and sequential univariable and multivariable logistic regression analyses were conducted to explore the risk factors. RESULTS: Of the 114 patients with a mean age of 78.6 years, two-thirds (76 patients) tolerated conservative treatment well, while 38 required surgical interventions for adjacent vertebral fractures. Both groups demonstrated similar baseline demographics and radiological parameters regarding AVFs (P>0.05). The multivariable logistic regression analyses revealed that the development of AVFs later than six months post-vertebroplasty and their caudal location to the index vertebroplasty were the independent risk factors of unsuccessful conservative treatment, with odds ratios of 3.57 (95% confidence interval [CI]: 1.14-11.1, P=0.029) and 2.50 (95% CI: 1.09-5.88, P=0.032), respectively. CONCLUSION: Adjacent vertebral fractures following percutaneous vertebroplasty generally have favorable outcomes under conservative treatment. However, the timing and the relative anatomical location of adjacent vertebral fractures are associated with treatment efficacy. Adjacent vertebral fractures occurring later than six months following the initial vertebroplasty or situated in the caudal location to the index vertebroplasty may exhibit reduced responsiveness to conservative treatment. These patients might benefit from a more aggressive therapeutic approach. LEVEL OF EVIDENCE: 3.

3.
J Chem Phys ; 161(1)2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38953451

RESUMO

Inspired by biological channels, achieving precise separation of ion/water and ion/ion requires finely tuned pore sizes at molecular dimensions and deliberate exposure of charged groups. Covalent organic frameworks (COFs), a class of porous crystalline materials, offer well-defined nanoscale pores and diverse structures, making them excellent candidates for nanofluidic channels that facilitate ion and water transport. In this study, we perform molecular simulations to investigate the structure and kinetics of water and ions confined within the typical COFs with varied exposure of charged groups. The COFs exhibit vertically arrayed nanochannels, enabling diffusion coefficients of water molecules within COFs to remain within the same order of magnitude as in the bulk. The motion of water molecules manifests in two distinct modes, creating a mobile hydration layer around acid groups. The ion diffusion within COFs displays a notable disparity between monovalent (M+) and divalent (M2+) cations. As a result, the selectivity of M+/M2+ can exceed 100, while differentiation among M+ is less pronounced. In addition, our simulations indicate a high rejection (R > 98%) in COFs, indicating their potential as ideal materials for desalination. The chemical flexibility of COFs indicates that would hold significant promise as candidates for advanced artificial ion channels and separation membranes.

4.
PLoS Genet ; 20(6): e1011313, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38870230

RESUMO

A quarter of humanity is estimated to have been exposed to Mycobacterium tuberculosis (Mtb) with a 5-10% risk of developing tuberculosis (TB) disease. Variability in responses to Mtb infection could be due to host or pathogen heterogeneity. Here, we focused on host genetic variation in a Peruvian population and its associations with gene regulation in monocyte-derived macrophages and dendritic cells (DCs). We recruited former household contacts of TB patients who previously progressed to TB (cases, n = 63) or did not progress to TB (controls, n = 63). Transcriptomic profiling of monocyte-derived DCs and macrophages measured the impact of genetic variants on gene expression by identifying expression quantitative trait loci (eQTL). We identified 330 and 257 eQTL genes in DCs and macrophages (False Discovery Rate (FDR) < 0.05), respectively. Four genes in DCs showed interaction between eQTL variants and TB progression status. The top eQTL interaction for a protein-coding gene was with FAH, the gene encoding fumarylacetoacetate hydrolase, which mediates the last step in mammalian tyrosine catabolism. FAH expression was associated with genetic regulatory variation in cases but not controls. Using public transcriptomic and epigenomic data of Mtb-infected monocyte-derived dendritic cells, we found that Mtb infection results in FAH downregulation and DNA methylation changes in the locus. Overall, this study demonstrates effects of genetic variation on gene expression levels that are dependent on history of infectious disease and highlights a candidate pathogenic mechanism through pathogen-response genes. Furthermore, our results point to tyrosine metabolism and related candidate TB progression pathways for further investigation.


Assuntos
Células Dendríticas , Macrófagos , Mycobacterium tuberculosis , Locos de Características Quantitativas , Tuberculose , Humanos , Peru , Tuberculose/genética , Tuberculose/microbiologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Mycobacterium tuberculosis/patogenicidade , Mycobacterium tuberculosis/genética , Feminino , Células Dendríticas/metabolismo , Masculino , Adulto , Predisposição Genética para Doença , Variação Genética , Regulação da Expressão Gênica , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Perfilação da Expressão Gênica
5.
Environ Pollut ; 358: 124472, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945190

RESUMO

In recent years, there has been a growing concern about air pollution and its impact on the air quality and human health, especially for fine particulate matter (PM2.5) and its associated secondary aerosols in urban areas. This study conducted a year-long field campaign to collect PM2.5 samples day and night in an urban area of central Taiwan. Higher PM2.5 mass concentrations were observed in winter (27.7 ± 9.7 µg/m3), followed by autumn (22.5 ± 8.3 µg/m3), spring (19.2 ± 6.4 µg/m3), and summer (11.0 ± 3.1 µg/m3). The dominant formation mechanism of secondary inorganic aerosols was heterogeneous reactions of NO3- at night and homogeneous reactions of SO42- during the day. Additionally, significant correlations were observed between aerosol liquid water content (ALWC) and NO3- during nighttime, indicating the importance of aqueous-phase NO3- formation. The role of aerosol acidity was explored and a unique alkaline condition was found in spring and summer, which showed lower PM2.5 concentrations than the neutralized condition. Under the neutralized condition, higher PM2.5 concentrations were commonly found when combining the ammonium-rich regime with molar ratios of [NO3-]/[SO42-] exceeding 1.6, suggesting the importance of reducing both NH3 and NOx. Furthermore, the results showed that reducing NH3 should be prioritized under high temperature conditions, while reducing NOx became important under low temperature conditions. Clustering of backward trajectories showed that long-range transport could enhance the formation of secondary aerosols, but local emissions emerged as the main factor driving high PM2.5 concentrations. This study provides insights for policymakers to improve air quality, suggesting that different mitigation strategies should be formulated based on meteorological variables and that using clean energy for vehicles and electricity generation is important to alleviate air pollution.

6.
Clin Immunol ; 265: 110285, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880201

RESUMO

Effective treatment of systemic lupus erythematosus (SLE) remains an unmet need. Different subsets of macrophages play differential roles in SLE and the modulation of macrophage polarization away from M1 status is beneficial for SLE therapeutics. Given the pathogenic roles of type I interferons (IFN-I) in SLE, this study investigated the effects and mechanisms of a mitochondria localization molecule ubiquitin specific peptidase 18 (USP18) preserving anti-IFN effects and isopeptidase activity on macrophage polarization. After observing USP18 induction in monocytes from SLE patients, we studied mouse bone marrow-derived macrophages and showed that USP18 deficiency increased M1signal (LPS + IFN-γ treatment)-induced macrophage polarization, and the effects involved the induction of glycolysis and mitochondrial respiration and the expression of several glycolysis-associated enzymes and molecules, such as hypoxia-inducible factor-1α. Moreover, the effects on mitochondrial activities, such as mitochondrial DNA release and mitochondrial reactive oxygen species production were observed. In contrast, the overexpression of USP18 inhibited M1signal-mediated and enhanced interleukin-4 (IL-4)-mediated polarization of macrophages and the related cellular events. Moreover, the levels of USP18 mRNA expression showed tendency of correlation with the expression of metabolic enzymes in monocytes from patients with SLE. We thus concluded that by preserving anti-IFN effect and downregulating M1 signaling, promoting USP18 activity may serve as a useful approach for SLE therapeutics.

8.
ACS Nano ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922204

RESUMO

Engineering atomic-scale defects has become an important strategy for the future application of transition metal dichalcogenide (TMD) materials in next-generation electronic technologies. Thus, providing an atomic understanding of the electron-defect interactions and supporting defect engineering development to improve carrier transport is crucial to future TMDs technologies. In this work, we utilize low-temperature scanning tunneling microscopy/spectroscopy (LT-STM/S) to elicit how distinct types of defects bring forth scattering potential engineering based on intervalley quantum quasiparticle interference (QPI) in TMDs. Furthermore, quantifying the energy-dependent phase variation of the QPI standing wave reveals the detailed electron-defect interaction between the substitution-induced scattering potential and the carrier transport mechanism. By exploring the intrinsic electronic behavior of atomic-level defects to further understand how defects affect carrier transport in low-dimensional semiconductors, we offer potential technological applications that may contribute to the future expansion of TMDs.

9.
Neuroreport ; 35(10): 648-656, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38813901

RESUMO

Mitochondria play a crucial role in maintaining cellular energy supply and serve as a source of energy for repairing nerve damage following a stroke. Given that exercise has the potential to enhance energy metabolism, investigating the impact of exercise on mitochondrial function provides a plausible mechanism for stroke treatment. In our study, we established the middle cerebral artery occlusion (MCAO) model in Sprague-Dawley rats and implemented early exercise intervention. Neurological severity scores, beam-walking test score, and weight were used to evaluate neurological function. The volume of cerebral infarction was measured by MRI. Nerve cell apoptosis was detected by TUNEL staining. Mitochondrial morphology and structure were detected by mitochondrial electron microscopy. Mitochondrial function was assessed using membrane potential and ATP measurements. Western blotting was used to detect the protein expression of AMPK/PGC-1α/GLUT4. Through the above experiments, we found that early exercise improved neurological function in rats after MCAO, reduced cerebral infarction volume and neuronal apoptosis, promoted the recovery of mitochondrial morphology and function. We further examined the protein expression of AMPK/PGC-1α/GLUT4 signaling pathway and confirmed that early exercise was able to increase its expression. Therefore, we suggest that early exercise initiated the AMPK/PGC-1α/GLUT4 signaling pathway, restoring mitochondrial function and augmenting energy supply. This, in turn, effectively improved both nerve and body function in rats following ischemic stroke.


Assuntos
Proteínas Quinases Ativadas por AMP , Mitocôndrias , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Condicionamento Físico Animal , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais/fisiologia , Masculino , Proteínas Quinases Ativadas por AMP/metabolismo , Mitocôndrias/metabolismo , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/métodos , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/terapia , Isquemia Encefálica/metabolismo , Ratos , Modelos Animais de Doenças , Apoptose/fisiologia
10.
World Neurosurg ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38777315

RESUMO

BACKGROUND: The rise of minimally invasive lumbar fusions and advanced imaging technologies has facilitated the introduction of novel surgical techniques with the trans-facet approach being one of the newest additions. We aimed to quantify any pathology-driven anatomic changes to the trans-facet corridor, which could thereby alter the ideal laterality of approach to the disc space. METHODS: In this retrospective cohort study, we measured the areas and maximum permissible cannula diameters of the trans-facet corridor using commercially available software (BrainLab, Munich, Germany). Exiting and traversing nerve roots, thecal sacs, and lumbar vertebrae were manually segmented on T2-SPACE magnetic resonance imaging. Spondylolisthesis, disc protrusions, and disc space heights were recorded. RESULTS: A total of 118 trans-facet corridors were segmented bilaterally in 16 patients (65.6 ± 12.1 years, 43.8% female, body mass index 29.2 ± 5.1 kg/m2). The mean areas at L1-L2, L2-L3, L3-L4, and L4-L5 were 89.4 ± 24.9 mm2, 124 ± 39.4 mm2, 123 ± 26.6 mm2, and 159 ± 42.7 mm2, respectively. The mean permissible cannula diameter at the same levels were 7.85 ± 1.43 mm, 8.98 ± 1.72 mm, 8.93 ± 1.26 mm, and 10.2 ± 1.94 mm, respectively. Both parameters increased caudally. Higher degrees for spondylolisthesis were associated with larger areas and maximum cannula diameters on regression analysis (P < 0.001). CONCLUSIONS: Our results illustrate that pathology, like spondylolisthesis, can increase the area of the trans-facet corridor. By understanding this effect, surgeons can better decide on the optimal approach to the disc while taking into consideration a patient's unique anatomy.

11.
Methods Mol Biol ; 2800: 189-202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709485

RESUMO

Understanding how signaling networks are regulated offers valuable insights into how cells and organisms react to internal and external stimuli and is crucial for developing novel strategies to treat diseases. To achieve this, it is necessary to delineate the intricate interactions between the nodes in the network, which can be accomplished by measuring the activities of individual nodes under perturbation conditions. To facilitate this, we have recently developed a biosensor barcoding technique that enables massively multiplexed tracking of numerous signaling activities in live cells using genetically encoded fluorescent biosensors. In this chapter, we detail how we employed this method to reconstruct the EGFR signaling network by systematically monitoring the activities of individual nodes under perturbations.


Assuntos
Técnicas Biossensoriais , Transdução de Sinais , Técnicas Biossensoriais/métodos , Humanos , Receptores ErbB/metabolismo , Receptores ErbB/genética
12.
Bioresour Technol ; 402: 130762, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692371

RESUMO

Ionic cadmium (Cd (II)) in water is a significant threat to ecosystems, the environment, and human health. Research is currently focused on developing efficient adsorption materials to combat Cd (II) pollution in water. One promising solution involves co-pyrolyzing solid residue from anaerobic digestion of food waste with oil-based drill cuttings pyrolysis residue to create a biochar with high organic matter content. This biochar has a lower heavy metal content and leaching toxicity compared to China's national standards, making it both safe and resourceful. It exhibits a high adsorption capacity for Cd (II) in water, reaching up to 47.80 ± 0.37 mg/g. Raising the pyrolysis temperature above 600 °C and increasing the amount of pyrolysis residue beyond 30 % enhances the biochar's adsorption capacity. The adsorption process is primarily driven by mineral precipitation, offering a promising approach for dual waste resource management and reducing heavy metal pollution.


Assuntos
Cádmio , Carvão Vegetal , Resíduos Sólidos , Cádmio/química , Carvão Vegetal/química , Adsorção , Pirólise , Poluentes Químicos da Água/química , Minerais/química , Precipitação Química , Purificação da Água/métodos
13.
Emerg Infect Dis ; 30(6): 1115-1124, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38781680

RESUMO

The World Health Organization's end TB strategy promotes the use of symptom and chest radiograph screening for tuberculosis (TB) disease. However, asymptomatic early states of TB beyond latent TB infection and active disease can go unrecognized using current screening criteria. We conducted a longitudinal cohort study enrolling household contacts initially free of TB disease and followed them for the occurrence of incident TB over 1 year. Among 1,747 screened contacts, 27 (52%) of the 52 persons in whom TB subsequently developed during follow-up had a baseline abnormal radiograph. Of contacts without TB symptoms, persons with an abnormal radiograph were at higher risk for subsequent TB than persons with an unremarkable radiograph (adjusted hazard ratio 15.62 [95% CI 7.74-31.54]). In young adults, we found a strong linear relationship between radiograph severity and time to TB diagnosis. Our findings suggest chest radiograph screening can extend to detecting early TB states, thereby enabling timely intervention.


Assuntos
Características da Família , Programas de Rastreamento , Radiografia Torácica , Humanos , Peru/epidemiologia , Masculino , Feminino , Adulto , Adolescente , Adulto Jovem , Programas de Rastreamento/métodos , Estudos Longitudinais , Pessoa de Meia-Idade , Criança , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/diagnóstico por imagem , Busca de Comunicante/métodos , Pré-Escolar , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Tuberculose Latente/diagnóstico por imagem , Lactente , Tuberculose/epidemiologia , Tuberculose/diagnóstico , Tuberculose/diagnóstico por imagem
14.
J Clin Med ; 13(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38592365

RESUMO

The transfacet minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a novel approach available for the management of lumbar spondylolisthesis. It avoids the need to manipulate either of the exiting or traversing nerve roots, both protected by the bony boundaries of the approach. With the advancement in operative technologies such as navigation, mapping, segmentation, and augmented reality (AR), surgeons are prompted to utilize these technologies to enhance their surgical outcomes. A 36-year-old male patient was complaining of chronic progressive lower back pain. He was found to have grade 2 L4/5 spondylolisthesis. We studied the feasibility of a trans-Kambin or a transfacet MIS-TLIF, and decided to proceed with the latter given the wider corridor it provides. Preoperative trajectory planning and level segmentation in addition to intraoperative navigation and image merging were all utilized to provide an AR model to guide us through the surgery. The use of AR can build on the safety and learning of novel surgical approaches to spine pathologies. However, larger high-quality studies are needed to further objectively analyze its impact on surgical outcomes and to expand on its application.

15.
Lab Anim Res ; 40(1): 16, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649958

RESUMO

BACKGROUND: Therapeutic interventions for diabetes are most effective when administered in the newly onset phase, yet determining the exact onset moment can be elusive in practice. Spontaneous autoimmune diabetes among NOD mice appears randomly between 12 and 32 weeks of age with an incidence range from 60 to 90%. Furthermore, the disease often progresses rapidly to severe diabetes within days, resulting in a very short window of newly onset phase, that poses significant challenge in early diagnosis. Conventionally, extensive blood glucose (BG) testing is typically required on large cohorts throughout several months to conduct prospective survey. We incorporated ultrasensitive urine glucose (UG) testing into an ordinary BG survey process, initially aiming to elucidate the lag period required for excessive glucose leaking from blood to urine during diabetes progression in the mouse model. RESULTS: The observations unexpectedly revealed that small amounts of glucose detected in the urine often coincide with, sometimes even a couple days prior than elevated BG is diagnosed. Accordingly, we conducted the UG-based survey protocol in another cohort that was validated to accurately identified every individual near onset, who could then be confirmed by following few BG tests to fulfill the consecutive BG + criteria. This approach required fewer than 95 BG tests, compared to over 700 tests with traditional BG survey, to diagnose all the 37-38 diabetic mice out of total 60. The average BG level at diagnosis was slightly below 350 mg/dl, lower than the approximately 400 mg/dl observed with conventional BG monitoring. CONCLUSIONS: We demonstrated a near perfect correlation between BG + and ultrasensitive UG + results in prospective survey with no lag period detected under twice weekly of testing frequency. This led to the refined protocol based on surveying with noninvasive UG testing, allowing for the early identification of newly onset diabetic mice with only a few BG tests required per mouse. This protocol significantly reduces the need for extensive blood sampling, lancet usage, labor, and animal distress, aligning with the 3Rs principle. It presents a convenient, accurate, and animal-friendly alternative for early diabetes diagnosis, facilitating research on diagnosis, pathogenesis, prevention, and treatment.

16.
J Clin Med ; 13(8)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38673544

RESUMO

The transforaminal lumbar interbody fusion (TLIF) has seen significant evolution since its early inception, reflecting advancements in surgical techniques, patient safety, and outcomes. Originally described as an improvement over the posterior lumbar interbody fusion (PLIF), the TLIF began as an open surgical procedure, that notably reduced the need for the extensive neural retractation that hindered the PLIF. In line with the broader practice of surgery, trending toward minimally invasive access, the TLIF was followed by the development of the minimally invasive TLIF (MIS-TLIF), a technique that further decreased tissue trauma and postoperative complications. Subsequent advancements, including Trans-Kambin's Triangle TLIF (percLIF) and transfacet LIF, have continued to refine surgical access, minimize surgical footprint, and reduce the risk of injury to the patient. The latest evolution, as we will describe it, the patient-specific TLIF, is a culmination of the aforementioned adaptations and incorporates advanced imaging and segmentation technologies into perioperative planning, allowing surgeons to tailor approaches based on individual patient anatomy and pathology. These developments signify a shift towards more precise methods in spine surgery. The ongoing evolution of the TLIF technique illustrates the dynamic nature of surgery and emphasizes the need for continued adaptation and refinement.

17.
J Transl Med ; 22(1): 378, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649894

RESUMO

BACKGROUND: Bacteria-based cancer therapy have demonstrated innovative strategies to combat tumors. Recent studies have focused on gram-negative bacterial outer membrane vesicles (OMVs) as a novel cancer immunotherapy strategy due to its intrinsic properties as a versatile carrier. METHOD: Here, we developed an Human Papillomavirus (HPV)-associated E7 antigen displaying Salmonella-derived OMV vaccine, utilizing a Poly(L-arginine) cell penetrating peptide (CPP) to enhance HPV16 E7 (aa49-67) H-2 Db and OMV affinity, termed SOMV-9RE7. RESULTS: Due to OMV's intrinsic immunogenic properties, SOMV-9RE7 effectively activates adaptive immunity through antigen-presenting cell uptake and antigen cross-presentation. Vaccination of engineered OMVs shows immediate tumor suppression and recruitment of infiltrating tumor-reactive immune cells. CONCLUSION: The simplicity of the arginine coating strategy boasts the versatility of immuno-stimulating OMVs that can be broadly implemented to personalized bacterial immunotherapeutic applications.


Assuntos
Arginina , Vacinas Anticâncer , Proteínas E7 de Papillomavirus , Proteínas E7 de Papillomavirus/imunologia , Vacinas Anticâncer/imunologia , Humanos , Animais , Membrana Externa Bacteriana/imunologia , Camundongos Endogâmicos C57BL , Feminino
18.
Ann Plast Surg ; 92(4S Suppl 2): S279-S283, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556690

RESUMO

BACKGROUND: Burns constitute a major global health challenge, causing over 11 million injuries and 300,000 deaths annually and surpassing the economic burden of cervical cancer and HIV combined. Despite this, patient-level financial consequences of burn injuries remain poorly quantified, with a significant gap in data from low- and middle-income countries. In this study, we evaluate financial toxicity in burn patients. METHODS: A prospective, multicenter cohort study was conducted across two tertiary care hospitals in India, assessing 123 adult surgical in-patients undergoing operative interventions for burn injuries. Patient sociodemographic, clinical, and financial data were collected through surveys and electronic records during hospitalization and at 1, 3, and 6 months postoperatively. Out-of-pocket costs (OOPCs) for surgical burn treatment were evaluated during hospitalization. Longitudinal changes in income, employment status, and affordability of basic subsistence needs were assessed at the 1-, 3-, and 6-month postoperative time point. Degree of financial toxicity was calculated using a combination of the metrics catastrophic health expenditure and financial hardship. Development of financial toxicity was compared by sociodemographic and clinical characteristics using logistic regression models. RESULTS: Of the cohort, 60% experienced financial toxicity. Median OOPCs was US$555.32 with the majority of OOPCs stemming from direct nonmedical costs (US$318.45). Cost of initial hospitalization exceeded monthly annual income by 80%. Following surgical burn care, income decreased by US$318.18 within 6 months, accompanied by a 53% increase in unemployment rates. At least 40% of the cohort consistently reported inability to afford basic subsistence needs within the 6-month perioperative period. Significant predictors of developing financial toxicity included male gender (odds ratio, 4.17; 95% confidence interval, 1.25-14.29; P = 0.02) and hospital stays exceeding 20 days (odds ratio, 11.17; 95% confidence interval, 2.11-59.22; P ≤ 0.01). CONCLUSIONS: Surgical treatment for burn injuries is associated with substantial financial toxicity. National and local policies must expand their scope beyond direct medical costs to address direct nonmedical and indirect costs. These include burn care insurance, teleconsultation follow-ups, hospital-affiliated subsidized lodging, and resources for occupational support and rehabilitation. These measures are crucial to alleviate the financial burden of burn care, particularly during the perioperative period.


Assuntos
Queimaduras , Estresse Financeiro , Adulto , Humanos , Masculino , Queimaduras/epidemiologia , Queimaduras/cirurgia , Estudos de Coortes , Efeitos Psicossociais da Doença , Complicações Intraoperatórias , Estudos Prospectivos , Feminino
19.
J Clin Med ; 13(7)2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38610887

RESUMO

Cervical endoscopic spine surgery is rapidly evolving and gaining popularity for the treatment of cervical radiculopathy and myelopathy. This approach significantly reduces muscular damage and blood loss by minimizing soft tissue stripping, leading to less postoperative pain and a faster postoperative recovery. As scientific evidence accumulates, the efficacy and safety of cervical endoscopic spine surgery are continually affirmed. Both anterior and posterior endoscopic approaches have surfaced as viable alternative treatments for various cervical spine pathologies. Newer techniques, such as endoscopic-assisted fusion, the anterior transcorporeal approach, and unilateral laminotomy for bilateral decompression, have been developed to enhance clinical outcomes and broaden surgical indications. Despite its advantages, this approach faces challenges, including a steep learning curve, increased radiation exposure for both surgeons and patients, and a relative limitation in addressing multi-level pathologies. However, the future of cervical endoscopic spine surgery is promising, with potential enhancements in clinical outcomes and safety on the horizon. This progress is fueled by integrating advanced imaging and navigation technologies, applying regional anesthesia for improved and facilitated postoperative recovery, and incorporating cutting-edge technologies, such as augmented reality. With these advancements, cervical endoscopic spine surgery is poised to broaden its scope in treating cervical spine pathologies while maintaining the benefits of minimized tissue damage and rapid recovery.

20.
J Magn Reson Imaging ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38686707

RESUMO

BACKGROUND: Artificial intelligence shows promise in assessing knee osteoarthritis (OA) progression on MR images, but faces challenges in accuracy and interpretability. PURPOSE: To introduce a temporal-regional graph convolutional network (TRGCN) on MR images to study the association between knee OA progression status and network outcome. STUDY TYPE: Retrospective. POPULATION: 194 OA progressors (mean age, 62 ± 9 years) and 406 controls (mean age, 61 ± 9 years) from the OA Initiative were randomly divided into training (80%) and testing (20%) cohorts. FIELD STRENGTH/SEQUENCE: Sagittal 2D IW-TSE-FS (IW) and 3D-DESS-WE (DESS) at 3T. ASSESSMENT: Anatomical subregions of cartilage, subchondral bone, meniscus, and the infrapatellar fat pad at baseline, 12-month, and 24-month were automatically segmented and served as inputs to form compartment-based graphs for a TRGCN model, which containing both regional and temporal information. The performance of models based on (i) clinical variables alone, (ii) radiologist score alone, (iii) combined features (containing i and ii), (iv) composite TRGCN (combining TRGCN, i and ii), (v) radiomics features, (vi) convolutional neural network based on Densenet-169 were compared. STATISTICAL TESTS: DeLong test was performed to compare the areas under the ROC curve (AUC) of all models. Additionally, interpretability analysis was done to evaluate the contributions of individual regions. A P value <0.05 was considered significant. RESULTS: The composite TRGCN outperformed all other models with AUCs of 0.841 (DESS) and 0.856 (IW) in the testing cohort (all P < 0.05). Interpretability analysis highlighted cartilage's importance over other structures (42%-45%), tibiofemoral joint's (TFJ) dominance over patellofemoral joint (PFJ) (58%-67% vs. 12%-37%), and importance scores changes in compartments over time (TFJ vs. PFJ: baseline: 44% vs. 43%, 12-month: 52% vs. 39%, 24-month: 31% vs. 48%). DATA CONCLUSION: The composite TRGCN, capturing temporal and regional information, demonstrated superior discriminative ability compared with other methods, providing interpretable insights for identifying knee OA progression. TECHNICAL EFFICACY: Stage 2.

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