Acute Kidney Injury After Percutaneous Coronary Intervention Guided by Intravascular Ultrasound.

Purpose We investigated the impact of intravascular ultrasound guidance on reducing the incidence of contrast-induced acute kidney injury (CI-AKI) in patients undergoing percutaneous coronary intervention (PCI). Methods Ninety-nine patients were enrolled in this prospective cohort who were not randomly assigned to angiography-guided percutaneous coronary intervention or intravascular ultrasound-guided percutaneous coronary intervention. The patients were hospitalized at the Vietnam National Heart Institute - Bach Mai Hospital between 2019 and 2020. Acute kidney injury incidence during hospitalization was the primary endpoint. Results A total of 99 patients were divided into two groups: the intravascular ultrasound-guided group (33 participants) and the angiography-guided group (66 participants). The mean ± SD contrast volume of each group was 95.2 ± 37.1 mL and 133.0 ± 36.0 mL for the ultrasound-guided and angiography-guided groups, with P < 0.0001. Intravascular imaging-guided percutaneous coronary intervention (IVUS-guided PCI) was associated with reduced acute kidney injury incidence during hospitalization: 0.0% vs. 12.12% and P = 0.049. Conclusions Intravascular ultrasound is a safe imaging tool that guides percutaneous coronary intervention and significantly reduces the rate of acute kidney injury compared to angiography alone. Patients who have a high chance of experiencing acute kidney injury benefit from using intravascular ultrasound.

Antibody Response after a Booster COVID-19 Vaccine Mixing in Vietnam.

BACKGROUND: The booster vaccine is essential for maintaining the antibody against the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) virus. This study sought to evaluate the antibody response after booster coronavirus disease 2019 (COVID-19) vaccines and compare the immunogenic by different vaccine combination strategies. METHODS: A cross-sectional study in Hanoi, Vietnam was conducted on 679 adult participants who received two doses of vaccines with any combination of AstraZeneca, Pfizer, and Moderna during the COVID-19 vaccination campaign in 2021. The SARS-CoV-2 S1/S2 Immunoglobulin G (IgG) antibody concentrations were measured by the LIAISON SARS-CoV-2 S1/S2 IgG and presented as arbitrary units. RESULTS: We found that the median (interquartile range (IQR)) of IgG level among those who completed two doses of Moderna and Pfizer was 484.55 (284.80) AU/mL and 349.00 (362.50) AU/mL, respectively. Meanwhile, the counterpart of AstraZeneca was 110.00 (128.10) AU/mL. Mixing two doses of AstraZeneca-Pfizer has higher odds of having high IgG level than two doses of Pfizer (Odds Ratios (OR) = 2.94, 95% Confidence Intervals (CI): 1.57-5.51), AstraZeneca (OR = 28.50, 95% CI: 15.00-54.14). CONCLUSIONS: We found that the matching two doses of mRNA vaccines are more immunogenic as compared to the DNA vector vaccines. Furthermore, mixing AstraZeneca-Pfizer has higher antibody quantities as compared to matching vaccines, while lower the rate of advert events.

Early administration of tecovirimat shortens the time to mpox clearance in a model of human infection.

Despite use of tecovirimat since the beginning of the 2022 outbreak, few data have been published on its antiviral effect in humans. We here predict tecovirimat efficacy using a unique set of data in nonhuman primates (NHPs) and humans. We analyzed tecovirimat antiviral activity on viral kinetics in NHP to characterize its concentration-effect relationship in vivo. Next, we used a pharmacological model developed in healthy volunteers to project its antiviral efficacy in humans. Finally, a viral dynamic model was applied to characterize mpox kinetics in skin lesions from 54 untreated patients, and we used this modeling framework to predict the impact of tecovirimat on viral clearance in skin lesions. At human-recommended doses, tecovirimat could inhibit viral replication from infected cells by more than 90% after 3 to 5 days of drug administration and achieved over 97% efficacy at drug steady state. With an estimated mpox within-host basic reproduction number, R0, equal to 5.6, tecovirimat could therefore shorten the time to viral clearance if given before viral peak. We predicted that initiating treatment at symptom onset, which on average occurred 2 days before viral peak, could reduce the time to viral clearance by about 6 days. Immediate postexposure prophylaxis could not only reduce time to clearance but also lower peak viral load by more than 1.0 log10 copies/mL and shorten the duration of positive viral culture by about 7 to 10 days. These findings support the early administration of tecovirimat against mpox infection, ideally starting from the infection day as a postexposure prophylaxis.

Parental knowledge and practice on childhood caries prevention in northern Vietnam.

This study was conducted to describe the knowledge and practices on dental caries prevention among parents of preschool children in Vietnam and identify associated factors. A cross-sectional study was conducted in three preschools in Northern Vietnam in 2020. A total of 316 parents of preschool children were randomly recruited. Knowledge and practices regarding early dental caries prevention were asked by using a structured questionnaire. Multivariate Tobit regression was used to examine factors associated with knowledge and practice scores. Results showed four aspects of knowledge that had the lowest proportion of parents having correct responses included timing of complete primary tooth replacement (12.3%), benefits of undergoing regular dental examination (31.7%), technique for brushing a child's teeth (33.9%), and duration for brushing (36.7%). The knowledge of parents was moderately low at 6.3/12 (SD = 2.3). The practices of parents were moderately good with the mean practice score at 6.1/9 (SD = 2.0). The proportion of parents taking children for regular checkups (56.2%) and replacing toothbrush every 3 months (53.7%) were the lowest. Information source, occupation, education and perceived necessity of oral care were found to be associated with parents' knowledge and practices. To conclude, parents had moderate levels of knowledge and practices regarding early dental caries prevention in preschool children. Further studies and interventions should be performed to improve parental knowledge and practices that could enhance the oral health of children.

Further Understanding the Roles of Solvent, Brønsted Acids, and Hydrogen Bonding in Iron Porphyrin-Mediated Carbon Dioxide Reduction.

Improving our understanding of how molecules and materials mediate the electrochemical reduction of carbon dioxide (CO2) to upgraded products is of great interest as a means to address climate change. A leading class of molecules that can facilitate the electrochemical conversion of CO2 to carbon monoxide (CO) is iron porphyrins. These molecules can have high rate constants for CO2-to-CO conversion; they are robust, and they rely on abundant and inexpensive synthetic building blocks. Important foundational work has been conducted using chloroiron 5,10,15,20-tetraphenylporphyrin (FeTPPCl) in N,N-dimethylformamide (DMF) solvent. A related and recent report points out that the corresponding perchlorate complex, FeTPPClO4, can have superior function due to its solubility in other organic solvents. However, the importance of hydrogen bonding and solvent effects was not discussed. Herein, we present a detailed kinetic study of the triflate (CF3SO3-) complex of FeTPP in DMF and in MeCN using a range of phenol Brønsted acid additives. We also detected the formation of Fe(III)TPP-phenolate complexes using cyclic voltammetry experiments. Importantly, our new analysis of apparent rate constants with different added phenols allows for a modification to the established mechanistic model for CO2-to-CO conversion. Critically, our improved model accounts for hydrogen bonding and solvent effects by using simple hydrogen bond acidity and basicity descriptors. We use this augmented model to rationalize function in other reported porphyrin systems and to make predictions about operational conditions that can enhance the CO2 reduction chemistry.

High-Valent Ni and Cu Complexes of a Tetraanionic Bis(amidateanilido) Ligand.

High-valent metal species are often invoked as intermediates during enzymatic and synthetic catalytic cycles. Anionic donors are often required to stabilize such high-valent states by forming strong bonds with the Lewis acidic metal centers while decreasing their oxidation potentials. In this report, we discuss the synthesis of two high-valent metal complexes [ML]+ in which the NiIII and CuIII centers are ligated by a new tetradentate, tetraanionic bis(amidateanilido) ligand. [ML]+, obtained via chemical oxidation of ML, exhibits UV-vis-NIR, EPR, and XANES spectra characteristic of square planar, high-valent MIII species, suggesting the locus of oxidation for both [ML]+ is predominantly metal-based. This is supported by theoretical analyses, which also support the observed visible transitions as ligand-to-metal charge transfer transitions characteristic of square planar, high-valent MIII species. Notably, [ML]+ can also be obtained via O2 oxidation of ML due to its remarkably negative oxidation potentials (CuL/[CuL]+: -1.16 V, NiL/[NiL]+: -1.01 V vs Fc/Fc+ in MeCN). This demonstrates the exceptionally strong donating nature of the tetraanionic bis(amidateanilido) ligation and its ability to stabilize high-valent metal centers..

Total RNA sequencing reveals gene expression and microbial alterations shared by oral pre-malignant lesions and cancer.

Head and neck cancers are a complex malignancy comprising multiple anatomical sites, with cancer of the oral cavity ranking among the deadliest and the most disfiguring cancers globally. Oral cancer (OC) constitutes a subset of head and neck cancer cases, presenting primarily as tobacco- and alcohol-associated oral squamous cell carcinoma (OSCC), with a 5-year survival rate of ~ 65%, partly due to the lack of early detection and effective treatments. OSCC arises from premalignant lesions (PMLs) in the oral cavity through a multi-step series of clinical and histopathological stages, including varying degrees of epithelial dysplasia. To gain insights into the molecular mechanisms associated with the progression of PMLs to OSCC, we profiled the whole transcriptome of 66 human PMLs comprising leukoplakia with dysplasia and hyperkeratosis non-reactive (HkNR) pathologies, alongside healthy controls and OSCC. Our data revealed that PMLs were enriched in gene signatures associated with cellular plasticity, such as partial EMT (p-EMT) phenotypes, and with immune response. Integrated analyses of the host transcriptome and microbiome further highlighted a significant association between differential microbial abundance and PML pathway activity, suggesting a contribution of the oral microbiome toward PML evolution to OSCC. Collectively, this study reveals molecular processes associated with PML progression that may help early diagnosis and disease interception at an early stage.

Modifying the trajectory of epicardial leads can substantially reduce MRI-induced RF heating in pediatric patients with a cardiac implantable electronic device at 1.5T.

PURPOSE: After epicardial cardiac implantable electronic devices are implanted in pediatric patients, they become ineligible to receive MRI exams due to an elevated risk of RF heating. We investigated whether simple modifications in the trajectories of epicardial leads could substantially and reliably reduce RF heating during MRI at 1.5 T, with benefits extending to abandoned leads. METHODS: Electromagnetic simulations were performed to assess RF heating of two common 35-cm epicardial lead trajectories exhibiting different degrees of coupling with MRI incident electric fields. Experiments in anthropomorphic phantoms implanted with commercial cardiac implantable electronic devices confirmed the findings. Both electromagnetic simulations and experimental measurements were performed using head-first and feet-first positioning and various landmarks. Transfer function approach was used to assess the performance of suggested modifications in realistic body models. RESULTS: Simulations (head-first, chest landmark) of a 35-cm epicardial lead with a trajectory where the excess length of the lead was looped and placed on the inferior surface of the heart showed an 87-fold reduction in the 0.1 g-averaged specific absorption rate compared with the lead where the excess length was looped on the anterior surface. Repeated experiments with a commercial epicardial device confirmed this. For fully implanted systems following low-specific absorption rate trajectories, there was a 16-fold reduction in the average temperature rise and a 28-fold reduction for abandoned leads. The transfer function method predicted a 7-fold reduction in the RF heating in 336 realistic scenarios. CONCLUSION: Surgical modification of epicardial lead trajectory can substantially reduce RF heating at 1.5 T, with benefits extending to abandoned leads.

Risk factors for cannula-associated arterial thrombosis following extracorporeal membrane oxygenation support: a retrospective study.

BACKGROUND: Hemostatic dysfunction during extracorporeal membrane oxygenation (ECMO) due to blood-circuit interaction and the consequences of shear stress imposed by flow rates lead to rapid coagulation cascade and thrombus formation in the ECMO system and blood vessels. We aimed to identify the incidence and risk factors for cannula-associated arterial thrombosis (CaAT) post-decannulation. METHODS: A retrospective study of patients undergoing arterial cannula removal following ECMO was performed. We evaluated the incidence of CaAT and compared the characteristics, ECMO machine parameters, cannula sizes, number of blood products transfused during ECMO, and daily hemostasis parameters in patients with and without CaAT. Multivariate analysis identified the risk factors for CaAT. RESULTS: Forty-seven patients requiring venoarterial ECMO (VA-ECMO) or hybrid methods were recruited for thrombosis screening. The median Sequential Organ Failure Assessment score was 11 (interquartile range, 8-13). CaAT occurred in 29 patients (61.7%), with thrombosis in the superficial femoral artery accounting for 51.7% of cases. The rate of limb ischemia complications in the CaAT group was 17.2%. Multivariate analysis determined that the ECMO flow rate-body surface area (BSA) ratio (100 ml/min/m2) was an independent factor for CaAT, with an odds ratio of 0.79 (95% confidence interval, 0.66-0.95; P=0.014). CONCLUSIONS: We found that the incidence of CaAT was 61.7% following successful decannulation from VA-ECMO or hybrid modes, and the ECMO flow rate-BSA ratio was an independent risk factor for CaAT. We suggest screening for arterial thrombosis following VA-ECMO, and further research is needed to determine the risks and benefits of such screening.

Induction of Aryl Hydrocarbon Receptor-Mediated Cancer Cell-Selective Apoptosis in Triple-Negative Breast Cancer Cells by a High-Affinity Benzimidazoisoquinoline.

Triple-negative breast cancer (TNBC) remains a disease with a paucity of targeted treatment opportunities. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is involved in a wide range of physiological processes, including the sensing of xenobiotics, immune function, development, and differentiation. Different small-molecule AhR ligands drive strikingly varied cellular and organismal responses. In certain cancers, AhR activation by select small molecules induces cell cycle arrest or apoptosis via activation of tumor-suppressive transcriptional programs. AhR is expressed in triple-negative breast cancers, presenting a tractable therapeutic opportunity. Here, we identify a novel ligand of the aryl hydrocarbon receptor that potently and selectively induces cell death in triple-negative breast cancer cells and TNBC stem cells via the AhR. Importantly, we found that this compound, Analog 523, exhibits minimal cytotoxicity against multiple normal human primary cells. Analog 523 represents a high-affinity AhR ligand with potential for future clinical translation as an anticancer agent.

Giant schwannoma on the lower leg: A case report and review of the literature.

INTRODUCTION AND IMPORTANCE: Peripheral nerve sheath tumors are common neoplasm with different biological features ranging from benign to malignant. The majority of these tumors are smaller than 5 cm, whereas those larger are termed giant schwannomas. When localized in the lower legs, the maximum length of the schwannoma is less than 10 cm. We report a case of giant schwannoma of the leg and its management. CASE PRESENTATION: A 11-year-old boy presented with a 13 cm × 5 cm firm, smooth, well-defined margin mass in the posterior-medial aspect of right leg. The tumor was fusiform, well capsulated, multi-lobulated soft tissue with 13 cm × 4 cm × 3 cm in size at the biggest region. On MRI the tumor was low signal, isointense with adjacent tissue on T1S, hyper-intense on T2-FS sequences and surrounded by a thin fat-like intense rim. Biopsy findings were considered most consistent with Schwannoma (Antoni A). Tumor resection was performed. The mass appeared capsulated, white, and glistening with 132 mm × 45 mm × 34 mm in size. Postoperative course was uneventful without neurological deficit. CLINICAL DISCUSSION AND CONCLUSION: Schwannomas are the most common peripheral nerve sheath tumors that derived almost entirely from Schwann cells. Schwannomas usually affect the head and neck region, localization in the lower extremity is rare. When located in lower extremity, the maximum diameter of 5 cm is described in most studies. Clinical presentation of schwannomas is unclear and unspecific. Diagnosis is based on ultrasound, MRI, and histology. The recommended treatment for schwannoma is surgical enucleation or resection without damaging the involved nerve.

Suppression of Ah Receptor (AhR) increases the aggressiveness of TNBC cells and 11-Cl-BBQ-activated AhR inhibits their growth.

Triple-negative breast cancer (TNBC) represents around 15% of the 2.26 million breast cancers diagnosed worldwide annually and has the worst outcome. Despite recent therapeutic advances, there remains a lack of targeted therapies for this breast cancer subtype. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with biological roles in regulating development, xenobiotic metabolism, cell cycle progression and cell death. AhR activation by select ligands can promote tumor suppression in multiple cancer types. AhR can negatively regulate the activity of different oncogenic signaling pathways and can directly upregulate tumor suppressor genes such as p27Kip1. To determine the role of AhR in TNBC, we generated AhR-deficient cancer cells and investigated the impact of AhR loss on TNBC cell growth phenotypes. We found that AhR-deficient MDA-MB-468 TNBC cells have increased proliferation and formed significantly more colonies compared to AhR expressing cells. These cells without AhR expression grew aggressively in vivo. To determine the molecular targets driving this phenotype, we performed transcriptomic profiling in AhR expressing and AhR knockout MDA-MB-468 cells and identified tyrosine receptor kinases, as well as other genes involved in proliferation, survival and clonogenicity that are repressed by AhR. In order to determine therapeutic targeting of AhR in TNBC, we investigated the anti-cancer effects of the novel AhR ligand 11-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (11-Cl-BBQ), which belongs to a class of high affinity, rapidly metabolized AhR ligands called benzimidazoisoquinolines (BBQs). 11-Cl-BBQ induced AhR-dependent cancer cell-selective growth inhibition and strongly inhibited colony formation in TNBC cells.

Survival Rates in Elderly Patients on Continuous Ambulatory Peritoneal Dialysis.

Purpose: The present study aimed at evaluating the survival rate, its associated factors, and the causes of death in elderly patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in Vietnam. Patients and Methods: This is a retrospective, observational study conducted among patients aged ≥65 years who underwent CAPD at Thong Nhat Hospital, Ho Chi Minh City, Vietnam, from April 2012 to December 2020. The Kaplan-Meier method was used to calculate the cumulative survival rate, and the Log rank test was used to analyze the factors associated with the survival rate of patients. Results: This study enrolled a total of 68 patients with a mean age of 71.93 ± 7.44 years at the initiation of CAPD. The most common complication among kidney failure patients was diabetic nephropathy (39.71%). The rate of concomitant cardiovascular diseases was 58.82%. The average survival rate was 45.59 ± 4.01 months. Peritonitis was the most common factor causing death (31.25%), followed by cardiovascular diseases (28.12%) and malnutrition (25%). The factors that impacted the survival rate included concomitant cardiovascular diseases, low serum albumin (<35 g/dL), and an indication of CAPD due to exhausted vascular access for hemodialysis at baseline. The main factor associated with a shorter survival time was concomitant cardiovascular diseases. Conclusion: It is necessary to improve the survival time beyond 5 years for elderly patients undergoing CAPD, especially for those with concomitant cardiovascular diseases. Besides the prevention of peritonitis, adequate measures to protect from cardiovascular diseases and malnutrition will reduce the mortality rate in patients on CAPD.

Arteriovenous fistula creation by nephrologist and its outcomes: a prospective cohort study from Vietnam.

BACKGROUND: Arteriovenous fistula (AVF) is the gold standard vascular access for effective hemodialysis. There is a growing interest in AVF creations performed by nephrologists to help reduce vascular surgeons' workload and enhance the timely treatment of patients with end-stage renal disease (ESRD). However, little is known about the feasibility and effectiveness of this approach in the low-resource settings. We examined the AVF surgical success and failure rates and associated predictors as well as early complications of AVF creations by a trained nephrologist with supports from vascular surgeons in Vietnam. METHODS: A prospective cohort study was conducted on all adult ESRD patients at the Hemodialysis Department of Thong Nhat Hospital between April 2018 and October 2020. Information on demographic characteristics, comorbidities, and AVF creations was collected using a standardized questionnaire. All patients were followed up until 18 weeks post-surgery. RESULTS: Among 100 patients with a mean age of 61.22 ± 17.11 years old, male accounted for 54%. Common causes of ESRD included hypertension (57%) and diabetes (32%). Just more than half (52%) of them reported having an AVF creation prior to ESRD. The successful first-time AVF creation rate was 98% (13/99, 95%CI: 8.74-21.18%). The primary and secondary AVF failure rates were 13.13% (13/99, 95%CI: 8.74-21.18%) and 16.87% (14/83, 95%CI: 10.32-26.25%), respectively. Early complications included bleeding (1%) and early thrombosis of the anastomosis (2%). There was a statistically significant association between age and primary AVF failure (P = 0.005) and between operation time and secondary AVF failure (P = 0.038). CONCLUSIONS: AVF creations performed by well-trained and skilled interventional nephrologists with supports from vascular surgeons can result in favorable short- and long-term outcomes. It is important to follow up older patients and those with a long operation time to detect AVF failures. A standardized AVF creation training program and practice for nephrologists is needed to increase successful rates.

Total RNA sequencing reveals gene expression and microbial alterations shared by oral pre-malignant lesions and cancer.

Head and neck cancers are a complex malignancy comprising multiple anatomical sites, with cancer of the oral cavity ranking among the deadliest and most disfiguring cancers globally. Oral cancer (OC) constitutes a subset of head and neck cancer cases, presenting primarily as tobacco-and alcohol-associated oral squamous cell carcinoma (OSCC), with a 5-year survival rate of ∻65%, partly due to the lack of early detection and effective treatments. OSCC arises from premalignant lesions (PMLs) in the oral cavity through a multi-step series of clinical and histopathological stages, including varying degrees of epithelial dysplasia. To gain insights into the molecular mechanisms associated with the progression of PMLs to OSCC, we profiled the whole transcriptome of 66 human PMLs comprising leukoplakia with dysplasia and hyperkeratosis non-reactive (HkNR) pathologies, alongside healthy controls and OSCC. Our data revealed that PMLs were enriched in gene signatures associated with cellular plasticity, such as partial EMT (p-EMT) phenotypes, and with immune response. Integrated analyses of the host transcriptome and microbiome further highlighted a significant association between differential microbial abundance and PML pathway activity, suggesting a contribution of the oral microbiome towards PML evolution to OSCC. Collectively, this study reveals molecular processes associated with PML progression that may help early diagnosis and disease interception at an early stage. AUTHOR SUMMARY: Patients harboring oral premalignant lesions (PMLs) have an increased risk of developing oral squamous cell carcinoma (OSCC), but the underlying mechanisms driving transformation of PMLs to OSCC remain poorly understood. In this study, Khan et al., analyzed a newly generated dataset of gene expression and microbial profiles of oral tissues from patients diagnosed with PMLs from differing histopathological groups, including hyperkeratosis not reactive ( HkNR ) and dysplasia, comparing these profiles with OSCC and normal oral mucosa. Significant similarities between PMLs and OSCC were observed, with PMLs manifesting several cancer hallmarks, including oncogenic and immune pathways. The study also demonstrates associations between the abundance of multiple microbial species and PML groups, suggesting a potential contribution of the oral microbiome to the early stages of OSCC development. The study offers insights into the nature of the molecular, cellular and microbial heterogeneity of oral PMLs and suggests that molecular and clinical refinement of PMLs may provide opportunities for early disease detection and interception.

11-Cl-BBQ, a select modulator of AhR-regulated transcription, suppresses lung cancer cell growth via activation of p53 and p27Kip1.

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and functions as a tumour suppressor in different cancer models. In the present study, we report detailed characterization of 11-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (11-Cl-BBQ) as a select modulator of AhR-regulated transcription (SMAhRT) with anti-cancer actions. Treatment of lung cancer cells with 11-Cl-BBQ induced potent and sustained AhR-dependent anti-proliferative effects by promoting G1 phase cell cycle arrest. Investigation of 11-Cl-BBQ-induced transcription in H460 cells with or without the AhR expression by RNA-sequencing revealed activation of p53 signalling. In addition, 11-Cl-BBQ suppressed multiple pathways involved in DNA replication and increased expression of cyclin-dependent kinase inhibitors, including p27Kip1 , in an AhR-dependent manner. CRISPR/Cas9 knockout of individual genes revealed the requirement for both p53 and p27Kip1 for the AhR-mediated anti-proliferative effects. Our results identify 11-Cl-BBQ as a potential lung cancer therapeutic, highlight the feasibility of targeting AhR and provide important mechanistic insights into AhR-mediated-anticancer actions.

A comparative study of RF heating of deep brain stimulation devices in vertical vs. horizontal MRI systems.

The majority of studies that assess magnetic resonance imaging (MRI) induced radiofrequency (RF) heating of the tissue when active electronic implants are present have been performed in horizontal, closed-bore MRI systems. Vertical, open-bore MRI systems have a 90° rotated magnet and a fundamentally different RF coil geometry, thus generating a substantially different RF field distribution inside the body. Little is known about the RF heating of elongated implants such as deep brain stimulation (DBS) devices in this class of scanners. Here, we conducted the first large-scale experimental study investigating whether RF heating was significantly different in a 1.2 T vertical field MRI scanner (Oasis, Fujifilm Healthcare) compared to a 1.5 T horizontal field MRI scanner (Aera, Siemens Healthineers). A commercial DBS device mimicking 30 realistic patient-derived lead trajectories extracted from postoperative computed tomography images of patients who underwent DBS surgery at our institution was implanted in a multi-material, anthropomorphic phantom. RF heating around the DBS lead was measured during four minutes of high-SAR RF exposure. Additionally, we performed electromagnetic simulations with leads of various internal structures to examine this effect on RF heating. When controlling for RMS B1+, the temperature increase around the DBS lead-tip was significantly lower in the vertical scanner compared to the horizontal scanner (0.33 ± 0.24°C vs. 4.19 ± 2.29°C). Electromagnetic simulations demonstrated up to a 17-fold reduction in the maximum of 0.1g-averaged SAR in the tissue surrounding the lead-tip in the vertical scanner compared to the horizontal scanner. Results were consistent across leads with straight and helical internal wires. Radiofrequency heating and power deposition around the DBS lead-tip were substantially lower in the 1.2 T vertical scanner compared to the 1.5 T horizontal scanner. Simulations with different lead structures suggest that the results may extend to leads from other manufacturers.

Loss of the aryl hydrocarbon receptor increases tumorigenesis in p53-deficient mice.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates cell fate via activation of a diverse set of genes. There are conflicting reports describing the role of AhR in cancer. AhR-knockout mice do not develop tumors spontaneously, yet the AhR can act as a tumor suppressor in certain contexts. Loss of tumor suppression by p53 is common in human cancer. To investigate AhR function in the absence of p53, we generated mice lacking both AhR and p53. Mice deficient for AhR and p53 had shortened lifespan, increased tumorigenesis, and an altered tumor spectrum relative to control mice lacking only p53. In addition, knockout of both AhR and p53 resulted in reduced embryonic survival and neonatal fitness. We also examined the consequences of loss of AhR in p53-heterozygous mice and observed a significantly reduced lifespan and enhanced tumor burden. These findings reveal an important role for the AhR as a tumor suppressor in the absence of p53 signaling and support the development of anti-cancer therapeutics that would promote the tumor suppressive actions of the AhR.

The cyclin-dependent kinase inhibitor p27Kip1 interacts with the aryl hydrocarbon receptor and negatively regulates its transcriptional activity.

p27Kip1 functions to coordinate cell cycle progression through the inhibition of cyclin-dependent kinase (CDK) complexes. p27Kip1 also exerts distinct activities beyond CDK-inhibition, including functioning as a transcriptional regulator. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with diverse biological roles. The regulatory inputs that control AhR-mediated transcriptional responses are an active area of investigation. AhR was previously established as a direct regulator of p27Kip1 transcription. Here, we report the physical interaction of AhR and p27Kip1 and show that p27Kip1 expression negatively regulates AhR-mediated transcription. p27Kip1 knockout cells display increased AhR nuclear localisation and significantly higher expression of AhR target genes. This work thus identifies new regulatory cross-talk between p27Kip1 and AhR.