BACKGROUND Four-dimensional(4D)flow magnetic resonance imaging(MRI)is used as a noninvasive modality for assessing hemodynamic information with neurovascular and body applications.The application of 4D flow MRI for as...BACKGROUND Four-dimensional(4D)flow magnetic resonance imaging(MRI)is used as a noninvasive modality for assessing hemodynamic information with neurovascular and body applications.The application of 4D flow MRI for assessment of bowel disease in children has not been previously described.AIM To determine feasibility of superior mesenteric venous and arterial flow quantitation in pediatric patients using 4D flow MRI.METHODS Nine pediatric patients(7-14 years old,5 male and 4 female)with history or suspicion of bowel pathology,who underwent magnetic resonance(MR)enterography with 4D flow MR protocol from November 2022 to October 2023.Field strength/sequence:3T MRI using 4D flow MR protocol.Flow velocity and peak speed measurements were performed by two diagnostic radiologists placing the region of interest in perpendicular plane to blood flow on each cross section of superior mesenteric artery(SMA)and superior mesenteric vein(SMV)at three predetermined levels.Bland-Altman analysis,showed good agreement of flow velocity and peak speed measurements of SMV and SMA between two readers.RESULTS Mean SMV flow velocity increased from proximal to mid to distal(0.14 L/minute,0.17 L/minute,0.22 L/minute respectively).Mean SMA flow velocity decreased from proximal to mid to distal(0.35 L/minute,0.27 L/minute,0.21 L/minute respectively).Observed agreement was good for flow velocity measurements of SMV(mean bias-0.01 L/minute and 95%limits of agreement,-0.09 to 0.08 L/minute)and SMA(mean bias-0.03 L/minute and 95%limits of agreement,-0.23 to 0.17 L/minute)between two readers.Good agreement for peak speed measurements of SMV(mean bias-1.2 cm/second and 95%limits of agreement,-9.4 to 7.0 cm/second)and SMA(mean bias-3.2 cm/second and 95%limits of agreement,-31.4 to 24.9 cm/second).CONCLUSION Flow quantitation using 4D Flow is feasible to provide hemodynamic information for SMV and SMA in children.展开更多
Deubiquitination has emerged as an important mechanism of p53 regulation. A number of deubiquitinating enzymes(DUBs) from the ubiquitin-specific protease family have been shown to regulate the p53-MDM2-MDMX networks. ...Deubiquitination has emerged as an important mechanism of p53 regulation. A number of deubiquitinating enzymes(DUBs) from the ubiquitin-specific protease family have been shown to regulate the p53-MDM2-MDMX networks. We recently reported that Otub1, a DUB from the OTU-domain containing protease family, is a novel p53 regulator. Interestingly, Otub1 abrogates p53 ubiquitination and stabilizes and activates p53 in cells independently of its deubiquitinating enzyme activity. Instead, it does so by inhibiting the MDM2 cognate ubiquitin-conjugating enzyme(E2) UbcH5. Otub1 also regulates other biological signaling through this non-canonical mechanism, suppression of E2, including the inhibition of DNA-damage-induced chromatin ubiquitination. Thus, Otub1 evolves as a unique DUB that mainly suppresses E2 to regulate substrates. Here we review the current progress made towards the understanding of the complex regulation of the p53 tumor suppressor pathway by DUBs, the biological function of Otub1 including its positive regulation of p53, and the mechanistic insights into how Otub1 suppresses E2.展开更多
We present a case of significant, persistent, and relatively refractory hypotension during general anesthesia in a reasonably healthy 50-year-old man thought to be caused by a direct rennin inhibitor. This case is of ...We present a case of significant, persistent, and relatively refractory hypotension during general anesthesia in a reasonably healthy 50-year-old man thought to be caused by a direct rennin inhibitor. This case is of particular significance because the medication thought responsible for the hemodynamic abnormalities is a relatively novel antihypertensive agent and remains largely unknown to clinical anesthesia providers.展开更多
Insomnia is a major health problem affecting millions of people around the globe, particularly in the developed world, substantially impacting on individual work performance and raising disability costs. Insomnias can...Insomnia is a major health problem affecting millions of people around the globe, particularly in the developed world, substantially impacting on individual work performance and raising disability costs. Insomnias can be broadly divided into primary and secondary types. Primary insomnias can further be divided into parasomnias and dyssomnias. Diagnostic approaches to insomnias can be challenging, thereby complicating the treatment process. Obstructive sleep apnea (OSA) falls under the category of primary insomnias and is a good example of frequently missed diagnoses. The goal of this paper is to document the development of a self-reporting sleep apnea scale based on graded percentage scores to correlate with primary, secondary and tertiary risks. Scores falling under fifty percent represent primary prevention risks of OSA and suggest possible interventions. A score of fifty percent highlights three core symptoms on the scale as described in detail below to represent early detection of OSA or secondary prevention. Finally, scores exceeding fifty percent will include associated risks of comorbidities as well as other factors contributing to OSA, or tertiary prevention, with separate scores assigned to individual risk factors. Analysis of final scores on the proposed scale would therefore, in our opinion help achieve the goal of grading the risk of OSA from a multidisciplinary preventive care aspect.展开更多
Hepatocellular carcinoma(HCC)is a leading cause of morbidity and mortality worldwide,with rising clinical and economic burden as incidence increases.There are a multitude of evolving treatment options,including locore...Hepatocellular carcinoma(HCC)is a leading cause of morbidity and mortality worldwide,with rising clinical and economic burden as incidence increases.There are a multitude of evolving treatment options,including locoregional therapies which can be used alone,in combination with each other,or in combination with systemic therapy.These treatment options have shown to be effective in achieving remission,controlling tumor progression,improving disease free and overall survival in patients who cannot undergo resection and providing a bridge to transplant by debulking tumor burden to downstage patients.Following locoregional therapy(LRT),it is crucial to provide treatment response assessment to guide management and liver transplant candidacy.Therefore,Liver Imaging Reporting and Data Systems(LI-RADS)Treatment Response Algorithm(TRA)was created to provide a standardized assessment of HCC following LRT.LIRADS TRA provides a step by step approach to evaluate each lesion independently for accurate tumor assessment.In this review,we provide an overview of different locoregional therapies for HCC,describe the expected post treatment imaging appearance following treatment,and review the LI-RADS TRA with guidance for its application in clinical practice.Unique to other publications,we will also review emerging literature supporting the use of LI-RADS for assessment of HCC treatment response after LRT.展开更多
Background Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and a number of studies showed the appearance of increased reactive oxygen species （ROS） and reactiv...Background Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and a number of studies showed the appearance of increased reactive oxygen species （ROS） and reactive nitrogen species （RNS） during and after noise exposure. This study was designed to investigate the noise exposure induced nitrotyrosine change and the mechanism of outer hair cells death in guinea pig cochlea. Method Thirty guinea pigs were used in this study. The experimental animals were either exposed for 4 hours per day to broadband noise at 122 dB SPL （A-weighted） for 2 consecutive days or perfused cochleae with 5 mg/ml of the SIN1 solutions, an exogenous NO and superoxide donor, for 30 minutes. Then the cochleae of the animals were dissected. Propidium iodide （PI）, a DNA intercalating fluorescent probe, was used to trace morphological changes in OHC nuclei. The distribution of nitrotyrosine （NT） in the organ of Corti and the cochlear lateral wall tissue from the guinea pigs were examined using fluorescence immunohistochemistry method. Whole mounts of organ of Corti were prepared. Morphological and fluorescent changes were examined under a confocal microscope. Results Either after noise exposure or after SIN1 perfusion, outer hair cells （OHCs） death with characteristics of both apoptotic and necrotic degradation appeared. Nitrotyrosine immunolabeling could be observed in the OHCs from the control animals. After noise exposure, NT immunostaining became much greater than the control animals in OHCs. The apoptotic OHC has significant increase of nitrotyrosine in and around the nucleus following noise exposure. In the normal later wall of cochleae, relatively weak nitrotyrosine immunolabeling could be observed. After noise exposure, nitrotyrosine immunoactivity became stronger in stria vascularis. Conclusion Noise exposure induced increase of nitrotyrosine production is associated with OHCs death suggesting reactive nitrogen species participation in the cochlear pathophysiology of noise-induced hearing loss.展开更多
The transcription factor c-MYC(MYC thereafter)controls diverse transcription programs and plays a key role in the development of many human cancers.Cells develop multiple mechanisms to ensure that MYC levels and activ...The transcription factor c-MYC(MYC thereafter)controls diverse transcription programs and plays a key role in the development of many human cancers.Cells develop multiple mechanisms to ensure that MYC levels and activity are precisely controlled in normal physiological context.As a short half-lived protein,MYC protein levels are tightly regulated by the ubiquitin proteasome system.Over a dozen of ubiquitin ligases have been found to ubiquitinate MYC whereas a number of deubiquitinating enzymes counteract this process.Recent studies show that SUMOylation and deSUMOylation can also regulate MYC protein stability and activity.Interestingly,evidence suggests an intriguing crosstalk between MYC ubiquitination and SUMOylation.Deregulation of the MYC ubiquitination-SUMOylation regulatory network may contribute to tumorigenesis.This review is intended to provide the current understanding of the complex regulation of the MYC biology by dynamic ubiquitination and SUMOylation and their crosstalk.展开更多
Scalp and cranial defects can occur as a result of cutaneous or bony malignancies,trauma,or surgical intervention for intracranial tumors.Soft tissue cranial reconstruction of composite defects presents a unique chall...Scalp and cranial defects can occur as a result of cutaneous or bony malignancies,trauma,or surgical intervention for intracranial tumors.Soft tissue cranial reconstruction of composite defects presents a unique challenge given the relative tissue inelasticity of the scalp,need for tension free closure,and convex shape of the cranium.An added complexity is found in patients with large defects,cerebrospinal fluid leak,prior failed reconstruction,infection,or previous radiation.Methods and materials for skull reconstruction have evolved significantly over the years,allowing surgeons to repair even the most challenging composite defects with excellent success rates.This review aims to discuss and evaluate the available soft tissue options for cranioplasty coverage,with particular focus on hostile reconstructive fields and the use of free tissue transfer.展开更多
文摘BACKGROUND Four-dimensional(4D)flow magnetic resonance imaging(MRI)is used as a noninvasive modality for assessing hemodynamic information with neurovascular and body applications.The application of 4D flow MRI for assessment of bowel disease in children has not been previously described.AIM To determine feasibility of superior mesenteric venous and arterial flow quantitation in pediatric patients using 4D flow MRI.METHODS Nine pediatric patients(7-14 years old,5 male and 4 female)with history or suspicion of bowel pathology,who underwent magnetic resonance(MR)enterography with 4D flow MR protocol from November 2022 to October 2023.Field strength/sequence:3T MRI using 4D flow MR protocol.Flow velocity and peak speed measurements were performed by two diagnostic radiologists placing the region of interest in perpendicular plane to blood flow on each cross section of superior mesenteric artery(SMA)and superior mesenteric vein(SMV)at three predetermined levels.Bland-Altman analysis,showed good agreement of flow velocity and peak speed measurements of SMV and SMA between two readers.RESULTS Mean SMV flow velocity increased from proximal to mid to distal(0.14 L/minute,0.17 L/minute,0.22 L/minute respectively).Mean SMA flow velocity decreased from proximal to mid to distal(0.35 L/minute,0.27 L/minute,0.21 L/minute respectively).Observed agreement was good for flow velocity measurements of SMV(mean bias-0.01 L/minute and 95%limits of agreement,-0.09 to 0.08 L/minute)and SMA(mean bias-0.03 L/minute and 95%limits of agreement,-0.23 to 0.17 L/minute)between two readers.Good agreement for peak speed measurements of SMV(mean bias-1.2 cm/second and 95%limits of agreement,-9.4 to 7.0 cm/second)and SMA(mean bias-3.2 cm/second and 95%limits of agreement,-31.4 to 24.9 cm/second).CONCLUSION Flow quantitation using 4D Flow is feasible to provide hemodynamic information for SMV and SMA in children.
基金Supported by NIH/NCI,No.R00 CA127134 and No.R01CA160474a Department of Defense,No.W81XWH-10-1-1029,to Dai MSA Grant from Medical Research Foundation(MRF)of Oregon,to Sun XX
文摘Deubiquitination has emerged as an important mechanism of p53 regulation. A number of deubiquitinating enzymes(DUBs) from the ubiquitin-specific protease family have been shown to regulate the p53-MDM2-MDMX networks. We recently reported that Otub1, a DUB from the OTU-domain containing protease family, is a novel p53 regulator. Interestingly, Otub1 abrogates p53 ubiquitination and stabilizes and activates p53 in cells independently of its deubiquitinating enzyme activity. Instead, it does so by inhibiting the MDM2 cognate ubiquitin-conjugating enzyme(E2) UbcH5. Otub1 also regulates other biological signaling through this non-canonical mechanism, suppression of E2, including the inhibition of DNA-damage-induced chromatin ubiquitination. Thus, Otub1 evolves as a unique DUB that mainly suppresses E2 to regulate substrates. Here we review the current progress made towards the understanding of the complex regulation of the p53 tumor suppressor pathway by DUBs, the biological function of Otub1 including its positive regulation of p53, and the mechanistic insights into how Otub1 suppresses E2.
文摘We present a case of significant, persistent, and relatively refractory hypotension during general anesthesia in a reasonably healthy 50-year-old man thought to be caused by a direct rennin inhibitor. This case is of particular significance because the medication thought responsible for the hemodynamic abnormalities is a relatively novel antihypertensive agent and remains largely unknown to clinical anesthesia providers.
文摘Insomnia is a major health problem affecting millions of people around the globe, particularly in the developed world, substantially impacting on individual work performance and raising disability costs. Insomnias can be broadly divided into primary and secondary types. Primary insomnias can further be divided into parasomnias and dyssomnias. Diagnostic approaches to insomnias can be challenging, thereby complicating the treatment process. Obstructive sleep apnea (OSA) falls under the category of primary insomnias and is a good example of frequently missed diagnoses. The goal of this paper is to document the development of a self-reporting sleep apnea scale based on graded percentage scores to correlate with primary, secondary and tertiary risks. Scores falling under fifty percent represent primary prevention risks of OSA and suggest possible interventions. A score of fifty percent highlights three core symptoms on the scale as described in detail below to represent early detection of OSA or secondary prevention. Finally, scores exceeding fifty percent will include associated risks of comorbidities as well as other factors contributing to OSA, or tertiary prevention, with separate scores assigned to individual risk factors. Analysis of final scores on the proposed scale would therefore, in our opinion help achieve the goal of grading the risk of OSA from a multidisciplinary preventive care aspect.
文摘Hepatocellular carcinoma(HCC)is a leading cause of morbidity and mortality worldwide,with rising clinical and economic burden as incidence increases.There are a multitude of evolving treatment options,including locoregional therapies which can be used alone,in combination with each other,or in combination with systemic therapy.These treatment options have shown to be effective in achieving remission,controlling tumor progression,improving disease free and overall survival in patients who cannot undergo resection and providing a bridge to transplant by debulking tumor burden to downstage patients.Following locoregional therapy(LRT),it is crucial to provide treatment response assessment to guide management and liver transplant candidacy.Therefore,Liver Imaging Reporting and Data Systems(LI-RADS)Treatment Response Algorithm(TRA)was created to provide a standardized assessment of HCC following LRT.LIRADS TRA provides a step by step approach to evaluate each lesion independently for accurate tumor assessment.In this review,we provide an overview of different locoregional therapies for HCC,describe the expected post treatment imaging appearance following treatment,and review the LI-RADS TRA with guidance for its application in clinical practice.Unique to other publications,we will also review emerging literature supporting the use of LI-RADS for assessment of HCC treatment response after LRT.
基金This research was supported by the grants from National Natural Science Foundation of China，Nuttal Alfred's Grant (NIH NIDCD DC 000105 and Shi Xiaorui's Grant
文摘Background Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and a number of studies showed the appearance of increased reactive oxygen species （ROS） and reactive nitrogen species （RNS） during and after noise exposure. This study was designed to investigate the noise exposure induced nitrotyrosine change and the mechanism of outer hair cells death in guinea pig cochlea. Method Thirty guinea pigs were used in this study. The experimental animals were either exposed for 4 hours per day to broadband noise at 122 dB SPL （A-weighted） for 2 consecutive days or perfused cochleae with 5 mg/ml of the SIN1 solutions, an exogenous NO and superoxide donor, for 30 minutes. Then the cochleae of the animals were dissected. Propidium iodide （PI）, a DNA intercalating fluorescent probe, was used to trace morphological changes in OHC nuclei. The distribution of nitrotyrosine （NT） in the organ of Corti and the cochlear lateral wall tissue from the guinea pigs were examined using fluorescence immunohistochemistry method. Whole mounts of organ of Corti were prepared. Morphological and fluorescent changes were examined under a confocal microscope. Results Either after noise exposure or after SIN1 perfusion, outer hair cells （OHCs） death with characteristics of both apoptotic and necrotic degradation appeared. Nitrotyrosine immunolabeling could be observed in the OHCs from the control animals. After noise exposure, NT immunostaining became much greater than the control animals in OHCs. The apoptotic OHC has significant increase of nitrotyrosine in and around the nucleus following noise exposure. In the normal later wall of cochleae, relatively weak nitrotyrosine immunolabeling could be observed. After noise exposure, nitrotyrosine immunoactivity became stronger in stria vascularis. Conclusion Noise exposure induced increase of nitrotyrosine production is associated with OHCs death suggesting reactive nitrogen species participation in the cochlear pathophysiology of noise-induced hearing loss.
基金We thank members of the Dai and Sears laboratories for active discussion.This work was supported by NIH/NCI grant R01 CA186241 to M-S.D.and R.S.
文摘The transcription factor c-MYC(MYC thereafter)controls diverse transcription programs and plays a key role in the development of many human cancers.Cells develop multiple mechanisms to ensure that MYC levels and activity are precisely controlled in normal physiological context.As a short half-lived protein,MYC protein levels are tightly regulated by the ubiquitin proteasome system.Over a dozen of ubiquitin ligases have been found to ubiquitinate MYC whereas a number of deubiquitinating enzymes counteract this process.Recent studies show that SUMOylation and deSUMOylation can also regulate MYC protein stability and activity.Interestingly,evidence suggests an intriguing crosstalk between MYC ubiquitination and SUMOylation.Deregulation of the MYC ubiquitination-SUMOylation regulatory network may contribute to tumorigenesis.This review is intended to provide the current understanding of the complex regulation of the MYC biology by dynamic ubiquitination and SUMOylation and their crosstalk.
文摘Scalp and cranial defects can occur as a result of cutaneous or bony malignancies,trauma,or surgical intervention for intracranial tumors.Soft tissue cranial reconstruction of composite defects presents a unique challenge given the relative tissue inelasticity of the scalp,need for tension free closure,and convex shape of the cranium.An added complexity is found in patients with large defects,cerebrospinal fluid leak,prior failed reconstruction,infection,or previous radiation.Methods and materials for skull reconstruction have evolved significantly over the years,allowing surgeons to repair even the most challenging composite defects with excellent success rates.This review aims to discuss and evaluate the available soft tissue options for cranioplasty coverage,with particular focus on hostile reconstructive fields and the use of free tissue transfer.
