1.Intestinal epithelial cell NCoR deficiency ameliorates obesity and metabolic syndrome.
Shaocong HOU ; Hengcai YU ; Caihong LIU ; Andrew M F JOHNSON ; Xingfeng LIU ; Qian JIANG ; Qijin ZHAO ; Lijuan KONG ; Yanjun WAN ; Xiaowei XING ; Yibing CHEN ; Jingwen CHEN ; Qing WU ; Peng ZHANG ; Changtao JIANG ; Bing CUI ; Pingping LI
Acta Pharmaceutica Sinica B 2024;14(12):5267-5285
Nuclear receptor corepressor (NCoR1) interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids. An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development. In this study, we found that the deletion of NCoR1 in intestinal epithelial cells (IECs) mainly activated the nuclear receptor PPARα and attenuated metabolic syndrome by stimulating thermogenesis. The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate, whose production was significantly enhanced by PPARα activation in the fed state. Additionally, NCoR1 deletion derepressed intestinal LXR, increased cholesterol excretion, and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity, thereby reversing the possible negative effects of intestinal PPARα activation. Therefore, the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.
2.Assessing Patient Risk, Benefit, and Outcomes in Drug Development: A Decade of Abiraterone Clinical Trials
Matthew RASHID ; Eli OLDHAM ; Griffin K. HUGHES ; Andriana M. PEÑA ; Chase LADD ; Brooke GARDNER ; Ryan MCINTIRE ; Bradley JOHNSON ; Jordan TUIA ; Alyson HASLAM ; Vinay PRASAD ; Matt VASSAR
Journal of Urologic Oncology 2024;22(3):211-223
Purpose:
Our study aimed to evaluate the risk and benefit profiles of clinical trials using abiraterone in cancer treatment.
Materials and Methods:
A comprehensive search was conducted on May 24, 2023, using databases such as PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. We extracted data on adverse events, progression-free survival, overall survival, objective response rate (ORR), and prostate-specific antigen response rate (PSA-RR). The Common Terminology Criteria for Adverse Events were used to assess risks, while ORR and PSA-RR were used to assess benefits. Trials were categorized as positive, negative, or indeterminate based on their safety profiles and efficacy outcomes.
Results:
Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint. Our study supports abiraterone’s use in prostate cancer, its only U.S. Food and Drug Administration-approved indication to treat, with a median ORR of 20.0% and a median PSA-RR of 42.0%. However, when looking at the 3 novel indications tested, the risk-to-benefit profile was similar to that of its original approval. Even though most novel indications failed to meet their primary endpoint, the overall toxicity profile was similar to that found in prostate cancer.
Conclusion
Abiraterone showed an overall risk-to-benefit portfolio that supports the use of its treatment in prostate cancer. Although the primary endpoints in ovarian and breast cancer trials were not met, the use was appropriate when assessing how the mechanism of action for abiraterone could be beneficial in patients with these types of cancers.
3.The correlation between carotid artery Doppler and stroke volume during central blood volume loss and resuscitation
Isabel KERREBIJN ; Sarah ATWI ; Mai ELFARNAWANY ; Andrew M. EIBL ; Joseph K. EIBL ; Jenna L. TAYLOR ; Chul Ho KIM ; Bruce D. JOHNSON ; Jon-Émile S. KENNY
Acute and Critical Care 2024;39(1):162-168
Using peripheral arteries to infer central hemodynamics is common among hemodynamic monitors. Doppler ultrasound of the common carotid artery has been used in this manner with conflicting results. We investigated the relationship between changing common carotid artery Doppler measures and stroke volume (SV), hypothesizing that more consecutively-averaged cardiac cycles would improve SV-carotid Doppler correlation. Methods: Twenty-seven healthy volunteers were recruited and studied in a physiology laboratory. Carotid artery Doppler pulse was measured with a wearable, wireless ultrasound during central hypovolemia and resuscitation induced by a stepped lower body negative pressure protocol. The change in maximum velocity time integral (VTI) and corrected flow time of the carotid artery (ccFT) were compared with changing SV using repeated measures correlation. Results: In total, 73,431 cardiac cycles were compared across 27 subjects. There was a strong linear correlation between changing SV and carotid Doppler measures during simulated hemorrhage (repeated-measures linear correlation [Rrm ]=0.91 for VTI; 0.88 for ccFT). This relationship improved with larger numbers of consecutively-averaged cardiac cycles. For ccFT, beyond four consecutively-averaged cardiac cycles the correlation coefficient remained strong (i.e., Rrm of at least 0.80). For VTI, the correlation coefficient with SV was strong for any number of averaged cardiac cycles. For both ccFT and VTI, Rrm remained stable around 25 consecutively-averaged cardiac cycles. Conclusions: There was a strong linear correlation between changing SV and carotid Doppler measures during central blood volume loss. The strength of this relationship was dependent upon the number of consecutively-averaged cardiac cycles.
4.The correlation between carotid artery Doppler and stroke volume during central blood volume loss and resuscitation
Isabel KERREBIJN ; Sarah ATWI ; Mai ELFARNAWANY ; Andrew M. EIBL ; Joseph K. EIBL ; Jenna L. TAYLOR ; Chul Ho KIM ; Bruce D. JOHNSON ; Jon-Émile S. KENNY
Acute and Critical Care 2024;39(1):162-168
Using peripheral arteries to infer central hemodynamics is common among hemodynamic monitors. Doppler ultrasound of the common carotid artery has been used in this manner with conflicting results. We investigated the relationship between changing common carotid artery Doppler measures and stroke volume (SV), hypothesizing that more consecutively-averaged cardiac cycles would improve SV-carotid Doppler correlation. Methods: Twenty-seven healthy volunteers were recruited and studied in a physiology laboratory. Carotid artery Doppler pulse was measured with a wearable, wireless ultrasound during central hypovolemia and resuscitation induced by a stepped lower body negative pressure protocol. The change in maximum velocity time integral (VTI) and corrected flow time of the carotid artery (ccFT) were compared with changing SV using repeated measures correlation. Results: In total, 73,431 cardiac cycles were compared across 27 subjects. There was a strong linear correlation between changing SV and carotid Doppler measures during simulated hemorrhage (repeated-measures linear correlation [Rrm ]=0.91 for VTI; 0.88 for ccFT). This relationship improved with larger numbers of consecutively-averaged cardiac cycles. For ccFT, beyond four consecutively-averaged cardiac cycles the correlation coefficient remained strong (i.e., Rrm of at least 0.80). For VTI, the correlation coefficient with SV was strong for any number of averaged cardiac cycles. For both ccFT and VTI, Rrm remained stable around 25 consecutively-averaged cardiac cycles. Conclusions: There was a strong linear correlation between changing SV and carotid Doppler measures during central blood volume loss. The strength of this relationship was dependent upon the number of consecutively-averaged cardiac cycles.
5.The correlation between carotid artery Doppler and stroke volume during central blood volume loss and resuscitation
Isabel KERREBIJN ; Sarah ATWI ; Mai ELFARNAWANY ; Andrew M. EIBL ; Joseph K. EIBL ; Jenna L. TAYLOR ; Chul Ho KIM ; Bruce D. JOHNSON ; Jon-Émile S. KENNY
Acute and Critical Care 2024;39(1):162-168
Using peripheral arteries to infer central hemodynamics is common among hemodynamic monitors. Doppler ultrasound of the common carotid artery has been used in this manner with conflicting results. We investigated the relationship between changing common carotid artery Doppler measures and stroke volume (SV), hypothesizing that more consecutively-averaged cardiac cycles would improve SV-carotid Doppler correlation. Methods: Twenty-seven healthy volunteers were recruited and studied in a physiology laboratory. Carotid artery Doppler pulse was measured with a wearable, wireless ultrasound during central hypovolemia and resuscitation induced by a stepped lower body negative pressure protocol. The change in maximum velocity time integral (VTI) and corrected flow time of the carotid artery (ccFT) were compared with changing SV using repeated measures correlation. Results: In total, 73,431 cardiac cycles were compared across 27 subjects. There was a strong linear correlation between changing SV and carotid Doppler measures during simulated hemorrhage (repeated-measures linear correlation [Rrm ]=0.91 for VTI; 0.88 for ccFT). This relationship improved with larger numbers of consecutively-averaged cardiac cycles. For ccFT, beyond four consecutively-averaged cardiac cycles the correlation coefficient remained strong (i.e., Rrm of at least 0.80). For VTI, the correlation coefficient with SV was strong for any number of averaged cardiac cycles. For both ccFT and VTI, Rrm remained stable around 25 consecutively-averaged cardiac cycles. Conclusions: There was a strong linear correlation between changing SV and carotid Doppler measures during central blood volume loss. The strength of this relationship was dependent upon the number of consecutively-averaged cardiac cycles.
6.The correlation between carotid artery Doppler and stroke volume during central blood volume loss and resuscitation
Isabel KERREBIJN ; Sarah ATWI ; Mai ELFARNAWANY ; Andrew M. EIBL ; Joseph K. EIBL ; Jenna L. TAYLOR ; Chul Ho KIM ; Bruce D. JOHNSON ; Jon-Émile S. KENNY
Acute and Critical Care 2024;39(1):162-168
Using peripheral arteries to infer central hemodynamics is common among hemodynamic monitors. Doppler ultrasound of the common carotid artery has been used in this manner with conflicting results. We investigated the relationship between changing common carotid artery Doppler measures and stroke volume (SV), hypothesizing that more consecutively-averaged cardiac cycles would improve SV-carotid Doppler correlation. Methods: Twenty-seven healthy volunteers were recruited and studied in a physiology laboratory. Carotid artery Doppler pulse was measured with a wearable, wireless ultrasound during central hypovolemia and resuscitation induced by a stepped lower body negative pressure protocol. The change in maximum velocity time integral (VTI) and corrected flow time of the carotid artery (ccFT) were compared with changing SV using repeated measures correlation. Results: In total, 73,431 cardiac cycles were compared across 27 subjects. There was a strong linear correlation between changing SV and carotid Doppler measures during simulated hemorrhage (repeated-measures linear correlation [Rrm ]=0.91 for VTI; 0.88 for ccFT). This relationship improved with larger numbers of consecutively-averaged cardiac cycles. For ccFT, beyond four consecutively-averaged cardiac cycles the correlation coefficient remained strong (i.e., Rrm of at least 0.80). For VTI, the correlation coefficient with SV was strong for any number of averaged cardiac cycles. For both ccFT and VTI, Rrm remained stable around 25 consecutively-averaged cardiac cycles. Conclusions: There was a strong linear correlation between changing SV and carotid Doppler measures during central blood volume loss. The strength of this relationship was dependent upon the number of consecutively-averaged cardiac cycles.
7.Assessing Patient Risk, Benefit, and Outcomes in Drug Development: A Decade of Abiraterone Clinical Trials
Matthew RASHID ; Eli OLDHAM ; Griffin K. HUGHES ; Andriana M. PEÑA ; Chase LADD ; Brooke GARDNER ; Ryan MCINTIRE ; Bradley JOHNSON ; Jordan TUIA ; Alyson HASLAM ; Vinay PRASAD ; Matt VASSAR
Journal of Urologic Oncology 2024;22(3):211-223
Purpose:
Our study aimed to evaluate the risk and benefit profiles of clinical trials using abiraterone in cancer treatment.
Materials and Methods:
A comprehensive search was conducted on May 24, 2023, using databases such as PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. We extracted data on adverse events, progression-free survival, overall survival, objective response rate (ORR), and prostate-specific antigen response rate (PSA-RR). The Common Terminology Criteria for Adverse Events were used to assess risks, while ORR and PSA-RR were used to assess benefits. Trials were categorized as positive, negative, or indeterminate based on their safety profiles and efficacy outcomes.
Results:
Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint. Our study supports abiraterone’s use in prostate cancer, its only U.S. Food and Drug Administration-approved indication to treat, with a median ORR of 20.0% and a median PSA-RR of 42.0%. However, when looking at the 3 novel indications tested, the risk-to-benefit profile was similar to that of its original approval. Even though most novel indications failed to meet their primary endpoint, the overall toxicity profile was similar to that found in prostate cancer.
Conclusion
Abiraterone showed an overall risk-to-benefit portfolio that supports the use of its treatment in prostate cancer. Although the primary endpoints in ovarian and breast cancer trials were not met, the use was appropriate when assessing how the mechanism of action for abiraterone could be beneficial in patients with these types of cancers.
8.Assessing Patient Risk, Benefit, and Outcomes in Drug Development: A Decade of Abiraterone Clinical Trials
Matthew RASHID ; Eli OLDHAM ; Griffin K. HUGHES ; Andriana M. PEÑA ; Chase LADD ; Brooke GARDNER ; Ryan MCINTIRE ; Bradley JOHNSON ; Jordan TUIA ; Alyson HASLAM ; Vinay PRASAD ; Matt VASSAR
Journal of Urologic Oncology 2024;22(3):211-223
Purpose:
Our study aimed to evaluate the risk and benefit profiles of clinical trials using abiraterone in cancer treatment.
Materials and Methods:
A comprehensive search was conducted on May 24, 2023, using databases such as PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. We extracted data on adverse events, progression-free survival, overall survival, objective response rate (ORR), and prostate-specific antigen response rate (PSA-RR). The Common Terminology Criteria for Adverse Events were used to assess risks, while ORR and PSA-RR were used to assess benefits. Trials were categorized as positive, negative, or indeterminate based on their safety profiles and efficacy outcomes.
Results:
Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint. Our study supports abiraterone’s use in prostate cancer, its only U.S. Food and Drug Administration-approved indication to treat, with a median ORR of 20.0% and a median PSA-RR of 42.0%. However, when looking at the 3 novel indications tested, the risk-to-benefit profile was similar to that of its original approval. Even though most novel indications failed to meet their primary endpoint, the overall toxicity profile was similar to that found in prostate cancer.
Conclusion
Abiraterone showed an overall risk-to-benefit portfolio that supports the use of its treatment in prostate cancer. Although the primary endpoints in ovarian and breast cancer trials were not met, the use was appropriate when assessing how the mechanism of action for abiraterone could be beneficial in patients with these types of cancers.
9.Distribution of the intraosseous branch of the posterior superior alveolar artery relative to the posterior maxillary teeth
Carsen R. MCDANIEL ; Thomas M. JOHNSON ; Brian W. STANCOVEN ; Adam R. LINCICUM
Imaging Science in Dentistry 2024;54(2):121-127
Purpose:
Preoperative identification of the intraosseous posterior superior alveolar artery (PSAA) is critical when planning sinus surgery. This study was conducted to determine the distance between the cementoenamel junction and the PSAA, as well as to identify factors influencing the detection of the PSAA on cone-beam computed tomography (CBCT).
Materials and Methods:
In total, 254 CBCT scans of maxillary sinuses, acquired with 2 different scanners, were examined to identify the PSAA. The distance from the cementoenamel junction (CEJ) to the PSAA was recorded at each maxillary posterior tooth position. Binomial logistic regression and multiple linear regression were employed to evaluate the effects of scanner type, CBCT parameters, sex, and age on PSAA detection and CEJ-PSAA distance, respectively. P-values less than 0.05 were considered to indicate statistical significance.
Results:
The mean CEJ-PSAA distances at the second molar, first molar, second premolar, and first premolar positions were 17.0±4.0 mm, 21.8±4.1 mm, 19.5±4.7 mm, and 19.9±4.9 mm for scanner 1, respectively, and 17.3±3.5 mm, 16.9±4.3 mm, 18.5±4.1 mm, and 18.4±4.3 mm for scanner 2. No independent variable significantly influenced PSAA detection. However, tooth position (b = - 0.67, P<0.05) and scanner type (b = - 1.3, P<0.05) were significant predictors of CEJ-PSAA distance.
Conclusion
CBCT-based estimates of CEJ-PSAA distance were comparable to those obtained in previous studies involving cadavers, CT, and CBCT. The type of CBCT scanner may slightly influence this measurement. No independent variable significantly impacted PSAA detection.

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