1.Pleotropic effects of hypoxia-inducible factor-prolyl hydroxylase domain inhibitors: are they clinically relevant?
Yu-Hsiang CHOU ; Szu-Yu PAN ; Shuei-Liong LIN
Kidney Research and Clinical Practice 2023;42(1):27-38
Anemia is common in patients with chronic kidney disease (CKD) and is mainly caused by insufficient production of erythropoietin from fibrotic kidney. Because anemia impairs quality of life and overall prognosis, recombinant human erythropoietin-related products (erythropoiesis-stimulating agents, ESAs) have been developed to increase hemoglobin level for decades. However, many safety concerns have been announced regarding the use of ESAs, including an increased occurrence of cardiovascular events, vascular access thrombosis, cancer progression, and recurrence. Hypoxia-inducible factor (HIF) is crucial to erythropoietin production, as a result, prolyl hydroxylase domain (PHD) enzyme inhibitors have been new therapeutic agents for the treatment of anemia in CKD. They can be administered orally, which is a preferred route for patients not undergoing hemodialysis. In clinical trials, PHD inhibitor could induce noninferior effect on erythropoiesis and improve functional iron deficiency compared with ESAs. Although no serious adverse events were reported, safety is still a concern because HIF stabilization induced by PHD inhibitor has pleotropic effects, such as angiogenesis, metabolic change, and cell survival, which might lead to unwanted deleterious effects, including fibrosis, inflammation, cardiovascular risk, and tumor growth. More molecular mechanisms of PHD inhibition and long-term clinical trials are needed to observe these pleotropic effects for the confirmation of safety and efficacy of PHD inhibitors.
2.A Neurofeedback Protocol for Executive Function to Reduce Depression and Rumination: A Controlled Study
Sheng-Hsiang YU ; Chao-Yuan TSENG ; Wei-Lun LIN
Clinical Psychopharmacology and Neuroscience 2020;18(3):375-385
Objective:
Rumination is a maladaptive emotional-regulation strategy that is strongly associated with depression. Impaired executive function can lead to difficulties in disengaging from rumination, thus exacerbating depression. In this study, we inspect an electroencephalograph neurofeedback protocol that enhance the target peak alpha frequency (PAF) activation in the prefrontal region. We examine the protocol’s effects on depression and rumination.
Methods:
We randomly assigned 30 dysphoric participants into either the neurofeedback training group or the control group. We then evaluated their depression, rumination, and executive function at pre- and posttraining so as to examine the effects of the neurofeedback.
Results:
The results show that this neurofeedback protocol can specifically enhance participants’ target PAF. The participants’ executive function performances significantly improved after undergoing 20 neurofeedback sessions. Compared with those in the control group, those in the neurofeedback group had significantly fewer depressive symptoms and significantly reduced rumination. Moreover, as target PAF and executive function improved, depression and rumination both declined.
Conclusion
Our data are in line with those of previous studies that indicated a relationship between upper-band alpha activity and executive function. This PAF neurofeedback can effectively enhance participants’ executive function, which can reduce rumination and ameliorate depression. This neurofeedback training is based on basic cognitive neuroscience, so it sheds light on depression’s pathological factors and etiology.
3.Novel Biomarkers of Alzheimer’s Disease: Based Upon N-methylD-aspartate Receptor Hypoactivation and Oxidative Stress
Ting-I CHIANG ; Yi-Hsiang YU ; Chieh-Hsin LIN ; Hsien-Yuan LANE
Clinical Psychopharmacology and Neuroscience 2021;19(3):423-433
Early detection and prevention of Alzheimer's disease (AD) is important. The current treatment for early AD is acetylcholine esterase inhibitors (AChEIs); however, the efficacy is poor. Besides, AChEI did not show efficacy in mild cognitive impairment (MCI). Beta-amyloid (Aβ) deposits have been regarded to be highly related to the pathogenesis of AD. However, many clinical trials aiming at the clearance of Aβ deposits failed to improve the cognitive decline of AD, even at its early phase. There should be other important mechanisms unproven in the course of AD and MCI. Feasible biomarkers for the diagnosis and treatment response of AD are lacking to date. The N-methyl-D-aspartate receptor (NMDAR) activation plays an important role in learning and memory. On the other hand, oxidative stress has been regarded to contribute to aging with the assumption that free radicals damage cell constituents and connective tissues. Our recent study found that an NMDAR enhancer, sodium benzoate (the pivotal inhibitor of D-amino acid oxidase [DAAO]), improved the cognitive and global function of patients with early-phase AD. Further, we found that peripheral DAAO levels were higher in patients with MCI and AD than healthy controls. We also found that sodium benzoate was able to change the activity of antioxidant. These pieces of evidence suggest that the NMDAR function is associated with anti-oxidation, and have potential to be biomarkers for the diagnosis and treatment response of AD.
4.Novel Biomarkers of Alzheimer’s Disease: Based Upon N-methylD-aspartate Receptor Hypoactivation and Oxidative Stress
Ting-I CHIANG ; Yi-Hsiang YU ; Chieh-Hsin LIN ; Hsien-Yuan LANE
Clinical Psychopharmacology and Neuroscience 2021;19(3):423-433
Early detection and prevention of Alzheimer's disease (AD) is important. The current treatment for early AD is acetylcholine esterase inhibitors (AChEIs); however, the efficacy is poor. Besides, AChEI did not show efficacy in mild cognitive impairment (MCI). Beta-amyloid (Aβ) deposits have been regarded to be highly related to the pathogenesis of AD. However, many clinical trials aiming at the clearance of Aβ deposits failed to improve the cognitive decline of AD, even at its early phase. There should be other important mechanisms unproven in the course of AD and MCI. Feasible biomarkers for the diagnosis and treatment response of AD are lacking to date. The N-methyl-D-aspartate receptor (NMDAR) activation plays an important role in learning and memory. On the other hand, oxidative stress has been regarded to contribute to aging with the assumption that free radicals damage cell constituents and connective tissues. Our recent study found that an NMDAR enhancer, sodium benzoate (the pivotal inhibitor of D-amino acid oxidase [DAAO]), improved the cognitive and global function of patients with early-phase AD. Further, we found that peripheral DAAO levels were higher in patients with MCI and AD than healthy controls. We also found that sodium benzoate was able to change the activity of antioxidant. These pieces of evidence suggest that the NMDAR function is associated with anti-oxidation, and have potential to be biomarkers for the diagnosis and treatment response of AD.
5.Fixing Cho Type IIC Distal Clavicle Fractures with Hook Plates Leads to a High Incidence of Subacromial Osteolysis: A Retrospective Study and Literature Review
Po-Hsiang CHEN ; Chun-Yu CHEN ; Kai-Cheng LIN ; Yih-Wen TARNG
Clinics in Orthopedic Surgery 2024;16(5):694-701
Background:
This retrospective study investigates the complications, particularly subacromial osteolysis (SAO), associated with hook plate (HP) fixation, in the treatment of unstable distal clavicle fractures characterized by complete coracoclavicular (CC) ligament rupture. The decision-making process for employing HP in fractures of this nature, such as Neer types IIB and V and Cho classification IIC, involves considerations of distal fragment size and displacement. While HP offers advantages in clinical practice, it is not without complications, with SAO being a notable concern. Factors such as non-anatomic hook tip placement and fracture classification may influence the risk of SAO.
Methods:
The study comprises a retrospective analysis of unstable distal clavicle fractures treated with HP at our institution from 2019 to 2022. Exclusions include non-displaced fractures, those treated with other locking plates, and pathologic fractures. A total of 91 patients with displaced distal clavicle fractures underwent open reduction and internal fixation with HP. Cho classification was employed to differentiate cases with CC ligament rupture. Patient demographics, classifications, postoperative radiographs, distal fragment size, plate position, timing of implant removal, and complications, including SAO, were recorded.
Results:
Among the 91 patients, 32 were classified as Cho IIB, 43 as Cho IIC, and 16 as Cho IID. Ninety-one percent exhibited solid union before implant removal. The prevalence of SAO was 43.8%, 76.7%, and 62.5% in Cho IIB, IIC, and IID, respectively. Univariate analysis revealed a significant difference only in Cho classification (p = 0.014). Binary logistic regression identified Cho classification type IIC as the sole risk factor for SAO (p = 0.021; odds ratio, 4.48; 95% confidence interval, 1.56–12.87).
Conclusions
Cho type IIC fractures, characterized by CC ligament deficiency causing horizontal instability, demonstrated the highest SAO rate. In contrast, Neer type IIB fractures retained the trapezoid ligament, and Neer type V fractures had intact CC ligaments, resulting in lower SAO rates. Biomechanically, combining HPs with CC ligament reconstruction provided better structural stability than using HPs alone in treating Cho type IIC fractures.
6.Fixing Cho Type IIC Distal Clavicle Fractures with Hook Plates Leads to a High Incidence of Subacromial Osteolysis: A Retrospective Study and Literature Review
Po-Hsiang CHEN ; Chun-Yu CHEN ; Kai-Cheng LIN ; Yih-Wen TARNG
Clinics in Orthopedic Surgery 2024;16(5):694-701
Background:
This retrospective study investigates the complications, particularly subacromial osteolysis (SAO), associated with hook plate (HP) fixation, in the treatment of unstable distal clavicle fractures characterized by complete coracoclavicular (CC) ligament rupture. The decision-making process for employing HP in fractures of this nature, such as Neer types IIB and V and Cho classification IIC, involves considerations of distal fragment size and displacement. While HP offers advantages in clinical practice, it is not without complications, with SAO being a notable concern. Factors such as non-anatomic hook tip placement and fracture classification may influence the risk of SAO.
Methods:
The study comprises a retrospective analysis of unstable distal clavicle fractures treated with HP at our institution from 2019 to 2022. Exclusions include non-displaced fractures, those treated with other locking plates, and pathologic fractures. A total of 91 patients with displaced distal clavicle fractures underwent open reduction and internal fixation with HP. Cho classification was employed to differentiate cases with CC ligament rupture. Patient demographics, classifications, postoperative radiographs, distal fragment size, plate position, timing of implant removal, and complications, including SAO, were recorded.
Results:
Among the 91 patients, 32 were classified as Cho IIB, 43 as Cho IIC, and 16 as Cho IID. Ninety-one percent exhibited solid union before implant removal. The prevalence of SAO was 43.8%, 76.7%, and 62.5% in Cho IIB, IIC, and IID, respectively. Univariate analysis revealed a significant difference only in Cho classification (p = 0.014). Binary logistic regression identified Cho classification type IIC as the sole risk factor for SAO (p = 0.021; odds ratio, 4.48; 95% confidence interval, 1.56–12.87).
Conclusions
Cho type IIC fractures, characterized by CC ligament deficiency causing horizontal instability, demonstrated the highest SAO rate. In contrast, Neer type IIB fractures retained the trapezoid ligament, and Neer type V fractures had intact CC ligaments, resulting in lower SAO rates. Biomechanically, combining HPs with CC ligament reconstruction provided better structural stability than using HPs alone in treating Cho type IIC fractures.
7.Fixing Cho Type IIC Distal Clavicle Fractures with Hook Plates Leads to a High Incidence of Subacromial Osteolysis: A Retrospective Study and Literature Review
Po-Hsiang CHEN ; Chun-Yu CHEN ; Kai-Cheng LIN ; Yih-Wen TARNG
Clinics in Orthopedic Surgery 2024;16(5):694-701
Background:
This retrospective study investigates the complications, particularly subacromial osteolysis (SAO), associated with hook plate (HP) fixation, in the treatment of unstable distal clavicle fractures characterized by complete coracoclavicular (CC) ligament rupture. The decision-making process for employing HP in fractures of this nature, such as Neer types IIB and V and Cho classification IIC, involves considerations of distal fragment size and displacement. While HP offers advantages in clinical practice, it is not without complications, with SAO being a notable concern. Factors such as non-anatomic hook tip placement and fracture classification may influence the risk of SAO.
Methods:
The study comprises a retrospective analysis of unstable distal clavicle fractures treated with HP at our institution from 2019 to 2022. Exclusions include non-displaced fractures, those treated with other locking plates, and pathologic fractures. A total of 91 patients with displaced distal clavicle fractures underwent open reduction and internal fixation with HP. Cho classification was employed to differentiate cases with CC ligament rupture. Patient demographics, classifications, postoperative radiographs, distal fragment size, plate position, timing of implant removal, and complications, including SAO, were recorded.
Results:
Among the 91 patients, 32 were classified as Cho IIB, 43 as Cho IIC, and 16 as Cho IID. Ninety-one percent exhibited solid union before implant removal. The prevalence of SAO was 43.8%, 76.7%, and 62.5% in Cho IIB, IIC, and IID, respectively. Univariate analysis revealed a significant difference only in Cho classification (p = 0.014). Binary logistic regression identified Cho classification type IIC as the sole risk factor for SAO (p = 0.021; odds ratio, 4.48; 95% confidence interval, 1.56–12.87).
Conclusions
Cho type IIC fractures, characterized by CC ligament deficiency causing horizontal instability, demonstrated the highest SAO rate. In contrast, Neer type IIB fractures retained the trapezoid ligament, and Neer type V fractures had intact CC ligaments, resulting in lower SAO rates. Biomechanically, combining HPs with CC ligament reconstruction provided better structural stability than using HPs alone in treating Cho type IIC fractures.
8.Fixing Cho Type IIC Distal Clavicle Fractures with Hook Plates Leads to a High Incidence of Subacromial Osteolysis: A Retrospective Study and Literature Review
Po-Hsiang CHEN ; Chun-Yu CHEN ; Kai-Cheng LIN ; Yih-Wen TARNG
Clinics in Orthopedic Surgery 2024;16(5):694-701
Background:
This retrospective study investigates the complications, particularly subacromial osteolysis (SAO), associated with hook plate (HP) fixation, in the treatment of unstable distal clavicle fractures characterized by complete coracoclavicular (CC) ligament rupture. The decision-making process for employing HP in fractures of this nature, such as Neer types IIB and V and Cho classification IIC, involves considerations of distal fragment size and displacement. While HP offers advantages in clinical practice, it is not without complications, with SAO being a notable concern. Factors such as non-anatomic hook tip placement and fracture classification may influence the risk of SAO.
Methods:
The study comprises a retrospective analysis of unstable distal clavicle fractures treated with HP at our institution from 2019 to 2022. Exclusions include non-displaced fractures, those treated with other locking plates, and pathologic fractures. A total of 91 patients with displaced distal clavicle fractures underwent open reduction and internal fixation with HP. Cho classification was employed to differentiate cases with CC ligament rupture. Patient demographics, classifications, postoperative radiographs, distal fragment size, plate position, timing of implant removal, and complications, including SAO, were recorded.
Results:
Among the 91 patients, 32 were classified as Cho IIB, 43 as Cho IIC, and 16 as Cho IID. Ninety-one percent exhibited solid union before implant removal. The prevalence of SAO was 43.8%, 76.7%, and 62.5% in Cho IIB, IIC, and IID, respectively. Univariate analysis revealed a significant difference only in Cho classification (p = 0.014). Binary logistic regression identified Cho classification type IIC as the sole risk factor for SAO (p = 0.021; odds ratio, 4.48; 95% confidence interval, 1.56–12.87).
Conclusions
Cho type IIC fractures, characterized by CC ligament deficiency causing horizontal instability, demonstrated the highest SAO rate. In contrast, Neer type IIB fractures retained the trapezoid ligament, and Neer type V fractures had intact CC ligaments, resulting in lower SAO rates. Biomechanically, combining HPs with CC ligament reconstruction provided better structural stability than using HPs alone in treating Cho type IIC fractures.
9.Comparative Study of Heavy Metal Blood Serum Level Between Organic and Conventional Farmers in Eastern Taiwan
Mei-Hua CHUNG ; Kuo-Hsiang HUNG ; Mi-Chia MA ; Mei-Yu LIU ; Ru-Wei LIN
Safety and Health at Work 2024;15(1):110-113
Numerous studies have indicated that organic fertilizers (OFer) might contain heavy metals (HMs) that present health risks to organic farmers (OFar). This study compared the concentrations of six HMs (Zn, Ni, Cd, Cu, Pb, Cr) in the blood of two distinct groups of farmers: 30 OFar from a designated organic area in eastern Taiwan, and 74 conventional farmers (CFar) from neighboring non-organic designated regions. The findings revealed that the OFar exhibited higher levels of Zn (1202.70 ± 188.74 μg/L), Cr (0.20 ± 0.09 μg/L), and Ni (2.14 ± 1.48 μg/L) in their blood compared to the CFar (988.40 ± 163.16 μg/L, 0.18 ± 0.15 μg/L, and 0.77 ± 1.23 μg/L), respectively. The disparities in Zn, Cr, and Ni levels were measured at 214.3 μg/L, 0.02 μg/L, and 1.37 μg/L, respectively. Furthermore, among the OFar, those who utilized green manures (GM) displayed significantly elevated blood levels of Zn (1279.93 ± 156.30 μg/L), Cr (0.24 ± 0.11 μg/L), and Ni (1.94 ± 1.38 μg/L) compared to individuals who exclusively employed chemical fertilizers (CFer) (975.42 ± 165.35 μg/L, 0.19 ± 0.16 μg/L, and 0.74 ± 1.20 μg/L), respectively. The differences in Zn, Cr, and Ni levels were measured at 304.51 μg/L, 0.05 μg/L, and 1.20 μg/L, respectively. As a result, OFar should be careful in choosing OFer and avoid those that may have heavy metal contamination.