No abstract available.
Goiter* ; Pneumonia, Aspiration* ; Thyroid Gland*

OBJECTIVE: Anxiety trait, anxiety and depression states have all been reported to increase risks for cardiovascular disease (CVD), possibly through altering cardiac autonomic regulation. Our aim was to investigate whether the relationship between harm avoidance (HA, an anxiety-related personality trait) and cardiac autonomic regulation is independent of anxiety and depression states in healthy adults. METHODS: We recruited 535 physically and mentally healthy volunteers. Participants completed the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Tri-dimensional Personality Questionnaire. Participants were divided into high or low HA groups as discriminated by the quartile value. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV). We obtained the time and frequency-domain indices of HRV including variance (total HRV), the low-frequency power (LF; 0.05-0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15-0.40 Hz), which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. RESULTS: The BDI and HA scores showed associations with HRV parameters. After adjustment for the BDI scores and other control variables, HA is still associated with reduced variance, LF and HF power. Compared with the participants with low HA, those with high HA displayed significant reductions in variance, LF and HF power and a significant increase in their LF/HF ratio. CONCLUSION: This study highlights the independent role of HA in contributing to decreased autonomic cardiac regulation in healthy adults and provides a potential underlying mechanism for anxiety trait to confer increased risk for CVD.
Adult* ; Anxiety ; Baroreflex ; Cardiovascular Diseases ; Depression ; Healthy Volunteers ; Heart Rate* ; Heart* ; Humans

Background: and Purpose Although amyloid positron emission tomography (PET) might provide a molecular diagnosis for cerebral amyloid angiopathy (CAA), it does not have sufficient specificity for this condition relative to incipient Alzheimer’s disease (AD). To identify a regional amyloid uptake pattern specific to CAA, we attempted to reduce this overlap by selecting “pure CAA” (i.e., fulfilling the criteria for probable CAA but without tau PET AD signature) and “pure AD” (i.e., positive amyloid PET and presence of tau PET AD signature, but without lobar hemorrhagic lesions). We hypothesized that occipital tracer uptake relative to the whole cortex (WC) would be higher in patients with pure CAA and may serve as a specific diagnostic marker. Methods: Patients who fulfilled these criteria were identified. In addition to the occipital region of interest (ROI), we assessed the frontal and posterior cingulate cortex (PCC) ROIs that are sensitive to AD. Amyloid PET uptake was expressed as the absolute standardized uptake value ratio (SUVR) and ROI/WC ratio. The diagnostic utility of amyloid PET was assessed using the Youden index cutoff. Results: Eighteen patients with AD and 42 patients with CAAs of comparable age were eligible. The occipital/WC was significantly higher in CAA than AD (1.02 [0.97–1.06] vs. 0.95 [0.87–1.01], P=0.001), with an area under curve of 0.762 (95% confidence interval [CI] 0.635–0.889) and a specificity of 72.2% (95% CI 46.5–90.3) at Youden cutoff (0.98). The occipital lobe, frontal lobe, PCC and WC SUVRs were significantly lower in CAA than in AD. The frontal/WC and PCC/WC ratios did not differ significantly between the groups. Conclusion Using stringent patient selection to minimize between-condition overlap, this study demonstrated the specificity of higher relative occipital amyloid uptake in CAA than in AD.

Background: and Purpose Although amyloid positron emission tomography (PET) might provide a molecular diagnosis for cerebral amyloid angiopathy (CAA), it does not have sufficient specificity for this condition relative to incipient Alzheimer’s disease (AD). To identify a regional amyloid uptake pattern specific to CAA, we attempted to reduce this overlap by selecting “pure CAA” (i.e., fulfilling the criteria for probable CAA but without tau PET AD signature) and “pure AD” (i.e., positive amyloid PET and presence of tau PET AD signature, but without lobar hemorrhagic lesions). We hypothesized that occipital tracer uptake relative to the whole cortex (WC) would be higher in patients with pure CAA and may serve as a specific diagnostic marker. Methods: Patients who fulfilled these criteria were identified. In addition to the occipital region of interest (ROI), we assessed the frontal and posterior cingulate cortex (PCC) ROIs that are sensitive to AD. Amyloid PET uptake was expressed as the absolute standardized uptake value ratio (SUVR) and ROI/WC ratio. The diagnostic utility of amyloid PET was assessed using the Youden index cutoff. Results: Eighteen patients with AD and 42 patients with CAAs of comparable age were eligible. The occipital/WC was significantly higher in CAA than AD (1.02 [0.97–1.06] vs. 0.95 [0.87–1.01], P=0.001), with an area under curve of 0.762 (95% confidence interval [CI] 0.635–0.889) and a specificity of 72.2% (95% CI 46.5–90.3) at Youden cutoff (0.98). The occipital lobe, frontal lobe, PCC and WC SUVRs were significantly lower in CAA than in AD. The frontal/WC and PCC/WC ratios did not differ significantly between the groups. Conclusion Using stringent patient selection to minimize between-condition overlap, this study demonstrated the specificity of higher relative occipital amyloid uptake in CAA than in AD.

Background: and Purpose Although amyloid positron emission tomography (PET) might provide a molecular diagnosis for cerebral amyloid angiopathy (CAA), it does not have sufficient specificity for this condition relative to incipient Alzheimer’s disease (AD). To identify a regional amyloid uptake pattern specific to CAA, we attempted to reduce this overlap by selecting “pure CAA” (i.e., fulfilling the criteria for probable CAA but without tau PET AD signature) and “pure AD” (i.e., positive amyloid PET and presence of tau PET AD signature, but without lobar hemorrhagic lesions). We hypothesized that occipital tracer uptake relative to the whole cortex (WC) would be higher in patients with pure CAA and may serve as a specific diagnostic marker. Methods: Patients who fulfilled these criteria were identified. In addition to the occipital region of interest (ROI), we assessed the frontal and posterior cingulate cortex (PCC) ROIs that are sensitive to AD. Amyloid PET uptake was expressed as the absolute standardized uptake value ratio (SUVR) and ROI/WC ratio. The diagnostic utility of amyloid PET was assessed using the Youden index cutoff. Results: Eighteen patients with AD and 42 patients with CAAs of comparable age were eligible. The occipital/WC was significantly higher in CAA than AD (1.02 [0.97–1.06] vs. 0.95 [0.87–1.01], P=0.001), with an area under curve of 0.762 (95% confidence interval [CI] 0.635–0.889) and a specificity of 72.2% (95% CI 46.5–90.3) at Youden cutoff (0.98). The occipital lobe, frontal lobe, PCC and WC SUVRs were significantly lower in CAA than in AD. The frontal/WC and PCC/WC ratios did not differ significantly between the groups. Conclusion Using stringent patient selection to minimize between-condition overlap, this study demonstrated the specificity of higher relative occipital amyloid uptake in CAA than in AD.

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

BACKGROUND AND PURPOSE: It is essential to develop a reliable predictive serum biomarker for Parkinson's disease (PD). The accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. The purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. METHODS: Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. RESULTS: The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutoff age than in the group above the cutoff age. CONCLUSIONS: Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.
alpha-Synuclein ; Humans ; Multiple System Atrophy ; Parkinson Disease ; ROC Curve ; Supranuclear Palsy, Progressive

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. Results: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). Conclusions SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. Results: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). Conclusions SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.