TRIM24 directs replicative stress responses to maintain ALT telomeres via chromatin signaling.

An inability to replicate the genome can cause replication stress and genome instability. Here, we develop BLOCK-ID, a proteomic method to identify and visualize proteins at stressed replication forks. This approach successfully identified novel mediators of the replication stress response, including the chromatin acetylation reader protein TRIM24. In validating TRIM24 function, we uncovered its crucial role in coordinating Alternative Lengthening of Telomeres (ALT), a cancer-specific telomere extension pathway involving replication stress. Our data reveal that TRIM24 is directed to telomeres via a p300/CBP-dependent acetylation chromatin signaling cascade, where it organizes ALT-associated PML bodies (APBs) to promote telomere DNA synthesis. Strikingly, we demonstrate that when artificially tethered at telomeres, TRIM24 can stimulate new telomere DNA synthesis in a SUMO-dependent manner, independently of p300/CBP or PML-dependent APBs. Thus, this study identifies a TRIM24 chromatin signaling pathway required for ALT telomere maintenance.

Impact of cerebral collateral flow on stroke outcomes after carotid stenting.

OBJECTIVE: Internal carotid artery stenosis is a main contributor to recurrent ischemic stroke. This study aimed to evaluate associations between recurrent stroke and changes in prestenting flow direction in the primary collaterals or both primary and secondary collaterals, and the potential interaction between extra- and intracranial arteries. METHODS: This longitudinal study recruited stroke patients without intracranial stenosis who underwent right-side carotid stenting between 2011 and 2019. The main study outcome was recurrent stroke. Predictive factors were anterior circulation flow direction change (ACFDC), posterior circulation flow direction change, and reversal of ophthalmic artery/leptomeningeal anastomosis (ROALA) detected by transcranial color-coded duplex (TCCD) before carotid stenting. Patient follow-up was 9 years. Risk factors for recurrent stroke were identified by Kaplan-Meier plot and Cox regression analyses. RESULTS: A total of 234 patients (mean age 70.88 ± 10.3 years, 86.32% male) were included, and 115 had recurrent stroke. Kaplan-Meier plot showed that patients with left ACFDC and ROALA had worse outcomes than those with ACFDC only, while patients with left ACFDC had worse outcome than those with right ACFDC (both p < 0.001). Cox regression analysis showed that recurrent stoke was associated with ACFDC at right (hazard ratio [95% CI]: 20.988 [2.549-172.790], p < 0.01), left (151.441 [20.100-1140.993], p < 0.001), and both sides (144.889 [19.089-1099.710], p < 0.001). INTERPRETATION: Anterior circulation flow direction change is significantly associated with recurrent stroke in patients with unilateral carotid stenosis. Patients with ACFDC and ROALA together have worse outcomes compared to those with ACFDC only. Prestenting TCCD images help provide definitive information to predict outcomes after carotid stenting.

Ophthalmic artery flow direction change predicts recurrence of ischemic stroke after carotid stenting: a longitudinal observational study.

BACKGROUND AND PURPOSE: The implantation of carotid artery stents prevents recurrent ischemic stroke in patients with carotid stenosis. This study aimed to investigate associations between change of ophthalmic artery flow (COAF) post carotid stenting and recurrent ischemic stroke, as well as the link toward the anterior and posterior circulations and patients' prognosis after carotid stenting. METHODS: This retrospective, longitudinal cohort study recruited 87 left side carotid stenosed ischemic stroke patients undergoing left side carotid stenting between year of 2009 and 2013, and patients were followed up to 9 years after carotid procedures. Clinical data were derived from medical records. The primary outcome was stroke recurrence. Predictive factors were stenosis > 50% in one intracranial artery and ROAF. Kaplan-Meier and Cox regression analyses were used to identify risk factors associated with stroke recurrence. RESULTS: Among 87 included patients undergone left side carotid stent treatment, 44 had stroke recurrence within 3 years after carotid stenting. The recurrence group had significantly greater proportions of COAF after stenting (p = 0.001), and middle cerebral artery (MCA) and basilar artery or vertebral artery (BA/VA) stenosis > 50% (all p < 0.001) than the no-recurrence group. Survival was significantly shorter in patients with COAF than in those without (p < 0.01). Regression analysis showed that COAF was associated with stroke recurrence (HR: 3.638, 95% CI 1.54-8.62, p = 0.003). The recurrence rate was highest in patients with bilateral MCA stenosis > 50% (100%), followed by left MCA stenosis > 50% plus BA/VA stenosis > 50% (83.33%) or COAF (82.14%). Patients with bilateral MCA stenosis < 50% had no recurrence within 3-year follow-up. CONCLUSIONS: Prognosis after carotid stenting is poorer for patients with MCA stenosis > 50%, BA/VA stenosis > 50% and/or COAF. Carotid duplex and magnetic resonance angiography provide definitive information for prognosis prediction.

Functional outcome prediction of ischemic stroke patients with atrial fibrillation accepting post-acute care training.

Background: Ischemic stroke poses a major threat to human health and represents the third leading cause of death worldwide and in Taiwan. Post-acute care (PAC) training has been reported to be beneficial for post-index stroke events. However, knowledge is still lacking on the outcome of stroke events with cardiac origin. The focus of the current study is to investigate the effectiveness of PAC in this subgroup of patients as well as identify key baseline pointers that are capable of early prediction of patients' physical recovery. In addition, the authors hypothesize that the routinely arranged non-invasive carotid duplex that evaluates the characteristics of the carotid lumen could play a significant role in providing an early outcome prediction. Methods: For the current research, 142 ischemic stroke patients with underlying cardiac arrhythmia (atrial fibrillation) were retrospectively recruited. The patients' basic demographics, neuroimaging, carotid duplex, and basic biochemistry datasets were accurately documented. The pre and post-admission National Institutes of Health Stroke Scale (NIHSS) (6-month follow-ups), Barthel Index, and mRS score (12-month follow-ups) were also recorded. All statistical analyses were performed using R for Windows (version 3.6.3). Barthel Index, NIHSS, and mRS scores obtained before and after hospitalization were compared to determine the patients' outcomes and were classified as improved or unimproved. A multivariate logistic analysis was designed and applied to assess the significance of risk factors and to obtain the odds ratios (ORs). The receiver operating characteristic (ROC) curve and the Youden Index was used to find the important cut-off point information, and the area under the curve (AUC) was calculated to provide accuracy. Results: The average age of the 142 ischemic stroke patients enrolled in the current study was about 66 years, of which 88 patients were male and 54, female. Many of them had other comorbidities: 86 patients had mixed hyperlipidemia (60.56%), 115 had hypertension (80.99%), and 49 suffered from diabetes mellitus (34.51%). The mRS showed an improvement in the condition of only 40 patients (28.175%), whereas the Barthel Index showed improvement in 71 patients (50%), and 68 patients (47.89%) showed recovery on the NIHSS. The Barthel Index and NIHSS were selected because they already had an almost equal number of samples among the improved and unimproved groups (50%), rather than mRS, which had a lower number (28.17%) of improved cases. While conducting the EuroQol-5 Dimension (EQ-5D) assessment, anxiety/depression stood out as the most prominent issue, affecting 44 patients (30.99%). Self-care was another factor that was involved in the ongoing improvement of 36 patients (25.35%). Multivariate logistic analysis of both NIHSS and Barthel Index showed improvement with a contralateral plaque index statistical significance (P<0.05), whereas NIHSS showed a relevant significance in anxiety/depression and Barthel Index registered usual activity in the data analysis (P<0.05). ROC curve and Youden index analysis showed similar results in both NIHSS and Barthel Index of contralateral plaque index of 4.5, this being the cutoff point value for this group of patients. Conclusion: In the current study, nearly half of the enrolled patients showed favorable functional recovery. The outcome assessments seem to correlate well with NIHSS and Barthel Index scores, rather than mRS. The anxiety/depression and usual activities domains of the EQ-5D results are associated with and have a great impact after the patients undertake the PAC rehabilitative strategy. Moreover, the variables obtained through carotid duplex and plaque index might also play a significant role in determining the patient's functional outcome.

Predictive Factors of Cerebral Aneurysm Rerupture After Clipping.

BACKGROUND: We aimed to estimate the risk of rerupture after first-time aneurysmal clipping surgery, explore the possible related factors, and assess long-term physical functionality. We hypothesized that the modified Rankin scale (mRS) could serve as an effective substitute for Hunter and Hess scale. METHODS: This retrospective study included 171 patients with cerebral aneurysmal rupture who had completed aneurysmal clipping treatment and collected their demographic data and medical records. The outcome assessments include neuroimaging records, Hunter and Hess scale, and the mRS scale during hospitalization and follow-up after discharge. The mean length of follow-up was 4.28 years. RESULTS: After aneurysmal clipping treatment, 83 patients (48.5%) had subsequently ruptured aneurysms. The scores of the reruptured group on the Hunt and Hess scale and mRS were significantly higher than those of the non-reruptured group. Multiple Cox proportional-hazards regression also showed that postoperative mRS >2, smoking, and two or more aneurysms were potentially important risk factors leading to aneurysm rupture again [the corresponding hazard ratios (HRs) were 5.209, 2.109, and 2.775, respectively] in patients. In addition, the location of an aneurysm on the anterior cerebral artery (ACA) or the posterior communicating (Pcom) artery had a higher risk of rerupture (the corresponding HRs were 1.996 and 2.934, respectively). CONCLUSIONS: Nearly half of the collected participants experienced the rerupture episode, who had undergone the second-time clipping surgery. Smoking and multiple aneurysms are potential risk factors for aneurysmal rerupture. Most aneurysms are located along the ICA, but aneurysms located at the ACA or Pcom site are most likely to rerupture. As compared with the Hunter and Hess scale, the mRS scale does not have inferior predicting power in following patients' long-term functionalities.

The prediction of acute ischemic stroke patients' long-term functional outcomes treated with bridging therapy.

BACKGROUND: Intravenous thrombolysis therapy (IVT) bridged with intra-arterial thrombectomy (IAT) has recently been recommended as favorable treatment option to ensure that the thrombolytic effect is delivered to the affected region for acute ischemic stroke patients. However, there remains a lack of studies reporting outcome prediction in this group of patients. In this study, we aimed to identify indicators from baseline data that could be used for early prediction of long-term functional outcomes. METHODS: This retrospective single center cohort study included acute ischemic stroke (AIS) patients (n = 92) who received IVT and IAT. Functional outcomes were assessed by the National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index. We investigated the relationship between functional outcomes at one-year post-procedure and potential predictors such as occlusion site, modified thrombolysis in cerebral infarction (mTICI) score following the IVT/IAT procedure, and degree of stenosis measured by carotid duplex. RESULTS: 67.4% of the studied patients had satisfactory outcomes with mTICI grades of 2b or 3. From baseline to one-year post-procedure, the NIHSS score improved in 88.0%, the mRS score improved in 69.6%, and the Barthel index improved with 59.8%. Patients with internal carotid artery (ICA) or vertebral artery (VA) stenosis detected by carotid duplex had significantly poorer functional outcomes, measured by the mRS score and Barthel index. In patients with a satisfactory mTICI grade, improvement in the mRS score was only observed in 60.0% of patients with ICA stenosis, compared to 93.8% without ICA stenosis. The VA stenosis was the most significant factor associated with the improvement of mRS (OR = 0.08; 95% CI: 0.01-0.63; P = 0.017) and Barthel Index (OR = 0.06; 95% CI: 0.01-0.47; P = 0.008) in multiple regression analysis. CONCLUSIONS: ICA or VA stenosis detected by carotid duplex could serve as predictors of significantly poorer functional outcomes in stroke patients treated with bridging therapy; they might be useful clinical markers, particularly as stenosis could be detected by a non-invasive and portable method.

Smoking, but not alcohol, is associated with risk of psoriasis in a Taiwanese population-based cohort study.

BACKGROUND: Alcohol consumption and smoking have long been suspected of increasing the risk of developing psoriasis. Most evidence to date has derived from cross-sectional or case-control studies. OBJECTIVE: We sought to investigate the effects of alcohol and smoking on incident psoriasis. METHODS: Alcohol consumption, smoking status, and other covariates were collected from four rounds (2001, 2005, 2009, and 2013) of the Taiwan National Health Interview Survey. Incident psoriasis was identified from the National Health Insurance database. Cox regression model was used for the analysis. RESULTS: Of 60,136 subjects, 242 (0.40%) developed psoriasis. After controlling for demographics and comorbidities, alcohol consumption was not significantly associated with psoriasis risk. Conversely, psoriasis risk was higher for current smokers than never smokers (adjusted hazard ratio 1.47 [95% confidence interval 1.04-2.07]). The risks were higher among subjects who smoked >25 cigarettes per day and for >20 pack-years. In subgroup analysis, current smoking was significantly associated with risk of psoriasis without psoriatic arthritis but not psoriatic arthritis alone. LIMITATIONS: Alcohol consumption was not assessed based on the number of drinks consumed. CONCLUSION: Current smoking increased the risk of psoriasis, particularly augmented for individuals who smoked >25 cigarettes per day and for >20 pack-years, while alcohol consumption was not significantly associated with psoriasis development.

The characterization of trachelectomy for benign and precancerous indications in Taiwan: A population-based study, 1998-2013.

OBJECTIVE: The study aimed to update the utilization trend and characterize the trachelectomy for benign and precancerous indications in Taiwanese women by comparing associated women, surgeon, and hospital-related characteristics. MATERIALS AND METHODS: We conducted a population-based trend study using inpatient admission claims data from Taiwan's National Health Insurance program from 1998 to 2013. After excluding those who had prior subtotal hysterectomy, women who underwent trachelectomy for benign and precancerous indications were compared by age at surgery (younger than 40 years, n = 130; 40 and 59 years, n = 429; and 60 years or older, n = 439). Trend analysis by age groups and indication was performed for the utilization of trachelectomy. A separate descriptive analysis was also performed to evaluate the surgeon's total trachelectomy case volume during the study period. RESULTS: A total of 998 women who underwent trachelectomy for benign and precancerous indications were included in the study cohort. The overall utilization increased considerably by 100% over the study period. The most common indications for trachelectomy were genital prolapse (75.2%) and precancerous cervical lesion (21.0%). The majority of trachelectomies were performed with concomitant colporrhaphy for genital prolapse among older women without comorbid illness or any prior catastrophic illness. Most women (62.9%) were operated by a relatively small number of surgeons with high case volume (12.6%) during the study period. Compared to women older than 40 years, younger women had less comorbidities, more likely to be treated at private medical institution by surgeons of high case volume, and were less likely to undergo concomitant anterior and posterior colporrhaphy. CONCLUSIONS: The overall utilization of trachelectomy for benign and precancerous indications has increased over the past 16-years from 1998 to 2013, particularly among older Taiwanese women without comorbid illness or any prior catastrophic illness.

Scatterometry-based metrology with feature region signatures matching.

Scatterometry takes advantage of the sensitivity exhibited by optical diffraction from periodic structures, and hence is an efficient technique for lithographic process monitoring. A feature region measurement algorithm has been developed to extract accurately and quickly the relevant constitutive parameters from diffraction data. It is a method for efficiently determining grating structure by seeking the reflectance at some angles contains more information about the structure of the surface relief profile than the reflectance at other angles in a library data match process. The number of measurements and size of signature matching library will be reduced in a great percentage by performing the feature region algorithm.

Effects of a continuing education program on nurses' practices of cancer pain assessment and their acceptance of patients' pain reports.

A hospital-based quasi-experimental (pretest and post-test) study was conducted in Kaohsiung Veteran General Hospital, Taiwan. This study was to evaluate a continuing education program (CEP) on nurses' practices of cancer pain assessment and their acceptance of patients' pain reports with respect to four types of misconceptions. A questionnaire was sent to on-duty nurses or head nurses with patient care responsibilities before the implementation of CEP (n=645) and six months after the program (n=630). The response rates were 92.6% and 91.3% for pretest and post-test surveys, respectively. The CEP was implemented in 8 weeks with four-repeated sessions of 4-hour lectures. A one-day workshop focused on cancer pain assessment and treatment was held 3 months after the four-repeated sessions. Several educational strategies and teaching materials were used in the CEP. The results showed that CEP made statistically significant yet moderate improvement in nurses' practices of pain assessment using pain rating scales (pretest 3.29+/-0.76 vs. post-test 3.48+/-0.75, P<0.001) and acceptance of patient's pain reports without misconceptions on addiction (3.12+/-0.80 vs. 3.39+/-0.90, P<0.001), phantom pain (3.91+/-0.96 vs. 4.07+/-0.92, P=0.005), and placebo testing (3.63+/-0.72 vs. 3.81+/-0.73, P<0.001), except on patient gender-age-related doubts (3.60+/-0.72 vs. 3.67+/-0.77, P=0.109). In order to achieve further improvement, additional follow-up CEP combined with a hospital-wide institutionalization of pain assessment should be promoted and implemented in the future.