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Background: Brain 18F-AV-45 amyloid positron emission tomography (PET) in Taiwanese patients with familial Alzheimer's disease with the amyloid precursor protein (APP) p.D678H mutation tends to involve occipital and cerebellar cortical areas. However, tau pathology in patients with this specific Taiwan mutation remains unknown. In this study, we aimed to study the Tau PET images in these patients. Methods: Clinical features, brain magnetic resonance imaging/computed tomography (MRI/CT), and brain 18F-THK-5351 PET were recorded in five patients with the APP p.D678H mutation and correlated with brain 18F-AV-45 PET images. We also compared the tau deposition patterns among five patients with familial mild cognitive impairment (fMCI), six patients with sporadic amnestic mild cognitive impairment (sMCI), nine patients with mild to moderate dementia due to Alzheimer's disease (AD), and 12 healthy controls (HCs). All of the subjects also received brain 18F-AV-45 PET. Results: The nine patients with sAD and six patients with sMCI had a positive brain AV-45 PET scans, while the 12 HCs had negative brain AV-45 PET scans. All five patients with fMCI received a tau PET scan with the age at onset ranging from 46 to 53 years, in whom increased standard uptake value ratio (SUVR) of 18F-THK-5351 was noted in all seven brain cortical areas compared with the HCs. In addition, the SUVRs of 18F-THK-5351 were increased in the frontal, medial parietal, lateral parietal, lateral temporal, and occipital areas (P < 0.001) in the patients with sAD compared with the HCs. The patients with fMCI had a significant higher SUVR of 18F-THK-5351 in the cerebellar cortex compared to the patients with sMCI. The correlations between regional SUVR and Mini-Mental State Examination score and between regional SUVR and clinical dementia rating (sum box) scores within volumes of interest of Braak stage were statistically significant. Conclusion: Tau deposition was increased in the patients with fMCI compared to the HCs. Increased regional SUVR in the cerebellar cortical area was a characteristic finding in the patients with fMCI. As compared between amyloid and tau PET, the amyloid deposition is diffuse, but tau deposition is limited to the temporal lobe in the patients with fMCI. [ABSTRACT FROM AUTHOR]

Background: Low lipid level is associated with better cardiovascular outcome. However, lipid paradox indicating low lipid level having worse outcomes could be seen under acute injury in some diseases. The present study was designed to clarify the prognostic significance of acute-phase lipid levels within 1 day after admission for stroke on mortality in first-ever statin-naïve acute ischemic stroke (IS) and hemorrhagic stroke (HS). Methods: This observational study was conducted using the data collected from Stroke Registry In Chang-Gung Healthcare System (SRICHS) between 2009 and 2012. Patients with recurrent stroke, onset of symptoms >1 day, and history of the use of lipid-lowering agents prior to index stroke were excluded. Stroke was classified into IS and hypertension-related HS. The primary outcomes were 30-day and 1-year mortality identified by linkage to national death registry for date and cause of death. Receiver operating characteristic (ROC) curve analysis and multivariate Cox proportional hazard models were used to examine the association of lipid profiles on admission with mortality. Results: Among the 18,268 admitted stroke patients, 3,746 IS and 465 HS patients were eligible for analysis. In IS, total cholesterol (TC) <163.5 mg/dL, triglyceride (TG) <94.5 mg/dL, low-density lipoprotein (LDL) <100 mg/dL, non-high-density lipoprotein cholesterol (non-HDL-C) <130.5 mg/dL, and TC/HDL ratio <4.06 had significantly higher risk for 30-day/1-year mortality with hazard ratio (HR) of 2.05/1.37, 1.65/1.31, 1.68/1.38, 1.80/1.41, and 1.58/1.38, respectively, compared with high TC, TG, LDL, non-HDL-C, and TC/HDL ratio (p < 0.01 in all cases). In HS, lipid profiles were not associated with mortality, except HDL for 30-day mortality (p = 0.025) and high uric acid (UA) concentrations for 30-day and 1-year mortality (p = 0.002 and 0.012, respectively). High fasting glucose and high National Institute of Health Stroke Scale (NIHSS) score at admission were associated with higher 30-day and 1-year mortality in both IS and HS and low blood pressure only in IS (p < 0.05). Synergic effects on mortality were found when low lipids were incorporated with high fasting glucose, low blood pressure, and high NIHSS score in IS (p < 0.05). Conclusions: Lipid paradox showing low acute-phase lipid levels with high mortality could be seen in statin-naïve acute IS but not in HS. The mortality in IS was increased when low lipids were incorporated with high fasting glucose, low blood pressure, and high NIHSS score. [ABSTRACT FROM AUTHOR]

Abstract: The adaptive cellular response to low oxygen tensions is mediated by the hypoxia‐inducible factors (HIFs), a family of heterodimeric transcription factors composed of HIF‐α and HIF‐β subunits. Prolonged HIF expression is a key contributor to cellular transformation, tumorigenesis and metastasis. As such, HIF degradation under hypoxic conditions is an essential homeostatic and tumour‐suppressive mechanism. LIMD1 complexes with PHD2 and VHL in physiological oxygen levels (normoxia) to facilitate proteasomal degradation of the HIF‐α subunit. Here, we identify LIMD1 as a HIF‐1 target gene, which mediates a previously uncharacterised, negative regulatory feedback mechanism for hypoxic HIF‐α degradation by modulating PHD2‐LIMD1‐VHL complex formation. Hypoxic induction of LIMD1 expression results in increased HIF‐α protein degradation, inhibiting HIF‐1 target gene expression, tumour growth and vascularisation. Furthermore, we report that copy number variation at the LIMD1 locus occurs in 47.1% of lung adenocarcinoma patients, correlates with enhanced expression of a HIF target gene signature and is a negative prognostic indicator. Taken together, our data open a new field of research into the aetiology, diagnosis and prognosis of LIMD1‐negative lung cancers. [ABSTRACT FROM AUTHOR]

The analysis described in this article shows that a high static stiffness of the bearing is attainable as two design parameters of membrane-type restrictor are properly chosen. The first one is the dimensionless stiffness of the membrane and the other one is the design restriction ratio of the bearing system. When the deformation-load relationship of the restrictor is compliance with the ideal trend, the stiffness of the bearing should theoretically approach infinite in most application range. It was derived that a dimensionless membrane stiffness of 1.33 and a design restriction ratio of 0.25 is the solution for such condition. The film thickness for the bearing will be maintained at designed levels over a loading range. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT), an attractive strategy for cancer treatment, can kill tumor cells and avoid injury to surrounding healthy cells. 4-Borono-2-[18F]fluorophenylalanine ([18F]FBPA) positron emission tomography (PET) is a reliable tool for patient screening. Due to the relatively low radiochemical yield when employing the electrophilic route, this study was able to develop a new method to produce no-carrier-added (NCA) [18F]FBPA and compare the biological characteristics with carrier-added (CA) characteristics. By starting from 4-bromo-2-nitrobenzaldehyde, NCA [18F]FBPA was prepared using radiofluorination, alkylation, borylation, and hydrolysis. Cellular uptake analyses, microPET imaging, and biodistribution analyses were conducted to characterize the biological properties of NCA and CA [18F]FBPA. The radiochemical yield of NCA [18F]FBPA was 20 % ± 6 % (decay corrected) with a radiochemical purity of >98 % and molar activity of 56 ± 15 GBq/μmol in a 100-min synthesis. The in vitro accumulation was significantly higher for NCA [18F]FBPA than for CA [18F]FBPA in both SAS and CT-26 cells. However, no apparent differences in tumor uptake were observed between NCA and CA [18F]FBPA-injected tumor-bearing mice. We successfully prepared NCA [18F]FBPA through nucleophilic substitution and achieved improved radiochemical yield and purity. We also demonstrated the effects of the amount of nonradioactive FBPA on in vitro cellular uptake and in vivo imaging studies. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: To investigate if initial blood pressure (BP) on admission is associated with stroke severity and predictive of admission costs and one-year-outcome in acute ischemic (IS) and hemorrhagic stroke (HS).Methods: This is a single-center retrospective cohort study. Stroke patients admitted within 3 days after onset between January 1st and December 31st in 2009 were recruited. The initial BP on admission was subdivided into high (systolic BP ≥ 211 mmHg or diastolic BP ≥ 111 mmHg), medium (systolic BP 111-210 mmHg or diastolic BP 71-110 mmHg), and low (systolic BP ≤ 110 mmHg or diastolic BP ≤ 70 mmHg) groups and further subgrouped with 25 mmHg difference in systole and 10 mmHg difference in diastole for the correlation analysis with demographics, admission cost and one-year modified Rankin scale (mRS).Results: In 1173 IS patients (mean age: 67.8 ± 12.8 years old, 61.4% male), low diastolic BP group had higher frequency of heart disease (p =0.001), dehydration (p =0.03) and lower hemoglobin level (p <0.001). The extremely high and low systolic BP subgroups had worse National Institutes of Health Stroke Scale (NIHSS) score (p =0.03), higher admission cost (p <0.001), and worse one-year mRS (p =0.03), while extremely high and low diastolic BP subgroups had higher admission cost (p <0.01). In 282 HS patients (mean age: 62.4 ± 15.4 years old, 60.6% male), both low systolic and diastolic BP groups had lower hemoglobin level (systole: p =0.05; diastole: p <0.001). The extremely high and low BP subgroups had worse NIHSS score (p =0.01 and p <0.001, respectively), worse one-year mRS (p =0.002 and p =0.001, respectively), and higher admission cost (diastole: p <0.002).Conclusions: Stroke patients with extremely high and low BP on admission have not only worse stroke severity but also higher admission cost and/or worse one-year outcome. In those patients with low BP, low admission hemoglobin might be a contributing factor. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the clinical predictors of unfavorable prognosis in patients with venous catheter-related cerebral air embolism.Methods: An extensive review of English literature was performed to obtain reports on cerebral air embolism published between January 1982 and July 2014 through PubMed, Journal at Ovid, and Web of Science using the Mesh terms and keywords "cerebral air embolism" and "cerebral gas embolism." Reports not fulfilling the diagnosis of cerebral air embolism and iterant articles were excluded. Demographics, clinical manifestations, and imaging findings were recorded. The air distribution on initial brain computed tomography (CT) was recorded as gyriform air (GF), cavernous sinus bubble, venous sinus bubble, and parenchymal and subarachnoid bubble. The enrolled subjects were further divided into favorable and unfavorable outcome groups for analyses.Results: Of the 33 cases enrolled, 31 had documented follow-up outcomes, including 14 with favorable and 17 with unfavorable prognoses. Patients with unfavorable outcome had older onset age (67.5 ± 15.8 versus 46.7 ± 17.0 years, P < .001), higher frequency of GF on brain CT (58.8% versus 0%, P < .01), initial consciousness disturbance (100% versus 42.9%, P < .001), and hemiparesis (100% versus 42.9%, P < .001), but lower frequency of cardiopulmonary symptoms (5.9% versus 64.3%, P < .01). In patients with central venous catheter-related cerebral air embolism, the retrograde mechanism had a tendency for worse outcomes (43.8% versus 0%, P = .023).Conclusions: In patients with venous catheter-related cerebral air embolism, the presence of GF on brain CT imaging, old age, initial conscious disturbance, and hemiparesis may predict unfavorable outcomes. [ABSTRACT FROM AUTHOR]