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Background: Glioblastoma multiforme (GBM) faces challenges with standard treatments, prompting exploration into alternative approaches. Reactive oxygen species (ROS) are implicated in cancer development, making antioxidants from natural sources, such as lycopene in tomatoes, promising candidates. This study aimed to assess the effectiveness of lycopene in GBM. Materials and Methods: The PAMPA-BBB assay predicted lycopene penetration. After treating GBM8401 and T98G GBM cells with lycopene, flow cytometry assessed cell cycle and apoptosis, while the CCK-8 assay measured antiproliferative efficacy. Colony formation assay examined cell growth, and intracellular and mitochondrial ROS levels were quantified. Western blot analyzed protein levels of p-ERK/ERK, p53, and cyclin-related proteins. Results: Our results demonstrated lycopene penetration across the blood-brain barrier and its induction of apoptosis, inhibiting proliferation in GBM8401 and T98G GBM cells. In addition, lycopene promoted p53 upregulation and suppressed cyclins B and cyclin D, leading to cell cycle arrest through ROS-activated ERK pathways. Conclusions: In conclusion, our study focused on lycopene's potential in GBM treatment, revealing its ability to induce apoptosis, inhibit proliferation, and regulate the cell cycle through ROS-activated ERK pathways. These findings suggest lycopene as a promising candidate for preventing and treating GBM by targeting ROS-induced cell proliferation, paving the way for future research. [ABSTRACT FROM AUTHOR]

RTA dh404 is a novel synthetic oleanolic acid derivative that has been reported to possess anti-allergic, neuroprotective, antioxidative, and anti-inflammatory properties, and exerts therapeutic effects on various cancers. Although CDDO and its derivatives have anticancer effects, the actual anticancer mechanism has not been fully explored. Therefore, in this study, glioblastoma cell lines were exposed to different concentrations of RTA dh404 (0, 2, 4, and 8 µM). Cell viability was evaluated using the PrestoBlue™ reagent assay. The role of RTA dh404 in cell cycle progression, apoptosis, and autophagy was analyzed using flow cytometry and Western blotting. The expression of cell cycle-, apoptosis-, and autophagy-related genes was detected by next-generation sequencing. RTA dh404 reduces GBM8401 and U87MG glioma cell viability. RTA dh404 treated cells had a significant increase in the percentage of apoptotic cells and caspase-3 activity. In addition, the results of the cell cycle analysis showed that RTA dh404 arrested GBM8401 and U87MG glioma cells at the G2/M phase. Autophagy was observed in RTA dh404-treated cells. Subsequently, we found that RTA dh404-induced cell cycle arrest, apoptosis, and autophagy were related to the regulation of associated genes using next-generation sequencing. Our data indicated that RTA dh404 causes G2/M cell cycle arrest and induces apoptosis and autophagy by regulating the expression of cell cycle-, apoptosis-, and autophagy-related genes in human glioblastoma cells, suggesting that RTA dh404 is a potential drug candidate for the treatment of glioblastoma. [ABSTRACT FROM AUTHOR]

The purpose of the present work was to investigate the potential for application and the effectiveness of osteoconductive scaffolds with bicontinuous phases of 3D printed bioceramics (3DP-BCs) based on reverse negative thermoresponsive hydrogels (poly[(N -isopropylacrylamide)- co-(methacrylic acid)]; p(NiPAAm-MAA)). 3DP-BCs have bioceramic objects and microchannel pores when created using robotic deposition additive manufacturing. We evaluated the benefits of silicone oil sealing on the 3DP-BC green body during the sintering process in terms of densification and structural stability. The shrinkage, density, porosity, element composition, phase structure and microstructural analyses and compression strength measurements of sintered 3DP-BC objects are presented and discussed in this study. In addition, the results of cell viability assays and bone healing analyses of the calvarial bone defects in a rabbit model were used to evaluate 3DP-BC performance. The main results indicated that these 3DP-BC scaffolds have optimal continuous pores and adequate compressive strength, which can enable the protection of calvarial defects and provide an environment for cell growth. Therefore, 3DP-BC scaffolds have better new bone regeneration efficiency in rabbit calvarial bone defect models than empty scaffolds and mold-forming bioceramic scaffolds (MF-BCs). [ABSTRACT FROM AUTHOR]

Morphology is an important grain scale property that substantially influences the macroscopic behavior of granular materials. Particle-based methods such as discrete element method are suitable to study the morphology effect because the particle geometry can be systematically controlled. However, coupling realistic particle morphology with simulation involves significant computational costs. Therefore, considerably simplified particle morphology has been typically adopted in the particle-based simulations to keep the computational costs manageable. This paper aims to systematically address how modeling error results from the morphology simplification and investigates how the modeled fidelity of particle morphology influences the simulated granular material behavior. To this end, a spectrum of particle morphology is developed by gradually simplifying a polyhedral particle model that represents a realistic particle morphology. The modeled fidelity is then quantified in term of Shape Factor and Angularity Factor to characterize the global form and the local angularity of the particle morphology. A set of 3D printed particles is developed from the numerical particle models and used in laboratory testing for systematic parametric study. A series of triaxial compression tests is performed on the synthetic specimens with the 3D printed particles. The result indicates the relative importance of high-fidelity modeling of (1) local angularity under low-confining pressure and (2) global form under high-confining pressure. This study also demonstrates the potential of leveraging 3D printed synthetic particles to study the morphology-dependent mechanical behavior of granular materials. [ABSTRACT FROM AUTHOR]

Introduction: Pedicle screws are commonly employed to restore spinal stability and correct deformities. The Renaissance robotic system was developed to improve the accuracy of pedicle screw placement. Purpose: In this study, we developed an intraoperative classification system for evaluating the accuracy of pedicle screw placements through secondary registration. Furthermore, we evaluated the benefits of using the Renaissance robotic system in pedicle screw placement and postoperative evaluations. Finally, we examined the factors affecting the accuracy of pedicle screw implantation. Results: Through use of the Renaissance robotic system, the accuracy of Kirschner-wire (K-wire) placements deviating <3 mm from the planned trajectory was determined to be 98.74%. According to our classification system, the robot-guided pedicle screw implantation attained an accuracy of 94.00% before repositioning and 98.74% after repositioning. However, the malposition rate before repositioning was 5.99%; among these placements, 4.73% were immediately repositioned using the robot system and 1.26% were manually repositioned after a failed robot repositioning attempt. Most K-wire entry points deviated caudally and laterally. Conclusion: The Renaissance robotic system offers high accuracy in pedicle screw placement. Secondary registration improves the accuracy through increasing the precision of the positioning; moreover, intraoperative evaluation enables immediate repositioning. Furthermore, the K-wire tends to deviate caudally and laterally from the entry point because of skiving, which is characteristic of robot-assisted pedicle screw placement. [ABSTRACT FROM AUTHOR]

Objectives: Osteoporosis Self-Assessment Tool for Asians (OSTA) has been proved to be a simple and effective tool for recognizing osteoporosis risk. Our previous study has demonstrated that the preoperative OSTA index was a good prognostic predictor for stage II and III colon cancer patients after surgery. We aim to evaluate the value of OSTA index in prognostication of isolated traumatic brain injury with moderate severity (GCS 9-13). Methods: We retrospectively reviewed all patients visiting Kaohsiung Medical University Hospital emergency department due to isolated moderate traumatic brain injury from Jan. 2010 to Dec. 2012. Background data (including the OSTA index), clinical presentations, management and outcomes (ICU admission days, total admission days, complications, Glasgow outcome score (GOS) at discharge, mortality) of the patients were recorded for further analysis. Our major outcome was good neurologic recovery defined as GOS of 5. Pearson chi-square test and the Mann-Whitney U test were used to compare demographic features. Multiple logistic regression was used to identify independent risk factors. Results: 107 isolated moderate TBI patients were studied. 40 patients (37.4%) showed good recovery and 10 (9.3%) died at discharge. The univariate analysis revealed that younger age, higher OSTA index, lower ISS, lower AIS-H, and avoidance to neurosurgery were associated with better neurologic outcome for all moderate TBI patients. Multivariate analysis revealed that lower ISS, higher OSTA, and the avoidance of neurosurgery were independent risk factors predicting good neurologic recovery. Conclusion: Higher ISS, lower OSTA index and exposure to neurosurgery were the independent risk factors for poorer recovery from isolated moderate TBI. In addition to labeling the cohort harboring osteoporotic risk, OSTA index could predict neurologic prognosis in patients with isolated moderate traumatic brain injury. [ABSTRACT FROM AUTHOR]

Abstract: Background: Coldness, numbness, or causalgia usually affects the lower limbs in patients after back surgeries. The treatment of causalgia is still the source of continuing debate. We treated patients presenting with causalgia secondary to LD with CT-guided CLS and determined the therapeutic outcome at long-term follow-up. Methods: From January 2002 to December 2002, a total of 15 patients (16 limbs) with causalgia after LD underwent the percutaneous CT-guided CLS. There were 7 male patients and 8 female patients, with an average age of 49.1 years. A total of 14 patients underwent unilateral procedures, and 1 patient underwent staged bilateral procedures. We followed up our patients for at least 24 months (24-36 months). Results: There were 13 patients (14 limbs) diagnosed as Drucker stage I and 2 patients as stage II. There were 88% (14 limbs) that had an early satisfactory outcome after CLS and 75% (12 limbs) that had a late satisfactory outcome (more than 24 months after CLS). Stage I patients had more satisfying early and late outcome than stage II patients (P = .014 and P = .039, respectively). Female patients were more likely to have satisfactory late outcome than male patients (P = .034). There was no operative mortality. A patient had a complication of genitofemoral neuralgia, which had recovered in a month. Conclusions: We concluded that the percutaneous CT-guided CLS is an easy, safe, and reproducible technique, and it carries long-term benefit to patients with pain after LD presenting with causalgia, especially for patients with Drucker stage I and female patients. [Copyright &y& Elsevier]

• MiR-1271 is down-regulated in glioma cell lines and high-grade gliomas tissues. • MiR-1271 reduces proliferation and invasion of human glioma cells. • MiR-1271 directly targeted the untranslated region of CAMMK2. This study explored the regulatory role of microRNA-1271 (miR-1271) in glioblastoma multiforme (GBM) proliferation and invasion via calcium/calmodulin-dependent protein kinase 2 (CaMKK2). MiR-1271 and CaMKK2 expression were quantified in normal human astrocyte cells, GBM cell lines, and low- and high-grade glioma tissues. MKI67 expression in GBM cells was measured using quantitative real-time polymerase chain reaction. The target relationship between miR-1271 and the CAMKK2 gene was confirmed using the luciferase reporter assay. MTT and Transwell assays were used to analyze the role of miR-1271 and CAMKK2 in cell proliferation and invasion. Finally, CaMKK2 expression and AKT phosphorylation were detected by western blotting. MiR-1271 was significantly downregulated in high-grade glioma tissues and GBM cell lines. Conversely, CAMKK2 mRNA expression was upregulated in high-grade glioma tissues and GBM cell lines. We observed that miR-1271 directly targeted the 3′-untranslated region of CAMKK2 , indicating an inverse relationship with miR-1271. Overexpressing miR-1271 inhibited GBM cell proliferation and invasion, whereas inhibiting miR-1271 increased cell proliferation and invasion. Silencing CAMKK2 expression also inhibited GBM cell proliferation and invasion. Furthermore, overexpressing miR-1271 inhibited AKT phosphorylation and MKI67 mRNA expression by targeting CAMKK2. These results indicate that miR-1271 regulates GBM cell proliferation and invasion, and that these effects involve directly targeting the CAMKK2 gene. Therefore, miR-1271 may serve as a new therapeutic target for developing GBM treatments. [ABSTRACT FROM AUTHOR]

Reconstruction of severe osteochondral defects in articular cartilage and subchondral trabecular bone remains a challenging problem. The well-integrated bilayer osteochondral graft design expects to be guided the chondrogenic and osteogenic differentiation for stem cells and provides a promising solution for osteochondral tissue repair in this study. The subchondral bone scaffold approach is based on the developed finer and denser 3D β-tricalcium phosphate (β-TCP) bioceramic scaffold process, which is made using a digital light processing (DLP) technology and the novel photocurable negative thermo-responsive (NTR) bioceramic slurry. Then, the concave-top disc sintered 3D-printed bioceramic incorporates the human adipose-derived stem cells (hADSCs) laden photo-cured hybrid biohydrogel (HG + 0.5AFnSi) comprised of hyaluronic acid methacryloyl (HAMA), gelatin methacryloyl (GelMA), and 0.5% (w/v) acrylate-functionalized nano-silica (AFnSi) crosslinker. The 3D β-TCP bioceramic compartment is used to provide essential mechanical support for cartilage regeneration in the long term and slow biodegradation. However, the apparent density and compressive strength of the 3D β-TCP bioceramics can be obtained for ~ 94.8% theoretical density and 11.38 ± 1.72 MPa, respectively. In addition, the in vivo results demonstrated that the hADSC + HG + 0.5AFnSi/3D β-TCP of the bilayer osteochondral graft showed a much better osteochondral defect repair outcome in a rabbit model. The other word, the subchondral bone scaffold of 3D β-TCP bioceramic could accelerate the bone formation and integration with the adjacent host cancellous tissue at 12 weeks after surgery. And then, a thicker cartilage layer with a smooth surface and uniformly aligned chondrocytes were observed by providing enough steady mechanical support of the 3D β-TCP bioceramic scaffold. [ABSTRACT FROM AUTHOR]

A pseudoplastic metal nanoparticle fluid (PMNF) is used in nanoimprint to fabricate semiconductors and functional devices. The evaporation of the solvent and the sintering of the Au PMNF are investigated. The key parameters, which influence the morphology of patterning, such as the radius of metal particles, the concentration of metal particles, the Hamaker constant of the solvent, viscosity of the fluids and the evaporation velocity, are analyzed. Based on a two-sphere sintering model, the equations are derived, which represent the relationships between the relative shrinkage and radius of the metal particles, sintering temperature and time. The optimal parameters for the heat treatment are provided in nanoimprint. [ABSTRACT FROM AUTHOR]

2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid-9,11-dihydro-trifluoroethyl amide (CDDO-dhTFEA) has antioxidant and anti-inflammatory activities; however, whether CDDO-dhTFEA has anticancer effects is unclear. The objective of this research was to investigate the possibility of CDDO-dhTFEA as a potential cancer-fighting treatment in glioblastoma cells. Our experiments were performed on U87MG and GBM8401 cells, and we found that CDDO-dhTFEA was effective in reducing cell proliferation in both cell lines, in a manner that was dependent on both time and concentration. Additionally, we observed that CDDO-dhTFEA had a significant impact on the regulation of cell proliferation, which was evident in the increase in DNA synthesis that was observed in both cell types. CDDO-dhTFEA induced G2/M cell cycle arrest and mitotic delay, which may be associated with the inhibition of proliferation. Treatment with CDDO-dhTFEA led to cell cycle G2/M arrest and inhibited proliferation of U87MG and GBM8401 cells by regulating G2/M cell cycle proteins and gene expression in GBM cells in vitro. [ABSTRACT FROM AUTHOR]

Whether traumatic brain injury (TBI) is causally related to substance related disorder (SRD) is still debatable, especially in persons with no history of mental disorders at the time of injury. This study analyzed data in the Taiwan National Health Insurance Research Database for 19,109 patients aged ≥18 years who had been diagnosed with TBI during 2000–2010. An additional 19,109 randomly selected age and gender matched patients without TBI (1 : 1 ratio) were enrolled in the control group. The relationship between TBI and SRD was estimated with Cox proportional hazard regression models. During the follow-up period, SRD developed in 340 patients in the TBI group and in 118 patients in the control group. After controlling for covariates, the overall incidence of SRD was 3.62-fold higher in the TBI group compared to the control group. Additionally, patients in the severe TBI subgroup were 9.01 times more likely to have SRD compared to controls. Notably, patients in the TBI group were prone to alcohol related disorders. The data in this study indicate that TBI is significantly associated with the subsequent risk of SRD. Physicians treating patients with TBI should be alert to this association to prevent the occurrence of adverse events. [ABSTRACT FROM AUTHOR]

Meningiomas are common in nonglial intracranial brain tumors. However, cystic meningiomas, such as hemangioblastoma, pilocytic astrocytoma, metastatic brain tumor, and neuroblastoma, are rare and should be differentiated from other brain tumors with cystic characteristics. Accurate diagnosis is crucial for patients with brain tumors, but diagnosing cystic meningiomas is difficult despite the advances in computed tomography, magnetic resonance imaging, and magnetic resonance spectrometry. In this report, we share our experience regarding a case of cystic meningioma mimicking hemangioblastoma and discuss its management. An intraoperative frozen section is warranted to overcome the difficulty in disease diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Transforming growth factor-beta 1 (TGF-β1) has been reported to be a possible marker for a number of tumors, including brain tumors. The aim of this study was to measure the plasma levels of TGF-β1 in patients with low- and high-grade astrocytomas before and after surgery. This prospective study included 14 patients with low-grade astrocytomas and 25 with high-grade astrocytomas who underwent tumor removal and 13 controls (patients who underwent cranioplasty for skull bone defects). Plasma levels of TGF-β1 were measured in all subjects using enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis showed that when the level of TGF-β1 before tumor removal was ⩾2.52ng/ml, astrocytoma was predicted with a sensitivity of 94.9% and specificity of 100%. The mean plasma level of TGF-β1 in both the low-grade and high-grade astrocytoma groups significantly decreased after tumor removal (p <0.05); there was no significant change in TGF-β1 plasma level of the controls following surgery. Patients with high-grade astrocytomas had a significantly higher mortality rate than patients with low-grade astrocytomas (p =0.019) and significantly shorter survival (p =0.008). A positive correlation between TGF-β1 level after tumor removal and tumor volume was only found in the high-grade astrocytoma group (γ =0.597, p =0.002). The findings show that plasma TGF-β1 level was increased in patients with low-grade and high-grade astrocytoma, and that the levels significantly decreased after tumor removal in both groups. The results provide additional evidence that TGF-β1 might be useful as a tumor marker for astrocytomas. [Copyright &y& Elsevier]

Objective. Decompressive craniectomy reduces fatality in patients with space-occupying infarctions. However, mortality remains high. We aimed to identify predictors of in-hospital mortality and outcomes in a cohort of patients with large hemispheric stroke receiving decompressive craniectomy. Methods. We retrospectively reviewed all patients diagnosed with complete middle cerebral artery infarction and receiving decompressive craniectomy. Hospital characteristics were compared among different groups (survivors versus non-survivors, good outcome versus poor outcome). A total of 71 consecutive patients were enrolled. Results. From 2004 January to 2010 April, 71 patients were enrolled whose mean age was 65.11 ± 13.13 years and 33 (46.5%) of these were men. The in-hospital mortality was 28.2% overall. Of the patients who survived and were discharged, 37 (77.1%) had poor outcome (mRS 4-6) and 11 (22.9%) had good outcome (mRS 0-3). Pre-operation brain computed tomography (CT) hypodensity volume (p = 0.001) was significantly associated with mortality. In binary logistic regression model, pre-operation brain CT hypodensity volume (OR = 1.015; 95% CI, 1.001 to 1.030) and age (OR = 1.112; 95% CI, 1.017 to 1.215) were both significantly associated with outcomes. Conclusions. In patients with large hemispheric stroke receiving decompressive craniectomy, pre-operation brain CT hypodensity volume was significantly associated with in-hospital mortality whereas age was not. Pre-operation brain CT hypodensity volume and age were predictors of outcomes in those who survived the acute phase. [ABSTRACT FROM AUTHOR]

A subarachnoid hemorrhage (SAH), leading to severe disability and high fatality in survivors, is a devastating disease. Neuro-inflammation, a critical mechanism of cerebral vasospasm and brain injury from SAH, is tightly related to prognoses. Interestingly, studies indicate that 2-[(pyridine-2-ylmethyl)-amino]-phenol (2-PMAP) crosses the blood–brain barrier easily. Here, we investigated whether the vasodilatory and neuroprotective roles of 2-PMAP were observed in SAH rats. Rats were assigned to three groups: sham, SAH and SAH+2-PMAP. SAHs were induced by a cisterna magna injection. In the SAH+2-PMAP group, 5 mg/kg 2-PMAP was injected into the subarachnoid space before SAH induction. The administration of 2-PMAP markedly ameliorated cerebral vasospasm and decreased endothelial apoptosis 48 h after SAH. Meanwhile, 2-PMAP decreased the severity of neurological impairments and neuronal apoptosis after SAH. Furthermore, 2-PMAP decreased the activation of microglia and astrocytes, expressions of TLR-4 and p-NF-κB, inflammatory markers (TNF-α, IL-1β and IL-6) and reactive oxygen species. This study is the first to confirm that 2-PMAP has vasodilatory and neuroprotective effects in a rat model of SAH. Taken together, the experimental results indicate that 2-PMAP treatment attenuates neuro-inflammation, oxidative stress and cerebral vasospasm, in addition to ameliorating neurological deficits, and that these attenuating and ameliorating effects are conferred through the TLR-4/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Background: Stroke is a leading cause of death, morbidity and disability worldwide. Infection is a common complication in the acute phase after stroke. Herpes zoster is a common viral disease, in which the most debilitating complication is post-herpetic neuralgia, which can have a very large negative impact on quality of life. The aim of this study was to investigate whether stroke increases the risk of herpes zoster. Methods: This cohort study compared patients who had herpes zoster with and without a first incident of stroke. The Taiwan National Health Insurance Research Database was utilized to identify 20,551 stroke patients and 20,551 controls matched for age, gender, age categories and Charlson Comorbidity Index (CCI) score categories at a one-to-one ratio. Cox proportional-hazards regression models were employed to estimate herpes zoster risk in the stroke group relative to general population. Results: Compared to the control group, the stroke group had a greater risk for herpes zoster, especially within 1 year after stroke (adjust HR = 25.27). Both hemorrhagic stroke and ischemic stroke were significantly associated with herpes zoster (hemorrhagic type (IRR = 2.31, 95% CI, 1.67–3.20); ischemic type (IRR = 2.51, 95% CI 2.09–3.02)). However, the hemorrhagic stroke patients had a higher risk of herpes zoster ophthalmicus (IRR = 12.46, 95% CI 4.00–38.76) whereas the ischemic stroke patients had a higher risk of post-herpetic neuralgia (IRR = 2.24, 95% CI 1.56–3.20). Conclusion: Physicians should know about that adults with stroke have a higher than normal risk of herpes zoster. Thus, physicians must be acquainted with proper antiviral therapy and pain control to bring down the morbidity that ensues from herpes zoster. Use of herpes zoster vaccine may be considered in stroke patients. [ABSTRACT FROM AUTHOR]

Primary melanocytic neoplasms (PMNs) are rare neoplasms, especially within the central nervous system. Meningeal melanocytomas, a subtype of PMN, are even rarer. Nevus of Ota results from the incomplete migration of melanocytes from the neural crest. Synchronous nevus of Ota and meningeal melanocytoma are infrequently encountered in clinical practice. To evaluate and elucidate 12 cases of synchronous meningeal melanocytoma and nevus of Ota, thereby improving the understanding of the relationship between these 2 diseases. We reviewed cases and searched the English-language literature from the PubMed database and collected clinical parameters of 12 cases of synchronously occurring nevus of Ota and meningeal melanocytoma. Among the 12 cases, 90.90% and 91.66% of the lesions were located ipsilaterally and supratentorially, respectively. Our findings indicated a trend for both types of lesion to be located ipsilaterally and supratentorially. When a patient with nevus of Ota is found to harbor an intracranial neoplasm, the most likely diagnosis is PMN. [ABSTRACT FROM AUTHOR]

Highlights • Morphological factors of two different types of aggregate are systemically quantified using an image-based morphology analysis. • Three hypotheses are postulated to elaborate the angularity-dependent behavior of CBM. • Particle surface area is a critical mediator correlating the morphology with the mechanical performance. • Angular aggregate 'negatively' impacts the small-strain material performance. • Angular aggregate 'positively' impacts the ultimate state property. Abstract This study aims to fundamentally understand the influence of angularity of coarse aggregate on the mechanical performance of cement-based materials. Three hypotheses are postulated to address the influence of aggregate angularity that negatively impacts the small-strain performances, while positively influences the property in the ultimate state at a large strain level. The morphology of two types of coarse aggregates is systemically quantified using an image-based analysis. This study experimentally corroborates the efficacy of the postulated hypotheses through a set of laboratory tests on cement-based cylinders. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate osteoporosis risk in atopic dermatitis (AD) patients. This study included patients in the Taiwan National Health Insurance Research dataset. The population-based study included all patients aged 20–49 years who had been diagnosed with AD during 1996–2010. In total, 35,229 age and gender-matched patients without AD in a 1:1 ratio were randomly selected as the non-AD group. Cox proportional-hazards regression and Kaplan–Meier analyses were used to measure the hazard ratios and the cumulative incidences of osteoporosis, respectively. During the follow-up period, 360(1.02%) AD patients and 127(0.36%) non-AD patients developed osteoporosis. The overall incidence of osteoporosis was4.72-fold greater in the AD patients compared to the non-AD patients (1.82 vs. 0.24 per 1,000 person-years, respectively) after adjusting for potential confounding factors. Osteoporosis risk factors included female gender, age, advanced Charlson Comorbidity Index, depression and use of corticosteroids. The dataset analysis showed that AD was significantly associated with subsequent risk of osteoporosis. [ABSTRACT FROM AUTHOR]

The aims of this study were to investigate the risk of hip fracture and contributing factors in patients with erectile dysfunction(ED). This population-based study was performed using the Taiwan National Health Insurance Research Database. The analysis included4636 patients aged ≥ 40 years who had been diagnosed with ED (International Classification of Diseases, Ninth Revision, Clinical Modification codes 302.72, 607.84) during 1996–2010. The control group included 18,544 randomly selected age-matched patients without ED (1:4 ratio). The association between ED and hip fracture risk was estimated using a Cox proportional hazard regression model. During the follow-up period, 59 (1.27%) patients in the ED group and 140 (0.75%) patients in the non-ED group developed hip fracture. After adjusting for covariates, the overall incidence of hip fracture was 3.74-times higher in the ED group than in the non-ED group (2.03 vs. 0.50 per 1000 person-years, respectively). The difference in the overall incidence of hip fracture was largest during the 3-year follow-up period (hazard ratio = 7.85; 95% confidence interval = 2.94–20.96; P <0.0001). To the best of our knowledge, this nationwide population-based study is the first to investigate the relationship between ED and subsequent hip fracture in an Asian population. The results showed that ED patients had a higher risk of developing hip fracture. Patients with ED, particularly those aged 40–59 years, should undergo bone mineral density examinations as early as possible and should take measures to reduce the risk of falls. [ABSTRACT FROM AUTHOR]

A large body of evidence over many years suggests that clinical decision support systems (CDSSs) can be helpful in improving both clinical outcomes and adherence to evidence-based guidelines. CDSSs have however failed to show their effectiveness due to poor ease of use and integration within clinical workflows. This research therefore emphasizes a cognitive fit design approach to developing an effective CDSS to solve those issues. According to the cognitive fit theory CDSS should align with the problem and task representation in order to match the physician's mental model to reduce cognitive effort. Several guidelines based on the cognitive fit design are proposed. A stroke CDSS prototype following the design guidelines is developed to demonstrate its feasibility. The system usability test results showed that the developed stroke CDSS was acceptably accurate, able to lessen the cognitive effort as desired, and preferable for use due to the significant reduction in cognitive load. The developed artifact has shown the potential to benefit physicians. Finally, implications and conclusions are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Background: Apoptosis is implicated in vasospasm and the long-term sequelae of subarachnoid hemorrhage (SAH). This study tested the hypothesis that attenuation of SAH-induced apoptosis after 17β-estradiol (E2) treatment is associated with an increase in phosphorylation of Akt via estrogen receptor-α (ER-α) in rats. Materials and methods: We examined the expression of phospho-Akt, ERα and ERβ, and apoptosis in cerebral cortex, hippocampus, and dentate gyrus in a two-hemorrhage SAH model in rats. We subcutaneously implanted other rats with a silicone rubber tube containing E2; they received daily injections of nonselective estrogen receptor antagonist (ICI 182,780), selective ERα-selective antagonist (methyl-piperidino-pyrazole), or ERβ-selective antagonist (R,R-tetrahydrochrysene) after the first hemorrhage. Results: At 7 d after the first SAH, protein levels of phospho-Akt and ERα were significantly decreased and caspase-3 was significantly increased in the dentate gyrus. The cell death assay revealed that DNA fragmentation was significantly increased in the dentate gyrus. Those actions were reversed by E2 and blocked by ICI 182,780 and methyl-piperidino-pyrazole, but not R,R-tetrahydrochrysene. However, there were no significant changes in the expression of the protein levels of phospho-Akt, ERα, ERβ, and caspase-3, and DNA fragmentation after SAH. Conclusions: The present study shows that a beneficial effect of E2 in attenuating SAH-induced apoptosis is associated with activation of the expression of phospho-Akt and ERα, and alteration in caspase-3 protein expression via an ERα-dependent mechanism in the dentate gyrus. These data support further the investigation of E2 in the treatment of SAH in humans. [Copyright &y& Elsevier]

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating emergent event associated with high mortality and morbidity. Survivors usually experience functional neurological sequelae caused by vasospasm-related delayed ischemia. In this study, male Sprague-Dawley rats were randomly assigned to five groups: sham (non-SAH) group, SAH group, and three groups with SAH treated with different doses of valproic acid (VPA) (10, 20, 40 mg/kg, once-daily, for 7 days). The severity of vasospasm was determined by the ratio of cross-sectional areas to intima-media thickness of the basilar arteries (BA) on the seventh day after SAH. The BA showed decreased expression of phospho-Akt proteins. The dentate gyrus showed increased expression of cleaved caspase-3 and Bax proteins and decreased expression of Bcl-2, phospho-ERK 1/2, phospho-Akt and acetyl-histone H3 proteins. The incidence of SAH-induced vasospasm was significantly lower in the SAH group treated with VPA 40 mg/kg (p < 0.001). Moreover, all groups treated with VPA showed reversal of the above-mentioned protein expression in BA and the dentate gyrus. Treatment with VPA upregulated histone H3 acetylation and conferred anti-vasospastic and neuro-protective effects by enhancing Akt and/or ERK phosphorylation. This study demonstrated that VPA could alleviate delayed cerebral vasospasm induced neuro-apoptosis after SAH. [ABSTRACT FROM AUTHOR]

Therapeutic resistance in recurrent glioblastoma multiforme (GBM) after concurrent chemoradiotherapy (CCRT) is a challenging issue. Although standard fractionated radiation is essential to treat GBM, it has led to local recurrence along with therapy-resistant cells in the ionizing radiation (IR) field. Lines of evidence showed cancer stem cells (CSCs) play a vital role in therapy resistance in many cancer types, including GBM. However, the molecular mechanism is poorly understood. Here, we proposed that autophagy could be involved in GSC induction for radioresistance. In a clinical setting, patients who received radiation/chemotherapy had higher LC3II expression and showed poor overall survival compared with those with low LC3 II. In a cell model, U87MG and GBM8401 expressed high level of stemness markers CD133, CD44, Nestin, and autophagy marker P62/LC3II after receiving standard fractionated IR. Furthermore, Wnt/β-catenin proved to be a potential pathway and related to P62 by using proteasome inhibitor (MG132). Moreover, pharmacological inhibition of autophagy with BAF and CQ inhibit GSC cell growth by impairing autophagy flux as demonstrated by decrease Nestin, CD133, and SOX-2 levels. In conclusion, we demonstrated that fractionated IR could induce GSCs with the stemness phenotype by P62-mediated autophagy through the Wnt/β-catenin for radioresistance. This study offers a new therapeutic strategy for targeting GBM in the future. [ABSTRACT FROM AUTHOR]

The article describes the case of a 32-year-old male patient who complained of intermittent headaches for several weeks. Intracerebral hemorrhage was detected in the left temporal lobe via computed tomography (CT) scans. Also mentioned are CT angiography findings, arteriovenous malformation diagnosis, and histopathological examination results.