Chlorpyrifos-induced suppression of the antioxidative defense system leads to cytotoxicity and genotoxicity in macrophages.

Chlorpyrifos, widely used for pest control, is known to have various harmful effects, although its toxic effects in macrophages and the mechanisms underlying its toxicity remain unclear. The present study investigated the toxic effects of chlorypyrifos in a macrophage cell line. Here, we found that chlorpyrifos induced cytotoxicity and genotoxicity in RAW264.7 macrophages. Moreover, chlorpyrifos induced intracellular ROS production, subsequently leading to lipid peroxidation. Chlorpyrifos reduced the activation of antioxidative enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Chlorpyrifos upregulated HO-1 expression and activated the Keap1-Nrf2 pathway, as indicated by enhanced Nrf2 phosphorylation and Keap1 degradation. Chlorpyrifos exerted effects on the following in a dose-dependent manner: cytotoxicity, genotoxicity, lipid peroxidation, intracellular ROS production, antioxidative enzyme activity reduction, HO-1 expression, Nrf2 phosphorylation, and Keap1 degradation. Notably, N-acetyl-L-cysteine successfully inhibited chlorpyrifos-induced intracellular ROS generation, cytotoxicity, and genotoxicity. Thus, chlorpyrifos may induce cytotoxicity and genotoxicity by promoting intracellular ROS production and suppressing the antioxidative defense system activation in macrophages.

Cyclizine induces cytotoxicity and apoptosis in macrophages through the extrinsic and intrinsic apoptotic pathways.

Cyclizine, an over-the-counter and prescription antihistamine, finds widespread application in the prevention and treatment of motion sickness, encompassing symptoms such as nausea, vomiting, dizziness, along with its effectiveness in managing vertigo. However, the overuse or misuse of cyclizine may lead to hallucinations, confusion, tachycardia, and hypertension. The molecular mechanisms underlying cyclizine-induced cytotoxicity and apoptosis remain unclear. During the 24 h incubation duration, RAW264.7 macrophages were exposed to different concentrations of cyclizine. Cytotoxicity was assessed through the lactate dehydrogenase assay. Flow cytometry employing annexin V-fluorescein isothiocyanate and propidium iodide was utilized to evaluate apoptosis and necrosis. Caspase activity and mitochondrial dysfunction were evaluated through a fluorogenic substrate assay and JC-1 dye, respectively. Flow cytometry employing fluorogenic antibodies was utilized to evaluate the release of cytochrome c and expression of death receptor, including tumor necrosis factor-α receptor and Fas receptor. Western blotting was utilized to evaluate the expression of the Bcl2 and Bad apoptotic regulatory proteins. The findings unveiled from the present study demonstrated that cyclizine exerted a concentration-dependent effect on RAW264.7 macrophages, leading to the induction of cytotoxicity, apoptosis, and necrosis. This compound further activated the intrinsic apoptotic pathway by inducing mitochondrial dysfunction, Bcl2/Bad exchange expression, cytochrome c liberation, and activation of caspases contained caspase 3, 8, and 9. Moreover, the activation of the extrinsic apoptotic pathway was observed as cyclizine induced the upregulation of death receptors and increased caspase activities. Based on our investigations, it can be inferred that cyclizine prompts cytotoxicity and apoptosis in RAW264.7 macrophages in a concentration-dependent manner by triggering both the intrinsic and extrinsic apoptotic pathways.

Development and Validation of a 3D Resnet Model for Prediction of Lymph Node Metastasis in Head and Neck Cancer Patients.

The accurate diagnosis and staging of lymph node metastasis (LNM) are crucial for determining the optimal treatment strategy for head and neck cancer patients. We aimed to develop a 3D Resnet model and investigate its prediction value in detecting LNM. This study enrolled 156 head and neck cancer patients and analyzed 342 lymph nodes segmented from surgical pathologic reports. The patients' clinical and pathological data related to the primary tumor site and clinical and pathology T and N stages were collected. To predict LNM, we developed a dual-pathway 3D Resnet model incorporating two Resnet models with different depths to extract features from the input data. To assess the model's performance, we compared its predictions with those of radiologists in a test dataset comprising 38 patients. The study found that the dimensions and volume of LNM + were significantly larger than those of LNM-. Specifically, the Y and Z dimensions showed the highest sensitivity of 84.6% and specificity of 72.2%, respectively, in predicting LNM + . The analysis of various variations of the proposed 3D Resnet model demonstrated that Dual-3D-Resnet models with a depth of 34 achieved the highest AUC values of 0.9294. In the validation test of 38 patients and 86 lymph nodes dataset, the 3D Resnet model outperformed both physical examination and radiologists in terms of sensitivity (80.8% compared to 50.0% and 91.7%, respectively), specificity(90.0% compared to 88.5% and 65.4%, respectively), and positive predictive value (77.8% compared to 66.7% and 55.0%, respectively) in detecting individual LNM + . These results suggest that the 3D Resnet model can be valuable for accurately identifying LNM + in head and neck cancer patients. A prospective trial is needed to evaluate further the role of the 3D Resnet model in determining LNM + in head and neck cancer patients and its impact on treatment strategies and patient outcomes.

Outcome of Thromboembolic Events and Its Influence on Survival Time of Advanced NSCLC Patients Treated with Antiangiogenic Therapy.

Background: Antiangiogenetic therapy and lung cancer, per se, are associated with an increased risk of thromboembolic events (TE). We aim to evaluate the pattern and outcome of TE as well as its influence on survival time of advanced non-small cell lung cancer (NSCLC) patients receiving antiangiogenic therapy. Methods: This was a retrospective cohort study, which included advanced NSCLC patients receiving antiangiogenic therapy. All TE were confirmed by objective image studies. We disclosed the presentation and risk factors of TE and evaluated its influence on outcome. Results: A total of 427 patients were included. TE occurred in 43 patients (10.1%). Deep vein thrombosis (DVT) was the most common TE (n = 20). Up to 46.2% of DVT did not occur in the typical lower extremities. Two patients died of TE. Among patients with continuous use or reuse of antiangiogenetic therapy, 18.2% had recurrent TE events. At the occurrence of TE, 28 patients experienced progressive disease (TE with PD), while tumor status remained stable in another 15 patients (TE without PD). The post-TE survival of patients without and with PD were 8.9 months (95% CI 3.9-13.9) vs 2.2 months (95% CI 0.1-4.3), P = 0.012. As compared with patients without TE (31.4 months [95% CI 27.1-35.7]), TE with PD patients experienced a significantly shorter overall survival (20.1 months [95% CI 15.5-24.6]), but TE without PD patients had comparable survival time (32.7 months [95% CI 7.4-28.1]) (P = 0006). The use of hormone analogue and proteinuria predicted the events among TE with PD group (aOR 2.79 [95% CI 1.13=6.92]; P = 0.027) and TE without PD group (aOR 4.30 [95% CI 1.13-16.42]; P = 0.033), respectively. Conclusion: Owing to the different risk factors and influences on the survival time, TE with and without PD may be two different disease entities.

Influence of the Components and Orientation of Hydroxyapatite Fibrous Substrates on Osteoblast Behavior.

Synthetic hydroxyapatite has good biocompatibility, bioactivity and osteoconductive ability because its chemical properties and biological properties are similar to those of bioapatite in bone tissue. Strontium-substituted hydroxyapatite has better degradability than hydroxyapatite and can both promote osteogenesis and inhibit adipogenesis in mesenchymal stem cells. Hence, hydroxyapatite and strontium-substituted hydroxyapatite are widely used as bone graft materials, cell carriers and drug/gene delivery carriers. In addition, osteoblasts cultured on aligned nanofibrous substrates had higher expression of osteogenesis-related genes than did those cultured on random nanofibrous substrates. However, to date, no study has explored the effects of the components and orientation of hydroxyapatite nanofibrous substrates on osteoblastic behavior. In this study, a random hydroxyapatite nanofibrous substrate (R-HANF), a random strontium-substituted hydroxyapatite nanofibrous substrate (R-SrHANF), an aligned hydroxyapatite nanofibrous substrate (A-HANF) and an aligned strontium-substituted hydroxyapatite nanofibrous substrate (A-SrHANF) were successfully fabricated by using the electrospinning technique. The effect of fiber composition on osteoblast-like MG63 cells was assessed by evaluating cell morphology, cell proliferation and osteogenesis-related gene expression. The results showed that MG63 cells cultured on A-SrHANF had higher osteogenesis-related gene expression than those cultured on A-HANF. Additionally, MG63 cells were cultured on R-SrHANF and A-SrHANF to evaluate the effects of fiber orientation on cell behavior. On A-SrHANF, the cells aligned along the direction of the nanofibers, with typical bipolar morphologies, and exhibited higher osteogenesis-related gene expression than cells on R-SrHANF. Hence, the components and orientation of hydroxyapatite nanofibrous substrates are critical parameters affecting the osteogenesis process.

Reactivation of Hepatitis B Virus in Lung Cancer Patients Receiving Tyrosine Kinase Inhibitor Treatment.

(1) Background: We aimed to evaluate the risk of hepatitis B virus (HBV) reactivation in lung cancer patients treated with tyrosine kinase inhibitor (TKI), particularly in those with resolved HBV infection. (2) Methods: In this retrospective hospital-based cohort study, we screened all lung cancer patients with positive hepatitis B core antibodies (anti-HBc) receiving systemic antineoplastic treatment during the period from January 2011 to December 2020. Cumulative incidences of HBV reactivation, and their hazard ratios (HRs), were evaluated after adjusting patient mortality as a competing risk. (3) Results: Among 1960 anti-HBc-positive patients receiving systemic therapy, 366 were HBsAg-positive and 1594 were HBsAg-negative. In HBsAg-positive patients without prophylactic NUC, 3-year cumulative incidences of HBV reactivation were similar between patients receiving chemotherapy and patients receiving TKI (15.0%, 95% confidence interval (CI): 0−31.2% vs. 21.2%, 95% CI: 10.8−31.7%; p = 0.680). Likewise, 3-year cumulative incidences of HBV-related hepatitis were similar between the two groups (chemotherapy vs. TKI: 15.0%, 95% CI: 0−31.2% vs. 9.3%, 95% CI: 2.8−15.7%; p = 0.441). In 521 HBsAg-negative TKI users, the 3-year cumulative incidence of HBV reactivation was only 0.6% (95% CI: 0.0−1.9%). From multivariable regression analysis, we found that the only independent risk factor for HBV reactivation in TKI users was HBsAg positivity (HR 53.8, 95% CI: 7.0−412.9; p < 0.001). (4) Conclusion: Due to high risks of HBV reactivation in HBsAg-positive TKI users, NUC prophylaxis can be considered. However, in patients with resolved HBV infection, such risks are lower, and therefore regular monitoring is recommended.

The Effect of Strontium-Substituted Hydroxyapatite Nanofibrous Matrix on Osteoblast Proliferation and Differentiation.

Natural bone tissue consists primarily of bioapatite and collagen. Synthetic hydroxyapatite (HA) possesses good biocompatibility, bioactivity, and osteoconductivity due to its chemical and biological similarity to bioapatite. Hence, HA has been widely used as a bone graft, cell carrier and drug/gene delivery carrier. Moreover, strontium-substituted hydroxyapatite (SrHA) can enhance osteogenic differentiation and inhibit adipogenic differentiation of mesenchymal stem cells. Hence, SrHA has the potential to be used as a bone graft for bone regeneration. It is widely accepted that cell adhesion and most cellular activities are sensitive to the topography and molecular composition of the matrix. Electrospun polymer or polymer-bioceramic composite nanofibers have been demonstrated to enhance osteoblast differentiation. However, to date, no studies have investigated the effect of nanofibrous bioceramic matrices on osteoblasts. In this study, hydroxyapatite nanofiber (HANF) and strontium-substituted hydroxyapatite nanofiber (SrHANF) matrices were fabricated by electrospinning. The effect of the HANF components on MG63 osteoblast-like cells was evaluated by cell morphology, proliferation, alkaline phosphatase activity (ALP) and gene expression levels of RUNX2, COLI, OCN and BSP. The results showed that MG63 osteoblast-like cells exhibited higher ALP and gene expression levels of RUNX2, COLI, BSP and OCN on the SrHANF matrix than the HANF matrix. Hence, SrHANFs could enhance the differentiation of MG63 osteoblast-like cells.

Enhanced Sensing Ability of Brush-Like Fe2O3-ZnO Nanostructures towards NO2 Gas via Manipulating Material Synergistic Effect.

Brush-like α-Fe2O3-ZnO heterostructures were synthesized through a sputtering ZnO seed-assisted hydrothermal growth method. The resulting heterostructures consisted of α-Fe2O3 rod templates and ZnO branched crystals with an average diameter of approximately 12 nm and length of 25 nm. The gas-sensing results demonstrated that the α-Fe2O3-ZnO heterostructure-based sensor exhibited excellent sensitivity, selectivity, and stability toward low-concentration NO2 gas at an optimal temperature of 300 °C. The α-Fe2O3-ZnO sensor, in particular, demonstrated substantially higher sensitivity compared with pristine α-Fe2O3, along with faster response and recovery speeds under similar test conditions. An appropriate material synergic effect accounts for the considerable enhancement in the NO2 gas-sensing performance of the α-Fe2O3-ZnO heterostructures.

Case history on Epstein-Barr Virus-associated smooth muscle tumor (EBV-SMT) of cranio-cervical junction in an immunocompetent patient.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor that almost exclusively occurs in immunocompromised hosts. Here, we report a 75-year-old Taiwanese woman without definite immune-deficient history presenting with progressive occipital neuralgia, low cranial nerve deficits (CN9-12) and cervical (C1-C5) radiculopathy. Magnetic resonance imaging revealed a 4.5*4.0*6.7 cm infiltrating mass occupying posterior skull base and C1-C2 vertebra and C1-5 epidural extension with bone destruction and vertebral artery (VA) encasement. There was also a synchronous 2.7 cm tonsillar tumor. A two-stage operation for cranio-cervical tumor excision and stabilization was performed. Tumor was confirmed directly arising from VA intraoperatively. Pathology reported a spindle cell neoplasm and the diagnosis of EBV-SMT was confirmed by EBER (EBV-encoded small RNA) in situ hybridization. An immune survey and reconstruction should be conducted for patient with EBV-SMT. A near-total resection of tumor may be beneficial for local control, however, the role of surgical resection in treating CNS EBV-SMT remains to be determined.

Role of surgery in treating epstein-barr virus-associated smooth muscle tumor (EBV-SMT) with central nervous system invasion: A systemic review from 1997 to 2019.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor occurred almost exclusively in immunocompromised hosts. This article provides a systematic review of literature under PRISMA guideline on clinical features, treatment modalities, roles of surgical intervention, and outcomes of all 65 reported EBV-SMTs with central nervous system (CNS) invasion. Over 95% of reported cases were immunocompromised, while human immunodeficiency virus infection and post-organ transplantation were the most commonly associated underlying causes (near 90%). Despite a heterogeneous follow-up period, a 1-year survival rate of 76.0% and 5-year survival rate of 59.6% may support the indolent and non-deadly nature of EBV-SMT even with CNS invasion. Immune survey and reconstruction should be conducted for every patient with CNS EBV-SMT. Surgical resection is mostly adopted as primary treatment to obtain diagnosis and relieve compressive effect. A total resection of tumor may be beneficial if tumor was symptomatic and had intracranial invasion.

Biomarker discovery in highly invasive lung cancer cell through proteomics approaches.

Lung cancer is one of the leading causes of cancer-related death worldwide. The most common type of lung cancer is non-small cell lung cancer (NSCLC). When NSCLC is detected, patients are typically already in a metastatic stage. Metastasized cancer is a major obstacle of effective treatment and understanding the mechanisms underlying metastasis is critical to treat cancer. Herein, we selected an invasive subpopulation from the human lung cancer cell line A549 using the transwell system and named it as A549-I5. Invasive and migratory activities of this cell line were analysed using wound healing, invasion, and migration assays. In addition, epithelial-mesenchymal transition (EMT) markers, such as Snail 1, Twist, Vimentin, N-cadherin and E-cadherin, were assessed through immunoblotting. In comparison to A549 cells, the invasive A549-I5 lung cancer cells had enhanced invasiveness, motility and EMT marker expression. Proteomic analysis identified 83 significantly differentially expressed proteins in A549-I5 cells. These identified proteins were classified according to their cellular functions and most were involved in cytoskeleton, redox regulation, protein degradation and protein folding. In summary, our results provide potential diagnostic markers and therapeutic candidates for the treatment of NSCLC metastasis. SIGNIFICANCE OF THE STUDY: When NSCLC is detected, most patients are already in a metastatic stage. Herein, we selected an invasive subpopulation from a human lung cancer cell line which had increased EMT markers as well as high wound healing, invasion and migration abilities. Proteomic analysis identified numerous proteins associated with functions in cytoskeleton, redox regulation, protein degradation and protein folding that were differentially expressed in these cells. These results may provide potential diagnostic markers and therapeutic candidates for the treatment of NSCLC metastasis.

Association of genetic variants in migraineurs with and without restless legs syndrome.

OBJECTIVE: Several single-nucleotide polymorphisms (SNPs) are associated with restless legs syndrome (RLS). This study investigated whether or not additional SNP variants increase the risk of RLS in migraineurs and in migraine with aura (MA) and migraine without aura (MoA) subgroups. METHODS: Migraineurs with and without RLS were genotyped using an Affymetrix array. We performed association analyses for the entire cohort and the MA and MoA subgroups, which were divided further into episodic migraine (EM) and chronic migraine (CM). Potential correlations between SNPs and clinical indices in migraineurs with RLS were examined by multivariate regression analysis. RESULTS: The rs77234324 and rs79004933 SNPs were found in migraineurs with (P = 2.57E-07) and without (P = 3.03E-07) RLS. The A allele frequency for rs77234324 (on LGR6) was 0.1321 in migraineurs with RLS and 0.0166 in those without RLS (odds ratio, 8.978). The T allele frequency for rs79004933 (in the intergenic region) was 0.1981 in migraineurs with RLS and 0.0446 in those without (odds ratio, 5.281). rs2858654, rs76770509, rs4243475 in UTRN, rs150762626, and rs2668375 were identified in migraine with and without RLS in the MoA subgroup (P = 7.56E-09, P = 2.30E-08, P = 1.19E-07, P = 6.86E-07, and P = 8.05E-07, respectively). There was a suggestion of an association between rs10510331 (P = 1.50E-06) and CM and EM in patients with MoA and RLS. Multivariate regression showed a significant relationship between rs79004933 and the Beck Depression Inventory score. INTERPRETATION: rs77234324 in LGR6 and rs79004933 in the intergenic region were associated with RLS in migraineurs. Five SNPs increased the risk of RLS in patients with MoA.

Indicators of rapid cognitive decline in amnestic mild cognitive impairment: The role of plasma biomarkers using magnetically labeled immunoassays.

Plasma levels of biomarkers change with the progression of Alzheimer's disease (AD), which involves the accumulation of pathological amyloid ß (Aß) and Tau protein tangles. However, few studies have investigated the association between plasma biomarkers and rapid cognitive decline in patients with amnestic mild cognitive impairment (aMCI) and AD. A total of 10 healthy controls, 24 patients with aMCI, and 19 patients with AD were enrolled. All participants underwent twice Mini-Mental State Examination (MMSE), with a mean 1.2 year interval. Immunomagnetic reduction was utilized to evaluate levels of plasma biomarkers, including amyloid ß 1-40 (Aß1-40), Aß1-42, total Tau protein, phosphorylated Tau protein (Threonine 181), and α-synuclein (α-Syn). The correlations between plasma levels of biomarkers and MMSE change were examined. Our analysis reveals that current higher plasma levels of Aß1-42 and α-Syn with the cut-off value of plasma Aß1-42 >17.26 pg/mL and α-Syn >105 fg/mL had a moderate-to-high discriminatory capacity (area under the curve >0.70) for identifying cognitive deterioration in patients with aMCI. Our results thus suggest that plasma levels of Aß1-42 and α-Syn may be considered as useful markers to assess the severity of global cognitive decline in patients with aMCI.

Collagen Scaffolds Containing Hydroxyapatite-CaO Fiber Fragments for Bone Tissue Engineering.

Collagen (COL) and hydroxyapatite (HAp) are the major components of bone, therefore, COL-HAp composites have been widely used as bone substitutes to promote bone regeneration. We have reported that HAp-CaO fibers (HANFs), which were fabricated by a sol-gel route followed by an electrospinning technique, possessed good drug-loading efficiency and limited the burst release of tetracycline. In the present study, we used HANF fragments to evaluate the effects of COL-HANF scaffolds on MG63 osteoblast-like cell behaviors. COL-HANF composite scaffolds in which the average diameter of HANFs was approximately 461 ± 186 nm were fabricated by a freeze-drying process. The alkaline phosphatase activity and the protein expression levels of OCN and BSP showed that compared with COL alone, the COL-HANF scaffold promoted the differentiation of MG63 osteoblast-like cells. In addition, the bone regeneration ability of the COL-HANF scaffold was examined by using a rabbit condylar defect model in vivo. The COL-HANF scaffold was biodegradable and promoted bone regeneration eight weeks after the operation. Hence, we concluded that the COL-HANF scaffold has potential as a bone graft for bone tissue engineering.

Associations between migraine occurrence and the effect of aura, age at onset, family history, and sex: A cross-sectional study.

INTRODUCTION: The relationships between family history, sex, age at onset, and migraine occurrence have been documented. However, the associations between these factors across different sexes and subgroups of patients have yet to be elucidated. This study evaluated the association between family history and migraine in male and female patients experiencing episodic and chronic migraine with and without aura. METHODS: This cross-sectional, case-control study included 299 headache-free controls and 885 patients receiving outpatient treatment for migraine. Participants were classified into episodic (1-14 days/month) and chronic (≥15 days/month) migraine groups. RESULTS: Positive family history was significantly more frequently observed in the episodic group than in the chronic group (49.5% vs. 26%; P < 0.001) in male patients, particularly in male patients without aura (50.3% vs. 21.9%; P = 0.003); it was less frequently observed (58.7% vs. 73.7%; P = 0.048) in female patients with aura. Family history was correlated with an earlier age at onset (20.7 years vs. 22.8 years; P = 0.002), particularly in patients without aura (21 years vs. 23.7 years; P = 0.002), who were women (20.9 years vs. 23.9 years; P = 0.002). CONCLUSIONS: Different patterns of association between family history and migraine can be observed between men and women. A positive family history of migraine is correlated with an earlier age at onset, particularly among female patients without aura.

Fabrication and Characteristics of PCL Membranes Containing Strontium-Substituted Hydroxyapatite Nanofibers for Guided Bone Regeneration.

Poly(ε-caprolactone) (PCL) membranes have been widely used in guided tissue regeneration (GTR) and guided bone regeneration (GBR). In addition, hydroxyapatite is the major inorganic component and an essential composition of hard bone and teeth. Recently, numerous studies have demonstrated that strontium-substituted hydroxyapatite (SrHA) not only enhances osteogenesis but also inhibits adipogenesis of mesenchymal stem cells. Therefore, SrHA incorporated into PCL could be an alternative material for GBR. In this study, strontium-substituted hydroxyapatite nanofibers (SrHANFs) were fabricated by a sol-gel route followed by electrospinning. We then fabricated PCL-SrHANF membranes as cell culture substrates and assessed the cellular behavior of osteoblast-like cells. Based on the observations of alkaline phosphatase (ALP) activity, bone sialoprotein (BSP) and osteocalcin (OCN) immunofluorescence staining, and Alizarin Red-S staining of cells cultured on the PCL-SrHANF and PCL membranes, we concluded that SrHANFs can promote the differentiation and mineralization of osteoblast-like cells and that PCL-SrHANF membranes have potential for GBR applications.

Fabrication and Characterization of Strontium-Substituted Hydroxyapatite-CaO-CaCO3 Nanofibers with a Mesoporous Structure as Drug Delivery Carriers.

Hydroxyapatite (HAp) is the main inorganic component and an essential part of hard bone and teeth. Due to its excellent biocompatibility, bioactivity, and osteoconductivity, synthetic HAp has been widely used as a bone substitute, cell carrier, and therapeutic gene or drug carrier. Recently, numerous studies have demonstrated that strontium-substituted hydroxyapatite (SrHAp) not only enhances osteogenesis but also inhibits adipogenesis in mesenchymal stem cells. Mesoporous SrHAp has been successfully synthesized via a traditional template-based process and has been found to possess better drug loading and release efficiencies than SrHAp. In this study, strontium-substituted hydroxyapatite-CaO-CaCO3 nanofibers with a mesoporous structure (mSrHANFs) were fabricated using a sol⁻gel method followed by electrospinning. X-ray diffraction analysis revealed that the contents of CaO and CaCO3 in the mSrHANFs decreased as the doping amount of Sr increased. Scanning electron microscopy (SEM) images showed that the average diameter of the mSrHANFs was approximately 200~300 nm. The N2 adsorption⁻desorption isotherms demonstrated that the mSrHANFs possessed a mesoporous structure and that the average pore size was approximately 20~25 nm. Moreover, the mSrHANFs had excellent drug- loading efficiency and could retard the burst release of tetracycline (TC) to maintain antibacterial activity for over 3 weeks. Hence, mSrHANFs have the potential to be used as drug carriers in bone tissue engineering.

Fabrication and Characteristics of Porous Hydroxyapatite-CaO Composite Nanofibers for Biomedical Applications.

Hydroxyapatite (HAp), a major inorganic and essential component of normal bone and teeth, is a promising biomaterial due to its excellent biocompatibility, bioactivity, and osteoconductivity. Therefore, synthetic HAp has been widely used as a bone substitute, cell carrier, and delivery carrier of therapeutic genes or drugs. Mesoporous materials have attracted considerable attention due to their relatively high surface area, large pore volume, high porosity, and tunable pore size. Recently, mesoporous HAp has also been successfully synthesized by the traditional template-based process and has been demonstrated to possess better drug-loading and release efficiencies than traditional HAp. It is widely accepted that cell adhesion and most cellular activities, including spreading, migration, proliferation, gene expression, surface antigen display, and cytoskeletal functioning, are sensitive to the topography and molecular composition of the matrix. The native extracellular matrix is a porous, nanofibrous structure. The major focus of this study is the fabrication of porous hydroxyapatite-CaO composite nanofibers (p-HApFs) and the investigation of its drug-release property. In this study, nanofibers were prepared by the sol-gel route and an electrospinning technique to mimic the three-dimensional structure of the natural extracellular matrix. We analyzed the components of fibers using X-ray diffraction and determined the morphology of fibers using scanning and transmission electron microscopy. The average diameter of the nanofibers was approximately 461 ± 186 nm. The N2 adsorption⁻desorption isotherms were type IV isotherms. Moreover, p-HApFs had better drug-loading efficiency and could retard the burst release of tetracycline and maintain antibacterial activity for a period of 7 days. Hence, p-HApFs have the potential to become a new bone graft material.

Acute Onset of Parkinsonism an End-Stage Renal Disease Patient.

PURPOSE: The osmotic demyelination syndrome (ODS) has been identified as a neurological complication of the rapid correction of hyponatremia. In recent years, however, various medical conditions have been associated with the development of ODS, irrelevant to changes in serum sodium. We present a rare case of a eunatremic patient who developed ODS with manifestation of parkinsonism. CASE: A 55 years old woman who has hypertension, type 2 diabetes nephropathy in end-stage renal disease under maintenance hemodialysis came to us with complaint about newly developed resting tremor of bilateral upper limbs, slowness of movements and small shuffling steps. Brain magnetic resonance imaging (MRI) showed bilateral lentiform nuclei demyelination. ODS was diagnosed concerning the comorbidities and her medical history. Her neurological deficits improved dramatically after treatment of Ropinirole. CONCLUSION: ODS may develop in patient with risk factors regardless of change in serum sodium concentration. Brain MRI could help in early detection of the demyelination. Secondary parkinsonism may occur as a rare manifestation of ODS. Supportive treatment, monitoring of vital signs and neurological deficits are warranted. Dopaminergic agent may be beneficial in symptomatic control.

Refractory Facial Paralysis: A Case Report.

PURPOSE: To present a case of salivary gland malignancy initially mimicking Bell's palsy. CASE REPORT: A 75-year-old woman with hypertension visited our neurological outpatient department,complaining of persistent right facial paralysis for more than a year after oral glucocorticoid therapy with recent development of vertigo and unsteady gait. She was previously diagnosed as having Bell's palsy and was prescribed oral glucocorticoid. However, her right facial muscles were still completely paralyzed, with no signs of improvement. The patient visited the outpatient department of neurology for 3 weeks, seeking treatment for the recent onset of vertigo and ataxia. Brain contrast magnetic resonance imaging (MRI) revealed the right mastoid air cells to be filled with high T2 signal intensity and low T1 signal, with destruction of the bony structure of mastoid, extending to the right jugular bulb. Results obtained from excisional biopsy and pathological analyses were used to diagnose the patient with adenoid cystic carcinoma of the salivary gland. The patient then received a thorough cancer workup and chemoradiotherapy, with the malignancy being under control. However, after a 1-year follow-up, the patient still had permanent right facial palsy. CONCLUSION: Salivary gland malignancy should be considered in patients with acute and subacute facial nerve paralysis, in addition to Bell's palsy. Brain imaging with contrast agents should be performed for differential diagnosis.