Design, Manufacture, and Characterization of a Critical-Sized Gradient Porosity Dual-Material Tibial Defect Scaffold.

This study proposed a composite tibia defect scaffold with radial gradient porosity, utilizing finite element analysis to assess stress in the tibial region with significant critical-sized defects. Simulations for scaffolds with different porosities were conducted, designing an optimal tibia defect scaffold with radial gradient porosity for repairing and replacing critical bone defects. Radial gradient porosity scaffolds resulted in a more uniform stress distribution, reducing titanium alloy stiffness and alleviating stress shielding effects. The scaffold was manufactured using selective laser melting (SLM) technology with stress relief annealing to simplify porous structure fabrication. The study used New Zealand white rabbits' tibia defect sites as simulation parameters, reconstructing the 3D model and implanting the composite scaffold. Finite element analysis in ANSYS-Workbench simulated forces under high-activity conditions, analyzing stress distribution and strain. In the simulation, the titanium alloy scaffold bore a maximum stress of 122.8626 MPa, while the centrally encapsulated HAp material delivered 27.92 MPa. The design demonstrated superior structural strength, thereby reducing stress concentration. The scaffold was manufactured using SLM, and the uniform design method was used to determine a collection of optimum annealing parameters. Nanoindentation and compression tests were used to determine the influence of annealing on the elastic modulus, hardness, and strain energy of the scaffold.

Prostaglandin F2 receptor inhibitor overexpression predicts advanced who grades and adverse prognosis in human glioma tissue.

Prostaglandin F2 receptor inhibitor (PTGFRN) promotes neoplastic cell migration and metastasis in some human cancers. However, the role of PTGFRN in human gliomas is still undetermined. First of all, PTGFRN messenger ribonucleic acid (mRNA) overexpression correlated with some poor prognostic factors of glioma after analyzing The Cancer Genome Atlas and Chinese Glioma Genome Atlas database. In order to detect the effect of PTGFRN expression on tumor characteristics of gliomas, U87MG, LN229, and glioblastoma 8401 glioma cell lines were cultured and prepared for western blot analysis and real-time polymerase chain reaction, respectively. The results revealed the overexpression of PTGFRN in all glioma cell lines as compared to normal brain cells. In addition, PTGFRN immunohistochemical (IHC) staining was performed on two sets of glioma tissue microarrays. Consistent with the results of in vitro studies, cytoplasmic PTGFRN immunostaining scores positively correlated with tumor grades and poor prognosis of gliomas. Therefore, PTGFRN IHC staining may be useful for the evaluation of tumor grades and overall survival time to facilitate the tailoring of appropriate treatment strategy. PTGFRN may serve as a potential pharmacologic target for the suppression of gliomagenesis.

Preoperative grading of intracranial meningioma by magnetic resonance spectroscopy (1H-MRS).

Although proton magnetic resonance spectroscopy (1H-MRS) is a common method for the evaluation of intracranial meningiomas, controversy exists regarding which parameter of 1H-MRS best predicts the histopathological grade of an intracranial meningioma. In this study, we evaluated the results of pre-operative 1H-MRS to identify predictive factors for high-grade intracranial meningioma. Thirteen patients with World Health Organization (WHO) grade II-III meningioma (confirmed by pathology) were defined as high-grade; twenty-two patients with WHO grade I meningioma were defined as low-grade. All patients were evaluated by 1H-MRS before surgery. The relationships between the ratios of metabolites (N-acetylaspartate [NAA], creatine [Cr], and choline [Cho]) and the diagnosis of high-grade meningioma were analyzed. According to Mann-Whitney U test analysis, the Cho/NAA ratio in cases of high-grade meningioma was significantly higher than in cases of low-grade meningioma (6.34 ± 7.90 vs. 1.58 ± 0.77, p<0.05); however, there were no differences in age, Cho/Cr, or NAA/Cr. According to conditional inference tree analysis, the optimal cut-off point for the Cho/NAA ration between high-grade and low-grade meningioma was 2.409 (sensitivity = 61.54%; specificity = 86.36%). This analysis of pre-operative 1H-MRS metabolite ratio demonstrated that the Cho/NAA ratio may provide a simple and practical predictive value for high-grade intracranial meningiomas, and may aid neurosurgeons in efforts to design an appropriate surgical plan and treatment strategy before surgery.

Dose Comparison Using Thermoluminescent Dosimeters During Multislice Computed Tomography With Different Parameters for Simulated Spine Tumor Examination.

This study aims to compare the effect of Philips' Brilliance 64-slice and 256-slice (multislice) computed tomography on effective doses when changing the operating parameters for simulated examinations of patients' spine tumors, including changes in pitch, tube voltage (kV), and effective tube current-time product (mA s). This study considers the possibility of using other probable operating conditions to reduce patients' effective doses. The absorbed doses to organs and skin are measured by taking data from thermoluminescent dosimeters (GR-200 and GR-200F) in relevant positions on the anthropomorphic Rando phantom. We also used an American College of Radiology computed tomography accreditation phantom to experiment with image spatial resolution under various scan conditions in order to achieve results over 5 line pairs per cm, the analytical capability required to meet diagnostic needs. The results show that, in general, when we change the pitch, effective tube current-time product, and tube voltage, the effective doses from 256-slice computed tomography exceed those from 64-slice computed tomography.

The Efficacy of Therapeutic Plasma Exchange in Antiphospholipid Antibody-positive Patients With Spontaneous Intracerebral Hemorrhage and High D-dimer Levels.

OBJECTIVE: We investigated the efficacy of plasma exchange (PE) in antiphospholipid antibody (aPL)-positive patients with a spontaneous intracerebral hemorrhage (ICH) and high D-dimer levels. MATERIALS AND METHODS: From May 2013 to May 2016, we evaluated 32 patients who were below the age of 50 and presented with spontaneous ICH. Five patients were positive for aPL antibody and 3 had a higher level of D-dimer. These 3 patients underwent 5 sessions of PE using fresh frozen plasma as replacement fluid. We analyzed the days postadmission until PE-start, the days of intensive care unit (ICU) hospitalization, D-dimer series, Glasgow Coma Scale (GCS) scores, and modified Rankin scale (mRS) scores. D-dimer levels and GCS scores were recorded at both pre-PE and post-PE stages. The mRS scores were recorded at pre-PE stage and 3 months post-PE. RESULTS: The mean postadmission period until PE-start was 8.33 days. The mean ICU hospitalization was 17.33 days. The D-dimer level pre-PE ranged from 2.34 to 5.44 mg/L fibrinogen equivalent unit (FEU). The D-dimer level post-PE ranged from 1.05 to 3.30 mg/L FEU. The amount of decline of the D-dimer level between pre-PE and post-PE ranged from 0.65 to 2.14 mg/L FEU. The GCS score pre-PE was between 7 and 8. The highest post-PE GCS score was 14. The improved GCS scores post-PE ranged from 3 to 6. The improved mRS scores of 3 months post-PE ranged from 3 to 4. CONCLUSIONS: The concurrent presence of positive aPL and a higher D-dimer level may worsen the neurological outcome of patients with a spontaneous ICH. Aggressive PE is effective for the treatment of such patients, decreasing the extent of the ICU hospitalization.

Fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery for a pituitary tumor: A case report.

INTRODUCTION: The fatal type of antiphospholipid syndrome is a rare but life-threating condition. It may be triggered by surgery or infection. Endoscopic transnasal-transsphenoidal surgery is a common procedure for pituitary tumor. We report a catastrophic case of a young woman died of fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery. METHODS AND RESULT: A 31-year-old woman of a history of stroke received endoscopic transnasal-transsphenoidal surgery for a pituitary tumor. The whole procedure was smooth. However, the patient suffered from acute delirium on postoperative day 4. Then, her consciousness became comatose state rapidly with dilatation of pupils. Urgent magnetic resonance imaging of brain demonstrated multiple acute lacunar infarcts. The positive antiphosphoipid antibody and severe thrombocytopenia were also noted. Fatal antiphospholipid syndrome was diagnosed. Plasma exchange, corticosteroids, anticoagulant agent were prescribed. The hemodynamic condition was gradually stable. However, the consciousness was still in deep coma. The patient died of organ donation 2 months later. CONCLUSION: If patients have a history of cerebral stroke in their early life, such as a young stroke, the APS and higher risk of developing fatal APS after major surgery should be considered. The optimal management of APS remains controversial. The best treatment strategies are only early diagnosis and aggressive therapies combing of anticoagulant, corticosteroid, and plasma exchange. The intravenous immunoglobulin is prescribed for patients with refractory APS.

Quantitative analysis of anatomical relationship between cavernous segment internal carotid artery and pituitary macroadenoma.

Cavernous segment internal carotid artery (CSICA) injury during endoscopic transsphenoidal surgery for pituitary tumor is rare but fatal. The aim of this study is to investigate anatomical relationship between pituitary macroadenoma and corresponding CSICA using quantitative means with a sense to improve safety of surgery.In this retrospective study, a total of 98 patients with nonfunctioning pituitary macroadenomas undergoing endoscopic transsphenoidal surgeries were enrolled from 2005 to 2014. Intercarotid distances between bilateral CSICAs were measured in the 4 coronal levels, namely optic strut, convexity of carotid prominence, median sella turcica, and dorsum sellae. Parasellar extension was graded and recorded by Knosp-Steiner classification.Our findings indicated a linear relationship between size of pituitary macroadenoma and intercarotid distance over CSICA. The correlation was absent in pituitary macroadenoma with Knosp-Steiner grade 4 parasellar extension.Bigger pituitary macroadenoma makes more lateral deviation of CSICA. While facing larger tumor, sufficient bony graft is indicated for increasing surgical field, working area and operative safety.

A Clinical Pitfall: Optimal Management of Single Dural-based Metastatic Carcinoma of the Breast Mimicking Meningioma.

Meningioma is the most common benign brain lesion in adults. Conservative treatment is suggested if there is no obvious neurological symptom or mass effect, but cerebral metastases require aggressive therapy. Single dural-based metastatic carcinoma mimicking meningioma is uncommon. Here is a case of clinical dilemma between meningioma and metastatic carcinoma mimicking meningioma. A woman with a history of invasive ductal carcinoma of the breast presented with headache and blurred vision. Brain computed tomography and magnetic resonance imaging (MRI) both gave the impression of meningioma. After surgical resection of the brain lesion, histopathology revealed that it was a metastatic lesion from the breast. This report discussed the optimal management of single dural-based metastatic carcinoma mimicking meningioma.

Image analysis of open-door laminoplasty for cervical spondylotic myelopathy: comparing the influence of cord morphology and spine alignment.

OBJECTIVES: Previous studies have identified the factors affecting the surgical outcome of cervical spondylotic myelopathy (CSM) following laminoplasty. Nonetheless, the effect of these factors remains controversial. It is unknown about the association between pre-operative cervical spinal cord morphology and post-operative imaging result following laminoplasty. The goal of this study is to analyze the impact of pre-operative cervical spinal cord morphology on post-operative imaging in patients with CSM. METHODS: Twenty-six patients with CSM undergoing open-door laminoplasty were classified according to pre-operative cervical spine bony alignment and cervical spinal cord morphology, and the results were evaluated in terms of post-operative spinal cord posterior drift, and post-operative expansion of the antero-posterior dura diameter. RESULTS: By the result of study, pre-operative spinal cord morphology was an effective classification in predicting surgical outcome - patients with anterior convexity type, description of cervical spinal cord morphology, had more spinal cord posterior migration than those with neutral or posterior convexity type after open-door laminoplasty. Otherwise, the interesting finding was that cervical spine Cobb's angle had an impact on post-operative spinal cord posterior drift in patients with neutral or posterior convexity type spinal cord morphology - the degree of kyphosis was inversely proportional to the distance of post-operative spinal cord posterior drift, but not in the anterior convexity type. CONCLUSIONS: These findings supported that pre-operative cervical spinal cord morphology may be used as screening for patients undergoing laminoplasty. Patients having neutral or posterior convexity type spinal cord morphology accompanied with kyphotic deformity were not suitable candidates for laminoplasty.

Coordination of the filament stabilizing versus destabilizing activities of cofilin through its secondary binding site on actin.

Cofilin is a ubiquitous modulator of actin cytoskeleton dynamics that can both stabilize and destabilize actin filaments depending on its concentration and/or the presence of regulatory co-factors. Three charge-reversal mutants of yeast cofilin, located in cofilin's filament-specific secondary binding site, were characterized in order to understand why disruption of this site leads to enhanced filament disassembly. Crystal structures of the mutants showed that the mutations specifically affect the secondary actin-binding interface, leaving the primary binding site unaltered. The mutant cofilins show enhanced activity compared to wild-type cofilin in severing and disassembling actin filaments. Electron microscopy and image analysis revealed long actin filaments in the presence of wild-type cofilin, while the mutants induced many short filaments, consistent with enhanced severing. Real-time fluorescence microscopy of labeled actin filaments confirmed that the mutants, unlike wild-type cofilin, were functioning as constitutively active severing proteins. In cells, the mutant cofilins delayed endocytosis, which depends on rapid actin turnover. We conclude that mutating cofilin's secondary actin-binding site increases cofilin's ability to sever and de-polymerize actin filaments. We hypothesize that activators of cofilin severing, like Aip1p, may act by disrupting the interface between cofilin's secondary actin-binding site and the actin filament.

A modified cornish pasty method for ex ovo culture of the chick embryo.

Early stages of avian development are not well-suited for in ovo studies. A critical limitation of ex ovo culture is the short period of growth that can be attained for explanted embryos. Here we report a modified and simplified version of an existing ex ovo culture method, the cornish pasty culture. We show that this modified method, referred to as MC culture, can be used to grow chick and quail embryos from Hamburger and Hamilton (HH) Stage 3 to at least HH18 with normal developmental morphology. The MC culture is also applicable to generate parabiosed twins. Combination of the MC culture with electroporation and labeling techniques will be a valuable new tool in cell lineage tracing and molecular functional analyses of early avian embryogenesis.

Overlapping and distinct functions for cofilin, coronin and Aip1 in actin dynamics in vivo.

Actin-filament disassembly is crucial for actin-based motility, to control filament network architecture and to regenerate subunits for assembly. Here, we examined the roles of three actin cytoskeletal proteins, coronin, cofilin and Aip1, which have been suggested to combine in various ways to control actin dynamics by promoting or regulating disassembly. We studied their functions during the endocytosis process in budding yeast, where actin-filament dynamics at the cortical actin 'patch' contribute to the formation and movement of endocytic vesicles. We found that all three proteins were recruited during the late phase of the life of the actin patch. They all arrived at the same time, when actin and other actin-associated proteins were leaving the patch. Cofilin point mutations influenced the localization of coronin and Aip1, but the complete loss of coronin had no effect on localization of cofilin or Aip1. Using quantitative patch motion analysis and comparing mutant alleles, the phenotypes for mutations of the three genes showed some commonalities, but also some striking differences. Cofilin was clearly the most important; it displayed the most severe mutant phenotypes affecting actin-patch assembly and movement. Together, the results suggest that all three proteins work together to promote actin disassembly, but not in a simple way, and not with equal importance.

Threshold response of C15 to the Dpp gradient in Drosophila is established by the cumulative effect of Smad and Zen activators and negative cues.

Morphogen gradients determine a range of cell fates by specifying multiple transcriptional threshold responses. In the dorsal ectoderm of the Drosophila embryo, a BMP gradient is translated into an activated Smad transcription factor gradient, which elicits at least three threshold responses - high, intermediate and low. However, the mechanism underlying differential response to Dpp is poorly understood, due in part to the insufficient number of well-studied target genes. We analyzed the regulation of the C15 gene, which can be activated in cells containing intermediate levels of Dpp. We show that C15 expression requires both dpp and zen, thus forming a genetic feed-forward loop. The C15 regulatory element contains clusters of Smad- and Zen-binding sites in close proximity. Mutational analysis shows that the number of intact Smad- and Zen-binding sites is essential for the C15 transcriptional response, and that the spatial limits of C15 expression are established through a repression mechanism in the dorsolateral cells of the embryo. Thus, the combinatorial action of Smad and Zen activators bound to a number of adjacent sites, and competing negative cues allows for proper gene response to lower than peak levels of the Dpp morphogen.

vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock.

The Drosophila circadian clock consists of two interlocked transcriptional feedback loops. In one loop, dCLOCK/CYCLE activates period expression, and PERIOD protein then inhibits dCLOCK/CYCLE activity. dClock is also rhythmically transcribed, but its regulators are unknown. vrille (vri) and Par Domain Protein 1 (Pdp1) encode related transcription factors whose expression is directly activated by dCLOCK/CYCLE. We show here that VRI and PDP1 proteins feed back and directly regulate dClock expression. Repression of dClock by VRI is separated from activation by PDP1 since VRI levels peak 3-6 hours before PDP1. Rhythmic vri transcription is required for molecular rhythms, and here we show that the clock stops in a Pdp1 null mutant, identifying Pdp1 as an essential clock gene. Thus, VRI and PDP1, together with dClock itself, comprise a second feedback loop in the Drosophila clock that gives rhythmic expression of dClock, and probably of other genes, to generate accurate circadian rhythms.

Controlled mechanical ventilation leads to remodeling of the rat diaphragm.

Little is known about the structural response of the diaphragm to controlled mechanical ventilation. We examined effects of this intervention on muscle mass, myosin heavy chain isoforms, and contractile function in the rat diaphragm. Animals were mechanically ventilated for up to 4 days, and comparisons were made with normal control rats as well as spontaneously breathing animals anesthetized for the same duration as the mechanical ventilation group. The diaphragm-to-body weight ratio was significantly reduced in the mechanical ventilation group only. After mechanical ventilation, an increase in hybrid fibers coexpressing both type I (slow) and type II (fast) myosin isoforms was found within the diaphragm, which occurred at the expense of the pure type I fiber population. In contrast, the percentages of type I, type II, and hybrid fibers in the limb muscles (soleus and extensor digitorum longus) did not differ between experimental groups. The optimal length for force production, as well as maximal force-generating capacity of the diaphragm, was also significantly decreased in mechanically ventilated animals. We conclude that even short-term controlled mechanical ventilation produces significant remodeling and functional alterations of the diaphragm, which could impede efforts at discontinuing ventilatory support.