Laser-assisted manipulation of Volta potential pattern on the TC4 surface for improved hBMSCs osteogenesis.

The Ti6Al4V (TC4) alloy, a prevalent biomedical material in orthopedics, still faces limitation of the insufficient osseointegration. To improve the bioactivity of TC4, introducing the electric environment onto the TC4 surface may be an effective way in the view of the necessity of endogenous electric microenvironment in bone regeneration. Herein, a Volta potential pattern was engendered on the TC4 surface via parallel laser patterning, so as to promote the osteogenic differentiation of cells. A 15 W laser successfully transformed the original α + ß dual phase towards radially distributed lath-like martensite phase in the laser treated region. The atomic lattice distortion between the heterogeneous microstructures of the laser treated and untreated regions leads to a significant Volta potential fluctuation on the TC4 surface. The Volta potential pattern as well as the laser-engraved microgrooves respectively induced mutually orthogonal cell alignments. The hBMSCs osteogenic differentiation was significantly enhanced on the laser treated TC4 surfaces in comparison to the surface without the laser treatment. Moreover, a drastic Volta potential gradient on the TC4 surface (treated with 15 W power and 400 µm interval) resulted in the most pronounced osteogenic differentiation tendency compared to other groups. Modulating the electric environment on the TC4 surface by manipulating the phase transformation may provide an effective way in evoking favorable cell response of bone regeneration, thereby improving the bioactivity of TC4 implant.

Impacts of permeability and effective diffusivity of porous scaffolds on bone ingrowth: In silico and in vivo analyses.

The permeability and the effective diffusivity of a porous scaffold are critical in the bone-ingrowth process. However, design guidelines for porous structures are still lacking due to inadequate understanding of the complex physiological processes involved. In this study, a model integrating the fundamental biological processes of bone regeneration was constructed to investigate the roles of permeability and effective diffusivity in regulating bone deposition in scaffolds. The in silico analysis results were confirmed in vivo by examining bone depositions in three diamond lattice scaffolds manufactured using selective laser melting. The findings show that the scaffolds with better permeability and effective diffusivity had deeper bone ingrowth and greater bone volume. Compared to permeability, effective diffusivity exhibited greater sensitivity to the orientation of porous structures, and bone ingrowth was deeper in the directions with higher effective diffusivity in spite of identical pore size. A 4.8-fold increase in permeability and a 1.6-fold increase in effective diffusivity by changing the porous structure led to a 1.5-fold increase in newly formed bone. The effective diffusivity of the porous scaffold affects the distribution of osteogenic growth factor, which in turn impacts cell migration and bone deposition through chemotaxis effects. Therefore, effective diffusivity may be a more suitable indicator for porous scaffolds because our study shows changes in this parameter determine changes in bone distribution and bone volume.

Distribution and correlation of refractive parameters in children with different corneal curvatures in southeast China.

AIM: To analyze the distribution of refractive status in school-age children with different corneal curvatures (CC) and the correlation between CC and refractive status. METHODS: A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included. Uncorrected distance visual acuity (UCDVA), non-cycloplegic refraction, axial length (AL), horizontal and vertical corneal curvature (K1, K2) were measured and spherical equivalent (SE), corneal curvature radius (CCR) and axial length/corneal radius of curvature ratio (AL/CR) were calculated. UCDVA<5.0 and SE≤-0.50 D were classified as school-screening myopia. According to the different CCRs, the patients were divided into the lower corneal curvature (LCC) group (CCR≥7.92) and the higher corneal curvature (HCC) group (CCR<7.92). Each group was further divided into the normal AL subgroup and the long AL subgroup. The refractive parameters were compared to identify any differences between the two groups. RESULTS: Both SE and AL were greater in the LCC group (P=0.013, P<0.001). The prevalence of myopia was 38% in the LCC group and 44% in the HCC group (P<0.001). The proportion of children without screening myopia was higher in the LCC group (62%) than in the HCC group (56%). Among these children without screening myopia, the proportion of long AL in the LCC group (24%) was significantly higher than that in the HCC group (0.012%; P<0.001). The change of SE in the LCC group was less affected by the increase of AL than that in the HCC group. CONCLUSION: School-aged children in the LCC group have a lower incidence of screening myopia and longer AL. Low CC can mask SE reduction and AL growth to some extent, and the change of AL growth change more in children with low CC than high CC. Before the onset of myopia, its growth rate is even faster than that after the onset of myopia.

Metallurgical manipulation of surface Volta potential in bimetals and cell response of human mesenchymal stem cells.

Bioelectricity plays an overriding role in directing cell migration, proliferation, differentiation etc. Tailoring the electro-extracellular environment through metallurgical manipulation could modulate the surrounding cell behaviors. In this study, different electric potential patterns, in terms of Volta potential distribution and gradient, were created on the metallic surface as an electric microenvironment, and their effects on adherent human mesenchymal stem cells were investigated. Periodically and randomly distributed Volta potential pattern, respectively, were generated on the surface through spark plasma sintering of two alternatively stacked dissimilar metals films and of a mixture of metallic powders. Actin cytoskeleton staining demonstrated that the Volta potential pattern strongly affected cell attachment and deformation. The cytoskeletons of cells were observed to elongate along the Volta potential gradient and across the border of adjacent regions with higher and lower potentials. Moreover, the steepest potential gradient resulting from the drastic compositional changes on the periodic borders gave rise to the strongest osteogenic tendency among all the samples. This study suggests that tailoring the Volta potential distribution and gradient of metallic biomaterials via metallurgical manipulation is a promising approach to activate surrounding cells, providing an extra degree of freedom for designing desirable bone-repairing metallic implants.

Automatic 3-D spine curve measurement in freehand ultrasound via structure-aware reinforcement learning spinous process localization.

Freehand 3-D ultrasound systems have been advanced in scoliosis assessment to avoid radiation hazards, especially for teenagers. This novel 3-D imaging method also makes it possible to evaluate the spine curvature automatically from the corresponding 3-D projection images. However, most approaches neglect the three-dimensional spine deformity by only using the rendering images, thus limiting their usage in clinical applications. In this study, we proposed a structure-aware localization model to directly identify the spinous processes for automatic 3-D spine curve measurement using the images acquired with freehand 3-D ultrasound imaging. The pivot is to leverage a novel reinforcement learning (RL) framework to localize the landmarks, which adopts a multi-scale agent to boost structure representation with positional information. We also introduced a structure similarity prediction mechanism to perceive the targets with apparent spinous process structures. Finally, a two-fold filtering strategy was proposed to screen the detected spinous processes landmarks iteratively, followed by a three-dimensional spine curve fitting for the spine curvature assessments. We evaluated the proposed model on 3-D ultrasound images among subjects with different scoliotic angles. The results showed that the mean localization accuracy of the proposed landmark localization algorithm was 5.95 pixels. Also, the curvature angles on the coronal plane obtained by the new method had a high linear correlation with those by manual measurement (R = 0.86, p < 0.001). These results demonstrated the potential of our proposed method for facilitating the 3-D assessment of scoliosis, especially for 3-D spine deformity assessment.

In silico and in vivo studies of the effect of surface curvature on the osteoconduction of porous scaffolds.

Recent evidence shows that the curvature of porous scaffold plays a significant role in guiding tissue regeneration. However, the underlying mechanism remains controversial to date. In this study, we developed an in silico model to simulate the effect of surface curvature on the osteoconduction of scaffold implants, which comprises the primary aspects of bone regeneration. Selective laser melting was used to manufacture a titanium scaffold with channels representative of different strut curvatures for in vivo assessment. The titanium scaffold was implanted in the femur condyles of rabbits to validate the mathematical model. Simulation results suggest that the curvature affected the distribution of growth factors and subsequently induced the migration of osteoblast lineage cells and bone deposition to the locations with higher curvature. The predictions of the mathematical model are in good agreement with the in vivo assessment results, in which newly formed bone first appeared adjacent to the vertices of the major axes in elliptical channels. The mechanism of curvature-guided osteoconduction may provide a guide for the design optimization of scaffold implants to achieve enhanced bone ingrowth.

Physical optics framework for electromagnetic scattering from electrically large targets coated with a uniaxial electric anisotropic medium based on point-source excitation.

Aiming to determine the scattered estimation of complex and electrically large targets coated with the uniaxial electric anisotropic medium (UEAM) from a distributed excitation source, the demanding study is simplified by constructing the physical optics (PO) architecture which consists of three aspects, the discrete facet modeling, the tangent plane approximation, and the scattering of an infinite PEC plate coated with the UEAM based on point-source excitation, including the electric and magnetic dipole. We depict the outer surface of an electrically large scatterer as the constitution of countless tiny triangular facets. From the tangent plane approximation employed in the PO method, the scattered fields of any discretized facet induced by the equivalent electromagnetic currents (EECs) can be further evaluated as the surface fields of an infinite UEAM-coated PEC slab. Therefore, the rigorous solution of the dyadic Green's function (DGFs) for an infinite anisotropic-medium-coated PEC plate under point-source incidence is computed first. Moreover, characterizing the ray propagation process of the plane wave spectrum, the asymptotic technique of the saddle point is employed to obtain the scattered ray field in the spatial domain. Finally, the total scattered fields are obtained by the field superposition of the overall illuminated facets under point-source excitation. Compared with the reference solution, the proposed method is validated, and the simulation results of the representative shapes coated with the UEAM layer from a point source are presented.

Microscopic Volta potential difference on metallic surface promotes the osteogenic differentiation and proliferation of human mesenchymal stem cells.

Endogenous microscopic electric cues play an essential role in bone's remodeling and self-repair. Modulating the extracellular electrical environment, by means of external electric stimulation or changing surface potential of implants, was manifested to facilitate the osteointegration. The microscopic potential difference, originating from heterogeneous microstructures of materials, may mimic the endogenous electric signals to stimulate surrounding cells. In this study, the spark-plasma sintered Ti/Ta hybrid metal was fabricated and utilized to realize a surface microscopic potential difference at the same magnitude as endogenous potentials. Activated by the electric stimulation, the mesenchymal stem cells exhibited the anisotropic and polygonal cellular morphology on the Ti/Ta hybrid metal. The microscopic electric potential difference coordinated the cells proliferation on the subsequent days. Moreover, the results showed that the osteo-lineage differentiation on Ti/Ta hybrid metal were in vitro boosted over the control groups. Tailoring microstructures of material to obtain a reasonable electric microenvironment may be a necessary principle to achieve more favorable cell responses to implants, suggesting an extra degree of freedom in bone-repairing material design.

Bone marrow infiltrated natural killer cells predicted the anti-leukemia activity of MCL1 or BCL2 inhibitors in acute myeloid leukemia.

Acute myeloid leukemia (AML) is still incurable due to its heterogeneity and complexity of tumor microenvironment. It is imperative therefore to understand the molecular pathogenesis of AML and identify leukemia-associated biomarkers to formulate effective treatment strategies. Here, we systematically analyzed the clinical characters and natural killer (NK) cells portion in seventy newly-diagnosis (ND) AML patients. We found that the proportion of NK cells in the bone marrow of ND-AML patients could predict the prognosis of patients by analyzing the types and expression abundance of NK related ligands in tumor cells. Furthermore, MCL1 inhibitor but not BCL2 inhibitor combined with NK cell-based immunotherapy could effectively improve the therapeutic efficiency via inhibiting proliferation and inducing apoptosis of AML primary cells as well as cell lines in vitro. There results provide valuable insights that could help for exploring new therapeutic strategies for leukemia treatment.

Comprehensive analysis of two potential novel SARS-CoV-2 entries, TMPRSS2 and IFITM3, in healthy individuals and cancer patients.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, with acute respiratory failure as the most significant symptom, has led to a global pandemic. Angiotensin-converting enzyme 2 (ACE2) is considered as the most important receptor of SARS-CoV-2 and wildly expressed in human tissues. Whereas, the extremely low expression of ACE2 in lung could hardly interpret the severe symptom of pneumonia in COVID-19 patients. Here we profiled two SARS-CoV-2 infection related genes, the transmembrane serine protease 2 (TMPRSS2) and the interferon-inducible transmembrane protein 3 (IFITM3), in human tissues and organs. Consistent with the expression and distribution of ACE2, TMPRSS2 was also highly expressed in digestive, urinary and reproductive systems, but low expressed in lung. Notably, the anti-virus protein IFITM3 also expressed much lower in lung than other tissues, which might be related to the severe lung symptoms of COVID-19. In addition, the low expression of IFITM3 in immune cells suggested that SARS-CoV-2 might attack lymphocytes and induce the cytokine release syndrome (CRS). Furthermore, cancer patients were considered as more susceptible to SARS-CoV-2 infection. Our data supposed that fourteen types of tumors might have different susceptibility to the virus according to ACE2, TMPRSS2 and IFITM3 expression patterns. Interestingly the prognosis of six types of cancers including breast carcinoma (BRCA), lung adenocarcinoma (LUAD), uterine corpus endometrial carcinoma (UCEC), renal clear cell carcinoma (KIRC), prostate adenocarcinoma (PRAD), and hepatocellular carcinoma (LIHC) were closely related to these gene expressions. Our study explored the expression and distribution profiles of two potential novel molecules that might participate in SARS-CoV-2 infection and involved in immunity, which may provide a functional basis for preventing infection of SARS-CoV-2.

Modeling osteoinduction in titanium bone scaffold with a representative channel structure.

Optimizing scaffold architecture for perfect osteointegration depends on good understanding of bone ingrowth in the porous space of implants. This study developed an immunoregulatory agent-based model to discover the osteoinduction mechanism in porous scaffolds. Immunoreaction, macrophage polarization, and the corresponding growth factors were combined in the model, and all played critical roles in recruiting osteogenic cells that migrated into the scaffolds. Angiogenesis was also considered in this model. The bone ingrowth predicted by the model coincides with results from published in vivo experiments. Simulation results suggested that the pore architecture affected the diffusion process of chemotactic factors in the scaffolds, subsequently influencing the complex reactions of diverse cells and the osteoinduction location. In flexural pore spaces, bone formation spread from the periphery into the center of scaffolds due to larger M2 phenotype macrophage populations colonizing boundary regions and the distribution of corresponding growth factors concentration. In straight channels, osteogenic cells migrated further inward and osteoinduction initiated in deeper position as a result of the deeper distribution of osteogenic cytokines concentration field.

Epigenetic landscape analysis of lncRNAs in acute myeloid leukemia with DNMT3A mutations.

BACKGROUND: Acute myeloid leukemia (AML) is a type of cancer that consists of a group of hematological malignancies with high heterogeneity. DNA methyltransferase 3A (DNMT3A)-mutated AML patients have a poor prognosis. Some long non-coding RNAs (lncRNAs) have been reported to enhance therapeutic sensitivity, and so could affect the overall survival rate of elderly cytogenetically normal acute myeloid leukemia (CN-AML) patients; however, studies on the lncRNA signature in DNMT3A-mutated AML are rare. METHOD: The DNMT3A R878H conditional knock-in mouse model was constructed to explore the lncRNAs of DNMT3A mutation by using the Cuffcomparison method. Cis and trans regulation networks were used to predict candidate genes. The expression levels in leukemic cell lines and the prognostic index of these candidate genes were analyzed with the Broad Institute Cancer Cell Line Encyclopedia (CCLE) and OncoLnc databases. The data for each sample were statistically analyzed using GraphPad Prism. RESULTS: In this study, we applied the DNMT3A R878H conditional knock-in mouse model to explore the lncRNA epigenetic landscape of DNMT3A mutation by using the Cuffcomparison method. Twenty-three differentially expressed lncRNAs were identified in Dnmt3aR878H/WTMx1-Cre+ mice. We next predicted the downstream targetable genes regulated by these lncRNAs through cis and trans regulation networks and found 124 candidate genes are related to these lncRNAs. In further analysis of 124 genes, we found that increased mRNA expression levels of interleukin 1 receptor type 2 (IL1R2), Krüppel-like factor 13 (KLF13), ATPase H+ transporting V1 subunit A (ATP6V1A), proteasome 26S Subunit, non-ATPase 3 (PSMD3), and pyrroline-5-carboxylate reductase 2 (PYCR2) were associated with poor prognosis in AML. Functional analysis of these genes demonstrated that the pathways involved in autophagy, cell cycle, and hematopoietic stem cell differentiation were more enriched in Dnmt3aR878H/WTMx1-Cre+ mice. CONCLUSION: Our study was the first to use DNMT3A R878H conditional knock-in mouse model to predict the specific lncRNAs regulated by the DNMT3A mutation in AML. Six candidate genes were found to be associated with DNMT3A mutation with poor prognosis. Our results provided a possible treatment strategy for this disease.

Identification of cancer stem cell characteristics in liver hepatocellular carcinoma by WGCNA analysis of transcriptome stemness index.

Cancer stem cells (CSCs) are characterized by self-renewal and -differential potential as compared to common cancer cells and play an important role in the development and therapeutic resistance of liver hepatocellular carcinoma (LIHC). However, the specific pathogenesis of LIHC stem cells is still unclear, and the genes involved in the stemness of LIHC stem cells are currently unknown. In this study, we investigated novel biomarkers associated with LIHC and explored the expression characteristics of stem cell-related genes in LIHC. We found that mRNA expression-based stemness index (mRNAsi) was significantly overexpressed in liver cancer tissues. Further, mRNAsi expression in LIHC increased with the tumor pathological grade, with grade 4 tumors harboring the greatest stem cell features. Upon establishing mRNAsi scores based on mRNA expression of every gene, we found an association with poor overall survival in LIHC. Moreover, modules of interest were determined based on weighted gene co-expression network analysis (WGCNA) inclusion criteria, and three significant modules (red, green, and brown) and 21 key genes (DCN, ECM1, HAND2, PTGIS, SFRP1, SRPX, COLEC10, GRP182, ADAMTS7, CD200, CDH11, COL8A1, FAP, LZTS1, MAP1B, NAV1, NOTCH3, OLFML2A, PRR16, TMEM119, and VCAN) were identified. Functional analysis of these 21 genes demonstrated their enrichment in pathways involved in angiogenesis, negative regulation of DNA-binding transcription factor activity, apoptosis, and autophagy. Causal relationship with proteins indicated that the Wnt, Notch, and Hypoxia pathways are closely related to LIHC tumorigenesis. To our knowledge, this is the first report of a novel CSC biomarker, mRNAsi, to predict the prognosis of LIHC. Further, we identified 21 key genes through mRNA expression network analysis, which could be potential therapeutic targets to inhibit the stemness of cancer cells in LIHC.

Critical pharmaceutical process identification considering chemical composition, biological activity, and batch-to-batch consistency: A case study of notoginseng total saponins.

Objective: Critical pharmaceutical process identification (CPPI) is an important step in the implementation of quality by design concept to traditional Chinese medicines (TCMs). Risk assessment methods are usually used in CPPI. However, risk evaluation is usually subjective. The purpose of this work is to present a more objective CPPI method. Methods: A CPPI method considering chemical composition, biological activity, and batch-to-batch consistency was presented in this work. The manufacturing process of notoginseng total saponins (NTS) was investigated as an example. The changes of chemical composition, biological activity, and chemical composition consistency after main processes were measured and compared. A significant change of them indicated a critical process. Results: After extraction process and chromatography process, saponin purity and chemical composition similarity remarkably increased, and saponin content variations decreased. Thrombin inhibitory activity was remarkably decreased after chromatography process. Because of the large influences on NTS quality, extraction process and chromatography process were identified to be critical processes of NTS. Conclusion: Based on a comprehensive and objective examination of the role of each process, critical pharmaceutical processes can be identified. A similar method can also be applied to other TCM processes.

Lower long-term mortality in obese patients with community-acquired pneumonia: possible role of CRP.

OBJECTIVE: The present study aimed to investigate the relationship between obesity and mortality in patients with community-acquired pneumonia (CAP) in China. METHODS: In total, 909 patients with CAP were recruited for this study from January 2010 to June 2015. All patients were selected and divided into 4 groups according to their body mass index (BMI) values. All patients' clinical information was recorded. The associations among mortality; BMI; the 30-day, 6-month and 1-year survival rates for different BMI classes; the etiology of pneumonia in each BMI group; and the risk factors for 1-year mortality in CAP patients were analyzed. RESULT: With the exception of the level of C-reactive protein (CRP), no other clinical indexes showed significant differences among the different BMI groups. No significant differences were observed among all groups in terms of the 30-d and 6-month mortality rates (p>0.05). There was a significantly lower risk of 1-year mortality in the obese group than in the nonobese group, (p<0.05). Logistic regression analysis showed that there were seven independent risk factors for 1-year mortality in CAP patients, namely, age, cardiovascular disease, cerebrovascular disease, obesity, APACHE II score, level of CRP and CAP severity. CONCLUSION: Compared with nonobese patients with CAP, obese CAP patients may have a lower mortality rate, especially with regard to 1-year mortality, and CRP may be associated with the lower mortality rate in obese individuals than in nonobese individuals.

Lower long-term mortality in obese patients with community-acquired pneumonia: possible role of CRP

OBJECTIVE: The present study aimed to investigate the relationship between obesity and mortality in patients with community-acquired pneumonia (CAP) in China. METHODS: In total, 909 patients with CAP were recruited for this study from January 2010 to June 2015. All patients were selected and divided into 4 groups according to their body mass index (BMI) values. All patients' clinical information was recorded. The associations among mortality; BMI; the 30-day, 6-month and 1-year survival rates for different BMI classes; the etiology of pneumonia in each BMI group; and the risk factors for 1-year mortality in CAP patients were analyzed. RESULT: With the exception of the level of C-reactive protein (CRP), no other clinical indexes showed significant differences among the different BMI groups. No significant differences were observed among all groups in terms of the 30-d and 6-month mortality rates (p>0.05). There was a significantly lower risk of 1-year mortality in the obese group than in the nonobese group, (p<0.05). Logistic regression analysis showed that there were seven independent risk factors for 1-year mortality in CAP patients, namely, age, cardiovascular disease, cerebrovascular disease, obesity, APACHE II score, level of CRP and CAP severity. CONCLUSION: Compared with nonobese patients with CAP, obese CAP patients may have a lower mortality rate, especially with regard to 1-year mortality, and CRP may be associated with the lower mortality rate in obese individuals than in nonobese individuals.

Structural and developmental expression of Ss-riok-2, an RIO protein kinase encoding gene of Strongyloides stercoralis.

RIO kinases are essential atypical protein kinases in diverse prokaryotic and eukaryotic organisms, playing significant roles in yeast and humans. However, little is known about their functions in parasitic nematodes. In the present study, we have isolated and characterized the full-length cDNA, gDNA and a putative promoter of a RIOK-2 protein kinase (Ss-RIOK-2) encoding gene (Ss-riok-2) from Strongyloides stercoralis, a medically important parasitic nematode (Order Rhabditida). A three-dimensional structure (3D) model of Ss-RIOK-2 was generated using the Chaetomium thermophilum RIOK-2 protein kinase (Ct-RIOK-2) crystal structure 4GYG as a template. A docking study revealed some critical sites for ATP binding and metal binding. The putative promoter of Ss-riok-2 contains a number of conserved elements. RNAseq analysis revealed the highest levels of the Ss-riok-2 transcript in free-living females and parasitic females. To identify anatomical patterns of Ss-riok-2 expression in S. stercoralis, we observed expression patterns of a transgene construct encoding green fluorescent protein under the Ss-riok-2 promoter in post free-living S. stercoralis. Expression driven by this promoter predominated in intestinal cells. This study demonstrates significant advancement in molecular and cellular biological study of S. stercoralis and of parasitic nematodes generally, and provides a foundation for further functional genomic studies.

Ray-tracing method for creeping waves on arbitrarily shaped nonuniform rational B-splines surfaces.

An accurate creeping ray-tracing algorithm is presented in this paper to determine the tracks of creeping waves (or creeping rays) on arbitrarily shaped free-form parametric surfaces [nonuniform rational B-splines (NURBS) surfaces]. The main challenge in calculating the surface diffracted fields on NURBS surfaces is due to the difficulty in determining the geodesic paths along which the creeping rays propagate. On one single parametric surface patch, the geodesic paths need to be computed by solving the geodesic equations numerically. Furthermore, realistic objects are generally modeled as the union of several connected NURBS patches. Due to the discontinuity of the parameter between the patches, it is more complicated to compute geodesic paths on several connected patches than on one single patch. Thus, a creeping ray-tracing algorithm is presented in this paper to compute the geodesic paths of creeping rays on the complex objects that are modeled as the combination of several NURBS surface patches. In the algorithm, the creeping ray tracing on each surface patch is performed by solving the geodesic equations with a Runge-Kutta method. When the creeping ray propagates from one patch to another, a transition method is developed to handle the transition of the creeping ray tracing across the border between the patches. This creeping ray-tracing algorithm can meet practical requirements because it can be applied to the objects with complex shapes. The algorithm can also extend the applicability of NURBS for electromagnetic and optical applications. The validity and usefulness of the algorithm can be verified from the numerical results.

Multiple sclerosis and sexual dysfunction.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by episodic and progressive neurologic dysfunction resulting from inflammatory and autoimmune reactions. The underlying pathogenesis of MS remains largely unclear. However, it is currently accepted as a T cell-mediated autoimmune disease. Among other clinical manifestations, sexual dysfunction (SD) is a painful but still underreported and underdiagnosed symptom of the disorder. SD in MS patients may result from a complex set of conditions and may be associated with multiple anatomic, physiologic, biologic, medical and psychological factors. SD arises primarily from lesions affecting the neural pathways involved in physiologic function. In addition, psychological factors, the side effects of medications and physical symptoms such as fatigue, muscular weakness, menstrual changes, pain and concerns about bladder and bowel incontinence may also be involved. Since MS primarily affects young people, SD secondary to MS may have a great impact on quality of life. Thus, maintaining a healthy sexual life with MS is an important priority. The treatment of SD requires multidisciplinary teamwork and cooperation among specialists, individual patients, partners and the society.