Removal of endocrine disruptors and pharmaceuticals by graphene oxide-based membranes in water: A review.

Membrane-based water treatment has emerged as a promising solution to address global water challenges. Graphene oxide (GO) has been successfully employed in membrane filtration processes owing to its reversible properties, large-scale production potential, layer-to-layer stacking, great oxygen-based functional groups, and unique physicochemical characteristics, including the creation of nano-channels. This review evaluates the separation performance of various GO-based membranes, manufactured by coating or interfacial polymerization with different support layers such as polymer, metal, and ceramic, for endocrine-disrupting compounds (EDCs) and pharmaceutically active compounds (PhACs). In most studies, the addition of GO significantly improved the removal efficiency, flux, porosity, hydrophilicity, stability, mechanical strength, and antifouling performance compared to pristine membranes. The key mechanisms involved in contaminant removal included size exclusion, electrostatic exclusion, and adsorption. These mechanisms could be ascribed to the physicochemical properties of compounds, such as molecular size and shape, hydrophilicity, and charge state. Therefore, understanding the removal mechanisms based on compound characteristics and appropriately adjusting the operational conditions are crucial keys to membrane separation. Future research directions should explore the characteristics of the combination of GO derivatives with various support layers, by tailoring diverse operating conditions and compounds for effective removal of EDCs and PhACs. This is expected to accelerate the development of surface modification strategies for enhanced contaminant removal.

Circulating miRNAs in extracellular vesicles related to treatment response in patients with idiopathic membranous nephropathy.

BACKGROUND: Extracellular vesicle (EV)-microRNAs (miRNAs) are potential biomarkers for various renal diseases. This study attempted to identify the circulating EV-miRNA signature not only for discriminating idiopathic membranous nephropathy (IMN) from idiopathic nephrotic syndrome (INS), but also to predict the treatment response of patients with IMN. METHODS: We prospectively enrolled 60 participants, including those with IMN (n = 19) and INS (n = 21) and healthy volunteers (HVs; n = 20) in this study. Using RNA sequencing, we assessed the serum EV-miRNA profiles of all participants. To identify the EV-miRNAs predictive of treatment response in IMN, we also analyzed EV-miRNAs among patients with IMN with and without clinical remission. RESULTS: The expression levels of 3 miRNAs differed between IMN patients, INS patients and HVs. In addition, compared to HVs, RNA sequencing revealed differential expression of 77 and 44 EV-miRNAs in patients with IMN without and with remission, respectively. We also identified statistically significant (|fold change ≥ 2, p < 0.05) differences in the expression levels of 23 miRNAs in IMN without remission. Biological pathway analysis of miRNAs in IMN without remission indicated that they are likely involved in various pathways, including renal fibrosis. CONCLUSION: Our study identified EV-miRNAs associated with IMN as well as those associations with therapeutic response. Therefore, these circulating EV-miRNAs may be used as potential markers for the diagnosis and prediction of treatment response in patients with IMN.

Experimentally and spectroscopically evidenced mechanistic study of butyl peroxyacid oxidative degradation of benzo[a]pyrene in soil.

Benzo[a]pyrene (BaP) is a major indicator of soil contamination and categorized as a highly persistent, carcinogenic, and mutagenic polycyclic aromatic hydrocarbon. An advanced peroxyacid oxidation process was developed to reduce soil pollution caused by BaP originating from creosote spills from railroad sleepers. The pH, organic matter, particle size distribution of soil, and concentrations of BaP and heavy metals (Cd, Cu, Zn, Pb, and As) in the BaP-contaminated soils were estimated. A batch experiment was conducted to determine the effects of organic acid type, soil particle size, stirring speed, and reaction time on the peroxyacid oxidation of BaP in the soil samples. Additionally, the effect of the organic acid concentration on the peroxyacid degradation of BaP was investigated using an oxidizing agent in spiked soil with and without hydrogen peroxide. The results of the oxidation process indicated that BaP and heavy metal residuals were below acceptable Korean standards. A significant difference in the oxidative degradation of BaP was observed between the spiked and natural soil samples. The formation of a peroxyacid intermediate was primarily responsible for the enhanced BaP oxidation. Further, butyric acid could be reused thrice without losing the efficacy (<90%). The systematic peroxyacid oxidative degradation mechanism of BaP was also discussed. A qualitative analysis of the by-products of the BaP reaction was conducted, and their corresponding toxicities were determined for possible field applications. The findings conclude that the developed peroxyacid oxidation method has potential applications in the treatment of BaP-contaminated soils.

Design and synthesis of acrylate and acrylamide substituted pyrimidinediones as potential PPO herbicides.

PPO herbicides emerge to be widely use in the agricultural field and a focus of research to many scientists due to its environmentally-friendly properties. In lieu with this, this study presents acrylate and acrylamide substituted pyrimidinediones as PPO herbicide candidates. Most synthesized compounds exhibits herbicidal activities against both monocot and dicot weeds, especially, compound 5a which showed non-selective superior activity against the commercialized, Saflufenacil. Compound 5a was further tested for residual effect and showed promising results as shorter period is needed to cultivate the next crops. The synthesized acrylate and acrylamide substituted pyrimidinediones, especially, 5a could potentially be utilized in the development of commercial protoporphyrinogen oxidase inhibitors with further tests and studies.

Prevalence and Characteristics of Onychomycosis in Patients with Knee Osteoarthritis: A Single-centre Prospective Cross-sectional Study.

Knee disorders that compromise patients' lower leg movements and self-care may put these patients at greater risk of onychomycosis. However, little is known about the prevalence of onychomycosis in patients with knee diseases. This study evaluated the prevalence and characteristics of onychomycosis in patients with knee osteoarthritis. A total of 520 consecutive patients with symptomatic knee osteoarthritis who visited the Department of Orthopedics for a potential knee surgery were evaluated for onychomycosis by PCR-based reverse blot hybridization assay. Of the 520 patients, 308 (59.2%) were diagnosed with onychomycosis. Age (p = 0.004), male sex (p = 0.015), and being barefooted (p = 0.031) were statistically significant risk factors for onychomycosis. Knee disease severity, based on Kellgren-Lawrence grade, was associated with severity of onychomycosis. The impairment of physical function and self-care caused by knee disorders may increase the prevalence of onychomycosis in these patients.

Enhancement of Liposomal Plasmid DNA and siRNA Delivery by Itraconazole through Intracellular Cholesterol Accumulation.

PURPOSE: Efficient and safe vehicle that can enhance gene transfer is still needed. Since intracellular cholesterol is known to have an important role in gene delivery and itraconazole alters intracellular cholesterol trafficking, we investigated the effect of itraconazole on pDNA and siRNA delivery. METHODS: The pDNA and Bcl2 siRNA transfection efficiency was measured by luciferase assay and cytotoxicity. Cellular cholesterol was observed using filipin staining, and intracellular uptake was analyzed by flow cytometry. Lipoplex localization was observed by fluorescent labeling of DNA and lysosome after treatment of itraconazole or co-treatment of itraconazole and bafilomycin A1. RESULTS: Itraconazole enhanced the transfection efficiency of pDNA and siRNA compared to that of control through the accumulation of cholesterol. Bafilomycin A1 diminished the effect of itraconazole on gene delivery and the increment of cholesterol. Itraconazole did not increase the cellular uptake of lipoplex, but increased free pDNA during the endosome-lysosome pathway was observed during the endosome-lysosome pathway. Treating cells with both imipramine and itraconazole caused an additive effect in pDNA and siRNA delivery. CONCLUSIONS: Itraconazole enhanced gene delivery of pDNA and siRNA, and it can be used to potentiate nucleic acid therapeutics.

The First Reported Case of Fibrous Hamartoma of Infancy with Hyperhidrosis and Hypertrichosis in Korea.

Fibrous hamartoma of infancy (FHI) is a rare entity with a benign nature. The typical clinical features are a single, slowly growing, painless mass on the trunk that appears within the first 2 years of life. We report a 13-month-old boy who presented with a plaque on the lower back since 4 months of age. The plaque had gradually become larger and firm, and hyperhidrosis and hypertrichosis were noticed. No visible connection between the spinal cord and the lesion was found in radiologic studies, indicating a disease other than spinal dysraphism. Histopathological findings showed well-defined fibrous trabeculae, mature adipose tissue, and primitive mesenchymal cells, all consistent with FHI. This is the first case of FHI presenting with hyperhidrosis and hypertrichosis reported in Korea.

Synthesis of cholesteryl doxorubicin and its anti-cancer activity.

Doxorubicin (dox) has been used as anti-cancer agent, but there are disadvantages such as rapid excretion, short retention time and cardiotoxicity. For giving lipophilic properties to dox, it was modified with cholesterol derivatives that were validated as a component of liposomal gene delivery. This article describes the synthesis of dox derivatives (lipo-dox A-D), their cytotoxicity and cellular uptake. In A549, HeLa, MCF7 and MDA MB 231 cell lines, lipo-dox A and lipo-dox B substituted at alcohol group showed similar anti-cancer effect as dox, but lipo-dox C and lipo-dox D substituted at amino group did not. As a result, the amino group of dox seems an important site for its cancer cell inhibition. Lipophilic property of lipo-dox A and lipo-dox B induced more accumulation in cells compared to parent drug. Therefore, the newly synthesized lipo-dox A and lipo-dox B would be a good candidate for anti-cancer agent.

DOTAP/DOPE ratio and cell type determine transfection efficiency with DOTAP-liposomes.

The effects of lipid compositions on their physicochemical properties and transfection efficiencies were investigated. Four liposome formulations with different 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) to dioleoylphosphatidylethanolamine (DOPE) weight ratios were investigated, that is, weight ratios 1:0 (T1P0), 3:1 (T3P1), 1:1 (T1P1), and 1:3 (T1P3). Mean sizes of liposomes were influenced by their lipid composition and the preparation concentration at the time of sonication. Zeta potentials of liposomes were inversely correlated with their liposome sizes. However, neither liposome sizes nor zeta potentials were correlated with transfection efficiency. The optimum composition of liposomes was cell-line dependent (T1P0 and T3P1 for Huh7 and AGS, T3P1 and T1P1 for COS7, and T1P1 and T1P3 for A549). The shape of lipoplexes was changed from lamellar to inverted hexagonal structure according to the increased ratio of DOPE, but there was no definite advantage of specific structure in transfection efficiency throughout all used cell lines. However, cellular internalization was consistently faster in T1P0, T3P1, T1P1 compared to T1P3 in all cell lines, suggesting the importance of endosomal escape. Our findings show that the transfection efficiency of DOTAP liposomes is mainly influenced by lipid composition and cell type, and not by size or zeta potential.

Synthesis and validation of novel cholesterol-based fluorescent lipids designed to observe the cellular trafficking of cationic liposomes.

Cholesterol-based fluorescent lipids with ether linker were synthesized using NBD (Chol-E-NBD) or Rhodamine B (Chol-E-Rh), and the usefulnesses as fluorescent probes for tracing cholesterol-based liposomes were validated. The fluorescent intensities of liposomes containing these modified lipids were measured and observed under a microscope. Neither compound interfered with the expression of GFP plasmid, and live cell images were obtained without interferences. Changes in the fluorescent intensity of liposomes containing Chol-E-NBD were followed by flow cytometry for up to 24h. These fluorescent lipids could be useful probes for trafficking of cationic liposome-mediated gene delivery.

Rapid detection of dermatophytes and Candida albicans in onychomycosis specimens by an oligonucleotide array.

BACKGROUND: Onychomycosis is a fungal infection of nails, leading to the gradual destruction of the nail plate. Treatment of onychomycosis may need long-time oral antifungal therapy that can have potential side effects, thus accurate diagnosis of the disease before treatment is important. Culture for diagnosis of onychomycosis is time-consuming and has high false-negative rates. To expedite the diagnosis, an oligonucleotide array, based on hybridization between immobilized oligonucleotide probes and PCR products, for direct detection of dermatophytes and Candida albicans in clinical specimens was evaluated. METHODS: Species-specific oligonucleotide probes designed from the internal transcribed spacer (ITS) regions of the rRNA gene were immobilized on a nylon membrane. The assay procedures consisted of PCR amplification of the ITS using universal primers, followed by hybridization of the digoxigenin-labeled amplicons to probes on the array. Thirty two nail samples (29 patients) were analyzed by the array, and the results were compared with those obtained by culture. Array-positive but culture-negative samples were confirmed by cloning and re-sequencing of the amplified ITS and by reviewing patient's clinical data. The total recovery of culture and confirmed array-positive but culture-negative results was considered 100% and was used for performance evaluation of both methods. RESULTS: Concordant results were obtained in 21 samples (10 positives and 11 negatives) by both methods. Eleven samples were array-positive but culture-negative; among them, 9 samples were considered true positives after discrepant analysis. Comparing with culture, the array had significantly higher sensitivity [100% (95% CI 82.2% -100%) vs 52.6% (28.9% -75.5%), p <0.001] and negative predictive value [100% (71.3% -100%) vs 59.1% (36.4% -79.3%), p <0.05), while no significant differences were observed in specificity (84.6% vs 100%, p =0.48) and positive predictive value (90.5% vs 100%, p =1.0). The whole procedures of the array were about 24 h, whilst results from culture take 1 to 3 weeks. CONCLUSIONS: The array offers an accurate and rapid alternative to culture. Rapid diagnosis can expedite appropriate antifungal treatment of onychomycosis. However, the single site nature of this study conducted at a referral hospital invites caution.

Efficient sequestration of cesium ions using phosphoric acid-modified activated carbon fibers from aqueous solutions.

In this study, acid-modified activated carbon fibers (ACF-Ps) were synthesized by phosphorylation. Three different types of ACF-based adsorbents functionalized with PO43-, P2O74-, or P3O105- ions, namely, ACF-P1, ACF-P2, and ACF-P3, were prepared by phosphorylating ACF with trisodium phosphate (Na3PO4), sodium dihydrogen pyrophosphate (Na2H2P2O5), and sodium tripolyphosphate (Na5P3O10), respectively, and utilized as adsorbents to remove cesium ions (Cs+) from aqueous solutions. Among the tested adsorbents, ACF-P3 exhibited the highest Cs+ adsorption capacity of 37.59 mg g-1 at 25 °C and pH 7 which is higher than that of ACF (5.634 mg g-1), ACF-P1 (19.38 mg g-1), and ACF-P2 (30.12 mg g-1) under the same experimental conditions. More importantly, the Cs+ removal efficiencies of ACF-P3 (82.90%), ACF-P2 (66.2%), ACF-P1 (34.2%) were 29.3-, 23.4-, and 12.11-fold higher than that of un-treated ACF (2.83%). The results suggested that the phosphorylation with Na5P3O10 is highly suitable for Cs+ adsorption which effectively functionalizes ACF with a greater number of phosphate functional groups. Adsorption and kinetic data well-fitted the Langmuir isotherm and pseudo-second-order model, respectively, which indicated the monolayer adsorption of Cs+ onto ACF-P1, ACF-P2, and ACF-P3 which were largely controlled by chemisorption. Overall, phosphoric acids containing different phosphate-based polyanions (PO43-, P2O74-, or P3O105-) enriched -OH and/or -COOH surface functional groups of ACF in addition to P-containing surface groups (PO, C-P-O, C-O-P, and P-O) and facilitated the Cs+ adsorption through surface complexation and electrostatic interactions.

Ultrasonic treatment of dye chemicals in wastewater: A review.

The existence of pollutants, such as toxic organic dye chemicals, in water and wastewater raises concerns as they are inadequately eliminated through conventional water and wastewater treatment methods, including physicochemical and biological processes. Ultrasonic treatment has emerged as an advanced treatment process that has been widely applied to the decomposition of recalcitrant organic contaminants. Ultrasonic treatment has several advantages, including easy operation, sustainability, non-secondary pollutant production, and saving energy. This review examines the elimination of dye chemicals and categorizes them into cationic and anionic dyes based on the existing literature. The objectives include (i) analyzing the primary factors (water quality and ultrasonic conditions) that influence the sonodegradation of dye chemicals and their byproducts during ultrasonication, (ii) assessing the impact of the different sonocatalysts and combined systems (with ozone and ultraviolet) on sonodegradation, and (iii) exploring the characteristics-based removal mechanisms of dyes. In addition, this review proposes areas for future research on ultrasonic treatment of dye chemicals in water and wastewater.

Ultrasonic treatment of endocrine disrupting compounds, pharmaceuticals, and personal care products in water: An updated review.

Pharmaceuticals, personal care products (PPCPs), and endocrine-disrupting compounds (EDCs) have seen a recent sustained increase in usage, leading to increasing discharge and accumulation in wastewater. Conventional water treatment and disinfection processes are somewhat limited in effectively addressing this micropollutant issue. Ultrasonication (US), which serves as an advanced oxidation process, is based on the principle of ultrasound irradiation, exposing water to high-frequency waves, inducing thermal decomposition of H2O while using the produced radicals to oxidize and break down dissolved contaminants. This review evaluates research over the past five years on US-based technologies for the effective degradation of EDCs and PPCPs in water and assesses various factors that can influence the removal rate: solution pH, temperature of water, presence of background common ions, natural organic matter, species that serve as promoters and scavengers, and variations in US conditions (e.g., frequency, power density, and reaction type). This review also discusses various types of carbon/non-carbon catalysts, O3 and ultraviolet processes that can further enhance the degradation efficiency of EDCs and PPCPs in combination with US processes. Furthermore, numerous types of EDCs and PPCPs and recent research trends for these organic contaminants are considered.

Photocatalytic and electrocatalytic degradation of bisphenol A in the presence of graphene/graphene oxide-based nanocatalysts: A review.

Bisphenol A (BPA), a widely recognized endocrine disrupting compound, has been discovered in drinking water sources/finished water and domestic wastewater influent/effluent. Numerous studies have shown photocatalytic and electrocatalytic oxidation to be very effective for the removal of BPA, particularly in the addition of graphene/graphene oxide (GO)-based nanocatalysts. Nevertheless, the photocatalytic and electrocatalytic degradation of BPA in aqueous solutions has not been reviewed. Therefore, this review gives a comprehensive understanding of BPA degradation during photo-/electro-catalytic activity in the presence of graphene/GO-based nanocatalysts. Herein, this review evaluated the main photo-/electro-catalytic degradation mechanisms and pathways for BPA removal under various water quality/chemistry conditions (pH, background ions, natural organic matter, promotors, and scavengers), the physicochemical characteristics of various graphene/GO-based nanocatalysts, and various operating conditions (voltage and current). Additionally, the reusability/stability of graphene/GO-based nanocatalysts, hybrid systems combined with ozone/ultrasonic/Fenton oxidation, and prospective research areas are briefly described.

The attitudes of Korean cancer patients, family caregivers, oncologists, and members of the general public toward advance directives.

PURPOSE: The purpose of this study was to investigate Korean attitudes toward advance directives (ADs) among cancer patients, family caregivers, oncologists, and the general public. METHODS: A multicenter survey study explored the attitudes of participants to ADs, and hospice-palliative care (HPC) was conducted. A total of 1,242 cancer patients, 1,289 family caregivers, 303 oncologists, and 1,006 members of the general public participated in the survey. RESULTS: The majority of patients, family caregivers, oncologists, and general public agreed with the necessity of ADs. However, oncologists regard "when became terminal status" as an optimal timing for completion of ADs (52.2 %), while other groups regard earlier periods as it. More than 95 % oncologist answered that cardiopulmonary resuscitation and mechanical ventilator are necessity items for ADs form, while around 70 % of other groups answered so. Multivariate analysis revealed that several factors including agreement with terminal disclosures and a positive attitude toward HPC were independently associated with necessity of ADs. CONCLUSIONS: We found that attitudes toward ADs among cancer patients, family caregivers, oncologists, and the general public were significantly different. Our study also suggests that favorable attitudes toward comfort end-of-life care and HPC are keys that influence the perceived need for ADs.

Analysis of the impact of low impact development on runoff from a new district in Korea.

An analysis of the impact of a low impact development (LID) on runoff was performed using a Storm Water Management Model 5 (SWMM5)-LID model. The SWMM5 package has been developed to facilitate the analysis of the hydrologic impacts of LID facilities. Continuous simulation of urban stormwater runoff from the district which included the LID design was conducted. In order to examine the impact of runoff in the LID district the first, second and third highest ranked flood events over the past 38 years were analyzed. The assessment estimated that a LID system under historical storm conditions would reduce peak runoff by approximately 55-66% and runoff volume by approximately 25-121% in comparison with that before the LID design. The impact on runoff was also simulated under 50, 80 and 100 year return period conditions. Under these conditions, the runoff reductions within the district were estimated to be about 6-16% (peak runoff) and 33-37% (runoff volume) in comparison with conditions prior to the LID. It is concluded from these results that LID is worthy of consideration for urban flood control in future development and as part of sewer and stormwater management planning.

Stable and recyclable lanthanum hydroxide-doped graphene oxide biopolymer foam for superior aqueous arsenate removal: Insight mechanisms, batch, and column studies.

In this study, a graphene oxide-based lanthanum hydroxide/chitosan foam (CSGOL foam) was synthesized for arsenate (As(V)) remediation in surface water. The synthesized CSGOL foam texture and purity was assessed using scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) surface area, X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS) studies. The results proved that the foam was highly porous, stable, and had high surface functionality that facilitated adsorption for water pollutant removal. The sorption results proved that the As(V) removal was high (146.20 mg/g at pH 6 with 0.5 g/L CSGOL foam) when compared to the similar type of materials, endothermic chemisorption due to the production of monodentate and bidentate inner-sphere complexes. Furthermore, continuous column results indicated that the As(V) concentration in real surface waters was reduced to WHO standards (less than 10 µg As/L of water) of As(V) in drinking water for up to 10,000 bed volume. Further it can be used up to four cycles without loss of efficacy less than 93%. Because of its excellent removal capabilities and simple synthesis technique, CSGOL foam shows significant promise for treating As(V)-containing water. Further, the XPS analysis and batch studies results suggests that As(V) removal mechanism was involved electrostatic and surface complexation through chemical interaction predominately.

Development of ultra-high surface area polyaniline-based activated carbon for the removal of volatile organic compounds from industrial effluents.

Removing volatile organic compounds (VOCs) from aqueous solutions is critical for reducing VOC emissions in the environment. Activated carbons are widely used for removal of VOCs from water. However, they show less application feasibility and low removal due to less surface area. Here, a cost-effective and high surface area activated carbonized polyaniline (ACP) was synthesized to sustainable removal of VOCs from water. The ACP microstructure, surface properties, and pore structure were investigated using Brunauer-Emmett-Teller (BET) theory, Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM). The specific surface area of ACP6:1 (2988.13 m2/g) was greater than that of commercial activated carbon (PAC) (1094.49 m2/g), indicating that it has excellent VOC adsorption capacity. The effects of pH, initial VOC concentration, time, temperature, and ionic strength were studied. According to kinetic and thermodynamic studies on VOCs adsorption, it is an exothermic and spontaneous process involving rate-limiting kinetics. Adsorption isotherms follow the Freundlich isotherm model, suggesting that the adsorbent surface is heterogeneous with multilayer adsorption and maximum ACP adsorption capacities of 1913.9, 2453.3, 1635.8, and 3327.0 mg/g at 293 K for benzene, toluene, ethylbenzene, and perchloroethylene, respectively, representing a 3- to 5-fold improvement over PAC. ACP is a promising adsorbent with a high adsorption efficiency for VOC removal.

Intradermal Low-Fat Spindle Cell Lipoma: A Case Report.

Spindle cell lipoma is a rare benign neoplasm that features a mixture of evenly aligned spindle cells, mature adipocytes, and ropey collagen. Most cases of spindle cell lipoma are found in the subcutaneous tissue, and intradermal spindle cell lipoma is rarely reported. We present a case of intradermal spindle cell lipoma in a 46-year-old female who presented with a 0.7-cm flesh-colored and dome-shaped nodule on the right temple that had developed 6 years ago. This mass was excised, and upon histopathologic examination, an unencapsulated lesion was located in the dermis, which consisted of bland spindle cells, scanty mature adipocytes, rare lipoblasts, and ropey collagen bundles with prominent basophilic myxoid stroma. Immunohistochemical staining showed diffuse positivity for CD34, negativity for the S-100 protein, and loss of retinoblastoma protein expression. Based on these features, intradermal low-fat spindle cell lipoma was diagnosed. No evidence of local recurrence was observed 4 months after excision. Intradermal low-fat spindle cell lipomas are extremely rare and can easily be mistaken for tumors that have similar clinical and histopathological findings. Herein, we report a globally rare case of an intradermal low-fat spindle cell lipoma.