Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy for the Treatment of Hypothalamic Hamartomas: A Retrospective Review.
Neurosurgery. 2018 Jan 13;:
Authors: Xu DS, Chen T, Hlubek RJ, Bristol RE, Smith KA, Ponce FA, Kerrigan JF, Nakaji P
BACKGROUND: Hypothalamic hamartomas (HH) are rare lesions associated with treatment-resistant epilepsy. Open surgery results in modest seizure control (about 50%) but has a significant associated morbidity. Radiosurgery is limited to a subset of patients due to latent therapeutic effects. Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) offers a novel minimally invasive option.
OBJECTIVE: To evaluate a single center's outcomes for the LITT treatment of HH.
METHODS: We retrospectively reviewed our experience with LITT for the treatment of HH using our institution's prospectively maintained patient database.
RESULTS: Eighteen patients (mean age, 21.1 yr; median age, 11 yr) underwent 21 total LITT treatments for HH. Mean follow-up was 17.4 mo. The length of stay was 1 night for 16 (89%) patients. At the end of follow-up, 11 of 18 patients (61%) had full disconnection of the HH, and 12 of 15 (80%) patients with gelastic seizures and 5 (56%) of 9 patients with nongelastic seizures were seizure free (International League Against Epilepsy Class 1). Immediate complications included a 39% (7/18) incidence of neurological deficits, including 1 case of hemiparesis. At the end of follow-up, 22% of patients (4/18) had persistent deficits. The hypothyroidism that occurred was delayed in 11% of patients (2/18), as was short-term memory loss (22%, 4/18) and weight gain (22%, 4/18).
CONCLUSION: LITT therapy for HH can achieve excellent rates of seizure control with low morbidity and a short postoperative stay in a majority of patients. Additional research is needed to assess the durability of results and the full spectrum of cognitive outcomes.
PMID: 29346599 [PubMed - as supplied by publisher]
Treatment Outcomes and Adverse Events Following In-Office Angiolytic Laser With or Without Concurrent Polypectomy for Vocal Fold Polyps.
JAMA Otolaryngol Head Neck Surg. 2018 Jan 18;:
Authors: Lin YH, Wang CT, Lin FC, Liao LJ, Lo WC, Cheng PW
Importance: In-office angiolytic laser procedures have been used successfully as an alternative treatment for vocal fold polyps; little is known in detail about the treatment outcomes and adverse events.
Objective: To examine the outcomes and incidence rates of adverse events associated with in-office angiolytic laser procedures with or without concurrent polypectomy as an alternative treatment for vocal fold polyps.
Design, Setting, and Participants: Retrospective cohort study at a tertiary medical center. We identified 114 consecutive patients with vocal polyps who underwent in-office angiolytic laser treatments between January 1, 2014, and August 31, 2016. After the exclusion of 17 with missing or incomplete data, 97 were enrolled.
Interventions: In-office 532-nm laser procedures with or without concurrent polypectomy.
Main Outcomes and Measures: Between 1 and 2 months after the surgical procedures, we collected the following outcome data: videolaryngostroboscopy, perceptual rating of voice quality, acoustic analysis, maximal phonation time, and subjective rating of voice quality using a visual analogue scale and 10-item voice handicap index.
Results: This study enrolled 97 patients (mean [SD] age, 45.6 [11.3] years; 48 [49%] male). The mean duration of symptoms was 10.1 months (range, 1-60 months). Twenty-nine patients (30%) had angiolytic laser procedures only, while 68 (70%) received laser with concurrent polypectomy. Both treatment modalities offered significant improvements. Only 1 patient (1%) receiving angiolytic laser with concurrent polypectomy underwent another treatment session, so this group had significantly less need for multiple treatments than those receiving laser treatment alone (6 [21%]; effect size, -1.57; 95% CI, -2.77 to -0.36). We identified 8 adverse events (8% of the cases): vocal fold edema (n = 5), vocal hematoma (n = 2), and vocal ulceration (n = 1). Patients treated with laser plus concurrent polypectomy had significantly fewer adverse events than those treated with angiolytic laser alone (2 [3%] vs 6 [21%]; effect size, 1.20; 95% CI, 0.26 to 2.13).
Conclusions and Relevance: In-office angiolytic laser procedures can be an effective alternative treatment for vocal polyps, although with possible need for multiple treatment sessions and occasional occurrence of minor postoperative adverse events. Concurrent polypectomy following laser coagulation allows less laser energy delivery and reduces the risk of postoperative adverse events and the need for additional treatment sessions.
PMID: 29346486 [PubMed - as supplied by publisher]
Effect of Novel Quercetin Titanium Dioxide-Decorated Multi-Walled Carbon Nanotubes Nanocomposite on Bacillus subtilis Biofilm Development.
Materials (Basel). 2018 Jan 18;11(1):
Authors: Raie DS, Mhatre E, El-Desouki DS, Labena A, El-Ghannam G, Farahat LA, Youssef T, Fritzsche W, Kovács ÁT
The present work was targeted to design a surface against cell seeding and adhering of bacteria, Bacillus subtilis. A multi-walled carbon nanotube/titanium dioxide nano-power was produced via simple mixing of carbon nanotube and titanium dioxide nanoparticles during the sol-gel process followed by heat treatment. Successfully, quercetin was immobilized on the nanocomposite via physical adsorption to form a quercetin/multi-walled carbon nanotube/titanium dioxide nanocomposite. The adhesion of bacteria on the coated-slides was verified after 24 h using confocal laser-scanning microscopy. Results indicated that the quercetin/multi-walled carbon nanotube/titanium dioxide nanocomposite had more negativity and higher recovery by glass surfaces than its counterpart. Moreover, coating surfaces with the quercetin-modified nanocomposite lowered both hydrophilicity and surface-attached bacteria compared to surfaces coated with the multi-walled carbon nanotubes/titanium dioxide nanocomposite.
PMID: 29346268 [PubMed]
Laser-Capture Microdissection and RNA Extraction from Perfusion-Fixed Cartilage and Bone Tissue from Mice Implanted with Human iPSC-Derived MSCs in a Calvarial Defect Model.
Methods Mol Biol. 2018;1723:385-396
Authors: Xin X, Jiang X, Lichtler A, Kronenberg M, Rowe D, Pachter JS
Laser-capture microdissection (LCM) coupled to downstream RNA analysis poses unique difficulties for the evaluation of mineralized tissues. A rapid protocol was thus developed to enable sufficient integrity of bone and cartilage tissue for reliable sectioning, while minimizing RNA loss associated with prolonged decalcification and purification steps. Specifically, the protocol involves pump-assisted, cardiac perfusion-fixation with paraformaldehyde, and moderate digestion of LCM-acquired tissue with proteinase K followed by DNase treatment and separation of RNA using magnetic beads. Reverse transcription and cDNA synthesis are performed immediately after RNA purification, without need for further protein removal.
PMID: 29344873 [PubMed - in process]
Bilateral Hypopyon Uveitis in Chronic Myeloid Leukemia.
Ocul Oncol Pathol. 2017 Dec;4(1):12-15
Authors: Tyagi M, Govindhari V, Pappuru RR, Ambiya V
Background: A leukemic hypopyon is considered an early sign of central nervous system involvement or systemic relapse. A differential diagnosis of masquerade syndromes should be considered in cases of hypopyon uveitis that are atypical or unresponsive to treatment. We report a case of a 45-year-old man who presented with bilateral hypopyon uveitis and was subsequently diagnosed as having chronic myeloid leukemia.
Method: Retrospective case review.
Results: A 45-year-old diabetic male presented with diminished vision in both eyes for 10 days. Ophthalmic evaluation revealed rubeosis iridis, hypopyon, and signs of proliferative diabetic retinopathy with panretinal laser photocoagulation scars. He subsequently presented 1 week later with a bloodstained hypopyon in his right eye and a persistent hypopyon in his left eye. A peripheral blood smear and subsequent bone marrow trephine biopsy confirmed the diagnosis of chronic myeloid leukemia in blast crisis and he was referred to an oncologist for further management.
Conclusion: A recalcitrant or atypical hypopyon uveitis can be an indicator of a blast crisis or a central nervous system involvement or sign of a relapse in cases of leukemia. The presence of unusual bloodstained hypopyon helped in identifying the presence of chronic myeloid leukemia and aided in a prompt oncology consultation.
PMID: 29344492 [PubMed]
Adenocarcinoma of the Retinal Pigment Epithelium Arising in Conjunction with Late Recurrence and Systemic Metastasis of Retinoblastoma.
Ocul Oncol Pathol. 2017 Nov;3(4):296-300
Authors: Roelofs K, Kherani F, Russell L, Heathcote JG, Weis E
In 1974, an 8-month-old male was diagnosed with bilateral retinoblastoma. His left eye was enucleated, while the right eye was salvaged with a combination of external beam radiotherapy (4,000 cGy total, divided in 20 fractions) and retinal laser treatment. Thirty-nine years later, he developed intraocular recurrence of retinoblastoma with extrascleral spread. Histopathological examination also identified a second distinct malignancy, retinal pigment epithelium adenocarcinoma, arising in continuity with the retinoblastoma. Further investigation revealed foci of metastatic retinoblastoma in his parotid gland. He was subsequently treated with a combination of orbital exenteration, extensive neck dissection, and resection of metastatic foci, followed by a high-dose ablative chemotherapeutic regimen consisting of cisplatin, vincristine, and cyclophosphamide. Although very rare, late recurrence of retinoblastoma with systemic metastasis is possible, and continued clinical observation and appropriate long-term follow-up should be considered. Additionally, it is important to consider a second primary intraocular tumor in the differential diagnosis, especially in a patient with heritable retinoblastoma who has undergone radiation therapy.
PMID: 29344484 [PubMed]
Acne Scarring-Pathogenesis, Evaluation, and Treatment Options.
J Clin Aesthet Dermatol. 2017 Sep;10(9):12-23
Authors: Connolly D, Vu HL, Mariwalla K, Saedi N
Acne vulgaris is a ubiquitous problem affecting 80 percent of people ages 11 to 30 years, with many patients experiencing some degree of scarring. This review focuses on atrophic scars, the most common type of acne scar. We briefly address the cellular sequelae that lead to scar formation and the initial evaluation of patients with acne scars. We then discuss an algorithmic approach to the treatment of acne scarring based on the classification of scars into erythematous and atrophic types. Lastly, we discuss the future treatment of acne scars and ongoing clinical trials.
PMID: 29344322 [PubMed]
A Topical Anti-inflammatory Healing Regimen Utilizing Conjugated Linolenic Acid for Use Post-ablative Laser Resurfacing of the Face: A Randomized, Controlled Trial.
J Clin Aesthet Dermatol. 2017 Oct;10(10):12-17
Authors: Wu DC, Goldman MP
Background: Fractionated, ablative lasers are usually associated with post-treatment erythema, edema, and crusting, which can last from 5 to 14 days. Conjugated linolenic acid, an omega-5 fatty acid, has significant antioxidant and anti-inflammatory properties, and has been shown to stimulate keratinocyte proliferation and epidermal regeneration. By modulating the early inflammatory milieu and directly affecting skin structure and function, conjugated linolenic acid might therefore shorten downtime following fractionated ablative laser resurfacing of the face. Objective: To evaluate the efficacy and subject satisfaction of a topical regimen containing conjugated linolenic acid derived from pomegranate seed extract in accelerating wound healing and improving skin quality following fractionated ablative laser resurfacing of the face. Materials and Methods: Thirty-four subjects were enrolled and received fractionated CO2 laser resurfacing. Subjects were randomized to use the test healing regimen (n=24) or 1% dimethicone ointment (n=10) post-procedure. The primary endpoint was the degree of erythema, edema, crusting, and exudation evaluated by a blinded clinician at post-treatment Days 1,3,7,10, 14, and 30. Secondary endpoints included a blinded evaluator assessment of the degree of wrinkling and elastosis using the Fitzpatrick-Goldman Wrinkle and Elastosis Scale; subject-assessed degree of pain, itching, tightness, oozing, and crusting; and subject overall satisfaction. Results: Subjects who applied the topical conjugated linolenic acid healing regimen experienced significantly reduced edema on post-procedure Day 3 (p=0.04), and itching on Days 1 and 3 (p=0.03 and p=0.04). Both regimens produced significant improvements in wrinkling and elastosis at Days 14 and 30 post-treatment, with conjugated linolenic acid outperforming placebo in improvements in wrinkling at Day 14. Both regimens were well tolerated with no statistical differences in adverse events or subject satisfaction. Conclusion: The topical conjugated linolenic acid formulation outperformed placebo by decreasing acute pruritus and edema, and enabling a faster positive outcome in wrinkle improvement. Additionally, topical conjugated linolenic acid does not raise any safety or tolerability issues as compared to current standard of care.
PMID: 29344315 [PubMed]
An Endogenous Vaccine Based on Fluorophores and Multivalent Immunoadjuvants Regulates Tumor Micro-Environment for Synergistic Photothermal and Immunotherapy.
Authors: Li L, Yang S, Song L, Zeng Y, He T, Wang N, Yu C, Yin T, Liu L, Wei X, Wu Q, Wei Y, Yang L, Gong C
Recently, near-infrared (NIR) light-based photothermal therapy (PTT) has been widely applied in cancer treatment. However, in most cases, the tissue penetration depth of NIR light is not sufficient and thus photothermal therapy is unable to completely eradicate deep, seated tumors inevitably leading to recurrence of the tumor. Due to this significant limitation of NIR, improved therapeutic strategies are urgently needed. Methods: We developed an endogenous vaccine based on a novel nanoparticle platform for combinatorial photothermal ablation and immunotherapy. The design was based on fluorophore-loaded liposomes (IR-7-lipo) coated with a multivalent immunoadjuvant (HA-CpG). In vitro PTT potency was assessed in cells by LIVE/DEAD and Annexin V-FITC/PI assays. The effect on bone marrow-derived dendritic cells (BMDC) maturation and antigen presentation was evaluated by flow cytometry (FCM) with specific antibodies. After treatment, the immune cell populations in tumor micro-environment and the cytokines in the serum were detected by FCM and Elisa assay, respectively. Finally, the therapeutic outcome was investigated in an animal model. Results: Upon irradiation with 808 nm laser, IR-7-lipo induced tumor cell necrosis and released tumor-associated antigens, while the multivalent immunoadjuvant improved the expression of co-stimulatory molecules on BMDC and promoted antigen presentation. The combination therapy of PTT and immunotherapy regulated the tumor micro-environment, decreased immunosuppression, and potentiated host antitumor immunity. Most significantly, due to an enhanced antitumor immune response, combined photothermal immunotherapy was effective in eradicating tumors in mice and inhibiting tumor metastasis. Conclusion: This endogenous vaccination strategy based on synergistic photothermal and immunotherapy may provide a potentially effective approach for treatment of cancers, especially those difficult to be surgically removed.
PMID: 29344312 [PubMed - in process]
131I-Labeled Copper Sulfide-Loaded Microspheres to Treat Hepatic Tumors via Hepatic Artery Embolization.
Authors: Liu Q, Qian Y, Li P, Zhang S, Liu J, Sun X, Fulham M, Feng D, Huang G, Lu W, Song S
Purpose: Transcatheter hepatic artery embolization therapy is a minimally invasive alternative for treating inoperable liver cancer but recurrence is frequent. Multifunctional agents, however, offer an opportunity for tumor eradication. In this study, we were aim to synthesized poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating hollow CuS nanoparticles (HCuSNPs) and paclitaxel (PTX) that were then labeled with radioiodine-131 (131I) to produce 131I-HCuSNPs-MS-PTX. This compound combines the multi-theranostic properties of chemotherapy, radiotherapy and photothermal therapy. In addition, it can also be imaged with single photon emission computed tomography (SPECT) imaging and photoacoustic imaging. Methods: We investigated the value of therapeutic and imaging of 131I-HCuSNPs-MS-PTX in rats bearing Walker-256 tumor transplanted in the liver. After the intra-arterial (IA) injection of 131I-HCuSNPs-MS-PTX, 18F-Fluorodeoxyglucose (18F-FDG) micro-positron emission tomography/computed tomography (micro-PET/CT) imaging was used to monitor the therapeutic effect. PET/CT findings were verified by immunohistochemical analysis. SPECT/CT and photoacoustic imaging were performed to demonstrate the distribution of 131I-HCuSNPs-MS-PTX in vivo. Results: We found that embolization therapy in combination with chemotherapy, radiotherapy and photothermal therapy offered by 131I-HCuSNPs-MS-PTX completely ablated the transplanted hepatic tumors at a relatively low dose. In comparison, embolization monotherapy or combination with one or two other therapies had less effective anti-tumor efficacy. The combination of SPECT/CT and photoacoustic imaging effectively confirmed microsphere delivery to the targeted tumors in vivo and guided the near-infrared laser irradiation. Conclusion: Our study suggests that there is a clinical theranostic potential for imaging-guided arterial embolization with 131I-HCuSNPs-MS-PTX for the treatment of liver tumors.
PMID: 29344306 [PubMed - in process]
Enhanced Synergism of Thermo-chemotherapy For Liver Cancer with Magnetothermally Responsive Nanocarriers.
Authors: Li M, Bu W, Ren J, Li J, Deng L, Gao M, Gao X, Wang P
A combination of magnetic hyperthermia and magnetothermally-facilitated drug release system was developed as a promising strategy for liver cancer therapy. The thermosensitive copolymer, 6sPCL-b-P(MEO2MA-co-OEGMA) shows a good temperature-controlled drug release response. Mn-Zn ferrite magnetic nanoparticles (MZF-MNPs) exhibit a strong magnetic thermal effect with an alternating magnetic field (AMF). Owing to its high magnetic sensitivity, the magnetothermally-responsive nanocarrier/doxorubicin (MTRN/DOX) can be concentrated in the tumor site efficiently through magnetic targeting. Given this information, we synthesized MTRN/DOX which was composed of MZF-MNPs, thermosensitive copolymer drug carriers, and the chemotherapeutic drug---DOX, to study its anticancer effects both in vitro and in vivo.METHODS: MTRN/DOX was designed and prepared. Firstly, we investigated the accumulation effects of MTRN/DOX by Prussian blue staining, transmission electron microscopy (TEM), laser scanning confocal microscopy (LSCM) and conducted 7.0 T MRI. Following this, the magnetothermal effects of MTRN/DOX were studied using an infrared thermal camera. DOX uptake, distribution, and retention in tumor cells and the distribution of MTRN/DOX in vivo were then analyzed via LSCM, flow cytometry and live fluorescence imaging. Lastly, its anticancer effects were evaluated by MTT, AM/PI staining, Annexin-VFITC/PI staining and comparison of relative tumor volume. RESULTS: We found that MTRN/DOX can be efficiently concentrated in the tumor site through magnetic targeting, increasing the uptake of DOX by tumor cells, and prolonging the retention time of the drug within the tumors. MTRN/DOX showed good magnetothermal effects both in vitro and in vivo. Based on the above results, MTRN/DOX had significant anticancer effects. CONCLUSIONS: MTRN/DOX causes temporal-spatial synchronism of thermo-chemotherapy and together with chemotherapeutic drugs, produces a synergistic effect, which enhances the sensitivity of tumor cells to DOX and reduces their side effects.
PMID: 29344299 [PubMed - in process]
Mesoporous Carbon Nanospheres as a Multifunctional Carrier for Cancer Theranostics.
Authors: Zhou L, Jing Y, Liu Y, Liu Z, Gao D, Chen H, Song W, Wang T, Fang X, Qin W, Yuan Z, Dai S, Qiao ZA, Wu C
Optical nanomaterials with intense absorption in near-infrared (NIR) region hold great promise for biomedical applications such as photothermal therapy (PTT) and photoacoustic imaging (PAI). In this work, we report mesoporous carbon nanospheres (Meso-CNs) with broadband and intense absorption in the UV-Vis-NIR region (300-1400 nm) and explore their potential as a multifunctional platform for photoacoustic imaging and chemo-photothermal therapy. Methods: Meso-CNs were prepared by a "silica-assisted" synthesis strategy and characterized by transmission electron microscope and optical spectroscopy. We investigated the photothermal conversion and photoacoustic imaging of Meso-CNs in comparison with single-walled carbon nanotubes (SWCNTs), graphene and gold nanorods (GNRs). In vitro cellular assays and in vivo chemo-photothermal combination therapy were performed. Results: The absorption coefficients of Meso-CNs are 1.5-2 times higher than those of SWCNTs and graphene and are comparable to those of GNRs in both the first and the second near-infrared optical windows (NIR-I and NIR-II) of tissues. When exposed to an NIR laser, the photothermal and photoacoustic signal generation of Meso-CNs are also stronger than those of SWCNTs, graphene, and GNRs. DOX was loaded into Meso-CNs with a high efficiency (35 wt%) owing to the unique mesoporous structure. Particularly, the drug release from Meso-CNs is sensitive to both pH and NIR light stimulation. In vivo chemo-photothermal combination therapy demonstrates a remarkable inhibition effect on tumor growth under NIR laser treatment. Conclusions: We have developed Meso-CNs for photothermal conversion and photoacoustic imaging. The porous structure also serves as a drug carrier and the drug release can be controlled by pH and external light. The high drug loading capacity, superior photothermal and photoacoustic generation, together with the apparent chemo-photothermal therapeutic effect, make Meso-CNs a promising platform for cancer theranostics.
PMID: 29344297 [PubMed - in process]
Antitumor effect of a new nano-vector with miRNA-135a on malignant glioma.
Int J Nanomedicine. 2018;13:209-220
Authors: Liang C, Sun W, He H, Zhang B, Ling C, Wang B, Huang T, Hou B, Guo Y
Introduction: MiR-135a is found to selectively induce apoptosis in glioma cell but not in normal neurons and glial cells. However, low transfection efficacy limits its application in vivo as other miRNAs. We prepared a new kind of nano-vector based on polyethylene glycol methyl ether (mPEG) and hyper-branched polyethylenimine (hy-PEI) in order to improve the miRNA delivery system into the glioma cells.
Methods: The mPEG-g-PEI/miR-135a was constructed and detected by 1H NMR and FTIR analyses. Transmission electron microscope was utilized for its characteristics. Stability and release efficiency was assessed by electrophoresis. Biocompatibility was observed and analyzed through co-culture with astrocytes and malignant glioma cells (C6). Transfection rate was monitored by laser confocal microscopy and flow cytometry. The antitumor effect of mPEG-g-PEI/miR-135a to C6 was confirmed in vivo by MR scanning, pathology and survival curve. RT-PCR was used to assay transfection efficiency of mPEG-g-PEI/miR-135a in vitro and in vivo. And Western blotting was used to assess the expressions of the targeted proteins of miR-135a.
Results: In this experiment, we found the optimal N/P ratio of mPEG-g-PEI/miR-135a was about 6 judged by Zeta potential, particle size and encapsulation ability. The stability of mPEG-g-PEI/miR-135a in serum and the release efficiency in acid(pH=5.0) of mPEG-g-PEI/miR-135a were simulated the environment in vivo and in tumor. The mPEG-g-PEI nano-vector was co-cultured with malignant glioma cell C6 and normal astrocytes in vitro and showed good biocompatibility evaluated by CCK8 assay. The cell experiments in vitro indicated that mPEG-g-PEI could significantly improve miR-135a transfection by enhancing uptake effect of both normal glial and glioma cells. Given the C6 implanted in situ model, we discovered that the mPEG-g-PEI/miR-135a could obviously increase the survival period and inhibit the growth of glioma confirmed by MRI and histochemistry. In addition, the transfection efficiency of mPEG-g-PEI was better than that of other transfection agents either in vitro or in vivo confirmed by RT-PCR. Moreover, the expressions of the targeted proteins of miR-135a were consistent with the in vitro results.
Conclusion: These results suggest that mPEG-g-PEI is expected to provide a new effective intracellular miRNA delivery system with low toxicity for glioma therapy.
PMID: 29343959 [PubMed - in process]
A heterogeneous tissue model for treatment planning for magnetic resonance-guided laser interstitial thermal therapy.
Int J Hyperthermia. 2018 Jan 17;:1-35
Authors: Mitchell D, Fahrenholtz S, MacLellan C, Bastos D, Rao G, Prabhu S, Weinberg J, Hazle J, Stafford J, Fuentes D
We evaluated a physics-based model for planning for magnetic resonance-guided laser interstitial thermal therapy for focal brain lesions. Linear superposition of analytical point source solutions to the steady-state Pennes bioheat transfer equation simulates laser-induced heating in brain tissue. The line integral of the photon attenuation from the laser source enables computation of the laser interaction with heterogeneous tissue. Magnetic resonance thermometry data sets (n = 31) were used to calibrate and retrospectively validate the model's thermal ablation prediction accuracy, which was quantified by the Dice similarity coefficient (DSC) between model-predicted and measured ablation regions (T > 57°C). A Gaussian mixture model was used to identify independent tissue labels on pretreatment anatomical magnetic resonance images. The tissue-dependent optical attenuation coefficients within these labels were calibrated using an interior point method that maximizes DSC agreement with thermometry. The distribution of calibrated tissue properties formed a population model for our patient cohort. Model prediction accuracy was cross-validated using the population mean of the calibrated tissue properties. A homogeneous tissue model was used as a reference control. The median DSC values in cross-validation were 0.829 for the homogeneous model and 0.840 for the heterogeneous model. In cross-validation, the heterogeneous model produced a DSC higher than that produced by the homogeneous model in 23 of the 31 brain lesion ablations. Results of a paired, two-tailed Wilcoxon signed-rank test indicated that the performance improvement of the heterogeneous model over that of the homogeneous model was statistically significant (p < 0.01).
PMID: 29343140 [PubMed - as supplied by publisher]
Preimplantation Factor (PIF) Promotes HLA-G, -E, -F, -C Expression in JEG-3 Choriocarcinoma Cells and Endogenous Progesterone Activity.
Cell Physiol Biochem. 2017;43(6):2277-2296
Authors: Hakam MS, Miranda-Sayago JM, Hayrabedyan S, Todorova K, Spencer PS, Jabeen A, Barnea ER, Fernandez N
BACKGROUND/AIMS: Pregnancy success requires mandatory maternal tolerance of the semi/ allogeneic embryo involving embryo-derived signals. Expression levels of PreImplantation Factor (PIF), a novel peptide secreted by viable embryos, correlate with embryo development, and its early detection in circulation correlates with a favourable pregnancy outcome. PIF enhances endometrial receptivity to promote embryo implantation. Via the p53 pathway, it increases trophoblast invasion, improving cell survival / immune privilege. PIF also reduces spontaneous and LPS-induced foetal death in immune naïve murine model. We examined PIF effect on gene expression of human leukocyte antigen (HLA-G, -E -F and -C) and the influence of PIF on local progesterone activity in JEG-3 choriocarcinoma cells.
METHODS: PIF and progesterone (P4) effects on JEG-3 cells surface and intracellular HLA molecules was tested using monoclonal antibodies, flow cytometry, and Western blotting. PIF and IL17 effects on P4 and cytokines secretion was determined by ELISA. PIF and P4 effects on JEG-3 cells proteome was examined using 2D gel staining followed by spot analysis, mass spectrometry and bioinformatic analysis.
RESULTS: In cytotrophoblastic JEG-3 cells PIF increased intracellular expression of HLA-G, HLA-F, HLA-E and HLA-C and surface expression of HLA-G, HLA-E and HLA-C in dose and time dependent manner. In case of HLA-E, -F results were confirmed also by Western blot. Proteome analysis confirmed an increase in HLA-G, pro-tolerance FOXP3+ regulatory T cells (Tregs), coagulation factors and complement regulator. In contrast, PIF reduced PRDX2 and HSP70s to negate oxidative stress and protein misfolding. PIF enhanced local progesterone activity, increasing steroid secretion and the receptor protein. It also promoted the secretion of the Th1/Th2 cytokines (IL-10, IL-1β, IL-8, GM-CSF and TGF-β1), resulting in improved maternal signalling.
CONCLUSION: PIF can generate a pro-tolerance milieu by enhancing the expression of HLA molecules and by amplifying endogenous progesterone activity. A Fast-Track clinical trial for autoimmune disease has been satisfactorily completed. The acquired data warrants PIF use for the treatment of early pregnancy disorders.
PMID: 29073617 [PubMed - indexed for MEDLINE]
A Tissue Displacement-based Contusive Spinal Cord Injury Model in Mice.
J Vis Exp. 2017 Jun 18;(124):
Authors: Wu X, Zhang YP, Qu W, Shields LBE, Shields CB, Xu XM
Producing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between experimental animals. Several contusive SCI models have been developed to produce injuries using different mechanisms. The severity of the SCI is based on the height that a given weight is dropped, the injury force, or the spinal cord displacement. In the current study, we introduce a novel mouse contusive SCI device, the Louisville Injury System Apparatus (LISA) impactor, which can create a displacement-based SCI with high injury velocity and accuracy. This system utilizes laser distance sensors combined with advanced software to produce graded and highly-reproducible injuries. We performed a contusive SCI at the 10th thoracic vertebral (T10) level in mice to demonstrate the step-by-step procedure. The model can also be applied to the cervical and lumbar spinal levels.
PMID: 28654063 [PubMed - indexed for MEDLINE]
Urothelial Tumors and Dual-Band Imaging: A New Concept in Confocal Laser Endomicroscopy.
J Endourol. 2017 May;31(5):538-544
Authors: Marien A, Rock A, Maadarani KE, Francois C, Gosset P, Mauroy B, Bonnal JL
OBJECTIVES: Confocal laser endomicroscopy (CLE) uses a low-energy laser light source to obtain microscopic histology images of bladder tissue exposed to a fluorescent dye. To evaluate the feasibility of using CLE with two fluorophores: fluorescein (FLUO) and hexylaminolevulinate (HAL) to determine histologic and cytologic bladder cancer criteria.
METHODS: Patients eligible for HAL-photodynamic diagnosis-assisted transurethral resection of bladder tumor were included. The procedures were performed with the patient under regional or general anesthesia (60-90 minutes) after bladder instillation of HAL (50 mL, 8 mmol/L; Hexvix®; Ipsen, France). Resected tissue was examined ex vivo using CLE either with Cellvizio® system (CVI) single laser (488 nm) or with Cellvizio Dual system (CVII) double laser (488, 660 nm).
RESULTS: Twenty-one patients were included, 12 examined by CVI and 9 by CVII. Sample examination on CVI after HAL-CLE-only histologic analysis was not possible because HAL is mostly cytoplasmic and gives poor details on cellular architecture. On the contrary, FLUO-CLE gives good extracellular architecture and not clear information of nucleocytoplasmic abnormality. Samples on CVII for seven out of nine patients clearly showed cytoplasm of suspect cells and nuclei. In real time, fluorescence observed on bandwidth (673-800 nm) with HAL and FLUO was associated with the presence of cancer, with a sensibility and specificity of 80% and 100%, respectively.
CONCLUSIONS: Real-time cytodetection was feasible using two fluorophores (FLUO and HAL) and the new system of CVII. This technology was useful to observe cytoplasm, nuclei, and nucleocytoplasmic abnormality, but an improved system is necessary (to overcome the overlapping of fluorescence) to increase the specificity.
PMID: 28326794 [PubMed - indexed for MEDLINE]
Perfusion Controlled Mobilization after Lower Extremity Free Flaps-Pushing the Limits of Time and Intensity.
J Reconstr Microsurg. 2017 Mar;33(3):179-185
Authors: Dornseifer U, Kleeberger C, Kargl L, Schönberger M, Rohde D, Ninkovic M, Schilling A
Background The current standard to gradually adapt the fragile perfusion in lower extremity free flaps to an upright posture is the dangling maneuver. This type of flap training neither fits the orthostatic target load of an upright posture, nor does it assist in mobilizing the patients effectively. In this study, we quantitatively analyzed training effects of an early and full mobilization on flap perfusion. Methods A total of 15 patients with gracilis flaps for distal lower extremity reconstruction were included. Flap training was performed daily by mobilizing the patients on a tilt table into a fully upright posture for 5 minutes between the third and fifth postop days (PODs). Changes in micro- and macrocirculation were analyzed by laser Doppler flowmetry, remission spectroscopy, and an implanted Doppler probe. Results All flaps healed without complications. Yet, in three patients, the increased orthostatic load required an adjustment of the training duration due to a critical blood flow. The others showed an increasing compensation in the microcirculation. When tilting the patients, blood flow and oxygen saturation dropped significantly less on POD5 than on POD3. Furthermore, a significant increase of the blood flow was noted after an initial decrease during the mobilization on all days. An increasing compensation in the macrocirculation could not be determined. Conclusion Full mobilization of patients with lower extremity free flaps can be performed safely under perfusion monitoring, already starting on POD3. Additionally, monitoring allows a consideration of the individual orthostatic competence and therefore, exploitation of the maximum mobilization potential.
PMID: 27894154 [PubMed - indexed for MEDLINE]
Rutin-loaded chitosan microspheres: Characterization and evaluation of the anti-inflammatory activity.
Carbohydr Polym. 2016 Nov 05;152:583-591
Authors: Cosco D, Failla P, Costa N, Pullano S, Fiorillo A, Mollace V, Fresta M, Paolino D
Rutin was microencapsulated in a chitosan matrix using the spray-drying technique and the resulting system was investigated. High amounts of rutin were efficiently entrapped within polymeric microspheres, and these microparticles were characterized by a smooth surface and afforded a controlled release of the active compound. The anti-inflammatory activity of rutin-loaded microspheres was investigated in in vitro models of NCTC 2544 and C-28 cells treated with LPS by determining the levels of IL-1β and IL-6. The rutin-loaded microspheres showed an increase of in vitro anti-inflammatory activity with respect to the free active compound. Confocal laser scanning microscopy demonstrated that massive intracellular uptake of the chitosan microspheres took place after a few hours of incubation and that the drug was localized in the cytosol compartment of the treated cells. The improved anti-inflammatory activity of the rutin-loaded microspheres was further confirmed by an in vivo model of carrageenan-induced paw edema.
PMID: 27516307 [PubMed - indexed for MEDLINE]
Synthesis of selenium-containing Artemisia sphaerocephala polysaccharides: Solution conformation and anti-tumor activities in vitro.
Carbohydr Polym. 2016 Nov 05;152:70-78
Authors: Wang J, Li Q, Bao A, Liu X, Zeng J, Yang X, Yao J, Zhang J, Lei Z
It has been reported in our previous work that selenized Artemisia sphaerocephala polysaccharides (SeASPs) with the Se content range of 168-1703μg/g were synthesized by using Na2SeO3/HNO3/BaCl2 system. In the present work, the solution property of SeASP was studied by using size exclusion chromatography combined with multi angle laser light scattering (SEC-MALLS). A decrease in df values indicated that SeASPs with different conformational features that were highly dependent on MW. SeASPs exhibited a more rigid conformation (df value of 1.29-1.52) in low molecular weight range (MW of 1.026-1.426×10(4)g/mol) and compact spherical conformation in high molecular weight range (MW of 2.268-4.363×10(4)g/mol). It could be due to the degradation of polysaccharide chains in HNO3, which was supported in monosaccharide composition analysis. Congo red (CR) spectrophotometric method and atomic force microscopy (AFM) results also confirmed the conformational transition and the evidence on the shape of the rigid chains. In vitro anti-tumor assays, SeASP2 displayed greater anti-proliferative effects against three tumor cell lines (hepatocellular carcinoma HepG-2 cells, lung adenocarcinom A549 cells and cervical squamous carcinoma Hela cells) in a dose-dependent manner. This suggested that selenylation could significantly enhance the anti-tumor activities of polysaccharide derivatives in vitro.
PMID: 27516251 [PubMed - indexed for MEDLINE]
Gold nanoparticle-conjugated pepsin for efficient solution-like heterogeneous biocatalysis in analytical sample preparation protocols.
Anal Bioanal Chem. 2016 Aug;408(20):5415-27
Authors: Höldrich M, Sievers-Engler A, Lämmerhofer M
Immobilization of enzymes on mesoporous microparticulate carriers has traditionally been accompanied by reduction in enzyme activity. Herein, we document that immobilization of pepsin via amide coupling on gold nanoparticles (GNPs) with a carboxy-terminated hydrophilic PEG7 shell resulted in a heterogeneous nanobiocatalyst with essentially equivalent turnover rates, k cat (90 %), and enhanced catalytic efficiencies, k cat/K M (107 %), compared to homogeneous catalysis with pepsin in free solution for cytochrome C as model substrate. This heterogeneous catalyst showed further at least equivalent bioactivity in a digestion reaction of a protein mixture consisting of cytochrome C, bovine serum albumin, and myoglobin. UHPLC-ESI-QTOF-MS/MS analysis of the digests with subsequent Mascot database search allowed unequivocal identification of all proteins with high score and good sequence coverage. The functionalized nanoparticles were further characterized by Vis spectroscopy in terms of the surface plasmon resonance (SPR) band, by dynamic light scattering (DLS) with regard to hydrodynamic diameters, and in view of their ζ potentials at each step of synthesis and surface modification. These measurements also revealed that the pepsin-functionalized GNPs were sufficiently stable over at least 1 month; thus providing a satisfactory shelf life to the heterogeneous catalyst. Advantageously, the pepsin-GNP bioconjugate can be conveniently removed after reaction by simple centrifugation steps which makes them a useful tool for analysis of therapeutic peptides and proteins, including monoclonal antibodies. The practical utility of the nanobiocatalyst was documented by digestion of a monoclonal antibody which yielded the F(ab')2 fragment with a mass of 97,619.4 Da. Graphical Abstract Pepsin conjugated to pegylated gold nanoparticles exhibit properties of homogeneous catalysis such as enzyme activity like pepsin in solution and ability to pipette the stable colloidal suspension whereas one can take benefit from easy removal by centrifugation and re-use which are characteristics of heterogeneous catalysis.
PMID: 27271318 [PubMed - indexed for MEDLINE]
Synthesis of bifunctional [email protected](OH)[email protected]@TiO2 sandwich-like nanosheets for sequential selective enrichment of phosphopeptides and glycopeptides for mass spectrometric analysis.
Anal Bioanal Chem. 2016 Aug;408(20):5489-97
Authors: Xu D, Gao M, Deng C, Zhang X
In this work, the bifunctional [email protected](OH)[email protected]@TiO2 sandwich-like nanosheets were designed and synthesized for the sequential selective enrichment of phosphopeptides and glycopeptides. Due to the bifunctional property of the titanium dioxide and the boronic acid group, the nanosheets were successfully applied to the enrichment of phosphopeptides and glycopeptides sequentially, evaluated by capturing phosphopeptides from tryptic digestion of model phosphoprotein bovine β-casein diluted to 0.02 ng/μL (8 × 10(-16) mol/μL) and glycopeptides from tryptic digestion of model glycoprotein horseradish peroxidase (HRP) diluted to 0.1 ng/μL (2.5 × 10(-15) mol/μL). The enrichment selectivity of the bifunctional nanosheets was evaluated by capturing phosphopeptides from a peptide mixture of β-casein and bovine serum albumin (BSA) with the molar ratio of 1:1000 (8.3 × 10(-12) mol of β-casein and 8.3 × 10(-9) mol of BSA in 100 μL) and glycopeptides from a peptide mixture of HRP and BSA up to the ratio of 1:50 (5.0 × 10(-11) mol of HRP and 2.5 × 10(-9) mol of BSA in 100 μL). Graphical Abstract A workflow of the sequential enrichment strategy for phosphopeptides and glycopeptides by the bifunctional [email protected](OH)[email protected]@TiO2 sandwich-like nanosheets.
PMID: 27236315 [PubMed - indexed for MEDLINE]
Diffuse optical spectroscopic imaging of subcutaneous adipose tissue metabolic changes during weight loss.
Int J Obes (Lond). 2016 Aug;40(8):1292-300
Authors: Ganesan G, Warren RV, Leproux A, Compton M, Cutler K, Wittkopp S, Tran G, O'Sullivan T, Malik S, Galassetti PR, Tromberg BJ
BACKGROUND: Changes in subcutaneous adipose tissue (AT) structure and metabolism have been shown to correlate with the development of obesity and related metabolic disorders. Measurements of AT physiology could provide new insight into metabolic disease progression and response to therapy. An emerging functional imaging technology, diffuse optical spectroscopic imaging (DOSI), was used to obtain quantitative measures of near infrared (NIR) AT optical and physiological properties.
METHODS: Ten overweight or obese adults were assessed during 3 months on calorie-restricted diets. DOSI-derived tissue concentrations of hemoglobin, water and lipid and the wavelength-dependent scattering amplitude (A) and slope (b) obtained from 30 abdominal locations and three time points (T0, T6, T12) were calculated and analyzed using linear mixed-effects models and were also used to form 3D surface images.
RESULTS: Subjects lost a mean of 11.7±3.4% of starting weight, while significant changes in A (+0.23±0.04 mm(-1), adj. P<0.001),b (-0.17±0.04, adj. P<0.001), tissue water fraction (+7.2±1.1%, adj. P<0.001) and deoxyhemoglobin (1.1±0.3 μM, adj. P<0.001) were observed using mixed-effect model analysis.
DISCUSSION: Optical scattering signals reveal alterations in tissue structure that possibly correlate with reductions in adipose cell volume, while water and hemoglobin dynamics suggest improved AT perfusion and oxygen extraction. These results suggest that DOSI measurements of NIR optical and physiological properties could be used to enhance understanding of the role of AT in metabolic disorders and provide new strategies for diagnostic monitoring of obesity and weight loss.
PMID: 27089996 [PubMed - indexed for MEDLINE]
The Application of Noninvasive Headspace Analysis to Media Fill Inspection.
PDA J Pharm Sci Technol. 2016 May-Jun;70(3):230-47
Authors: Duncan D, Cundell T, Levac L, Veale J, Kuiper S, Rao R
UNLABELLED: The results of a proof-of-principle study demonstrating a new analytical technique for detecting microbial growth directly in pharmaceutical containers are described. This analytical technique, laser-based headspace analysis, uses tunable diode laser absorption spectroscopy to nondestructively determine gas concentrations in the headspace of a media-filled pharmaceutical container. For detecting microbial growth, the levels of headspace oxygen and carbon dioxide are measured. Once aerobic microorganisms begin to divide after the lag phase and enter the exponential growth phase, there will be significant consumption of oxygen and concomitant production of carbon dioxide in the sealed container. Laser-based headspace analysis can accurately measure these changes in the headspace gas composition. The carbon dioxide and oxygen measurement data for the representative microorganisms Staphylococcus aureus, Bacillus subtilis, Candida albicans, and Aspergillus brasiliensis were modeled using the Baranyi-Roberts equation. The mathematical modeling allowed quantitative comparisons to be made between the data from the different microorganisms as well as to the known growth curves based on microbial count. Because laser-based headspace analysis is noninvasive and can be automated to analyze the headspace of pharmaceutical containers at inspection speeds of several hundred containers per minute on-line, some potential new applications are enabled. These include replacing the current manual human visual inspection with an automated analytical inspection machine to determine microbial contamination of media fill and pharmaceutical drug product vials.
LAY ABSTRACT: A novel analytical technique has been demonstrated for detecting microbial growth in media-filled pharmaceutical containers. This analytical technique, laser-based headspace analysis, uses tunable diode laser absorption spectroscopy to determine gas concentrations in the headspace of a pharmaceutical container. For detecting microbial growth, the levels of headspace oxygen and carbon dioxide are measured. The study shows that once aerobic microorganisms begin to grow after the lag phase and enter the exponential growth phase there will be a significant consumption of oxygen in the sealed container as well as a corresponding production of carbon dioxide. Headspace analysis can accurately measure and monitor these changes in the headspace gas composition and could therefore be used to detect contaminated pharmaceutical containers. Because the technique can be automated to analyze hundreds of containers a minute on-line, there are opportunities for implementing a headspace inspection machine to perform automated inspection of media fills used to validate aseptic filling operations.
PMID: 26865678 [PubMed - indexed for MEDLINE]
The effect of photon-initiated photoacoustic streaming, ultrasonically and sonically irrigation techniques on the push-out bond strength of a resin sealer to the root dentin.
Clin Oral Investig. 2015 Jun;19(5):1055-61
Authors: Akcay M, Arslan H, Mese M, Sahin NN
OBJECTIVES: The present study investigated the effects of various irrigation activation techniques, including laser-activated irrigation using a laser with a novel tip design (photon-induced photoacoustic streaming, PIPS) on the bond strength of an epoxy resin-based sealer to root dentin.
MATERIALS AND METHODS: Seventy-two single-rooted human mandibular premolars were prepared using the rotary system to size 40 and randomly divided into four groups (n = 18) according to the final irrigation activation technique used as follows: conventional irrigation (CI), laser-activated irrigation with PIPS (LAI-PIPS), passive ultrasonic irrigation (PUI), and sonic irrigation (SI) with 5 mL of 17 % EDTA and 2.5 % NaOCl. The root canals were then obturated with gutta-percha and AH PlusJet sealer. A push-out test was used to measure the bond strength between the root canal dentin and the sealer. The data were analyzed using the two-way analysis of variance and least significant difference (LSD) post hoc tests (P = 0.05).
RESULTS: The LAI-PIPS and PUI resulted in higher push-out values compared to CI and SI (P < 0.05). There were no statistically significant differences between CI and SI (P = 0.978) and between LAI-PIPS and PUI (P = 0.051). There was a statistically significant interaction between the final irrigant activation techniques used and root canal thirds (P < 0.05). A chi-square test revealed no significant differences in the failure mode within the groups (P > 0.05).
CONCLUSIONS: The use of LAI-PIPS and PUI can provide higher bond strength of resin sealer to root dentin compared to CI and SI techniques.
CLINICAL RELEVANCE: The activation of the irrigant and the creation of the streaming have a positive effect on the bond strength of the resin sealer to root dentin.
PMID: 25315971 [PubMed - indexed for MEDLINE]