Endothelial Progenitor Cell-Derived Factors Exert Neuroprotection in Cultured Cortical Neuronal Progenitor Cells.

There is substantial evidence that stem and progenitor cells secrete trophic factors that have potential for repairing injured tissues. We have previously reported that the conditioned medium (CM) obtained from endothelial progenitor cells (EPC) cultures protects striatal neurons against 3-nitropropionic acid-induced toxicity. In the present study we tested the hypothesis that EPC-CM may support cortical neuronal cell function and/or survival. EPC were isolated from the peripheral blood of healthy human donors and cultured in hypoxic conditions (1.5% O2) to stimulate the secretion of growth factors. The supernatant or conditioned medium (EPC-CM) was then collected and used for the various experiments. Primary cultures of cerebral cortex from fetal rat embryonic day 14 were treated with EPC-CM and challenged by glucose and serum deprivation. We observed that EPC-CM treatment significantly increased total cell number and cell viability in the cultures. Similarly, the number of lba1-expressing cells was significantly upregulated by EPC-CM, while western blot analyses for the astroglial marker glial fibrillary acidic protein did not show a marked difference. Importantly, the number of beta-lll-tubulin-positive neurons in the cultures was significantly augmented after EPC-CM treatment. Similarly, western blot analyses for beta-III-tubulin showed significant higher signal intensities. Furthermore, EPC-CM administration protected neurons against glucose- and serum deprivation-induced cell loss. In sum, our findings identified EPC-CM as a means to promote viability and/or differentiation of cortical neurons and suggest that EPC-CM might be useful for neurorestorative approaches

Toward finding the best machine learning classifier for LIBS-based tissue differentiation

Lasers have become generally accepted devices in surgical applications, especially as a cutting tool, for cutting both soft and hard tissues including bone (laserosteotomy). It has been shown that applying lasers in osteotomy have important advantages over mechanical tools, including faster healing, more precise cut and functional cutting geometries as well as less trauma [1, 2]. However, the ability of detecting the type of tissue that being cut during surgery can extend the application and safety of laserosteotomes in practice. As a result, the laser could be stopped automatically in case of cutting a tissue that should be preserved. Authors have previously demonstrated that laser-induced breakdown spectroscopy (LIBS) is a potential candidate to differentiate surrounding soft tissue from the bone in ex vivo condition [3]. In the current study, different machine learning classifiers were examined to find the best possible method to differentiate bone from soft tissues based on LIBS data. These methods include decision tree, K Nearest Neighbor (KNN), linear and quadratic Support Vector Machine (SVM) as well as linear and quadratic discriminant analysis. All classifiers were applied on LIBS data obtained from bone, muscle, and fat tissues using an Nd:YAG laser and an Echelle spectrometer. Confusion matrix and Receiver Operating Characteristic (ROC) curve were obtained for each classifier afterwards. Moreover, in order to estimate the model's performance on new data and also to protect the model against overfitting, cross-validation was applied. All mentioned examinations were performed with MATLAB (R2017b)

All fiber-based LIBS feedback system for endoscopic laser surgery

There has been a particular interest to use laser-induced breakdown spectroscopy (LIBS) as a feedback mechanism for laser surgeries in the past decade 1-6. However, none of the mentioned setups 1-6 is suitable for endoscopic applications due to their bulky free-space configurations. In minimally nvasive surgeries, the major challenge is to integrate ablating laser waveguides and also all sensors inside the narrow channel of the endoscope. In this paper, we present a LIBS setup, which uses a multimode silica fiber for both delivering the inducing laser pulse and collecting the plasma emission light through the endoscope. The fiber-based LIBS setup consists of a frequency-doubled Q-switched Nd:YAG laser (Q-smart 450, Quantel, 532 nm, 5 ns, 60 mJ, 1 Hz), a cleaved large-core silica fiber (1.5 m-long, 1500 um-core, 0.39-NA, 70 mm-bending radius), and an in-house Echelle spectrometer (See Fig. 1). A 75 cm plano-convex laser line lens (Thorlabs, LA1978-YAG) was used to couple the laser beam into a multimode step-index silica fiber. Such a long focal length convex lens was used to avoid breakdown process in air. Moreover, the input face of the fiber was placed at 1 cm behind the focal point to maintain the laser power density below the damage threshold of the fiber. Two tight focusing lenses were placed in front of the fiber end face to collimate the highly divergent laser beam and refocus it onto the sample surface. The light emitted from the microplasma generated at the surface of the sample (bone and its surrounding soft tissues) was collected by the same optics and directed to the spectrometer for characterization. The performance of the developed fiber-based LIBS setup for classification of different tissues has been investigated and compared with the free-space LIBS. The feedback provided by this fiber-based LIBS setup can be used in minimally invasive laserosteotomies in order to stop the laser before causing any collateral damage to surrounding tissues. References [1] F. Yueh, H. Zheng, J.P. Singh, S. Burgess, Preliminary evaluation of laser-induced breakdown spectroscopy for tissue classification, Spectrochim. Acta B 64 (2009) 1059-1067. [2] R. Kanawade, F. Mehari, C. Knipfer, M. Rohde, K. Tangermann-Gerk, et al., Pilot study of laser induced breakdown spectroscopy for tissue differentiation by monitoring the plume created during laser surgery-An approach on a feedback Laser control mechanism, Spectrochim. Acta B 87 (2013) 175-181. [3] K. Henn, G.G. Gubaidullin, J. Bongartz, J. Wahrburg, H. Roth, et al., A spectroscopic approach to monitor the cut processing in pulsed laser osteotomy, Lasers Med. Sci. 28 (2013) 87-92. [4] H. Huang, L.-M. Yang, S. Bai, J. Liu, Smart surgical tool, J. Biomed. Opt. 20 (2015) 028001. [5] R.K. Gill, Z.J. Smith, C. Lee, S. Wachsmann-Hogiu, The effects of laser repetition rate on femtosecond laser ablation of dry bone: a thermal and LIBS study, J. Biophotonics 9 (2016) 171-180. [6] H. Abbasi, G. Rauter, R. Guzman, P.C. Cattin, A. Zam, Laser-induced breakdown spectroscopy as a potential tool for auto carbonization detection in laserosteotomy, J. Biomed. Opt. 23 (2018) 071206

Design and implementation of a compact high-throughput echelle spectrometer using off-the-shelf off-axis parabolic mirrors for analysis of biological samples by LIBS (Conference Presentation)

This work presents the development of an Echelle spectrometer that is optimized for the characterization of laser-driven plasma emission of biological samples for application in smart laser surgery systems. Despite the compact (portable) and cost-efficient design of the developed spectrometer, it allows analyzing the spectrum of a plasma emitted from bone, and its surrounding soft tissues (bone marrow, muscle, and fat) in nearly the same way as a full-sized Echelle spectrometer as used in commercial laser-induced breakdown spectroscopy (LIBS) systems. Most of the commercially available Echelle spectrometers on the market use a long focal length on-axis mirror to have a reasonable F number (which defines the optical throughput of the system) and low aberration. While a long focal length requires less tilting of the mirror than a shorter focal length (the higher the tilt angle, the higher the aberration), a long focal length increases the system size and decreases sensitivity (i.e., less optical throughput). In this work, a parabolic 90o off-axis mirror with a focal length of 152.4 mm and a diameter of 50.8 mm, which leads to an F-number of 3, has been used. This low F-number provides a high optical throughput compared to other similar commercial Echelle spectrometers with F-numbers of 10 or more [1-5]. Since most of the important peaks in biological tissue are in the interval of 240 to 840 nm [6], the design was done by using off-the-shelf aluminum mirrors with a UV-enhanced coating for both collimating and focusing purposes to cover this range with sub-Angstrom resolution. Both collimating and focusing mirrors were chosen with the same radius of curvature and declination angle (opposite direction) to cancel the coma. In this antiparallel configuration, the second parabolic mirror largely eliminates the aberrations from the first one. Moreover, we positioned the Echelle grating under the condition of quasi-Littrow design to have high diffraction efficiency with an off-axis angle in the horizontal plane. A ruled reflection grating with dispersion perpendicular to that of the Echelle grating was utilized as a cross dispenser (order separator) after the Echelle grating to distinguish the overlapping diffraction harmonics. The spectrometer has been connected to a gated ICCD to measure time-resolved spectra. The developed spectrometer was installed on a 3-tier utility cart, the inducing laser (Q-switched Nd:YAG) for LIBS was placed on the middle tier, and the last tier was dedicated for calibration instruments (a NIST traceable balanced Deuterium-Halogen light source for intensity calibration, and some gas/vapor spectral lamps including Mercury-Argon, Argon, Neon, and Krypton for wavelength calibration). The portability feature of this LIBS setup provides a remarkable value for testing and characterizing different biological samples on-site. This is a great capability especially if the target sample has the potential of being contagious. This setup is meant to be used for so-called smart laser osteotomies, i.e., the osteotome will be able to identify the type of the tissue being cut through the feedback provided by LIBS [6-8]

Highly flexible fiber delivery of a high peak power nanosecond Nd:YAG laser beam for flexiscopic applications

Minimally invasive laser surgeries that require the use of a flexible endoscope (flexiscope) could benefit from high-energy nanosecond laser pulses delivered through fibers for real-time tissue characterization and phenotyping. The damage threshold of the fiber's glass material limits the maximum amount of deliverable peak power. To transmit high-energy pulses without damaging the fiber material, large-diameter fibers are typically used, leading to a limited bending radius. Moreover, in a large-core fiber, self-focusing can damage the fiber even if the tip remains intact. In this work, we tested a fused-end fiber bundle combined with a beam shaper capable of delivering more than 20 MW (>100 mJ/5 ns). The fiber bundle was tested over more than eight hours of operation, with different bending radiuses down to 15 mm. The results demonstrate, to the best of our knowledge, the highest peak power delivered through a flexible fiber, for a frequency-doubled Q-switched Nd:YAG laser

Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments

INTRODUCTION: Women who have undergone a full-term pregnancy before the age of 20 have one-half the risk of developing breast cancer compared with women who have never gone through a full-term pregnancy. This protective effect is observed universally among women of all ethnic groups. Parity in rats and mice also protects them against chemically induced mammary carcinogenesis. METHODS: Seven-week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the rats were treated with natural or synthetic estrogens and progestins for 7–21 days by subcutaneous implantation of silastic capsules. RESULTS: In our current experiment, we demonstrate that short-term sustained exposure to natural or synthetic estrogens along with progestins is effective in preventing mammary carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for 3 weeks significantly reduced the incidence of mammary cancer. Short-term exposure to ethynyl estradiol plus megesterol acetate or norethindrone was effective in decreasing the incidence of mammary cancers. Tamoxifen plus progesterone treatment for 3 weeks was able to confer only a transient protection from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was effective in conferring protection against mammary cancers. CONCLUSIONS: The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations

Using bioabsorbable fixation systems in the treatment of pediatric skull deformities leads to good outcomes and low morbidity

Background: Bioabsorbable fixation systems have been widely employed in pediatric patients for cranial reconstruction, obviating the complications of hardware migration and imaging artifact occurring with metallic implants. Recent concern over complications unique to bioabsorbable materials, such as inflammatory reaction and incomplete resorption, necessitates additional conclusive studies to further validate their use in pediatric neurosurgery and craniofacial surgery. Likewise, long-term follow-up in this clinical cohort has not previously been described. Methods: We included consecutive pediatric patients under the age of 2, from Lucile Packard Children's Hospital, who underwent cranial vault reconstruction with the use of a bioabsorbable fixation system between 2003 and 2010. Hospital records were queried for patient characteristics, intraoperative data, and postoperative complications. Results: Ninety-five patients with the following preoperative pathologies were analyzed: craniosynostosis (87), cloverleaf skull (5), frontonasal dysplasia (1), and frontonasal encephalocele (2). Median age was 6months (range 1-24months). Average case duration was 204minutes (range 40-392min), with median of 154mL blood loss (range 30-500mL). Ninety-three percent of patients had 1-4 plates implanted with 48% receiving three plates. The median number of screws used was 59 (range 0-130). The median length of hospital stay was 4days (range 2-127days) with an average follow-up of 22months (five postoperative visits). The complications related to hardware implantation included swelling (1%) and broken hardware (1%), the latter of which required reoperation. Discussion: The bioabsorbable fixation systems for cranial vault reconstruction in children less than 2years of age is safe with tolerable morbidity rate

Preoperative transarterial embolization of vertebral metastases

The aim of this study was to evaluate the impact of preoperative devascularization of spinal metastases in relation to the preembolization tumor vascularization degree and in relation to the intraoperative blood loss. Twenty-four patients underwent preoperative transarterial embolization of hypervascular spinal metastases. Each tumor was assigned a vascularization grade (I-III) according to tumor blush after contrast agent injection in the main feeding artery. Embolization was performed with polyvinyl alcohol particles in all patients. Surgical reports were reviewed in terms of estimated blood loss. A mild hypervascularization was found in three patients (group I), medium in six patients (group II) and extensive in 15 patients (group III). In 22 out of 24 patients embolization could be performed with a complete devascularization. In two patients, only partial embolization could be performed, due to the main feeding artery arising from the artery of Adamkiewicz. In patients with complete devascularization the mean intraoperative blood loss was 1,900ml, whereas in the two patients who were not embolized it was 5,500ml. Intraoperative blood loss was not correlated to the vascularization grade. Angiography and embolization could be performed in all patients without causing permanent neurologic deficit, skin or muscle necrosis. The surgeons concluded that radical tumor resection after embolization was facilitated. Intraoperative blood loss is not correlated with the pre-interventional vascularization degree, if complete devascularization can be achieved with embolization. Preoperative embolization of vertebral hypervascular tumors is safe, effective and facilitates tumor resectio

Endovascular and surgical treatment of spinal dural arteriovenous fistulas

Introduction: The aim of this retrospective study was to evaluate the clinical outcome of patients with spinal dural arteriovenous fistulas (SDAVFs) that were treated with surgery, catheter embolization, or surgery after incomplete embolization. Methods: The study included 21 consecutive patients with SDAVFs of the thoracic, lumbar, or sacral spine who were treated in our institution from 1994 to 2007. Thirteen patients were treated with catheter embolization alone. Four patients underwent hemilaminectomy and intradural interruption of the fistula. Four patients were treated by endovascular techniques followed by surgery. The clinical outcome was assessed using the modified Aminoff-Logue scale (ALS) for myelopathy and the modified Rankin scale (MRS) for general quality of life. Patient age ranged from 44 to 77years (mean 64.7years). Results: Surgical as well as endovascular treatment resulted in a significant improvement in ALS (−62.5% and −31.4%, respectively, p < 0.05) and a tendency toward improved MRS (−50% and −32%, respectively) scores. Patients that underwent surgery after endovascular treatment due to incomplete occlusion of the fistula showed only a tendency for improvement in the ALS score (−16.7%), whereas the MRS score was not affected. Conclusion: We conclude that both endovascular and surgical treatment of SDAVFs resulted in a good and lasting clinical outcome in the majority of cases. In specific situations, when a secondary neurosurgical approach was required after endovascular treatment to achieve complete occlusion of the SDAVF, the clinical outcome was rather poor. The best first line treatment modality for each individual patient should be determined by an interdisciplinary tea

Adult Medulloblastoma: Updates on Current Management and Future Perspectives

Simple Summary Adult medulloblastoma is an extremely rare tumor of the central nervous system. Standard multimodal treatment, comprising maximal safe surgical resection followed by craniospinal radiotherapy and multi-agent chemotherapy, can improve the prognosis of this disease, producing, however, important acute and long-term toxicities. Herein, we review the state of the art for adult medulloblastoma diagnosis and treatment, presenting novel molecular advances and their therapeutic implications and discussing the central role of hub centers to guarantee the highest quality of care and a better overall outcome for this rare tumor. Medulloblastoma (MB) is a malignant embryonal tumor of the posterior fossa belonging to the family of primitive neuro-ectodermic tumors (PNET). MB generally occurs in pediatric age, but in 14-30% of cases, it affects the adults, mostly below the age of 40, with an incidence of 0.6 per million per year, representing about 0.4-1% of tumors of the nervous system in adults. Unlike pediatric MB, robust prospective trials are scarce for the post-puberal population, due to the low incidence of MB in adolescent and young adults. Thus, current MB treatments for older patients are largely extrapolated from the pediatric experience, but the transferability and applicability of these paradigms to adults remain an open question. Adult MB is distinct from MB in children from a molecular and clinical perspective. Here, we review the management of adult MB, reporting the recent published literature focusing on the effectiveness of upfront chemotherapy, the development of targeted therapies, and the potential role of a reduced dose of radiotherapy in treating this disease