Recent Submissions

  • Lead induced differences in bone properties in osteocalcin +/+ and −/− female mice

    Yildirim, G.; Budell, W.C.; Berezovska, O.; Yagerman, S.; Maliath, S.S.; Mastrokostas, P.; Tommasini, S.; Dowd, T.L. (Elsevier BV, 2023-06)
    Lead (Pb) toxicity is a major health problem and bone is the major reservoir. Lead is detrimental to bone, affects bone remodeling and is associated with elderly fractures. Osteocalcin (OC) affects bone remodeling, improves fracture resistance and decreases with age and in some diseases. The effect of lead in osteocalcin depleted bone is unknown and of interest. We compared bone mineral properties of control and Pb exposed (from 2 to 6 months) femora from female adult C57BL6 OC+/+ and OC-/- mice using Fourier Transform Infrared Imaging (FTIRI), Micro-computed tomography (uCT), bone biomechanical measurements and serum turnover markers (P1NP, CTX). Lead significantly increased turnover in OC+/+ and in OC-/- bones producing increased total volume, area and marrow area/total area with decreased BV/TV compared to controls. The increased turnover decreased mineral/matrix vs. Oc+/+ and increased mineral/matrix and crystallinity vs. OC-/-. PbOC-/- had increased bone formation, cross-sectional area (Imin) and decreased collagen maturity compared OC-/- and PbOC+/+. Imbalanced turnover in PbOC-/- confirmed the role of osteocalcin as a coupler of formation and resorption. Bone strength and stiffness were reduced in OC-/- and PbOC-/- due to reduced material properties vs. OC+/+ and PbOC+/+ respectively. The PbOC-/- bones had increased area to compensate for weaker material properties but were not proportionally stronger for increased size. However, at low lead levels osteocalcin plays the major role in bone strength suggesting increased fracture risk in low Pb2+ exposed elderly could be due to reduced osteocalcin as well. Years of low lead exposure or higher blood lead levels may have an additional effect on bone strength.
  • Publication rates of abstracts presented at American Shoulder and Elbow Surgeons annual open and closed conferences: 2015-2019

    Mastrokostas, Paul G.; Klein, Brandon; Cappellino, Anthony L.; Bartlett, Lucas E.; Parada, Stephen A.; Cohn, Randy M. (Elsevier BV, 2024-05)
    Background: The annual meetings hosted by the American Shoulder and Elbow Surgeons (ASES) present the latest prepublication literature in shoulder and elbow surgery, facilitating early dissemination of novel findings that impact clinical decision-making. Evaluating the publication rate of presented abstracts at ASES conferences becomes crucial in assessing the quality of research showcased, as these presentations often precede the peer-review process. Methods: The ASES conference programs from 2015-2019 were reviewed to identify presented abstracts. For each abstract, the title, author(s), conference year, and meeting type (open vs. closed) were recorded. The names of the author(s) of each abstract were searched in the PubMed and Google Scholar databases to determine if there was an associated published manuscript. For each identified manuscript, the title, author(s), date of publication, publishing journal, impact factor of the publishing journal, level of evidence, and number of citations were recorded. Results: A total of 316 abstracts were presented as podium lectures at ASES open and closed meetings between 2015 and 2019. Within 3 years of presentation, 240 (75.9%) of the presented abstracts resulted in publication. There was an increase in the proportion of abstracts resulting in publication within 3 years of the presentation from 2015-2019 (R = 0.8733, P = .053). Overall, the proportion of presented abstracts that went on to publication in peer-reviewed journals also increased (R = 0.8907, P = .043). Manuscripts of abstracts presented at open meetings had a shorter time to publication (8.78 vs. 11.82 months; P = .0160) and were cited more often (40.89 vs. 30.11, P = .0099) than those presented at closed meetings. Conclusion: There has been an increase in the publication rate of abstracts presented at ASES annual meetings in the study period. Published manuscripts of abstracts presented at ASES open conferences were published faster, and were cited more often, than closed conferences. ASES conferences allow for the presentation of high-quality prepublication literature in shoulder and elbow surgery.
  • Modern Internet Search Analytics: Is There a Difference in What Patients are Searching Regarding the Operative and Nonoperative Management of Scoliosis?

    Mastrokostas, Paul G.; Mastrokostas, Leonidas E.; Emara, Ahmed K.; Wellington, Ian J.; Ginalis, Elizabeth; Houten, John K.; Khalsa, Amrit S.; Saleh, Ahmed; Razi, Afshin E.; Ng, Mitchell K. (SAGE Publications, 2024-04-13)
    Study design: Observational Study. Objectives: This study aimed to investigate the most searched types of questions and online resources implicated in the operative and nonoperative management of scoliosis. Methods: Six terms related to operative and nonoperative scoliosis treatment were searched on Google's People Also Ask section on October 12, 2023. The Rothwell classification was used to sort questions into fact, policy, or value categories, and associated websites were classified by type. Fischer's exact tests compared question type and websites encountered between operative and nonoperative questions. Statistical significance was set at the .05 level. Results: The most common questions concerning operative and nonoperative management were fact (53.4%) and value (35.5%) questions, respectively. The most common subcategory pertaining to operative and nonoperative questions were specific activities/restrictions (21.7%) and evaluation of treatment (33.3%), respectively. Questions on indications/management (13.2% vs 31.2%, P < .001) and evaluation of treatment (10.1% vs 33.3%, P < .001) were associated with nonoperative scoliosis management. Medical practice websites were the most common website to which questions concerning operative (31.9%) and nonoperative (51.4%) management were directed to. Operative questions were more likely to be directed to academic websites (21.7% vs 10.0%, P = .037) and less likely to be directed to medical practice websites (31.9% vs 51.4%, P = .007) than nonoperative questions. Conclusions: During scoliosis consultations, spine surgeons should emphasize the postoperative recovery process and efficacy of conservative treatment modalities for the operative and nonoperative management of scoliosis, respectively. Future research should assess the impact of website encounters on patients' decision-making.
  • Successful Percutaneous Coronary Intervention in a Patient With Absent Right Coronary Artery Ostium: A Case Report and Literature Review

    Zaveri, Sahil; Schrem, Ezra; Aykent, Kazim; McFarlane, Samy I; Gandotra, Puneet; Budzikowski, Adam S (Springer Science and Business Media LLC, 2024-04-30)
    Coronary artery anomalies present unique interventional challenges, particularly when associated with significant coronary artery disease. This case report contributes to the limited literature on congenital coronary artery anomalies, emphasizing the need for tailored approaches to optimize patient care. We present a case of a 70-year-old male with refractory angina and a rare congenital coronary anomaly characterized by the absence of the right coronary artery ostium, necessitating reliance on the left coronary system for myocardial perfusion. Cardiac catheterization revealed mid-left anterior descending artery stenosis, prompting percutaneous coronary intervention. Despite the anatomical complexities encountered, the procedure was successfully performed. This case underscores the importance of meticulous diagnostic evaluation, advanced imaging techniques, and a multidisciplinary approach to managing patients with rare coronary anomalies. This report also emphasizes the unique diagnostic and therapeutic considerations by providing a comprehensive literature review and identifying areas for further research to advance treatment strategies and improve outcomes
  • Arrhythmias and ion channelopathies causing sudden cardiac death in Hispanic/Latino and Indigenous populations

    Zaveri, Sahil; Chahine, Mohamed; Boutjdir, Mohamed (Wiley, 2024-04-23)
    The limited literature and increasing interest in studies on cardiac electrophysiology, explicitly focusing on cardiac ion channelopathies and sudden cardiac death in diverse populations, has prompted a comprehensive examination of existing research. Our review specifically targets Hispanic/Latino and Indigenous populations, which are often underrepresented in healthcare studies. This review encompasses investigations into genetic variants, epidemiology, etiologies, and clinical risk factors associated with arrhythmias in these demographic groups. The review explores the Hispanic paradox, a phenomenon linking healthcare outcomes to socioeconomic factors within Hispanic communities in the United States. Furthermore, it discusses studies exemplifying this observation in the context of arrhythmias and ion channelopathies in Hispanic populations. Current research also sheds light on disparities in overall healthcare quality in Indigenous populations. The available yet limited literature underscores the pressing need for more extensive and comprehensive research on cardiac ion channelopathies in Hispanic/Latino and Indigenous populations. Specifically, additional studies are essential to fully characterize pathogenic genetic variants, identify population-specific risk factors, and address health disparities to enhance the detection, prevention, and management of arrhythmias and sudden cardiac death in these demographic groups.
  • Prevalence of concomitant rheumatologic diseases and autoantibody specificities among racial and ethnic groups in SLE patients

    Denvir, Brendan; Carlucci, Philip M.; Corbitt, Kelly; Buyon, Jill P.; Belmont, H. Michael; Gold, Heather T.; Salmon, Jane E.; Askanase, Anca; Bathon, Joan M.; Geraldino-Pardilla, Laura; et al. (Frontiers Media SA, 2024-03-06)
    Objective: Leveraging the Manhattan Lupus Surveillance Program (MLSP), a population-based registry of cases of systemic lupus erythematosus (SLE) and related diseases, we investigated the proportion of SLE with concomitant rheumatic diseases, including Sjögren's disease (SjD), antiphospholipid syndrome (APLS), and fibromyalgia (FM), as well as the prevalence of autoantibodies in SLE by sex and race/ethnicity. Methods: Prevalent SLE cases fulfilled one of three sets of classification criteria. Additional rheumatic diseases were defined using modified criteria based on data available in the MLSP: SjD (anti-SSA/Ro positive and evidence of keratoconjunctivitis sicca and/or xerostomia), APLS (antiphospholipid antibody positive and evidence of a blood clot), and FM (diagnosis in the chart). Results: 1,342 patients fulfilled SLE classification criteria. Of these, SjD was identified in 147 (11.0%, 95% CI 9.2-12.7%) patients with women and non-Latino Asian patients being the most highly represented. APLS was diagnosed in 119 (8.9%, 95% CI 7.3-10.5%) patients with the highest frequency in Latino patients. FM was present in 120 (8.9%, 95% CI 7.3-10.5) patients with non-Latino White and Latino patients having the highest frequency. Anti-dsDNA antibodies were most prevalent in non-Latino Asian, Black, and Latino patients while anti-Sm antibodies showed the highest proportion in non-Latino Black and Asian patients. Anti-SSA/Ro and anti-SSB/La antibodies were most prevalent in non-Latino Asian patients and least prevalent in non-Latino White patients. Men were more likely to be anti-Sm positive. Conclusion: Data from the MLSP revealed differences among patients classified as SLE in the prevalence of concomitant rheumatic diseases and autoantibody profiles by sex and race/ethnicity underscoring comorbidities associated with SLE.
  • GPT-4 as a Source of Patient Information for Anterior Cervical Discectomy and Fusion: A Comparative Analysis Against Google Web Search

    Mastrokostas, Paul G.; Mastrokostas, Leonidas E.; Emara, Ahmed K.; Wellington, Ian J.; Ginalis, Elizabeth; Houten, John K.; Khalsa, Amrit S.; Saleh, Ahmed; Razi, Afshin E.; Ng, Mitchell K. (SAGE Publications, 2024-03-21)
    Study design: Comparative study. Objectives: This study aims to compare Google and GPT-4 in terms of (1) question types, (2) response readability, (3) source quality, and (4) numerical response accuracy for the top 10 most frequently asked questions (FAQs) about anterior cervical discectomy and fusion (ACDF). Methods: "Anterior cervical discectomy and fusion" was searched on Google and GPT-4 on December 18, 2023. Top 10 FAQs were classified according to the Rothwell system. Source quality was evaluated using JAMA benchmark criteria and readability was assessed using Flesch Reading Ease and Flesch-Kincaid grade level. Differences in JAMA scores, Flesch-Kincaid grade level, Flesch Reading Ease, and word count between platforms were analyzed using Student's t-tests. Statistical significance was set at the .05 level. Results: Frequently asked questions from Google were varied, while GPT-4 focused on technical details and indications/management. GPT-4 showed a higher Flesch-Kincaid grade level (12.96 vs 9.28, P = .003), lower Flesch Reading Ease score (37.07 vs 54.85, P = .005), and higher JAMA scores for source quality (3.333 vs 1.800, P = .016). Numerically, 6 out of 10 responses varied between platforms, with GPT-4 providing broader recovery timelines for ACDF. Conclusions: This study demonstrates GPT-4's ability to elevate patient education by providing high-quality, diverse information tailored to those with advanced literacy levels. As AI technology evolves, refining these tools for accuracy and user-friendliness remains crucial, catering to patients' varying literacy levels and information needs in spine surgery.
  • Cell-cell interactions in spheroids maintained in suspension

    Djordjevic, Bozidar; Lange, Christopher S. (Medical Journals Sweden AB, 2009-07-08)
    We have developed a system of mixed aggregates of cultured cells, to model in situ cell interactions. This three-dimensional (3D) system of floating cell aggregates, termed spheroids for their round shape, enables one to monitor their growth in both size and number of constituent clonogens and to measure survival curves for cells having 3D cell-cell interactions. This system was used to measure the three-dimensional cell-cell interactions on growth, and clonogenicity of either AG1522 fibroblasts, or HeLa cervical cancer cells (pure spheroids, or if both feeder and test cells are the same type, pseudohybrid spheroids), and/or of mixtures of both (hybrid spheroids). By following the increase or decrease in size of, or number of clonogens per, spheroid over time, one obtains growth or inhibition curves. By relating these clonogen numbers, one obtains, after a suitable growth period, relative survival. The system allows one to score the effects of irradiation and of other treatments, as well as the effect of interaction of the constituent cells on their survival. Floating pure, or pseudohybrid (composed of 10% live fibroblasts and 90% supralethally irradiated fibroblast feeder cells) spheroids, shrank to about 10-20% of their volume in three days and then remained at that size for up to six days. In contrast, pure spheroids composed of live HeLa cells increased their volume by an order of magnitude over the same period. Survival of cells in spheroids was measured by the ability of individual spheroids to grow beyond a size implying a ten-fold increase. A caveat to be observed is to correct survival for cellular multiplicity, i.e. reduce survival values to compensate for more than one colony former at the time of irradiation. The system of spheroids floating and growing in nutrient medium provides a selective system for evaluating growth of HeLa, and by implication, other neoplastic cells, without interference from (overgrowth by) normal fibroblasts. Thus it is possible to discriminate between normal and neoplastic cells by virtue of whether or not cells grow in suspension. Such a system seems ideal for testing novel strategies (radiation in combination with chemicals), in an in vivo-like environment.
  • Prostatic irradiation-induced sexual dysfunction: A review and multidisciplinary guide to management in the radical radiotherapy era (Part III on Psychosexual Therapy and the Masculine Self-Esteem)

    Ramirez-Fort, Marigdalia K.; Suarez, Paula; Carrion, Margely; Weiner, Daniel; Postl, Claire; Arribas, Ricardo; Sayyah, Mehdi; Forta, Digna V.; Niaz, M. Junaid; Feily, Amir; et al. (VM Media SP. zo.o VM Group SK, 2020-07)
    Psychological morbidity, sexuality, and health/system information have been identified as the highest areas of support needs in patients undergoing management of their prostate cancer (PCa). Management of a patient's sexual function prior to, during and after PCa radiotherapy requires multidisciplinary coordination of care between radiation oncologists, urologists, dermatologists, pharmacists, and psychiatrists. The finale of this three-part review provides a framework for clinicians to better understand the role of mental healthcare providers in the management of sexual toxicities associated with prostatic radiotherapy. The authors recommend that patients be referred for psychological evaluation and possibly to individual, couples or group general or cognitive behavioral sex therapy at the time of their PCa diagnosis, for a more specialized focus on management of sexual toxicities and sexual recovery. The importance and implications of the masculine self-esteem, sexual orientation, gender identification, cultural expectations, relationship status and patient education are reviewed. Well-informed patients tend to have a better quality of life outcomes compared to patients that take on a passive role in their cancer management.
  • Prostatic irradiation-induced sexual dysfunction: A review and multidisciplinary guide to management in the radical radiotherapy era (Part II on Urological Management)

    Rogers, Marc J.; Ramirez-Fort, Marigdalia K.; Kashanian, James A.; Broster, Seth A.; Matta, Jaime; Mahase, Sean S.; Fort, Digna V.; Niaz, M. Junaid; McClelland, Shearwood; Bander, Neil H.; et al. (VM Media SP. zo.o VM Group SK, 2020-07)
    Prostate cancer is the most common malignancy in men and the second leading cause of cancer-related death in men. Radiotherapy is a curative option that is administered via external beam radiation, brachytherapy, or in combination. Sexual dysfunction is a common toxicity following radiotherapy, similar to men undergoing radical prostatectomy, but the etiology is different. The pathophysiology of radiation-induced sexual dysfunction is multi-factorial, and the toxicity is a major cause of impaired quality of life among long-term prostate cancer survivors. Management of a patient's sexual function during and after radiotherapy requires multidisciplinary coordination of care between radiation oncology, urology, psychiatry, pharmacy, and dermatology. This review provides a framework for clinicians to better understand prostatic radiotherapy-induced sexual dysfunction diagnosis, evaluation, and a patient-centered approach to toxicity preventive strategies and management.
  • Prostatic irradiation-induced sexual dysfunction: a review and multidisciplinary guide to management in the radical radiotherapy era (Part I defining the organ at risk for sexual toxicities)

    Ramirez-Fort, Marigdalia K.; Rogers, Marc J.; Santiago, Roberto; Mahase, Sean S.; Mendez, Melissa; Zheng, Yi; Kong, Xiang; Kashanian, James A.; Niaz, M. Junaid; McClelland, Shearwood; et al. (VM Media SP. zo.o VM Group SK, 2020-05)
    Prostate cancer is the most common malignancy and the second leading cause of cancer-related death in men. Radiotherapy is a curative option that is administered via external beam radiation, brachytherapy, or in combination. Erectile, ejaculatory and orgasm dysfunction(s) is/are known potential and common toxicities associated with prostate radiotherapy. Our multidisciplinary team of physicians and/or scientists have written a three (3) part comprehensive review of the pathogenesis and management radiation-induced sexual dysfunction. Part I reviews pertinent anatomy associated with normal sexual function and then considers the pathogenesis of prostate radiation-induced sexual toxicities. Next, our team considers the associated radiobiological (including the effects of time, dose and fractionation) and physical (treatment planning and defining a novel Organ at Risk (OAR)) components that should be minded in the context of safe radiation treatment planning. The authors identify an OAR (i.e., the prostatic plexus) and provide suggestions on how to minimize injury to said OAR during the radiation treatment planning process.
  • Follicular Transplantation, Microneedling, and Adjuvant Narrow-band Ultraviolet-B Irradiation as Cost-Effective Regimens for Palmar-Plantar Vitiligo: A Pilot Study

    Feily, Amir; Firoozifard, Abdollah; Sokhandani, Toktam; Elosegui-Rodriguez, Perla; Perez-Rivera, Evian; Lange, Christopher S; Hosseinpoor, Masoomeh; Ramirez-Fort, Marigdalia K (Springer Science and Business Media LLC, 2020-04-28)
    Treatment of refractory palmar-plantar vitiligo is particularly challenging because the skin in these regions has a limited supply of follicle-derived melanocytic stem cells. Autologous hair transplantation monotherapy is effective in some forms of vitiligo through the provision of melanocytic stem cells. CO2 laser followed by exposure to light (i.e., sunlight or narrow-band ultraviolet-B [nbUVB]) has independently shown to be an effective treatment strategy. Recently, it was found that the combination of hair transplantation and CO2 laser followed by nbUVB exposure had superior efficacy to either modality as monotherapy. Similar to CO2 laser, microneedling produces skin cell proliferation and releases pro-pigmentary cytokines. Given the important role of the cytokines in vitiliginous skin, microneedling may also be an effective therapeutic modality for refractory vitiligo. Herein, we conducted a pilot study to evaluate the efficacy of hair transplantation and CO2 laser or microneedling followed by nbUVB. Microneedling and fractional CO2 laser in combination with hair transplantation and nbUVB both demonstrated utility in the induction of repigmentation in refractory palmar-plantar vitiligo; however, a larger trial would be needed to determine a difference in treatment efficacy. Nonetheless, microneedling is cost-effective and requires minimal training; therefore, microneedling can be easily incorporated into standard dermatological practice.
  • Folate hydrolase‐1 (FOLH1) is a novel target for antibody‐based brachytherapy in Merkel cell carcinoma

    Ramirez‐Fort, M. K.; Meier‐Schiesser, B.; Lachance, K.; Mahase, S. S.; Church, C. D.; Niaz, M. J.; Liu, H.; Navarro, V.; Nikolopoulou, A.; Kazakov, D. V.; et al. (Wiley, 2020-11-28)
    Backgrounds: Folate Hydrolase-1 (FOLH1; PSMA) is a type II transmembrane protein, luminally expressed by solid tumour neo-vasculature. Monoclonal antibody (mAb), J591, is a vehicle for mAb-based brachytherapy in FOLH1+ cancers. Brachytherapy is a form of radiotherapy that involves placing a radioactive material a short distance from the target tissue (e.g., on the skin or internally); brachytherapy is commonly accomplished with the use of catheters, needles, metal seeds and antibody or small peptide conjugates. Herein, FOLH1 expression in primary (p) and metastatic (m) Merkel cell carcinoma (MCC) is characterized to determine its targeting potential for J591-brachytherapy. Materials & methods: Paraffin sections from pMCC and mMCC were evaluated by immunohistochemistry for FOLH1. Monte Carlo simulation was performed using the physical properties of conjugated radioisotope lutetium-177. Kaplan-Meier survival curves were calculated based on patient outcome data and FOLH1 expression. Results: Eighty-one MCC tumours were evaluated. 67% (54/81) of all cases, 77% (24/31) pMCC and 60% (30/50) mMCC tumours were FOLH1+. Monte Carlo simulation showed highly localized ionizing tracks of electrons emitted from the targeted neo-vessel. 42% (34/81) of patients with FOLH1+/- MCC had available survival data f or analysis. No significant differences in our limited data set were detected based on FOLH1 status (p = 0.4718; p = 0.6470), staining intensity score (p = 0.6966; p = 0.9841) or by grouping staining intensity scores (- and + vs. ++, +++, +++) (p = 0.8022; p = 0.8496) for MCC-specific survival or recurrence free survival, respectively. Conclusions: We report the first evidence of prevalent FOLH1 expression within MCC-associated neo-vessels, in 60-77% of patients in a large MCC cohort. Given this data, and the need for alternatives to immune therapies it is appropriate to explore the safety and efficacy o f FOLH1-targeted brachytherapy for MCC.
  • Preservation of male fertility in patients undergoing pelvic irradiation

    Ramirez-Fort, Marigdalia K; Kardoust-Parizi, Mehdi; Flannigan, Ryan; Bach, Phil; Gilman, Casey; Suarez, Paula; Fort, Digna; McClelland III, Shearwood; Lange, Christopher S.; Mulhall, John P.; et al. (VM Media Group sp. z o.o, 2024-01-08)
    As the number of cancer survivors increases, so does the demand for preserving male fertility after radiation. It is important for healthcare providers to understand the pathophysiology of radiation-induced testicular injury, the techniques of fertility preservation both before and during radiation, and their role in counseling patients on the risks to their fertility and the means of mitigating these risks. Impaired spermatogenesis is a known testicular toxicity of radiation in both the acute and the late settings, as rapidly dividing spermatogonial germ cells are exquisitely sensitive to irradiation. The threshold for spermatogonial injury and subsequent impairment in spermatogenesis is ~ 0.1 Gy and the severity of gonadal injury is highly dose-dependent. Total doses < 4 Gy may allow for recovery of spermatogenesis and fertility potential, but with larger doses, recovery may be protracted or impossible. All patients undergoing gonadotoxic radiation therapy should be counseled on the possibility of future infertility, offered the opportunity for semen cryopreservation, and offered referral to a fertility specialist. In addition to this, every effort should be made to shield the testes (if not expected to contain tumor) during therapy.
  • Recycling of Previously Transplanted Hair: A Novel Indication for Follicular Unit Extraction

    Mohebipour, Alireza; Gianfaldoni, Serena; Lotti, Torello; Ramirez-Fort, Marigdalia K.; Lange, Christopher S.; Sadeghi-Bazargani, Homayoun; Wollina, Uwe; Tchernev, Georgi; Feily, Amir (Scientific Foundation SPIROSKI, 2018-06-17)
    Background: Hair transplantation has enhanced the realm of procedural dermatology. Before the advent of follicular transplantation, androgenetic alopecia was a difficult disease to manage, as there is a limited armamentarium of topical and systemic pharmaceuticals. However, as with other novel surgical procedures, there is a steep learning curve, that may result in poor transplantation or cosmesis. Case report: We present a case of androgenetic alopecia, where previously, poorly implanted hairs were recycled by follicular unit extraction to increase hair density at the vertex of the scalp, which resulted in improved cosmesis and patient satisfaction. Conclusion: We have demonstrated that re-transplantation is not only feasible but is effective; therefore redesigning of previous transplantations should be considered as a possible indication follicle unit extraction, particularly in the setting of scarce follicular reserves. The utility of our recycling method may also inspire hope in patients that have undergone failed or unsatisfactory hair transplantations.
  • Melanoma Induces Endothelial Folate Hydrolase-1 (FOLH1) Expression and Facilitated Internalization of Immunotheragnostic Agent, J591

    Ramirez-Fort, M.K.; Meier, B.; Vissicchio, J.R.; Moy, J.; Liu, H.; Contassot, E.; Robinson, B.D.; Navarro, V.; Kim, S.; Leconet, W.; et al. (Elsevier BV, 2016-10)
  • Necessity of Hippocampal Neurogenesis for the Therapeutic Action of Antidepressants in Adult Nonhuman Primates

    Perera, Tarique D.; Dwork, Andrew J.; Keegan, Kathryn A.; Thirumangalakudi, Lakshmi; Lipira, Cecilia M.; Joyce, Niamh; Lange, Christopher; Higley, J. Dee; Rosoklija, Gorazd; Hen, Rene; et al. (Public Library of Science (PLoS), 2011-04-15)
    Background: Rodent studies show that neurogenesis is necessary for mediating the salutary effects of antidepressants. Nonhuman primate (NHP) studies may bridge important rodent findings to the clinical realm since NHP-depression shares significant homology with human depression and kinetics of primate neurogenesis differ from those in rodents. After demonstrating that antidepressants can stimulate neurogenesis in NHPs, our present study examines whether neurogenesis is required for antidepressant efficacy in NHPs. MATERIALS/METHODOLOGY: Adult female bonnets were randomized to three social pens (N = 6 each). Pen-1 subjects were exposed to control-conditions for 15 weeks with half receiving the antidepressant fluoxetine and the rest receiving saline-placebo. Pen-2 subjects were exposed to 15 weeks of separation-stress with half receiving fluoxetine and half receiving placebo. Pen-3 subjects 2 weeks of irradiation (N = 4) or sham-irradiation (N = 2) and then exposed to 15 weeks of stress and fluoxetine. Dependent measures were weekly behavioral observations and postmortem neurogenesis levels. Results: Exposing NHPs to repeated separation stress resulted in depression-like behaviors (anhedonia and subordinance) accompanied by reduced hippocampal neurogenesis. Treatment with fluoxetine stimulated neurogenesis and prevented the emergence of depression-like behaviors. Ablation of neurogenesis with irradiation abolished the therapeutic effects of fluoxetine. Non-stressed controls had normative behaviors although the fluoxetine-treated controls had higher neurogenesis rates. Across all groups, depression-like behaviors were associated with decreased rates of neurogenesis but this inverse correlation was only significant for new neurons in the anterior dentate gyrus that were at the threshold of completing maturation. Conclusion: We provide evidence that induction of neurogenesis is integral to the therapeutic effects of fluoxetine in NHPs. Given the similarity between monkeys and humans, hippocampal neurogenesis likely plays a similar role in the treatment of clinical depression. Future studies will examine several outstanding questions such as whether neuro-suppression is sufficient for producing depression and whether therapeutic neuroplastic effects of fluoxetine are specific to antidepressants.
  • Extracellular Matrix (ECM) and Cytoskeletal Modulation of Cellular Radiosensitivity

    Stevenson, Abraham F. G.; Lange, Christopher S. (Informa UK Limited, 2009-07-08)
    Modulation of radiosensitivity by components of the extracellular matrix (ECM) and cytoskeletal elements has not been adequately studied. Although differences in the radiosensitivities of cells grown as monolayers, as spheroids, or grown in vitro in animal models are known, explanations have in the past neglected possible influences by the ECM and cytoskeleton. Using collagen gel cultures, it is shown that the fibrillar component of the ECM (which is responsible for cell anchorage) induces shifts in radiosensitivity. The effect is critically dependent on the affinity of the cell type towards collagen. The shifts in radiosensitivity induced by ECM alteration are manifested as changed Dq values. By applying four specific cytoskeletal poisons which either stabilize or destabilize specific cytoskeletal elements, the involvement of microfilaments and microtubuli was qualitatively appraised. Cytochalasin B, which destabilizes microfilaments (by preventing polymerization), caused a significant rise in radioresistance. This rise was due to increased D0. Although the cellular morphological change accompanying cytochalasin B treatment was essentially similar to that obtained with trypsin, the respective shifts in radioresponses were qualitatively different and opposite, suggesting differences in mechanism of action.
  • Hybrid spheroids as a tool for prediction of radiosensitivity in tumor therapy.

    Djordjevic, Bozidar; Lange, Christopher S (2004-05)
    Optimization in radiotherapy may be conceivably achieved by individualized treatment regimens. For this, the radiosensitivity of the tumor cells to be treated must be known. A method is presented to show that the effect of radiation on tumor cells in spheroids can be quantitatively evaluated without complicated cell determinations of spheroid composition. This evaluation is based on the dynamics of inactivation of the colony forming ability of whole spheroids composed chiefly of non-transformed diploid fibroblasts and a minority of HeLa "test" cells. Here, spheroids of identical composition, but of different sizes are inactivated proportional to their sizes, thus obviating the need for tedious single cell procedures. The use of spheroids of different sizes permits the deduction of dose-effect relationships, and the innate radiosensitivity of tumors cells. This is a novel method for measuring the radio and chemosensitivity of tumors in primary culture, i.e. cells directly isolated from tumors.
  • Clonogenic Inactivation of Colon Cancer-derived Cells Treated with 5-Fluorouracil and Indomethacin in Hybrid Spheroids

    Djordjevic, Bozidar; Lange, Christopher S.; Schwartz, Michael S.; Rotman, Marvin (MJS Publishing, Medical Journals Sweden AB, 1998-07-08)
    The clonogenic hybrid spheroid assay has been used to determine the toxicity of 5-fluorouracil (5-FU), alone or in combination with indomethacin, in LoVo cells (a human colon adenocarcinoma line). The principal finding was that 5-FU toxicity, determined as loss of colony-forming ability, increased as a function of dose (concentration x duration of exposure), and that indomethacin causes a generalized alleviation of 5-FU toxicity, but only if given concurrently with 5-FU. The implications of these findings in the control of cancer cells by 5-FU are discussed.

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