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1.
Acta Neurochir (Wien) ; 166(1): 246, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831229

RESUMO

BACKGROUND: Endoscopic spine surgery has recently grown in popularity due to the potential benefits of reduced pain and faster recovery time as compared to open surgery. Biportal spinal endoscopy has been successfully applied to lumbar disc herniations and lumbar spinal stenosis. Obesity is associated with increased risk of complications in spine surgery. Few prior studies have investigated the impact of obesity and associated medical comorbidities with biportal spinal endoscopy. METHODS: This study was a prospectively collected, retrospectively analyzed comparative cohort design. Patients were divided into cohorts of normal body weight (Bone Mass Index (BMI)18.0-24.9), overweight (BMI 25.0-29.9) and obese (BMI > 30.0) as defined by the World Health Organization (WHO). Patients underwent biportal spinal endoscopy by a single surgeon at a single institution for treatment of lumbar disc herniations and lumbar spinal stenosis. Demographic data, surgical complications, and patient-reported outcomes were analyzed. Statistics were calculated amongst treatment groups using analysis of variance and chi square where appropriate. Statistical significance was determined as p < 0.05. RESULTS: Eighty-four patients were followed. 26 (30.1%) were normal BMI, 35 (41.7%) were overweight and 23 (27.4%) were obese. Patients with increasing BMI had correspondingly greater American Society of Anesthesiologist (ASA) scores. There were no significant differences in VAS Back, VAS Leg, and ODI scores, or postoperative complications among the cohorts. There were no cases of surgical site infections in the cohort. All cohorts demonstrated significant improvement up to 1 year postoperatively. CONCLUSIONS: This study demonstrates that obesity is not a risk factor for increased perioperative complications with biportal spinal endoscopy and has similar clinical outcomes and safety profile as compared to patients with normal BMI. Biportal spinal endoscopy is a promising alternative to traditional techniques to treat common lumbar pathology.


Assuntos
Índice de Massa Corporal , Descompressão Cirúrgica , Endoscopia , Vértebras Lombares , Obesidade , Estenose Espinal , Humanos , Obesidade/cirurgia , Obesidade/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Descompressão Cirúrgica/métodos , Descompressão Cirúrgica/efeitos adversos , Vértebras Lombares/cirurgia , Estenose Espinal/cirurgia , Idoso , Resultado do Tratamento , Adulto , Estudos Retrospectivos , Endoscopia/métodos , Endoscopia/efeitos adversos , Deslocamento do Disco Intervertebral/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos de Coortes
2.
Spine Surg Relat Res ; 6(6): 671-680, 2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36561152

RESUMO

Introduction: Surgical management of degenerative lumbar spine disorders is effective at improving patient pain, disability, and quality of life; however, obtaining a durable posterolateral fusion after decompression remains a challenge. Interbody fusion technologies are viable means of improving fusion rates in the lumbar spine, specifically various graft materials including autograft, structural allograft, titanium, and polyether ether ketone. This study assesses the effectiveness of Tritanium posterolateral cage in the treatment of degenerative disk disease. Methods: Nearest-neighbor 1:1 matched control transforaminal lumbar interbody fusion with PEEK vs. Tritanium posterior lumbar (PL) cage interbody fusion patients were identified using propensity scoring from patients that underwent elective surgery for degenerative disk diseases. Line graphs were generated to compare the trajectories of improvement in patient-reported outcomes (PROs) from baseline to 3 and 12 months postoperatively. The nominal data were compared via the χ2 test, while the continuous data were compared via Student's t-test. Results: The two groups had no difference regarding either the 3- or 12-month Euro-Qol-5D (EQ-5D), numeric rating scale (NRS) leg pain, and NRS back pain; however, the Tritanium interbody cage group had better Oswestry Disability Index (ODI) scores compared to the control group of the PEEK interbody cage at both 3 and 12 months (p=0.013 and 0.048). Conclusions: Our results indicate the Tritanium cage is an effective alternative to the previously used PEEK cage in terms of PROs, surgical safety, and radiological parameters of surgical success. The Tritanium cohort showed better ODI scores, higher fusion rates, lower subsidence, and lower indirect costs associated with surgical management, when compared to the propensity-matched PEEK cohort.

3.
Global Spine J ; : 21925682221124101, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050879

RESUMO

STUDY DESIGN: Retrospective review of multicentric data. OBJECTIVES: The modified 5-item frailty index is a relatively new tool to assess the post-operative complication risks. It has been recently shown a good predictive value after posterior lumbar fusion. We aimed to compare the predictive value of the modified 5-item frailty index in cervical, thoracic and lumbar surgery. METHODS: The American College of Surgeons - National Surgical Quality Improvement Program (ACS-NSQIP) Database 2015-2020 was used to identify patients who underwent elective posterior cervical, thoracic, or lumbar fusion surgeries for degenerative conditions. The mFI-5 score was calculated based on the presence of 5 co-morbidities: congestive heart failure within 30 days prior to surgery, insulin-dependent or noninsulin-dependent diabetes mellitus, chronic obstructive pulmonary disease or pneumonia, partially dependent or totally dependent functional health status at time of surgery, and hypertension requiring medication. Multivariate analysis was used to assess the independent impact of increasing mFI-5 score on the postoperative morbidity while controlling for baseline clinical characteristics. RESULTS: 53 252 patients were included with the mean age of 64.2 ± 7.2. 7946 suffered medical complications (14.9%), 1565 had surgical complications (2.9%), and 3385 were readmitted (6.3%), 363 died (.68%) within 30 days postoperative (6.3%). The mFI-5 items score was significantly associated with higher rates of complications, readmission, and mortality in cervical, thoracic, and lumbar posterior fusion surgery. CONCLUSION: The modified 5-item frailty score is a reliable tool to predict complications, readmission, and mortality in patients planned for elective posterior spinal fusion surgery.

4.
Surg Neurol Int ; 13: 359, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36128104

RESUMO

Background: Preoperative optimization in patients undergoing posterior spinal fusion is essential to limit the number and severity of postoperative complications. Here, we, additionally, evaluated the impact of hypoalbuminemia on morbidity and mortality after posterior spinal fusion surgery. Methods: This retrospective analysis was performed using data from a prospective multicentric database (ACSNSQIP:2015-2020) regarding patients undergoing posterior spinal fusions. Factors studied included; baseline demographics and 30-day postoperative complications (i.e., reoperations, readmissions, and mortality rates). Results: There were 6805 patients who met the inclusion criteria. They averaged 62 years of age and had an average BMI of 30.2. Within the 30-day postoperative period, 634 (9.3%) sustained complications; 467 (6.9%) were readmitted, 263 (3.9%) required reoperations, and 37 (0.5%) expired. Although multiple preoperative risk factors were analyzed, hypoalbuminemia, severe hypoalbuminemia, and dialysis were the strongest independent risk factors associated with complications (i.e., reoperations, readmissions, and mortality). Conclusion: Hypoalbuminemia, severe hypoalbuminemia, and dialysis were significant predictors for morbidity and mortality after posterior spinal fusion surgery.

6.
World Neurosurg ; 137: 350-356, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32032785

RESUMO

BACKGROUND: Chronic subdural hematoma evacuation can be achieved in select patients through bedside placement of the Subdural Evacuation Port System (SEPS; Medtronic, Inc., Dublin, Ireland). This procedure involves drilling a burr hole at the thickest part of the hematoma. Identifying this location is often difficult, given the variable tilt of available imaging and distant anatomic landmarks. This paper evaluates the feasibility and accuracy of a bedside navigation system that relies on visible light-based 3-dimensional (3D) scanning and image registration to a pre-procedure computed tomography scan. The information provided by this system may increase accuracy of the burr hole location. METHODS: In Part 1, the accuracy of this system was evaluated using a rigid 3D printed phantom head with implanted fiducials. In Part 2, the navigation system was tested on 3 patients who underwent SEPS placement. RESULTS: The error in registration of this system was less than 2.5 mm when tested on a rigid 3D printed phantom head. Fiducials located in the posterior aspect of the head were difficult to reliably capture. For the 3 patients who underwent 5 SEPS placements, the distance between anticipated SEPS burr hole location based on registration and actual burr hole location was less than 1cm. CONCLUSIONS: A bedside cranial navigation system based on 3D scanning and image registration has been introduced. Such a system may increase the success rate of bedside procedures, such as SEPS placement. However, technical challenges such as the ability to scan hair and practical challenges such as minimization of patient movement during scans must be overcome.


Assuntos
Craniotomia/métodos , Hematoma Subdural Crônico/cirurgia , Imageamento Tridimensional , Neuronavegação , Humanos , Modelos Anatômicos , Procedimentos Neurocirúrgicos/métodos , Impressão Tridimensional , Tomografia Computadorizada por Raios X
7.
IEEE ASME Trans Mechatron ; 25(3): 1432-1443, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33746503

RESUMO

Open surgical approaches are still often employed in neurosurgery, despite the availability of neuroendoscopic approaches that reduce invasiveness. The challenge of maneuvering instruments at the tip of the endoscope makes neuroendoscopy demanding for the physician. The only way to aim tools passed through endoscope ports is to tilt the entire endoscope; but, tilting compresses brain tissue through which the endoscope passes and can damage it. Concentric tube robots can provide necessary dexterity without endoscope tilting, while passing through existing ports in the endoscope and carrying surgical tools in their inner lumen. In this paper we describe the mechatronic design of a new concentric tube robot that can deploy two concentric tube manipulators through a standard neuroendoscope. The robot uses a compact differential drive and features embedded motor control electronics and redundant position sensors for safety. In addition to the mechatronic design of this system, this paper contributes experimental validation in the context of colloid cyst removal, comparing our new robotic system to standard manual endoscopy in a brain phantom. The robotic approach essentially eliminated endoscope tilt during the procedure (17.09° for the manual approach vs. 1.16° for the robotic system). The robotic system also enables a single surgeon to perform the procedure - typically in a manual approach one surgeon aims the endoscope and another operates the tools delivered through its ports.

8.
Oper Neurosurg (Hagerstown) ; 18(3): 339-346, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31232434

RESUMO

BACKGROUND: The concept of the S2-alar-iliac (S2AI) screw was developed approximately one decade ago and has rapidly become an important component of spinal arthrodesis. Two challenges to placing S2AI screws are gaining an intuition for free-hand screw placement trajectory and acquisition of the appropriate radiograph to both guide screw placement and diagnose misplacement. OBJECTIVE: To present the design and manufacture of an S2AI screw placement simulator and teaching module that addresses both challenges. METHODS: This simulator involves using a 3D printer to create a life-sized pelvis. Participants first used this print to practice placing free-hand S2AI screws. Then participants used another print to practice taking radiographs showing the posterior superior iliac spine-anterior superior iliac spine corridor (teardrop) view. RESULTS: The accuracy of screw placement increased from 17 to 80% on the left side and 7 to 100% on the right side. The number of radiographs taken by each participant to obtain the teardrop view decreased after practice with the simulator compared to baseline. CONCLUSION: Practice with the S2AI simulator led to an improved intuition of an appropriate free-hand S2AI screw trajectory and a decrease in the number of radiographs needed for obtaining the correct diagnostic view.


Assuntos
Sacro , Fusão Vertebral , Parafusos Ósseos , Humanos , Ílio/diagnóstico por imagem , Ílio/cirurgia , Impressão Tridimensional
9.
World Neurosurg ; 127: 20-23, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30928598

RESUMO

BACKGROUND: Sports-related structural brain injury (SRSBI) is a rare, but potentially catastrophic, injury. Limited data exist outlining its epidemiology, pathophysiology, and outcomes. We have presented a case of an epidural hematoma (EDH) that occurred during a high school soccer game. CASE DESCRIPTION: A 16-year-old boy had experienced a head-to-ball collision and head-to-head collision with another player. He denied loss of consciousness, endorsed retrograde amnesia, and complained of a minor headache. On the sidelines, he subsequently passed brief orientation and physical exertion tests. However, on returning to play, he experienced blurry vision, along with headache and nausea/vomiting. At the local hospital, he was found to have a 2.6-cm right frontal EDH. After transfer to our institution, increasing somnolence was noted, prompting emergent evacuation of the EDH. His postoperative course was unremarkable, and he was discharged on postoperative day 2. At the 2-week and 3-month follow-up visits, he did not express any complaints or residual deficits and was cleared for full sporting activity. CONCLUSIONS: The present case highlights one of the few SRSBIs that have occurred in soccer. Because of their rarity and severity, a concerted effort should be made to report these cases of SRSBIs regarding the mechanism, postcollision symptoms, and long-term outcomes.


Assuntos
Traumatismos em Atletas/complicações , Lesões Encefálicas/etiologia , Hematoma Epidural Craniano/etiologia , Adolescente , Traumatismos em Atletas/patologia , Lesões Encefálicas/patologia , Hematoma Epidural Craniano/patologia , Humanos , Masculino , Instituições Acadêmicas , Futebol
10.
Oper Neurosurg (Hagerstown) ; 16(4): 496-502, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29873765

RESUMO

BACKGROUND: External ventricular drain (EVD) placement is one of the most commonly performed procedures in neurosurgery, frequently by the junior neurosurgery resident. Simulators for EVD placement are often costly, time-intensive to create, and complicated to set up. OBJECTIVE: To describe creation of a simulator that is inexpensive, time-efficient, and simple to set up. METHODS: This simulator involves printing a hollow head using a desktop 3-dimensional (3D) printer. This head is registered to a commercially available image-guidance system. A total of 11 participants volunteered for this simulation module. EVD placement was assessed at baseline, after verbal teaching, and after live 3D view instruction. RESULTS: Accurate placement of an EVD on the right side at the foramen of Monro or the frontal horn of the lateral ventricle increased from 44% to 98% with training. Similarly, accurate placement on the left increased from 42% to 85% with training. CONCLUSION: During participation in the simulation, accurate placement of EVDs increased significantly. All participants believed that they had a better understanding of ventricular anatomy and that this module would be useful as a teaching tool for neurosurgery interns.


Assuntos
Competência Clínica , Análise Custo-Benefício/métodos , Drenagem/métodos , Imageamento Tridimensional/métodos , Procedimentos Neurocirúrgicos/métodos , Impressão Tridimensional , Competência Clínica/economia , Competência Clínica/normas , Análise Custo-Benefício/normas , Drenagem/economia , Drenagem/normas , Humanos , Imageamento Tridimensional/economia , Imageamento Tridimensional/normas , Internato e Residência/economia , Internato e Residência/métodos , Internato e Residência/normas , Procedimentos Neurocirúrgicos/economia , Procedimentos Neurocirúrgicos/normas , Impressão Tridimensional/economia , Impressão Tridimensional/normas , Fatores de Tempo , Tomografia Computadorizada por Raios X/economia , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/normas
11.
Neurosurg Focus ; 45(4): E2, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30269595

RESUMO

There is inadequate pediatric neurosurgical training to meet the growing burden of disease in low- and middle-income countries (LMIC). Subspecialty expertise in the management of hydrocephalus and spina bifida-two of the most common pediatric neurosurgical conditions-offers a high-yield opportunity to mitigate morbidity and avoid unnecessary death. The CURE Hydrocephalus and Spina Bifida (CHSB) fellowship offers an intensive subspecialty training program designed to equip surgeons from LMIC with the state-of-the-art surgical skills and equipment to most effectively manage common neurosurgical conditions of childhood. Prospective fellows and their home institution undergo a comprehensive evaluation before being accepted for the 8-week training period held at CURE Children's Hospital of Uganda (CCHU) in Mbale, Uganda. The fellowship combines anatomy review, treatment paradigms, a flexible endoscopic simulation lab, daily ward and ICU rounds, radiology rounds, and clinic exposure. The cornerstone of the fellowship is the unique operative experience that includes a high volume of endoscopic third ventriculostomy with choroid plexus cauterization, myelomeningocele closure, and ventriculoperitoneal shunting, among many other procedures performed at CCHU. Upon completion, fellows return to their home institution to establish or rejuvenate a robust pediatric practice as part of a worldwide network of CHSB trainees committed to the care of underserved children. To date, the fellowship has graduated 33 surgeons from 20 different LMIC who are independently performing thousands of hydrocephalus and spina bifida operations each year.


Assuntos
Bolsas de Estudo , Hidrocefalia/cirurgia , Neurocirurgia/educação , Pediatria/educação , Disrafismo Espinal/cirurgia , Plexo Corióideo/cirurgia , Países em Desenvolvimento , Bolsas de Estudo/métodos , Recursos em Saúde , Humanos , Modelos Educacionais , Terceiro Ventrículo/cirurgia , Uganda , Ventriculostomia/métodos
12.
Neuro Oncol ; 17(1): 70-80, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25053853

RESUMO

BACKGROUND: 3-bromopyruvate (3-BrPA) and dichloroacetate (DCA) are inhibitors of cancer-cell specific aerobic glycolysis. Their application in glioma is limited by 3-BrPA's inability to cross the blood-brain-barrier and DCA's dose-limiting toxicity. The safety and efficacy of intracranial delivery of these compounds were assessed. METHODS: Cytotoxicity of 3-BrPA and DCA were analyzed in U87, 9L, and F98 glioma cell lines. 3-BrPA and DCA were incorporated into biodegradable pCPP:SA wafers, and the maximally tolerated dose was determined in F344 rats. Efficacies of the intracranial 3-BrPA wafer and DCA wafer were assessed in a rodent allograft model of high-grade glioma, both as a monotherapy and in combination with temozolomide (TMZ) and radiation therapy (XRT). RESULTS: 3-BrPA and DCA were found to have similar IC50 values across the 3 glioma cell lines. 5% 3-BrPA wafer-treated animals had significantly increased survival compared with controls (P = .0027). The median survival of rats with the 50% DCA wafer increased significantly compared with both the oral DCA group (P = .050) and the controls (P = .02). Rats implanted on day 0 with a 5% 3-BrPA wafer in combination with TMZ had significantly increased survival over either therapy alone. No statistical difference in survival was noted when the wafers were added to the combination therapy of TMZ and XRT, but the 5% 3-BrPA wafer given on day 0 in combination with TMZ and XRT resulted in long-term survivorship of 30%. CONCLUSION: Intracranial delivery of 3-BrPA and DCA polymer was safe and significantly increased survival in an animal model of glioma, a potential novel therapeutic approach. The combination of intracranial 3-BrPA and TMZ provided a synergistic effect.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/metabolismo , Ácido Dicloroacético/administração & dosagem , Glioblastoma/metabolismo , Glicólise/efeitos dos fármacos , Piruvatos/administração & dosagem , Implantes Absorvíveis , Animais , Antineoplásicos/toxicidade , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/toxicidade , Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/radioterapia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Dacarbazina/toxicidade , Ácido Dicloroacético/toxicidade , Vias de Administração de Medicamentos , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos , Feminino , Glioblastoma/prevenção & controle , Glioblastoma/radioterapia , Humanos , Estimativa de Kaplan-Meier , Polímeros , Piruvatos/toxicidade , Ratos , Ratos Endogâmicos F344 , Temozolomida
14.
J Neurosurg ; 120(3): 662-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24359008

RESUMO

OBJECT: Over the past several years, there has been increasing interest in combining angiogenesis inhibitors with radiotherapy and temozolomide chemotherapy in the treatment of glioblastoma. Although the US FDA approved bevacizumab for the treatment of glioblastoma in 2009, the European Medicines Agency rejected its use due to its questionable impact on patient survival. One factor contributing to the failure of angiogenesis inhibitors to increase overall patient survival may be their inability to cross the blood-brain barrier. Here the authors examined in a 9L glioma model whether intracranial polymer-based delivery of the angiogenesis inhibitor minocycline potentiates the effects of both radiotherapy and temozolomide chemotherapy in increasing median survival. The authors also investigated whether the relative timing of minocycline polymer implantation with respect to radiotherapy affects the efficacy of radiotherapy. METHODS: Minocycline was incorporated into the biodegradable polymer polyanhydride poly(1,3-bis-[p-carboxyphenoxy propane]-co-[sebacic anhydride]) (CPP:SA) at a ratio of 50:50 by weight. Female Fischer 344 rats were implanted with 9L glioma on Day 0. The minocycline polymer was then implanted on either Day 3 or Day 5 posttumor implantation. Cohorts of rats were exposed to 20 Gy focal radiation on Day 5 or were administered oral temozolomide (50 mg/kg daily) on Days 5-9. RESULTS: Both minocycline polymer implantations on Days 3 and 5 increased survival from 14 days to 19 days (p < 0.001 vs control). Treatment with a combination of both minocycline polymer and radiotherapy on Day 5 resulted in a 139% increase in median survival compared with treatment with radiotherapy alone (p < 0.005). There was not a statistically significant difference in median survival between the group that received minocycline implanted on the same day as radiotherapy and the group that received minocycline polymer 2 days prior to radiotherapy. Lastly, treatment with a combination of minocycline polymer with oral temozolomide resulted in a 38% extension of median survival compared with treatment of oral temozolomide alone (p < 0.001). CONCLUSIONS: These results show that minocycline delivered locally potentiates the effects of both radiotherapy and oral temozolomide in increasing median survival in a rodent glioma model. More generally, these results suggest that traditional therapy in combination with local, as opposed to systemic, delivery of angiogenesis inhibitors may be able to increase median survival for patients with glioblastoma.


Assuntos
Neoplasias Encefálicas/terapia , Quimiorradioterapia/métodos , Dacarbazina/análogos & derivados , Gliossarcoma/terapia , Minociclina/farmacologia , Administração Oral , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Animais , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Terapia Combinada , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos/métodos , Feminino , Minociclina/uso terapêutico , Transplante de Neoplasias , Polímeros/farmacologia , Ratos , Ratos Endogâmicos F344 , Temozolomida
15.
Acad Med ; 88(6): 766-70, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23619061

RESUMO

During their preclinical course work, medical students must memorize and recall substantial amounts of information. Recent trends in medical education emphasize collaboration through team-based learning. In the technology world, the trend toward collaboration has been characterized by the crowdsourcing movement. In 2011, the authors developed an innovative approach to team-based learning that combined students' use of flashcards to master large volumes of content with a crowdsourcing model, using a simple informatics system to enable those students to share in the effort of generating concise, high-yield study materials. The authors used Google Drive and developed a simple Java software program that enabled students to simultaneously access and edit sets of questions and answers in the form of flashcards. Through this crowdsourcing model, medical students in the class of 2014 at the Johns Hopkins University School of Medicine created a database of over 16,000 questions that corresponded to the Genes to Society basic science curriculum. An analysis of exam scores revealed that students in the class of 2014 outperformed those in the class of 2013, who did not have access to the flashcard system, and a survey of students demonstrated that users were generally satisfied with the system and found it a valuable study tool. In this article, the authors describe the development and implementation of their crowdsourcing model for creating study materials, emphasize its simplicity and user-friendliness, describe its impact on students' exam performance, and discuss how students in any educational discipline could implement a similar model of collaborative learning.


Assuntos
Crowdsourcing , Educação de Graduação em Medicina/métodos , Modelos Educacionais , Materiais de Ensino
16.
Integr Biol (Camb) ; 5(2): 414-22, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23254624

RESUMO

Artesunate (ART) is widely used for the treatment of malaria, but the mechanisms of its effects on parasitized red blood cells (RBCs) are not fully understood. We investigated ART's influence on the dynamic deformability of ring-stage Plasmodium falciparum infected red blood cells (iRBCs) in order to elucidate its role in cellular mechanobiology. The dynamic deformability of RBCs was measured by passing them through a microfluidic device with repeated bottleneck structures. The quasi-static deformability measurement was performed using micropipette aspiration. After ART treatment, microfluidic experiments showed 50% decrease in iRBC transit velocity whereas only small (~10%) velocity reduction was observed among uninfected RBCs (uRBCs). Micropipette aspiration also revealed ART-induced stiffening in RBC membranes. These results demonstrate, for the first time, that ART reduces the dynamic and quasi-static RBC deformability, which may subsequently influence blood circulation through the microvasculature and spleen cordal meshwork, thus adding a new aspect to artesunate's mechanism of action.


Assuntos
Artemisininas/farmacologia , Eritrócitos/fisiologia , Eritrócitos/parasitologia , Fluidez de Membrana/fisiologia , Plasmodium falciparum/fisiologia , Antimaláricos/farmacologia , Artesunato , Células Cultivadas , Módulo de Elasticidade/efeitos dos fármacos , Módulo de Elasticidade/fisiologia , Eritrócitos/efeitos dos fármacos , Dureza/efeitos dos fármacos , Humanos , Fluidez de Membrana/efeitos dos fármacos
17.
Sci Rep ; 2: 614, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22937223

RESUMO

Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host.


Assuntos
Eritrócitos/metabolismo , Eritrócitos/parasitologia , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Membrana Celular/metabolismo , Humanos , Plasmodium falciparum/crescimento & desenvolvimento , Temperatura
18.
Lab Chip ; 12(21): 4441-8, 2012 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-22955573

RESUMO

We demonstrate continuous-flow biomolecule concentration and detection in a microfabricated slanted sieving structure, which we term a herringbone nanofilter array (HNA). The HNA structure consists of periodically-patterned deep and shallow nanoslits meeting at right angles. In addition to concentration, we can discriminate different sized analytes by mixing a fluorescent probe with the sample and measuring the extent of the concentrating effect. Using this principle, we interrogate biomolecular interactions, including protein-DNA binding, protein-protein interaction and antibody-antigen binding. The final example demonstrates a novel method to perform a homogeneous immunoassay for detecting a disease marker, human C-reactive protein (CRP), using fluorescent-labeled antibodies at clinically relevant concentrations. The signal amplification potential and continuous flow operation provide a significant advantage over other microfluidic batch separation techniques for the easy integration of this device into a common point-of-care diagnostic platform.


Assuntos
Anticorpos/análise , Antígenos/análise , Proteína C-Reativa/análise , DNA/análise , Técnicas Analíticas Microfluídicas/métodos , Nanotecnologia/métodos , Reações Antígeno-Anticorpo , Fluorescência , Humanos , Técnicas Analíticas Microfluídicas/instrumentação , Nanotecnologia/instrumentação
19.
Biomaterials ; 33(23): 5768-75, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22591609

RESUMO

Primary malignant brain tumors (BT) are the most common and aggressive malignant brain tumor. Treatment of BTs is a daunting task with median survival just at 21 months. Methods of localized delivery have achieved success in treating BT by circumventing the blood brain barrier and achieving high concentrations of therapeutic within the tumor. The capabilities of localized delivery can be enhanced by utilizing mirco-electro-mechanical systems (MEMS) technology to deliver drugs with precise temporal control over release kinetics. An intracranial MEMS based device was developed to deliver the clinically utilized chemotherapeutic temozolomide (TMZ) in a rodent glioma model. The device is a liquid crystalline polymer reservoir, capped by a MEMS microchip. The microchip contains three nitride membranes that can be independently ruptured at any point during or after implantation. The kinetics of TMZ release were validated and quantified in vitro. The safety of implanting the device intracranially was confirmed with preliminary in vivo studies. The impact of TMZ release kinetics was investigated by conducting in vivo studies that compared the effects of drug release rates and timing on animal survival. TMZ delivered from the device was effective at prolonging animal survival in a 9L rodent glioma model. Immunohistological analysis confirmed that TMZ was released in a viable, cytotoxic form. The results from the in vivo efficacy studies indicate that early, rapid delivery of TMZ from the device results in the most prolonged animal survival. The ability to actively control the rate and timing of drug(s) release holds tremendous potential for the treatment of BTs and related diseases.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Sistemas de Liberação de Medicamentos/instrumentação , Gliossarcoma/tratamento farmacológico , Animais , Antineoplásicos Alquilantes/farmacocinética , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/patologia , Dacarbazina/administração & dosagem , Dacarbazina/farmacocinética , Dacarbazina/uso terapêutico , Desenho de Equipamento , Feminino , Gliossarcoma/patologia , Ratos , Ratos Endogâmicos F344 , Temozolomida
20.
Lab Chip ; 11(6): 1065-73, 2011 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-21293801

RESUMO

Malaria resulting from Plasmodium falciparum infection is a major cause of human suffering and mortality. Red blood cell (RBC) deformability plays a major role in the pathogenesis of malaria. Here we introduce an automated microfabricated "deformability cytometer" that measures dynamic mechanical responses of 10(3) to 10(4) individual RBCs in a cell population. Fluorescence measurements of each RBC are simultaneously acquired, resulting in a population-based correlation between biochemical properties, such as cell surface markers, and dynamic mechanical deformability. This device is especially applicable to heterogeneous cell populations. We demonstrate its ability to mechanically characterize a small number of P. falciparum-infected (ring stage) RBCs in a large population of uninfected RBCs. Furthermore, we are able to infer quantitative mechanical properties of individual RBCs from the observed dynamic behavior through a dissipative particle dynamics (DPD) model. These methods collectively provide a systematic approach to characterize the biomechanical properties of cells in a high-throughput manner.


Assuntos
Eritrócitos/parasitologia , Citometria de Fluxo/métodos , Plasmodium falciparum/crescimento & desenvolvimento , Deformação Eritrocítica , Eritrócitos/fisiologia , Citometria de Fluxo/instrumentação , Humanos , Malária Falciparum/parasitologia , Microtecnologia , Pressão
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