Beyond medical knowledge: a didactic curriculum focused on knowledge, wisdom, and application.

OBJECTIVE: The aim of this study was to determine whether a flipped classroom curriculum coupled with case-based learning would improve residents' perceptions of the learning environment, improve education outcomes, and increase faculty engagement. Research suggests that active learning yields better educational results compared with passive learning. However, faculty are more comfortable providing lectures that require only passive participation from learners. METHODS: A council was created to identify issues with the current format of the resident didactic curriculum and to redesign the neurosurgical curriculum and conference per Accreditation Council for Graduate Medical Education (ACGME) requirements. Trends from the authors' 2022 and 2023 ACGME Resident Surveys were tracked to assess changes in the organizational learning environment. Surveys of resident participants were conducted to assess learner satisfaction. RESULTS: Between July 2022 and June 2023, the authors gathered 127 survey responses from neurosurgical residents. The majority of respondents, comprising 50.4% (n = 64), were postgraduate year (PGY)-4 and PGY-5 residents. Sixty-six percent (n = 84) reported that the new format ranked within the top third of sessions they had experienced. On analysis of trends from these 2022 and 2023 ACGME Resident Surveys, the authors observed a positive trajectory in various key components. Notably, there was an upward trend in achieving an appropriate balance between service and education, in the availability of protected time for structured learning, faculty engagement and interest in education, and amount of clinical and didactic teaching. CONCLUSIONS: The results of this study suggest that this innovative educational model can have a positive impact on residents' perceptions of the learning environment, their educational outcomes, and faculty engagement. As residency education continues to evolve, the flipped classroom model offers an exciting avenue for enhancing the quality of residency education.

Laser ablation of a sphenoid wing meningioma: A case report and review of the literature.

Background: Meningiomas are the most common primary central nervous system neoplasm in the United States. While the majority of meningiomas are benign, the World Health Organization (WHO) Grade I tumors, a not-insignificant proportion of tumors are in anatomically complex locations or demonstrate more aggressive phenotypes, presenting a challenge for local disease control with surgery and radiation. Laser interstitial thermal therapy (LITT) consists of stereotactic delivery of laser light for tumor ablation and is minimally invasive, requiring implantation of a laser fiber through a cranial burr hole. Herein, we demonstrate the first use of this technology in a progressive atypical sphenoid wing meningioma for a previously resected and irradiated tumor. Case Description: A 47-year-old female was diagnosed with a left-sided atypical meningioma, the WHO 2, of the sphenoid wing following acute worsening of bitemporal headache and dizziness. Given neurovascular involvement, a subtotal resection was performed, followed by stereotactic radiosurgery. Following progression 9 months from resection, the patient elected to proceed with LITT. The patient's postoperative course was uncomplicated and she remains progression free at 24 months following LITT. Conclusion: We present the first use of LITT for a sphenoid wing meningioma documented in the literature, which demonstrated enhanced disease control for a lesion that was refractory to both surgery and radiation. LITT could represent an additional option for local control of progressive meningiomas, even in locations that are challenging to access surgically. More evidence is needed regarding the technical nuances of LITT for lesions of the skull base.

Revisiting flow augmentation bypass for cerebrovascular atherosclerotic vaso-occlusive disease: Single-surgeon series and review of the literature.

OBJECTIVE: Despite advances in the nonsurgical management of cerebrovascular atherosclerotic steno-occlusive disease, approximately 15-20% of patients remain at high risk for recurrent ischemia. The benefit of revascularization with flow augmentation bypass has been demonstrated in studies of Moyamoya vasculopathy. Unfortunately, there are mixed results for the use of flow augmentation in atherosclerotic cerebrovascular disease. We conducted a study to examine the efficacy and long term outcomes of superficial temporal artery to middle cerebral artery (STA-MCA) bypass in patients with recurrent ischemia despite optimal medical management. METHODS: A single-institution retrospective review of patients receiving flow augmentation bypass from 2013-2021 was conducted. Patients with non-Moyamoya vaso-occlusive disease (VOD) who had continued ischemic symptoms or strokes despite best medical management were included. The primary outcome was time to post-operative stroke. Time from cerebrovascular accident to surgery, complications, imaging results, and modified Rankin Scale (mRS) scores were aggregated. RESULTS: Twenty patients met inclusion criteria. The median time from cerebrovascular accident to surgery was 87 (28-105.0) days. Only one patient (5%) had a stroke at 66 days post-op. One (5%) patient had a post-operative scalp infection, while 3 (15%) developed post-operative seizures. All 20 (100%) bypasses remained patent at follow-up. The median mRS score at follow up was significantly improved from presentation from 2.5 (1-3) to 1 (0-2), P = .013. CONCLUSIONS: For patients with high-risk non-Moyamoya VOD who have failed optimal medical therapy, contemporary approaches to flow augmentation with STA-MCA bypass may prevent future ischemic events with a low complication rate.

Quantifying the Opportunity Cost of Neurosurgical Resident Education.

BACKGROUND/OBJECTIVE: Education is at the core of neurosurgical residency, but little research in to the cost of neurosurgical education exists. This study aimed to quantify costs of resident education in an academic neurosurgery program using traditional teaching methods and the Surgical Autonomy Program (SAP), a structured training program. METHODS: SAP assesses autonomy by categorizing cases into zones of proximal development (opening, exposure, key section, and closing). All first-time, 1-level to 4-level anterior cervical discectomy and fusion (ACDF) cases between March 2014 and March 2022 from 1 attending surgeon were divided into 3 groups: independent cases, cases with traditional resident teaching, and cases with SAP teaching. Surgical times for all cases were collected and compared within levels of surgery between groups. RESULTS: The study found 2140 ACDF cases, with 1758 independent, 223 with traditional teaching, and 159 with SAP. For 1-level to 4-level ACDFs, teaching took longer than it did with independent cases, with SAP teaching adding additional time. A 1-level ACDF performed with a resident (100.1 ± 24.3 minutes) took about as long as a 3-level ACDF performed independently (97.1 ± 8.9 minutes). The average time for 2-level cases was 72.0 ± 18.2 minutes independently, 121.7 ± 33.7 minutes traditional, and 143.4 ± 34.9 minutes SAP, with significant differences among all groups. CONCLUSIONS: Teaching takes significant time compared with operating independently. There is also a financial cost to educating residents, because operating room time is expensive. Because attending neurosurgeons lose time to perform more surgeries when teaching residents, there is a need to acknowledge surgeons who devote time to training the next generation of neurosurgeons.

Construct validity of the Surgical Autonomy Program for the training of neurosurgical residents.

OBJECTIVE: There is no standard way in which physicians teach or evaluate surgical residents intraoperatively, and residents are proving to not be fully competent at core surgical procedures upon graduating. The Surgical Autonomy Program (SAP) is a novel educational model that combines a modified version of the Zwisch scale with Vygotsky's social learning theory. The objective of this study was to establish preliminary validity evidence that SAP is a reliable measure of autonomy and a useful tool for tracking competency over time. METHODS: The SAP breaks each surgical case into 4 parts, or zones of proximal development (ZPDs). Residents are evaluated on a 4-tier autonomy scale (TAGS scale) for each ZPD in every surgical case. Attendings were provided with a teaching session about SAP and identified appropriate ZPDs for surgical cases under their area of expertise. All neurosurgery residents at Duke University Hospital from July 2017 to July 2021 participated in this study. Chi-square tests and ordinal logistic regression were used for the analyses. RESULTS: Between 2017 and 2021, there were 4885 cases logged by 27 residents. There were 30 attendings who evaluated residents using SAP. Faculty completed evaluations on 91% of cases. The ZPD of focus directly correlated with year of residency (postgraduate year) (χ2 = 1221.1, df = 15, p < 0.001). The autonomy level increased with year of residency (χ2 = 3553.5, df = 15, p < 0.001). An ordinal regression analysis showed that for every year increase in postgraduate year, the odds of operating at a higher level of independence was 2.16 times greater (95% CI 2.11-2.21, p < 0.001). The odds of residents performing with greater autonomy was lowest for the most complex portion of the case (ZPD3) (OR 0.18, 95% CI 0.17-0.20, p < 0.001). Residents have less autonomy with increased case complexity (χ2 = 160.28, df = 6, p < 0.001). Compared with average cases, residents were more likely to operate with greater autonomy on easy cases (OR 1.44, 95% CI 1.29-1.61, p < 0.001) and less likely to do so on difficult cases (OR 0.72, 95% CI 0.67-0.77, p < 0.001). CONCLUSIONS: This study demonstrates preliminary evidence supporting the construct validity of the SAP. This tool successfully tracks resident autonomy and progress over time. The authors' smartphone application was widely used among surgical faculty and residents, supporting integration into the perioperative workflow. Wide implementation of SAP across multiple surgical centers will aid in the movement toward a competency-based residency education system.

Predictors of Blood Transfusion for Endoscopic Assisted Craniosynostosis Surgery.

ABSTRACT: Blood loss is a main cause of morbidity after craniofacial procedures. The purpose of this study is to identify the incidence and predictors for transfusion of blood products in the endoscopic assisted strip craniectomy population. Data was prospectively collected from a single-center multi-surgeon cohort of 78 consecutive patients who underwent endoscopic assisted strip craniectomy for craniosynostosis between July 2013 and December 2020. The authors reviewed patient and treatment characteristics and outcomes. Of the 78 patients, 26 patients were transfused yielding an overall rate of transfusion of 33%. The most common fused suture was sagittal (n = 42, 54%) followed by metopic (n = 15, 19%), multiple (n = 10, 13%), coronal (n = 7, 9%) and finally lambdoid (n = 4, 5%). On univariate analysis, patients' weight in the transfusion cohort were significantly lower than those who did not receive a transfusion (5.6 ± 1.1 versus 6.5 ± 1.1 kg, P = 0.0008). The transfusion group also had significantly lower preoperative hemoglobin compared to the non-transfusion group (10.6 versus 11.1, P = .049). Eleven percent patients admitted to step-down received a transfusion, whereas 39% of patients admitted to the pediatric intensive care unit received a transfusion ( P = 0.042). On multivariate analysis, only higher patient weight (operating room [OR] 0.305 [0.134, 0.693], P = 0.005) was protective against a transfusion, whereas colloid volume (OR 1.018 [1.003, 1.033], P = 0.019) predicted the need for a transfusion.Our results demonstrate that endoscopic craniosynostosis cases carry a moderate risk of transfusion. individuals with lower weight and those that receive colloid volume are also at elevated risk.

The Surgical Autonomy Program: A Pilot Study of Social Learning Theory Applied to Competency-Based Neurosurgical Education.

Over the last decade, strict duty hour policies, pressure for increased work related value units from faculty, and the apprenticeship model of education have coalesced to make opportunities for intraoperative teaching more challenging. Evidence is emerging that graduating residents are not exhibiting competence by failing to recognize major complications, and perform routine operations independently. In this pilot study, we combine Vygotsky's social learning theory with a modified version of the competency-based scale called TAGS to study 1 single operation, anterior cervical discectomy and fusion, with 3 individual residents taught by a single faculty member. In order for the 3 residents to achieve "Solo and Observe" in all 4 zones of proximal development, the number of cases required was 10 cases for postgraduate year (PGY)-3a, 19 cases for PGY 3b, and 22 cases for the PGY 2. In this pilot study, the time required to complete an independent 2-level anterior cervical discectomy and fusion by the residents correlated with the number of cases to reach competence. We demonstrate the Surgical Autonomy Program's ability to track neurosurgical resident's educational progress and the feasibility of using the Surgical Autonomy Program (SAP) to teach residents in the operating room and provide immediate formative feedback. Ultimately, the SAP represents a paradigm shift towards a modern, scalable competency-focused subspecialty teaching, evaluation and assessment tool that provides increases in resident's autonomy and metacognitive skills, as well as immediate formative feedback.

Quantitative analysis of a rare disease network's international contact database and E-repository provides insights into biobanking in the electronic consent era.

BACKGROUND: Castleman disease (CD) describes a group of rare and poorly understood lymphoproliferative disorders that include unicentric CD (UCD), Human Herpes Virus-8 (HHV8)-associated multicentric CD (HHV8 + MCD), and HHV8-negative/idiopathic MCD (iMCD). Efforts to advance research and drug discovery for CD have been slowed by challenges shared by other rare diseases, such as collecting and centralizing data and biospecimens for research. To collect disease characteristic data and identify individuals interested in contributing biospecimens for research, a global research organization - the Castleman Disease Collaborative Network (CDCN) - established an international Contact Database and electronic repository (E-repository). Herein, we performed analyses of these datasets to further characterize CD and gain insights into research biospecimen acquisition. RESULTS: Descriptive statistical analyses were performed on 891 participants from the Contact Database and 166 patients in the E-repository. The median age of patients at the time of enrollment in the Contact Database and E-repository was 42 ± 15.7 and 35 ± 14.8, respectively. The E-repository had increased representation from patients with MCD and the iMCD subtype compared to other sub-groups. Though the majority of participants were from the USA, a total of 49 countries on 6 continents were represented. Several patient characteristics in the Contact Database were associated with subsequent enrollment in the E-repository. There were significantly more MCD patients (p < 0.0001) and females (p = 0.002) enrolled in the E-repository compared to the Contact Database. Patient's year of birth, date of registration, preferred method of communication, and relationship to the patient were also significantly associated with enrollment in the e-Repository. CONCLUSIONS: This study of the largest- dataset of CD patients worldwide provides insights into disease phenotypes, characteristics of patients interested in contributing data and biospecimens for research, and methods for successfully acquiring data and biospecimens. Generally, the factors associated with enrollment in the E-repository represented severity of disease subtype, proximity to the research, and patient motivation. We hope that these findings and the sample documentation (e.g., electronic consent, recruitment materials) provided with this article will assist future rare disease efforts with overcoming hurdles.

Rehabilitación del paciente laringectomizado. Recomendaciones de la Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello / Rehabilitation of the laryngectomised patient. Recommendations of the Spanish Society of Otolaryngology and Head and Neck Surgery

La laringectomía total permanece como tratamiento fundamental para el carcinoma de laringe localmente avanzado asociándose a una mayor supervivencia. Sin embargo, supone para el paciente una serie de cambios, como la incapacidad de comunicarse verbalmente, la respiración o el cambio estético, que inciden en su calidad de vida y obligan a su rehabilitación integral. El presente documento ha sido elaborado por el grupo de trabajo de rehabilitación del paciente laringectomizado de la Comisión de Cabeza y Cuello y Base de Cráneo de la Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello con el objeto de unificar las recomendaciones sobre materiales, técnicas y medidas que aúnen la rehabilitación integral del paciente sometido a una laringectomía total para la mejora de su calidad de vida y está destinado a especialistas en otorrinolaringología, a profesionales relacionados con el cuidado del paciente laringectomizado total y también a los propios pacientes. Las recomendaciones del documento tienen como objetivo mejorar la atención del paciente al cual se le ha realizado una laringectomía total teniendo en cuenta las necesidades de personal y material, las consideraciones sobre los procedimientos necesarios antes de la cirugía, durante el propio acto quirúrgico y tras el alta hospitalaria del paciente. Se dan también recomendaciones específicas sobre los tipos de rehabilitación y seguimiento de la misma, así como la necesidad de llevar un registro de dichas actividades. Las recomendaciones expuestas pretenden ayudar a los profesionales sanitarios relacionados con el tratamiento de los pacientes laringectomizados totales a llevar a cabo la tarea de hacer que la vida de estos pacientes sea lo más parecida posible a la vida que llevaban antes de realizarse una laringectomía total

Total laryngectomy remains essential treatment for locally advanced laryngeal carcinoma, related to better survival rates. However, it involves changes for the patient, such as the inability to communicate verbally, breathing or aesthetic changes, which affect their quality of life and require comprehensive rehabilitation. This paper was written by the total laryngectomy rehabilitation workgroup of the National Head and Neck and Skull Base working committee of the Spanish Society of Otolaryngology and Head and Neck Surgery. The purpose of the article is to combine materials, surgical procedures and means towards the comprehensive rehabilitation of total laryngectomy patients, so that they can achieve a good quality of life. This paper is aimed at all health care professionals caring for total laryngectomy patients. It is also aimed at the patients themselves, as well as ENT surgeons. We have considered staffing and material needs, all procedures before, during and after surgery and after hospital discharge. There are also detailed recommendations about types of rehabilitation and follow-up, and the need for recording these events. The comprehensive rehabilitation total laryngectomy patients is very important if we want to improve their quality of life. The recommendations we mention aim to help the healthcare professionals involved in the treatment of total laryngectomy patients to help them achieve a good quality of life, as similar as possible to the life they led before surgery

Rehabilitation of the laryngectomised patient. Recommendations of the Spanish Society of Otolaryngology and Head and Neck Surgery. / Rehabilitación del paciente laringectomizado. Recomendaciones de la Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello.

Total laryngectomy remains essential treatment for locally advanced laryngeal carcinoma, related to better survival rates. However, it involves changes for the patient, such as the inability to communicate verbally, breathing or aesthetic changes, which affect their quality of life and require comprehensive rehabilitation. This paper was written by the total laryngectomy rehabilitation workgroup of the National Head and Neck and Skull Base working committee of the Spanish Society of Otolaryngology and Head and Neck Surgery. The purpose of the article is to combine materials, surgical procedures and means towards the comprehensive rehabilitation of total laryngectomy patients, so that they can achieve a good quality of life. This paper is aimed at all health care professionals caring for total laryngectomy patients. It is also aimed at the patients themselves, as well as ENT surgeons. We have considered staffing and material needs, all procedures before, during and after surgery and after hospital discharge. There are also detailed recommendations about types of rehabilitation and follow-up, and the need for recording these events. The comprehensive rehabilitation total laryngectomy patients is very important if we want to improve their quality of life. The recommendations we mention aim to help the healthcare professionals involved in the treatment of total laryngectomy patients to help them achieve a good quality of life, as similar as possible to the life they led before surgery.

International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease.

Human herpesvirus-8 (HHV-8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare and life-threatening disorder involving systemic inflammatory symptoms, polyclonal lymphoproliferation, cytopenias, and multiple organ system dysfunction caused by a cytokine storm often including interleukin-6. iMCD accounts for one third to one half of all cases of MCD and can occur in individuals of any age. Accurate diagnosis is challenging, because no standard diagnostic criteria or diagnostic biomarkers currently exist, and there is significant overlap with malignant, autoimmune, and infectious disorders. An international working group comprising 34 pediatric and adult pathology and clinical experts in iMCD and related disorders from 8 countries, including 2 physicians that are also iMCD patients, was convened to establish iMCD diagnostic criteria. The working group reviewed data from 244 cases, met twice, and refined criteria over 15 months (June 2015 to September 2016). The proposed consensus criteria require both Major Criteria (characteristic lymph node histopathology and multicentric lymphadenopathy), at least 2 of 11 Minor Criteria with at least 1 laboratory abnormality, and exclusion of infectious, malignant, and autoimmune disorders that can mimic iMCD. Characteristic histopathologic features may include a constellation of regressed or hyperplastic germinal centers, follicular dendritic cell prominence, hypervascularization, and polytypic plasmacytosis. Laboratory and clinical Minor Criteria include elevated C-reactive protein or erythrocyte sedimentation rate, anemia, thrombocytopenia or thrombocytosis, hypoalbuminemia, renal dysfunction or proteinuria, polyclonal hypergammaglobulinemia, constitutional symptoms, hepatosplenomegaly, effusions or edema, eruptive cherry hemangiomatosis or violaceous papules, and lymphocytic interstitial pneumonitis. iMCD consensus diagnostic criteria will facilitate consistent diagnosis, appropriate treatment, and collaborative research.

Taking Control of Castleman Disease: Leveraging Precision Medicine Technologies to Accelerate Rare Disease Research.

Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in "omics" technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and identifying novel therapies for iMCD. However, in order to leverage precision medicine approaches in rare diseases like CD, stakeholders need to overcome several challenges. To address these challenges, the Castleman Disease Collaborative Network (CDCN) was founded in 2012. In the past 3 years, the CDCN has worked to transform the understanding of the pathogenesis of CD, funded and initiated genomics and proteomics research, and united international experts in a collaborative effort to accelerate progress for CD patients. The CDCN's collaborative structure leverages the tools of precision medicine and serves as a model for both scientific discovery and advancing patient care.

Abundancia y diversidad de especies de Culicinae (Diptera: Culicidae) del Alto Orinoco, estado Amazonas, Venezuela / Abundance and species diversity of Culicinae (Diptera: Culicidae) from Alto Orinoco, Amazonas, Venezuela

Se realizó un estudio longitudinal en 18 comunidades o shabonos de las localidades Yanomami Ocamo y Mavaca del municipio Alto Orinoco entre Junio 1998 y Diciembre 2000 para caracterizar la fauna de culicinos. Se colocaron trampas CDC dentro de viviendas entre 1900 y 0600 horas a fin de capturar los mosquitos atraídos por personas protegidas por mosquiteros. Se capturaron un total de 4.635 culicinos pertenecientes a nueve géneros y 25 especies. Del total de especies identificadas, 18 especies (72%) constituyen nuevos registros para el estado Amazonas. Las especies más abundantes fueron Mansonia (Mansonia) titillans (48%), Aedes (Ochlerotatus) fulvus (16,9%) y Culex (Melanoconion) spissipes (12%). Se observaron correlaciones negativamente significativas entre precipitación, nivel del río y abundancia de Ma. titillans y Ae. fulvus. La abundancia y diversidad de especies resultó diferente entre comunidades. La mayor diversidad y abundancia se encontró en las comunidades Santa María de los Guaicas y Carlitos. El esfuerzo de captura, disponibilidad de criaderos y diversidad de hábitats en estas comunidades influye en esta diferencia con respecto a las otras comunidades. El presente constituye el primer y único estudio longitudinal realizado en el estado Amazonas para caracterizar la fauna de culicinos, la cual incluye especies de importancia en salud pública.

A longitudinal study was conducted in 18 communities or "shabonos" in the Yanomami inhabited Ocamo and Mavaca regions in the Alto Orinoco municipality between June 1998 and December 2000. CDC light traps were placed inside dwellings to catch mosquitoes attracted to humans protected by mosquito nets between 1900 and 0600 hours. A total of 4.635 culicines belonging to 9 genera and 25 species were captured. Of the total number of species identified, 18 (72%) are new reports for Amazonas state. The most abundant species were Mansonia (Mansonia) titillans (48%), Aedes (Ochlerotatus) fulvus (16.9%) and Culex (Melanoconion) spissipes (12%). There were significantly negative correlations between rainfall and river levels, and the abundance of Ma. titillans and Ae. fulvus. The abundance and species diversity of culicines differed among communities, with the highest values of both these parameters found in Santa María de los Guiacas and Carlitos. These differences were partly due to sampling effort but could also have been produced by the availability of larval habitats and niche diversity in these communities compared to the others surveyed. Up until, now this is the only longitudinal study to characterize the culicine fauna in Amazonas state, which includes several species of public health importance.

Predicting wear and blood metal ion levels in metal-on-metal hip resurfacing.

Suboptimal component position and design are thought to lead to edge wear and raised blood metal ion levels in metal-on-metal hip resurfacing (MOM-HR). These factors are thought to influence the "contact patch to rim distance" (CPRD), and calculation of this distance may improve prediction of wear and blood metal ion levels. We measured blood cobalt and chromium ion levels and the wear rates of the bearing surfaces in 165 MOM-HR retrieval cases. We then determined the contribution and effect sizes of cup inclination and version angles, component size and design, and CPRD (calculated from case-specific data) on blood metal ion levels and component wear rates. Acetabular orientation explained between 16.3% and 28.5% of the variation in wear rates and metal ion levels, whereas component size and design explained between 7.3% and 21.8% of the variability. In comparison, CPRD explained up to 67.7% of the variability, significantly greater than any other variable (all p < 0.0001). CPRD is a good predictor of wear and improves our understanding of wear performance and the mechanisms leading to edge loading.

Strain within the native and reconstructed MPFL during knee flexion.

There is little published data on the strain within the medial patellofemoral ligament (MPFL) and medial retinaculum through knee motion. This study was undertaken to evaluate the three-dimensional strain across the MPFL in the native state, using a proprietary visible-light stereophotogrammetry (VLS) system, and to compare the findings to the strain in a MPFL injury model and in two different reconstructed states. This is a controlled laboratory study. Eight cadaveric knees were marked along the MPFL and medial retinaculum, placed in an activity simulator, and taken through a range a motion. A proprietary VLS system was used to calculate the strain across the medial retinaculum and MPFL at 10 different degrees of knee flexion. This process was repeated in an MPFL injury model, as well as after standardized reconstruction of the MPFL using hamstring autograft performed in both 20 and 45 degrees of flexion. Averaged over all the measurement sites, the maximum principal strain (ε1) within the native MPFL increased rapidly from full extension to 120 degrees of flexion. The highest value of ε1 (87%) was observed at 120 degrees of knee flexion in the MPFL region. The largest change in strain occurred between 25 and 30 degrees (10% increase). The strain patterns in the knees reconstructed at 45 degrees of flexion more closely resembled the strain in the native state than did the strain in the knees reconstructed at 20 degrees. Strain within the native MPFL increases as the knee flexion angle increases, with the largest change occurring between 25 and 30 degrees. Reconstruction of the MPFL at 45 degrees is preferable to reconstruction at 20 degrees as the strain across the medial retinaculum more closely resembles the strain in the native state. Knowledge of the strain across the MPFL should allow for more accurate reconstruction of the MPFL, potentially reducing the risk of patellar maltracking or cartilage overload. The proprietary VLS system used in this study has many potential uses for experimental analysis of strain in the human body.

Vaginosis bacteriana: aspectos colposcópicos / Bacterial vaginosis: colposcopic aspects

Determinar mediante los criterios de Amsel, la vaginosis bacteriana en las pacientes estudiadas y definir los aspectos colposcópicos más frecuentes asociados a esta patología. Estudio descriptivo y transversal de pacientes que acudieron a la consulta de ginecología por leucorrea. A las pacientes que presentaron vaginosis bacteriana, se les realizó la evaluación colposcópica. Para el análisis estadístico de variables no paramétricas se aplicó la prueba de hipótesis de proporción. Departamento de Obstetricia y Ginecología, Hospital Universitario “Antonio Patricio de Alcalá ”, Cumaná. Se encontraron 65 pacientes con vaginosis bacteriana y en la evaluación colposcópica de la misma, lo más frecuente fue la colpitis a puntos finos rojos, difusa, con un patrón vascular de capilar simple y a la prueba de lugol, la imagen colposcópica fue el caoba irregular con 82 por ciento (P<0,05), estadísticamente significativo. El aspecto colposcópico característico de la vaginosis bacteriana con un patrón vascular capilar simple es la colpitis a puntos finos rojo difusa y a la prueba de lugol caoba irregular.

Interindividual variability and parent of origin DNA methylation differences at specific human Alu elements.

We investigated the CpG methylation of 19 specific members of Alu sub-families in human DNA isolated from whole blood, using an assay based on methylation-sensitive restriction endonuclease digestion of genomic DNA and 'hot-stop' polymerase chain reaction. We found significant interindividual variability in the level of methylation for specific Alu elements among the members of 48 three-generation families. Surprisingly, some of the elements also displayed quantitative parent of origin methylation differences; i.e. the mean level of methylation differed significantly when the insertions were transmitted through paternal versus maternal meiosis. Bisulfite sequence analysis of individual elements at such loci suggests, further, that maternal and paternal elements differ in the propensity of particular CpG sites to become unmethylated. Some individuals who exhibited high levels of methylation at specific Alu elements came from families in which more than one member also exhibited abnormal patterns of methylation at the differentially methylated regions of the IGF2/H19 or IGF2R loci, suggesting that there may be heritable differences between individuals in the fidelity with which allelic DNA methylation differences are established or maintained. Quantitative parental origin differences in methylation were identified only for Alu elements that lie in sub-telomeric or sub-centromeric bands of human chromosomes, whereas those assayed at intermediate positions did not exhibit any significant differences. The centromere/telomere restricted location of the methylation differences and the fact that none of these differences occur in regions of chromosomes known to contain transcriptionally imprinted genes suggest that maternal/paternal epigenetic modifications may play additional roles in processes other than transcriptional control.

Postepizootic persistence of Venezuelan equine encephalitis virus, Venezuela.

Five years after the apparent end of the major 1995 Venezuelan equine encephalitis (VEE) epizootic/epidemic, focal outbreaks of equine encephalitis occurred in Carabobo and Barinas States of western Venezuela. Virus isolates from horses in each location were nearly identical in sequence to 1995 isolates, which suggests natural persistence of subtype IC VEE virus (VEEV) strains in a genetically stable mode. Serologic evidence indicated that additional outbreaks occurred in Barinas State in 2003. Field studies identified known Culex (Melanoconion) spp. vectors and reservoir hosts of enzootic VEEV but a dearth of typical epidemic vectors. Cattle serosurveys indicated the recent circulation of enzootic VEEV strains, and possibly of epizootic strains. Persistence of VEEV subtype IC strains and infection of horses at the end of the rainy season suggest the possibility of an alternative, cryptic transmission cycle involving survival through the dry season of infected vectors or persistently infected vertebrates.

Familial aggregation of abnormal methylation of parental alleles at the IGF2/H19 and IGF2R differentially methylated regions.

Loss of imprinting (LOI) has been observed in many types of human tumors and may be a predisposing event in some colon cancers. LOI is strongly associated with alteration of normal DNA methylation patterns in differentially methylated regions (DMRs) of affected loci but it is not known whether LOI is caused by stochastic, environmental or genetic factors. We have developed a simple, quantitative assay for measurement of allelic methylation ratios based on methylation-sensitive restriction endonuclease digestion of genomic DNA and 'hot-stop' PCR. We examined allelic methylation ratios at DMRs within the IGF2/H19- and IGF2R-loci in a panel of 48 three-generation families. We observed familial clustering of individuals with abnormal methylation ratios at the IGF2/H19 DMR, as well as stability of this trait over a period of nearly two decades, consistent with the possibility that constitutional LOI at this locus is due largely to genetic factors. At the IGF2R DMR, we observed more variability in the allelic methylation ratios over time but also observed familial clustering of abnormal methylation ratios. Overall, our observations at IGF2R suggest that shared genetic factors are responsible for a major fraction of inter-individual variability in parental origin-dependent epigenetic modifications. However, temporal changes also occur in isolated cases, as well as within multiple individuals in the same family, indicating that environmental factors may also play a role.