The Effect of Adolescent Idiopathic Scoliosis on Natural Delivery and Epidural Use in Pregnant Females: A Matched Cohort Study.

STUDY DESIGN: Retrospective matched cohort study. OBJECTIVE: The aim of this study was to determine whether females with idiopathic scoliosis (IS), both with and without spine fusion, experience different rates of cesarean section (CS) and epidural anesthesia (EA) than females without scoliosis. SUMMARY OF BACKGROUND DATA: IS is a common spine condition with a higher prevalence in females. It is unclear whether females with scoliosis, treated nonoperatively or operatively, have different rates of cesarean delivery or EA. MATERIALS AND METHODS: Patients with IS who delivered in our integrated health care system during a 6-year period were identified (N = 1810). They were matched with a group without scoliosis who delivered during the same period (N = 1810). Rates and relative risk (RR) of CS and EA between cohorts and subgroups were calculated. RESULTS: The scoliosis cohort had significantly higher rates and RR of EA ( P = 0.002 and P = 0.004, respectively). Scoliosis patients treated nonoperatively had an 8% greater RR of EA ( P = 0.004) and had a significantly lower rate of CS (23.2% vs . 26%, P = 0.048) compared with the control group. Among only scoliosis patients, those treated with spine fusion had a 38% decreased RR of EA ( P < 0.001). Distal fusion level did not seem to influence the RR of EA or CS. CONCLUSIONS: Females with scoliosis were significantly more likely to receive EA at delivery compared with females without scoliosis. Rates and RR of cesarean delivery were not significantly lower among women with scoliosis, but females treated nonoperatively for scoliosis had a significantly lower CS rate than those without scoliosis. Females treated with spine fusion for scoliosis were far less likely to receive EA than both females without scoliosis and females with scoliosis treated nonoperatively.

The Demographics and Epidemiology of Infantile, Juvenile, and Adolescent Idiopathic Scoliosis in a Southern California Integrated Health Care System.

STUDY DESIGN: Prognostic study, Level III. OBJECTIVES: The aim of this study was to determine the incidence and demographics of idiopathic scoliosis (IS) in a large cohort of children in a Southern California integrated healthcare system, and to identify the demographic or clinical factors associated with the greatest risk of IS. SUMMARY OF BACKGROUND DATA: Although many authors have reported on the incidence and prevalence of IS in children, there have been few incidence studies in the United States on large, self-contained populations. METHODS: A retrospective chart analysis was done on diagnosed cases of IS within our integrated health care system in patients under age 18 years during the entire 2013 calendar year. Patient demographics were recorded and the incidence of IS was determined. Odds ratios (ORs) for having IS and for having more severe initial curve magnitudes based on demographics were determined using logistic regression models. RESULTS: IS Incidence was 3.9, 28.6, and 393 per 100,000, respectively, for the infantile, juvenile, and adolescent group. The female incidence was more than twice that of males in all age groups. Multivariate logistic regression analysis showed Asians and non-Hispanic Whites had the highest OR of IS (OR 1.54 and 1.32 with 95% confidence interval [CI] 1.33-1.79 and 1.19-1.47). Whites, Blacks, and mixed-race patients had a significantly higher initial curve magnitude than Hispanics; females also had a significantly greater initial curve magnitude than boys (18.1° vs. 16.7°). Underweight patients had a 50% increased OR of IS versus normal weight (95% CI 1.16-1.94) with a progressively decreased OR of IS as weight increased. CONCLUSION: Our study of a large integrated healthcare system sheds light on the incidence of IS and the ORs based on weight, sex, and ethnicity/race. The overall incidence was lower overall than previously thought.Level of Evidence: 3.

Effect of an RN-Led Medication Teaching Initiative on Psychiatric Recidivism.

This quality improvement (QI) project analyzed the impact of RN-led medication teaching on readmissions of adult patients discharged from a Midwest psychiatric veterans' hospital. Data on patient participation in the initiative, outpatient medication adherence, and annual 30-day readmission rates were gathered from electronic medical records (EMR) and patient discharge logs from years 2017 and 2018. Forty-three percent of RNs engaged in the initiative. Percentages of patients, who received medication teaching throughout the year, ranged from 27% to 40%. However, self-reported medication adherence following discharge was much higher (73-85%). The RN-led medication teaching initiative did not impact recidivism, and low staff participation was reflected by the downtrend in numbers of patients who received medication teaching throughout the year. Compared to previous years, annual recidivism increased. Fifty-three percent of recidivist patients who received medication teaching reported complete outpatient medication adherence prior to readmission, possibly indicating it is not a significant factor in preventing readmissions or, alternatively, that patients tend to over-report adherence. A small group of patients (19%) accounted for the majority of readmissions annually (70%). This group appears to be most at risk for continued recidivism. Future attempts to improve unit recidivism might benefit from aligning interventional strategies to the common risk factors of chronic recidivists.

What are the Demographics and Epidemiology of Legg-Calvé-Perthes Disease in a Large Southern California Integrated Health System?

BACKGROUND: Although many authors have reported the incidence of Legg-Calvé-Perthes disease (LCPD), there have been few incidence studies in the United States on large, self-contained populations such as those within an integrated health system. Understanding the epidemiology and demographics of LCPD in this setting may help clinicians identify patients at the greatest risk and aid in diagnosis and subsequent treatment. QUESTIONS/PURPOSES: In this study we sought (1) to determine the incidence and demographics of LCPD in a large cohort of children and adolescents in a Southern California integrated healthcare system, and (2) to identify any demographic or clinical factors (such as age, sex, race/ethnicity, or BMI) that are independently associated with LCPD. METHODS: A retrospective chart analysis was done on patients diagnosed with LCPD within our integrated healthcare system in patients aged 2 to 12 years over a 3-year period between 2010-2012. There were nearly 800,000 children in this cohort. Patient demographics were recorded; the incidence of LCPD was determined for the entire group and by sex, age, and race/ethnicity. Odds ratios for an association with LCPD based on age, sex, BMI and race/ethnicity were determined using logistic regression models. RESULTS: The LCPD incidence per 100,000 for all children was 2.84, with the highest incidence in 2- to 5-year-old children (3.05; 95% CI, 1.51-4.59) and the lowest in 9- to 12-year-old children (1.06; 95% CI, 0.21-1.91). Incidence varied markedly among ethnicities, with the highest incidence in whites (5.69; 95% CI, 3.13-8.24) and the lowest in Asians (0.78; 95% CI, 0.00-2.32). Data analysis revealed a 3.13-times increased odds ratio (OR) of LCPD in 2- to 5-year-old patients versus 9- to 12-year-olds (p = 0.011), and boys had a 12.44 times greater OR of LCPD than girls (p < 0.001). Data analysis showed an increased OR for LCPD (3.41; 95% CI, 1.28-9.09) in patients with extreme obesity (BMI-for-age ≥ 1.2 × 95th percentile or a BMI ≥ 35 kg/m) compared with patients with a normal BMI. CONCLUSIONS: Our study of a large integrated healthcare system in Southern California revealed an increased association of male sex and young age (2 to 5 years old) with LCPD. The overall incidence was lower overall than previously reported, although the incidence seen in white patients was similar to that in prior studies. The finding that patients with extreme obesity may have an increased association with LCPD merits further study. These findings may increase providers' awareness of the risk of the disease in younger patients and in extremely obese patients, and it also merits further future investigation as to whether there is a cause or effect relationship between extreme obesity and LCPD. LEVEL OF EVIDENCE: Level IV, prognostic study.

Childhood Obesity is Associated With Osteochondritis Dissecans of the Knee, Ankle, and Elbow in Children and Adolescents.

BACKGROUND: Osteochondritis dissecans (OCD) is a joint disorder of the subchondral bone and articular cartilage whose association with obesity in children is not clearly known. The purpose of this study was to assess the magnitude of the association between childhood obesity and the occurrence of OCD of the knee, ankle, and elbow in children. METHODS: A retrospective chart review of an integrated health system was performed on OCD patients aged 2 to 19 from 2007 to 2011, with over 1 million patients in this cohort. Lesion location, laterality, and all patient demographics were recorded. The body mass index (BMI) for each patient in the cohort was used to stratify patients into 5 weight classes (underweight, normal weight, overweight, moderately obese, and extremely obese) based on BMI-for-age. The associations between the 5 weight classes and OCD of the ankle, knee, and elbow were assessed using multiple logistic regression models to estimate odds ratios (OR) and 95% confidence intervals using multivariate analysis to adjust for patient demographic variables. RESULTS: In total, 269 patients fit the inclusion criteria. Mean BMI, both absolute and percentile, was significantly higher for patients with OCD of the knee, elbow, and ankle than patients without OCD. In the multivariate analysis, extremely obese patients were found to have an increased OR of OCD for all patients, with an 86% increased risk of any OCD compared with normal weight patients. In addition, assessment by different types of OCD revealed that extremely obese patients had an increased OR of OCD of the elbow and ankle individually, with a 3.1 times increased OCD elbow risk and 3.0 times increased risk of ankle OCD in extremely obese patients. Although extremely obese patients did not have a statistically significant increased risk of knee OCD, moderately obese patients did have a 1.8 times increased risk of knee OCD as compared with normal weight children. There were no significantly different risks of any type of OCD seen in overweight or underweight patients as compared with normal weight patients. CONCLUSIONS: In this population-based cohort study, extreme obesity is strongly associated with an increased risk of OCD overall and OCD of the elbow and ankle specifically. In addition, moderate obesity is associated with an increased risk of knee OCD. All types of OCD were also found to have a significantly greater average BMI when compared with patients without OCD. LEVEL OF EVIDENCE: Level IV-descriptive epidemiology study.

Incidence of Osteochondritis Dissecans in Adults.

BACKGROUND: Osteochondritis dissecans (OCD) has frequently been described in children and adolescents, but cases of OCD in adults are certainly encountered. Little has been published on the epidemiology of OCD in adult patients. PURPOSE: To assess the frequency of OCD lesions in adults and assess the risk by age, sex, and ethnicity. STUDY DESIGN: Descriptive epidemiology study. METHODS: The authors assessed all patients aged 20 to 45 years from the entire database of patients enrolled as members of Kaiser Permanente Southern California from January 2011 until December 2013. Kaiser Southern California is an integrated health care system serving a racially, ethnically, and socioeconomically diverse population of >3.5 million patients. A retrospective chart review was done on OCD during this period. Inclusion criteria included OCD of any joint. Exclusion criteria included traumatic osteochondral fractures and coexistence of intra-articular lesions other than OCD. Joint involvement/location, laterality, and all patient demographics were recorded. RESULTS: Among 122 patients, a total of 124 OCD lesions were found. The majority of lesions were in the ankle (n = 76) and knee (n = 43), with 3 foot lesions and 2 elbow lesions identified. OCD lesions were identified in 75 men (62%) and 47 women (38%). Overall incidence rates per 100,000 person-years were 3.42 for all OCD, 2.08 for ankle OCD, and 1.21 for knee OCD. The relative risk of adult OCD for men was twice that of women. The relative risk of adult OCD for white patients was 2.3 that of Asians and 1.7 that of Hispanics. Risk of knee OCD was 3.6 times higher for men than women. As compared with women, men had a higher risk for lateral femoral condyle OCD lesions versus the medial femoral condyle ( P = .05; odds ratio [OR], 5.19). CONCLUSION: This large cohort study of Southern California adults with OCD demonstrated an increased OR for men (vs women) of OCD in all joints. The majority of symptomatic lesions were present in the ankle rather than the knee, as previously found in children. White and black patients had the highest OR of OCD; men had a significantly greater OR of lateral femoral condyle knee lesions as compared with women.

Demographics and Epidemiology of Osteochondritis Dissecans of the Elbow Among Children and Adolescents.

BACKGROUND: Osteochondritis dissecans (OCD) of the elbow is a disorder of subchondral bone and articular cartilage, of which the incidence among children is not clearly known. PURPOSE: To assess the demographics and epidemiology of OCD of the elbow among children. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A retrospective chart review of an integrated health system for the years 2007 through 2011 was performed for patients with elbow OCD aged 2 to 19 years. Lesion location, laterality, and all patient demographics were recorded. OCD incidence was determined for the group as a whole as well as by sex and age group (2-5, 6-11, 12-19 years). Patient differences based on age, sex, and ethnicity were analyzed, and multivariable logistic regression models were used to assess the risk of elbow OCD by group. RESULTS: A total of 37 patients with 40 OCD lesions fit the inclusion criteria. No lesion was found among 2- to 5-year-olds. A majority of lesions (n = 39, 97.5%) were in the capitellum, and 1 (2.5%) was in the trochlea. Twenty-five patients (67.6%) had right-sided lesions; 9 (24.3%), left-sided; and 3 (8.1%), bilateral. The incidence of elbow OCD for patients aged 6 to 19 years was 2.2 per 100,000 overall and 3.8 and 0.6 per 100,000 for males and females, respectively. The majority of OCD cases were seen in those aged 12 to 19 years, with an incidence of 3.4 per 100,000 versus 0.38 among 6- to 11-year-olds. Multivariable logistic regression analysis revealed a 21.7-times increased odds ratio of elbow OCD among patients aged 12 to 19 years versus 6 to 11 years, and males had a 6.8-times greater odds ratio of elbow OCD than females (P < .0001 for both). Based on race and ethnicity, non-Hispanic whites had the highest incidence of elbow OCD as compared with all other ethnic groups. CONCLUSION: In this population-based cohort study of pediatric elbow OCD, males had almost 7 times the risk of elbow OCD as compared with females, and 12- to 19-year-olds had nearly 22 times the risk of elbow OCD versus 6- to 11-year-olds. In keeping with many prior studies, the majority of patients had right-sided lesions.

The Incidence of Surgery in Osteochondritis Dissecans in Children and Adolescents.

BACKGROUND: The frequency of osteochondritis dissecans (OCD), a disorder of the subchondral bone and articular cartilage, is not well described. PURPOSE: To assess the frequency of pediatric OCD lesions that progress to surgery based on sex, joint involvement, and age. STUDY DESIGN: Descriptive epidemiology study. METHODS: A retrospective chart review (2007-2011) was performed on OCD. Inclusion criteria included OCD of any joint and patients aged 2 to 19 years. Exclusion criteria included traumatic osteochondral fractures or coexistence of non-OCD intra-articular lesions. Differences in progression toward surgery were compared between age groups, sex, and joint location. Logistical regression analysis was performed by sex, age, and ethnicity. RESULTS: Overall, 317 patients with a total of 334 OCD lesions were found. The majority of lesions (61.7%) were in the knee, with ankle, elbow, shoulder, and foot lesions representing 25.4%, 12.0%, 0.6%, and 0.3% of all lesions, respectively. The majority of joints needing surgery were in the knee (58.5%), with ankle and elbow lesions representing 22.9% and 18.6% of surgeries performed, respectively. The percentage of all OCD lesions progressing to surgery was 35.3%; surgical progression for knee, ankle, and elbow joints was 33.5%, 31.8%, and 55.0%, respectively. Logistic regression analysis found no statistically significant different risk of progressing to surgery for OCD of the knee, elbow, and ankle between sexes. Patients aged 12 to 19 years had a 7.4-times greater risk of progression to surgery for knee OCD lesions than 6- to 11-year-olds. Patients aged 12 to 19 years were 8.2 times more likely to progress to surgery for all OCD lesions than patients aged 6 to 11 years. Progression to surgery of ankle OCD did not significantly differ based on location. Three of 4 trochlear lesions progressed to surgery, along with 1 of 1 tibial, 1 of 3 patellar, 40.3% of lateral femoral condylar, and 28.2% of medial femoral condylar lesions. CONCLUSION: In this large cohort study of pediatric OCD patients, 35% progressed to surgery. Progression to surgery did not differ significantly between sexes with OCD of any joint. Progression to surgery for OCD of the knee, elbow, and ankle strongly correlated with patient age at the time of diagnosis. CLINICAL RELEVANCE: The knowledge of likelihood of progression to surgery of OCD by location, sex, and age is useful in counseling patients and in planning treatment. This study confirms a worse prognosis in the nonoperative treatment of older patients with OCD.

Osteochondritis dissecans of the ankle in children and adolescents: demographics and epidemiology.

BACKGROUND: Osteochondritis dissecans (OCD) of the ankle is a disorder of the talar or distal tibial subchondral bone and articular cartilage whose incidence in children is not clearly known. PURPOSE: To assess the demographics and epidemiology of OCD of the ankle in children. STUDY DESIGN: Descriptive epidemiologic study. METHODS: A retrospective chart review of an integrated health system was conducted on patients with ankle OCD aged 2 to 19 years from 2007 to 2011, with >1 million patients in this cohort. Lesion location, laterality, and all patient demographics were recorded. Ankle OCD incidence was determined for the group as a whole and by both sex and age group (divided into age groups of 2-5, 6-11, and 12-19 years). The risk for ankle OCD for age group, sex, and ethnicity was assessed using multivariate logistic regression models. RESULTS: A total of 85 patients fit the inclusion criteria, and 71.8% of lesions found were in the medial talus, 56.5% of lesions were right sided, and none were bilateral. No ankle OCD lesions were found in 2- to 5-year-olds. The incidence of ankle OCD in patients aged 6 to 19 years was 4.6 per 100,000 overall and 3.2 and 6.0 per 100,000 for male and female patients, respectively. Patients aged 12 to 19 years represented the vast majority of those with OCD, with an incidence of 6.8 per 100,000 compared with 1.1 per 100,000 in those 6 to 11 years of age. In those aged 6 to 11 and 12 to 19 years, female patients had a respective incidence of 1.5 and 8.9 per 100,000, whereas male patients had a respective incidence of 0.7 and 4.8 per 100,000. The overall female/male ratio of ankle OCD was 1.6:1. Multivariate logistic regression analysis revealed a 6.9 times increased risk for ankle OCD in patients aged 12 to 19 years compared with those aged 6 to 11 years (95% CI, 3.8-12.5; P < .0001), and female patients had a 1.5 times greater risk for ankle OCD than male patients (95% CI, 1.0-2.3; P = .06). On the basis of race and ethnicity, non-Hispanic whites had the highest relative risk for disease and African Americans the lowest risk. CONCLUSION: In this population-based cohort study of pediatric ankle OCD, female patients had a greater incidence of OCD and a 1.5 times greater risk for ankle OCD compared with male patients. Teenagers had nearly 7 times the risk for ankle OCD compared with children 6 to 11 years of age.

Osteochondritis dissecans of the knee: pathoanatomy, epidemiology, and diagnosis.

Although several hypotheses have been described to explain the cause of osteochondritis dissecans, no single hypothesis has been accepted in the orthopedic community. Given its increased incidence among athletes, most in the sports medicine community agree that repetitive microtrauma plays at least some role in its development. Knowledge regarding the epidemiology and pathoanatomy of osteochondritis dissecans has helped the understanding of osteochondritis dissecans; however, much is still to be learned about this condition and its cause. This article reviews the history of osteochondritis as it pertains to the current understanding of its pathoanatomy, epidemiology, and diagnostic features.

The demographics and epidemiology of osteochondritis dissecans of the knee in children and adolescents.

BACKGROUND: Osteochondritis dissecans (OCD) is a disorder of subchondral bone and articular cartilage whose incidence in children is not clearly known. PURPOSE: The purpose of this study was to assess the demographics and epidemiology of OCD of the knee in children. STUDY DESIGN: Descriptive epidemiology study. METHODS: A retrospective chart review of an integrated health system was performed on patients with OCD of the knee aged 2 to 19 years from 2007 to 2011, with over 1 million patients in this cohort. Lesion location, laterality, and all patient demographics were recorded. The incidence of OCD was determined for the group as a whole and by sex and age group (2-5 years, 6-11 years, and 12-19 years). Patient differences based on age, sex, and ethnicity were analyzed, and using multivariable logistic regression models, associations between age, sex, ethnicity, and diagnosis of OCD of the knee were evaluated. RESULTS: One hundred ninety-two patients with 206 OCD lesions of the knee fit the inclusion criteria. No OCD lesion of the knee was found in 2- to 5-year-old children. One hundred thirty-one (63.6%) lesions were in the medial femoral condyle, 67 (32.5%) were in the lateral femoral condyle, 96 (50.0%) lesions were right sided, 82 (42.7%) were left sided, and 14 (7.3%) were bilateral. The incidence of patients with OCD of the knee aged 6 to 19 years was 9.5 per 100,000 overall and 15.4 and 3.3 per 100,000 for male and female patients, respectively. Those aged 12 to 19 years represented the vast majority of OCD, with an incidence of 11.2 per 100,000 versus 6.8 per 100,000 for those aged 6 to 11 years. For those aged 6 to 11 and 12 to 19 years, female patients had an incidence of 2.3 and 3.9 per 100,000, respectively, while male patients had an incidence of 11.1 and 18.1 per 100,000, respectively. Multivariable logistic regression analysis revealed a 3.3-fold increased risk of OCD of the knee in patients aged 12 to 19 years compared with those aged 6 to 11 years (P < .001; 95% confidence interval [CI], 2.37-4.48), and male patients had 3.8 times a greater risk of OCD of the knee than female patients (P < .001; 95% CI, 2.71-5.41). Based on race and ethnicity, blacks had the highest odds ratio of OCD of the knee compared with all other ethnic groups. CONCLUSION: In this population-based cohort study of pediatric OCD of the knee, male patients had a much greater incidence of OCD and almost 4 times the risk of OCD compared with female patients. Also, patients aged 12 to 19 years had 3 times the risk of OCD of the knee as compared with 6- to 11-year-old children.

Associations between childhood obesity and upper and lower extremity injuries.

OBJECTIVES: To estimate the overall and age-specific associations between obesity and extremity musculoskeletal injuries and pain in children. METHODS: This cross-sectional study used information from electronic medical records of 913178 patients aged 2-19 years enrolled in an integrated health plan in the period 2007-2009. Children were classified as underweight, normal weight, overweight, or moderately/extremely obese and, using multivariable logistic regression methods, the associations between weight class and diagnosis of upper or lower extremity fractures, sprains, dislocations and pain were calculated. RESULTS: Overweight (OR 1.18, 95% CI 1.15 to 1.20), moderately obese (OR 1.24, 95% CI 1.20 to 1.27) and extremely obese (OR 1.34, 95% CI 1.30 to 1.39) children had statistically significantly higher odds of lower extremity injuries/pain compared to normal weight, adjusted for sex, age, race/ethnicity and insurance status. Age-stratified analyses yielded similar results. No consistent association was observed between body mass index and injuries/pain of the upper extremities. CONCLUSIONS: Greater body mass index is associated with increased odds of lower extremity injuries and pain issues. Because the benefits of physical activity may still outweigh the risk of injury, attention should be paid to injury prevention strategies for these children at greater risk for lower extremity injuries.

Efficacy of a new computer-aided design/computer-aided manufacture orthosis in the treatment of adolescent idiopathic scoliosis.

To report on the initial experience with the Los Angeles brace, a new computer-aided design/computer-aided manufacture brace used in the treatment of idiopathic scoliosis. This was a retrospective review of 40 idiopathic scoliosis patients who completed treatment with this new computer-aided design/computer-aided manufacture brace. In-brace correction averaged 51% for the primary curves, with corrections of 53 and 22% for girls and boys, respectively. Only six patients (15%) had curve progression at brace completion. This preliminary study suggests that the new Los Angeles brace is effective in the treatment of scoliosis in girls, while avoiding some obstacles involved in traditional bracing.

A new flexible brace used in the Ponseti treatment of talipes equinovarus.

The objective was to introduce a flexible brace abduction brace in the Ponseti treatment of clubfeet. Eight patients undergoing Ponseti treatment for talipes equinovarus were assessed. Brace compliance and incidence of relapses were assessed. Patients first used rigid abduction braces, but because of brace noncompliance were switched to a new flexible brace. Seven of 11 feet with compliance issues in a rigid brace had improved compliance when switching to the flexible brace. All seven feet with initial deformity relapse are deformity-free after switching to flexible bracing. This new flexible clubfoot brace may improve compliance in Ponseti clubfoot treatment.

The impact of the E46K mutation on the properties of alpha-synuclein in its monomeric and oligomeric states.

The third and most recently identified Parkinson's disease-linked variant of the neuronal protein alpha-synuclein to be identified (E46K) results in widespread brain pathology and early onset Parkinson symptoms (Zarranz et al. (2004) Ann. Neurol. 55, 164-173). Herein, we present biochemical and biophysical characterization of E46K alpha-synuclein in various states of aggregation. Circular dichroism and nuclear magnetic resonance spectroscopy illustrate that the E46K mutation results in subtle changes in the conformation of the monomeric protein both free in solution and in the presence of SDS micelles. However, it does not alter the overall helical propensity of the protein in the presence of phospholipids. E46K alpha-synuclein formed insoluble fibrils in vitro more rapidly than the wild type protein, and electron microscopy revealed that E46K alpha-synuclein fibrils possess a typical amyloid ultrastructure. E46K alpha-synuclein protofibrils, soluble aggregates that form during the transition from the monomeric form to the fibrillar form of alpha-synuclein, were characterized by electron microscopy and gel filtration and were found to include annular species. The unique ability of a subfraction of E46K and wild type alpha-synuclein protofibrils containing porelike species to permeabilize lipid vesicles was demonstrated in vitro using a real-time chromatographic method. In contrast to simplistic expectations, the total amount of protofibrils and the amount of permeabilizing activity per mole protein in the protofibril fraction were reduced by the E46K mutation. These results suggest that if the porelike activity of alpha-synuclein is important for neurotoxicity, there must be factors in the neuronal cytoplasm that reverse the trends in the intrinsic properties of E46K versus WT alpha-synuclein that are observed in vitro.

Impact of an Electronic Health Record on oncologists' clinic time.

The use of Electronic Health Records (EHRs) has been widely advocated to transform health-care delivery by improving quality, safety, and efficiency. Compared to a paper-based system, EHRs offer better access to clinical data and facilitate order entry and decision support. However, the benefits provided by EHRs do not eliminate the need to assess how such systems alter clinician time utilization. A major barrier to EHR use has been the concern that the EHR will take longer to use than paper-based systems. Few studies have addressed this issue in specialty clinic settings. We performed a time-motion study to evaluate how oncologists' time utilization differed before and after EHR implementation.

The N-terminal repeat domain of alpha-synuclein inhibits beta-sheet and amyloid fibril formation.

The conversion of alpha-synuclein into amyloid fibrils in the substantia nigra is linked to Parkinson's disease. Alpha-synuclein is natively unfolded in solution, but can be induced to form either alpha-helical or beta-sheet structure depending on its concentration and the solution conditions. The N-terminus of alpha-synuclein comprises seven 11-amino acid repeats (XKTKEGVXXXX) which can form an amphipathic alpha-helix. Why seven repeats, rather than six or eight, survived the evolutionary process is not clear. To probe this question, two sequence variants of alpha-synuclein, one with two fewer (del2) and one with two additional (plus2) repeats, were studied. As compared to wild-type alpha-synuclein, the plus2 variant disfavors the formation of beta-sheet-rich oligomers, including amyloid fibrils. In contrast, the truncated variant, del2, favors beta-sheet and fibril formation. We propose that the repeat number in WT alpha-synuclein represents an evolutionary balance between the functional conformer of alpha-synuclein (alpha-helix and/or random coil) and its pathogenic beta-sheet conformation. N-terminal truncation of alpha-synuclein may promote pathogenesis.