Biocompatibility of single-walled carbon nanotube composites for bone regeneration.

OBJECTIVES: The purpose of this study was to evaluate in vivo biocompatibility of novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic acid) (PLAGA) composites for applications in bone and tissue regeneration. METHODS: A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight and 12 weeks post-implantation were compared with control (Sham) and PLAGA (five rats per group/point in time). Rats were observed for signs of morbidity, overt toxicity, weight gain and food consumption, while haematology, urinalysis and histopathology were completed when the animals were killed. RESULTS: No mortality and clinical signs were observed. All groups showed consistent weight gain, and the rate of gain for each group was similar. All groups exhibited a similar pattern for food consumption. No difference in urinalysis, haematology, and absolute and relative organ weight was observed. A mild to moderate increase in the summary toxicity (sumtox) score was observed for PLAGA and SWCNT/PLAGA implanted animals, whereas the control animals did not show any response. Both PLAGA and SWCNT/PLAGA showed a significantly higher sumtox score compared with the control group at all time intervals. However, there was no significant difference between PLAGA and SWCNT/PLAGA groups. CONCLUSIONS: Our results demonstrate that SWCNT/PLAGA composites exhibited in vivo biocompatibility similar to the Food and Drug Administration approved biocompatible polymer, PLAGA, over a period of 12 weeks. These results showed potential of SWCNT/PLAGA composites for bone regeneration as the low percentage of SWCNT did not elicit a localised or general overt toxicity. Following the 12-week exposure, the material was considered to have an acceptable biocompatibility to warrant further long-term and more invasive in vivo studies. Cite this article: Bone Joint Res 2015;4:70-7.

Rasch analysis of professional behavior in medical education.

The use of students' "consumer feedback" to assess faculty behavior and improve the process of medical education is a significant challenge. We used quantitative Rasch measurement to analyze pre-categorized student comments listed by 385 graduating medical students. We found that students differed little with respect to the number of comments they provided and that their comments indeed form a probabilistic Rasch hierarchy. However, different hierarchies were found across medical departments and faculty. An analysis of these interactions provides valuable, detailed, and quantitative information that can augment qualitative research approaches. In addition, we suggest how the Rasch scaling of student comments can assist researchers in the design and implementation of new faculty evaluation instruments. Finally, the interactions between student and department identified a subset of behaviors that appear to guide and possibly elicit students' comments.

Expression of CXCR3 and its ligands CXCL9, -10 and -11 in paediatric opsoclonus-myoclonus syndrome.

Opsoclonus-myoclonus syndrome (OMS) is a neuroinflammatory disorder associated with remote cancer. To understand more clearly the role of inflammatory mediators, the concentration of CXCR3 ligands CXCL10, CXCL9 and CXCL11 was measured in 245 children with OMS and 81 paediatric controls using enzyme-linked immunosorbent assay (ELISA), and CXCR3 expression on CD4(+) T cells was measured by flow cytometry. Mean cerebrospinal fluid (CSF) CXCL10 was 2·7-fold higher in untreated OMS than controls. Intrathecal production was demonstrated by significantly different CXCL10 CSF : serum ratios. The dichotomized 'high' CSF CXCL10 group had higher CSF leucocyte count (P = 0·0007) and B cell activating factor (BAFF) and CXCL13 concentrations (P < 0·0001). CSF CXCL10 did not correlate with clinical severity or relapse using grouped data, although it did in some patients. Among seven types of immunotherapy, including rituximab or chemotherapy, only adrenocorticotrophic hormone (ACTH) monotherapy showed reduced CSF CXCL10, but prospective longitudinal studies of ACTH combination therapies indicated no reduction in CXCL10 despite clinical improvement (P < 0·0001). CXCL10 concentrations were 11-fold higher in CSF and twofold higher in serum by multiplexed fluorescent bead-based immunoassay than enzyme-linked immunosorbent assay, but the two correlated (r = 0·7 and 0·83). In serum, no group differences for CXCL9 or CXCL11 were found. CXCR3 expression on CD4(+) T cells was fivefold higher in those from CSF than blood, but was not increased in OMS or altered by conventional immunotherapy. These data suggest alternative roles for CXCL10 in OMS. Over-expression of CXCL10 was not reduced by clinical immunotherapies as a whole, indicating the need for better therapeutic approaches.

B- and T-cell markers in opsoclonus-myoclonus syndrome: immunophenotyping of CSF lymphocytes.

BACKGROUND: Although many lines of evidence suggest an autoimmune etiology, the pathophysiology of opsoclonus-myoclonus syndrome (OMS) remains poorly understood and no immunologic abnormalities have correlated with neurologic severity. Conventional immunotherapies often do not prevent relapse or permanent sequelae. OBJECTIVE: To test the cellular immune hypothesis of OMS in a cross-sectional study and determine if CSF lymphocyte subset analysis provides biomarkers of disease activity. METHODS: The expression of lymphocyte surface antigens was investigated in CSF and blood of 36 children with OMS and 18 control subjects, using a comprehensive panel of monoclonal antibodies to adhesion and activation proteins in combination with anti-CD3 and anti-CD45 antibodies in four-color fluorescence-activated cell sorting. RESULTS: Although most children with OMS had normal CSF cell counts, they exhibited expansion of CD19+ B-cell (up to 29%) and gammadelta T-cell (up to 26%) subsets and a lower percentage of CD4+ T-cells and CD4/CD8 ratio, which persisted even years after disease onset and conventional treatments. The percentage of activated CSF T-cells was also higher. Abnormalities correlated with neurologic severity, as scored blinded from videotapes using a 12-item motor scale, and disease duration. No significant differences were found between tumor and no-tumor groups. In children with neuroblastoma, tumor resection or cancer chemotherapy did not alter immunologic abnormalities. CONCLUSIONS: CSF B- and T-cell recruitment is linked to neurologic signs in pediatric OMS, which may relate to relapses and disease progression.

Strain differences in sleep patterns of healthy and influenza-infected inbred mice.

Influenza-infected C57BL/6J and BALB/cByJ mice respectively develop increased slow-wave sleep (SWS) during the dark phase and reduced SWS during the light phase of the 24 hour circadian cycle. To determine whether similar or alternative variations in SWS develop after influenza infection in other inbred strains of mice, we characterized the sleep patterns of additional strains both before and after influenza infection. Three strains (A/J, BALB/cByJ, and C3H/HeJ) showed light-phase SWS suppression, two strains (C57BL/6J and DBA/2J) showed dark-phase SWS enhancement, and one strain (A/J) showed dark-phase SWS suppression. Three strains (AKR/J, C57BR/cdJ, and FVB/NJ) did not show significant changes in SWS time on day two post-inoculation. Core temperatures were correlated to change in SWS time after infection, but were not correlated to SWS during the baseline period. These data support and expand the existing literature that indicates genetic modulation of sleep both in healthy mice and in mice undergoing viral infection.

The effect of heel elevation on strain within the plantar aponeurosis: in vitro study.

Mild, temporary reduction of symptoms from plantar fasciitis have been reported with the use of high heeled shoes (i.e. cowboy boots, ladies pumps). However, little is known on how heel elevation may contribute to a decrease in the pain and inflammation. The aim of this study was to quantify strain in the plantar aponeurosis in cadaveric feet with the use of various heel elevation configurations. An in vitro method that simulated "static" stance was used to determine the loading characteristics of the plantar aponeurosis (n = 12). Heel elevation was evaluated with blocks placed beneath the heel and with a contoured platform that simulated the arch profile of a shoe at three different heel heights (2.0, 4.0, 6.0 cm) with a level plane serving as the control. Strain in the plantar aponeurosis decreased with elevations of the heel that simulated the arch profile of a shoe at load levels (337, 450 N) (P < 0.05). Elevations of the heel with blocks did not significantly affect strain in the plantar aponeurosis (P < 0.05). Contrasting results of some specimen limbs compared with the overall means suggests that the influence of heel elevation on loading of the plantar aponeurosis may be dependent on individual variation and foot structure differences. Therefore, clinicians should be cautious in recommending heel elevation as a treatment for plantar fasciitis since some subjects may not achieve the desired decrease in plantar aponeurosis strain.

Predictive utility of the Bayley Infant Neurodevelopmental Screener (BINS) risk status classifications: clinical interpretation and application.

Predictive validity and clinical implications of the increasingly popular Bayley Infant Neurodevelopmental Screener (BINS) risk status classifications have not been previously reported. In this longitudinal follow-up study, the BINS was administered to high-risk infants at 6, 12, and 24 months of age, and the McCarthy Scales at 3 years of age. Ninety-two children were evaluated at 6 and 36 months, 105 at 12 and 36 months, and 118 at 24 and 36 months; 190, 125, and 140 infants were included in the comparisons at 6 to 12, 6 to 24, and 12 to 24 months. BINS risk status was classified as low, moderate, or high; or as a binary variable, LOWRISK/HIGHRISK. The three BINS items groups were moderately correlated. Consistency was most variable in the moderate-risk group. BINS risk was predictive of 36-month function in 18 out of 18 comparisons. Odds ratios, ranging from 2.76 to 54.70, were significant in 15 out of 18 logistic models. An early high-risk classification was associated with increased probability of later developmental morbidity. The BINS offers an alternative to detailed assessment in high-volume clinical applications and has good concurrent and predictive validity.

Stabilization of eyelid height after aponeurotic ptosis repair.

OBJECTIVE: To develop guidelines for revision of ptosis surgery in the early postoperative period by establishing what percentage of eyelids after anterior levator advancement have reached their final height by the first postoperative week. DESIGN: Prospective noncomparative case series. PARTICIPANTS: An analysis was performed on 164 eyelids in 97 patients with involutional aponeurotic ptosis. INTERVENTION: Anterior levator advancement was performed on each of these 164 eyelids. Exclusion criterion consisted of a history or evidence of neurologic or muscular disease, preceding trauma, an anophthalmic socket, or prior eyelid surgery. MAIN OUTCOME MEASURES: The marginal reflex distance, eyelid excursion, and degree of swelling were recorded perioperatively; additionally, photographs were obtained before surgery and at 1 and 6 weeks after surgery. RESULTS: At 1 week after surgery, only 40% of eyelids had reached their final height; 52% continued to rise a mean of 1.1 mm. The percentage of eyelids continuing to rise after the first postoperative week varied with the amount of swelling present at 1 week, although a direct correlation did not exist (Pearson correlation, 0.22; P < 0.26). Although this increase ranged from 0.5 to 3.0 mm for 71% of eyelids, the subsequent increase was 1 mm or less. Maximal eyelid height was achieved almost universally by 6 weeks, after which 18% of eyelids subsequently dropped a mean of 0.8 mm. CONCLUSIONS: Based on this study, the authors suggest revision at 1 week after anterior levator advancements in which minimal-to-moderate eyelid swelling exists for contour abnormalities, if the eyelid height is 0.5 mm or more above or more than 1.0 mm below the target height, or if asymmetry between the eyelids is 1.0 mm or more. The authors do not advise early revision for patients with excessive swelling still present 1 week after surgery.

Patellar tilt in total knee arthroplasty.

Eighty-nine consecutive primary total knee arthroplasties performed for osteoarthrosis were evaluated to determine the effect of patellar thickness, alignment, joint line, patellar height, type of patellar prosthesis, and length of follow-up on patellar tilt. Preoperatively, 62% of the patellae were tilted neutrally and 38% tilted laterally on standard 45 degrees Merchant-view radiographs. At 3-week follow-up, 52% were neutral, 32% tilted laterally and 16% tilted medially. At the most recent follow-up (mean 36 months), 41% were neutral, 46% tilted laterally and 13% tilted medially. Five (5.6%) required reoperation for patellar complications. Change in joint line, in alignment, and in patellar height had no effect on postoperative patellar tilt. Patients who required a lateral release had postoperative patellar tilt measurements that were not statistically different from those who did not require a lateral release. Metal-back domed patellae were more likely to tilt laterally than all-polyethylene domed patellae; however, the metal-back patellae had a longer mean follow-up (41 months) compared with the all-polyethylene patellae (27 months). The positive correlation between preoperative patellar thickness and postoperative patellar tilt was statistically significant. The negative correlation between change in patellar thickness and postoperative patellar tilt also was statistically significant. Finally, postoperative medically tilted patellae moved toward neutral with time and laterally tilted patellae not only remained laterally tilted but also the tilt increased with time.

Serum prolactin levels and neonatal seizures.

To assess the effects of neonatal seizures on the hypothalamus and to test clinical use of prolactin as a neonatal seizure marker, we studied postictal and recovery baseline serum prolactin levels in 19 neonates whose seizures were classified according to their clinical and EEG features. Postictal prolactin levels were obtained 30 min after the seizure, and recovery levels were ascertained 2-4 days later. The ratio of postictal prolactin level to recovery baseline level (prolactin ratio) was used as an indicator of postictal prolactin increase. The specificity and sensitivity of a prolactin ratio of > 2 was compared with the current standard of diagnosis (seizure discharges recorded by ictal EEG). Infants with electroclinical seizures had significantly higher prolactin ratios than control infants or infants with seizures without EEG correlation. Marked prolactin increases were noted only in infants with focal tonic seizures and temporal electrode involvement. A prolactin ratio of > 2 had a specificity of 100% and a sensitivity of 40%. We conclude that neonatal seizures have variable effects on the hypothalamus and that the low sensitivity and the need to await recovery levels limit the clinical value of prolactin ratio as a neonatal seizure marker.

Evaluation of an educational program for asthmatic children ages 4-8 and their parents.

BACKGROUND: Evaluation of a number of asthma education programs for children 8-13 has shown improved self-management behaviors and decreased use of healthcare services. However, nearly 80% of children with asthma develop symptoms by age 5. MATERIALS & METHODS: We evaluated a program (Huff and Puff: The Children's Asthma Program) that addresses the developmental learning needs of children ages 4-8. This multicenter study employed a pre- and post-test design to evaluate the impact of the Program on cognitive, behavioral, and affective learning and medical care utilization. We report here data on 128 of the 130 children who completed the program and on the 125 households on which we have nonduplicated data. RESULTS: Statistically significant changes were observed in all categories of learning in those who completed the Program. Medical care utilization (including hospitalizations, days of hospitalization, emergency room visits and sick visits to the physician for "out-of-control" asthma) demonstrated statistically significant decreases. CONCLUSION: The Program was shown to be an effective educational intervention for children 4-8 years of age and their parents in this cohort (nonrandomized, noncontrolled study of volunteers). Future research should also explore ways to utilize and adapt the program for specific populations such as inner-city children and parents and non-English speaking groups.

Predictors of frequent middle school health room use.

Disproportionately high use of school health room (HR) services by small groups of users has been reported. This study investigated predictors of frequent HR use in two suburban middle schools involving 1089 students who made at least one HR visit during a single academic year. Subsets of high and low users were compared using logistic regression. Predictor variables included gender, grade, academic ability, and existence of a chronic health condition. Although demographic characteristics of the study schools varied significantly, a pattern of increasing HR use associated with progressive lowering of academic ability was demonstrated in both schools. Existence of a chronic health condition was associated with increased HR use, even when controlling for routine medication visits. Gender and grade were not predictive. These findings suggest that HR use reflects more than medical concerns. Patterns of HR use by students with chronic health conditions deserve additional study to determine whether current strategies to meet their needs are adequate.

Attention deficits in children and adolescents with hearing loss. A survey.

OBJECTIVES: To determine the prevalence of reported attention deficits in a sample of children who are deaf or hard of hearing and to examine associated variables. DESIGN: Cross-sectional survey. SETTING: Residential school for the deaf. PARTICIPANTS: All students attending the school (n = 238; median age, 16.0 years; range, 4 to 21 years). Subjects were subgrouped by cause of deafness for further analyses. INTERVENTION: None. MEASUREMENTS/MAIN RESULTS: School personnel completed questionnaires that are commonly used in the assessment of attention problems. Teachers completed the Attention Deficit Disorder With Hyperactivity (ADD-H) Comprehensive Teacher Rating Scale (ACTeRS) and an abbreviated version of the Attention-Activity section of the ANSER (Aggregate Neurobehavioral Student Health and Education Review) System Questionnaires. Dormitory supervisors rated students on the Conners' Parent Rating Scale and the ANSER System Questionnaires. The mean factor scores for the total sample of deaf and hard-of-hearing students on the Attention and Hyperactivity scales of the ACTeRS and Conners' questionnaires did not differ from the normative data. The 64 students with hereditary deafness received significantly better ratings than the 75 with an acquired cause of deafness such as bacterial meningitis or congenital rubella. Raw scores on the ACTeRS were converted to percentile equivalents based on the normative sample. On the Attention Scale, 38.7% of those with acquired deafness were rated below the 20th percentile (indicative of problems); only 14.1% of the students with hereditary deafness were in this range (P = .002). CONCLUSIONS: Ratings of attention for students with hearing loss, attending a residential school, did not differ from the normative data. However, the subgroup of children with acquired sensorineural deafness appear to be at increased risk for attention problems.

Causes of urinary incontinence after acute hemispheric stroke.

BACKGROUND AND PURPOSE: We prospectively studied bladder function in stroke patients to determine the mechanisms responsible for poststroke urinary incontinence. METHODS: Fifty-one patients with recent unilateral ischemic hemispheric stroke admitted to a neurorehabilitation unit were enrolled. The presence of urinary incontinence was correlated with infarct location, neurological deficits, and functional status. Urodynamic studies were performed on all incontinent patients. RESULTS: Nineteen patients (37%) were incontinent. Incontinence was associated with large infarcts, aphasia, cognitive impairment, and functional disability (p < 0.05) but not with age, sex, side of stroke, or time from stroke to entry in the study. Urodynamic studies, performed on all 19 incontinent patients, revealed bladder hyperreflexia in 37%, normal studies in 37%, bladder hyporeflexia in 21%, and detrusor-sphincter dyssynergia in 5%. All of the patients with normal urodynamic studies were aphasic, demented, or severely functionally impaired. All of the patients with hyporeflexic bladders had underlying diabetes or were taking anticholinergic medications. Forty-six percent of incontinent patients treated with scheduled voiding alone were continent at discharge compared with 17% of patients treated pharmacologically. CONCLUSIONS: There are three major mechanisms responsible for poststroke urinary incontinence: 1) disruption of the neuromicturition pathways, resulting in bladder hyperreflexia and urgency incontinence; 2) incontinence due to stroke-related cognitive and language deficits, with normal bladder function; and 3) concurrent neuropathy or medication use, resulting in bladder hyporeflexia and overflow incontinence. Urodynamic studies are of benefit in establishing the cause of incontinence. Scheduled voiding is a useful first-line treatment in many cases of incontinence.

Clinical performance-based test sensitivity and specificity in predicting first-year residency performance.

To assess the use of a standardized-patient-based postclerkship examination (PCX) to predict students' performances in their first year of residency, the authors used data from 202 students of the classes of 1987, 1988, and 1990 at the Southern Illinois University School of Medicine. The PCX was found to be more sensitive than specific in that it identified more correctly those students who received high ratings in their first year of residency than those who received low ratings. Consequently, while the rate of false negatives was low across the three classes, the rate of false positives was relatively high. Analyses of the supervisors' written comments on residents' performances indicated that more than half of the false positives and false negatives resulted mostly from problems found with the supervisors' ratings, rather than from the inaccuracy of the PCX in predicting students' residency performances. The supervisors' ratings did not always match their written comments and did not always represent pure assessments of the residents' cognitive performances. Finally, because of the large number of missing residency performance ratings among the graduates who had performed unsatisfactorily on the PCX, it is expected that the sensitivity of the PCX may be overestimated and its specificity underestimated. Overall, the results suggest that the standardized-patient-based PCX is a useful indicator of students' readiness for and performance in residency.

Examination of nonresponse bias in a major residency follow-up study.

Nonresponse bias is a potential problem for follow-up studies that track medical school graduates into their residencies. There are two main types of nonresponse: when residents' supervisors do not complete the study evaluation forms and when medical students refuse permission to allow follow-up evaluations during their residencies. The present study discloses the biases that each of these types of nonresponse produced on a set of standard measures of 508 residents from eight 1980s medical school classes at Southern Illinois University. The standard measures (e.g., MCAT scores, grade-point averages, NBME scores) were collected when the residents were medical students. The findings clearly indicate that the scores of the medical students who granted permission for follow-up evaluations had significantly larger means than did the scores on the same measures of those students not granting permission, clearly a source of nonresponse bias. On the other hand, no significant difference in scores (thus negligible bias) was found in cases where supervisors did not complete forms. The authors offer suggestions for medical school policies based on these findings.

Standardized (simulated) patients' accuracy in recording clinical performance check-list items.

In large-scale performance-based assessment of medical professionals' clinical competence, simulated patients (standardized patients-SPs) are used not only to simulate case problems but also to record on check-list the examinees' clinical performance during their encounter with the SPs. The purposes of this study were to determine the SPs' overall accuracy in recording check-list items, and whether their accuracy was affected by the various characteristics of the check-list, and by the different times during a day and the different days within the examination when the recordings were obtained. Results showed that the SPs' accuracy in recording check-list items was good to very good and was affected by the length of the check-list, as well as by the type and the clarity of the check-list item. It was further found that the SPs' accuracy was consistent and did not vary over the course of a one-day or a 15-day examination.