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Prior research has indicated adolescent idiopathic scoliosis (AIS) patients have lower bone mineral density and lower vitamin D levels than healthy peers. Vitamin D deficiency has been associated with higher levels of pain. This study investigated whether vitamin D-deficient AIS patients had higher pain before or immediately after posterior spine fusion (PSF) surgery. 25-Hydroxy vitamin D levels were tested in all AIS patients at their pre-operative appointment. Patients were grouped by serum 25-hydroxy vitamin D level: deficient

Many patients with presumed idiopathic scoliosis are found to have Chiari I malformation (CM-I) on MRI. The objective of this study is to report on scoliosis progression in CM-I with no syringomyelia. A retrospective review of patients with scoliosis and CM-I was conducted from 1997 to 2015. Patients with syringomyelia and/or non-idiopathic scoliosis were excluded. Clinical and radiographic characteristics were recorded at presentation and latest follow-up. CM-I was defined as the cerebellar tonsil extending 5 mm or more below the foramen magnum on MRI. Thirty-two patients (72% female) with a mean age of 11 years (range 1–16) at scoliosis diagnosis were included. The average initial curve was 30.3° ± SD 16.3. The mean initial Chiari size was 9.6 mm SD ± 4.0. Fifteen (46.9%) experienced Chiari-related symptoms, and three (9%) patients underwent Posterior Fossa Decompression (PFD) to treat these symptoms. 10 (31%) patients went on to fusion, progressing on average 13.6° (95% CI 1.6–25.6°). No association was detected between decompression and either curve progression or fusion (p = 0.46, 0.60). For those who did not undergo fusion, curve magnitude progressed on average 1.0° (95% CI − 4.0 to 5.9°). There was no association between age, Chiari size, presence of symptoms, initial curve shape, or bracing treatment and fusion. Patients with CM-I and scoliosis may not require surgical treatment, including PFD and fusion. Scoliosis curvature stabilized in the non-surgical population at an average progression of 1.0°. These results suggest that CM-I with no syringomyelia has minimal effect on scoliosis progression.

Prospective cerebral palsy (CP) registry review. (1) Evaluate the incidence/risk factors of gastrointestinal (GI) complications in CP patients after spinal fusion (SF); and (2) investigate the validity of the modified Clavien–Dindo–Sink classification. Perioperative GI complications result in increased length of stay (LOS) and patient morbidity/mortality. However, none have analyzed the outcomes of GI complications using an objective classification system. A prospective/multicenter CP database identified 425 children (mean, 14.4 ± 2.9 years; range, 7.9–21 years) who underwent SF. GI complications were categorized using the modified Clavien–Dindo–Sink classification. Grades I–II were minor complications and grades III–V major. Patients with and without GI complications were compared. 87 GI complications developed in 69 patients (16.2%): 39 minor (57%) and 30 major (43%). Most common were pancreatitis (n = 45) and ileus (n = 22). Patients with preoperative G-tubes had 2.2 × odds of developing a GI complication compared to oral-only feeders (OR 2.2; 95% CI 0.98–4.78; p = 0.006). Similarly, combined G-tube/oral feeders had 6.7 × odds compared to oral-only (OR 6.7; 95% CI 3.10–14.66; p

Retrospective case-series. To evaluate the outcomes of bracing in skeletally immature patients with moderate–severe idiopathic scoliosis (IS) curves ≥ 40°. In contrast to prior beliefs, the recent studies have reported successful outcomes with brace treatment may occur in some patients with moderate–severe scoliosis ≥ 40°. Despite other encouraging case-series, non-operative treatment is rarely attempted and the efficacy of bracing large curves remains uncertain. 100 skeletally immature children (mean 11.8 ± 2.36 years; range 6.1–16.5) with IS ≥ 40° were identified. 80 were adolescent IS (80%) and 20 juvenile IS (20%). The Risser plus score was used to evaluate skeletal maturity. 66 children were Risser 0 (66%). SRS-SOSORT outcome guidelines were used: > 5° progression, stabilization between − 5° and 5° and, > 5° improvement. Mean initial Cobb was 45° ± 3.9° (range 40°–59°), with in-brace and % correction of 30° ± 8.7° (range 7°–48°) and 34 ± 17.5% (range 2–84%), respectively. 57 progressed (57%), 32 stabilized (32%), and 11 improved (11%) after a median of 1.8 years (IQR 1.2–2.9). Open triradiate cartilage at presentation (p = 0.005) and less in-brace correction (p = 0.009) were associated with progression. 58 children (58%) underwent surgery after a mean of 3.0 years (range 0.7–7.3). Surgical patients were younger (11.2 vs. 12.7 years; p = 0.003), more often Risser 0 (79% vs. 48%; p

Retrospective comparative study. We hypothesize that preoperative bracing for idiopathic scoliosis results in increased stiffness, as measured by reduced correction on bending films, ultimately leading to decreased surgical correction. Bracing is the primary nonoperative treatment for immature AIS patients with mild to moderate curves. For patients who fail bracing and proceed to operative intervention, it is unknown whether their nonoperative treatment impacts their surgical results. We conducted a single-center, retrospective, comparative study on 181 consecutive adolescent idiopathic scoliosis patients, aged 11–17 years, who underwent posterior spine fusion between 2011 and 2013. Patient flexibility was measured as percent change in the curve angle of the spine from standing to supine bend. Overall curve correction was calculated as the preoperative to postoperative change in standing coronal measure divided by the preoperative measurement and reported as a percentage. One hundred and twelve subjects (62%) underwent bracing prior to fusion. Braced patients had similar preoperative major Cobb angles than unbraced patients (56.5 vs 59.0, p = 0.07). Preoperatively, braced patients achieved less primary curve correction in bending films (33.6%) than unbraced patients (40.6%, p = 0.003). Postoperatively, Cobb angle correction was not different between the braced (75.7%) and unbraced group (77.2%) overall (p = 0.41). There was no difference in blood loss (p = 0.14) or surgical time (p = 0.96) between braced and unbraced groups when adjusted for surgeon and number of levels fused. While braced patients may demonstrate less preoperative flexibility, there is no evidence that braced patients experience decreased curve correction compared to unbraced patients. Bracing treatment did not impact operative results, as indicated by similar Cobb angle correction, estimated blood loss, and surgical time in both groups. III.

Antibiotics that are normally used to treat infections caused by Gram-positive bacteria might be made effective against Gram-negative bacterial infections, if they can circumvent permeability barriers and antibiotic deactivation processes associated with Gram-negative bacteria. Herein we report syntheses of bis-catechol–teicoplanin and mixed ligand catechol–hydroxamate–teicoplanin conjugates. Antibacterial activity assays revealed that conjugation of teicoplanin, which is only known to be active against Gram-positive bacteria, to the siderophore mimics induced potent activity against multidrug resistant strains of select Gram-negative bacteria (Acinetobacter baumannii) while retaining moderate activity against Gram-positive bacteria (Staphylococcus aureus).

Design Retrospective comparative study. Objective The purpose of this study is to measure SSI outcomes before and after implementation of our center’s multidisciplinary clinical pathway protocol for high-risk spinal surgery. Background Surgical site infections (SSIs) after spinal fusion harm patients and are associated with significant health care costs. Given the high rate of SSI in neuromuscular populations, there is a rationale to develop infection prevention strategies. Methods An institutional clinical pathway was created in 2012 and based on nationally published Best Practice Guidelines as well as hospital practices with a goal of reducing the rate of deep SSI in high-risk patients. Patient and procedure characteristics were compared prior to (2008-2011) and after (2012-2016) implementation of the pathway. Logistic regression using penalized maximum likelihood was used to assess differences in rate of infection before and after implementation. Results Cohorts of 132 and 115 high-risk patients were analyzed before and after pathway implementation. Rate of deep infections decreased from 8% to 1% of patients (p = .005). Preoperative antibiotics were dosed within 1 hour in 90% of the postpathway cohort. Redosing was successful in 94% of patients for first redose and 79% for second redose. Betadine irrigation was used in 76% of cases and vancomycin administered in 86%. Multivariable analysis determined that instances of compliant antibiotics dosing had 63% lower odds of infection compared with instances of noncompliance (p = .04). Conclusions Implementation of a multidisciplinary pathway aimed to reduce infection in patients at high risk for SSI after spinal fusion led to a significant reduction in deep SSI rate. It is impossible to attribute the drop in the deep SSI rate to any one factor. Our results demonstrate that adherence to a protocol using multiple strategies to reduce infection results in a lower SSI rate, lower care costs, and improved patient-related outcomes. Level of Evidence Level III.

This study aims to propose and validate a new unified “Risser+” grade that combines the North American (NA) and European (EU) variants of the classic Risser score. The “Risser+ ” grade can effectively combine the North American and European Risser Classifications for skeletal maturity with adequate intra-rater/inter-rater reliability and agreement. Agreement and reliability were evaluated for 6 raters (3-NA, 3-EU) who assessed 120 pelvic radiographs from the BrAIST trial, all female, average age 13.4 (range 10.1–16.5 years). Blinded raters reviewed x-rays at two time-points. Intra- and inter-rater agreement (RA) were established with Krippendorff’s alpha (k-alpha), while intra- and inter-rater reliability (RR) were established with intraclass correlation coefficients (ICC). Acceptable agreement and reliability were set a priori at 0.80. Inter-RA for the second reading met study requirements (k-alpha = 0.86 [0.81–0.90]) compared to the first reading (0.72 [0.63–0.79]) while combined readings was close to target agreement (0.79 [0.74–0.84]). Removal of 20 readings demonstrating outlier tendencies increased agreement for the first, second, and combined reads (k-alpha = 0.85, 0.89, 0.87, respectively). Intra-RA was sufficient for 4 out of 6 raters (k-alpha > 0.80) and one rater from EU and NA presented subpar intra-RA (k-alpha = 0.64 and 0.74, respectively). Inter-RR met study requirements overall reads (ICC = 0.96 [0.95–0.97]) including the first (0.94 [0.92–0.95]) and second (0.97 [0.97–0.98]) reads, independently. The Risser+ system showed excellent reliability across multiple reads and raters and demonstrated 79% agreement overall reads and ratings. Agreement increased to over 85% when raters could distinguish Risser 0 + from Risser 5. These slides can be retrieved from electronic supplementary material.

Study Design Multi-center retrospective review. Objective The purpose of this study was to identify preoperative variables associated with postoperative complications in early-onset scoliosis (EOS) patients treated with traditional growing rods (TGR); and to develop a model to predict the incidence of postoperative complications based on preoperative variables. Summary of Background Data TGRs are commonly used to treat progressive EOS. Prior research has demonstrated a high rate of postoperative complications using this technique; however, few studies have identified preoperative factors that contribute to such complications. Methods A total of 110 patients who initiated TGR treatment before 10 years of age and completed final treatment were identified from a multi-center database. Overall treatment effect was calculated for major curve size, thoracic kyphosis, thoracic height, and total spine height. Univariable and multivariable logistic regression identified preoperative predictors of complications. An algorithm was developed and validated to calculate the probability of complications based on preoperative data. Results All patients completed TGR treatment (average follow-up 8.1 years). The overall treatment effect was a significant decrease in major curve magnitude, increase in thoracic height, increase in spine height, and no significant change in thoracic kyphosis. There were 263 total complications in 87 patients (79%) resulting in 84 unplanned surgeries. The most common complications were implant-related (49%), surgical site infection (23%), medical (19%), alignment (6%), and neurologic (3%). The significant independent preoperative predictors of complications were age at implantation and preoperative thoracic kyphosis. Multivariable regression showed that age less than 7.6 years, thoracic kyphosis greater than 38 degrees, or major curve magnitude greater than 84 degrees significantly increased the probability of complications. Conclusions Earlier age at implantation, greater thoracic kyphosis, and larger major curves increased the probability of complications following TGR instrumentation. These findings provide a valuable tool for predicting complications that may aid in surgical planning and shared decision making with patients and their families. Level of Evidence IV.

Unfortunately, the affiliation of the author Negrini S has been incorrectly published in the original version. The complete correct affiliation of this author should read as follows.

Accurate detection and classification of aspiration is a critical component of videofluoroscopic swallowing evaluation, the most commonly utilized instrumental method for dysphagia diagnosis and treatment. Currently published literature indicates that interjudge reliability for the identification of aspiration ranges from poor to fairly good depending on the amount of training provided to clinicians. The majority of extant studies compared judgments among clinicians. No studies included judgments made during the use of a postural compensatory strategy. The purpose of this study was to examine the accuracy of judgments made by speech-language pathologists (SLPs) practicing in hospitals compared with unblinded expert judges when identifying aspiration and using the 8-point Penetration/Aspiration Scale. Clinicians received extensive training for the detection of aspiration and minimal training on use of the Penetration/Aspiration Scale. Videofluoroscopic data were collected from 669 patients as part of a large, randomized clinical trial and include judgments of 10,200 swallows made by 76 clinicians from 44 hospitals in 11 states. Judgments were made on swallows during use of dysphagia compensatory strategies: chin-down posture with thin liquids and head-neutral posture with thickened liquids (nectar-thick and honey-thick consistencies). The subject population included patients with Parkinson's disease and/or dementia. Kappa statistics indicate high accuracy for all interventions by SLPs for identification of aspiration (all kappa0.86) and variable accuracy (range = 69-76%) using the Penetration/Aspiration Scale when compared to expert judges. It is concluded that while the accuracy of identifying the presence of aspiration by SLPs is excellent, more extensive training and/or image enhancement is recommended for precise use of the Penetration/Aspiration Scale.

Studies that examine the effects of exercise on children’s intelligence, cognition, or academic achievement were reviewed and results were discussed in light of (a) contemporary cognitive theory development directed toward exercise, (b) recent research demonstrating the salutary effects of exercise on adults’ cognitive functioning, and (c) studies conducted with animals that have linked physical activity to changes in neurological development and behavior. Similar to adults, exercise facilitates children’s executive function (i.e., processes required to select, organize, and properly initiate goal-directed actions). Exercise may prove to be a simple, yet important, method of enhancing those aspects of children’s mental functioning central to cognitive development.

Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution. © 2005 Nature Publishing Group., link_to_OA_fulltext

Chromosome 17q25 harbors a susceptibility locus for psoriasis ( PSORS2). This locus may overlap with loci for atopic dermatitis and rheumatoid arthritis. To further refine the location of PSORS2, we genotyped 242 primarily nuclear families for 15 polymorphic microsatellites mapping to chromosome 17q23-q25. Non-parametric linkage analysis revealed a linkage peak lying close to a novel cluster of genes from the immunoglobulin (Ig) superfamily. This cluster spans250 kb and harbors five CMRF35-like genes and a sixth inhibitory receptor ( CMRF35H) with three ITIM motifs that is transcribed in the opposite direction from the rest. The Ig domains encoded by these genes are most similar to those of the TREM (triggering receptor expressed selectively in myeloid cells) molecules, NKp44 and the polymeric immunoglobulin receptor. CMRF35-like genes are only expressed in sub-populations of cells of the myeloid lineage. In order to investigate the association of this region with psoriasis, we genotyped the families for 13 novel microsatellites and 19 SNPs from the region of linkage. A maximum NPL of 1.6 ( P=0.05) was obtained within the interval. Two SNP-based haplotypes revealed some evidence for association with psoriasis. One spanned CMRF35H and includes a non-synonymous polymorphism within CMRF35H (R111Q) (TDT P=0.03). The second was a three-locus haplotype lying within the first intron of CMRF35A2 ( TREM5) (TDT P=0.04). The novel markers described here will facilitate additional linkage and association studies between the CMRF35 family and disease.

One approach to understanding model-based reasoning in science is to examine how it develops during infancy, childhood, and adolescence. The way in which thinking changes sometimes provides clues to its nature. This paper examines cognitive developmental aspects of modeling practices and discusses how a developmental perspective can enrich the study of model-based scientific reasoning in adults. The paper begins with issues concerning developmental change, followed by a model of model-based reasoning. The rest of the paper describes how several key concepts from recent developmental work could contribute to current work on model-based reasoning. Specifically, developmental research shows that (a) social processes are involved in model-based reasoning and scientific discovery, (b) the development of a theory of mind contributes to the development of scientific reasoning, (c) changes in scientific reasoning are characterized by cognitive variability, and (d) microgenetic methods could clarify conceptual change during model-based reasoning.

Linkage disequilibrium (LD), or the non-random association of alleles, is poorly understood in the human genome1. Population genetic theory suggests that LD is determined by the age of the markers, population history, recombination rate, selection and genetic drift2. Despite the uncertainties in determining the relative contributions of these factors, some groups have argued that LD is a simple function of distance between markers3,4. Disease-gene mapping studies and a simulation study gave differing predictions on the degree of LD in isolated and general populations5,6. In view of the discrepancies between theory and experimental observations, we constructed a high-density SNP map of the Xq25–Xq28 region7 and analysed the male genotypes and haplotypes across this region for LD in three populations. The populations included an outbred European sample (CEPH males) and isolated population samples from Finland and Sardinia. We found two extended regions of strong LD bracketed by regions with no evidence for LD in all three samples. Haplotype analysis showed a paucity of haplotypes in regions of strong LD. Our results suggest that, in this region of the X chromosome, LD is not a monotonic function of the distance between markers, but is more a property of the particular location in the human genome.

For Ras oncoproteins to transform mammalian cells, they must be post-translationally modified with a farnesyl group in a reaction catalysed by the enzyme farnesyl-protein transferase (FPTase). Inhibitors of FPTase have therefore been proposed as anti-cancer agents. We show that L-744,832, which mimics the CaaX motif to which the farnesyl group is added, is a potent and selective inhibitor of FPTase. In MMTV-v-Ha-ras mice bearing palpable tumours, daily administration of L-744,832 caused tumour regression. Following cessation of treatment, tumours reappeared, the majority of which regressed upon retreatment. No systemic toxicity was found upon necropsy of L-744,832-treated mice. This first demonstration of anti-FPTase-mediated tumour regression suggests that FPTase inhibitors may be safe and effective anti-tumour agents in some cancers.

The purpose of this paper was to determine the incidence of depression in our sleep disorders clinics (and it's relation to patient characteristics) and to determine whether the incidence of depression varies in patients with and without sleep apnea.The Beck Depression Inventory (BDI) was administered to evaluate patients for depression. We reviewed records of all new patients between November, 1995 and May, 1996 and determined their BDI scores and polysomnogram (PSC) results. Patients were divided based on their respiratory disturbance index (RDI); a cut off value of 15 was chosen. Patients were re-divided based on the BDI score (13 or greater suggestive of depression). The age, sex, body mass index (BMI), BDI or RDI (as appropriate) and arousal indices were compared.Sixty-three patients were enrolled; 29% were depressed. BDI scores and PSG data were available in 42 patients. Those with a high RDI had significantly lower BDI scores and higher arousal indices. Those with a high and low BDI scores were not significantly different in any of the parameters evaluated.Symptoms of depression are commonly seen in a sleep clinic. In patients with symptoms suggestive of SA but with low RDI scores, a diagnosis of depression should be entertained. The presence of depression, however, should not negatively influence a decision to perform PSG.

Spontaneous and UV induced unequal mitotic sister chromatid recombination was examined in RAD+ and rad52-1 strains carrying the LEU2 gene inserted in the rDNA locus. The rad52-1 mutation does not affect spontaneous sister chromatid recombination but greatly reduces the frequency of UV induced sister chromatid recombination.

25 VLBW infants (BW 1.3 kg) had plasma ferritin levels (PF), Hgb, Hct, and MCV measured when they reached about 2 kg in weight. 10 of them had bronchopulmonary dysplasia (BPD). None of these infants were supplemented with medicinal iron or received iron-fortified formula. Estimated iron balance (EIB) was determined by calculating iron intake from milk ingested, whole blood and packed red cells, and losses from blood drawing. Plasma ferritin was measured by RIA. Their gestational age was 29 ±2.4 wks. Results are expressed in the table as × ± SD. Plasma ferritin levels ranged from 34 to 430 ug/l. There was no significant correlation between oral intake of iron and plasma ferritin levels. However, there was correlation between iron balance and plasma ferritin levels (y=43+1.43×, r:0.58, SEE:18.3, p 0.01). Infants with BPD had higher plasma ferritin levels than those without BPD, which may reflect the more frequent transfusions. These data suggest that in VLBW infants, iron supplementation is not indicated prior to their reaching 2 kg in weight.