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Introduction: Implicit racial bias has been well studied in adults, including among orthopaedic surgeons, through the Implicit Association Test (IAT). Recent studies suggest implicit race bias is also present among children. Explicit racial preference has been studied in children through The Clark Doll Test since the 1930s. The purpose of this study was to determine whether implicit and explicit racial biases are present among pediatric orthopaedic patients., Methods: A prospective, cross-sectional survey was administered to pediatric orthopaedic patients aged 7 to 18 years at clinics in a tertiary pediatric hospital setting. The survey included a Clark Doll Test to determine whether pediatric patients expressed explicit bias, followed by a race IAT to determine whether pediatric patients expressed implicit bias. Preference and magnitude of implicit bias as demonstrated on the IAT was calculated using standard D-scores., Results: A total of 96 patients were consented and included in this study. Overall, pediatric patients demonstrated a slight pro-White implicit bias (M = 0.22) on IAT testing. Pediatric patients who identified as White or European American and Hispanic or Latinx both had the strongest pro-White implicit bias (M = 0.35). Patients who identified as Black or African American demonstrated no implicit racial bias (M = -0.13) on IAT testing. No notable explicit bias was observed in participants of any racial background., Discussion: This study contributes evidence that pediatric orthopaedic patients express implicit racial bias on IAT testing, with an overall slight pro-White bias. It also provides insight into the dissociation of implicit and explicit racial bias in childhood and adolescence., Conclusion: We encourage future research on implicit bias among pediatric patients in the orthopaedic community to provide a better understanding and possible solutions to bias-related challenges in health care., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Modern glycoproteomics experiments require the use of search engines due to the generation of countless spectra. While these tools are valuable, manual validation of search engine results is often required for detailed analysis of glycopeptides as false-discovery rates are often not reliable for glycopeptide data. Near-isobaric mismatches are a common source of misidentifications for the popular glycopeptide-focused search engine pGlyco3.0, and in this technical note we share a strategy and script that improves the accuracy of the search utilizing two manually validated datasets of the glycoproteins CD16a and HIV-1 Env as proof-of-principle., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Competition-based learning (CBL) facilitates learning through competitions. At the 2022 & 2023 Annual SAGES meetings, we evaluated a CBL experience (TOP GUN Shootout) developed from a modified version of the previously validated TOP GUN Laparoscopic Skills and Suturing Program. The project sought to evaluate the TOP GUN Shootout's (TGS) ability to enhance participant engagement in pursuit of laparoscopic surgical skills., Methods: Participants competed in the TGS. Their scores (time and errors) were recorded for: Fundamentals of Laparoscopic Surgery Peg Pass, Cup Drop Task, and Intracorporeal Suturing. All participants completed a 10-question satisfaction survey on a 7-point Likert scale, with questions assessing 3 domains: (1) capability/confidence in MIS skill performance prior to the competition; (2) applicability and satisfaction with TGS's capacity to develop MIS skills; and (3) interest in seeking additional MIS training and appropriateness of CBL in MIS training. Descriptive statistics were used to evaluate these areas., Results: Overall, 121 participants completed the TGS, of whom 84 (69%) completed the satisfaction survey. The average age was 32.9 years, 67% were males. On average (+/- SD), participant satisfaction was 5.04 (+/- 2.08) for Domain 1, 6.20 (+/- 1.28) for Domain 2, and 6.58 (+/- .95) for Domain 3., Conclusion: Participants described an overall lack of confidence in their MIS skills prior to the 2022-2023 Annual SAGES conference. Participants felt that this brief CBL experience, aided in the development of their MIS skills. Furthermore, this brief CBL experience may inspire learners to seek out further training of their MIS skills., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Mr. Nicco Ruggiero, Dr. Joseph C. L’Huillier, Mr. Nigel Marine, Mr. Owen Burns, Ms. Farrah Mawani, 2nd LT. Muavé Sanders, Mr. Adam Abbas, Dr. Timothy Adams, and Dr. Yana R. Wirengard have no conflict of interest to disclose. Author Dr. Byron F. Santos shares royalties as a co-investor of the 3-Dmed Laparoscopic Common Bile Duct Exploration simulator and receives payment from Boston Scientific as well as Cook Medical. Author Dr. James “Butch” Rosser is an educational consultant for Boston Scientific, HumanXtensions, and Karl Storz as well as the CEO of Stealth Learning Company.

Potato is the third most important food crop in the world. Diverse pathogens threaten sustainable crop production but can be controlled, in many cases, through the deployment of disease resistance genes belonging to the family of nucleotide-binding, leucine-rich-repeat (NLR) genes. To identify effective disease resistance genes in established varieties, we have successfully established SMRT-AgRenSeq in tetraploid potatoes and have further enhanced the methodology by including dRenSeq in an approach that we term SMR-AgRenSeq-d. The inclusion of dRenSeq enables the filtering of candidates after the association analysis by establishing a presence/absence matrix across resistant and susceptible varieties that is translated into an F1 score. Using a SMRT-RenSeq-based sequence representation of the NLRome from the cultivar Innovator, SMRT-AgRenSeq-d analyses reliably identified the late blight resistance benchmark genes Rpi-R1 , Rpi-R2-like , Rpi-R3a , and Rpi-R3b in a panel of 117 varieties with variable phenotype penetrations. All benchmark genes were identified with an F1 score of 1, which indicates absolute linkage in the panel. This method also identified nine strong candidates for Gpa5 that controls the potato cyst nematode (PCN) species Globodera pallida (pathotypes Pa2/3). Assuming that NLRs are involved in controlling many types of resistances, SMRT-AgRenSeq-d can readily be applied to diverse crops and pathogen systems., Competing Interests: The authors declare that they have no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Background: In the ten years since the initial publication of the RenSeq protocol, the method has proved to be a powerful tool for studying disease resistance in plants and providing target genes for breeding programmes. Since the initial publication of the methodology, it has continued to be developed as new technologies have become available and the increased availability of computing power has made new bioinformatic approaches possible. Most recently, this has included the development of a k-mer based association genetics approach, the use of PacBio HiFi data, and graphical genotyping with diagnostic RenSeq. However, there is not yet a unified workflow available and researchers must instead configure approaches from various sources themselves. This makes reproducibility and version control a challenge and limits the ability to perform these analyses to those with bioinformatics expertise., Results: Here we present HISS, consisting of three workflows which take a user from raw RenSeq reads to the identification of candidates for disease resistance genes. These workflows conduct the assembly of enriched HiFi reads from an accession with the resistance phenotype of interest. A panel of accessions both possessing and lacking the resistance are then used in an association genetics approach (AgRenSeq) to identify contigs positively associated with the resistance phenotype. Candidate genes are then identified on these contigs and assessed for their presence or absence in the panel with a graphical genotyping approach that uses dRenSeq. These workflows are implemented via Snakemake, a python-based workflow manager. Software dependencies are either shipped with the release or handled with conda. All code is freely available and is distributed under the GNU GPL-3.0 license., Conclusions: HISS provides a user-friendly, portable, and easily customised approach for identifying novel disease resistance genes in plants. It is easily installed with all dependencies handled internally or shipped with the release and represents a significant improvement in the ease of use of these bioinformatics analyses., (© 2023. The Author(s).)

N-glycosylation is an essential eukaryotic posttranslational modification that affects various glycoprotein properties, including folding, solubility, protein-protein interactions, and half-life. N-glycans are processed in the secretory pathway to form varied ensembles of structures, and diversity at a single site on a glycoprotein is termed 'microheterogeneity'. To understand the factors that influence glycan microheterogeneity, we hypothesized that local steric and electrostatic factors surrounding each site influence glycan availability for enzymatic modification. We tested this hypothesis via expression of reporter N-linked glycoproteins in N-acetylglucosaminyltransferase MGAT1-null HEK293 cells to produce immature Man 5 GlcNAc 2 glycoforms (38 glycan sites total). These glycoproteins were then sequentially modified in vitro from high mannose to hybrid and on to biantennary, core-fucosylated, complex structures by a panel of N-glycosylation enzymes, and each reaction time course was quantified by LC-MS/MS. Substantial differences in rates of in vitro enzymatic modification were observed between glycan sites on the same protein, and differences in modification rates varied depending on the glycoenzyme being evaluated. In comparison, proteolytic digestion of the reporters prior to N-glycan processing eliminated differences in in vitro enzymatic modification. Furthermore, comparison of in vitro rates of enzymatic modification with the glycan structures found on the mature reporters expressed in WT cells correlated well with the enzymatic bottlenecks observed in vivo. These data suggest higher order local structures surrounding each glycosylation site contribute to the efficiency of modification both in vitro and in vivo to establish the spectrum of microheterogeneity in N-linked glycoproteins., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Thousands of nuclear and cytosolic proteins are modified with a single β-N-acetylglucosamine on serine and threonine residues in mammals, a modification termed O-GlcNAc. This modification is essential for normal development and plays important roles in virtually all intracellular processes. Additionally, O-GlcNAc is involved in many disease states, including cancer, diabetes, and X-linked intellectual disability. Given the myriad of functions of the O-GlcNAc modification, it is therefore somewhat surprising that O-GlcNAc cycling is mediated by only two enzymes: the O-GlcNAc transferase (OGT), which adds O-GlcNAc, and the O-GlcNAcase (OGA), which removes it. A significant outstanding question in the O-GlcNAc field is how do only two enzymes mediate such an abundant and dynamic modification. In this review, we explore the current understanding of mechanisms for substrate selection for the O-GlcNAc cycling enzymes. These mechanisms include direct substrate interaction with specific domains of OGT or OGA, selection of interactors via partner proteins, posttranslational modification of OGT or OGA, nutrient sensing, and localization alteration. Altogether, current research paints a picture of an exquisitely regulated and complex system by which OGT and OGA select substrates. We also make recommendations for future work, toward the goal of identifying interaction mechanisms for specific substrates that may be able to be exploited for various research and medical treatment goals., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Transcriptomics is being increasingly applied to generate new insight into the interactions between plants and their pathogens. For the wheat yellow (stripe) rust pathogen (Puccinia striiformis f. sp. tritici, Pst) RNA-based sequencing (RNA-Seq) has proved particularly valuable, overcoming the barriers associated with its obligate biotrophic nature. This includes the application of RNA-Seq approaches to study Pst and wheat gene expression dynamics over time and the Pst population composition through the use of a novel RNA-Seq based surveillance approach called "field pathogenomics". As a dual RNA-Seq approach, the field pathogenomics technique also provides gene expression data from the host, giving new insight into host responses. However, this has created a wealth of data for interrogation., Results: Here, we used the field pathogenomics approach to generate 538 new RNA-Seq datasets from Pst-infected field wheat samples, doubling the amount of transcriptomics data available for this important pathosystem. We then analysed these datasets alongside 66 RNA-Seq datasets from four Pst infection time-courses and 420 Pst-infected plant field and laboratory samples that were publicly available. A database of gene expression values for Pst and wheat was generated for each of these 1024 RNA-Seq datasets and incorporated into the development of the rust expression browser ( http://www.rust-expression.com ). This enables for the first time simultaneous 'point-and-click' access to gene expression profiles for Pst and its wheat host and represents the largest database of processed RNA-Seq datasets available for any of the three Puccinia wheat rust pathogens. We also demonstrated the utility of the browser through investigation of expression of putative Pst virulence genes over time and examined the host plants response to Pst infection., Conclusions: The rust expression browser offers immense value to the wider community, facilitating data sharing and transparency and the underlying database can be continually expanded as more datasets become publicly available.

The oomycete Phytophthora fragariae is a highly destructive pathogen of cultivated strawberry ( Fragaria × ananassa ), causing the root rotting disease, "red core". The host-pathogen interaction has a well described gene-for-gene resistance relationship, but to date neither candidate avirulence nor resistance genes have been identified. We sequenced a set of American, Canadian, and United Kingdom isolates of known race type, along with three representatives of the closely related pathogen of the raspberry ( Rubus idaeus ), P. rubi , and found a clear population structure, with a high degree of nucleotide divergence seen between some race types and abundant private variation associated with race types 4 and 5. In contrast, between isolates defined as United Kingdom races 1, 2, and 3 (UK1-2-3) there was no evidence of gene loss or gain; or the presence of insertions/deletions (INDELs) or Single Nucleotide Polymorphisms (SNPs) within or in proximity to putative pathogenicity genes could be found associated with race variation. Transcriptomic analysis of representative UK1-2-3 isolates revealed abundant expression variation in key effector family genes associated with pathogen race; however, further long read sequencing did not reveal any long range polymorphisms to be associated with avirulence to race UK2 or UK3 resistance, suggesting either control in trans or other stable forms of epigenetic modification modulating gene expression. This work reveals the combined power of population resequencing to uncover race structure in pathosystems and in planta transcriptomic analysis to identify candidate avirulence genes. This work has implications for the identification of putative avirulence genes in the absence of associated expression data and points toward the need for detailed molecular characterisation of mechanisms of effector regulation and silencing in oomycete plant pathogens., (Copyright © 2020 Adams, Armitage, Sobczyk, Bates, Tabima, Kronmiller, Tyler, Grünwald, Dunwell, Nellist and Harrison.)

Background: We looked at long-term follow-up of spine stapling with Nitinol Staples. This was a cohort of all adolescent idiopathic scoliosis (AIS) patients with curves at high risk to progress based on curve magnitude, premenarchal status in all females, failure of brace treatment, and skeletal immaturity., Methods: This is a single surgeon retrospective review of consecutive AIS patients treated with Nitinol staples for progressive scoliosis. Fourteen patients, 16 curves from 2005 to 2008 were eligible. Minimum curve for stapling was 30 degrees. Standard preoperative, intraoperative, and postoperative data were collected. All patients were followed for a minimum of 36 months and to skeletal maturity. Three groups were: improved (group 1), correction of any amount; minimal progression (group 2), progression ≤10 degrees; and failure (group 3), ≥10 degrees of progression., Results: A total of 13 thoracic curves and 2 compensatory lumbar curves met the inclusion criteria (94%). Average follow-up was 61 months. The mean preoperative main thoracic curve was 35 degrees. All but 1 patients progressed at least 9 degrees in a brace prior to stapling. Females were all premenarchal, 10 patients were Risser 0 and 3 Risser 1. The average number of vertebrae stapled per curve was 6. Group 1 included 6 curves (40%). Group 2, 5 curves (33%). Group 3, 4 curves (27%). Three patients went on to uncomplicated fusion. Final curve measurement at the end of follow-up or before fusion (P=0.0037), curve progression (P≤0.001), and percentage of coronal correction on first postoperative standing radiograph (P=0.042) were the significant differences between groups 1+2 (successful) versus group 3 (failures). In total, 73% of this group either progressed ≤10 degrees or improved., Conclusions: This is the first study that follows AIS patients treated with spine stapling to skeletal maturity. Staples likely changed natural history in some of our patients. Initial percentage of correction on first standing postoperative PA x-rays was the only predictor of success. Stapling was safe without any long-term complications., Level of Evidence: Level III-retrospective study.

Individuals with severe or profound intellectual disabilities may be at a greater risk of developing mental health problems. Despite this, evidence suggests individuals can face difficulties in getting mental health support, and little is known about effective psychological therapies for this population. Hence, this study explored mothers' experiences of seeking mental health support for their offspring. Semi-structured interviews were conducted with six mothers of adults with severe or profound intellectual disabilities, who had sought mental health support for their offspring. Interviews were audio-recorded and analysed using Interpretative Phenomenological Analysis. The three main themes were 'A struggle to understand, Challenges to getting mental health support, and A mother's approach to adapting therapy.' Mothers found it difficult to recognise signs of emotional difficulties in their offspring. However, they thought that their offspring faced discrimination when accessing services, and that professionals often lacked the knowledge and skills to work with people with severe impairments. The mothers also stressed the importance of the therapeutic relationship and the need to involve carers in therapy. This study highlights the need for more appropriate mental health support for individuals with severe and profound intellectual disabilities. The findings also suggest further research is needed about adapting psychological therapies for this population., Competing Interests: No potential conflict of interest was reported by the authors., (© The British Society of Developmental Disabilities 2019.)

Background: Diabetic patients undergoing total joint arthroplasty (TJA) with postoperative hyperglycemia >200 mg/dL have increased the risk of prosthetic joint infection (PJI). We investigated the correlation between preoperative hemoglobin A1c (A1c) and postoperative hyperglycemia in diabetic patients undergoing TJA., Methods: A retrospective review of 773 diabetic patients undergoing TJA was conducted. A Youden's J computational analysis determined the A1c where postoperative glucose levels >200 mg/dL were statistically more likely. Patients were then stratified into 3 groups: A1c <7%, A1c 7.0-8.0%, and A1c >8.0%. Outcomes included the highest postoperative in-hospital serum glucose level and PJI., Results: We determined an A1c >7.45% resulted in a greater chance of postoperative hyperglycemia >200 mg/dL. Average postoperative serum glucose increased with A1c (A1c < 7 = 167 mg/dL, A1c 7.0-8.0 = 240 mg/dL, and A1c > 8 = 276 mg/dL, P < .0001). PJI did not statistically increase with A1c (2.25%, 1.99%, and 4.55%, respectively, P = .4319)., Conclusion: Preoperative hemoglobin A1c levels correlate with postoperative glucose levels. We recommend using an A1c cutoff of 7.45% for patients undergoing TJA and suggest that caution should be exercised in patients with elevated A1c levels undergoing TJA., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To determine if use of cerclage in twin gestations with mid-trimester short cervix is associated with decreased preterm birth rate., Study Design: This is a retrospective cohort of twin gestations identified with cervical length of ≤2.5 cm before 24 weeks of gestation through the perinatal ultrasound database of two institutions from 2008 to 2014. Patients with and without cerclage were compared for a primary outcome of preterm birth at <35 weeks. A pre-planned sub-group analysis of patients with cervical length ≤1.5 cm was also performed., Results: Eighty-two patients were included; 43 received cerclage, 39 did not. Mean gestational age at cerclage placement was 20.8 weeks. There was no significant difference in rate of preterm birth <35 weeks between the groups (34.9% versus 48.7%, respectively). In the sub-group analysis of patients with cervical length ≤1.5 cm, there was a significant decreased risk of preterm birth <35 weeks [37% versus 71.4%; adjusted RR 0.49 (0.26-0.93)]., Conclusion: Cerclage placement for cervical length ≤2.5 cm in twin gestations did not decrease the rate of preterm birth at <35 weeks; however, cerclage placement for cervical length ≤1.5 cm was associated with a significantly decreased rate of preterm birth <35 weeks when compared to patients managed without cerclage.

Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

Impairments in verbal working memory are evident in major depression. Verbal working memory is comprised of the components of encoding, maintenance and retrieval. Whether the neural impairments are expressed in specific components, and how pharmacological therapy could modify the neural correlates are not well understood. We investigated the neural correlates of verbal working memory components in depression using the Sternberg task in a longitudinal magnetic resonance imaging study. Serial scans were acquired in 23 patients (mean age 39.8 years) during an acute depressive episode and following 12 weeks of pharmacological therapy with duloxetine and in 22 matched healthy controls (mean age 39.1 years) at the same time points. A significant group by time interaction was evident during the long maintenance phase, extending from the left middle frontal to the middle temporal and caudate regions, in which there was reduced activation in healthy participants at the follow -up scan but there were no changes in patients. Persistent neural engagement during the maintenance phase following treatment was revealed in major depression. The findings emphasize that impairments in verbal working memory may be initiated in the maintenance phase in major depression in order to sustain performance. Further research with larger sample size and using randomized, placebo-controlled double-blind studies are required to confirm our results.

Background: Cervical length by transvaginal ultrasound to predict preterm labor is widely used in clinical practice. Virtually no data exist on cervical length measurement to differentiate true from false labor in term patients who present for labor check. False-positive diagnosis of true labor at term may lead to unnecessary hospital admissions, obstetrical interventions, resource utilization, and cost., Objective: We sought to determine if cervical length by transvaginal ultrasound can differentiate true from false labor in term patients presenting for labor check., Study Design: This is a prospective observational study of women presenting to labor and delivery with labor symptoms at 37-42 weeks, singleton cephalic gestation, regular uterine contractions (≥4/20 min), intact membranes, and cervix ≤4 cm dilated and ≤80% effaced. Those patients with placenta previa and indications for immediate delivery were excluded. The shortest best cervical length of 3 collected images was used for analysis. Providers managing labor were blinded to the cervical length. True labor was defined as spontaneous rupture of membranes or spontaneous cervical dilation ≥4 cm and ≥80% effaced within 24 hours of cervical length measurement. In the absence of these outcomes, labor status was determined as false labor. Receiver operating characteristic curves were generated to assess the predictive ability of cervical length to differentiate true from false labor and were analyzed separately for primiparous and multiparous patients. The diagnostic accuracies of various cervical length cutoffs were determined. The relationship of cervical length and time to delivery was also analyzed including both use and nonuse of oxytocin., Results: In all, 77 patients were included in the study; the prevalence of true labor was 58.4% (45/77). Patients who were in true labor had shorter cervical length as compared to those in false labor: median 1.3 cm (range 0.5-4.1) vs 2.4 cm (range 1.0-5.0), respectively (P < .001). The area under the receiver operating characteristic curve for primiparous patients was 0.88 (P < .001) and for multiparous patients was 0.76 (P < .01), both demonstrating good correlation. The area under the receiver operating characteristic curves were not significantly different between primiparous and multiparous (P = .23). The area under the receiver operating characteristic curve for primiparous and multiparous patients combined was 0.8 (P < .0001), indicating a good overall correlation between cervical length and its ability to differentiate true from false labor. Overall, a cervical length cutoff of ≤1.5 cm to predict true labor had the highest specificity (81%), positive predictive value (83%), and positive likelihood ratio (4.2). There were no differences in cervical length prediction between primiparous and multiparous patients. Cervical length was positively correlated with time to delivery, regardless of the use of oxytocin., Conclusion: In differentiating true from false labor in term patients who present for labor check, a cervical length of ≤1.5 cm was the most clinically optimal cutoff with the lowest false positive rate-due to its highest specificity-and highest positive predictive value and positive likelihood ratios. Its use to decide admission in patients at term with labor symptoms may prevent unnecessary admissions, obstetrical interventions, resource utilization, and cost., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Untreated fetal pleural effusion can cause significant perinatal morbidity and mortality. Treatment of pleural effusions with pleuro-amniotic shunting has been shown to improve outcomes. Pleuro-amniotic shunting is associated with complications including ruptured membranes, preterm labor and shunt dislodgement into either the amniotic cavity or the fetal thorax. Shunt dislodgement into the thoracic cavity can cause prenatal complications from the shunt itself or may necessitate neonatal surgery for removal. We present a case where a novel ultrasound-guided technique was used to replace the dislodged pleural shunt in utero, thereby effectively draining the effusion while simultaneously obviating the need for neonatal surgery and decreasing possible perinatal complications., (© 2015 S. Karger AG, Basel.)

Objective: To determine the practice patterns of antenatal corticosteroid (AS) administration in women with threatened preterm labor., Methods: This was a retrospective cohort of patients who received betamethasone between 2009 and 2010, identified through a pharmacy database. Patients with high order multiples; incomplete records and indicated preterm delivery were excluded. Demographic and obstetrical factors were compared between women with an AS to delivery latency of ≤7 days versus >7 days. Parametric and non-parametric tests were used as appropriate. p < 0.05 denotes statistical significance; relative risks with 95% confidence intervals were calculated., Results: Three-hundred forty-five patients were included. Sixty-eight patients (20%) received AS within 7 days of delivery. Women who received AS ≤7 days before delivery (optimal timing) were more likely to have a transvaginal cervical length ≤2 cm (RR:2.53, CI: 1.2-5.6), cervical dilation ≥2 cm (RR: 3.86, CI: 2.7-5.6) and positive fFN (RR: 2.59, CI: 1.1-6.3). Preterm premature ruptured membranes were also associated with optimal timing of AS (RR: 4.86, CI: 3.4-6.8)., Conclusions: Eighty percent of patients receive suboptimal timing of AS administration. Factors associated with suboptimal timing are: cervical length >2 cm, cervical dilation <2 cm and negative fFN. Cervical assessment should be a key factor in the decision for AS administration. More research is needed for accurate timing of AS in women with threatened preterm labor.

Background: Successful management of chronic cough has varied in the primary research studies in the reported literature. One of the potential reasons relates to a lack of intervention fidelity to the core elements of the diagnostic and/or therapeutic interventions that were meant to be used by the investigators., Methods: We conducted a systematic review to summarize the evidence supporting intervention fidelity as an important methodologic consideration in assessing the effectiveness of clinical practice guidelines used for the diagnosis and management of chronic cough. We developed and used a tool to assess for five areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1998 to May 2014. Guideline recommendations and suggestions for those conducting research using guidelines or protocols to diagnose and manage chronic cough in the adult were developed and voted upon using CHEST Organization methodology., Results: A total of 23 studies (17 uncontrolled prospective observational, two randomized controlled, and four retrospective observational) met our inclusion criteria. These articles included 3,636 patients. Data could not be pooled for meta-analysis because of heterogeneity. Findings related to the five areas of intervention fidelity included three areas primarily related to the provider and two primarily related to the patients. In the area of study design, 11 of 23 studies appeared to be underpinned by a single guideline/protocol; for training of providers, two of 23 studies reported training, and zero of 23 reported the use of an intervention manual; and for the area of delivery of treatment, when assessing the treatment of gastroesophageal reflux disease, three of 23 studies appeared consistent with the most recent guideline/protocol referenced by the authors. For receipt of treatment, zero of 23 studies mentioned measuring concordance of patient-interventionist understanding of the treatment recommended, and zero of 23 mentioned measuring enactment of treatment, with three of 23 measuring side effects and two of 23 measuring adherence. The overall average intervention fidelity score for all 23 studies was poor (20.74 out of 48)., Conclusions: Only low-quality evidence supports that intervention fidelity strategies were used when conducting primary research in diagnosing and managing chronic cough in adults. This supports the contention that some of the variability in the reporting of patients with unexplained or unresolved chronic cough may be due to lack of intervention fidelity. By following the recommendations and suggestions in this article, researchers will likely be better able to incorporate strategies to address intervention fidelity, thereby strengthening the validity and generalizability of their results that provide the basis for the development of trustworthy guidelines.

Background: We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic., Methods: We followed the American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework. The Expert Cough Panel based their recommendations on data from the systematic review, patients' values and preferences, and the clinical context. Final grading was reached by consensus according to Delphi methodology., Results: The results of the systematic review revealed only low-quality evidence to support how to define or diagnose psychogenic or habit cough with no validated diagnostic criteria. With respect to treatment, low-quality evidence allowed the committee to only suggest therapy for children believed to have psychogenic cough. Such therapy might consist of nonpharmacologic trials of hypnosis or suggestion therapy, or combinations of reassurance, counseling, and referral to a psychologist, psychotherapy, and appropriate psychotropic medications. Based on multiple resources and contemporary psychologic, psychiatric, and neurologic criteria (Diagnostic and Statistical Manual of Mental Disorders, 5th edition and tic disorder guidelines), the committee suggests that the terms psychogenic and habit cough are out of date and inaccurate., Conclusions: Compared with the 2006 CHEST Cough Guidelines, the major change in suggestions is that the terms psychogenic and habit cough be abandoned in favor of somatic cough syndrome and tic cough, respectively, even though the evidence to do so at this time is of low quality.

Objective: We sought to determine the timing of administration of antenatal corticosteroids (AS) for indicated preterm births and to identify which indications are associated with the most optimal timing of administration., Study Design: This was a retrospective cohort of patients who received AS in anticipation of indicated preterm birth from 2009 through 2012 at Winthrop University Hospital, Mineola, NY. Medical records of patients who received AS, as identified through the hospital pharmacy database, were reviewed. Patients were included if they had a singleton or twin gestation and they received AS for maternal or fetal indications. Women were excluded if they received AS for spontaneous preterm labor or preterm rupture of membranes. Maternal demographic and obstetrical characteristics were compared between those who received AS≤7 days vs >7 days from delivery using parametric and nonparametric tests with relative risks and 95% confidence intervals. P<.05 was considered significant., Results: In all, 193 patients were included in this study. Median latency from AS administration to delivery was 9 days (range, 0-83); 93 patients (48%) received AS within 7 days of delivery. There were no significant differences between the 2 groups with regards to baseline maternal characteristics. Those delivering within 7 days of AS administration were more likely to have maternal vs fetal indications (84% vs 16%)., Conclusion: Only 48% of patients with an indication for preterm birth received AS within 7 days of its administration. AS appear to be more optimally timed in the presence of maternal rather than fetal indications., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Longitudinal neuroimaging studies of major depressive disorder (MDD) have most commonly assessed the effects of antidepressants from the serotonin reuptake inhibitor class and usually reporting a single measure. Multimodal neuroimaging assessments were acquired from MDD patients during an acute depressive episode with serial measures during a 12-week treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine., Methods: Participants were medication-free MDD patients (n = 32; mean age 40.2 years) in an acute depressive episode and healthy controls matched for age, gender, and IQ (n = 25; mean age 38.8 years). MDD patients received treatment with duloxetine 60 mg daily for 12 weeks with an optional dose increase to 120 mg daily after 8 weeks. All participants had serial imaging at weeks 0, 1, 8, and 12 on a 3 Tesla magnetic resonance imaging (MRI) scanner. Neuroimaging tasks included emotional facial processing, negative attentional bias (emotional Stroop), resting state functional MRI and structural MRI., Results: A significant group by time interaction was identified in the anterior default mode network in which MDD patients showed increased connectivity with treatment, while there were no significant changes in healthy participants. In the emotional Stroop task, increased posterior cingulate activation in MDD patients normalized following treatment. No significant group by time effects were observed for happy or sad facial processing, including in amygdala responsiveness, or in regional cerebral volumes. Reduced baseline resting state connectivity within the orbitofrontal component of the default mode network was predictive of clinical response. An early increase in hippocampal volume was predictive of clinical response., Conclusions: Baseline resting state functional connectivity was predictive of subsequent clinical response. Complementary effects of treatment were observed from the functional neuroimaging correlates of affective facial expressions, negative attentional bias, and resting state. No significant effects were observed in affective facial processing, while the interaction effect in negative attentional bias and individual group effects in resting state connectivity could be related to the SNRI class of antidepressant medication. The specificity of the observed effects to SNRI pharmacological treatments requires further investigation., Trial Registration: Registered at clinicaltrials.gov ( NCT01051466 ).

Validating competency to meet accreditation and safety demands is a major challenge many organizations face. Traditional testing methods may only reflect guessing and may not capture the amount of misinformation nurses are using for critical decision making. Using a confidence-based learning methodology allows learners to correct misinformation and gain confidence and competency., (Copyright 2013, SLACK Incorporated.)

Thrombocytopenia is a common complication encountered in pregnancy, and can have a wide range of prognostic implications, from completely benign to life threatening. It is important for obstetricians to be aware of the various causes of thrombocytopenia in pregnancy, and to be able to diagnose and manage these patients. This article reviews the various causes of thrombocytopenia in pregnancy, highlights clinical and laboratory features of the most common and most severe causes, and provides an overview of management for these disorders., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Sampling sites for determining lactate concentration [La(-)] have been debated for years. To date, none of the research that has been completed has taken into consideration the muscle group that is active during exercise, sample site, and the passivity of nonexercising muscle, collectively. The purpose of this study was to determine if this passive sink phenomenon could be visualized by using common sampling methods immediately after exercise and during the recovery period from 2 sample sites. Eleven male cyclists completed a subject-specific trial on a Velotron cycle ergometer. Plasma [La(-)] was measured from the finger and toe immediately postexercise and every 5 minutes after, for 25 minutes after the cycling trial. All 3 analyses were significant (p < 0.05) with the sample site × sample time interaction, sample time main effect, and sample site main effect being reported, respectively: Wilks' λ = 0.079, F (5,6) = 13.932, p = 0.003, Wilks' λ = 0.012, F (5,6) = 94.804, p = 0.000, and Wilks' λ = 0.492, F (1,10) = 10.316, p = 0.009. Post hoc paired t-tests on computed mean differences between sample sites for each sample time revealed statistically significant differences (p < 0.05) between several time intervals. Further analysis also revealed significant differences (p < 0.05) in the sample site main effect at each collection time. Blood lactate samples need to be obtained from the limb containing the exercising muscle(s) to negate the passive sink effect that has been observed to occur in nonexercising muscles. This recommendation needs to be followed to better establish future training volumes and outcomes.

Recognizing the ongoing need for continuing education for school nurses, the authors discuss the use of school nurse book clubs as an innovative lifelong-learning strategy. Current research supports the use of literature in nursing education. This article discusses the benefits of book club participation for school nurses and includes suggested fiction and nonfiction books that can be used to enhance nursing knowledge and practice. Through reading and discussion, school nurses can increase their knowledge of nursing history and current health care issues, thus becoming better prepared to address challenging issues that arise in practice. In addition, the use of literature as a learning strategy allows school nurses to broaden their understanding of unique cultural factors that influence the health beliefs and practices of students and their families. Book club participation can also assist school nurses in honing leadership and communication skills and becoming energized to become better advocates for children and families.

Crude oil spills represent a major ecological threat because of the chemical inertness of the constituent n-alkanes. The Gram-negative bacterium Pseudomonas aeruginosa is one of the few bacterial species able to metabolize such compounds. Three chromosomal genes, rubB, rubA1, and rubA2 coding for an NAD(P)H:rubredoxin reductase (RdxR) and two rubredoxins (Rdxs) are indispensable for this ability. They constitute an electron transport (ET) pathway that shuttles reducing equivalents from carbon metabolism to the membrane-bound alkane hydroxylases AlkB1 and AlkB2. The RdxR-Rdx system also is crucial as part of the oxidative stress response in archaea or anaerobic bacteria. The redox couple has been analyzed in detail as a model system for ET processes. We have solved the structure of RdxR of P. aeruginosa both alone and in complex with Rdx, without the need for cross-linking, and both structures were refined at 2.40- and 2.45-A resolution, respectively. RdxR consists of two cofactor-binding domains and a C-terminal domain essential for the specific recognition of Rdx. Only a small number of direct interactions govern mutual recognition of RdxR and Rdx, corroborating the transient nature of the complex. The shortest distance between the redox centers is observed to be 6.2 A.

Pseudomonas aeruginosa is both a ubiquitous environmental bacterium and an opportunistic human pathogen. A remarkable metabolic versatility allows it to occupy a multitude of ecological niches, including wastewater treatment plants and such hostile environments as the human respiratory tract. P. aeruginosa is able to degrade and metabolize biocidic SDS, the detergent of most commercial personal hygiene products. We identify SdsA1 of P. aeruginosa as a secreted SDS hydrolase that allows the bacterium to use primary sulfates such as SDS as a sole carbon or sulfur source. Homologues of SdsA1 are found in many pathogenic and some nonpathogenic bacteria. The crystal structure of SdsA1 reveals three distinct domains. The N-terminal catalytic domain with a binuclear Zn2+ cluster is a distinct member of the metallo-beta-lactamase fold family, the central dimerization domain ensures resistance to high concentrations of SDS, whereas the C-terminal domain provides a hydrophobic groove, presumably to recruit long aliphatic substrates. Crystal structures of apo-SdsA1 and complexes with substrate analog and products indicate an enzymatic mechanism involving a water molecule indirectly activated by the Zn2+ cluster. The enzyme SdsA1 thus represents a previously undescribed class of sulfatases that allows P. aeruginosa to survive and thrive under otherwise bacteriocidal conditions.

Intimins from pathogenic bacteria promote intimate bacterial adhesion to epithelial cells. Several structurally similar domains form on the bacterial cell surface an extended rigid rod that exposes the carboxy-terminal domain, which interacts with the translocated intimin receptor. We constructed a series of intimin-derived fusion proteins consisting of carboxy-terminally truncated intimin and the immunoglobulin light-chain variable domain REIv, ubiquitin, calmodulin, beta-lactamase inhibitor protein, or beta-lactamase. By systematically investigating the intimin-mediated cell surface exposure of these passenger domains in the presence or absence of compounds that interfere with outer membrane stability or passenger domain folding, we acquired experimental evidence that intimin-mediated protein export across the outer membrane requires, prior to export, the maintenance of a translocation-competent conformation that may be distinct from the final protein structure. We propose that, during export, competition exists between productive translocation and folding of the passenger domain in the periplasm into a stable conformation that is not compatible with translocation through the bacterial outer membrane. These results may expand understanding of the mechanism by which intimins are inserted into the outer membrane and expose extracellular domains on the cell surface.

Enzyme libraries displayed on the surface of microbial cells or microbeads can be screened with fluorogenic substrates that provide a physical linkage of the reaction product to the corresponding enzyme. Libraries exceeding 10(9) different variants can be quantitatively analysed and screened by flow cytometry at a rate of 30 000 cells/second. The promise of screening methods based on fluorescence-activated cell sorting for directed enzyme evolution is being realized and significantly improved enzymes have been reported recently.

Study Objective: To psychometrically evaluate a cough-specific quality-of-life questionnaire (CQLQ) in adults., Design: Prospective evaluation of CQLQ using three different cohorts of adult subjects with cough., Setting: Academic tertiary-care ambulatory medical facilities., Participants: One hundred fifty-four subjects complaining of chronic cough, 30 of acute cough, and 31 smokers with cough., Interventions: Self-administration of the CQLQ in acute coughers, smokers, and chronic coughers before and after therapy., Measurements: Psychometric analyses including factor analysis (FA), and assessments of reliability and validity., Results: Acute and chronic cough data were subjected to FA, and the Cronbach alpha and interitem correlations were computed. FA of chronic and acute cough data (n = 184) revealed six subscales. The Cronbach alpha for the total CQLQ was 0.92, and it was 0.62 to 0.86 (mean, 0.76) for the six subscales. Interitem correlations for the total CQLQ ranged from -0.06 to 0.72, with a mean of 0.28. Test-retest reliability in 52 chronic coughers demonstrated nonsignificant changes with readministration of the questionnaire, and the intraclass correlation for total CQLQ was 0.89, and for the subscales the range was 0.75 to 0.93. Analysis of variance followed by tests of contrasts among all possible pairings of chronic coughers, acute coughers, and smokers showed significant differences (p < or = 0.001) among the groups. Posttreatment cure scores were significantly lower (p < or = 0.001) than pretreatment scores in 24 chronic coughers., Conclusions: The 28-item CQLQ has dimensionality that is consistent with a cough-specific quality-of-life instrument. It is a valid and reliable method by which to assess the impact of cough on the quality of life of chronic and acute coughers, and the efficacy of cough therapies in chronic coughers.

A survey of alumni attitudes about their college physical education activity (PEA) program and current exercise habits was sent to a representative sample (N = 3169) of alumni who had graduated between 1970 and 1984 from four private colleges. The percent returned was 48, 31, 43, and 41 from Colleges A-D, respectively. Three of the four colleges had required PEA programs. College A had an eight-credit-hour requirement, College B required four credit-hours, College C required two credits, and College D did not have a PEA requirement. Results indicated a significant difference among the four colleges in the alumni's perceived value of their college PEA program in terms of its contribution to their knowledge about fitness, attitude towards fitness, and current exercise habits. Additionally, alumni differed in their perception of the health value of exercise and in their frequency of weekly exercise. When alumni exercise behaviors were quantified by aerobic points and classified according to type of activity, no statistically significant differences were found. The conclusion of the study was that the attitudes and exercise behaviors of alumni are related to the type of college PEA requirement; however, aerobic points earned are not affected. Students graduating from colleges with higher PEA requirements demonstrate more positive exercise attitudes and behaviors.

Twenty-seven patients with refractory leukemia were treated with 1-beta-D-arabinofuranosylcytosine (ara-C), 0.3 to 3.0 g/m2 as i.v. infusions over 1, 2, 4, or 24 h. The pharmacokinetics of ara-C in plasma and its 5'-triphosphate (ara-CTP) in leukemic cells from peripheral blood were studied after a single infusion of 3 g/m2 over 2 h in 13 patients. Accumulation of ara-CTP in leukemic cells remained linear until 1 to 2 h after the infusion. At the time when the rate of ara-CTP accumulation deviated from linearity, the plasma concentration of ara-C was 5- to 20-fold lower [8.1 +/- 4.4 (SD) microM] than the steady-state level during the infusion. Plasma ara-C and cellular ara-CTP pharmacokinetics were studied after two serial infusions in 14 additional patients. Varying the duration of infusion of an ara-C dose between 1, 2, and 4 h (corresponding to infusion rates of 3000, 1500, and 750 mg/m2/h) did not substantially change the rate of ara-CTP accumulation by leukemic cells. The peak ara-CTP concentration and the area under the concentration times time curve (AUC) of ara-CTP in leukemic cells increased with prolongation of the infusion. Although steady-state concentration of ara-C and AUC of ara-C in plasma were proportionally reduced by 1.0 or 0.5 g/m2 infusion over 2 h, ara-CTP accumulation rate and AUC in leukemic cells did not change compared with administration of 3 g/m2 over 2 h. However, when the infusion rate was further reduced to 0.4 or 0.3 g/m2 over 2 h, resulting in steady-state plasma ara-C concentrations of less than 7 microM, the accumulation rate of ara-CTP was substantially reduced as was the ara-CTP intracellular AUC. The cellular elimination rate of ara-CTP remained constant under all infusion conditions. These findings support the conclusion that high-dose ara-C therapy, as currently administered, results in plasma ara-C concentrations that saturate the accumulation of ara-CTP by circulating leukemic cells. We recommend that intermediate dose rates, 200 to 250 mg/m2/h, be evaluated in future studies as an alternative to the substantially higher ara-C dose rates currently in use.

Sludges containing high concentrations of zinc, copper or nickel and an uncontaminated sludge were added to two sandy loams (pH 6.5 and 7.1), a heavy clay (pH 6.3) and a calcareous clay (pH 7.8) to give ten sludge treatments for each soil. The mixtures were incubated fallow, cropped continuously with clover, or cropped with barley and red beet in rotation for 21 months. The quantity of added metal either in the soil solution or extracted by 0.1m CaCl(2) depended on the metal loading, pH and soil cation exchange capacity, and changed with time after mixing soils and sludges. Crop metal concentrations, and the occurrence of metal-induced yield reductions, also depended on soil properties as well as metal loading. The best chemical extractant for predicting plant metal concentrations was 0.1m CaCl(2).

The effects of pH on concentrations of zinc, copper and nickel extracted by calcium chloride from a clay loam and two sandy loam soils that had been treated with sewage sludge were studied. Concentrations of all the metals increased rapidly as pH decreased below a threshold value ranging from 6.2 to 7.0 for Zn, 6.2 to 7.2 for Ni and 4.7 to 5.7 for Cu. Both the total concentrations and the threshold pH values were influenced by differences in soil texture and (between the two light-textured soils) by differences in soil cation exchange capacity. The amount of zinc and copper extracted from the mixtures was considerably less than that extracted from the same quantity of sludge alone.