bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular tension encodes local Src-dependent differential β1 and β3 integrin mobility
Authors: De Mets Richard , Wang Irene , Balland Martial , Oddou Christiane , Moreau Philippe , Fourcade Bertrand , Albiges-Rizo Corinne , Delon Antoine , Destaing Olivier
Published: November 2018

Integrins are transmembrane receptors that have a pivotal role in mechanotransduction processes by connecting the extracellular matrix to the cytoskeleton. Although it is well established that integrin activation/inhibition cycles are due to highly dynamic interactions, whether integrin mobility depends on local tension and cytoskeletal organization remains surprisingly unclear. Using an original approach combining micropatterning on glass substrates to induce standardized local mechanical constraints within a single cell with temporal image correlation spectroscopy, we measured the mechanosensitive response of integrin mobility at the whole cell level and in adhesion sites under different mechanical constraints. Contrary to β1 integrins, high tension increases β3 integrin residence time in adhesive regions. Chimeric integrins and structure–function studies revealed that the ability of β3 integrins to specifically sense local tensional organization is mostly encoded by its cytoplasmic domain and is regulated by tuning the affinity of its NPXY domains through phosphorylation by Src family kinases.
Effects of cardiomyopathy-linked mutations K15N and R21H in tropomyosin on thin-filament regulation and pointed-end dynamics
Authors: Ly Thu , Pappas Christopher T. , Johnson Dylan , Schlecht William , Colpan Mert , Galkin Vitold E. , Gregorio Carol C. , Dong Wen-Ji , Kostyukova Alla S.
Published: November 2018

Missense mutations K15N and R21H in striated muscle tropomyosin are linked to dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), respectively. Tropomyosin, together with the troponin complex, regulates muscle contraction and, along with tropomodulin and leiomodin, controls the uniform thin-filament lengths crucial for normal sarcomere structure and function. We used Förster resonance energy transfer to study effects of the tropomyosin mutations on the structure and kinetics of the cardiac troponin core domain associated with the Ca2+-dependent regulation of cardiac thin filaments. We found that the K15N mutation desensitizes thin filaments to Ca2+and slows the kinetics of structural changes in troponin induced by Ca2+dissociation from troponin, while the R21H mutation has almost no effect on these parameters. Expression of the K15N mutant in cardiomyocytes decreases leiomodin’s thin-filament pointed-end assembly but does not affect tropomodulin’s assembly at the pointed end. Our in vitro assays show that the R21H mutation causes a twofold decrease in tropomyosin’s affinity for F-actin and affects leiomodin’s function. We suggest that the K15N mutation causes DCM by altering Ca2+-dependent thin-filament regulation and that one of the possible HCM-causing mechanisms by the R21H mutation is through alteration of leiomodin’s function.
Combinatorial processing of bacterial and host-derived innate immune stimuli at the single-cell level
Authors: Gutschow Miriam V. , Mason John C. , Lane Keara M. , Maayan Inbal , Hughey Jacob J. , Bajar Bryce T. , Amatya Debha N. , Valle Sean D. , Covert Markus W.
Published: November 2018

During the course of a bacterial infection, cells are exposed simultaneously to a range of bacterial and host factors, which converge on the central transcription factor nuclear factor (NF)-κB. How do single cells integrate and process these converging stimuli? Here we tackle the question of how cells process combinatorial signals by making quantitative single-cell measurements of the NF-κB response to combinations of bacterial lipopolysaccharide and the stress cytokine tumor necrosis factor. We found that cells encode the presence of both stimuli via the dynamics of NF-κB nuclear translocation in individual cells, suggesting the integration of NF-κB activity for these stimuli occurs at the molecular and pathway level. However, the gene expression and cytokine secretion response to combinatorial stimuli were more complex, suggesting that other factors in addition to NF-κB contribute to signal integration at downstream layers of the response. Taken together, our results support the theory that during innate immune threat assessment, a pathogen recognized as both foreign and harmful will recruit an enhanced immune response. Our work highlights the remarkable capacity of individual cells to process multiple input signals and suggests that a deeper understanding of signal integration mechanisms will facilitate efforts to control dysregulated immune responses.
Selective defects in gene expression control genome instability in yeast splicing mutants
Authors: Tam Annie S. , Sihota Tianna S. , Milbury Karissa L. , Zhang Anni , Mathew Veena , Stirling Peter C.
Published: November 2018

RNA processing mutants have been broadly implicated in genome stability, but mechanistic links are often unclear. Two predominant models have emerged: one involving changes in gene expression that perturb other genome maintenance factors and another in which genotoxic DNA:RNA hybrids, called R-loops, impair DNA replication. Here we characterize genome instability phenotypes in yeast splicing factor mutants and find that mitotic defects, and in some cases R-loop accumulation, are causes of genome instability. In both cases, alterations in gene expression, rather than direct cis effects, are likely to contribute to instability. Genome instability in splicing mutants is exacerbated by loss of the spindle-assembly checkpoint protein Mad1. Moreover, removal of the intron from the α-tubulin gene TUB1 restores genome integrity. Thus, differing penetrance and selective effects on the transcriptome can lead to a range of phenotypes in conditional mutants of the spliceosome, including multiple routes to genome instability.
Visualization and quantification of mitochondrial structure in the endothelium of intact arteries
Authors: Durand Matthew J , Ait-Aissa Karima , Levchenko Vladislav , Staruschenko Alexander , Gutterman David D , Beyer Andreas M
Published: November 2018

Aim

To quantify the mitochondrial structure of ECs in intact arteries vs. cultured cells.

Methods and results

Cre-stop mito-Dendra2 mice, expressing the fluorescent protein Dendra2 in the mitochondrial matrix only, were used to label EC mitochondria using Cre-recombinase under the control of the VE-cadherin promoter. Conduit arteries, resistance arterioles and veins were fixed, mounted on glass slides and fluorescent images were obtained using a laser scanning confocal microscope (ex 488 nm; em 550 nm). ImageJ was used to calculate form factor (FF) and aspect ratio (AR) of the mitochondrial segments. Mitochondrial fragmentation count (MFC) was calculated by counting non-contiguous mitochondrial particles and dividing by the number of pixels which comprise the mitochondrial network. Primary aortic EC cultures (48 h on culture plates) were generated to compare the mitochondrial structure of cultured ECs vs. intact arteries. Aortic segments were also exposed to high glucose overnight (33 mM) ex vivo, and separate groups of mice were either infused with a high-glucose saline solution (300 mM) via tail vein catheter for 1 h or injected with streptozotocin (STZ; 50 mg/kg) to cause hyperglycaemia. Compared with cultured ECs, the mitochondria of ECs from the intact aorta were more fragmented (MFC: 6.4 ± 2.5 vs. 18.6 ± 9.4, respectively; P < 0.05). The mitochondrial segments of ECs within the aorta were more circular in shape (FF: 3.5 ± 0.75 vs. 1.8 ± 0.30, respectively; P < 0.05) and had less branching (AR: 2.9 ± 0.60 vs. 2.0 ± 0.25, respectively; P < 0.05) compared with cultured ECs. Ex vivo exposure of the intact aorta to high glucose overnight caused mitochondrial fission compared with normal glucose conditions (5 mM; MFC: 25.5 ± 11.1 high glucose vs. 11.0 ± 3.6 normal glucose; P < 0.05). Both 1-h infusion of high glucose saline (MFC: 22.4 ± 4.3) and STZ treatment (MFC: 40.3 ± 14.2) caused mitochondrial fission compared with freshly fixed aortas from control mice (MFC: 18.6 ± 9.4; P < 0.05 vs. high-glucose infusion and STZ treatment).

Conclusions

Using a novel mouse model, we were able to, for the first time, obtain high resolution images of EC mitochondrial structure in intact arteries. We reveal the endothelial mitochondrial network is more fragmented in the intact aorta compared with cultured ECs, indicating that mitochondria assume a more elongated and branched phenotype in cell culture.
RNA-binding protein Ptbp1 is essential for BCR-mediated antibody production
Authors: Sasanuma Hiroki , Ozawa Manabu , Yoshida Nobuaki
Published: November 2018

The RNA-binding protein polypyrimidine tract-binding protein-1 (Ptbp1) binds to the pyrimidine-rich sequence of target RNA and controls gene expression via post-transcriptional regulation such as alternative splicing. Although Ptbp1 is highly expressed in B lymphocytes, its role to date is largely unknown. To clarify the role of Ptbp1 in B-cell development and function, we generated B-cell-specific Ptbp1-deficient (P1BKO) mice. B-cell development in the bone marrow, spleen and peritoneal cavity of the P1BKO mice was nearly normal. However, the P1BKO mice had significantly lower levels of natural antibodies in serum compared with those of the control mice. To investigate the effect of Ptbp1 deficiency on the immune response in vivo, we immunized the P1BKO mice with T-cell-independent type-2 (TI-2) antigen NP-Ficoll and T-cell-dependent (TD) antigen NP-CGG. We found that B-cell-specific Ptbp1 deficiency causes an immunodeficiency phenotype due to defective production of antibody against both TI-2 and TD antigen. This immunodeficiency was accompanied by impaired B-cell receptor (BCR)-mediated B-cell activation and plasmablast generation. These findings demonstrate that Ptbp1 is essential for the humoral immune response.
Between spilling over and boiling down: network-mediated spillovers, local knowledge base and productivity in European regions
Authors: Cortinovis Nicola , van Oort Frank
Published: November 2018

Productivity across European regions is related to three types of networks that mediate R&D-related knowledge spillovers: trade, co-patenting and geographical proximity. Both our panel and instrumental variable estimations for European regions suggest that network relations are crucial sources of R&D spillovers, but with potentially different features. Both import and co-patenting relations affect local productivity directly, but spillovers from innovation-leading regions are effective only when they are import-mediated and when recipient regions have a solid knowledge base. From a policy perspective, this may frustrate recent European policy initiatives, such as Smart Specialization, which are designed to benefit all regions in Europe.
Cirrus: An Automated Mammography-Based Measure of Breast Cancer Risk Based on Textural Features
Authors: Schmidt Daniel F , Makalic Enes , Goudey Benjamin , Dite Gillian S , Stone Jennifer , Nguyen Tuong L , Dowty James G , Baglietto Laura , Southey Melissa C , Maskarinec Gertraud , Giles Graham G , Hopper John L
Published: November 2018

Background

We applied machine learning to find a novel breast cancer predictor based on information in a mammogram.

Methods

Using image-processing techniques, we automatically processed 46 158 analog mammograms for 1345 cases and 4235 controls from a cohort and case–control study of Australian women, and a cohort study of Japanese American women, extracting 20 textural features not based on pixel brightness threshold. We used Bayesian lasso regression to create individual- and mammogram-specific measures of breast cancer risk, Cirrus. We trained and tested measures across studies. We fitted Cirrus with conventional mammographic density measures using logistic regression, and computed odds ratios (OR) per standard deviation adjusted for age and body mass index.

Results

Combining studies, almost all textural features were associated with case–control status. The ORs for Cirrus measures trained on one study and tested on another study ranged from 1.56 to 1.78 (all P < 10−6). For the Cirrus measure derived from combining studies, the OR was 1.90 (95% confidence interval [CI] = 1.73 to 2.09), equivalent to a fourfold interquartile risk ratio, and was little attenuated after adjusting for conventional measures. In contrast, the OR for the conventional measure was 1.34 (95% CI = 1.25 to 1.43), and after adjusting for Cirrus it became 1.16 (95% CI = 1.08 to 1.24; P = 4 × 10−5).

Conclusions

A fully automated personal risk measure created from combining textural image features performs better at predicting breast cancer risk than conventional mammographic density risk measures, capturing half the risk-predicting ability of the latter measures. In terms of differentiating affected and unaffected women on a population basis, Cirrus could be one of the strongest known risk factors for breast cancer.
“Hard Times Make for Hard Arteries and Hard Livers”: Deindustrialization, Biopolitics, and the Making of a New Working Class
Authors: Winant Gabriel
Published: November 2018

This article argues for a view of “actually existing neoliberalism,” identifying points of continuity from midcentury social democracy and showing how American neoliberalism developed unevenly across a preexisting landscape. It does so with a case study of labor market transformation in Pittsburgh, showing a causal relationship between the New Deal state’s institutional structures and the rise of low-wage employment in health care in the 1970s and 1980s. The low-wage service economy did not only come after the high-wage industrial economy: it grew out of it, sped by the decline of steel manufacturing and shaped within the distinctive matrix of the postwar public-private welfare. In establishing this historical process, the article also suggests that social history can play a useful conceptual role linking Foucauldian and Marxist accounts of neoliberalism, by showing concretely the role of the production of subjectivity and the governance of population in the establishment of the neoliberal economic regime. Pointing to a homology between the structural role of incarceration in neoliberalism and that of health care, the article suggests the term “biopolitical Keynesianism” for understanding this conceptual synthesis, which uncovers new contradictions within neoliberalism.
Impact of the Society for Research on Nicotine and Tobacco Health Disparities Network’s Scholarship on Professional Development of Its Recipients
Authors: Davis Danielle R , Hickman Norval J , Choi Kelvin , Robinson Cendrine D , Patten Christi A , Fagan Pebbles , Okuyemi Kolawole S , Nahvi Shadi
Published: November 2018

Introduction

Diversifying the workforce is an important strategy to reducing health disparities. Since 2007, the Society for Research on Nicotine and Tobacco (SRNT) Health Disparities Network has funded a travel scholarship to promote inclusion, professional development, and diversity among investigators interested in tobacco-related health disparities research. This study examined indicators of productivity among former scholarship recipients.

Methods: Scholarship recipients between 2007 and 2014 were invited to complete a survey online. The survey assessed demographic characteristics, academic productivity, and perceived professional benefit resulting from the scholarship.

Results: Of the 117 scholarships recipients, 89 (77%) responded. Respondents were 67% female and had a mean age of 37.8 years. Twenty eight percent were African American, 25% Asian American, and 17% Latino. Most respondents worked in academia (80%) and nearly three-quarters (74%) reported publishing manuscripts on tobacco-related disparities, with a mean of 3.8 (SD 4.4) disparities-related publications since receiving the scholarship. Respondents’ work focused on a wide range of health disparities topics and nearly all respondents reported that the scholarship removed barriers to attending the meeting and reported professional benefit from receiving the travel scholarship. Following receipt of the SRNT travel scholarship, a diverse group of scientists demonstrated scholarly productivity, professional development, and advancement of health disparities research. Similar efforts are encouraged in other professional societies.

Implications

This study examines the productivity of early career recipients of the SRNT Health Disparities Scholarship. Results suggest that the investment in annual travel scholarships by a professional organization is an important support system for emerging scientists from diverse backgrounds. This investment may help to advance the science of health disparities and engage researchers in an area where there are critical gaps in the research workforce.
Sex disparities in clinical characteristics and prognosis of immunoglobulin G4–related disease: a prospective study of 403 patients
Authors: Wang Liwen , Zhang Panpan , Zhang Xia , Lin Wei , Tang Hanqi , Li Jieqiong , Wang Mu , Liu Xiaowei , Fei Yunyun , Chen Hua , Peng Linyi , Zhang Li , Lai Yamin , Zeng Xuejun , Li Xuemei , Xue Huadan , Zhao Yan , Zhang Fengchun , Zhang Wen
Published: November 2018

Objectives

To study the impact of sex on the clinical presentation of IgG4-related disease (IgG4-RD).

Methods

We prospectively enrolled 403 newly diagnosed IgG4-RD patients. We compared the demographic features, clinical manifestations, organ involvement, laboratory tests and treatment outcomes between female and male patients. The organs involved were divided into superficial organs (salivary glands, lacrimal glands, orbit, sinus and skin) and internal organs (all the other organs). The patients treated with glucocorticoids with or without additional immunosuppressants were included in the assessment of treatment outcomes, and potential confounding factors were corrected by propensity score matching or multivariate Cox regression analysis.

Results

Female patients showed younger age at both symptom onset and diagnosis, and a longer interval between symptom onset and diagnosis. Allergy history, Mikulicz’s disease and thyroiditis were more common in female patients, while autoimmune pancreatitis, sclerosing cholangitis and retroperitoneal fibrosis were more common in male patients. In accordance, female patients more frequently presented with superficial organ involvement, while male patients more frequently had internal organ involvement, and the discrepancy was more prominent in the patients with older age. Male sex was associated with higher peripheral eosinophils, CRP and IgG4 levels at baseline. In response to glucocorticoid-based therapies, male sex was associated with a higher IgG4-RD responder index during follow-up as well as a greater risk of relapse (hazard ratio 3.14, P = 0.003).

Conclusion

Our study revealed the sex disparities in clinical characteristics of IgG4-RD, and indicated that male sex was independently associated with worse prognosis in response to glucocorticoid-based therapies.
DETRIMENTS IN NEURON MORPHOLOGY FOLLOWING HEAVY ION IRRADIATION: WHAT’S THE TARGET?
Authors: Cucinotta Francis A , Eliedonna Cacao Murat Alp
Published: November 2018

Neuron cells consist of the soma or cell body, axons, dendritic arbor with multiple branches, and dendritic spines which are the substrates for memory storage and synaptic transmission. Detriments in neuron morphology are suggested to play a key role in cognitive impairments following brain irradiation. Multiple molecular mechanisms are involved in the regulation and stability of neuron morphology, while the effects of radiation on these processes have not been studied extensively. In this report, we consider possible biological targets in neurons for energy deposition (ED) by charged particles that could lead to neuron morphology detriments, and the resulting dose and radiation quality dependence of such detriments. The track structures of heavy ions including high charge and energy (HZE) particles consists of core of high-ED events and a penumbra of sparse ED from δ-ray electrons produced in ionization of target molecules. We consider the role of track structure relative to possible targets causative in the degradation of morphology.
Adolescent Paranoia: Prevalence, Structure, and Causal Mechanisms
Authors: Bird Jessica C , Evans Robin , Waite Felicity , Loe Bao S , Freeman Daniel
Published: November 2018

Background

Adolescence can be a challenging time, characterized by self-consciousness, heightened regard for peer acceptance, and fear of rejection. Interpersonal concerns are amplified by unpredictable social interactions, both online and offline. This developmental and social context is potentially conducive to the emergence of paranoia. However, research on paranoia during adolescence is scarce.

Method

Our aim was to examine the prevalence, structure, and probabilistic causal mechanisms of adolescent paranoia. A representative school cohort of 801 adolescents (11–15 y) completed measures of paranoia and a range of affective, cognitive, and social factors. A Bayesian approach with Directed Acyclic Graphs (DAGs) was used to assess the causal interactions with paranoia.

Results

Paranoid thoughts were very common, followed a continuous distribution, and were hierarchically structured. There was an overall paranoia factor, with sub-factors of social fears, physical threat fears, and conspiracy concerns. With all other variables controlled, DAG analysis identified paranoia had dependent relationships with negative affect, peer difficulties, bullying, and cognitive-affective responses to social media. The causal directions could not be fully determined, but it was more likely that negative affect contributed to paranoia and paranoia impacted peer relationships. Problematic social media use did not causally influence paranoia.

Conclusions

There is a continuum of paranoia in adolescence and occasional suspicions are common at this age. Anxiety and depression are closely connected with paranoia and may causally contribute to its development. Paranoia may negatively impact adolescent peer relationships. The clinical significance of paranoia in adolescents accessing mental health services must now be established.
Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development: biochemical markers associated with emerging clinical phenotypes and molecular endotypes
Authors: Mobasheri Ali , van Spil Willem Evert , Budd Emma , Uzieliene Ilona , Bernotiene Eiva , Bay-Jensen Anne-Christine , Larkin Jonathan , Levesque Marc C. , Gualillo Oreste , Henrotin Yves
Published: November 2018

Purpose of review

This review focuses on the molecular taxonomy of osteoarthritis from the perspective of molecular biomarkers. We discuss how wet biochemical markers may be used to understand disease pathogenesis and progression and define molecular endotypes of osteoarthritis and how these correspond to clinical phenotypes.

Recent findings

Emerging evidence suggests that osteoarthritis is a heterogeneous and multifaceted disease with multiple causes, molecular endotypes and corresponding clinical phenotypes. Biomarkers may be employed as tools for patient stratification in clinical trials, enhanced disease management in the primary care centres of the future and for directing more rational and targeted osteoarthritis drug development. Proximal molecular biomarkers (e.g synovial fluid) are more likely to distinguish between molecular endotypes because there is less interference from systemic sources of biomarker noise, including comorbidities.

In this review, we have focused on the molecular biomarkers of four distinct osteoarthritis subtypes including inflammatory, subchondral bone remodelling, metabolic syndrome and senescent age-related endotypes, which have corresponding phenotypes. Progress in the field of osteoarthritis endotype and phenotype research requires a better understanding of molecular biomarkers that may be used in conjunction with imaging, pain and functional assessments for the design of more effective, stratified and individualized osteoarthritis treatments.
Incorporating risk factors in the development of the screening programme for developmental dysplasia of the hips
Authors: Tan Si Heng Sharon , Wong Keng Lin , Hui James Hoipo
Published: November 2018

In a 12-year cohort study, all newborns with suspected developmental dysplasia of the hips (DDHs) were scheduled for hip ultrasound at the sixth week of life. Female sex is the only isolated risk factor with a positive likelihood ratio predictive of DDH [1.26; 95% confidence interval (CI): 1.04–1.54]. In combination, the presence of two or more risk factors was predictive of DDH (positive likelihood ratio 1.10; 95% CI: 1.00–1.20). The sensitivity and specificity of two or more risk factors for the prediction of DDH were 93.6% (95% CI: 86.6–97.6) and 14.5% (95% CI: 8.70–22.2), respectively. The level of evidence for the cohort study is II.
Urinary N-Telopeptide Can Predict Pseudarthrosis After Anterior Cervical Decompression and Fusion
Authors: Steinhaus Michael E. , Hill Patrick S. , Yang Jingyan , Feuchtbaum Eric , Bronheim Rachel S. , Prabhakar Pooja , Lafage Virginie , Carlson Brandon B. , Saville Philip , Albert Todd J. , Lafage Renaud , Stein Emily M. , Kim Han J.
Published: November 2018

Study Design.

Prospective cohort study.

Objective.

To examine preoperative urinary cross-linked n-telopeptide (uNTx) and assess for association with fusion rates in patients undergoing single and multi-level anterior cervical decompression and fusion (ACDF).

Summary of Background Data.

Although high rates of fusion have been reported for ACDF, the risk of pseudarthrosis remains substantial. An established marker of bone turnover, uNTx may prove useful as a predictor of fusion.

Methods.

Patients undergoing primary ACDF with allograft/plating technique from 2015 to 2017 by a single surgeon were consecutively enrolled and preoperative uNTx was collected. Patients undergoing revision, with creatinine >1.2, and with improperly-collected uNTx were excluded. Demographics, laboratory values, and fusion status were assessed at 6 months, 1 year, and 2 years postoperatively.

Results.

Of the 97 patients enrolled, 69 met inclusion criteria. Of included cases, 41%, 33%, 18%, and 8% underwent 1-, 2-, 3-, and 4-level ACDF, respectively. Overall, fusion rates were 37.3%, 70.9%, and 95.3% at 6 months, 1 year, and 2 years, respectively. uNTx was higher in the fusion group (31.1 vs. 22.2, P = 0.001) at 6 months and 1 year (30.0 vs. 21.0, P = 0.006), with no difference at 2 years. No differences were identified in the proportion of smokers, immunomodulatory agents, corpectomies, or fusion levels between groups. Multivariate regression analysis demonstrated that uNTx is an independent predictor of fusion (odds ratio, OR, 1.124, P = 0.003). Both groups experienced improvements in NDI and VAS neck pain at 6 months with no significant differences noted between groups. Of 16 patients with pseudarthrosis at 1 year, 2 underwent posterior cervical fusion for symptoms.

Conclusion.

Preoperative uNTx was greater in patients with successful ACDF fusion compared with patients with pseudarthrosis at 6 months and 1 year. A negative correlation was found between preoperative uNTx and motion on dynamic imaging. These results suggest that uNTx could serve to identify patients at risk for pseudarthrosis after ACDF.

Level of Evidence: 3
Does Decreased Surgical Stress Really Improve the Psychosocial Health of Early-onset Scoliosis Patients?
Authors: Aslan Cihan , Olgun Z. Deniz , Ayik Gokhan , Karaokur Remzi , Ozusta Seniz , Demirkiran Gokhan Halil , Unal Fatih , Yazici Muharrem
Published: November 2018

Study Design.

Cross-sectional case-control study.

Objective.

Compare psychosocial profile of magnetically-controlled growing rod (MCGR) patients to traditional-growing rod (TGR) with an array of psychiatric tools, expecting improvement in MCGR due to decreased number of surgical procedures.

Summary of Background Data.

TGR treatment has had positive clinical and radiographic results; however, upward of 10 surgical sessions and high complication rates have called into question the quality of life of these children. Improvement with the introduction of the MCGR is expected.

Methods.

GR patients with minimum of 2-years follow-up were recruited. None had neurological conditions. All underwent testing with the Wechsler Intelligence Scale for Children-Revised, and only those in the normal range were included. Patients filled out questionnaires with mental health professionals to measure psychosocial status. MCGR patients’ results were compared to TGR patients.

Results.

Twenty-seven patients met criteria (10 MCGR, 17 TGR): average age at enrollment 11.8 years (range 5.9–17). MCGR group was significantly younger (9.1 vs. 13.3 yr) and had significantly shorter follow-up (45.6 vs. 82.8 mo) (P < 0.05). TGR patients underwent an average of 16 surgical procedures, MCGR an average of 1.5 (including complications, P < 0.05). Age at index surgery (6 yr), preoperative and postoperative major curve magnitudes (60°, 40° respectively) were statistically similar.

There was no difference in current psychiatric diagnoses between the groups. MCGR patients scored worse than TGR patients in general functionality domains. TGR patients showed increased functionality and prosocial scores with increased number of procedures. This effect was not observed in MCGR.

Conclusions.

The expected improvement in psychosocial status with the MCGR was not observed at a 31.6-month-follow-up. It appears that provided the patient spends enough time in the treatment process to notice benefit and does not experience major complications, noninvasiveness of lengthening procedures does not show up as an advantage with the psychosocial tools utilized in this study.

Level of Evidence: 3
Differential Psychometric Properties of EuroQoL 5-Dimension 5-Level and Short-Form 6-Dimension Utility Measures in Low Back Pain
Authors: Cheung Prudence Wing Hang , Wong Carlos King Ho , Cheung Jason Pui Yin
Published: November 2018

Study Design.

Prospective study.

Objective.

To examine the acceptability and validity of EuroQoL 5-dimension 5-level (EQ-5D-5L) and Short-Form 6-Dimension (SF-6D) health utility measures in patients with low back pain (LBP).

Summary of Background Data.

LBP requires multiple diagnostic tests and treatment that can incur high medical costs. It is thus desirable to have an appropriate measure for cost-utility analysis of various LBP-related interventions.

Methods.

Health-related quality of life (HRQoL) questionnaires including generic 12-item Short Form Health Survey (SF-12), EQ-5D-5L, and low back/back-related questionnaires were administered at a specialty clinic. SF-12 items responses were transformed to SF-6D utility scores using the Hong Kong population scoring algorithm whereas EQ-5D-5L responses were mapped onto EQ-5D-3L response, then converted to EQ-5D-5L utility scores using the Chinese-specific value set. Construct validity was determined by evaluating Spearman correlation between SF-12 and EQ-5D-5L scores. Correlation between back-specific questionnaires and HRQoL scores were assessed.

Results.

A total of 100 patients were recruited. No significant (>15%) floor and ceiling effects were observed for EQ-5D-5L and SF-6D scores. Detailed proportion of respondents for each EQ-5D-5L domain indicated that Pain/Discomfort domain was the most prevalent problem. SF-6D utility score and EQ-5D-5L had respective strong (0.600–0.855) and moderate-to-strong (0.455–0.700) correlations with SF-12 domain and summary scores. EQ-5D-5L and SF-6D scores were correlated (0.625), with adequate construct validity as both utility scores conceptually measure the similar construct. Patients with no previous spine surgery nor disc degeneration had significantly higher EQ-5D-5L scores. Both EQ-5D-5L and SF-6D significantly correlated with back-specific questionnaires.

Conclusion.

Both EQ-5D-5L and SF-6D appeared as applicable and valid measures in assessing HRQoL of LBP patients. Being the first study examining the differential psychometric properties and validation of the use of EQ-5D-5L and SF-6D in Chinese LBP population, this allows future exploration of the impact of utility score selection on assessing effectiveness of clinical intervention for LBP.

Level of Evidence: 2
Clinical Impact of Ossification of the Posterior Longitudinal Ligament Progression After Cervical Laminoplasty
Authors: Kawaguchi Yoshiharu , Nakano Masato , Yasuda Taketoshi , Seki Shoji , Suzuki Kayo , Yahara Yasuhito , Makino Hiroto , Kobayashi Kenji , Kanamori Masahiko , Kimura Tomoatsu
Published: November 2018

Study Design:

This is a retrospective study.

Objectives:

(1) To analyze the incidence of second surgery after initial laminoplasty for ossification of the posterior longitudinal ligament (OPLL) due to disease progression, (2) to examine factors associated with poor surgical outcome.

Summary of Background Data:

Neurological deterioration after laminoplasty is frequently encountered due to OPLL progression.

Patients and Methods:

Of 201 OPLL patients treated by laminoplasty at a single-institution, the 153 monitored for >3 years postsurgery were included in this analysis. Neurological findings were graded by the Japanese Orthopaedic Association (JOA) score. We retrospectively examined the incidence of second surgery due to OPLL progression. We also evaluated the clinical characteristics and the surgical outcomes after second operation to identify potential risk factors for poor outcome.

Results:

Eight patients required a second surgery due to OPLL progression. Neurological recovery was achieved in 5 of these patients, whereas 3 exhibited continued dysfunction. Patients with poor recovery showed kyphotic changes of spinal alignment and high-intensity regions in the spinal cord on T2-weighted magnetic resonance images (T2-MRI).

Conclusions:

Only a small fraction of OPLL patients required a second surgery due to OPLL progression. Recovery was poor in those with clear high-intensity T2-MRI signals in the spinal cord.
Safety of 2-level Anterior Cervical Discectomy and Fusion (ACDF) Performed in an Ambulatory Surgery Setting With Same-day Discharge
Authors: Vaishnav Avani , Hill Patrick , McAnany Steven , Gang Catherine H. , Qureshi Sheeraz
Published: November 2018

Study Design:

This was a retrospective review of prospectively collected data.

Objective:

To evaluate differences in patient factors, procedural factors, outcomes and safety in 2-level anterior cervical discectomy and fusion (ACDF) performed in ambulatory surgery centers (ASCs) versus the hospital setting.

Background:

Emphasis on reducing health care costs has led to numerous surgeries across specialties being performed in ASCs. Because of short operative times and moderate postoperative pain, 1-level ACDF is one of the most common spine surgeries successfully performed in ASCs. Despite the success of single-level ACDF, concerns over postoperative complications, including respiratory compromise have curtailed the performance of 2-level ACDF in ASCs.

Materials and Methods:

Patient demographics, operative factors and outcomes [blood loss, operative time, length of stay, complications and patient-reported outcomes (PROs)] of patients undergoing 2-level ACDF in an ASC and a hospital were compared using the Fisher exact test for categorical and the Student t test for continuous variables.

Results:

Of the 83 patients included, 25 underwent 2-level ACDF in an ASC, and 58 in a hospital. Mean age for the ASC group was 51.7±7.6 and 53.2±7.9 years for the hospital group (P=0.44). Body mass index was lower in the ASC group, at 27.3 kg/m2 versus 30.4 in the hospital group (P=0.03). Likewise, the ASC group had a lower ASA grade, favoring ASA 1 and 2 (P<0.001). There were no differences in blood loss (P=0.72) or complication rates, (P=0.16) with urinary retention being most common, and only 1 patient in the hospital setting requiring reintubation. In addition, no patients in the ASC setting required hospitalization. There were no differences in preoperative, 6-week and 6-month PROs.

Conclusions:

The results of our study suggest that 2-level ACDF can be performed safely in the ASC setting without increased risk of complications compared with the hospital setting in an appropriately selected patient. Specifically, body mass index, and ASA class should be taken into consideration. Importantly, the setting of the surgery does not impact early PROs.

Level of Evidence:

Level 3.
Internal Fixation of Nondisplaced Intracapsular Hip Fractures in Older Patients
Authors: Katz Tiberiu , Abo Naser Layalee , Moskovitch Hagai , Kachko Eric , Benharroch Daniel , Ohana Nissim
Published: November 2018

For the treatment of, nondisplaced intracapsular hip fractures, the choice of the implant type might be relevant to the postoperative response. A comparison was, therefore, initiated between the use of the cannulated screws and that of the Targon femoral neck nail. A retrospective survey included 110 patients who were subjected to an internal fixation surgery for nondisplaced intracapsular hip fracture and were 50 years old or older. This study was based on the computerized databases of the Orthopedic Outpatient Clinic. In 73 (66%) of the patients, internal fixation utilized cannulated screws, and, in 37 (34%), the Targon femoral neck nail was used. The rate of revision surgery during the 5-year follow-up was similar for the 2 subsets (16.4% vs. 10.8%, P=0.429). Secondary outcomes such as avascular necrosis, nonunion, infection, and mechanical sequels did not differ significantly in the 2 groups. The 2 types of internal fixation did not differ significantly in their outcome when used for nondisplaced intracapsular hip fractures. No variance was shown in the propensity to undergo a revision surgery, following the 2 implant types with this indication. Moreover, the other complications explored did not differ either.
Innovative Intraoperative Splints for Tendon Transfer Procedures
Authors: Kamath Jagannath B.N. , Madegowda Arkesh , Sujir Premjith , Pai Mithun , Jain Manesh
Published: November 2018

Tendon transfers are well accepted treatment modality for managing difficult neurological and musculo tendinous deficits of upper and lower extremities. The most important technical consideration in the final outcome of these procedures are the tension and position with which the donor tendon is attached to the recipient tendon. This technical aspect of the procedure has not been given due importance in the literature. We the authors share our experience of fabricating intra operative splints for various tendon transfer procedures using easily available components of external fixator.
Utility of Skin Biopsy and Culture in the Diagnosis and Classification of Chronic Ulcers: A Single-Institution, Retrospective Study
Authors: Khoobyari Shiva , Miller Timothy I. , Shinohara Michi M.
Published: November 2018

In the United States, chronic ulcers affect 6.5 million people, with a cost of ≈$20 million annually. The most common etiology of chronic ulcers in the United States is venous stasis, followed by arterial insufficiency and neuropathic ulcers. Less common causes of chronic ulcers include infection, inflammatory etiologies such as vasculitis and pyoderma gangrenosum, and neoplastic causes. Obtaining skin biopsy and tissue culture can be helpful in diagnosing unusual causes of chronic ulcers; however, there are little data on the diagnostic utility of skin biopsy in rendering a definitive diagnosis of the etiology of chronic ulcers. A retrospective study of all skin ulcers biopsied during a 10-year period at the University of Washington was undertaken. Re-excisions and surgical wounds were excluded. A total of 270 ulcer biopsy specimens were included. In 48% of cases, no specific diagnosis could be rendered histologically. 44.8% of chronic ulcers biopsied were due to atypical causes, with neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma, and cutaneous T-cell lymphoma) being the most common. Vasculitis and pyoderma gangrenosum each represented 1.5% of rendered diagnoses. Concomitant skin culture was performed in 28.9% of cases, and special stains [acid-fast bacilli, Brown and Brenn (B&B), Grocott's methenamine silver, and periodic acid-Schiff stains] were performed in 34.0%. Although more than half (49 of 78) of tissue cultures were positive, only 6.8% (12 of 175) of special stains on tissue sections were positive. We conclude that although the etiology of many ulcers cannot be determined by routine histology alone, skin biopsy of ulcers remains a critical part of the workup given that when a specific cause can be determined, atypical etiologies, including neoplasms, represent a significant proportion of chronic ulcers. Limitations of our study include referral bias. Our results also confirm the higher diagnostic yield of conventional tissue culture compared with special tissue stain biopsies of skin ulcers.
Linear IgA Bullous Dermatosis Preceding the Diagnosis of Primary Sclerosing Cholangitis and Ulcerative Colitis: A Case Report
Authors: Humphrey Victoria S. , Lee Jonathan J. , Supakorndej Teerawit , Malik Shahid M. , Huen Arthur C. , Jaroslaw Jedrych
Published: November 2018

Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder seen in the pediatric and adult populations that is often linked to a medication, infection, or underlying gastrointestinal, hepatobiliary, or autoimmune disease. In this study, we describe the case of a 23-year-old white man whose presentation and diagnosis of LABD ultimately led to the discovery of underlying primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). His dermatitis resolved with topical steroids and dapsone, and he is undergoing systemic treatment for his UC and PSC. This exceptional case further validates the association between LABD with UC, strengthens that with PSC, and underscores the importance of alerting clinicians to consider conducting a systemic workup in addition to thorough medication history on making the diagnosis of LABD.
Concurrent Metastatic Merkel Cell Carcinoma and Cutaneous Squamous Cell Carcinoma in the Same Lymph Node
Authors: Suaiti Lubna , Onajin Oluwakemi , Sangueza Omar
Published: November 2018

The coexistence of Merkel cell carcinoma (MCC) and squamous cell carcinoma (SCC) in the same cutaneous lesion is well known. The pathogenesis is believed to be distinct from conventional polyomavirus-related MCC, and it has a more aggressive course. Metastasis of MCC and SCC to the same lymph node is exceedingly rare with only one previously reported case in the English literature. To the best of our knowledge, this is the second case of MCC and SCC with metastasis to the same lymph node. Our case demonstrates the aggressive nature of the combined MCC and SCC in the setting of immunosuppression.
Proliferating Neurocristic Hamartoma Arising in a Giant Congenital Nevus: Comparative Genomic Hybridization Findings
Authors: Garrido Maria Concepcion , Maroñas-Jiménez Lidia , Ruano Yolanda , Rodriguez-Peralto Jose Luis
Published: November 2018

Neurocristic cutaneous hamartomas (NCHs) are rarely reported tumors with divergent differentiation derived from persistently active pluripotent cells from the neural crest. They result from aberrant development of the neuromesenchyme, and they can express fibrogenic, melanocytic, and/or neurosustentacular differentiation. Thus, congenital melanocytic nevus also represents a neurocristic dysplasia of the skin in which cells are melanogenic cells arrested in development located in the reticular dermis, and nodular proliferative neurocristic hamartoma may arise within a congenital melanocytic nevus. The real importance of NCHs is that, although few cases have been reported in the literature, some cases have shown development of melanoma. Moreover, the only previously reported case of a similar “proliferative neurocristic nodule” analyzed with comparative genomic hybridization showed an aberration pattern similar to melanoma. We present a rare case of NCH associated with a congenital nevus in a 7-year-old boy, with classical histological and immunohistochemical features suggesting a “proliferative neurocristic hamartoma”. Comparative genomic hybridization assay showed that chromosomal aberrations were absent in the congenital nevus, whereas, interestingly, the proliferative neurocristic proliferation had an aberration pattern similar to proliferative nodules with gains or losses of entire chromosomes only, similar to typical proliferative nodules and supporting the benign behavior of this lesion.
Comparison of Methods for Algorithmic Classification of Dementia Status in the Health and Retirement Study
Authors: Gianattasio Kan Z. , Wu Qiong , Glymour M. Maria , Power Melinda C.
Published: November 2018

Background:

Dementia ascertainment is time-consuming and costly. Several algorithms use existing data from the US-representative Health and Retirement Study (HRS) to algorithmically identify dementia. However, relative performance of these algorithms remains unknown.

Methods:

We compared performance across five algorithms (Herzog–Wallace, Langa–Kabeto–Weir, Crimmins, Hurd, Wu) overall and within sociodemographic subgroups in participants in HRS and Wave A of the Aging, Demographics, and Memory Study (ADAMS, 2000–2002), an HRS substudy including in-person dementia ascertainment. We then compared algorithmic performance in an internal (time-split) validation dataset including participants of HRS and ADAMS Waves B, C, and/or D (2002–2009).

Results:

In the unweighted training data, sensitivity ranged from 53% to 90%, specificity ranged from 79% to 97%, and overall accuracy ranged from 81% to 87%. Though sensitivity was lower in the unweighted validation data (range: 18%–62%), overall accuracy was similar (range: 79%–88%) due to higher specificities (range: 82%–98%). In analyses weighted to represent the age-eligible US population, accuracy ranged from 91% to 94% in the training data and 87% to 94% in the validation data. Using a 0.5 probability cutoff, Crimmins maximized sensitivity, Herzog–Wallace maximized specificity, and Wu and Hurd maximized accuracy. Accuracy was higher among younger, highly-educated, and non-Hispanic white participants versus their complements in both weighted and unweighted analyses.

Conclusion:

Algorithmic diagnoses provide a cost-effective way to conduct dementia research. However, naïve use of existing algorithms in disparities or risk factor research may induce nonconservative bias. Algorithms with more comparable performance across relevant subgroups are needed.