Now showing items 21-40 of 2097

    • Lipid-Lowering Efficacy of Ezetimibe in Patients with Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analyses

      Shaya, F.T.; Sing, K.; Milam, R. (Adis, 2019)
      Introduction: Patients with atherosclerotic cardiovascular disease (ASCVD), especially those with recent (< 1 year) acute coronary syndrome (ACS), are at high risk for recurrent cardiovascular events. This risk can be reduced by lowering low-density lipoprotein cholesterol (LDL-C) levels. A comprehensive meta-analysis on the LDL-C-lowering efficacy of ezetimibe is lacking. This study attempts to address this gap. Methods: A systematic literature review of randomized controlled trials evaluating the LDL-C-lowering efficacy of ezetimibe in the ASCVD population was conducted. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for publications from database inception to August 2018 and for conference abstracts from 2015 to August 2018. Meta-analyses were conducted to evaluate the LDL-C-lowering efficacy of ezetimibe in the ASCVD population and the recent ACS subgroup. Results: In total, 12 studies were eligible for the meta-analyses. Treatment with combination ezetimibe plus statin therapy showed greater absolute LDL-C reduction than statin monotherapy (mean difference − 21.86 mg/dL; 95% confidence interval [CI] − 26.56 to − 17.17; p < 0.0001) after 6 months of treatment (or at a timepoint closest to 6 months). Similarly, in patients with recent ACS, combination ezetimibe plus statin therapy was favorable compared with statin monotherapy (mean treatment difference − 19.19 mg/dL; 95% CI − 25.22 to − 13.16; p < 0.0001). Conclusions: Ezetimibe, when added to statin therapy, provided a modest additional reduction in LDL-C compared with statin monotherapy. However, this may not be sufficient for some patients with ASCVD who have especially high LDL-C levels despite optimal statin therapy. Copyright 2019, The Author(s).
    • Dosage Regimens for Meropenem in Children with Pseudomonas Infections Do Not Meet Serum Concentration Targets

      Hassan, H.E.; Ivaturi, V.; Gobburu, J. (Blackwell Publishing Ltd, 2019)
      There have been literature reports that some recommended meropenem dosage regimens may fail to meet therapeutic targets in some high‐risk children and adults. We evaluated this observation in children using literature studies conducted in infants and children. Observed and, as necessary, simulated data from the literature were combined, yielding a data set of 288 subjects (1 day to ~ 17 years). A population pharmacokinetic model was fit to the data and then used to simulate the recommended dosing regimens and estimate the proportion of subjects achieving recommended target exposures. A two‐compartment model best fit the data with weight, postnatal age, gestational age, and serum creatinine as covariates. The US Food and Drug Administration (FDA)‐approved dosing regimens achieved targets in ~ 90% or more of subjects > 3 months of age for organisms with minimum inhibitory concentration (MIC)'s of 2 and 4 mg/L; however, only 68.4% and 41.7% of subjects older than 3 months and weighing < 50 kg achieved target exposures for organisms with MIC's of 2 and 4 mg/L, respectively. Moreover, for subjects weighing more than 50 kg, only 41.3% and 17% achieved these respective targets. Simulation studies were used to explore the impact of changing dose, dosing interval, and infusion duration on the likelihood of achieving therapeutic targets in these groups. Our findings illustrate that current dosing recommendations for children over 3 months of age fail to meet therapeutic targets in an unacceptable fraction of patients. Further investigation is needed to develop new dosing strategies in these patients. Copyright 2019 The Authors.
    • Global Outcome Assessment Life-long after stroke in young adults initiative - The GOAL initiative: Study protocol and rationale of a multicentre retrospective individual patient data meta-analysis

      Ekker, M.; Jacob, M.; Kittner, S. (BMJ Publishing Group, 2019)
      Introduction Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. Methods and analysis The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence. Ethics and dissemination Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients. Copyright Author(s).
    • Immune responses to O-specific polysaccharide (OSP) in North American adults infected with Vibrio cholerae O1 Inaba

      Hossain, M.; Chen, W.H.; Levine, M.M. (Public Library of Open Science, 2019)
      BACKGROUND: Antibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae may protect against cholera; however, little is known about this immune response in infected immunologically naïve humans. METHODOLOGY: We measured serum anti-OSP antibodies in adult North American volunteers experimentally infected with V. cholerae O1 Inaba El Tor N16961. We also measured vibriocidal and anti-cholera toxin B subunit (CtxB) antibodies and compared responses to those in matched cholera patients in Dhaka, Bangladesh, an area endemic for cholera. PRINCIPAL FINDINGS: We found prominent anti-OSP antibody responses following initial cholera infection: these responses were largely IgM and IgA, and highest to infecting serotype with significant cross-serotype reactivity. The anti-OSP responses peaked 10 days after infection and remained elevated over baseline for ≥ 6 months, correlated with vibriocidal responses, and may have been blunted in blood group O individuals (IgA anti-OSP). We found significant differences in immune responses between naïve and endemic zone cohorts, presumably reflecting previous exposure in the latter. CONCLUSIONS: Our results define immune responses to O-specific polysaccharide in immunologically naive humans with cholera, find that they are largely IgM and IgA, may be blunted in blood group O individuals, and differ in a number of significant ways from responses in previously humans. These differences may explain in part varying degrees of protective efficacy afforded by cholera vaccination between these two populations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01895855.
    • The behavior of ions in water is controlled by their water affinity

      Collins, K.D. (Cambridge University Press, 2019)
      The strong, long-range electrostatic forces described by Coulomb’s law disappear for ions in water, and the behavior of these ions is instead controlled by their water affinity – a weak, short-range force which arises from their charge density. This was established experimentally in the mid-1980s by size-exclusion chromatography on carefully calibrated Sephadex® G-10 (which measures the effective volume and thus the water affinity of an ion) and by neutron diffraction with isotopic substitution (which measures the density and orientation of water molecules near the diffracting ion and thus its water affinity). These conclusions have been confirmed more recently by molecular dynamics simulations, which explicitly model each individual water molecule. This surprising change in force regime occurs because the oppositely charged ions in aqueous salt solutions exist functionally as ion pairs (separated by 0, 1 or 2 water molecules) as has now been shown by dielectric relaxation spectroscopy; this cancels out the strong long-range electrostatic forces and allows the weak, short-range water affinity effects to come to the fore. This microscopic structure of aqueous salt solutions is not captured by models utilizing a macroscopic dielectric constant. Additionally, the Law of Matching Water Affinity, first described in 1997 and 2004, establishes that contact ion pair formation is controlled by water affinity and is a major determinant of the solubility of charged species since only a net neutral species can change phases.
    • Stress during pregnancy: Fetal males pay the price

      McCarthy, M.M. (National Academy of Sciences, 2019)
    • Lipopolysaccharides from Different Burkholderia Species with Different Lipid A Structures Induce Toll-Like Receptor 4 Activation and React with Melioidosis Patient Sera

      Sengyee, S.; Yoon, S.H.; West, T.E. (American Society for Microbiology, 2019)
      Lipopolysaccharides (LPSs) of Gram-negative bacteria comprise lipid A, core, and O-polysaccharide (OPS) components. Studies have demonstrated that LPSs isolated from the pathogenic species Burkholderia pseudomallei and Burkholderia mallei and from less-pathogenic species, such as Burkholderia thailandensis, are potent immune stimulators. The LPS structure of B. pseudomallei, the causative agent of melioidosis, is highly conserved in isolates from Thailand; however, the LPSs isolated from other, related species have not been characterized to enable understanding of their immune recognition and antigenicities. Here, we describe the structural and immunological characteristics of the LPSs isolated from eight Burkholderia species and compare those for B. pseudomallei to those for the other seven species. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), gas chromatography (GC), SDS-PAGE, Toll-like receptor 4 (TLR4) stimulation, and immunoblot analysis were performed on these Burkholderia species. MALDI-TOF profiles demonstrated that Burkholderia lipid A contains predominantly penta-acylated species modified with 4-amino-4-deoxy-arabinose residues at both terminal phosphate groups. The lipid A could be differentiated based on mass differences at m/z 1,511, 1,642, 1,773, and 1,926 and on fatty acid composition. LPSs of all species induced TLR4-dependent NF-?B responses; however, while SDS-PAGE analysis showed similar LPS ladder patterns for B. pseudomallei, B. thailandensis, and B. mallei, these patterns differed from those of other Burkholderia species. Interestingly, immunoblot analysis demonstrated that melioidosis patient sera cross-reacted with OPSs of other Burkholderia species. These findings can be used to better understand the characteristics of LPS in Burkholderia species, and they have implications for serological diagnostics based on the detection of antibodies to OPS. Copyright 2019 Sengyee et al.
    • Study protocol: Design and rationale for an exploratory phase II randomized controlled trial to determine optimal vitamin D3 supplementation strategies for acute fracture healing

      Sprague, S.; Bzovsky, S.; Connelly, D. (BioMed Central Ltd., 2019)
      Background: Observational studies have found that 75% of healthy adult fracture patients (ages 18-50) have serum 25-hydroxyvitamin D (25(OH)D) levels &lt; 30 ng/mL. Although lower serum 25(OH)D levels have yet to be correlated to fracture healing complications or poor fracture outcomes, many orthopedic surgeons are routinely prescribing vitamin D supplements to improve fracture healing in healthy non-osteoporotic patients. To address this gap in the literature, we propose a phase II exploratory randomized controlled trial comparing three vitamin D3 dosing regimens for early surrogate treatment response. Methods: We will conduct a 4-arm blinded exploratory phase II trial in 96 adults aged 18-50 years with a closed or low-grade open (Gustilo type I or II) tibial or femoral shaft fracture. Eligible patients will be randomized in equal allocation ratio of 1:1:1:1 to one of the treatment groups: (1) 150,000 IU loading dose vitamin D3 plus daily dose placebo; (2) loading dose placebo plus 4000 IU vitamin D3 per day, (3) loading dose placebo plus 600 IU vitamin D3 per day, or (4) loading dose placebo plus daily dose placebo. The primary outcome is fracture healing, assessed as follows: (1) clinical fracture healing measured using the Function IndeX for Trauma, (2) radiographic fracture healing measured using the Radiographic Union Score for Tibial fractures, and (3) biological fracture healing measured using serum levels of cross-linked C-terminal telopeptides of type I collagen and amino-terminal procollagen propeptides of collagen type I. The main secondary outcome will be assessed by measuring serum 25(OH)D levels. All outcome analyses will be exploratory and adhere to the intention-to-treat principle. Per-protocol sensitivity analyses will also be conducted. Discussion: Study results will be disseminated through a publication in an academic journal and presentations at orthopedic conferences. Study results will inform dose selection for a large definitive randomized controlled trial and provide preliminary clinical data on which dose may improve acute fracture healing outcomes in healthy adult patients (18-50 years) at 3 months. Trial registration: Vita-Shock (A Blinded Exploratory Randomized Controlled Trial to Determine Optimal Vitamin D3 Supplementation Strategies for Acute Fracture Healing) was registered at ClinicalTrials.gov (identifier NCT02786498) prior to enrollment of participants. Copyright 2019 The Author(s).
    • The D-score: a metric for interpreting the early development of infants and toddlers across global settings

      Weber, A.M.; Rubio-Codina, M.; Black, M.M. (BMJ Publishing Group, 2019)
      Introduction Early childhood development can be described by an underlying latent construct. Global comparisons of children's development are hindered by the lack of a validated metric that is comparable across cultures and contexts, especially for children under age 3 years. We constructed and validated a new metric, the Developmental Score (D-score), using existing data from 16 longitudinal studies. Methods Studies had item-level developmental assessment data for children 0-48 months and longitudinal outcomes at ages >4-18 years, including measures of IQ and receptive vocabulary. Existing data from 11 low-income, middle-income and high-income countries were merged for >36 000 children. Item mapping produced 95 'equate groups' of same-skill items across 12 different assessment instruments. A statistical model was built using the Rasch model with item difficulties constrained to be equal in a subset of equate groups, linking instruments to a common scale, the D-score, a continuous metric with interval-scale properties. D-score-for-age z-scores (DAZ) were evaluated for discriminant, concurrent and predictive validity to outcomes in middle childhood to adolescence. Results Concurrent validity of DAZ with original instruments was strong (average r=0.71), with few exceptions. In approximately 70% of data rounds collected across studies, DAZ discriminated between children above/below cut-points for low birth weight (<2500 g) and stunting (-2 SD below median height-for-age). DAZ increased significantly with maternal education in 55% of data rounds. Predictive correlations of DAZ with outcomes obtained 2-16 years later were generally between 0.20 and 0.40. Correlations equalled or exceeded those obtained with original instruments despite using an average of 55% fewer items to estimate the D-score. Conclusion The D-score metric enables quantitative comparisons of early childhood development across ages and sets the stage for creating simple, low-cost, global-use instruments to facilitate valid cross-national comparisons of early childhood development. Copyright Author(s)2019.
    • Evaluation of Texture Analysis for the Differential Diagnosis of Mass-Forming Pancreatitis From Pancreatic Ductal Adenocarcinoma on Contrast-Enhanced CT Images

      Ren, S.; Zhang, J.; Chen, R. (Frontiers Media S.A., 2019)
      Purpose: To investigate the potential of computed tomography (CT) imaging features and texture analysis to differentiate between mass-forming pancreatitis (MFP) and pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: Thirty patients with pathologically proved MFP and 79 patients with PDAC were included in this study. Clinical data and CT imaging features of the two lesions were evaluated. Texture features were extracted from arterial and portal phase CT images using commercially available software (AnalysisKit). Multivariate logistic regression analyses were used to identify relevant CT imaging and texture parameters to discriminate MFP from PDAC. Receiver operating characteristic curves were performed to determine the diagnostic performance of predictions. Results: MFP showed a larger size compared to PDAC (p = 0.009). Cystic degeneration, pancreatic ductal dilatation, vascular invasion, and pancreatic sinistral portal hypertension were more frequent and duct penetrating sign was less frequent in PDAC compared to MFP. Arterial CT attenuation, arterial, and portal enhancement ratios of MFP were higher than PDAC (p < 0.05). In multivariate analysis, arterial CT attenuation and pancreatic duct penetrating sign were independent predictors. Texture features in arterial phase including SurfaceArea, Percentile40, InverseDifferenceMoment_angle90_offset4, LongRunEmphasis_angle45_offset4, and uniformity were independent predictors. Texture features in portal phase including LongRunEmphasis_angle135_offset7, VoxelValueSum, LongRunEmphasis_angle135_offset4, and GLCMEntropy_angle45_offset1 were independent predictors. Areas under the curve of imaging feature-based, texture feature-based in arterial and portal phases, and the combined models were 0.84, 0.96, 0.93, and 0.98, respectively. Conclusions: CT texture analysis demonstrates great potential to differentiate MFP from PDAC. Copyright 2019 The Authors.
    • Intraoperative REBOA: An analysis of the American Association for the Surgery of Trauma AORTA registry

      Vella, M.A.; Dubose, J.; Morrison, J. (BMJ Publishing Group, 2019)
      Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a less-invasive technique for aortic occlusion (AO). Commonly performed in the emergency department (ED), the role of intraoperative placement is less defined. We hypothesized that operating room (OR) placement is associated with increased in-hospital mortality. Methods The American Association for the Surgery of Trauma AORTA registry was used to identify patients undergoing REBOA. Injury characteristics and outcomes data were compared between OR and ED groups. The primary outcome was in-hospital mortality; secondary outcomes included total AO time, transfusion requirements, and acute kidney injury. Results Location and timing of catheter insertion were available for 305 of 321 (95%) subjects. 58 patients underwent REBOA in the OR (19%). There were no differences with respect to sex, admission lactate, and Injury Severity Score. The OR group was younger (33 years vs. 41 years, p=0.01) and with more penetrating injuries (36% vs. 15%, p<0.001). There were significant differences with respect to admission physiology. Time from admission to AO was longer in the OR group (75 minutes vs. 23 minutes, p<0.001) as was time to definitive hemostasis (116 minutes vs. 79 minutes, p=0.01). Unadjusted mortality was lower in the OR group (36.2% vs. 68.8%, p<0.001). There were no differences in secondary outcomes. After controlling for covariates, there was no association between insertion location and in-hospital mortality (OR 1.8, 95% CI 0.30 to 11.50). Discussion OR REBOA placement is common and generally employed in patients with more stable admission physiology. OR placement was not associated with increased in-hospital mortality despite longer times to AO and definite hemostasis when compared with catheters placed in the ED. Level of evidence IV; therapeutic/care management. Copyright Author(s)
    • Pubertal timing and breast density in young women: A prospective cohort study

      Houghton, L.C.; Jung, S.; Hoover, R.N. (BioMed Central Ltd., 2019)
      Background: Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. Methods: From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. Results: The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)). Conclusions: Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk. Copyright 2019 The Author(s).
    • Cocaine as a rare cause of locked-in syndrome: a case report

      Ali, O.; Bueno, M.G.; Verceles, A.C. (BioMed Central Ltd., 2019)
      INTRODUCTION: In the United States, cocaine is a commonly used drug of abuse. It is also a recognized contributing factor for both hemorrhagic and ischemic strokes. However, cocaine-induced basilar artery thrombosis has rarely been reported in the literature. CASE PRESENTATION: Our patient was a 51-year-old African American woman with a history of polysubstance abuse who presented to the emergency department for acute behavior changes. Later, during admission, she had a dramatic decrease in motor strength in all extremities and a positive Babinski reflex bilaterally. The results of her toxicology reports were positive for cocaine; in addition, results of magnetic resonance angiography and magnetic resonance imaging were consistent with acute thrombosis and subsequent infarction of the basilar artery. Her mental status improved, but she was only able to communicate via movements of her eyes. CONCLUSION: Our patient developed locked-in syndrome after use of cocaine. Given the prevalence of its use in the United States, cocaine use should be included among the potential causes of locked-in syndrome.
    • The role of ubiquitination and SUMOylation in telomere biology

      Zalzman, M.; Meltzer, W.A.; Portney, B.A.; Brown, R.A.; Gupta, A. (Caister Academic Press, 2020)
      Telomeres are a unique structure of DNA repeats covered by proteins at the ends of the chromosomes that protect the coding regions of the genome and function as a biological clock. They require a tight regulation of the factors covering and protecting their structure, as they are shortened with each cell division to limit the ability of cells to replicate uncontrollably. Additionally, they protect the chromosome ends from DNA damage responses and thereby, prevent genomic instability. Telomere dysfunction can lead to chromosomal abnormalities and cancer. Therefore, dysregulation of any of the factors that regulate the integrity of the telomeres will have implications to chromosomal stability, replicative lifespan and may lead to cell transformation. This review will cover the main factors participating in the normal function of the telomeres and how these are regulated by the ubiquitin and SUMO systems. Accumulating evidence indicate that the ubiquitin and SUMO pathways are significant regulators of the shelterin complex and other chromatin modifiers, which are important for telomere structure integrity. Furthermore, the crosstalk between these two pathways has been reported in telomeric DNA repair. A better understanding of the factors contributing to telomere biology, and how they are regulated, is important for the design of new strategies for cancer therapies and regenerative medicine. Copyright 2020, Caister Academic Press. All rights reserved.
    • FGF21 augments autophagy in random-pattern skin flaps via AMPK signaling pathways and improves tissue survival

      Zhou, K.; Chen, H.; Lin, J. (Nature Publishing Group, 2019)
      Random-pattern skin flap is commonly used for surgical tissue reconstruction due to its ease and lack of axial vascular limitation. However, ischemic necrosis is a common complication, especially in distal parts of skin flaps. Previous studies have shown that FGF21 can promote angiogenesis and protect against ischemic cardiovascular disease, but little is known about the effect of FGF21 on flap survival. In this study, using a rat model of random skin flaps, we found that the expression of FGF21 is significantly increased after establishment skin flaps, suggesting that FGF21 may exert a pivotal effect on flap survival. We conducted experiments to elucidate the role of FGF21 in this model. Our results showed that FGF21 directly increased the survival area of skin flaps, blood flow intensity, and mean blood vessel density through enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. Our studies also revealed that FGF21 administration leads to an upregulation of autophagy, and the beneficial effects of FGF21 were reversed by 3-methyladenine (3MA), which is a well-known inhibitor of autophagy, suggesting that autophagy plays a central role in FGF21's therapeutic benefit on skin flap survival. In our mechanistic investigation, we found that FGF21-induced autophagy enhancement is mediated by the dephosphorylation and nuclear translocation of TFEB; this effect was due to activation of AMPK-FoxO3a-SPK2-CARM1 and AMPK-mTOR signaling pathways. Together, our data provides novel evidence that FGF21 is a potent modulator of autophagy capable of significantly increasing random skin flap viability, and thus may serve as a promising therapy for clinical use. Copyright 2019, The Author(s).
    • EP4 and Class III β-tubulin expression in uterine smooth muscle tumors: Implications for prognosis and treatment

      Reader, J.; Harper, A.K.; Legesse, T.; Staats, P.N.; Goloubeva, O.; Rao, G.G.; Fulton, A.; Roque, D.M. (MDPI AG, 2019)
      The microtubule-stabilizing agent docetaxel in combination with gemcitabine represents one of the most effective regimens against the aggressive gynecologic tumor leiomyosarcoma (LMS). Upregulation of class III β-tubulin has previously been shown to confer taxane resistance in a variety of human cancers. Prostaglandin E2 receptor EP4 is linked to progression of a variety of human cancers and may represent a novel target for tumor inhibition in LMS. We evaluated the hypotheses that EP4 and class III β-tubulin have increased expression in LMS in comparison to normal myometrium or benign tumors and that expression of class III β-tubulin correlates with resistance to taxanes and poor clinical outcome. Gene expression was examined using TCGA data and correlated with clinicopathologic outcome which demonstrated that class III β-tubulin is more highly expressed in more aggressive sarcomas with EP4 being widely expressed in all subtypes of sarcoma. Immunohistochemistry for EP4 and class III β-tubulin was performed on patients with LMS, leiomyomatosis/STUMP, leiomyoma, and normal myometrium. Expression of EP4 and class III β-tubulin were characterized for cell lines SK-UT-1, SK-UT-1B, and PHM-41 and these cell lines were treated with docetaxel alone and in combination with EP4 inhibitors. In taxane-resistant cell lines that overexpress class III β-tubulin and EP4, treatment with EP4 inhibitor resulted in at least 2-fold sensitization to docetaxel. Expression of class III β-tubulin and EP4 in LMS may identify patients at risk of resistance to standard chemotherapies and candidates for augmentation of therapy through EP4 inhibition. Copyright 2019 by the authors.
    • Examination of 388 staphylococcus aureus isolates from intensive care unit patients

      Adedrian, T.; Hitchcock, S.; O'Hara, L.M.; Michalski, J.M.; Kristie, Johnson, J.; Hazen, T.H.; Rasko, D.A.; Harris, A.D. (American Society for Microbiology, 2019)
      We have examined the draft genomes of 388 methicillin-resistant Staphylococcus aureus isolates obtained from intensive care unit patients at three geographically distributed hospitals to determine genomic diversity associated with potential health care worker-associated transmission. Copyright 2019 Adedrian et al.
    • Navigating Complex Frontiers: Introduction to the Special Issue on "The Future of Human Service Organizational and Management Research"

      McBeath, B.; Hopkins, K. (Routledge, 2019)
      Research on human service organizations and managers is essential and is needed to support both practice and scholarship. In response to a proposed imbalance between the two (between what we do and what we know), this special issue presents 10 commentaries that identify longstanding practice dilemmas and suggest new avenues for practice and research in social work and related helping professions and disciplines. Review of the commentaries supports three interrelated themes: (1) increasing complexity facing the environment of practice; leading to (2) proposed approaches to managing complexity across levels of practice; resulting in (3) implications for the future of macro practice, research, and education. The introduction concludes with a brief reflection on the future of human service organizational and management research. The overall aim of our analysis and the special issue is to illuminate that which is often hidden in plain view.
    • A Two-step Technique for Neo-umbilicoplasty in the Abdominal Reconstructive Population

      Ngaage, L.M.; Kokosis, G.; Kachniarz, B.; Rada, E.M.; Nam, A.J.; Pearl, J.; Kavic, S.; Rasko, Y.M. (Lippincott Williams and Wilkins, 2019)
      The umbilicus is the centerpiece of the abdomen and an important cosmetic landmark. Secondary intention healing can be used to create the illusion of an umbilicus in reconstructive surgery. However, there is a sparsity of literature on the role of neo-umbilicoplasty in this subset of patients and how they perceive their new umbilicus. We conducted a retrospective review of patients who received a neo-umbilicus during an abdominal reconstructive operation in 2016-2018. The umbilicus was amputated intraoperatively and tacking sutures were placed to create an indentation in the soft tissue; an inverted-V incision was sutured to create the illusion of an umbilicus. Postoperatively, patients were asked to rate their satisfaction with umbilicus appearance on a 5-point Likert scale. Of the 10 patients included; the majority were female (9:1), with a mean age of 37 years (range: 26-50) and mean BMI 29 (range: 21-38). The most common procedure performed at time of neo-umbilicoplasty was hernia repair (80%). There were no wound complications associated with the neo-umbilicus. Satisfaction was high (median 5, range: 1-5) and independent of time since surgery. Three patients gave scores below 5 and cited reasons of "lack of indentation" (n = 3, scores 4, 4, and 1), and "insufficiently notable scar" (n = 1, score 1). We hereby describe a simple surgical technique for neo-umbilicoplasty in patients undergoing reconstructive abdominal surgery that leads to long-lasting cosmetic satisfaction. Further studies of patient-reported outcomes and refinement of the technique will maximize the aesthetically pleasing results. Copyright 2019 The Authors.