bluuebunny/crossref_metadata_2025_split huggingface dataset:
A qualitative study to explore psychological distress and illness burden associated with opioid-induced constipation in cancer patients with advanced disease
Authors: Dhingra Lara , Shuk Elyse , Grossman Bella , Strada Alessandra , Wald Emily , Portenoy Allison , Knotkova Helena , Portenoy Russell 
Published: June 2012

Background: Constipation affects many patients receiving long-term opioid therapy for cancer pain. Little is known about the nature of psychological distress and the burden associated with this problem. This information may inform the development of effective treatment strategies and ameliorate distress. Aim: The objective was to use qualitative research methods to better understand psychological distress and the burden associated with opioid-induced constipation and its treatment in advanced cancer patients. Design: In this qualitative study, semi-structured interviews explored perceptions of psychological distress and burden from opioid-induced constipation. Interviews were analyzed using a thematic content analysis approach involving descriptive and interpretive coding and identification of recurring themes. Setting/participants: Twelve advanced cancer patients with opioid-induced constipation were recruited from a large urban hospital. Results: Patients experienced various types of negative affect and cognitions associated with opioid-induced constipation. Analyses indicated three major themes: (1) irrational thoughts and educational needs; (2) psychological distress from constipation and (3) the effects of constipation on the decision to use opioid analgesics. Irrational thoughts and educational needs included beliefs that nutrition could improve constipation, the supposition that constipation indicated deteriorating health, and catastrophic beliefs. Psychological distress included depressive symptoms and anticipatory anxiety related to constipation. Decision-making revealed cognitive dissonance about using opioids and conflicting preferences about continuing use. Conclusions: Future investigation of the multiple components of cognitive and affective burden from opioid-induced constipation is warranted. Understanding the varied nature of this burden may improve clinical recognition and assessment and promote more intensive management consistent with the distress it produces.
Minimal clinically important change on the Headache Impact Test-6 questionnaire in patients with chronic tension-type headache
Authors: Castien René F , Blankenstein Annette H , Windt Daniëlle AWM van der , Dekker Joost 
Published: June 2012

Objective: To determine the minimal clinically important change (MCIC) in Headache Impact Test-6 (HIT-6) score in patients with chronic tension-type headache (CTTH). Methods: The HIT-6 was administered at baseline and at 8 weeks follow-up in a cohort of 186 participants with CTTH who received manual therapy or usual care by their general practitioner. An anchor-based method was used to determine the MCIC, with the external criterion (anchor) being based on general perceived improvement (‘much improved or very much improved’ on a 7-point Likert scale) in combination with 50% reduction in headache days. Using receiver operating characteristic (ROC) curve analysis we defined an optimal cut-off score discriminating between improved and not improved participants. Results: The optimal cut-off point for the MCIC for the HIT-6 was −8 points, on a total scale range of 42 points. Conclusion: A clinically relevant improvement in patients with CTTH is reflected by a decrease of at least 8 points on the HIT-6.
Bilateral Mini-Invasive Adductor Tenotomy for the Management of Chronic Unilateral Adductor Longus Tendinopathy in Athletes
Authors: Maffulli Nicola , Loppini Mattia , Longo Umile Giuseppe , Denaro Vincenzo 
Published: June 2012

Background: To date, the best management of chronic groin pain related to adductor longus tendinopathy has not been defined. Although there have been some studies investigating the effectiveness of adductor longus tenotomy, none have investigated bilateral adductor tenotomy for unilateral tendinopathy. Hypothesis: The use of bilateral percutaneous adductor tenotomy for the management of chronic unilateral groin pain as a result of adductor longus tendinopathy will result in improvement of overall function and facilitate a return to athletic activity. Study Design: Case series; Level of evidence, 4. Methods: During the period from 2004 to 2007, we prospectively enrolled 29 consecutive athletes (26 male and 3 female; median age, 28 years) with chronic groin pain from unilateral adductor longus tendinopathy who underwent bilateral adductor tenotomy. Functional outcome and health status were assessed with the Hip Disability and Osteoarthritis Outcome Score (HOOS), Short Form Health Survey (SF-36), and European Quality of Life–5 Dimensions scale (EQ-5D). The ability to participate in sport before and after surgery and the time to return to training and return to sport were also recorded. The median follow-up after surgery was 36 months. Results: All questionnaires showed a statistically significant improvement ( P < .0001) after surgery. At the time of latest follow-up, 20 of 29 patients (69%) returned to their preinjury level of sport and 2 of 29 patients (7%) to higher levels compared with preinjury status. However, 4 of 29 patients (14%) returned to sport at lower levels than those of preinjury status, and 3 of 29 patients (10%) ceased to participate in sport. The median time to return to training was 11 weeks and to return to sport was 18 weeks. Conclusion: Bilateral mini-invasive adductor tenotomy can be an effective treatment for athletes suffering from unilateral chronic groin pain associated with adductor longus tendinopathy refractory to nonoperative management.
Magnetic Resonance Imaging Identification of Rotator Cuff Retears After Repair
Authors: Khazzam Michael , Kuhn John E. , Mulligan Ed , Abboud Joseph A. , Baumgarten Keith M. , Brophy Robert H. , Jones Grant L. , Miller Bruce , Smith Matthew , Wright Rick W. 
Published: June 2012

Background: Magnetic resonance imaging (MRI) is the most commonly used imaging modality to assess the rotator cuff. Currently, there are a limited number of studies assessing the interobserver and intraobserver reliability of MRI after rotator cuff repair. Hypothesis: Fellowship-trained orthopaedic shoulder surgeons will have good inter- and intraobserver agreement with regard to features of the repaired rotator cuff (repair integrity, fat content, muscle volume, number of tendons involved, tear size, and retract) on MRI. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: Seven fellowship-trained orthopaedic shoulder surgeons reviewed 31 MRI scans from 31 shoulders from patients who had previous rotator cuff repair. The scans were evaluated for the following characteristics: rotator cuff repair status (full-thickness retear vs intact repair), tear location, tendon thickness, fatty infiltration, atrophy, number of tendons involved in retear, tendon retraction, status of the long head of the biceps tendon, and bone marrow edema in the humeral head. Surgeons were asked to review images at 2 separate time points approximately 9 months apart and complete an evaluation form for each scan at each time point. Multirater kappa (κ) statistics were used to assess inter- and intraobserver reliability. Results: The interobserver agreement was highest (80%, κ = 0.60) for identifying full-thickness retears, tendon retear retraction (64%, κ = 0.45), and cysts in the greater tuberosity (72%, κ = 0.43). All other variables were found to have fair to poor agreement. The worst interobserver agreement was associated with identifying rotator cuff footprint coverage (47%, κ = −0.21) and tendon signal intensity (29%, κ = −0.01). The mean intraobserver reproducibility was also highest (77%-90%, κ = 0.71) for full-thickness retears, quality of the supraspinatus (47%-83%, κ = 0.52), tears of the long head of the biceps tendon (58%-94%, κ = 0.49), presence of bone marrow edema in the humeral head (63%-87%, κ = 0.48), cysts in the greater tuberosity (70%-83%, κ = 0.47), signal in the long head of the biceps tendon (60%-80%, κ = 0.43), and quality of the infraspinatus (37-90%, κ = 0.43). The worst intraobserver reproducibility was found in identification of the location of bone marrow edema (22%-83%, κ = −0.03). Conclusion: The results of this study indicate that there is substantial variability when evaluating MRI scans after rotator cuff repair. Intact rotator cuff repairs or full-thickness retears can be identified with moderate reliability. These findings indicate that additional imaging modalities may be needed for accurate assessment of the repaired rotator cuff.
How I manage venous thromboembolism risk in hospitalized medical patients
Authors: Dobromirski Mark , Cohen Alexander T. 
Published: June 2012

AbstractVenous thromboembolism is a significant cause of illness and death worldwide. Large bodies of evidence support the heightened risk status of hospitalized medical patients, and that prophylactic measures significantly reduce the risk of thrombosis, yet these patients often fail to receive adequate prophylactic therapy. This failure may be accounted for by a lack of awareness of the relevant indications, poorly designed implementation systems, and clinical concerns over the side effects of anticoagulant medications. This article briefly summarizes our understanding of the clinical factors relevant to the evaluation of venous thromboembolism risk in hospitalized medical patients. We describe our approach to the use of thromboprophylaxis, through which we aim to minimize the disease burden of this under-recognized and preventable pathology.
Slc11a1 (Nramp1) impairs growth of Salmonella enterica serovar typhimurium in macrophages via stimulation of lipocalin-2 expression
Authors: Fritsche Gernot , Nairz Manfred , Libby Stephen J , Fang Ferric C , Weiss Günter 
Published: June 2012

Abstract
Nramp1 confers resistance of macrophages to Salmonella Typhimurium via NF-κB-dependent induction of the siderophore capturing peptide lipocalin-2.
The expression of the cation transporter Nramp1 (Slc11a1) in late phagolysosomes confers resistance to infection with several intracellular pathogens, such as Salmonella enterica, in mice. The antimicrobial actions of Nramp1 are attributable, in part, to modulation of macrophage immune function and cellular iron metabolism—the latter affecting the availability of the essential nutrient iron for intraphagosomal bacteria. Here, we provide novel evidence that Nramp1 functionality increases the expression of the peptide Lcn2, which exerts its antimicrobial activity by scavenging iron-loaded bacterial siderophores and mediating iron efflux from macrophages. With the use of macrophage cell lines expressing functional or nonfunctional Nramp1, we found significantly elevated Lcn2 mRNA and protein levels in Nramp1-expressing cells. These resulted from Nramp1-mediated alterations in the production of ROS, which stimulated NF-κB activity and subsequently, Lcn2 transcription. We observed that increased Lcn2 levels in primary Nramp1-positive macrophages resulted in a significant suppression of S. enterica serovar typhimurium growth. Stimulation of Lcn2 expression is a novel mechanism by which Nramp1 confers resistance against infection with the intracellular bacterium S. typhimurium.
Eosinophil contamination of thioglycollate-elicited peritoneal macrophage cultures skews the functional readouts of in vitro assays
Authors: Misharin Alexander V , Saber Rana , Perlman Harris 
Published: June 2012

Abstract
Eosinophil contamination affects thioglycollate-elicited peritoneal macrophage responses during in vitro stimulation.
Thioglycollate-elicited peritoneal cells are a common source of macrophages for various in vitro assays, including stimulation with TLR ligands, cell signaling assays, phagocytosis, toxicology studies, and cytokine/chemokine production. The most common method for enrichment of cultured thioglycollate-elicited peritoneal cells is adherence. However, the presence of other cell types in freshly isolated and cultured thioglycollate-elicited peritoneal cells has not been examined. Here, we demonstrate that thioglycollate-elicited peritoneal cavity contains 55–60% nonmacrophage cells, and even after adherence, there are still 12–20% nonmacrophage cells remaining. Excluding macrophages, eosinophils are the major cell type in the freshly elicited cavity (30–40%). Eosinophils are also the major cell type contaminating in vitro cultures of thioglycollate-elicited peritoneal macrophages. Moreover, the contamination of macrophage cultures by eosinophils significantly diminishes activation of p38 MAPK and the serine threonine kinase Akt and production of proinflammatory cytokines in response to LPS stimulation. Taken together, these data suggest that thioglycollate-elicited peritoneal cells are far more heterogeneous than reported previously. Further, a failure to remove contaminating eosinophils may greatly affect the interpretation of results obtained with cultured thioglycollate-elicited macrophages. Thus, our data indicate that future studies intent on accurately assessing cultured macrophage phenotype and activation require depletion of all cocontaminating cells, especially eosinophils.
The COP9 signalosome, cullin 3 and Keap1 supercomplex regulates CHOP stability and adipogenesis
Authors: Huang Xiaohua , Ordemann Jürgen , Müller Joachim M. , Dubiel Wolfgang 
Published: June 2012

Summary
Obesity is one of the most serious health problems of the 21st century. It is associated with highly increased risk of type 2 diabetes, high blood pressure, cardiovascular disease as well as several cancers. The expansion of the fat tissue needs the differentiation of preadipocytes to adipocytes, a process called adipogenesis. Dysfunction of adipogenesis is a hallmark of obesity and delineation of underlying mechanisms has high priority for identifying targets for pharmacological intervention. Here we investigate the impact of the COP9 signalosome (CSN), a regulator of cullin-RING ubiquitin ligases (CRLs), and of C/EBP homologous protein (CHOP) on the differentiation of LiSa-2 preadipocytes. CHOP induced by piceatannol or by permanent overexpression in LiSa-2 cells blocks adipocyte differentiation as characterized by inhibited fat droplet formation and vascular endothelial growth factor (VEGF) production. Knockdown of the CSN by permanent downregulation of CSN1 in LiSa-2 cells elevates CHOP and retards adipogenesis. The effect of the CSN knockdown on CHOP stability can be explained by the protection of the CRL component Keap1 by the CSN associated ubiquitin-specific protease 15 (USP15). Pulldowns and glycerol gradients reveal that CHOP interacts with a supercomplex consisting of the CSN, cullin 3 and Keap1. Transient knockdown of Keap1 increases CHOP steady state level and retards its degradation. We conclude that CHOP stability is controlled by a CSN-CRL3Keap1 complex, which is crucial for adipogenesis. Our data show that CHOP is a distinguished target for pharmacological intervention of obesity.
The endocytic adapter E-Syt2 recruits the p21 GTPase activated kinase PAK1 to mediate actin dynamics and FGF signalling
Authors: Jean Steve , Tremblay Michel G. , Herdman Chelsea , Guillou François , Moss Tom 
Published: June 2012

Summary
Fibroblast growth factor (FGF) signalling plays an essential role in early vertebrate development. However, the response to FGF requires endocytosis of the activated FGF receptor (FGFR) that is in part dependent on remodelling of the actin cytoskeleton. Recently we showed that the extended synaptotagmin family plasma membrane protein, E-Syt2, is an essential endocytic adapter for FGFR1. Here we show E-Syt2 is also an interaction partner for the p21-GTPase Activated Kinase PAK1. The phospholipid binding C2C domain of E-Syt2 specifically binds a site adjacent to the CRIB/GBD of PAK1. PAK1 and E-Syt2 selectively complex with FGFR1 and functionally cooperate in the FGF signalling. E-Syt2 binding suppresses actin polymerization and inhibits the activation of PAK1 by the GTPases Cdc42 and Rac. Interestingly, the E-Syt2 binding site on PAK1 extensively overlaps a site recently suggested to bind phospholipids. Our data suggest that PAK1 interacts with phospholipid membrane domains via E-Syt2, where it may cooperate in the E-Syt2-dependent endocytosis of activated FGFR1 by modulating cortical actin stability.
Intermediated Blind Portfolio Auctions
Authors: Padilla Michael , Van Roy Benjamin 
Published: June 2012

As much as 12%% of the daily volume on the New York Stock Exchange, and similar volumes on other major world exchanges, involves sales by institutional investors to brokers through blind portfolio auctions. Such transactions typically take the form of a first-price sealed-bid auction in which the seller engages a few potential brokers and provides limited information about the portfolio being sold. Uncertainty about the portfolio contents reduces bids, effectively increasing the transaction cost paid by the seller. We consider the use of a trusted intermediary or equivalent cryptographic protocol to reduce transaction costs. In particular, we propose a mechanism through which each party provides relevant private information to an intermediary who ultimately reveals only the portfolio contents and price paid, and only to the seller and winning broker. Through analysis of a game-theoretic model, we demonstrate substantial potential benefits to sellers. For example, under reasonable assumptions a seller can reduce expected transaction costs by more than 10%. This paper was accepted by Wei Xiong, finance.
Product Market Efficiency: The Bright Side of Myopic, Uninformed, and Passive External Finance
Authors: Noe Thomas H. , Rebello Michael J. , Rietz Thomas A. 
Published: June 2012

We model the effect of external financing on a firm's ability to maintain a reputation for high-quality production. Producing high quality is first best. Defecting to low quality is tempting because it lowers current costs while revenue remains unchanged because consumers and outside investors cannot immediately observe the defection. However, defection to low quality impairs the firm's reputation, which lowers cash flows and inhibits production over the long term. Financing via short-term claims discourages defection to low quality because the gains from defection are mostly captured by outside investors through an increase in the value of their claims. Therefore, if the firm relies on short-term external financing, it is more likely to produce over the long run, produce high-quality goods, and enjoy high profitability. The aggregate results from a laboratory experiment generally accord with these predictions. This paper was accepted by Brad Barber, finance.
More Than Just Skin Deep: Faciocutaneous Clues to Genetic Syndromes with Malignancies
Authors: Shen Zhu , Hoffman Jodi D. , Hao Fei , Pier Eric 
Published: June 2012

AbstractGenetic syndromes with dermatologic findings and multisystemic involvement (e.g., visceral cancer predisposition) are underrecognized. Patients may have incomplete penetrance and variable expressivity; some patients may solely exhibit subtle skin signs, which create a diagnostic challenge for physicians. Interdisciplinary diagnostic knowledge is required for the early diagnosis and monitoring of patients with these syndromes. Cutaneous changes in the face—one of the most highly exposed areas—can be easily noticed by patients themselves, their families and friends, and physicians; these changes may serve as early indicators of genetic syndromes with malignancies. In this article, we present examples of genetic syndromes with malignancies for which a thorough faciocutaneous examination is helpful in establishing a diagnosis. These examples include lentiginosis-related syndromes (e.g., Peutz-Jeghers syndrome, Carney complex), photosensitivity-related syndromes (Bloom syndrome, Rothmund-Thomson syndrome), and hamartoma-related syndromes (Cowden syndrome, multiple endocrine neoplasia syndrome, tuberous sclerosis complex, Gardner syndrome, Muir-Torre syndrome). The characteristics of these faciocutaneous clues are summarized and discussed. Objective evaluation of these faciocutaneous clues in combination with other clinical information (e.g., family history, histopathological findings, combination with other concomitant faciocutaneous lesions) is emphasized to narrow the diagnosis. The list of genetic syndromes with faciocutaneous manifestations is still expanding. Increased awareness of faciocutaneous markers can alert physicians to underlying syndromes and malignancies, render earlier screening and detection of associated medical issues, and allow for genetic counseling of family members.
Feasibility of Nurse-Led Antidepressant Medication Management of Depression in an HIV Clinic in Tanzania
Authors: Adams Julie L. , Almond Maria L. G. , Ringo Edward J. , Shangali Wahida H. , Sikkema Kathleen J. 
Published: June 2012

Objective: Sub-Saharan Africa has the highest HIV prevalence worldwide and depression is highly prevalent among those infected. The negative impact of depression on HIV outcomes highlights the need to identify and treat it in this population. A model for doing this in lower-resourced settings involves task-shifting depression treatment to primary care; however, HIV-infected individuals are often treated in a parallel HIV specialty setting. We adapted a model of task-shifting, measurement-based care (MBC), for an HIV clinic setting and tested its feasibility in Tanzania. MBC involves measuring depressive symptoms at meaningful intervals and adjusting antidepressant medication treatment based on the measure of illness. Method: Twenty adults presenting for care at an outpatient HIV clinic in Tanzania were enrolled and followed by a nurse care manager who measured depressive symptoms at baseline and every 4 weeks for 12 weeks. An algorithm-based decision-support tool was utilized by the care manager to recommend individualized antidepressant medication doses to participants' HIV providers at each visit. Results: Retention was high and fidelity of the care manager to the MBC protocol was exceptional. Follow through of antidepressant prescription dosing recommendations by the prescriber was low. Limited availability of antidepressants was also noted. Despite challenges, baseline depression scores decreased over the 12-week period. Conclusions: Overall, the model of algorithm-based nursing support of prescription decisions was feasible. Future studies should address implementation issues of medication supply and dosing. Further task-shifting to relatively more abundant and lower-skilled health workers, such as nurses' aides, warrants examination.