bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opioid Shopping Behavior: How Often, How Soon, Which Drugs, and What Payment Method
Authors: Cepeda M. Soledad , Fife Daniel , Chow Wing , Mastrogiovanni Gregory , Henderson Scott C. 
Published: February 2012

AbstractDoctor shopping (obtaining opioid prescriptions from multiple prescribers) is one example of opioid abuse and diversion. The authors assessed how soon shopping behavior was observed after opioid exposure, number of events per shopper, preferred opioids, and method of payment. This was a cohort study. Individuals with ≥1 dispensing for any opioid in 2008 were followed for 18 months. Shopping behavior was defined as ≥2 prescriptions by different prescribers with ≥1 day of overlap and filled at ≥3 pharmacies [Correction added May 23, 2013 after online publication: in the full article HTML only, the ≤ symbol was used instead of the ≥ symbol in the preceding two sentences. The PDF was correct.]. Of 25,161,024 subjects, 0.30% exhibited shopping behavior. Opioid‐experienced subjects were 13.7 times more likely to exhibit shopping behavior and had more shopping episodes than opioid‐naive subjects. Time to first shopping event was 246.90 ± 163.61 days. Number of episodes was 2.74 ± 4.66. Most subjects with shopping behavior (55.27%) had 1 shopping episode, whereas 9.52% had ≥6 episodes; [Correction added May 23, 2013 after online publication: in the full article HTML only, the ≤ symbol was used instead of the ≥ symbol in the preceding sentence. The PDF was correct.] 88.99% had ≤4 prescribers. Subjects with shopping behavior filled schedule II opioids more often than subjects without shopping behavior (19.51% vs 10.89%) and more often paid in cash (44.85% vs 18.54%). Three of 1000 people exposed to opioids exhibit shopping behavior, on average, 8 months after exposure. Opioid shoppers seek strong opioids, avoid combination products, often pay cash, and obtain prescriptions from few prescribers.
Return to Athletic Activity After Osteochondral Allograft Transplantation in the Knee
Authors: Krych Aaron J. , Robertson Catherine M. , Williams Riley J. ,   the Cartilage Study Group
Published: February 2012

Background: Fresh-stored osteochondral allografts have been used successfully to resurface large chondral and osteochondral defects of the knee. However, there are limited data available for the return to athletic activity. Purpose: To review the rate of return to athletic activity after osteochondral allograft transplantation in the knee and to identify any potential risk factors for not returning to sport. Study Design: Case series; Level of evidence, 4. Methods: Forty-three athletes were treated with fresh-stored osteochondral allograft transplantation for symptomatic large chondral or osteochondral defects of the knee from 2000 to 2010. The average age of the athletes (30 men, 13 women) was 32.9 years (range, 18-49 years). Patients were prospectively evaluated by International Knee Documentation Committee (IKDC), activities of daily living scale of the Knee Injury and Osteoarthritis Outcome Score (KOOS), Marx Activity Rating Scale, and Cincinnati Sports Activity Scale scores. A multivariable regression analysis was performed to identify potential risk factors for failure to return to sport at the preinjury level. Results: At an average 2.5-year follow-up, limited return to sport was possible in 38 of 43 athletes (88%), with full return to the preinjury level achieved in 34 of 43 athletes (79%). In these 34 athletes, time to return to sport was 9.6 ± 3.0 months. Age ≥25 years ( P = .04) and preoperative duration of symptoms greater than 12 months (odds ratio, 37; P = .003) negatively affected the ability to return to sport. In the athletes who returned to their previous level of competition, IKDC ( P < .001), KOOS ( P = .02), and Marx Activity Rating Scale ( P < .001) scores were all significantly greater than in those athletes who did not return to sport. Conclusion: Osteochondral allograft transplantation in an athletic population for chondral and osteochondral defects in the knee allows for a high rate of return to sport. Risk factors for not returning to sport included age ≥25 years and preoperative duration of symptoms ≥12 months.
Bulk Deal in Bagri Market
Authors: Mukherjee Jaydeep 
Published: February 2012

The case highlights the challenges of using the wholesalers as an element of distribution network. The case discusses the evolution of distribution channel of luggage, primarily following selective distribution strategy. The decision making focus is about the nature of actions the Branch Manager could take to control the very powerful dealers located in major wholesale market. These wholesale dealers had high turnover from retail and wholesale business. They traditionally enjoyed high discounts and credit which was used by them for price cutting. Their activities disturbed the rest of distribution channel of Aristocrat as well as all other competitors and prevented growth of the rest of the distribution channel. These dealers enjoyed enormous bargaining power and were known to throw tantrum and hold the branch sales to ransom by not giving order till the end of the month and then negotiating hard. The situation had reached such an impasse that the Branch Manager and sales officers were rendered ineffective in managing the sales.
Stroke With Transfusions Changing to Hydroxyurea (SWiTCH)
Authors: Ware Russell E. , Helms Ronald W. 
Published: February 2012

Abstract
Stroke is a devastating complication of sickle cell anemia (SCA) with high recurrence if untreated. Chronic transfusions reduce recurrent strokes but have associated morbidities including iron overload. Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) was a multicenter phase 3 randomized trial comparing standard treatment (transfusions/chelation) to alternative treatment (hydroxyurea/phlebotomy) for children with SCA, stroke, and iron overload. SWiTCH was a noninferiority trial with a composite primary end point, allowing an increased stroke risk but requiring superiority for removing iron. Subjects on standard treatment received monthly transfusions plus daily deferasirox iron chelation. Subjects on alternative treatment received hydroxyurea plus overlap transfusions during dose escalation to maximum tolerated dose (MTD), followed by monthly phlebotomy. Subjects on standard treatment (N = 66) maintained 30% sickle hemoglobin (HbS) and tolerated deferasirox at 28.2 ± 6.0 mg/kg/d. Subjects on alternative treatment (N = 67) initiated hydroxyurea and 60 (90%) reached MTD at 26.2 ± 4.9 mg/kg/d with 29.1% ± 6.7% fetal hemoglobin (HbF). Adjudication documented no strokes on transfusions/chelation but 7 (10%) on hydroxyurea/phlebotomy, still within the noninferiority stroke margin. The National Heart, Lung, and Blood Institute closed SWiTCH after interim analysis revealed equivalent liver iron content, indicating futility for the composite primary end point. Transfusions and chelation remain a better way to manage children with SCA, stroke, and iron overload. This clinical trial was registered at ClinicalTrials.gov NCT00122980.
Extracellular matrix alterations in experimental Leishmania amazonensis infection in susceptible and resistant mice
Authors: Silva-Almeida Mariana , Carvalho Luiz OP , Abreu-Silva Ana L , Souza Celeste SF , Hardoim Daiana J , Calabrese Kátia S 
Published: February 2012

Abstract

Leishmania is inoculated, by the bite of an infected sandfly, into the skin of the host, where the promastigotes are phagocyted by dermal macrophages. The dermal region comprises cells and abundant extracellular matrix. Studies show that matrix metalloproteinases play an important role in host defense responses against pathogens in mammals and that their activities lead to the production of antimicrobial peptides. The aim of this study is to evaluate the changes in the distribution of fibronectin and laminin as well as in the elastic system fibres during the course of infection caused by Leishmania amazonensis in mice with distinct genetic backgrounds of susceptibility to this parasite. The results showed that BALB/c presented an enhancement of fibronectin during the course of infection when compared to their control group while the infected or non-infected C3H.He showed a decrease of this protein at end of the experiment. Laminin, on the other hand, remained unaltered in both strains. Also in both BALB/c and C3H.He mice the elastic and elaunin fibres remained unchanged while the oxytalan fibres decreased along the experiment. Ninety days after the infection C3H.He mice had recovered their capacity to produce oxytalan fibres.
Cell-mediated and humoral immune responses in pigs following primary and challenge-exposure to Lawsonia intracellularis
Authors: Cordes Henriette , Riber Ulla , Jensen Tim K , Jungersen Gregers 
Published: February 2012

AbstractTo investigate immune responses upon re-infection withLawsonia intracellularis, local and peripheral humoral and cell-mediated immune responses to primary and challenge inoculations were studied in 22 pigs. Pigs were orally inoculated with virulentL. intracellularisat the age of 5-6 weeks, treated with antibiotics and challenged with a re-inoculation (RE) at the age of 12 weeks. Treatment control (TC) pigs received only the primary inoculation and challenge control (CC) pigs received only the secondary inoculation at 12 weeks of age. Following this regimen, all RE pigs were protected against the re-infection as defined by reduced colonisation and pathology of intestinal mucosa, absence of bacterial shedding and without increase in serum acute phase protein response. In the protected RE pigs, serum IgG responses were variable with both high and low responders. Serum IgA responses were not boosted by the re-inoculation, since identical intestinal IgA responses developed in response to the inoculation in both the susceptible CC pigs and the protected RE pigs. A memory recall cell-mediated immune response developed in RE pigs which was significantly stronger compared to the primary response in age-matched CC pigs as assessed by whole blood IFN-γ assay and by calculation of IFN-γ integrated median fluorescence intensity (iMFI) after flow cytometry. The major IFN-γ producing cells were identified as CD8+and CD4+CD8+double positive lymphocytes. The results indicate that cell-mediated immune responses are likely mediators of protective immunity againstL. intracellularis, with CD8+effector cells and CD4+CD8+double positive memory T cells as main contributors to the antigen-specific IFN-γ production.
A naturally occurring carotenoid, lutein, reduces PDGF and H2O2 signaling and compromises migration in cultured vascular smooth muscle cells
Authors: Lo Huey-Ming , Tsai Yih-Jeng , Du Wen-Yuan , Tsou Chih-Jen , Wu Wen-Bin 
Published: February 2012

Abstract

Background
Platelet-derived growth factor (PDGF) is a potent stimulator of growth and motility of vascular smooth muscle cells (VSMCs). Abnormalities of PDGF/PDGF receptor (PDGFR) are thought to contribute to vascular diseases and malignancy. We previously showed that a carotenoid, lycopene, can directly bind to PDGF and affect its related functions in VSMCs. In this study we examined the effect of the other naturally occurring carotenoid, lutein, on PDGF signaling and migration in VSMCs.

Methods
Western blotting was performed to examine PDGF and H2O2 signaling. Flowcytometry was used to determine PDGF binding to VSMCs. Fluorescence microscopy was performed to examine intracellular ROS production. Modified Boyden chamber system (Transwell apparatus) was used for migration assay.

Results
Lutein reduced PDGF signaling, including phosphorylation of PDGFR-β and its downstream protein kinases/enzymes such as phospholipase C-γ, Akt, and mitogen-activated protein kinases (MAPKs). Although lutein possesses a similar structure to lycopene, it was striking that lutein inhibited PDGF signaling through a different way from lycopene in VSMCs. Unlike lycopene, lutein not only interacted with (bound to) PDGF but also interfered with cellular components. This was evidenced that preincubation of PDGF with lutein and treatment of VSMCs with lutein followed by removing of lutein compromised PDGF-induced signaling. Lutein reduced PDGF-induced intracellular reactive oxygen species (ROS) production and attenuated ROS- (H2O2-) induced ERK1/2 and p38 MAPK activation. A further analysis indicated lutein could inhibit a higher concentration of H2O2-induced PDGFR signaling, which is known to act through an oxidative inhibition of protein tyrosine phosphatase. Finally, we showed that lutein functionally inhibited PDGF-induced VSMC migration, whereas its stereo-isomer zeaxanthin did not, revealing a special action of lutein on VSMCs.

Conclusions
Our study reveals a differential action mechanism of lutein from other reported caroteinoids and suggests a possible beneficial effect of lutein but not zeaxanthin on prevention of vascular diseases.
Lipid raft/caveolae signaling is required for Cryptococcus neoformans invasion into human brain microvascular endothelial cells
Authors: Long Min , Huang Sheng-He , Wu Chun-Hua , Shackleford Gregory M , Jong Ambrose 
Published: February 2012

Abstract

Background

Cryptococcus neoformans has a predilection for central nervous system infection. C. neoformans traversal of the blood brain barrier, composed of human brain microvascular endothelial cells (HBMEC), is the crucial step in brain infection. However, the molecular mechanism of the interaction between Cryptococcus neoformans and HBMEC, relevant to its brain invasion, is still largely unknown.

Methods
In this report, we explored several cellular and molecular events involving the membrane lipid rafts and caveolin-1 (Cav1) of HBMEC during C. neoformans infection. Immunofluorescence microscopy was used to examine the roles of Cav1. The knockdown of Cav1 by the siRNA treatment was performed. Phosphorylation of Cav1 relevant to its invasion functions was investigated.

Results
We found that the host receptor CD44 colocalized with Cav1 on the plasma membrane, and knockdown of Cav1 significantly reduced the fungal ability to invade HBMEC. Although the CD44 molecules were still present, HBMEC membrane organization was distorted by Cav1 knockdown. Concomitantly, knockdown of Cav1 significantly reduced the fungal crossing of the HBMEC monolayer in vitro. Upon C. neoformans engagement, host Cav1 was phosphorylated in a CD44-dependent manner. This phosphorylation was diminished by filipin, a disrupter of lipid raft structure. Furthermore, the phosphorylated Cav1 at the lipid raft migrated inward to the perinuclear localization. Interestingly, the phospho-Cav1 formed a thread-like structure and colocalized with actin filaments but not with the microtubule network.

Conclusion
These data support that C. neoformans internalization into HBMEC is a lipid raft/caveolae-dependent endocytic process where the actin cytoskeleton is involved, and the Cav1 plays an essential role in C. neoformans traversal of the blood-brain barrier.
Does place of residence affect risk of suicide? a spatial epidemiologic investigation in Kentucky from 1999 to 2008
Authors: Saman Daniel M , Walsh Sabrina , Borówko Anna , Odoi Agricola 
Published: February 2012

Abstract

Background
Approximately 32,000 people take their own lives every year in the United States. In Kentucky, suicide mortality rates have been steadily increasing since 1999. Few studies in the United States have assessed spatial clustering of suicides. The purpose of this study was to identify high-risk clusters of suicide at the county level in Kentucky and assess the characteristics of those suicide cases within the clusters.

Methods
A spatial epidemiological study was undertaken using suicide data for the period January 1, 1999 to December 31, 2008, obtained from the Kentucky Office of Vital Statistics. Descriptive analyses using Pearson's chi-square test and t-test were performed to determine whether differences existed in age, marital status, year, season, and suicide method between males and females, and between cases inside and outside high-risk spatial clusters. Annual age-adjusted cumulative incidence rates were also calculated. Suicide incidence rates were spatially smoothed using the Spatial Empirical Bayesian technique. Kulldorff's spatial scan statistic was applied on all suicide cases at the county level to identify counties with the highest risks of suicide. Temporal cluster analysis was also performed.

Results
There were a total of 5,551 suicide cases in Kentucky from 1999 to 2008, of which 5,237 (94%) were included in our analyses. The majority of suicide cases were males (82%). The average age of suicide victims was 45.4 years. Two statistically significant (p < 0.05) high-risk spatial clusters, involving 15 counties, were detected. The county level cumulative incidence rate in the most likely high-risk cluster ranged from 12.4 to 21.6 suicides per 100,000 persons. The counties inside both high-risk clusters had relative risks ranging from 1.24 to 1.38.

Conclusions
Statistically significant high-risk spatial clusters of suicide were detected at the county level. This study may be useful for guiding future research and intervention efforts. Future studies will need to focus on these high-risk clusters to investigate reasons for these occurrences.
Mechanical pain sensitivity of deep tissues in children - possible development of myofascial trigger points in children
Authors: Han Ting-I , Hong Chang-Zern , Kuo Fang-Chuan , Hsieh Yueh-Ling , Chou Li-Wei , Kao Mu-Jung 
Published: February 2012

Abstract

Background
It is still unclear when latent myofascial trigger points (MTrPs) develop during early life. This study is designed to investigate the mechanical pain sensitivity of deep tissues in children in order to see the possible timing of the development of latent MTrPs and attachment trigger points (A-TrPs) in school children.

Methods
Five hundreds and five healthy school children (age 4- 11 years) were investigated. A pressure algometer was used to measure the pressure pain threshold (PPT) at three different sites in the brachioradialis muscle: the lateral epicondyle at elbow (site A, assumed to be the A-TrP site), the mid-point of the muscle belly (site B, assumed to be the MTrP site), and the muscle-tendon junction as a control site (site C).

Results
The results showed that, for all children in this study, the mean PPT values was significantly lower (p < 0.05) at the assumed A-TrP site (site A) than at the other two sites, and was significantly lower (p < 0.05) at the assumed MTrP site (site B) than at the control site (site C). These findings are consistent if the data is analyzed for different genders, different dominant sides, and different activity levels.

Conclusions
It is concluded that a child had increased sensitivity at the tendon attachment site and the muscle belly (endplate zone) after age of 4 years. Therefore, it is likely that a child may develop an A-Trp and a latent MTrP at the brachioradialis muscle after the age of 4 years. The changes in sensitivity, or the development for these trigger points, may not be related to the activity level of children aged 7-11 years. Further investigation is still required to indentify the exact timing of the initial occurrence of a-Trps and latent MTrPs.
Stimulation of Peripheral Kappa Opioid Receptors Inhibits Inflammatory Hyperalgesia via Activation of the PI3Kγ/AKT/nNOS/NO Signaling Pathway
Authors: Cunha Thiago M , Souza Guilherme R , Domingues Andressa C , Carreira Eleonora U , Lotufo Celina M , Funez Mani I , Verri Waldiceu A , Cunha Fernando Q , Ferreira Sergio H 
Published: February 2012

Background: In addition to their central effects, opioids cause peripheral analgesia. There is evidence showing that peripheral activation of kappa opioid receptors (KORs) inhibits inflammatory pain. Moreover, peripheral μ-opioid receptor (MOR) activation are able to direct block PGE2-induced ongoing hyperalgesia However, this effect was not tested for KOR selective activation. In the present study, the effect of the peripheral activation of KORs on PGE2-induced ongoing hyperalgesia was investigated. The mechanisms involved were also evaluated. Results: Local (paw) administration of U50488 (a selective KOR agonist) directly blocked, PGE2-induced mechanical hyperalgesia in both rats and mice. This effect was reversed by treating animals with L-NMMA or N-propyl-L-arginine (a selective inhibitor of neuronal nitric oxide synthase, nNOS), suggesting involvement of the nNOS/NO pathway. U50488 peripheral effect was also dependent on stimulation of PI3Kγ/AKT because inhibitors of these kinases also reduced peripheral antinociception induced by U50488. Furthermore, U50488 lost its peripheral analgesic effect in PI3Kγ null mice. Observations made in vivo were confirmed after incubation of dorsal root ganglion cultured neurons with U50488 produced an increase in the activation of AKT as evaluated by western blot analyses of its phosphorylated form. Finally, immunofluorescence of DRG neurons revealed that KOR-expressing neurons also express PI3Kγ (≌ 43%). Conclusions: The present study indicates that activation of peripheral KORs directly blocks inflammatory hyperalgesia through stimulation of the nNOS/NO signaling pathway which is probably stimulated by PI3Kγ/AKT signaling. This study extends a previously study of our group suggesting that PI3Kγ/AKT/nNOS/NO is an important analgesic pathway in primary nociceptive neurons.
Anatomical relations of the superficial sensory branches of the radial nerve: a cadaveric study with clinical implications
Authors: Samarakoon Lasitha B , Lakmal Kasun C , Thillainathan Sharmila , Bataduwaarachchi Vipula R , Anthony Dimonge J , Jayasekara Rohan W 
Published: February 2012

Abstract

Background
Anatomically, it is difficult to give a systematic description of the superficial branch of the radial nerve (SBRN). Our aim was to describe the exact relationship of the SBRN to fixed bony points of radial styloid and Lister's tubercle, and to the cephalic vein. We also compared our data with other international studies.

Methods
The study was a descriptive anatomical study. Twenty-five forearms were dissected. Measurements were made from predefined fixed reference points.

Results
The mean distance to the point of emergence of the nerve from the radial styloid was 8.54 cm (SD = 1.32). The nerve branched at a mean distance of 5.57 cm (SD = 1.43) from the radial styloid. The mean distance to the point where the most medial and most lateral branches of the nerve crossing the wrist joint, measured from the Lister's tubercle were 2.51 cm (SD = 0.53) and 3.90 cm (SD = 0.64). In 17 specimens(68%) cephalic vein crossed the SBRN superficially once. Mean distance from the radial styloid to the most distal point where the vein crossed the nerve was 5.10 cm. Diffefrence between mean distance to the point of emergence and branching point, when compared with other international studies were not statistically significant. (P value > 0.05)

Conclusions
We recommend avoiding transverse incisions in the snuffbox region between 2.51 cm and 3.90 cm from the Listers tubercle. We also recommend avoiding cannulation of the cephalic vein in the distal forearm.