bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potent in vivo anti-malarial activity and representative snapshot pharmacokinetic evaluation of artemisinin-quinoline hybrids
Authors: Lombard Marli C , N’Da David D , Tran Van Ba Christophe , Wein Sharon , Norman Jennifer , Wiesner Lubbe , Vial Henri 
Published: February 2013

Abstract

Background
Because Plasmodium falciparum displays increase tolerance against the recommended artemisinin combination therapies (ACT), new classes of anti-malarial drugs are urgently required. Previously synthesized artemisinin-aminoquinoline hybrids were evaluated to ascertain whether the potent low nanomolar in vitro anti-plasmodial activity would carry over in vivo against Plasmodium vinckei. A snapshot pharmacokinetic analysis was carried out on one of the hybrids to obtain an indication of the pharmacokinetic properties of this class of anti-malarial drugs.

Methods

In vitro activity of hybrids 2 and 3 were determined against the 3D7 strain of P. falciparum. Plasmodium vinckei-infected mice were treated with hybrids 1 – 3 for four days at a dosage of 0.8 mg/kg, 2.5 mg/kg, 7.5 mg/kg or 15 mg/kg intraperitoneally (ip), or orally (per os) with 2.7 mg/kg, 8.3 mg/kg, 25 mg/kg or 50 mg/kg. Artesunate was used as reference drug. A snapshot oral and IV pharmacokinetic study was performed on hybrid 2.

Results
Hybrids 1 – 3 displayed potent in vivo anti-malarial activity with ED50 of 1.1, 1.4 and <0.8 mg/kg by the ip route and 12, 16 and 13 mg/kg per os, respectively. Long-term monitoring of parasitaemia showed a complete cure of mice (without recrudescence) at 15 mg/kg via ip route and at 50 mg/kg by oral route for hybrid 1 and 2, whereas artesunate was only able to provide a complete cure at 30 mg/kg ip and 80 mg/kg per os.

Conclusions
These compounds provide a new class of desperately needed anti-malarial drug. Despite a short half-life and moderate oral bioavailability, this class of compounds was able to cure malaria in mice at very low dosages. The optimum linker length for anti-malarial activity was found to be a diaminoalkyl chain consisting of two carbon atoms either methylated or unmethylated.
Expression of Interleukin-17 associated with disease progression and liver fibrosis with hepatitis B virus infection: IL-17 in HBV infection
Authors: Du Wen-Jun , Zhen Jun-Hui , Zeng Zhao-Qing , Zheng Zhao-Min , Xu Yan , Qin Lai-Ying , Chen Shi-Jun 
Published: February 2013

AbstractBackground/objectivesAs a proinflammatory cytokine, interleukin-17 (IL-17) contributes to the inflammation of many autoimmune diseases. We examined IL-17 levels in serum and tissues from patients with chronic hepatitis B virus infection (HBV), and especially evaluated the role of IL-17 in the pathogenesis and progression of liver fibrosis.Materials and methodsWhole venous blood was obtained from four patient groups: chronic hepatitis B (CHB, n = 47), liver cirrhosis (LC, n = 49), primary hepatocellular carcinoma (PHC, n = 44), chronic liver failure (CLF, n = 33), and a normal control group (n = 20). HBsAg was positive in all patients. Liver biopsy samples were acquired from asymptomatic HBsAg carriers (ASC, n = 35), CHB (n = 57), and LC (n = 31) patients. We performed ELISA to measure IL-17 levels in serum samples, and used reverse RT-PCR to measure IL-17 mRNA levels in peripheral blood mononuclear cells (PBMC). IL-17 protein expression was detected in liver biopsy tissues by immunohistochemistry.ResultsCompared to normal controls, serum IL-17 protein and mRNA levels were significantly higher in the four infection groups. LC patients exhibited the highest serum IL-17 and PBMC mRNA levels. No significant differences were found between the other three groups. High levels of IL-17 were also observed in tissues from CHB and LC patients, compared to ASC. IL-17 expression was mainly located in the portal area and was positively correlated with inflammation grade and fibrosis stage.ConclusionsIL-17 expression was found to be increased with increasing degrees of liver fibrosis. This suggests that IL-17 may not only induce the inflammation, but also contribute to disease progression and chronicity.Virtual SlidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/5306959258322482
Percutaneous endoscopic gastrostomy site metastasis from head and neck squamous cell carcinoma: Case series and literature review
Authors: Huang Andrew T , Georgolios Alexandros , Espino Sasa , Kaplan Brian , Neifeld James , Reiter Evan R 
Published: February 2013

Objectives To present our experience with head and neck squamous cell carcinoma (HNSCC) seeding of percutaneous endoscopic gastrostomy (PEG) sites and to review all reported cases to identify risk factors and develop strategies for complication avoidance. Materials and methods The records of 4 patients with PEG site metastasis from HNSCC were identified from the authors’ institution. Thirty-eight further cases were reviewed following a PubMed search and evaluation of references in pertinent articles. Results Review of 42 cases revealed the average time from PEG to diagnosis of metastatic disease to be 8 months. Average time to death from detection of PEG disease was 5.9 months. One-year survival following PEG metastasis was 35.5% with an overall mortality of 87.1%. Conclusion PEG site metastatic disease portends a poor prognosis. Early detection and aggressive therapy may provide a chance of cure. Changes in PEG technique or in timing of adjunctive therapies are possible avenues in further research to prevent this complication.
Activation and employment support policies in OECD countries. An overview of current approaches
Authors: Immervoll Herwig , Scarpetta Stefano 
Published: February 2013

Abstract
This note examines the balance of activation strategies in OECD countries, where this type of policy approach has a long tradition. Countries share the objective of strengthening employment and reducing benefit dependency and vulnerability among the working-age population, but the balance of policy measures differs widely. While debates on the effectiveness of active labour market policies have tended to focus on individual policy measures, this paper emphasizes the links between policy areas. We argue that an effective policy strategy rests on a finely tuned balance between income support, work incentives, as well as mutual obligations and active labour market programmes.

JEL codes

H31, H53, J08, J68
Experimental investigations on the phase equilibrium of semiclathrate hydrates of carbon dioxide in TBAB with small amount of surfactant
Authors: Joshi Abhishek , Sangwai Jitendra S , Das Kousik , Sami Nagham Amer 
Published: February 2013

Abstract
Experimental studies are carried out on a semiclathrate hydrate system of carbon dioxide in tetra-n-butyl-ammonium bromide (TBAB) with a small amount of surfactant, sodium dodecyl sulfate (SDS), for 5, 10, and 20 wt.% TBAB to determine the phase equilibrium temperature and pressure conditions. It is observed that the presence of SDS did not influence the equilibrium conditions of the semiclathrate hydrate. Re-nucleation (memory) effect of semiclathrate hydrates of CO2 is studied for few cases of TBAB concentration in an aqueous solution. The equilibrium pressure and temperature conditions obtained for memory effect and regular experimental run without memory effect were observed to be quite close. It is concluded that in the case of no memory effect, with increasing TBAB percentage in the system, the time required for nucleation is reduced. For the same TBAB concentration, the incipient pressure and temperature required for nucleation and re-nucleation of semiclathrate hydrates increase while the time required for re-nucleation decreases.
Leukocyte-specific protein 1 links TNF receptor-associated factor 1 to survival signaling downstream of 4-1BB in T cells
Authors: Sabbagh Laurent , Andreeva Daniela , Laramée Geneviève Dubeau , Oussa N A Eustache , Lew Déborah , Bisson Nicolas , Soumounou Youssouf , Pawson Tony , Watts Tania H 
Published: February 2013

Abstract
TRAF1 and LSP1 are direct binding partners, and cooperate to promote survival of primary T cells in response to 4-1BB co-stimulation.
4-1BB is a member of the TNFR superfamily, which contributes to the activation of signaling pathways required for the survival of activated and memory T cells. We have shown previously that TRAF1, an adaptor protein recruited to 4-1BB, is required for 4-1BB-mediated CD8 T cell survival in vivo. With the use of a proteomics approach in primary T cells, we have identified LSP1 as a novel protein recruited to the 4-1BB signaling complex in a TRAF1-dependent manner. Further characterization of the interaction between TRAF1 and LSP1 revealed that LSP1 requires the TRAF-N domain of TRAF1 for direct association. Similarly to TRAF1−/− T cells, LSP1−/− T cells exhibit impaired ERK activation following stimulation through 4-1BB and consequently, are unable to down-modulate expression of the proapoptotic Bcl-2 family member Bim. Moreover, we demonstrate that the absence of LSP1 expression leads to defective expansion and survival of T cells in response to 4-1BB stimulation. Thus, we have identified LSP1 as a new mediator involved in 4-1BB signaling and T cell survival. Collectively, our work shows that TRAF1 and LSP1 cooperate downstream of 4-1BB to activate ERK signaling and down-modulate the levels of Bim leading to enhanced T cell survival.
Forced-air patient warming blankets disrupt unidirectional airflow
Authors: Legg A. J. , Hamer A. J. 
Published: February 2013

We have recently shown that waste heat from forced-air warming blankets can increase the temperature and concentration of airborne particles over the surgical site. The mechanism for the increased concentration of particles and their site of origin remained unclear. We therefore attempted to visualise the airflow in theatre over a simulated total knee replacement using neutral-buoyancy helium bubbles. Particles were created using a Rocket PS23 smoke machine positioned below the operating table, a potential area of contamination. The same theatre set-up, warming devices and controls were used as in our previous study. This demonstrated that waste heat from the poorly insulated forced-air warming blanket increased the air temperature on the surgical side of the drape by > 5°C. This created convection currents that rose against the downward unidirectional airflow, causing turbulence over the patient. The convection currents increased the particle concentration 1000-fold (2 174 000 particles/m3 for forced-air warming vs 1000 particles/m3 for radiant warming and 2000 particles/m3 for the control) by drawing potentially contaminated particles from below the operating table into the surgical site. Cite this article: Bone Joint J 2013;95-B:407–10.
New polyethylenes in total hip replacement
Authors: García-Rey E. , García-Cimbrelo E. , Cruz-Pardos A. 
Published: February 2013

Between 1999 and 2001, 90 patients underwent total hip replacement using the same uncemented acetabular and femoral components with a 28 mm metallic femoral head but with prospective randomisation of the acetabular liner to either Durasul highly cross-linked polyethylene or nitrogen-sterilised Sulene polyethylene. We assessed 83 patients at a minimum follow-up of ten years. Linear penetration of the femoral head was estimated at six weeks, six and 12 months and annually thereafter, using the Dorr method, given the non-spherical shape of the acetabular component. There was no loosening of any component; only one hip in the Sulene group showed proximal femoral osteolysis. The mean penetration of the femoral head at six weeks was 0.08 mm (0.02 to 0.15) for the Durasul group and 0.16 mm (0.05 to 0.28) for the Sulene group (p = 0.001). The mean yearly linear penetration was 64.8% lower for the Durasul group at 0.05 mm/year (sd 0.035) for the Sulene group and 0.02 mm/year (sd 0.016) for the Durasul (p < 0.001). Mean linear femoral head penetration at ten years was 61% less in the Durasul than Sulene group. Highly cross-linked polyethylene gives excellent results at ten years. Cite this article: Bone Joint J 2013;95-B:326–32.
“When can I return to driving?”
Authors: MacLeod K. , Lingham A. , Chatha H. , Lewis J. , Parkes A. , Grange S. , Smitham P. J. 
Published: February 2013

Clinicians are often asked by patients, “When can I drive again?” after lower limb injury or surgery. This question is difficult to answer in the absence of any guidelines. This review aims to collate the currently available evidence and discuss the factors that influence the decision to allow a patient to return to driving. Medline, Web of Science, Scopus, and EMBASE were searched using the following terms: ‘brake reaction time’, ‘brake response time’, ‘braking force’, ‘brake pedal force’, ‘resume driving’, ‘rate of application of force’, ‘driving after injury’, ‘joint replacement and driving’, and ‘fracture and driving’. Of the relevant literature identified, most studies used the brake reaction time and total brake time as the outcome measures. Varying recovery periods were proposed based on the type and severity of injury or surgery. Surveys of the Driver and Vehicle Licensing Agency, the Police, insurance companies in the United Kingdom and Orthopaedic Surgeons offered a variety of opinions. There is currently insufficient evidence for any authoritative body to determine fitness to drive. The lack of guidance could result in patients being withheld from driving for longer than is necessary, or returning to driving while still unsafe. Cite this article: Bone Joint J 2013;95-B:290–4.
Pathology of the tendo Achillis
Authors: Ribbans W. J. , Collins M. 
Published: February 2013

The incidence of acute and chronic conditions of the tendo Achillis appear to be increasing. Causation is multifactorial but the role of inherited genetic elements and the influence of environmental factors altering gene expression are increasingly being recognised. Certain individuals’ tendons carry specific variations of genetic sequence that may make them more susceptible to injury. Alterations in the structure or relative amounts of the components of tendon and fine control of activity within the extracellular matrix affect the response of the tendon to loading with failure in certain cases. This review summarises present knowledge of the influence of genetic patterns on the pathology of the tendo Achillis, with a focus on the possible biological mechanisms by which genetic factors are involved in the aetiology of tendon pathology. Finally, we assess potential future developments with both the opportunities and risks that they may carry. Cite this article: Bone Joint J 2013;95-B:305–13.
The prognostic value of the serum level of C-reactive protein for the survival of patients with a primary sarcoma of bone
Authors: Nakamura T. , Grimer R. J. , Gaston C. L. , Watanuki M. , Sudo A. , Jeys L. 
Published: February 2013

The aim of this study was to determine whether the level of circulating C-reactive protein (CRP) before treatment predicted overall disease-specific survival and local tumour control in patients with a sarcoma of bone. We retrospectively reviewed 318 patients who presented with a primary sarcoma of bone between 2003 and 2010. Those who presented with metastases and/or local recurrence were excluded. Elevated CRP levels were seen in 84 patients before treatment; these patients had a poorer disease-specific survival (57% at five years) than patients with a normal CRP (79% at five years) (p < 0.0001). They were also less likely to be free of recurrence (71% at five years) than patients with a normal CRP (79% at five years) (p = 0.04). Multivariate analysis showed the pre-operative CRP level to be an independent predictor of survival and local control. Patients with a Ewing’s sarcoma or chondrosarcoma who had an elevated CRP before their treatment started had a significantly poorer disease-specific survival than patients with a normal CRP (p = 0.02 and p < 0.0001, respectively). Patients with a conventional osteosarcoma and a raised CRP were at an increased risk of poorer local control. We recommend that CRP levels are measured routinely in patients with a suspected sarcoma of bone as a further prognostic indicator of survival. Cite this article: Bone Joint J 2013;95-B:411–18.
The effect of osteoarthritis of the knee on the biomechanics of other joints in the lower limbs
Authors: Metcalfe A. J. , Stewart C. , Postans N. , Dodds A. L. , Holt C. A. , Roberts A. P. 
Published: February 2013

The aim of this study was to examine the loading of the other joints of the lower limb in patients with unilateral osteoarthritis (OA) of the knee. We recruited 20 patients with no other symptoms or deformity in the lower limbs from a consecutive cohort of patients awaiting knee replacement. Gait analysis and electromyographic recordings were performed to determine moments at both knees and hips, and contraction patterns in the medial and lateral quadriceps and hamstrings bilaterally. The speed of gait was reduced in the group with OA compared with the controls, but there were only minor differences in stance times between the limbs. Patients with OA of the knee had significant increases in adduction moment impulse at both knees and the contralateral hip (adjusted p-values: affected knee: p < 0.01, unaffected knee p = 0.048, contralateral hip p = 0.03), and significantly increased muscular co-contraction bilaterally compared with controls (all comparisons for co-contraction, p < 0.01). The other major weight-bearing joints are at risk from abnormal biomechanics in patients with unilateral OA of the knee. Cite this article: Bone Joint J 2013;95-B:348–53.
A Comparison of Initial Monotherapy with Norepinephrine Versus Vasopressin for Resuscitation in Septic Shock
Authors: Daley Mitchell J , Lat Ishaq , Mieure Katherine D , Jennings Heath R , Hall Jesse B , Kress John P 
Published: February 2013

BACKGROUND Early goal-directed therapy is a time-sensitive therapeutic algorithm with a tiered approach to target hypoperfusion and cardiovascular collapse within the first 6 hours of septic shock. The Surviving Sepsis Campaign guidelines recommend norepinephrine or dopamine as the initial vasoactive agent for resuscitation in septic shock, reserving the administration of vasopressin as adjunctive therapy. OBJECTIVE To determine whether vasopressin was noninferior to norepinephrine as the initial vasopressor to achieve a mean arterial pressure (MAP) goal in the first 6 hours of shock onset. METHODS This retrospective cohort study evaluated adults who received monotherapy with either norepinephrine or vasopressin as initial vasoactive therapy for the management of septic shock. Patients were excluded if the treatment arm was not monotherapy, if they were admitted to a cardiology or cardiothoracic surgery service, or if they lacked a comparator-based 1:1 frequency matching. RESULTS A total of 130 patients were included, 65 in each treatment arm. The proportion of patients who achieved a goal MAP in the vasopressin group was 63% (95% CI 51%–75%) and was 67.7% (95% CI 56%–79%) in the norepinephrine group. This observed difference between goal MAP attainment did not exceed the predefined noninferiority margin of −25% (CI for 4.7% difference −21.2% to 12%), suggesting noninferiority of vasopressin. No significant difference was identified between vasopressin and norepinephrine for final mean (SD) MAP achieved (75 [9.6] and 76.0 [8.2] mm Hg, respectively; p = 0.06) or the mean total change from baseline MAP to goal (14.1 [8.4] and 15.1 [9.1] mm Hg, respectively; p = 0.6). CONCLUSIONS Vasopressin was noninferior to norepinephrine for the achievement of a MAP goal in the first 6 hours from onset of septic shock. Further prospective analysis is warranted; however, the results are useful for consideration of alternative vasopressors in the setting of drug shortages.
Review on the Influence of Protocol Design on Clinical Outcomes in Rheumatoid Arthritis Treated with Rituximab
Authors: Shetty Shawn , Fisher Mark C , Ahmed A Razzaque 
Published: February 2013

OBJECTIVE To critically analyze the influence of protocol design on clinical outcome in patients with rheumatoid arthritis (RA) treated with rituximab. DATA SOURCES A PubMed and EMBASE search (January 2000-January 2012) using the key words rheumatoid arthritis and rituximab was performed. STUDY SELECTION AND DATA EXTRACTION A search of English-language studies from the data sources was conducted for randomized, double-blind, placebo-controlled studies with 100 patients or more assessing the efficacy and safety of rituximab in the treatment of RA. From these studies, 2 authors independently extracted, compiled, and aggregated the data. DATA SYNTHESIS Eight studies met the inclusion criteria. In these studies, some patients had not been treated with tumor necrosis factor-alfa (TNF-α) inhibitors, while most did not respond to it. The variables compared included dose (500 vs 1000 mg), duration of study (24 vs 48 weeks), and number of cycles (1 vs 2). They were statistically analyzed using the χ2 test. There was a statistically significant difference in the response to rituximab compared to the control (methotrexate) (p < 0.001). In patients who were studied for only 24 weeks, given 500 or 1000 mg for 1 or 2 cycles, a 90% or greater response rate was reported in those who achieved an ACR 20, but no statistically significant differences were observed (p = 0.75). In patients studied for 48 weeks who received 2 cycles of either 500 mg or 1000 mg of rituximab and achieved an ACR 20, a statistically significant difference (p < 0.001) was observed in those who received a dose of 1000 mg for 2 cycles (42.77% vs 67.49%). CONCLUSIONS In patients who are nonresponsive to disease-modifying antirheumatic drugs and TNF-α inhibitors, rituximab may be a promising and well-tolerated biologic agent. The capacity of rituximab to produce long-term, sustained remissions could not be evaluated because the duration of the studies was limited to 24 weeks or 48 weeks. Studies with longer periods of observation are warranted.
Transforming potential program implementers in professional development: the project P.A.T.H.S. in Hong Kong
Authors: Shek Daniel T.L. , Yim Eunice P.Y. , Sun Rachel C.F. 
Published: February 2013

Abstract
High quality pre-implementation professional training is the cornerstone for successful implementation of positive youth development programs. A qualitative evaluation study was conducted to understand the experiences of the potential program implementers of the Project P.A.T.H.S. in Hong Kong. The findings showed that participants highly valued the learning experiences acquired from the training program, particularly in the areas of knowledge acquisition and personal growth. Participants who benefited from these dimensions developed attitudes and skills that are desirable for the implementation of the Project P.A.T.H.S. Implications about the conditions that are conducive to the P.A.T.H.S. training program in promoting knowledge, skills acquisition, retention, application, and generalization are discussed.