bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burkholderia pseudomallei Triggers Altered Inflammatory Profiles in a Whole-Blood Model of Type 2 Diabetes-Melioidosis Comorbidity
Authors: Morris Jodie , Williams Natasha , Rush Catherine , Govan Brenda , Sangla Kunwarjit , Norton Robert , Ketheesan Natkunam 
Published: April 2012

ABSTRACTMelioidosis is a potentially fatal disease caused by the bacteriumBurkholderia pseudomallei. Type 2 diabetes (T2D) is the most common comorbidity associated with melioidosis.B. pseudomalleiisolates from melioidosis patients with T2D are less virulent in animal models than those from patients with melioidosis and no identifiable risk factors. We developed anex vivowhole-blood assay as a tool for comparison of early inflammatory profiles generated by T2D and nondiabetic (ND) individuals in response to aB. pseudomalleistrain of low virulence. Peripheral blood from individuals with T2D, with either poorly controlled glycemia (PC-T2D [n= 6]) or well-controlled glycemia (WC-T2D [n= 8]), and healthy ND (n= 13) individuals was stimulated withB. pseudomallei. Oxidative burst, myeloperoxidase (MPO) release, expression of pathogen recognition receptors (TLR2, TLR4, and CD14), and activation markers (CD11b and HLA-DR) were measured on polymorphonuclear (PMN) leukocytes and monocytes. Concentrations of plasma inflammatory cytokine (interleukin-6 [IL-6], IL-12p70, tumor necrosis factor alpha [TNF-α], monocyte chemoattractant protein 1 [MCP-1], IL-8, IL-1β, and IL-10) were also determined. Following stimulation, oxidative burst and MPO levels were significantly elevated in blood from PC-T2D subjects compared to controls. Differences were also observed in expression of Toll-like receptor 2 (TLR2), CD14, and CD11b on phagocytes from T2D and ND individuals. Levels of IL-12p70, MCP-1, and IL-8 were significantly elevated in blood from PC-T2D subjects compared to ND individuals. Notably, differential inflammatory responses of PC-T2D, WC-T2D, and ND individuals toB. pseudomalleioccur independently of bacterial load and confirm the efficacy of this model of T2D-melioidosis comorbidity as a tool for investigation of dysregulated PMN and monocyte responses toB. pseudomalleiunderlying susceptibility of T2D individuals to melioidosis.
Changing trends in incidence and aetiology of childhood acute non-traumatic coma over a period of changing malaria transmission in rural coastal Kenya: a retrospective analysis
Authors: Gwer Samson , Thuo Nahashon , Idro Richard , Ndiritu Moses , Boga Mwanamvua , Newton Charles , Kirkham Fenella 
Published: April 2012

ObjectivesRecent changes in malaria transmission have likely altered the aetiology and outcome of childhood coma in sub-Saharan Africa. The authors conducted this study to examine change in incidence, aetiology, clinical presentation, mortality and risk factors for death in childhood non-traumatic coma over a 6-year period.DesignRetrospective analysis of prospectively collected data.SettingSecondary level health facility: Kilifi, Coast, Kenya.ParticipantsChildren aged 9 months to 13 years admitted with acute non-traumatic coma (Blantyre Coma Score =2) between January 2004 and December 2009 to Kilifi District Hospital, Kenya. Exclusion criteria: delayed development, epilepsy and sickle cell disease.ResultsDuring the study period, 665 children (median age 32 (IQR 20–46) months; 46% were girls) were admitted in coma. The incidence of childhood coma declined from 93/100 000 children in 2004 to 44/100 000 children in 2009. There was a 64% overall drop in annual malaria-positive coma admissions and a 272% overall increase in annual admissions with encephalopathies of undetermined cause over the study period. There was no change in case death of coma. Vomiting, breathing difficulties, bradycardia, profound coma (Blantyre Coma Score=0), bacteraemia and clinical signs of meningitis were associated with increased risk of death. Seizures within 24 h prior to admission, and malaria parasitaemia, were independently associated with survival, unchanging during the study period.ConclusionThe decline in the incidence and number of admissions of childhood acute non-traumatic coma is due to decreased malaria transmission. The relative and absolute increase in admissions of encephalopathy of undetermined aetiology could represent aetiologies previously masked by malaria or new aetiologies.
Does antiretroviral therapy initiation increase sexual risk taking in Kenyan female sex workers? A retrospective case–control study
Authors: Mawji Elysha , McKinnon Lyle , Wachihi Charles , Chege Duncan , Thottingal Paul , Kariri Anthony , Plummer Francis , Ball T Blake , Jaoko Walter , Ngugi Elizabeth , Kimani Joshua , Gelmon Lawrence , Nagelkerke Nico , Kaul Rupert 
Published: April 2012

ObjectivesAlthough antiretroviral therapy (ART) prolongs life and reduces infectiousness, in some contexts, it has been associated with increased sexual risk taking.DesignRetrospective case–control study.SettingNairobi-based dedicated female sex worker (FSW) clinic.ParticipantsHIV-infected FSWs before and after ART initiation (n=62); HIV-infected and -uninfected control FSWs not starting ART during the same follow-up period (n=40).InterventionInitiation of ART.Primary outcome measuresSelf-reported condom use, client numbers and sexually transmitted infection incidence over the study period (before and after ART initiation in cases).ResultsSexual risk-taking behaviour with casual clients did not increase after ART initiation; condom use increased and sexually transmitted infection incidence decreased in both cases and controls, likely due to successful cohort-wide HIV prevention efforts.ConclusionsART provision was not associated with increases in unsafe sex in this FSW population.
Ruxolitinib: The First FDA Approved Therapy for the Treatment of Myelofibrosis
Authors: Mascarenhas John , Hoffman Ronald 
Published: April 2012

Abstract
The BCR-ABL1–negative myeloproliferative neoplasms (e.g., essential thrombocythemia, polycythemia vera, and primary myelofibrosis) are a group of heterogeneous hematologic malignancies that involve a clonal proliferation of hematopoietic stem cells. Thrombosis, bleeding, and transformation to acute leukemia reduce the overall survival of patients with myelofibrosis, a disease typified by progressive splenomegaly and disease-related symptoms such as fatigue, pruritus, and bony pains. Hematopoietic stem cell transplant offers the only potential for cure in a minority of eligible patients, leaving a serious unmet need for improved therapies. Recent advances in our understanding of the pathogenetic mechanisms underlying these diseases have led to an explosion of clinical trials evaluating novel therapies. The discovery of an activating mutation in the Janus-activated kinase 2 (JAK2) gene provided a therapeutic target to downregulate this activated signaling pathway, which influences the phenotype of these diseases. Ruxolitinib (Jakafi; Incyte) is a small-molecule inhibitor of JAK1/2 that has proved to be effective at reducing splenomegaly and ameliorating symptoms in myeloproliferative neoplasms. Based on the results of 2 pivotal randomized phase III clinical trials, ruxolitinib has become the first therapeutic to be approved by the U.S. Food and Drug Administration for treatment of patients with myelofibrosis. Ruxolitinib offers a well-tolerated oral therapeutic option for patients with myelofibrosis with symptomatic splenomegaly and debilitating disease-related symptoms, but it does not seem to be effective at eliminating the underlying hematological malignancy. Clin Cancer Res; 18(11); 3008–14. ©2012 AACR.
Graduated Endoscopic Multiangle Approach for Access to the Infratemporal Fossa
Authors: Eloy Jean Anderson , Murray Kim P. , Friedel Mark E. , Tessema Belachew , Liu James K. 
Published: April 2012

ObjectiveThe infratemporal fossa (ITF) has historically been one of the most difficult regions of the skull base to access surgically. Available open approaches are complex, are associated with high morbidity, and do not always afford optimal visualization. Endoscopic access to the ITF improves visualization for management of many sinonasal and lateral skull base lesions involving this region. The purpose of this study is to evaluate a graduated multiangle approach for endoscopic access to this area using a cadaveric model.Study Design and SettingCadaveric study at an academic medical center.MethodsEndoscopic dissection was performed on a total of 10 sides of 5 fresh cadaveric heads. Four different approaches to the ITF were studied: ipsilateral endonasal, endoscopically assisted Caldwell‐Luc, contralateral endonasal via septotomy, and endoscopically assisted Gillies transtemporal. High‐quality endoscopic pictures and high‐definition videos of each technique were obtained in order to document the differences in access achieved with each approach.ResultsThe combination of the 4 different endoscopic techniques allowed complete access to all areas of the ITF. The endoscopically assisted Caldwell‐Luc improved anteroposterior access, the contralateral septotomy approach resulted in excellent far lateral access, and the endoscopically assisted Gillies approach allowed posterosuperior visualization and instrumentation.ConclusionEndoscopic access to the ITF can be accomplished by each of the 4 methods described. A multiangle, graduated approach can provide surgeons the ability to customize surgical access depending on the location of a specific lesion within the ITF.
Hip Morphological Characteristics and Range of Internal Rotation in Femoroacetabular Impingement
Authors: Audenaert Emmanuel A. , Peeters Ian , Vigneron Lara , Baelde Nick , Pattyn Christophe 
Published: April 2012

Background: Radiographic features specifically related to the occurrence of femoroacetabular impingement (FAI) appear to be highly prevalent in the asymptomatic population. It remains unclear, however, how these incidental findings should be interpreted clinically and which other variables might differentiate between true incidental findings and preclinical patients. Purpose: To study the association between cam and overall hip morphological characteristics and range of motion in impingement patients, asymptomatic patients (healthy patients with radiographic features specific to FAI), and healthy controls. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Morphological parameters describing cam and overall hip anatomy were obtained from 30 patients (10 per subgroup) with use of 3-dimensional computational methods. In addition, the range of internal rotation in high flexion activities was evaluated, and its relation to hip morphological variables was analyzed in a multivariate regression model. Results: Size of the cam lesion and range of motion significantly differed between groups ( P < .05). The range of internal rotation on impingement testing was found to average 27.9° in the healthy control group compared with 21.1° in the asymptomatic control group with radiographic features specific to FAI ( P < .001) and 12.3° in the patient group ( P < .001). Cam size, acetabular coverage, and femoral version appeared to be predictive variables for the range of internal rotation. Seventy-five percent of variance between patients could be attributed to the combined effect of these 3 variables ( R = .86). The range of motion was decreased in cam patients and asymptomatic patients, and early femoroacetabular conflict was not restricted to the area of the cam lesion but involved the entire anterior femoral head-neck junction. Conclusion: Decreased range of motion, as found in FAI, is not solely dependent on the size or even the occurrence of a cam lesion but should be interpreted by taking into account the overall hip anatomy, specifically femoral version and acetabular coverage. Decreased femoral anteversion and increased acetabular coverage add to the risk of early femoroacetabular collision during sports and activities of daily living and therefore appear to be additional predictive variables, besides the finding of a cam lesion, for the risk of clinical hip impingement development. In addition, the findings suggest that surgical osteochondroplasty to restore a normal range of motion may necessitate more excessive bone resection than what simply appears to be a bump on imaging.
Patellar Tendon Healing With Platelet-Rich Plasma
Authors: de Almeida Adriano Marques , Demange Marco Kawamura , Sobrado Marcel Faraco , Rodrigues Marcelo Bordalo , Pedrinelli André , Hernandez Arnaldo José 
Published: April 2012

Background: The patellar tendon has limited ability to heal after harvesting its central third. Platelet-rich plasma (PRP) could improve patellar tendon healing. Hypothesis: Adding PRP to the patellar tendon harvest site would improve donor site healing and improve clinical outcome at 6 months after anterior cruciate ligament (ACL) reconstruction with a patellar tendon graft. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Twenty-seven patients were randomly divided to receive (n = 12) or not receive (n = 15) PRP in the patellar tendon harvest site during ACL reconstruction. The primary outcome was magnetic resonance imaging (MRI) assessment of patellar tendon healing (gap area) after 6 months. Secondary outcomes were questionnaires and isokinetic testing of ACL reconstruction with a patellar tendon graft comparing both groups. Results: Patellar tendon gap area was significantly smaller in the PRP group (4.9 ± 5.3 mm2; 95% confidence interval [CI], 1.1-8.8) than in the control group (9.4 ± 4.4 mm2; 95% CI, 6.6-12.2; P = .046). Visual analog scale score for pain was lower in the PRP group immediately postoperatively (3.8 ± 1.0; 95% CI, 3.18-4.49) than in the control group (5.1 ± 1.4; 95% CI, 4.24-5.90; P = .02). There were no differences after 6 months in questionnaire and isokinetic testing results comparing both groups. Conclusion: We showed that PRP had a positive effect on patellar tendon harvest site healing on MRI after 6 months and also reduced pain in the immediate postoperative period. Questionnaire and isokinetic testing results were not different between the groups at 6 months.
Tegafur–uracil is a safe alternative for the treatment of colorectal cancer in patients with partial dihydropyrimidine dehydrogenase deficiency: a proof of principle
Authors: Cubero Daniel I.G. , Cruz Felipe Melo , Santi Patrícia , Silva Ismael Dale C.G. , Giglio Auro del 
Published: April 2012

Objective: The objective of this study was to evaluate the safety of using tegafur–uracil (UFT) in colorectal cancer patients with partial dihydropyrimidine dehydrogenase (DPD) deficiency. Patients and Methods: The study included five colorectal cancer patients who presented with acute toxicity (grades 3 and 4) after being given the first cycle of chemotherapy using 5-fluorouracil. The DPD deficiency was confirmed by gene sequencing. After a full recovery from all side effects, we changed the regimen to UFT (300 mg/m2/day) associated with leucovorin (90 mg/day) for 21 days, with an empirical dose reduction of at least 10% in the first cycle. Results: We prospectively analysed 22 UFT cycles in 5 patients. We did not observe any episodes of grade 3 or 4 toxicity. The predominant toxicities were of grades 1 and 2 (nausea, vomiting and diarrhoea). Conclusion: Here, we demonstrate a complete absence of severe toxicity in all patients and cycles analysed. We believe that UFT is a safe alternative for the treatment of patients with partial DPD deficiency.
Differential pattern and prognostic significance of CD4+, FOXP3+ and IL-17+tumor infiltrating lymphocytes in ductal and lobular breast cancers
Authors: Droeser Raoul , Zlobec Inti , Kilic Ergin , Güth Uwe , Heberer Michael , Spagnoli Giulio , Oertli Daniel , Tapia Coya 
Published: April 2012

AbstractBackgroundClinical relevance of tumor infiltrating lymphocytes (TILs) in breast cancer is controversial. Here, we used a tumor microarray including a large series of ductal and lobular breast cancers with long term follow up data, to analyze clinical impact of TIL expressing specific phenotypes and distribution of TILs within different tumor compartments and in different histological subtypes.MethodsA tissue microarray (TMA) including 894 ductal and 164 lobular breast cancers was stained with antibodies recognizing CD4, FOXP3, and IL-17 by standard immunohistochemical techniques. Lymphocyte counts were correlated with clinico-pathological parameters and survival.ResultsCD4+lymphocytes were more prevalent than FOXP3+TILs whereas IL-17+TILs were rare. Increased numbers of total CD4+and FOXP3+TIL were observed in ductal, as compared with lobular carcinomas. High grade (G3) and estrogen receptor (ER) negative ductal carcinomas displayed significantly (p< 0.001) higher CD4+and FOXP3+lymphocyte infiltration while her2/neu over-expression in ductal carcinomas was significantly (p< 0.001) associated with higher FOXP3+TIL counts. In contrast, lymphocyte infiltration was not linked to any clinico-pathological parameters in lobular cancers. In univariate but not in multivariate analysis CD4+infiltration was associated with significantly shorter survival in patients bearing ductal, but not lobular cancers. However, a FOXP3+/CD4+ratio > 1 was associated with improved overall survival even in multivariate analysis (p= 0.033).ConclusionsDuctal and lobular breast cancers appear to be infiltrated by different lymphocyte subpopulations. In ductal cancers increased CD4+and FOXP3+TIL numbers are associated with more aggressive tumor features. In survival analysis, absolute numbers of TILs do not represent major prognostic indicators in ductal and lobular breast cancer. Remarkably however, a ratio > 1 of total FOXP3+/CD4+TILs in ductal carcinoma appears to represent an independent favorable prognostic factor.
Eye care utilization by older adults in low, middle, and high income countries
Authors: Vela Claudia , Samson Elodie , Zunzunegui Maria Victoria , Haddad Slim , Aubin Marie-Josée , Freeman Ellen E 
Published: April 2012

Abstract

Background
The risk of visual impairment increases dramatically with age and therefore older adults should have their eyes examined at least every 1 to 2 years. Using a world-wide, population-based dataset, we sought to determine the frequency that older people had their eyes examined. We also examined factors associated with having a recent eye exam.

Methods
The World Health Surveys were conducted in 70 countries throughout the world in 2002-2003 using a random, multi-stage, stratified, cluster sampling design. Participants 60 years and older from 52 countries (n = 35,839) were asked "When was the last time you had your eyes examined by a medical professional?". The income status of countries was estimated using gross national income per capita data from 2003 from the World Bank website. Prevalence estimates were adjusted to account for the complex sample design.

Results
Overall, only 18% (95% CI 17, 19) of older adults had an eye exam in the last year. The rate of an eye exam in the last year in low, lower middle, upper middle, and high income countries was 10%, 24%, 22%, and 37% respectively. Factors associated with having an eye exam in the last year included older age, female gender, more education, urban residence, greater wealth, worse self-reported health, having diabetes, and wearing glasses or contact lenses (p < 0.05).

Conclusions
Given that older adults often suffer from age-related but treatable conditions, they should be seen on a regular basis to prevent visual impairment and its disabling consequences.
Ingredients of Huangqi decoction slow biliary fibrosis progression by inhibiting the activation of the transforming growth factor-beta signaling pathway
Authors: Du Jin-Xing , Sun Ming-Yu , Du Guang-Li , Li Feng-Hua , Liu Cheng , Mu Yong-Ping , Chen Gao-Feng , Long Ai-Hua , Bian Yan-Qin , Liu Jia , Liu Cheng-Hai , Hu Yi-Yang , Xu Lie-Ming , Liu Ping 
Published: April 2012

Abstract

Background
Huangqi decoction was first described in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy in Song Dynasty (AD 1078), and it is an effective recipe that is usually used to treat consumptive disease, anorexia, and chronic liver diseases. Transforming growth factor beta 1 (TGFβ1) plays a key role in the progression of liver fibrosis, and Huangqi decoction and its ingredients (IHQD) markedly ameliorated hepatic fibrotic lesions induced by ligation of the common bile duct (BDL). However, the mechanism of IHQD on hepatic fibrotic lesions is not yet clear. The purpose of the present study is to elucidate the roles of TGFβ1 activation, Smad-signaling pathway, and extracellular signal-regulated kinase (ERK) in the pathogenesis of biliary fibrosis progression and the antifibrotic mechanism of IHQD.

Methods
A liver fibrosis model was induced by ligation of the common bile duct (BDL) in rats. Sham-operation was performed in control rats. The BDL rats were randomly divided into two groups: the BDL group and the IHQD group. IHQD was administrated intragastrically for 4 weeks. At the end of the fifth week after BDL, animals were sacrificed for sampling of blood serum and liver tissue. The effect of IHQD on the TGFβ1 signaling pathway was evaluated by western blotting and laser confocal microscopy.

Results
Decreased content of hepatic hydroxyproline and improved liver function and histopathology were observed in IHQD rats. Hepatocytes, cholangiocytes, and myofibroblasts in the cholestatic liver injury released TGFβ1, and activated TGFβ1 receptors can accelerate liver fibrosis. IHQD markedly inhibited the protein expression of TGFβ1, TGFβ1 receptors, Smad3, and p-ERK1/2 expression with no change of Smad7 expression.

Conclusion
IHQD exert significant therapeutic effects on BDL-induced fibrosis in rats through inhibition of the activation of TGFβ1-Smad3 and TGFβ1-ERK1/2 signaling pathways.
A histopathologic study of fatal paediatric cerebral malaria caused by mixed Plasmodium falciparum/Plasmodium vivax infections
Authors: Manning Laurens , Rosanas-Urgell Anna , Laman Moses , Edoni Henry , McLean Catriona , Mueller Ivo , Siba Peter , Davis Timothy ME 
Published: April 2012

Abstract
Microvascular sequestration of Plasmodium falciparum underlies cerebral malaria. Despite suggestive ex vivo evidence, this phenomenon has not been convincingly demonstrated in coma complicating Plasmodium vivax malaria. Severely-ill Papua New Guinean children with mixed P. falciparum/P. vivax infections are more likely to develop cerebral malaria and die than those with P. falciparum alone, possibly reflecting P. vivax sequestration. Nested PCR was performed on post mortem brain tissue from three such children dying from cerebral malaria due to mixed-species infections. No P. vivax DNA was detected. These findings do not support the hypothesis that P. vivax sequestration occurs in human brain.