tbuckley/cabot-search huggingface dataset:
The effect of real-time gait retraining on hip kinematics, pain and function in subjects with patellofemoral pain syndrome
Authors: B Noehren, J Scholz, I Davis
Journal: British Journal of Sports Medicine (2010)

Background Patellofemoral pain syndrome (PFPS) is the most common overuse injury in runners. Recent research suggests that hip mechanics play a role in the development of this syndrome. Currently, there are no treatments that directly address the atypical mechanics associated with this injury. Objective The purpose of this study was to determine whether gait retraining using real-time feedback improves hip mechanics and reduces pain in subjects with PFPS. Methods Ten runners with PFPS participated in this study. Real-time kinematic feedback of hip adduction (HADD) during stance was provided to the subjects as they ran on a treadmill. Subjects completed a total of eight training sessions. Feedback was gradually removed over the last four sessions. Variables of interest included peak HADD, hip internal rotation (HIR), contralateral pelvic drop, as well as pain on a verbal analogue scale and the lower-extremity function index. We also assessed HADD, HIR and contralateral pelvic drop during a single leg squat. Comparisons of variables of interest were made between the initial, final and 1-month follow-up visit. Results Following the gait retraining, there was a significant reduction in HADD and contralateral pelvic drop while running. Although not statistically significant, HIR decreased by 23% following gait retraining. The 18% reduction in HADD during a single leg squat was very close to significant. There were also significant improvements in pain and function. Subjects were able to maintain their improvements in running mechanics, pain and function at a 1-month follow-up. An unexpected benefit of the retraining was an 18% and 20% reduction in instantaneous and average vertical load rates, respectively. Conclusions Gait retraining in individuals with PFPS resulted in a significant improvement of hip mechanics that was associated with a reduction in pain and improvements in function. These results suggest that interventions for PFPS should focus on addressing the underlying mechanics associated with this injury. The reduction in vertical load rates may be protective for the knee and reduce the risk for other running-related injuries.
Epidemiology of scleroderma.
Authors: A J Silman
Journal: Annals of the Rheumatic Diseases (1991)

CriteriaThere is not a single diagnostic test for sclero- derma and until 1980 there were no published criteria.Many would argue, however, that the disease is sufficiently obvious and distinct clinically to obviate the need for specific criteria.A subcommittee of the American Rheumatism Association (ARA) undertook a study of 264 patients with 'definite' scleroderma from 29 centres and compared the clinical findings with those for some 400 patients with either systemic lupus erythematosus, dermatomyositis, poly- myositis, or Raynaud's phenomenon.' ARl patients studied were within two years of onset.The development of criteria was not difficult (table 1), and these criteria were 97% sensitive and had a specificity of 98% (990/o compared with the patients with systemic lupus erythe- matosus and 94% compared with those with Raynaud's phenomenon).The single criterion of proximal scleroderma was 100% specific (not surprisingly) and 91% sensitive.There is a problem here as such a feature is by definition absent from patients with the limited cutaneous form of the disease and thus the criteria are likely to be insensitive for that group, who account for about 50% of patients in published clinical series.Thus in 57 consecutive new patients from New Zealand the ARA criteria were only 79% sensitive.2 3By contrast, in a heavily selected group of 47 Belgian patients the criterion of proximal scleroderma was present in all.4Occurrence Scleroderma is a rare disease and virtually all the descriptive epidemiology is derived from either prospective or retrospective review of patients attending health service institutions serving a defined denominator population.
European Society of Gastrointestinal Endoscopy (ESGE) Guideline Development Policy
Authors: J.-M. Dumonceau, C. Hassan, A. Riphaus, T. Ponchon
Journal: Endoscopy (2012)

Numerous scientific publications explore the field of gastrointestinal (GI) endoscopy (a Pubmed search currently yields > 73000 results). Therefore, guidelines have become an indispensable tool for incorporating up-to-date knowledge into daily clinical care. Since the 1990 s, the issuing of guidelines has been a central task of the European Society of Gastrointestinal Endoscopy (ESGE). Here, the ESGE clarifies the types of policy documents that it issues and the methodology used to produce them, taking into account recent methodological developments.
Ipilimumab in Combination With Paclitaxel and Carboplatin As First-Line Treatment in Stage IIIB/IV Non–Small-Cell Lung Cancer: Results From a Randomized, Double-Blind, Multicenter Phase II Study
Authors: Thomas J. Lynch, Igor Bondarenko, Alexander Luft, Piotr Serwatowski, Fabrice Barlesi, Raju Chacko, Martin Sebastian, Joel Neal, Haolan Lu, Jean-Marie Cuillerot, Martin Reck
Journal: Journal of Clinical Oncology (2012)

Ipilimumab, which is an anti-cytotoxic T-cell lymphocyte-4 monoclonal antibody, showed a survival benefit in melanoma with adverse events (AEs) managed by protocol-defined guidelines. A phase II study in lung cancer assessed the activity of ipilimumab plus paclitaxel and carboplatin.Patients (N = 204) with chemotherapy-naive non-small-cell lung cancer (NSCLC) were randomly assigned 1:1:1 to receive paclitaxel (175 mg/m(2)) and carboplatin (area under the curve, 6) with either placebo (control) or ipilimumab in one of the following two regimens: concurrent ipilimumab (four doses of ipilimumab plus paclitaxel and carboplatin followed by two doses of placebo plus paclitaxel and carboplatin) or phased ipilimumab (two doses of placebo plus paclitaxel and carboplatin followed by four doses of ipilimumab plus paclitaxel and carboplatin).Treatment was administered intravenously every 3 weeks for ≤ 18 weeks (induction). Eligible patients continued ipilimumab or placebo every 12 weeks as maintenance therapy. Response was assessed by using immune-related response criteria and modified WHO criteria. The primary end point was immune-related progression-free survival (irPFS). Other end points were progression-free survival (PFS), best overall response rate (BORR), immune-related BORR (irBORR), overall survival (OS), and safety.The study met its primary end point of improved irPFS for phased ipilimumab versus the control (hazard ratio [HR], 0.72; P = .05), but not for concurrent ipilimumab (HR, 0.81; P = .13). Phased ipilimumab also improved PFS according to modified WHO criteria (HR, 0.69; P = .02). Phased ipilimumab, concurrent ipilimumab, and control treatments were associated with a median irPFS of 5.7, 5.5, and 4.6 months, respectively, a median PFS of 5.1, 4.1, and 4.2 months, respectively, an irBORR of 32%, 21% and 18%, respectively, a BORR of 32%, 21% and 14%, respectively, and a median OS of 12.2, 9.7, and 8.3 months. Overall rates of grade 3 and 4 immune-related AEs were 15%, 20%, and 6% for phased ipilimumab, concurrent ipilimumab, and the control, respectively. Two patients (concurrent, one patient; control, one patient) died from treatment-related toxicity.Phased ipilimumab plus paclitaxel and carboplatin improved irPFS and PFS, which supports additional investigation of ipilimumab in NSCLC.
Are the Roma population risk group for tuberculosis
Authors: Mirjana Trajcevska, Aleksandar Sandevski
Journal: European Respiratory Journal (2013)

Introduction: The latest data by WHO show that 80% of TB cases in Europe are in the countries which have numerous Roma population. The number of Roma in Macedonia is 53 870 (2.66%).  Aim: Our aim was to find out what is their participation in the total number of TB patients, what is their incidence and are they a risk group for TB and possible reasons for that.  Patients and methods: For this purpose we analyzed data in latest six (6) years with special accent on Roma population with TB (gender, age, incidence).  Results: We had 563 patients with TB in 2007; the incidence was 27.8/100 000 for general population, but the incidence for Roma people was 74.2/100 000. The next year incidence in Roma population was 59.4/100 000 and in general population 23.8/100 000. In 2009 the incidence in Roma population was 42.6/100 000 and in general population 23.4/100 000. The next year the incidence in Roma people was 70.5/100 000 and in general population 20.8/100 000. In 2011 the incidence in Roma people was 51.9/100 000 and in general population 17.9/100 000. The last year there were 356 regsitrated TB patients in the country with incidence of 17,2/100 000. The incidence of Roma people was 46,4/100 000.  Conclusions: Roma are more vulnerable community. They are risk group for TB because their incidence is three times higher than in general population. Possible reasons for this are: substandard living conditions, lack of education and low rate of employment.
Genetic Targeting or Pharmacologic Inhibition of NADPH Oxidase Nox4 Provides Renoprotection in Long-Term Diabetic Nephropathy
Authors: Jay C. Jha, Stephen P. Gray, David Barit, Jun Okabe, Assam El-Osta, Tamehachi Namikoshi, Vicki Thallas-Bonke, Kirstin Wingler, Cedric Szyndralewiez, Freddy Heitz, Rhian M. Touyz, Mark E. Cooper, Harald H.H.W. Schmidt, Karin A. Jandeleit-Dahm
Journal: Journal of the American Society of Nephrology (2014)

Diabetic nephropathy may occur, in part, as a result of intrarenal oxidative stress. NADPH oxidases comprise the only known dedicated reactive oxygen species (ROS)-forming enzyme family. In the rodent kidney, three isoforms of the catalytic subunit of NADPH oxidase are expressed (Nox1, Nox2, and Nox4). Here we show that Nox4 is the main source of renal ROS in a mouse model of diabetic nephropathy induced by streptozotocin administration in ApoE(-/-) mice. Deletion of Nox4, but not of Nox1, resulted in renal protection from glomerular injury as evidenced by attenuated albuminuria, preserved structure, reduced glomerular accumulation of extracellular matrix proteins, attenuated glomerular macrophage infiltration, and reduced renal expression of monocyte chemoattractant protein-1 and NF-κB in streptozotocin-induced diabetic ApoE(-/-) mice. Importantly, administration of the most specific Nox1/4 inhibitor, GKT137831, replicated these renoprotective effects of Nox4 deletion. In human podocytes, silencing of the Nox4 gene resulted in reduced production of ROS and downregulation of proinflammatory and profibrotic markers that are implicated in diabetic nephropathy. Collectively, these results identify Nox4 as a key source of ROS responsible for kidney injury in diabetes and provide proof of principle for an innovative small molecule approach to treat and/or prevent chronic kidney failure.
Effects of rest interval on isokinetic strength and functional performance after short-term high intensity training.
Authors: D M Pincivero, S M Lephart, R G Karunakara
Journal: British Journal of Sports Medicine (1997)

OBJECTIVES: The ability to maximally generate active muscle tension during resistance training has been established to be a primary determinant for strength development. The influence of intrasession rest intervals may have a profound effect on strength gains subsequent to short-term high intensity training. The purpose of this study was to examine the effects of rest interval on strength and functional performance after four weeks of isokinetic training. METHODS: Fifteen healthy college aged individuals were randomly assigned to either a short rest interval group (group 1, n = 8) or a long rest interval group (group 2, n = 7). Subjects were evaluated for quadriceps and hamstring isokinetic strength at 60 (five repetitions) and 180 (30 repetitions) degrees/second and functional performance with the single leg hop for distance test. One leg of each subject was randomly assigned to a four week, three days/week isokinetic strength training programme for concentric knee extension and flexion performed at 90 degrees/second. Subjects in group 1 received a 40 second rest interval in between exercise sets, whereas subjects in group 2 received a 160 second rest period. RESULTS: A two factor analysis of variance for the pre-test--post-test gain scores (%) showed significantly greater improvements for isokinetic hamstring total work and average power at 180 degrees/second for the trained limb of subjects in group 2 than their contralateral non-trained limb and the subjects in group 1. Significantly greater improvements for the single leg hop for distance were also found for the trained limbs of subjects in both groups as compared with the non-trained limbs. CONCLUSIONS: The findings indicate that a relatively longer intrasession rest period resulted in a greater improvement in hamstring muscle strength during short term high intensity training.
Treatment of small cell lung cancer with VP-16, vincristine, doxorubicin (Adriamycin), cyclophosphamide (EVAC), and high-dose chest radiotherapy.
Authors: G E Goodman, T P Miller, M M Manning, S L Davis, L J McMahon
Journal: Journal of Clinical Oncology (1983)

Seventy-one previously untreated patients with small cell lung cancer (SCLC) received a combination of VP-16, vincristine, doxorubicin (Adriamycin), and cyclophosphamide (EVAC) repeated every three weeks. Limited-disease (LD) patients and extensive-disease (ED) patients achieving a complete response (CR) or partial response (PR) after four to six cycles of EVAC received 4,000 rads over four weeks whole-brain radiotherapy (RT) and 5,000 rads over five weeks RT to the original pulmonary primary and mediastinum. ED patients with persisting disease outside the chest after six cycles of EVAC continued chemotherapy and did not receive RT. After RT was completed, EVAC was continued for a total treatment duration of 24 months. Of 65 patients evaluable for response 76% (25 of 33) of LD patients and 34% (11 of 32) of ED patients achieved a CR prior to RT; two additional ED patients achieved a CR after RT. Median survival for all 71 patients was 48 weeks (range, one to 207 weeks); median survival for 33 LD patients was 92 weeks and for 38 ED patients it was 36 weeks. Nine of 25 LD patients and 10 of 13 ED patients have relapsed from CR. The EVAC-RT protocol is promising in view of the high CR rate and long remission duration achieved, especially among patients with LD.
Results of treatment of advanced-stage lymphoblastic lymphoma at St Jude Children's Research Hospital from 1962 to 2002
Authors: J.T. Sandlund, C.H. Pui, Y. Zhou, M. Onciu, D. Campana, M.M. Hudson, H. Inaba, M.L. Metzger, D. Bhojwani, R.C. Ribeiro
Journal: Annals of Oncology (2013)
Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes.
Authors: J Grayson, N J Dooley, I R Koski, R M Blaese
Journal: Journal of Clinical Investigation (1981)

The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by [3H]thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells.
The pathogenesis of experimental membranous glomerulonephritis induced with homologous nephritogenic tubular antigen.
Authors: T Naruse, T Fukasawa, N Hirokawa, S Oike, Y Miyakawa
Journal: The Journal of Experimental Medicine (1976)

The renal tubular epithelial antigen (Tub-Ag) of rats was solublized by Pronase and purified by gel filtration and acrylamide gel electrophoresis. Purified Tub-Ag was a glycoprotein with S20,W value of 8.4. Utilizing radiolabeled Tug-Ag, a sensitive radioimmunoassay for Tub-Ag and homologous antibody (anti-Tub-Ag) was developed. Tub-Ag activity associated with a protein of the same molecular size was demonstrated in the serum, as well as in Pronase extracts of all the organs tested, including kidney, liver, lung, spleen, intestine, stomach, and heart. The physiochemical properties of the Tub-Ag of rats and its distribution were essentially the same as the Tub-Ag of humans, which had been found in immune deposits in the kidney of some patients with idiopathic membranous glomerulonephritis. Rats were immunized with the purified Tub-Ag emulsified in Freund's complete adjuvant and followed for Tub-Ag and anti-Tub-Ag in the serum, as well as for proteinuria and immunohistological changes in the kidney. Serum Tub-Ag dropped sharply after 20 days, when anti-Tub-Ag appeared in the circulation. Persistent, massive proteinuria appeared still later, more than 30 days after injection, when anti-Tub-Ag disappeared and Tub-Ag reappeared in the serum of some of those rats. In others, anti-Tub-Ag in the serum persisted throughout the observation period of 90 days. The pathology of the kidney of the rats with proteinuria was that of a typical membranous glomerulonephritis; thickening of glomerular capillary walls with granular deposits of gamma-globulin and Tub-Ag was observed. On the basis of these results, Tub-Ag in the serum, probably released from cellular membranes of various organs as a physiological metabolite, is considered to maintain the pathological process in the kidney by providing the antigen continuously to form immune complexes.
Connective tissue disease-associated pulmonary arterial hypertension in Chinese patients
Authors: Yan-Jie Hao, Xin Jiang, Wei Zhou, Yong Wang, Lan Gao, Yu Wang, Guang-Tao Li, Tao Hong, Yong Huo, Zhi-Cheng Jing, Zhuo-Li Zhang
Journal: European Respiratory Journal (2014)

We sought to investigate the characteristics, survival and risk factors for mortality in Chinese patients with connective tissue disease (CTD)-associated pulmonary arterial hypertension (APAH) in modern therapy era. 129 consecutive adult patients who visited one of three referral centres in China with a diagnosis of CTD-APAH confirmed by right heart catheterisation during the previous 5 years were enrolled. The end-point was all-cause death or data censoring. Systemic lupus erythematosus was the most common underlying CTD (49%) and systemic sclerosis just accounted for 6% in this cohort. The overall survival at 1 and 3 years was 92% and 80%, respectively. Pericardial effusion, a shorter 6-min walk distance, lower mixed venous oxygen saturation, higher pulmonary vascular resistance (PVR) and alkaline phosphatase (ALP), and lower total cholesterol levels were all associated with a higher risk of death among the study population. Higher PVR and ALP were independent predictors of mortality. In conclusion, unlike in western patients, systemic lupus erythematosus is the most common underlying disease in Chinese patients with CTD-APAH. The survival of Chinese patients with CTD-APAH in the modern treatment era is similar to that in western countries. Elevated PVR and ALP are independent risk factors for poor outcomes.
CB1 and CB2 cannabinoid receptors differentially regulate the production of reactive oxygen species by macrophages
Authors: K. H. Han, S. Lim, J. Ryu, C.-W. Lee, Y. Kim, J.-H. Kang, S.-S. Kang, Y. K. Ahn, C.-S. Park, J. J. Kim
Journal: Cardiovascular Research (2009)

We investigated the mechanism by which cannabinoid receptors-1 (CB1) and -2 (CB2) modulate inflammatory activities of macrophages. Real-time polymerase chain reaction showed the predominant CB2 expression in freshly isolated human monocytes. PMA, a potent inducer of differentiation, upregulated CB1 and increased CB1:CB2 transcript ratio from 1:17.5 to 1:3 in 5 days of culture. Immunohistochemistry showed that CB1 protein was colocalized in CD68- and CD36-positive macrophages in human atheroma. Through selective expression of CB1 or CB2 to thioglycollate-elicited peritoneal macrophages, we proved that CB1 and CB2 mediate opposing influences on the production of reactive oxygen species (ROS). Flow cytometry showed that cannabinoid-induced ROS production by macrophages was CB1-dependent. Immunoblotting assays confirmed that macrophage CB1, not CB2, induced phosphorylation of p38-mitogen-activated protein kinase, which modulated ROS production and the subsequent synthesis of tumour necrosis factor-α and monocyte chemoattractant protein-1. Pull-down assays showed that the Ras family small G protein, Rap1 was activated by CB2. Dominant-negative Rap1 profoundly enhanced CB1-dependent ROS production by macrophages, suggesting CB2 Rap1-dependently inhibits CB1-stimulated ROS production. CB1 promotes pro-inflammatory responses of macrophages through ROS production, which is negatively regulated by CB2 through Rap1 activation. Blocking CB1 together with selective activation of CB2 may suppress pro-inflammatory responses of macrophages.
Aldehyde Dehydrogenase 1 making molecular inroads into the differential vulnerability of nigrostriatal dopaminergic neuron subtypes in Parkinson’s disease
Authors: Huaibin Cai, Guoxiang Liu, Lixin Sun, Jinhui Ding
Journal: Translational Neurodegeneration (2014)

A preferential dysfunction/loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) accounts for the main motor symptoms of Parkinson's disease (PD), the most common degenerative movement disorder. However, the neuronal loss is not stochastic, but rather displays regionally selectivity, indicating the existence of different DA subpopulations in the SNpc. To identify the underlying molecular determinants is thereby instrumental in understanding the pathophysiological mechanisms of PD-related neuron dysfunction/loss and offering new therapeutic targets. Recently, we have demonstrated that aldehyde dehydrogenase 1 (ALDH1A1) is one such molecular determinant that defines and protects an SNpc DA neuron subpopulation preferentially affected in PD. In this review, we provide further analysis and discussion on the roles of ALDH1A1 in the function and survival of SNpc DA neurons in both rodent and human brains. We also explore the feasibility of ALDH1A1 as a potential biomarker and therapeutic target for PD.