tbuckley/cabot-search huggingface dataset:
Superior compliance with a neuromuscular training programme is associated with fewer ACL injuries and fewer acute knee injuries in female adolescent football players: secondary analysis of an RCT
Authors: Martin Hägglund, Isam Atroshi, Philippe Wagner, Markus Waldén
Journal: British Journal of Sports Medicine (2013)

Background Little is known about the influence of compliance with neuromuscular training (NMT) on the knee injury rate in football. Aim To evaluate team and player compliance with an NMT programme in adolescent female football and to study the association between compliance and acute knee injury rates. Methods Prospective cohort study based on a cluster randomised controlled trial on players aged 12–17 years with 184 intervention teams (2471 players) and 157 control teams (2085 players). Exposure and acute time loss knee injuries were recorded. Team and player compliance was recorded by the coaches on a player attendance form. The intervention group was divided into tertiles of compliance. Injury rates were compared by calculating rate ratios (RRs) and 95% CIs using exact Poisson tests with the low-compliance tertile as reference. Seasonal compliance trends were analysed using linear regression. Results Players in the high-compliance tertile had an 88% reduction in the anterior cruciate ligament (ACL) injury rate (RR 0.12, 95% CI 0.01 to 0.85), whereas the rate in the control group players was not significantly different from those in the low-compliance tertile (RR 0.77, 95% CI 0.27 to 2.21). A significant deterioration occurred in team (b=−3.0% per month, 95% CI −5.2 to −0.8) and player (b=−5.0% per month, 95% CI −7.1 to −2.9) compliance over the season. Conclusions Players with high compliance with the NMT programme had significantly reduced ACL injury rate compared with players with low compliance. Significant deterioration in team and player compliance occurred over the season.
Lymph-Borne Chemokines and Other Low Molecular Weight Molecules Reach High Endothelial Venules via Specialized Conduits While a Functional Barrier Limits Access to the Lymphocyte Microenvironments in Lymph Node Cortex
Authors: J. Elizabeth Gretz, Christopher C. Norbury, Arthur O. Anderson, Amanda E.I. Proudfoot, Stephen Shaw
Journal: The Journal of Experimental Medicine (2000)

Lymph-borne, soluble factors (e.g., chemokines and others) influence lymphocyte recirculation and endothelial phenotype at high endothelial venules (HEVs) in lymph node cortex. Yet the route lymph-borne soluble molecules travel from the subcapsular sinus to the HEVs is unclear. Therefore, we injected subcutaneously into mice and rats a wide variety of fluorophore-labeled, soluble molecules and examined their distribution in the draining lymph nodes. Rather than percolating throughout the draining lymph node, all molecules, including microbial lipopolysaccharide, were very visible in the subcapsular and medullary sinuses but were largely excluded from the cortical lymphocyte microenvironments. Exclusion prevailed even during the acute lymph node enlargement accompanying viral infection. However, low molecular mass (MW) molecules, including chemokines, did gain entry into the cortex, but in a very defined manner. Low MW, fluorophore-labeled molecules highlighted the subcapsular sinus, the reticular fibers, and the abluminal and luminal surfaces of the associated HEVs. These low MW molecules were in the fibers of the reticular network, a meshwork of collagen fibers ensheathed by fibroblastic reticular cells that connects the subcapsular sinus floor and the HEVs by intertwining with their basement membranes. Thus, low MW, lymph-borne molecules, including chemokines, traveled rapidly from the subcapsular sinus to the HEVs using the reticular network as a conduit.
INDIVIDUAL ANTIGENIC SPECIFICITY OF MYELOMA PROTEINS
Authors: Howard M. Grey, Mart Mannik, Henry G. Kunkel
Journal: The Journal of Experimental Medicine (1965)

The specific antigenic structure of individual myeloma proteins was investigated for the presence of similar antigenic determinants in pooled γ-globulin and for the localization of these determinants on the γ-globulin molecules. Quantitative precipitin analyses demonstrated that in most instances absorption of antisera specific for an individual myeloma protein with large amounts of γ-globulin markedly reduced or completely removed the reactivity of the antiserum for the homologous myeloma protein. In only one instance did strong specificity remain after absorption with 100 mg of Fr II per cc of antiserum. The antigenic determinants responsible for the individual specificity were localized in all cases studied solely to the Fab fragment produced by papain digestion. After reductive cleavage, three patterns of localization were observed. Individual specificity could be localized either to; (a) isolated heavy chains, (b) isolated light chains, (c) antigenic determinants present only when light and heavy chains were recombined. After immunization with whole myeloma proteins, individual specificity was localized in part at least to the isolated heavy chain in four of six proteins studied. It was localized to the light chains in three of five type L proteins but in none of six type K proteins. In the instances where individual specificity of the myeloma protein was present on the light chains, it was shown that the Bence Jones protein from the same patient also contained the individual specificity. Immunization with isolated heavy or light chains furnished further evidence for the individual specificity of both types of chains. These studies on myeloma proteins furnished evidence concerning the portions of the γ-globulin molecule subject to individual antigenic variation. The light chains, particularly the L type and the Fd portion of the heavy chains were primarily involved. Evidence for the importance of the quaternary structure was also obtained from the necessity in some instances for light and heavy chains to be associated in order for individual specificity to be observed. The Fc fragment of the heavy chains on the other hand showed very limited variation which was related to subgroup specificity.
Relapsed Refractory <i>BRAF-</i>Negative, <i>IGHV</i>4-34–Positive Variant of Hairy Cell Leukemia: A Distinct Entity?
Authors: Preetesh Jain, Chi Young Ok, Sergej Konoplev, Keyur P. Patel, Jeffrey Jorgensen, Zeev Estrov, Raja Luthra, Hagop Kantarjian, Farhad Ravandi
Journal: Journal of Clinical Oncology (2014)
O038 : Investigating paracetamol toxicity in HepaRG-based 3D human hepatic organotypic models with non-invasive optical coherence phase microscopy (OCPM)
Authors: L.J. Nelson, P. Treskes, K. Morgan, W. Gamal, C. Chesne, J.N. Plevris, P.O. Bagnaninchi
Journal: Journal of Hepatology (2015)
Only 3 in 20 new drugs approved in Germany in 2011 were an improvement, report says
Authors: N. Stafford
Journal: BMJ (2014)

<h3>Background</h3> Older patients with atrial fibrillation (AF) are increasingly offered direct oral anticoagulants (DOACs) to reduce the risk of catastrophic stroke, but clinical follow-up and compliance checks are still required to maintain patient safety. Although a recent qualitative meta-analysis has explored up-to-date research in this area, little is known qualitatively about clinicians’ or patients’ views and experiences of DOAC use in primary care in the UK. <h3>Aim</h3> To understand the experiences of healthcare practitioners and patients in relation to DOAC use in UK primary care. <h3>Design &amp; setting</h3> Semi-structured interviews were undertaken. Sixteen older patients with AF taking DOACs, 10 pharmacists, and six GPs were interviewed in Sheffield, England in 2018. <h3>Method</h3> Interview questions were developed following a systematic literature review. Interviews were audio-recorded, transcribed, and analysed using six-stage thematic analysis. <h3>Results</h3> The integrated perspectives show that all three participant groups preferred DOACs over warfarin, a preference driven mainly by the safety profile compared with warfarin. GPs valued pharmacists9 input in anticoagulant care, and pharmacists discussed patient safety in the context of anticoagulant audits, and highlighted the need for continuous patient education and counselling. Medication reviews by pharmacists were seen as a positive contribution to medicines optimisation. <h3>Conclusion</h3> Patients had an overriding trust in their doctors. GPs valued a collaborative approach with other clinicians, and community pharmacists appeared to highlight operational challenges in primary care that may limit the effectiveness of interventions.
Differential immune responses to α-gal epitopes on xenografts and allografts: implications for accommodation in xenotransplantation
Authors: Masahiro Tanemura, Dengping Yin, Anita S. Chong, Uri Galili
Journal: Journal of Clinical Investigation (2000)

Xenograft recipients produce large amounts of high-affinity anti-Gal IgG in response to Galα1-3Galβ1- 4GlcNAc-R (α-gal) epitopes on the graft. In contrast, ABO-mismatched allograft recipients undergo “accommodation,” a state of very weak immune response to ABO antigens. These differences in anti-carbohydrate immune response were studied in α1,3galactosyltransferase knock-out mice. Pig kidney membranes administered to these mice elicited extensive production of anti-Gal IgG, whereas allogeneic kidney membranes expressing α-gal epitopes elicited only a weak anti-Gal IgM response. Anti-Gal IgG response to xenograft membranes depended on helper T cell activation and was inhibited by anti-CD40L antibody. These T cells were activated by xenopeptides and not by α-gal epitopes. Moreover, allogeneic cell membranes manipulated to express xenoproteins also induced anti-Gal IgG response. Xenoglycoproteins with α-gal epitopes are processed by anti-Gal B cells. Xenopeptides presented by these cells activate a large repertoire of helper T cells required for the differentiation of anti-Gal B cells into cells secreting anti-Gal IgG. Alloglycoproteins with α- gal epitopes have very few immunogenic peptides and fail to activate helper T cells. Similarly, ineffective helper T-cell activation prevents a strong immune response to blood group antigens in ABO-mismatched allograft recipients, thus enabling the development of accommodation.
Physical inactivity: common pathway to peripheral muscle weakness in chronic respiratory diseases?
Authors: I. Vogiatzis, S. Zakynthinos
Journal: European Respiratory Journal (2009)

Lower limb muscle atrophy and weakness are common in patients with chronic obstructive pulmonary disease (COPD) and make an important contribution to limiting their exercise tolerance 1. Muscle disuse, hypoxaemia, malnutrition, oxidative stress and systemic inflammation have all been portrayed as possible causes of muscle dysfunction in COPD 2. As far as systemic inflammation is concerned, the available literature supports cytokine-mediated effects on peripheral muscle atrophy, dysfunction and regeneration 3.

The study by Swallow et al. 4 in the current issue of the European Respiratory Journal is the first to show that idiopathic scoliosis (a noninflammatory disease) and COPD (currently thought of as a systemic inflammatory disease affecting many tissues and organs in addition to the lungs) share skeletal muscle weakness and wasting as common phenomena. Muscle strength and exercise tolerance were shown to be compromised to a comparable degree in patients with scoliosis and COPD. Interestingly, quadriceps muscle molecular analyses were indicative of peripheral muscle dysfunction manifested in both disease entities by a reduced proportion of Type I myosin heavy-chain isoform (corresponding to Type I oxidative muscle fibres) and by upregulation of local muscle oxidative stress markers. Therefore, the study by Swallow et al. 4 presents an interesting paradigm that argues against inflammation as the principal aetiology of peripheral muscle wasting in chronic respiratory diseases and suggests another common aetiological mechanism.

This mechanism was not directly elucidated by Swallow et …
Portal-vein obstruction in children leads to growth retardation
Authors: Shiv K. Sarin, Anupam Bansal, Shailja Sasan, Aruna Nigam
Journal: Hepatology (1992)

The portal vein is the main source of blood and hepatotrophic factors to the liver. Partial portal-vein ligation in rats results in reduced growth compared with that in control rats. To investigate whether extrahepatic portal vein obstruction occurring in early childhood influences growth in humans, anthropometric and nutritional assessments were prospectively carried out in 61 patients with extrahepatic portal vein obstruction. Comparisons were made with 183 matched healthy controls using National Center of Health Statistics reference. Fifty-one percent of children with extrahepatic portal vein obstruction had stunted growth (height for age &lt;90% of normal), compared with 16% of controls (p &lt; 0.01). Growth retardation was severe in patients with longer (&gt;5 yr) than with shorter (&lt;2.5 yr) duration of clinical portal hypertension (height for age, 88.0 ± 3.2 vs. 95.1 ± 3.0; p &lt; 0.01). Little difference was seen in the energy intake (1,302 ± 463 kcal/day vs. 1,335 ± 449 kcal/day; p = not significant) and weight for height index (83.6 ± 9.3 vs. 88.0 ± 7.9; p = not significant) between extrahepatic portal vein obstruction patients and controls. This suggested that despite comparable nutrition, marked growth retardation occurred in extrahepatic portal vein obstruction patients. Incremental growth velocity was studied in 31 patients; in 24 (73%) the baseline Z score (-2.1 ± 0.2) had decreased further (-2.4 ± 0.2) at the end of follow-up (15.5 ± 1.6 mo). Although the incremental height velocity was only 56% of the expected height, incremental weight gain was 98% of the expected weight for the attained height. This indicates linear growth failure despite optimal nutrition. In conclusion, our results demonstrate that most children with extrahepatic portal vein obstruction have marked growth retardation and diminished growth velocity. The roles of hemodynamic and hormonal factors in modulation of growth in young extrahepatic portal vein obstruction patients must be studied. (Hepatology 1992;15:229-233).
Study of plasma redox biomarkers for accurate stress evaluation in athletes
Authors: M Paes de Barros, C O Soares, B Pereira, E J H Bechara, L R Silveira, R Curi, T P Souza-Junior
Journal: British Journal of Sports Medicine (2011)

Background A plethora of data revealed that reactive oxygen species (ROS) are normally produced during/after endurance or resistance exercise. Drastic drops in performance, precocious fatigue and injury risk are putative outcomes of the ROS-mediated biochemical changes. On the other hand, adequate ROS production is essential to provide the desired physiological adaptations of training and to avoid related immune depression. Objective This work aims to test plasma biomarkers of oxidative stress for an accurate evaluation of exhaustion in athletes. Design Subjects were prospectively randomised evaluated. Setting Male cyclists of Brazilian college league (university games) were selected. Participants Subjects (n=20) had no history of smoking, alcohol abuse, or systemic disease. Interventions A Wingate Test was carried out using a Cybex cycle ergometer with increasing loads up to 10% BW (preheat procedure for 5 min). Athletes were strongly encouraged during the test for maximum effort achievement. Main outcome measurements Blood samples (5 ml) were collected before and after the Wingate test, using EDTA-containing Vaccuntainer kits. Total iron, haemoglobin, uric acid, Ferric-reducing activity (FRAP), and malondialdehyde (biomarker of lipid oxidation) were measured in plasma. Results Plasma iron and FRAP levels varied consistently when total amounts released from time zero to 60 min after the Wingate test were evaluated (R=0.939). Remarkably, uric acid was identified as one of the major contributors for FRAP capacity, thus, restricting iron ions participation as catalysts for ROS overproduction during exercise. Lower indexes of lipid oxidation were reported under these circumstances. Conclusion The pool of plasma biomarkers – total iron, FRAP, uric acid and malondialdehyde – are good candidates for an efficient evaluation of oxidative stress related to exhaustion. Further investigations are necessary to precise how responsive those parameters are at different exercise intensities. Financial support: FAPESP, CAPES &amp; CNPq (Brazil); BioReal AB/Fuji Health Sciences (Sweden/Japan).
Perioperative change in albumin messenger RNA levels in patients with hepatocellular carcinoma
Authors: Tomonobu Gion, Akinobu Taketomi, Mitsuo Shimada, Ken Shirabe, Hirofumi Hasegawa, Kenji Takenaka, Keizo Sugimachi
Journal: Hepatology (1998)

A quantitative assay of albumin messenger RNA (mRNA) in blood samples was designed using the competitive reverse–transcription polymerase chain reaction, and the significance of measuring albumin mRNA levels in the blood of patients with hepatocellular carcinoma (HCC) in hepatic resection was evaluated. Albumin mRNA levels were measured in the following: (1) peripheral blood in 11 patients with HCC and 20 control subjects without liver disease, (2) blood in the portal and hepatic veins in five patients with HCC immediately after laparotomy, and (3) a perioperative series of peripheral blood in eight patients with HCC. Two patients with HCC whose albumin mRNA level in peripheral blood was markedly high were both at stage IVa. On the other hand, 20 control subjects showed negative or &lt;5 × 10 3 transcripts/μg RNA of albumin mRNA expression. Immediately after laparotomy, the albumin mRNA levels in the tumor–draining hepatic vein were greater than in the portal and non-tumor–draining hepatic veins in four of five patients with HCC. Albumin mRNA levels in peripheral blood showed a marked increase after mobilization and/or resection of the liver and, thereafter, gradually decreased at postoperative day 7 in all eight patients with HCC. A new method to measure the albumin mRNA levels in blood samples was developed, and high albumin mRNA levels in the peripheral blood of patients with advanced–stage HCC suggest the presence of HCC cells in the circulation. Increased levels in the tumor–draining hepatic vein could indicate the spontaneous release of tumor cells or nontumorous hepatocytes or an increased albumin transcription in activated blood mononuclear cells. An increase in the levels in peripheral blood during an operation is intermittent. Therefore, an increased albumin mRNA level in the tumor–draining vein suggests, but does not prove, that the increased albumin mRNA level reflects tumor cells entering the systemic circulation. This alone does not prove that the prognosis is worsened.
Molecular cues guiding inflammatory responses
Authors: O. Barreiro, P. Martin, R. Gonzalez-Amaro, F. Sanchez-Madrid
Journal: Cardiovascular Research (2010)

Alarm signals generated at inflammatory foci reach the vascular lumen to attract immune cells towards the affected tissue. Different leucocyte subsets decipher and integrate these complex signals in order to make adequate decisions for their migration towards the inflamed tissue. Soluble cues (cytokines and chemokines) and membrane receptors in both endothelium and leucocytes orchestrate the coordinated recruitment of specific inflammatory cell subsets. All these molecules are spatio-temporally organized in specialized structures at the luminal side of endothelium and the leucocyte membrane or are generated as chemical gradients in the damaged tissue. Thus, the repertoire of chemokines and their receptors as well as adhesion molecules expressed by each leucocyte subset determine their recruitment for participation in specific inflammatory pathologies. Whenever inflammatory signals are altered or misprocessed, inflammation can become chronic, causing extensive tissue damage. To combat chronic inflammation and autoimmune diseases, novel therapeutic strategies attempt to silence the predominant signals in each inflammatory scenario. In this review, we provide a general overview of all these aspects related to the molecular regulation of leucocyte guidance in inflammatory responses.
Lower Somatostatin Expression Is an Early Event in Diabetic Retinopathy and Is Associated With Retinal Neurodegeneration
Authors: Esther Carrasco, Cristina Hernández, Adela Miralles, Pere Huguet, Jaume Farrés, Rafael Simó
Journal: Diabetes Care (2007)

To test the hypothesis that a reduction of somatostatin (SST) in the retina exists in patients without clinically detectable diabetic retinopathy and that it is associated with retinal neurodegeneration.Human diabetic postmortem eyes (n = 10) without clinically detectable retinopathy were compared with eyes (n = 10) from nondiabetic donors. SST mRNA (RT-PCR) and SST-28 immunoreactivity (confocal laser) were measured separately in neuroretina and retinal pigment epithelium (RPE). In addition, SST-28 (radioimmunoassay) was measured in the vitreous fluid. Glial fibrillar acidic protein (GFAP) was assessed by immunofluorescence and Western blot. Apoptotic cells were quantified using transferase-mediated dUTP nick-end labeling.A higher expression of SST was detected in RPE than neuroretina in both groups. SST mRNA levels and SST-28 immunoreactivity were significantly lower in both RPE and the neuroretina from diabetic donors compared with nondiabetic donors. These results were in agreement with those obtained by measuring SST-28 in the vitreous fluid of the same donors. Increased GFAP and a higher degree of apoptosis were observed in diabetic retinas compared with nondiabetic retinas. These changes were most evident in patients with the higher deficit of SST.Underproduction of SST is an early event in the eyes of diabetic patients and is associated with glial activation and neural death. In addition, our results suggest that RPE is an important source of SST in the human eye. The possible role of the lower production of SST in the pathogenesis of diabetic retinopathy requires further investigation.
Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study
Authors: Pasi A Jänne, Alice T Shaw, José Rodrigues Pereira, Gaëlle Jeannin, Johan Vansteenkiste, Carlos Barrios, Fabio Andre Franke, Lynda Grinsted, Victoria Zazulina, Paul Smith, Ian Smith, Lucio Crinò
Journal: The Lancet Oncology (2012)
Folate Deficiency and Cervical Dysplasia
Authors: C. E. Butterworth
Journal: JAMA (1992)

<h3>Objective.</h3> —To test the hypothesis that nutritional deficiency affects the incidence of cervical dysplasia in young women. <h3>Design and Setting.</h3> —Case-control study. Participants were derived from community family-planning clinics and referrals to a colposcopy center. <h3>Participants.</h3> —A total of 726 subjects were screened, yielding 294 cases of dysplasia and 170 controls defined by coexistent cytologic and colposcopic evidence. <h3>Main Outcome Measures.</h3> —Planned prior to data collection. Odds ratios were computed using logistic regression models to evaluate association between cervical dysplasia and sociodemographic, sexual, and reproductive factors; smoking; oral contraceptive use; human papillomavirus (HPV) infection; and 12 nutritional indices determined by blind analysis of nonfasting blood specimens. <h3>Results.</h3> —The number of sexual partners, parity, oral contraceptive use, and HPV-16 infection were significantly associated with cervical dysplasia. Plasma nutrient levels were generally not associated with risk. However, red blood cell folate levels at or below 660 nmol/L interacted with HPV-16 infection. The adjusted odds ratio for HPV-16 was 1.1 among women with folate levels above 660 nmol/L but 5.1 (95% confidence interval, 2.3 to 11) among women with lower levels. Interactions of red blood cell folate levels with cigarette smoking and parity were also present but were not statistically significant. <h3>Conclusion.</h3> —Low red blood cell folate levels enhance the effect of other risk factors for cervical dysplasia and, in particular, that of HPV-16 infection. (<i>JAMA</i>. 1992;267:528-533)