tbuckley/cabot-search huggingface dataset:
Pleural thickening and gas transfer in asbestosis.
Authors: W O Cookson, A W Musk, J J Glancy
Journal: Thorax (1983)

Anomalies in the ratio of transfer factor to effective alveolar volume as an indicator of pulmonary gas exchange in cases of asbestosis may be related to diffuse pleural thickening. To examine the effect of pleural disease on gas transfer the plain chest radiographs of patients with asbestosis were assessed by two observers for profusion of parenchymal opacities and extent of pleural disease and the results were related to lung function. In 30 cases of category 1 profusion of parenchymal abnormality (according to the ILO international classification of radiographs for pneumoconiosis) transfer factor was independent of the degree of pleural thickening. The ratio of transfer factor to effective alveolar volume correlated directly with the degree of pleural thickening as alveolar volume fell with increasing severity of pleural disease. The results indicate that correcting transfer factor for alveolar volume does not provide an accurate reflection of severity of diffuse parenchymal fibrosis in patients with asbestosis and even minor pleural disease.
<i>ACVR1</i> <sup> <i>R206H</i> </sup> receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A
Authors: Sarah J. Hatsell, Vincent Idone, Dana M. Alessi Wolken, Lily Huang, Hyon J. Kim, Lili Wang, Xialing Wen, Kalyan C. Nannuru, Johanna Jimenez, Liqin Xie, Nanditha Das, Genevieve Makhoul, Rostislav Chernomorsky, David D’Ambrosio, Richard A. Corpina, Christopher J. Schoenherr, Kieran Feeley, Paul B. Yu, George D. Yancopoulos, Andrew J. Murphy, Aris N. Economides
Journal: Science Translational Medicine (2015)

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by episodically exuberant heterotopic ossification (HO), whereby skeletal muscle is abnormally converted into misplaced, but histologically normal bone. This HO leads to progressive immobility with catastrophic consequences, including death by asphyxiation. FOP results from mutations in the intracellular domain of the type I BMP (bone morphogenetic protein) receptor ACVR1; the most common mutation alters arginine 206 to histidine (ACVR1(R206H)) and has been thought to drive inappropriate bone formation as a result of receptor hyperactivity. We unexpectedly found that this mutation rendered ACVR1 responsive to the activin family of ligands, which generally antagonize BMP signaling through ACVR1 but cannot normally induce bone formation. To test the implications of this finding in vivo, we engineered mice to carry the Acvr1(R206H) mutation. Because mice that constitutively express Acvr1[R206H] die perinatally, we generated a genetically humanized conditional-on knock-in model for this mutation. When Acvr1[R206H] expression was induced, mice developed HO resembling that of FOP; HO could also be triggered by activin A administration in this mouse model of FOP but not in wild-type controls. Finally, HO was blocked by broad-acting BMP blockers, as well as by a fully human antibody specific to activin A. Our results suggest that ACVR1(R206H) causes FOP by gaining responsiveness to the normally antagonistic ligand activin A, demonstrating that this ligand is necessary and sufficient for driving HO in a genetically accurate model of FOP; hence, our human antibody to activin A represents a potential therapeutic approach for FOP.
Coca-Cola launches antiobesity advertisements
Authors: J. H. Tanne
Journal: BMJ (2013)

The Coca-Cola Company, the world’s largest beverage company, has begun broadcasting television advertisements showing what the company has done to contribute to the fight against obesity.1

Coca-Cola said that it had launched its global campaign “to help society beat one of the most serious, complex issues of this generation—obesity.”

The Coca-Cola commercial says, “The simple common-sense fact is that all calories count, no matter where they come from . . . If you eat or drink more calories than you burn off you will gain weight.”

Coca-Cola’s two …
<i>In vivo</i> Margin Assessment during Partial Mastectomy Breast Surgery Using Raman Spectroscopy
Authors: Abigail S. Haka, Zoya Volynskaya, Joseph A. Gardecki, Jon Nazemi, Joanne Lyons, David Hicks, Maryann Fitzmaurice, Ramachandra R. Dasari, Joseph P. Crowe, Michael S. Feld
Journal: Cancer Research (2006)

Abstract We present the first demonstration of in vivo collection of Raman spectra of breast tissue. Raman spectroscopy, which analyzes molecular vibrations, is a promising new technique for the diagnosis of breast cancer. We have collected 31 Raman spectra from nine patients undergoing partial mastectomy procedures to show the feasibility of in vivo Raman spectroscopy for intraoperative margin assessment. The data was fit with an established model, resulting in spectral-based tissue characterization in only 1 second. Application of our previously developed diagnostic algorithm resulted in perfect sensitivity and specificity for distinguishing cancerous from normal and benign tissues in our small data set. Significantly, we have detected a grossly invisible cancer that, upon pathologic review, required the patient to undergo a second surgical procedure. Had Raman spectroscopy been used in a real-time fashion to guide tissue excision during the procedure, the additional reexcision surgery might have been avoided. These preliminary findings suggest that Raman spectroscopy has the potential to lessen the need for reexcision surgeries resulting from positive margins and thereby reduce the recurrence rate of breast cancer following partial mastectomy surgeries. (Cancer Res 2006; 66(6): 3317-22)
Improvements in clinical response between 12 and 24 weeks in patients with rheumatoid arthritis on etanercept therapy with or without methotrexate
Authors: A Kavanaugh, L Klareskog, D van der Heijde, J Li, B Freundlich, M Hooper
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Background:</h3> Whereas many patients respond quickly to treatment with tumour necrosis factor (TNF) inhibitors, some patients may experience significant but delayed responses. <h3>Objective:</h3> To evaluate the clinical response between 12 and 24 weeks in subjects with rheumatoid arthritis from the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes. <h3>Methods:</h3> Clinical response was assessed at 24 weeks in 12-week non-responders, according to American College of Rheumatology (ACR) response criteria. The proportion of subjects who successfully maintained response to 52 weeks was analysed, as were radiographic outcomes. <h3>Results:</h3> Data from 682 subjects were included in the analysis. Non and partial responders in all three groups (etanercept, methotrexate and etanercept plus methotrexate) at week 12 showed an improvement in responses at week 24. Over 80% of the week 24 ACR20/50/70 responders in the etanercept plus methotrexate arm sustained their response to 52 weeks. In the etanercept arms, a delayed clinical response was not associated with increased radiographic progression at week 52. <h3>Conclusion:</h3> A significant proportion of non and partial responders to etanercept with or without methotrexate therapy at week 12 achieved a good clinical response or improved their overall clinical response at week 24. Discontinuing TNF inhibitor therapy at 12 weeks may be premature in some rheumatoid arthritis patients.
Cell Therapy for Heart Failure
Authors: Santosh K. Sanganalmath, Roberto Bolli
Journal: Circulation Research (2013)

Despite significant therapeutic advances, the prognosis of patients with heart failure (HF) remains poor, and current therapeutic approaches are palliative in the sense that they do not address the underlying problem of the loss of cardiac tissue. Stem cell–based therapies have the potential to fundamentally transform the treatment of HF by achieving what would have been unthinkable only a few years ago—myocardial regeneration. For the first time since cardiac transplantation, a therapy is being developed to eliminate the underlying cause of HF, not just to achieve damage control. Since the initial report of cell therapy (skeletal myoblasts) in HF in 1998, research has proceeded at lightning speed, and numerous preclinical and clinical studies have been performed that support the ability of various stem cell populations to improve cardiac function and reduce infarct size in both ischemic and nonischemic cardiomyopathy. Nevertheless, we are still at the dawn of this therapeutic revolution. Many important issues (eg, mechanism(s) of action of stem cells, long-term engraftment, optimal cell type(s), and dose, route, and frequency of cell administration) remain to be resolved, and no cell therapy has been conclusively shown to be effective. The purpose of this article is to critically review the large body of work performed with respect to the use of stem/progenitor cells in HF, both at the experimental and clinical levels, and to discuss current controversies, unresolved issues, challenges, and future directions. The review focuses specifically on chronic HF; other settings (eg, acute myocardial infarction, refractory angina) are not discussed.
Crusted (Norwegian) scabies in a patient with dystrophic epidermolysis bullosa
Authors: V.B. Van Der Wal, P.C. Van Voorst Vader, J.M. Mandema, M.F. Jonkman
Journal: British Journal of Dermatology (1999)

Journal Article Crusted (Norwegian) scabies in a patient with dystrophic epidermolysis bullosa Get access V.B. Van Der Wal, V.B. Van Der Wal Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar P.C. Van Voorst Vader, P.C. Van Voorst Vader Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar J.M. Mandema, J.M. Mandema Paediatrics, University Hospital, Hanzeplein 1, PO Box 30·001,NL‐9700 RB, Groningen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar M.F. Jonkman M.F. Jonkman Departments of Dermatology and Dr Marcel F.Jonkman.E‐mail: m.f.jonkman@ derm.azg.nl Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 141, Issue 5, 1 November 1999, Pages 918–921, https://doi.org/10.1046/j.1365-2133.1999.03170.x Published: 01 November 1999
Growth Plate Cartilage Formation and Resorption Are Differentially Depressed in Growth Retarded Uremic Rats
Authors: ANGELES COBO, JOSÉ LÓPEZ, EDUARDO CARBAJO, FERNANDO SANTOS, JESÚS ALVAREZ, MARTA FERNÁNDEZ, ANA WERUAGA
Journal: Journal of the American Society of Nephrology (1999)

Abstract. To characterize the modifications of growth plate in individuals with growth impairment secondary to chronic renal failure, young rats were made uremic by subtotal nephrectomy (NX) and, after 14 d, their tibial growth plates were studied and compared with those of sham-operated rats fed ad libitum (SAL) or pair-fed with NX (SPF). NX rats were growth retarded and severely uremic. Growth plate height (mean ± SD) was much greater ( P &lt; 0.05) in NX (868.4 ± 85.4 μm) than SAL (570.1 ± 93.5 μm) and SPF (551.9 ± 99.7 μm) rats as a result of a higher ( P &lt; 0.05) hypertrophic zone (661.0 ± 89.7 versus 362.8 ± 71.6 and 353.0 ± 93.9 μm, respectively). The increased size of the growth plate was associated with a greater number of chondrocytes and modifications in their structure, particularly in the hypertrophic zone adjacent to bone. In this zone, chondrocytes of NX animals were significantly ( P &lt; 0.05) smaller (12080.4 ± 1158.3 μm 3 ) and shorter (34.1 ± 2.5 μm) than those of SAL (16302.8 ± 1483.4 μm 3 and 37.8 ± 2.0 μm) and SPF (14465.8 ± 1521.0 μm 3 and 36.3 ± 1.8 μm). The interface between the growth plate cartilage and the metaphyseal bone appeared markedly irregular in NX rats. Kinetics of chondrocytes was also modified ( P &lt; 0.05) in the NX rats, which had lower cell turnover per column per day (5.4 ± 0.9), longer duration of hypertrophic phase (89.0 ± 15.2 h), and reduced cellular advance velocity (7.4 ± 2.2 μm/h) compared with SAL (8.0 ± 1.6, 32.1 ± 6.7 h, and 11.3 ± 2.7 μm/h) and SPF (7.2 ± 1.1, 34.8 ± 5.1 h, and 10.1 ± 2.5 μ/h). Cell proliferation was no different among the three groups. Because the growth plates of SPF and SAL rats were substantially not different, modifications observed in the NX rats cannot be attributed to the nutritional deficit associated with renal failure. These findings indicate that chronic renal failure depresses both the activity of the growth plate cartilage by altering chondrocyte hypertrophy and the replacement of cartilage by bone at the metaphyseal end. The two processes are differentially depressed since cartilage resorption is more severely lowered than cartilage enlargement and this leads to an accumulation of cartilage at the hypertrophic zone.
The diabetogenic mouse MHC class II molecule I-Ag7 is endowed with a switch that modulates TCR affinity
Authors: Kenji Yoshida, Adam L. Corper, Rana Herro, Bana Jabri, Ian A. Wilson, Luc Teyton
Journal: Journal of Clinical Investigation (2010)

Genetic susceptibility to autoimmunity is frequently associated with specific MHC alleles. Diabetogenic MHC class II molecules, such as human HLA-DQ8 and mouse I-Ag7, typically have a small, uncharged amino acid residue at position 57 of their beta chain (beta57); this results in the absence of a salt bridge between beta57 and Argalpha76, which is adjacent to the P9 pocket of the peptide-binding groove. However, the influence of Argalpha76 on the selection of the TCR repertoire remains unknown, particularly when the MHC molecule binds a peptide with a neutral amino acid residue at position P9. Here, we have shown that diabetogenic MHC class II molecules bound to a peptide with a neutral P9 residue primarily selected and expanded cells expressing TCRs bearing a negatively charged residue in the first segment of their complementarity determining region 3beta. The crystal structure of one such TCR in complex with I-Ag7 bound to a peptide containing a neutral P9 residue revealed that a network of favorable long-range (greater than 4 A) electrostatic interactions existed among Argalpha76, the neutral P9 residue, and TCR, which supported the substantially increased TCR/peptide-MHC affinity. This network could be modulated or switched to a lower affinity interaction by the introduction of a negative charge at position P9 of the peptide. Our results support the existence of a switch at residue beta57 of the I-Ag7 and HLA-DQ8 class II molecules and potentially link normal thymic TCR selection with abnormal peripheral behavior.
The Psychiatric Consultant as a Change Agent in the Community
Authors: MARTIN C. NALDER, CARLO A. WEBER, ARETA CROWELL
Journal: American Journal of Psychiatry (1974)

As the field of social and community psychiatry continues to expand, psychiatrists are obliged to bring their knowledge and experience to bear on matters of directing and implementing change. The authors describe the role of the psychiatrist as an active agent of change in coordinating a placement program for disturbed adolescents in Los Angeles County, Calif.
Hemoglobin Is Expressed by Mesangial Cells and Reduces Oxidant Stress
Authors: Hiroshi Nishi, Reiko Inagi, Hideki Kato, Masayuki Tanemoto, Ichiro Kojima, Daisuke Son, Toshiro Fujita, Masaomi Nangaku
Journal: Journal of the American Society of Nephrology (2008)

Hemoglobin (Hb) serves as the main oxygen transporter in erythrocytes, but it is also expressed in nonhematopoietic organs, where it serves an unknown function. In this study, microarray and proteomic analyses demonstrated Hb expression in the kidney. Rat kidneys were perfused extensively with saline, and glomeruli were isolated by several techniques (sieving, manual dissection, and laser capture-microdissection). Reverse transcriptase–PCR revealed glomerular α- and β-globin expression, and immunoblotting demonstrated expression of the protein. In situ hybridization studies showed expression of the globin subunits in the mesangium, and immunostaining confirmed this localization of Hb. Furthermore, globin mRNA expression was detected in primary cultures of rat mesangial cells but not in cultured glomerular endothelial or epithelial cells. For investigation of Hb function in mesangial cells, the SV40-MES13 murine mesangial cell line was transfected with a vector expressing α- and β-globins; this overexpression reduced production of hydrogen peroxide–induced intracellular radical oxygen species and enhanced cell viability against oxidative stress. In summary, Hb is expressed by rat mesangial cells, and its potential functions may include antioxidative defense.
Twenty-four–Hour Intensivist Presence
Authors: Allan Garland, Dan Roberts, Lesley Graff
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Around-the-clock intensivist presence in intensive care units (ICUs) has been promoted as necessary to optimize outcomes. Little data have addressed how it affects the multiple stakeholders in such care.To assess effects of around-the-clock intensivist presence on intensivists, patients, families, housestaff, and nurses.This 32-week, crossover pilot trial of two intensivist staffing models, performed in two Canadian ICUs, alternated 8-week blocks of two staffing models: the standard model, where one intensivist worked for 7 days, taking night call from home; and the shift work model, where one intensivist worked 7 day shifts, while other intensivists remained in the ICU at night.Surveys scaled from 0-100 points assessed outcomes for 24 intensivists (primary outcome: burnout); 119 families (satisfaction); 74 nurses (satisfaction with collaboration and communications, role conflict); and 34 housestaff (autonomy, supervision, and learning opportunities). Outcomes for 501 patients included mortality, length of stay, and resource use. Intensivists doing shift work experienced less burnout (-6.9 points; P = 0.04). Adjusted hospital mortality (odds ratio, 1.22; P = 0.44), ICU length of stay (-6 h; P = 0.46), and family satisfaction (0.9 points; P = 0.79) did not differ between staffing models. Under shift work staffing, nurses reported more role conflict (9 points; P < 0.001), whereas nighttime housestaff reported less autonomy, more supervision, but no difference in learning opportunities.Shiftwork staffing was better for intensivists and most were receptive once they had experienced it. Although there were no evident negative outcomes for patients or families, further evaluation is needed to clarify how around-the-clock intensivist staffing influences the various stakeholders in ICU care, given power considerations in this study. Clinical trial registered with www.clinicaltrials.gov (NCT 01146691).
The Genomic Rate of Molecular Adaptation of the Human Influenza A Virus
Authors: Samir Bhatt, Edward C. Holmes, Oliver G. Pybus
Journal: Molecular Biology and Evolution (2011)

Quantifying adaptive evolution at the genomic scale is an essential yet challenging aspect of evolutionary biology.Here, we develop a method that extends and generalizes previous approaches to estimate the rate of genomic adaptation in rapidly evolving populations and apply it to a large data set of complete human influenza A virus genome sequences.In accord with previous studies, we observe particularly high rates of adaptive evolution in domain 1 of the viral hemagglutinin (HA1).However, our novel approach also reveals previously unseen adaptation in other viral genes.Notably, we find that the rate of adaptation (per codon per year) is higher in surface residues of the viral neuraminidase than in HA1, indicating strong antibody-mediated selection on the former.We also observed high rates of adaptive evolution in several nonstructural proteins, which may relate to viral evasion of T-cell and innate immune responses.Furthermore, our analysis provides strong quantitative support for the hypothesis that human H1N1 influenza experiences weaker antigenic selection than H3N2.As well as shedding new light on the dynamics and determinants of positive Darwinian selection in influenza viruses, the approach introduced here is applicable to other pathogens for which densely sampled genome sequences are available, and hence is ideally suited to the interpretation of next-generation genome sequencing data.
Impact of image grading in athletes with low-risk fracture - is there a benefit?
Authors: O Dobrindt, B Hoffmeyer, J Ruf, I G Steffen, M Seidensticker, F Fischbach, C H Lohmann, H Amthauer
Journal: British Journal of Sports Medicine (2011)

Background Stress fractures (SFX) are classified by localisation (low- and high-risk) and severity, which can be determined by imaging modalities (low- and high-grade). Objective The objective was to determine whether a combined analysis of risk-localisation and image-grading in SFX allows a more accurate prediction of return-to-sports-time (RTST). Design Retrospective study. In a blinded read three independent specialists rated imaging-data (MRI and bone scintigraphy) as low- or high-grade SFX. SFX detection, risk-classification and RTST were determined by an interdisciplinary truth-panel providing a reference standard. Two-sided Wilcoxon's rank sum test and Kruskal-Wallis test were used for group comparisons. Setting Patients from an athlete boarding school, an Olympic training centre and from professional teams were included. Patients 50 consecutive athletes (male, n=20; female, n=30; mean age, 23.6 years) with SFX receiving imaging were included (track, n=18; long distance running, n=16; handball, n=11; other, n=5). In all athletes follow-up data was complete until full recovery. Interventions All patients received standardised treatment with adaptation to sport and injury-site with special focus on safe return-to-full activity. Main outcome measurements Estimation of RTST depending on risk-classification and image-based grading. Results In our study 21/50 SFX at a high-risk localisation had a mean RTST of 135 days (d) compared to 119 d for low-risk sites (p=0.18). RTST was significantly longer (p=0.01) in imaging-based high-grade lesions (mean=143 d) than in low-grade SFX (mean=96 d). Analysis of only high-risk SFX showed no difference in RTST (p=0.58) for high- and low-grade SFX (mean, 131 d vs 140 d). In contrast the difference was significant for low-risk SFX (p=0.004; mean, low-grade=61 d vs high-grade=153 d). Conclusion In low-risk SFX the significant difference in RTST between low- and high-grade lesions allow a more accurate estimation of the healing time needed. As a consequence, both risk localisation and image grading of SFX have to be considered for the prediction of RTST.