tbuckley/cabot-search huggingface dataset:
A randomised controlled trial of occupational therapy for people with early rheumatoid arthritis
Authors: A Hammond
Journal: Annals of the Rheumatic Diseases (2003)

Occupational therapy (OT) aims at improving performance of daily living tasks, facilitating successful adjustments in lifestyle, and preventing losses of function.To evaluate the effects of a pragmatic, comprehensive OT programme on self management and health status of people with early rheumatoid arthritis (RA) (<2.5 years).A randomised, controlled "assessor blinded" trial was conducted with assessments made at entry, 6, 12, and 24 months. Main outcomes were AIMS2: physical function (PF), pain visual analogue scale (VAS), and Arthritis Self-Efficacy Scale (ASES).Groups had similar disease duration (9 months OT (n = 162) v 10 months control (n = 164)). The OT group received 7.57 (SD 3.04) hours of therapy. Self management significantly increased in the OT group. Otherwise, there were no significant differences in any outcome measures, or between groups, by ACR functional class: AIMS2: PF (F = 0.04; p = 0.96); pain VAS (F = 0.29; p = 0.74); total ASES score (F = 0.93; p = 0.39).OT improved self management but not health status in early RA. Functional ability remains reasonably good for many in the first five years, so preventive benefits of self management may not yet be apparent and longer follow up is needed. Although many considered the education and therapy useful, insufficient numbers in the OT group used self management sufficiently to make a difference. Behavioural approaches can improve adherence and, potentially, the long term benefits. Future research should evaluate OT as a complex intervention and develop programmes from a theoretical and evidence base.
Classical Transient Receptor Potential Channel 1 in Hypoxia-induced Pulmonary Hypertension
Authors: Monika Malczyk, Christine Veith, Beate Fuchs, Katharina Hofmann, Ursula Storch, Ralph T. Schermuly, Martin Witzenrath, Katrin Ahlbrecht, Claudia Fecher-Trost, Veit Flockerzi, Hossein A. Ghofrani, Friedrich Grimminger, Werner Seeger, Thomas Gudermann, Alexander Dietrich, Norbert Weissmann
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Pulmonary hypertension (PH) is a life-threatening disease, characterized by pulmonary vascular remodeling. Abnormal smooth muscle cell proliferation is a primary hallmark of chronic hypoxia-induced PH. Essential for cell growth are alterations in the intracellular Ca(2+) homeostasis. Classical transient receptor potential (TRPC) proteins have been suggested to contribute to PH development, as TRPC1 and TRPC6 are predominantly expressed in precapillary pulmonary arterial smooth muscle cells (PASMC). Studies in a TRPC6-deficient mouse model revealed an essential function of TRPC6 in acute but not in chronic hypoxia.We aimed to identify the importance of TRPC1 in the pathogenesis of chronic hypoxia-induced PH in mice.TRPC1 expression analysis was performed using real-time polymerase chain reaction. TRPC1 function was assessed by in vivo experiments in TRPC1(-/-) animals as well as in isolated precapillary murine PASMC after TRPC1 knockdown by TRPC1-specific small interfering RNAs.Only TRPC1 mRNA was up-regulated under hypoxia in isolated murine PASMC (1% O2 for 72 h). Hypoxia-induced proliferation of murine PASMC was attenuated in cells treated with small interfering RNA against TRPC1 and in cells isolated from TRPC1(-/-) animals compared with untreated and wild-type cells. TRPC1(-/-) mice did not develop PH in response to chronic hypoxia (FI(O2) 0.10 for 21 d) and had less vascular muscularization but a similar degree of right ventricular hypertrophy compared with wild-type mice.Our results indicate an important role of TRPC1 in pulmonary vascular remodeling underlying the development of hypoxia-induced PH.
Central Catecholamine Neuron Systems: Anatomy and Physiology of the Norepinephrine and Epinephrine Systems
Authors: R. Y. Moore, F. E. Bloom
Journal: Annual Review of Neuroscience (1979)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
The over-determination of selflessness in villains and heroes
Authors: Benjamin Beit-Hallahmi
Journal: Behavioral and Brain Sciences (2014)

Abstract The suicidality hypothesis could be applied to other situations, such as cases in regular military organizations or in “terrorist” groups, where individuals put themselves in circumstances that are directly suicidal. Self-selection in these cases may be motivated by depression or short-term hopelessness. Both violent and charitable acts are over-determined, and a multiplicity of motives should be considered in explaining them.
Physical Activity and Life Expectancy With and Without Diabetes
Authors: Jacqueline T. Jonker, Chris De Laet, Oscar H. Franco, Anna Peeters, Johan Mackenbach, Wilma J. Nusselder
Journal: Diabetes Care (2006)

OBJECTIVE—Physical activity is associated with a reduced risk of developing diabetes and with reduced mortality among diabetic patients. However, the effects of physical activity on the number of years lived with and without diabetes are unclear. Our aim is to calculate the differences in life expectancy with and without type 2 diabetes associated with different levels of physical activity. RESEARCH DESIGN AND METHODS—Using data from the Framingham Heart Study, we constructed multistate life tables starting at age 50 years for men and women. Transition rates by level of physical activity were derived for three transitions: nondiabetic to death, nondiabetic to diabetes, and diabetes to death. We used hazard ratios associated with different physical activity levels after adjustment for age, sex, and potential confounders. RESULTS—For men and women with moderate physical activity, life expectancy without diabetes at age 50 years was 2.3 (95% CI 1.2–3.4) years longer than for subjects in the low physical activity group. For men and women with high physical activity, these differences were 4.2 (2.9–5.5) and 4.0 (2.8–5.1) years, respectively. Life expectancy with diabetes was 0.5 (−1.0 to 0.0) and 0.6 (−1.1 to −0.1) years less for moderately active men and women compared with their sedentary counterparts. For high activity, these differences were 0.1 (−0.7 to 0.5) and 0.2 (−0.8 to 0.3) years, respectively. CONCLUSIONS—Moderately and highly active people have a longer total life expectancy and live more years free of diabetes than their sedentary counterparts but do not spend more years with diabetes.
Modulation of human dendritic-cell function following transduction with viral vectors: implications for gene therapy
Authors: Peng H. Tan, Sven C. Beutelspacher, Shao-An Xue, Yao-He Wang, Peter Mitchell, James C. McAlister, D. Frank P. Larkin, Myra O. McClure, Hans J. Stauss, Mary A. Ritter, Giovanna Lombardi, Andrew J. T. George
Journal: Blood (2005)
Macrophage plasminogen activator: induction by products of activated lymphoid cells.
Authors: J D Vassalli, E Reich
Journal: The Journal of Experimental Medicine (1977)

Macrophages obtained from the peritoneal cavity of untreated mice do not ordinarily synthesize plasminogen activator. However, induction of enzyme synthesis and secretion occurs when such macrophages are cultured in presence of conditioned medium from Con A-stimulated spleen cells. Plasminogen activator production by macrophages from endotoxin or thioglycollate medium-injected mice, which spontaneously secrete substantial amounts of the enzyme, is also markedly increased in presence of such conditioned medium. These results suggest that macrophage plasminogen activatory production may be regulated in part by lymphocytes. They provide further evidence to link macrophage plasminogen activator with cell migration and inflammation, and also support the view that in macrophages, as in certain other cell types, synthesis and secretion of this enzyme are under hormonal control.
Physical activity interventions: an essential component in recovery from mental illness
Authors: Simon Rosenbaum, Anne Tiedemann, Philip B Ward, Jackie Curtis, Catherine Sherrington
Journal: British Journal of Sports Medicine (2014)

Mental illness is a common and costly public health problem. One-quarter of the population experience one or more of the broad range of mental health disorders throughout their lifetime. Mental illness costs an estimated £22.5 billion per year in the UK alone.1

People with serious mental illness face a ‘scandal of premature mortality’.2 Life expectancy is up to 15 years less for people with serious mental illness than for the rest of the population. This important and widening mortality gap is more due to cardiovascular disease than suicide, which is often incorrectly assumed to be the only driver of increased mortality in the mentally ill. People with mental illness have high rates of obesity and lifestyle-related diseases3 and smoking rates three times that of the general population.

The common conceptualisation of physical activity interventions as diversional, social or subtherapeutic strategies for people living with mental illness must be therefore reconsidered. Universal inclusion of …
Trastuzumab, Paclitaxel, Carboplatin, and Gemcitabine in Advanced Human Epidermal Growth Factor Receptor-2/<i>neu</i>–Positive Urothelial Carcinoma: Results of a Multicenter Phase II National Cancer Institute Trial
Authors: Maha H.A. Hussain, Gary R. MacVicar, Daniel P. Petrylak, Rodney L. Dunn, Ulka Vaishampayan, Primo N. Lara, Gurkamal S. Chatta, David M. Nanus, L. Michael Glode, Donald L. Trump, Helen Chen, David C. Smith
Journal: Journal of Clinical Oncology (2007)

Purpose We investigated the safety and efficacy (response rates, time to disease progression, survival) of trastuzumab, carboplatin, gemcitabine, and paclitaxel in advanced urothelial carcinoma patients and prospectively evaluated human epidermal growth factor receptor-2 (Her-2/neu) overexpression rates. Patients and Methods Advanced urothelial carcinoma patients were screened for Her-2/neu overexpression. Eligibility for therapy required human epidermal growth factor receptor-2 (Her-2/neu) overexpression by immunohistochemistry (IHC), gene amplification and/or elevated serum Her-2/neu, no prior chemotherapy for metastasis, and adequate organ function including a normal cardiac function. Treatment consisted of trastuzumab (T) 4 mg/kg loading dose followed by 2 mg/kg on days 1, 8, and 15; paclitaxel (P) 200 mg/m 2 on day 1; carboplatin (C; area under the curve, 5) on day 1; and gemcitabine (G) 800 mg/m 2 on days 1 and 8. The primary end point was cardiac toxicity. Results Fifty-seven (52.3%) of 109 registered patients were Her-2/neu positive, and 48.6% were positive by IHC. Her-2/neu–positive patients had more metastatic sites and visceral metastasis than did Her-2/neu negative patients. Forty-four of 57 Her-2/neu–positive patients were treated with TPCG. The median number of cycles was six (range, 1 to 12 cycles). The most common grade 3/4 toxicity was myelosuppression. Grade 3 sensory neuropathy occurred in 14% of patients, and 22.7% experienced grade 1 to 3 cardiac toxicity (grade 3, n = 2: one left ventricular dysfunction, one tachycardia). There were two therapy-related deaths. Thirty-one (70%) of 44 patients responded (five complete and 26 partial), and 25 (57%) of 44 were confirmed responses. Median time to progression and survival were 9.3 and 14.1 months, respectively. Conclusion We prospectively characterized Her-2/neu status in advanced urothelial carcinoma patients. TPCG is feasible; cardiac toxicity rates were higher than projected, but the majority were grade two or lower. Determining the true contribution of trastuzumab requires a randomized trial.
Sports medicine in Wonderland? Keep on running
Authors: Rhijn JA Visser, Johannes L Tol
Journal: British Journal of Sports Medicine (2011)

“Well, in our country,” said Alice, still panting a little, “you'd generally get to somewhere else – if you ran very fast for a long time, as we've been doing” “A slow sort of (lower land) country!” said the Queen. “Now, here, you see, it takes all the running you can do, to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!” 

This fairy tale excerpt from Lewis Carroll (1865) adeptly describes the current position of sports medicine in The Netherlands, and probably worldwide.1 2 For political and financial reasons, we need to run twice as fast to achieve our goals. Kinetic chain adepts would probably beg to differ, but doubling your speed seems to be easy and doable: just move your legs forward twice as fast! Increased speed will eventually grant recognised specialists status of sports medicine and, at the same time, this will be a tremendous stimulus for grant-funded research projects.2

We are proud as members of The Netherlands Association of Sports Medicine to see our speed increase significantly through our affiliation with BJSM . You are all kindly invited on our seventh annual congress to celebrate this milestone. The congress will take place at the Efteling, the largest fairy tale theme park in The Netherlands. This park is renowned for its fantasy forest and with over four million visitors each year, it …
B cells enhance early innate immune responses during bacterial sepsis
Authors: Kindra M. Kelly-Scumpia, Philip O. Scumpia, Jason S. Weinstein, Matthew J. Delano, Alex G. Cuenca, Dina C. Nacionales, James L. Wynn, Pui Y. Lee, Yutaro Kumagai, Philip A. Efron, Shizuo Akira, Clive Wasserfall, Mark A. Atkinson, Lyle L. Moldawer
Journal: The Journal of Experimental Medicine (2011)

Microbes activate pattern recognition receptors to initiate adaptive immunity. T cells affect early innate inflammatory responses to viral infection, but both activation and suppression have been demonstrated. We identify a novel role for B cells in the early innate immune response during bacterial sepsis. We demonstrate that Rag1−/− mice display deficient early inflammatory responses and reduced survival during sepsis. Interestingly, B cell–deficient or anti-CD20 B cell–depleted mice, but not α/β T cell–deficient mice, display decreased inflammatory cytokine and chemokine production and reduced survival after sepsis. Both treatment of B cell–deficient mice with serum from wild-type (WT) mice and repletion of Rag1−/− mice with B cells improves sepsis survival, suggesting antibody-independent and antibody-dependent roles for B cells in the outcome to sepsis. During sepsis, marginal zone and follicular B cells are activated through type I interferon (IFN-I) receptor (IFN-α/β receptor [IFNAR]), and repleting Rag1−/− mice with WT, but not IFNAR−/−, B cells improves IFN-I–dependent and –independent early cytokine responses. Repleting B cell–deficient mice with the IFN-I–dependent chemokine, CXCL10 was also sufficient to improve sepsis survival. This study identifies a novel role for IFN-I–activated B cells in protective early innate immune responses during bacterial sepsis.
Corecognition of HLA-A1 and HLA-DPw3 by a human CD4+ alloreactive T lymphocyte clone.
Authors: S Essaket, J Fabron, C de Preval, M Thomsen
Journal: The Journal of Experimental Medicine (1990)

We have generated an alloreactive proliferative T cell clone that only is stimulated by HLA-DPw3+ antigen presenting cells (APC) that at the same time carry HLA-A1. The T cell clone is CD4+, and the proliferation is blocked by anti-DP monoclonal antibodies and not by antibodies towards other class II or towards class I molecules. Family studies show that APC with A1 and DPw3 on different haplotypes (trans) are able to stimulate the clone, and an HLA recombinant family gives evidence that the class I-carrying part of the haplotype is necessary for stimulation to occur. Stimulation is also observed with mixtures of APC expressing DPw3 and APC expressing A1, and likewise, DPw3+ APC become stimulatory when preincubated with supernatants from A1-positive cells. Our studies suggest that major histocompatibility complex (MHC) class I peptides presented by class II are allostimulatory and that APC can process MHC molecules that presumably are presented as allele-specific peptides in the context of other MHC molecules. We hypothesize that presentation of MHC peptides by MHC molecules constitutes an important part of alloreactive phenomena in vivo and in vitro.
S15 Clinical Characteristics Of Hospitalised Patients Misdiagnosed With Community-acquired Pneumonia
Authors: H. Pick, J. Lacey, D. Hodgson, E. MacDonald, A. Turvey, T. Bewick
Journal: Thorax (2014)

<h3>Background</h3> The diagnosis and treatment of patients hospitalised with community-acquired pneumonia (CAP) is predicated on an acutely abnormal chest radiograph.<sup>1</sup> Little is known about patients who present with infective respiratory symptoms with no consolidation, who have clinically significant non-pneumonic lower respiratory tract infection (LRTI). <h3>Methods</h3> A prospective observational cohort study of consecutive patients admitted to hospital with infective respiratory symptoms and treated for suspected CAP over winter 2013/14. Management was at the discretion of the admitting team. <h3>Results</h3> Of 628 patients admitted to hospital during the study, 304 (48.4%) did not have acute consolidation on chest radiograph; 166 were reported as clear, and 138 as either longstanding abnormality or not acute infection. Patients with LRTI had lower admission C-reactive protein levels (median 49 mg/l vs. 85 mg/l; p &lt; 0.01), were older (median 80.0 years vs. 76.3 years; p = 0.005), and were more likely to be managed on a non-respiratory ward (174/304 (57.2%) vs. 127/324 (39.1%); p &lt; 0.001). A higher proportion of patients with LRTI were care home residents, although this did not reach statistical significance (56/304 (18.4%) vs. 45/324 (13.9%); p = 0.12). A microbiological diagnosis was made in only 9/304 (3.0%) patients with LRTI compared with 45/324 (13.9%) with CAP (p &lt; 0.0001). CAP patients had a discharge clinical code of CAP (J12–18) in 247/324 (76.2%) cases; 121/304 (39.8%) patients with LRTI were miscoded as CAP. Thirty-day mortality was similar in both groups (48/324 (14.8%) vs. 43/304 (14.1%) p = 0.82), but median length of hospital stay was longer for patients with CAP (7.0 days vs. 5.6 days; p = 0.002). <h3>Conclusion</h3> Almost half patients treated for CAP were misdiagnosed and over-treated with broad spectrum antibiotics. Patients with non-pneumonic LRTI were older, with lower C-reactive protein levels, but similar 30-day mortality. Acute respiratory illness in this group may therefore be driven by decompensated comorbidity rather than an underlying inflammatory condition; broad spectrum antibiotics may not be useful. No national guidance currently exists on the optimal management of this group, and further study is required. <h3>Reference</h3> Lim WS <i>et al</i>. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. <i>Thorax</i><b>2009</b>,64 Suppl 3,iii1-ii55
Impact of Transforming Growth Factor-β1 on Atrioventricular Node Conduction Modification by Injected Autologous Fibroblasts in the Canine Heart
Authors: T. Jared Bunch, Srijoy Mahapatra, G. Keith Bruce, Susan B. Johnson, Dylan V. Miller, Benjamin D. Horne, Xiao-Li Wang, Hon-Chi Lee, Noel M. Caplice, Douglas L. Packer
Journal: Circulation (2006)

Background— Atrioventricular (AV) nodal ablation for management of atrial fibrillation (AF) is irreversible and requires permanent pacemaker implantation. We hypothesized that as an alternative, implantation of autologous fibroblasts in the perinodal region would focally modify AV nodal conduction and that this modulation would be enhanced by pretreatment with transforming growth factor-β1 (TGF-β1), a stimulant of fibroblasts. Methods and Results— Skin biopsies were taken from 12 mongrel dogs, and derived fibroblasts were dissociated and grown in culture for 2 weeks. Multiple injections (0.25 mL) were made through an 8F NOGA catheter along the fast/slow AV nodal pathways as guided by an electroanatomic mapping system. Seven dogs received fibroblasts alone (1×10 6 cells/mL), 7 dogs received TGF-β1 (5 μg), 4 dogs received fibroblasts and TGF-β1 (1×10 6 cells/mL+5 μg), and 4 dogs received saline only. AV node function was assessed at baseline and after 4 weeks. Saline (80 mL) with assigned therapy (0.25 mL per injection) was injected into the peri-AV nodal region in each dog. At baseline, the AH interval (66±3 ms) and the average RR interval (331±17 ms) in pacing-induced AF were similar in each cohort. The increase in AH interval in normal sinus rhythm was longer after fibroblast (23±4 versus 5±5 ms; P =0.05) and fibroblast plus TGF-β1 (50±5 versus 5±5 ms; P &lt;0.001) injections than with saline alone, with similar findings during high right atrium and distal coronary sinus pacing. The AH interval was not significantly increased after TGF-β1 injections. The AH interval was significantly longer after fibroblast plus TGF-β1 injections than with either therapy (TGF-β1 or fibroblasts) alone. The RR interval during AF was increased in dogs that received fibroblasts alone (110±36 versus −41±34 ms) and to a greater extent with the addition of TGF-β1 (294±108 versus −41±34 ms). No AV block was seen in any cohort at 4 weeks. Labeled fibroblasts that expressed vimentin were identified in all dogs that received cell injections at 4 weeks. Conclusions— AV nodal modification can be achieved with injected fibroblasts without the creation of AV block. The effect on AV node conduction is substantially enhanced by pretreatment of fibroblasts with TGF-β1. These data have therapeutic potential for the management of rapid ventricular rate during AF without pacemaker implantation.