tbuckley/cabot-search huggingface dataset:
Natural History of Leber's Hereditary Optic Neuropathy: Longitudinal Analysis of the Retinal Nerve Fiber Layer by Optical Coherence Tomography
Authors: Piero Barboni, Michele Carbonelli, Giacomo Savini, Carolina do V.F. Ramos, Arturo Carta, Adriana Berezovsky, Solange R. Salomao, Valerio Carelli, Alfredo A. Sadun
Journal: Ophthalmology (2010)
Unconscious patient's airway
Authors: R. K. Gilbert
Journal: BMJ (1969)

implants inserted as far back as 1956) kindly allowed us to examine them ; papers were read and discussed." Irreparable damage" appeared to belong to the past.I agree that intraocular implants have no place in the management of the usual run of refractive errors, assuming that appropriate spectacles or contact lenses are available.But the optical correction of aphakiaespecially unilateral-is quite another story.Where young children are concerned-and perforating wounds involving the crystalline lens are unhappily not rare-the situation is further complicated by the rapid onset of amblyopia, almost invariably irreversible in later life.Neither spectacles nor contact lenses provide a satisfactory answer, so the insertion of an intraocular lens implant, plus temporary occlusion of the uninjured eye, is the only practicable means of preventing amblyopia and restoring binocularity-as I stressed in 19591 and has been stressed by me and others' ever since.-Iam, etc., London W.I.
Gamma G globulin subgroup composition of the glomerular deposits in human renal diseases
Authors: Edmund J. Lewis, George J. Busch, Peter H. Schur
Journal: Journal of Clinical Investigation (1970)

36 renal biopsies from patients with nephritis were studied for glomerular localization of the heavy chain subgroups of immunoglobulin G (IgG or γG). The deposition pattern of these subgroups was selective and did not reflect the normal serum concentration of these proteins. γG2, which comprises 18% of normal serum γG, was the predominant or unique subgroup deposited in five cases of lupus nephritis and four biopsies with other forms of nephritis associated with granular γG deposits. γG3, which normally makes up only 8% of the serum γG, was the dominant subgroup seen in one biopsy of lobular glomerulonephritis. Patients with linear γG deposits generally had a selective absence of γG3 and often had large amounts of γG4 (normally 3% of the serum γG) deposited. The deposition of complement components C1q, C4, and C3 was variable. One biopsy had only γG2 and no complement components in the deposits and had no neutrophile leukocyte infiltration. This latter observation correlates well with the poor ability of γG2 to fix complement in vitro. Similarly, deposits containing large amounts of γG4, which does not fix complement, also tended to have less inflammatory infiltrate than deposits devoid of this subgroup. The selective deposition of monotypic or restricted γG subgroups on the glomerulus supports the likelihood that the γG represents antibody. The nature of the subgroup involved in the deposit may represent one variable in the determination of the inflammatory and morphological picture that evolves in human glomerulonephritis.
Population Pharmacokinetics of Busulfan in Children–Response
Authors: Mirjam N. Trame, Martin Bergstrand, Mats O. Karlsson, Georg Hempel
Journal: Clinical Cancer Research (2012)

We thank Dr. Nguyen and his colleagues for their letter about our article “Population Pharmacokinetics of Busulfan in Children: Increased Evidence for Body Surface Area and Allometric Body Weight Dosing of Busulfan in Children” ([1][1]). We would like to respond to the issues raised in his
Are Patients Diagnosed With Breast Cancer Before Age 50 Years Ever Cured?
Authors: Hermann Brenner, Timo Hakulinen
Journal: Journal of Clinical Oncology (2003)

Breast cancer diagnosed before the age of 50 years has become a common disease in many developed countries. Although average remaining life expectancy in the affected age groups is usually several decades, data regarding survival perspectives beyond 10 to 20 years after diagnosis are sparse. The aim of this study was to assess long-term survival in a large population-based sample of patients diagnosed with breast cancer before age 50 years.Relative survival within up to 40 years after diagnosis was assessed for cohorts of women diagnosed with breast cancer before age 50 years and notified to the nationwide Finnish Cancer Registry within various time intervals since 1953. In addition, up-to-date estimates of 40-year relative survival were obtained by exclusively looking at the survival experience of breast cancer patients in recent years (1993 to 1999) using period analysis, a new method of survival analysis.Prognosis of patients diagnosed with breast cancer before age 50 years has considerably improved during the past decades. According to the latest estimates from period analysis, cumulative 40-year relative survival is now approximately 43% for all cancers combined, 57% for localized cancers, and 24% for cancers with regional tumor spread. Nevertheless, patients diagnosed with breast cancer before age 50 years continue to have increased mortality throughout at least four decades after diagnosis. This applies even if breast cancer is diagnosed in a localized stage and in the absence of a second primary breast cancer.Despite major improvement in prognosis over time, breast cancer occurring among patients who are younger than 50 years remains a chronic disease that affects prognosis for decades.
Factors Associated With Participation in Breast Cancer Treatment Clinical Trials
Authors: Nancy E. Avis, Kevin W. Smith, Carol L. Link, Gabriel N. Hortobagyi, Edgardo Rivera
Journal: Journal of Clinical Oncology (2006)

It is well established that recruitment to clinical trials (CTs) is difficult and time consuming. This article reports on factors related to CT participation among women who were invited to participate in a CT for breast cancer.Breast cancer patients who were eligible for a CT were identified by 16 different cancer centers. After their invitation to participate in a trial, patients who were undecided about participation in a CT were recruited into the present study at that time. After a patient made a decision about trial participation, a telephone interview was conducted to assess knowledge of CTs, perceived benefits and drawbacks of CTs, and personal factors affecting the women's decision regarding participation.A total of 208 patients participated in the study. Fifty-eight percent of the patients decided to participate in a trial. Logistic regression analyses showed that the factors best explaining participation were trial phase, perceived drawbacks, time and travel considerations, therapeutic benefit of trial, and physician recommendation. Participation rates were similar for both phase I and phase III trials. However, a higher percentage of women recruited to phase II trials accepted.This study suggests that reducing drawbacks of CT participation, particularly travel time, and improving physician communication of trials are needed to increase trial participation.
One-Year Coronary Bypass Graft Patency
Authors: Petr Widimsky, Zbynek Straka, Petr Stros, Karel Jirasek, Jaroslav Dvorak, Jan Votava, Libor Lisa, Tomas Budesinsky, Miroslav Kolesar, Tomas Vanek, Petr Brucek
Journal: Circulation (2004)

Off-pump coronary bypass surgery has become a widely used technique during recent years. However, limited data are available with regard to 1-year patency of bypass grafts implanted on the beating heart in unselected consecutive bypass surgery candidates. The aim of this study was to compare 1-year angiographic patency of bypass grafts done on the beating heart (off pump) with those done classically (on pump).The PRAGUE-4 trial randomized 400 consecutive nonselected cardiac surgery candidates into group A (on pump; n=192) and group B (off pump; n=208). One-year follow-up coronary angiography was done in 255 patients. The arterial graft patency after 1 year was 91% in both groups. Saphenous graft patency was 59% (on pump) versus 49% (off pump; P=NS). Saphenous graft patency per patient was lower in the off-pump group: 0.7 patent anastomosis per patient versus 1.1 patent anastomosis in the on-pump group (P<0.01). There were 46% on-pump patients with all grafts patent versus 52% off-pump patients (P=NS). Grafts anastomosed distally to collateralized chronic total occlusions of native coronary arteries remained patent in 100% on the left anterior descending artery compared with 23% on other arteries (P<0.0001).The patency of arterial coronary bypass grafts done on the beating heart is excellent and equal to grafts done on pump. The off-pump procedure in the unselected patient population results in fewer patent saphenous grafts per patient.
High affinity histamine-binding and antihistaminic activity of the salivary nitric oxide-carrying heme protein (nitrophorin) of Rhodnius prolixus.
Authors: J M Ribeiro, F A Walker
Journal: The Journal of Experimental Medicine (1994)

The salivary glands of Rhodnius prolixus contain a nitrosyl-heme protein, named nitrophorin, that releases the vasodilatory and antiplatelet compound nitric oxide (NO). Because imidazole compounds such as histamine can interact with Fe(III) heme proteins, we investigated whether such substances could interact with Rhodnius nitrophorins. Both imidazole and histamine, but not histidine can produce full of the difference spectra of the Soret band in the 1-3 microM concentration range (at a heme protein concentration of 0.4 microM). The apparent K0.5 for the binding of histamine with the heme protein is below 1 microM. Furthermore, the complex histamine-heme protein does not dissociate after molecular sieving chromatography. To investigate whether histamine could displace NO from the native nitrosyl nitrophorins, histamine was added to the native heme proteins, leading to displacement of the bound NO as observed by changes in the absorption spectra as well as by the production of nitrite. Finally, the antihistamine effect of the heme protein was demonstrated by its inhibition of the histamine-provoked contractures of the guinea pig ileum. It is concluded that histamine, a common autacoid found at the site of injury and exposure to antigenic substances such as the site of feeding by hematophagous arthropods, can be scavenged by the nitrosyl nitrophorin of R. prolixus, which, in return, will release the vasodilatory and platelet inhibiting NO to counteract the host hemostatic response.
Effect of Aqueous Cream BP on human stratum corneum <i>in vivo</i>
Authors: M. Tsang, R.H. Guy
Journal: British Journal of Dermatology (2010)

Background Aqueous Cream BP is widely prescribed to patients with eczema to relieve skin dryness. The formulation contains sodium lauryl sulphate (SLS), a chemical that is a known skin irritant and a commonly used excipient in personal care and household products. The chronic effects of Aqueous Cream BP application on skin barrier function have not been determined. Objectives To characterize and assess skin barrier function of healthy skin after application of Aqueous Cream BP and to study the physical effects of the formulation on the stratum corneum (SC). Methods The left and right volar forearms of six human volunteers were each separated into treated and control sides. The treated sides of each forearm were subjected to twice daily applications of Aqueous Cream BP for 4 weeks at the end of which concomitant tape stripping and transepidermal water loss (TEWL) measurements were made. The untreated sides of the forearms were not exposed to any products containing SLS during the study period. Results Changes in SC thickness, baseline TEWL and rate of increase in TEWL during tape stripping were observed in skin treated with Aqueous Cream BP. The mean decrease in SC thickness was 1·1 μm (12%) (P = 0·0015) and the mean increase in baseline TEWL was 2·5 g m−2 h−1 (20%) (P < 0·0001). Reduced SC thickness and an increase in baseline TEWL, as well as a faster rate of increase in TEWL during tape stripping, were observed in 16 out of 27 treated skin sites. Conclusions The application of Aqueous Cream BP, containing ∼1% SLS, reduced the SC thickness of healthy skin and increased its permeability to water loss. These observations call into question the continued use of this emollient on the already compromised barrier of eczematous skin.
Aggregation and neurotoxicity of recombinant α-synuclein aggregates initiated by dimerization
Authors: Alireza Roostaee, Simon Beaudoin, Antanas Staskevicius, Xavier Roucou
Journal: Molecular Neurodegeneration (2013)

Abstract Background Aggregation of the α-Synuclein (α-Syn) protein, amyloid fibril formation and progressive neurodegeneration are the neuropathological hallmarks of Parkinson's Disease (PD). However, a detailed mechanism of α-Syn aggregation/fibrillogenesis and the exact nature of toxic oligomeric species produced during amyloid formation process are still unknown. Results In this study, the rates of α-Syn aggregation were compared for the recombinant wild-type (WT) α-Syn and a structurally relevant chimeric homologous protein containing an inducible Fv dimerizing domain (α-Syn Fv ), capable to form dimers in the presence of a divalent ligand (AP20187). In the presence of AP20187, we report a rapid random coil into β-sheet conformational transformation of α-Syn Fv within 24 h, whereas WT α-Syn showed 24 h delay to achieve β-sheet structure after 48 h. Fluorescence ANS and ThT binding experiments demonstrate an accelerated oligomer/amyloid formation of dimerized α-Syn Fv , compared to the slower oligomerization and amyloidogenesis of WT α-Syn or α-Syn Fv without dimerizer AP20187. Both α-Syn Fv and α-Syn pre-fibrillar aggregates internalized cells and induced neurotoxicity when injected into the hippocampus of wild-type mice. These recombinant toxic aggregates further converted into non-toxic amyloids which were successfully amplified by protein misfolding cyclic amplification method, providing the first evidence for the in vitro propagation of synthetic α-Syn aggregates. Conclusions Together, we show that dimerization is important for α-Syn conformational transition and aggregation. In addition, α-Syn dimerization can accelerate the formation of neurotoxic aggregates and amyloid fibrils which can be amplified in vitro . A detailed characterization of the mechanism of α-Syn aggregation/amyloidogenesis and toxicity is crucial to comprehend Parkinson's disease pathology at the molecular level.
Longitudinal Changes in Obesity and Body Mass Index Among Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study
Authors: Edward G. Garmey, Qi Liu, Charles A. Sklar, Lillian R. Meacham, Ann C. Mertens, Marilyn A. Stovall, Yutaka Yasui, Leslie L. Robison, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2008)

We examined the rate of increase in the body mass index (BMI; kg/m(2)) after final height attainment in survivors of acute lymphoblastic leukemia (ALL) and a noncancer comparison group.Childhood Cancer Survivor Study (CCSS) is a retrospectively ascertained cohort study that prospectively tracks the health status of adults who were diagnosed with childhood cancer between 1970 and 1986 and a comparison group of siblings. Changes in BMI from baseline enrollment to time of completion of follow-up (mean interval, 7.8 years) were calculated for 1,451 ALL survivors (mean age, 32.3 years at follow-up) and 2,167 siblings of childhood cancer survivors (mean age, 35.9 years).The mean BMI of the CCSS sibling comparison group increased with age (women, 0.25 units/yr, 95% CI, 0.22 to 0.28 units; men, 0.23 units/yr, 95% CI, 0.20 to 0.25 units). Compared with CCSS siblings, ALL survivors who were treated with cranial radiation therapy (CRT) had a significantly greater increase in BMI (women, 0.41 units/yr, 95% CI, 0.37 to 0.45 units; men, 0.29 units/yr; 95% CI, 0.26 to 0.32 units). The rate of BMI increase was not significantly increased for ALL survivors who were treated with chemotherapy alone. Younger age at CRT exposure significantly modified risk.CRT used in the treatment of childhood ALL is associated with a greater rate of increasing BMI, particularly among women treated with CRT during the first decade of life. Health care professionals should be aware of this risk and interventions to reduce or manage weight gain are essential in this high-risk population.
Molecular Mechanism of β-Arrestin-Biased Agonism at Seven-Transmembrane Receptors
Authors: Eric Reiter, Seungkirl Ahn, Arun K. Shukla, Robert J. Lefkowitz
Journal: The Annual Review of Pharmacology and Toxicology (2011)

The concept of biased agonism has recently come to the fore with the realization that seven-transmembrane receptors (7TMRs, also known as G protein–coupled receptors, or GPCRs) activate complex signaling networks and can adopt multiple active conformations upon agonist binding. As a consequence, the “efficacy” of receptors, which was classically considered linear, is now recognized as pluridimensional. Biased agonists selectively stabilize only a subset of receptor conformations induced by the natural “unbiased” ligand, thus preferentially activating certain signaling mechanisms. Such agonists thus reveal the intriguing possibility that one can direct cellular signaling with unprecedented precision and specificity and support the notion that biased agonists may identify new classes of therapeutic agents that have fewer side effects. This review focuses on one particular class of biased ligands that has the ability to alter the balance between G protein–dependent and β-arrestin-dependent signal transduction.
The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled trials
Authors: D. A Lawlor
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To determine the effectiveness of exercise as an intervention in the management of depression. <b>Design:</b> Systematic review and meta-regression analysis of randomised controlled trials obtained from five electronic databases (Medline, Embase, Sports Discus, PsycLIT, Cochrane Library) and through contact with experts in the field, bibliographic searches, and hand searches of recent copies of relevant journals. <b>Main outcome measures:</b> Standardised mean difference in effect size and weighted mean difference in Beck depression inventory score between exercise and no treatment and between exercise and cognitive therapy. <b>Results:</b> All of the 14 studies analysed had important methodological weaknesses; randomisation was adequately concealed in only three studies, intention to treat analysis was undertaken in only two, and assessment of outcome was blinded in only one. The participants in most studies were community volunteers, and diagnosis was determined by their score on the Beck depression inventory. When compared with no treatment, exercise reduced symptoms of depression (standardised mean difference in effect size −1.1 (95% confidence interval −1.5 to −0.6); weighted mean difference in Beck depression inventory −7.3 (−10.0 to −4.6)). The effect size was significantly greater in those trials with shorter follow up and in two trials reported only as conference abstracts. The effect of exercise was similar to that of cognitive therapy (standardised mean difference −0.3 (95% confidence interval −0.7 to 0.1)). <b>Conclusions:</b> The effectiveness of exercise in reducing symptoms of depression cannot be determined because of a lack of good quality research on clinical populations with adequate follow up. <h3>What is already known on this topic</h3> Depression is common Management is often inadequate and many patients do not comply with antidepressant medication The effect of exercise on depression has been a subject of interest for many years <h3>What this study adds</h3> Most studies of the effect of exercise on depression are of poor quality, have brief follow up, and are undertaken on non-clinical volunteers Exercise may be efficacious in reducing symptoms of depression in the short term but its effectiveness in clinical populations is unknown A well designed, randomised controlled trial with long term follow up is needed
High inhaled corticosteroids adherence in childhood asthma: the role of medication beliefs
Authors: Francine M. Ducharme
Journal: European Respiratory Journal (2012)

For two decades, maintenance inhaled corticosteroids have been recommended by international guidelines as the mainstay of treatment in children and adults with persistent asthma. As asthma control criteria have become increasingly more stringent, an even larger proportion of individuals are labelled as having “uncontrolled persistent” asthma. Indeed, while in 1996, we accepted as criteria for acceptable control as up to 10 doses per week of rescue β2-agonists, that is to say one dose per day for the prevention of exercise-induced asthma and three doses per week for the relief of symptoms [1], they were progressively reduced to two doses per week since 2006 [2]. An expanding proportion of individuals with mild asthma now qualify for maintenance controller therapy. The preference for daily inhaled corticosteroids over leukotriene receptor antagonists and placebo is solidly supported by systematic reviews of the efficacy of randomised controlled trials [3, 4] in children and adults [5–7].

However, most patients with mild persistent asthma do not use maintenance inhaled corticosteroids and most individuals remain poorly controlled [8–10]. Insufficient use of inhaled corticosteroids may be due to suboptimal medical prescriptions and to limited patient access to healthcare and medications [11, 12]. However, even in settings where patients have free access to medications, adherence remains suboptimal; many discontinue asthma controllers when asymptomatic and restart therapy when deemed required [11–13]. Reasons for poor patient adherence include: side effects, fear of side effects, forgetfulness, inconvenience of medication use, the erroneous conception that no symptoms equate to no disease, and negative beliefs about always having asthma, having airway inflammation, and about the importance of using inhaled corticosteroids [10, 13, 14]. Yet, suboptimal adherence to …
Interkingdom Transfer of the Acne-Causing Agent, Propionibacterium acnes, from Human to Grapevine
Authors: Andrea Campisano, Lino Ometto, Stéphane Compant, Michael Pancher, Livio Antonielli, Sohail Yousaf, Claudio Varotto, Gianfranco Anfora, Ilaria Pertot, Angela Sessitsch, Omar Rota-Stabelli
Journal: Molecular Biology and Evolution (2014)

Here, we report the surprising and, to our knowledge, unique example of horizontal interkingdom transfer of a human opportunistic pathogen (Propionibacterium acnes) to a crop plant (the domesticated grapevine Vitis vinifera L.). Humans, like most organisms, have established a long-lasting cohabitation with a variety of microbes, including pathogens and gut-associated bacteria. Studies which have investigated the dynamics of such associations revealed numerous cases of bacterial host switches from domestic animals to humans. Much less is, however, known about the exchange of microbial symbionts between humans and plants. Fluorescent in situ hybridization localized P. acnes in the bark, in xylem fibers, and, more interestingly, inside pith tissues. Phylogenetic and population genetic analyses suggest that the establishment of the grapevine-associated P. acnes as obligate endophyte is compatible with a recent transfer event, likely during the Neolithic, when grapevine was domesticated.