tbuckley/cabot-search huggingface dataset:
Canaries in the coal mine
Authors: Maeve Barry
Journal: European Respiratory Journal (2013)

Up until 30 years ago, coalminers relied on canaries as warning systems against harmful gases and pollutants underground. The miners listened for birdsong and if the birds fell silent, then they knew there was danger to their health and to take action. Today we have much more sophisticated information and reporting on the quality of air. We know precisely the levels and composition of pollutants in the air that are responsible for almost 500,000 deaths annually [1]. The problem is however, that nobody appears to be listening.

The air we breathe reduces our life expectancy by on average 8.6 months in Europe (fig. 1) [2]. Fine particle pollution (particles with a 50% cut-off aerodynamic diameter of 2.5 µm) is estimated to account for some 5 million lost years of life in the European Economic Area (www.efta.int/eea) countries every year [3]. Exposure to ground-level ozone concentrations above critical health levels is associated with more than 20 000 premature deaths in the European Union (EU) annually [4]. Yet, 17 EU Member States are being taken to court by the European Commission …
A Syndrome Resembling Infectious Mononucleosis After Open-heart Surgery
Authors: D. R. Smith
Journal: BMJ (1964)

<h3>Background</h3> <i>De novo</i> mutations are emerging as an important cause of neurocognitive impairment, and whole exome sequencing of case-parent trios is a powerful way of detecting them. Here, we report the findings in four such trios. <h3>Methods</h3> The Deciphering Developmental Disorders study is using whole exome sequencing in family trios to investigate children with severe, sporadic, undiagnosed developmental delay. Three of our patients were ascertained from the first 1133 children to have been investigated through this large-scale study. Case 4 was a phenotypically isolated case recruited into an undiagnosed rare disorders sequencing study. <h3>Results</h3> Protein-altering <i>de novo</i> mutations in <i>PURA</i> were identified in four subjects. They include two different frameshifts, one inframe deletion and one missense mutation. <i>PURA</i> encodes Pur-α, a highly conserved multifunctional protein that has an important role in normal postnatal brain development in animal models. The associated human phenotype of <i>de novo</i> heterozygous mutations in this gene is variable, but moderate to severe neurodevelopmental delay and learning disability are common to all. Neonatal hypotonia, early feeding difficulties and seizures, or ‘seizure-like’ movements, were also common. Additionally, it is suspected that anterior pituitary dysregulation may be within the spectrum of this disorder. Psychomotor developmental outcomes appear variable between patients, and we propose a possible genotype–phenotype correlation, with disruption of Pur repeat III resulting in a more severe phenotype. <h3>Conclusions</h3> These findings provide definitive evidence for the role of <i>PURA</i> in causing a variable syndrome of neurodevelopmental delay, learning disability, neonatal hypotonia, feeding difficulties, abnormal movements and epilepsy in humans, and help clarify the role of <i>PURA</i> in the previously described 5q31.3 microdeletion phenotype.
Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease
Authors: Jane W. Newburger, Masato Takahashi, Michael A. Gerber, Michael H. Gewitz, Lloyd Y. Tani, Jane C. Burns, Stanford T. Shulman, Ann F. Bolger, Patricia Ferrieri, Robert S. Baltimore, Walter R. Wilson, Larry M. Baddour, Matthew E. Levison, Thomas J. Pallasch, Donald A. Falace, Kathryn A. Taubert
Journal: Circulation (2004)

Background— Kawasaki disease is an acute self-limited vasculitis of childhood that is characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in ∼15% to 25% of untreated children and may lead to ischemic heart disease or sudden death. Methods and Results— A multidisciplinary committee of experts was convened to revise the American Heart Association recommendations for diagnosis, treatment, and long-term management of Kawasaki disease. The writing group proposes a new algorithm to aid clinicians in deciding which children with fever for ≥5 days and ≤4 classic criteria should undergo echocardiography, receive intravenous gamma globulin (IVIG) treatment, or both for Kawasaki disease. The writing group reviews the available data regarding the initial treatment for children with acute Kawasaki disease, as well for those who have persistent or recrudescent fever despite initial therapy with IVIG, including IVIG retreatment and treatment with corticosteroids, tumor necrosis factor-α antagonists, and abciximab. Long-term management of patients with Kawasaki disease is tailored to the degree of coronary involvement; recommendations regarding antiplatelet and anticoagulant therapy, physical activity, follow-up assessment, and the appropriate diagnostic procedures to evaluate cardiac disease are classified according to risk strata. Conclusions— Recommendations for the initial evaluation, treatment in the acute phase, and long-term management of patients with Kawasaki disease are intended to assist physicians in understanding the range of acceptable approaches for caring for patients with Kawasaki disease. The ultimate decisions for case management must be made by physicians in light of the particular conditions presented by individual patients.
Investigating Population History Using Temporal Genetic Differentiation
Authors: Pontus Skoglund, Per Sjödin, Tobias Skoglund, Martin Lascoux, Mattias Jakobsson
Journal: Molecular Biology and Evolution (2014)

The rapid advance of sequencing technology, coupled with improvements in molecular methods for obtaining genetic data from ancient sources, holds the promise of producing a wealth of genomic data from time-separated individuals. However, the population-genetic properties of time-structured samples have not been extensively explored. Here, we consider the implications of temporal sampling for analyses of genetic differentiation and use a temporal coalescent framework to show that complex historical events such as size reductions, population replacements, and transient genetic barriers between populations leave a footprint of genetic differentiation that can be traced through history using temporal samples. Our results emphasize explicit consideration of the temporal structure when making inferences and indicate that genomic data from ancient individuals will greatly increase our ability to reconstruct population history.
Development and organization of human stratum corneum after birth: electron microscopy isotropy score and immunocytochemical corneocyte labelling as epidermal maturation's markers in infancy
Authors: J.W. Fluhr, N. Lachmann, C. Baudouin, P. Msika, R. Darlenski, C. De Belilovsky, J. Bossert, E. Colomb, B. Burdin, M. Haftek
Journal: British Journal of Dermatology (2014)

There is growing evidence for the ongoing structural and functional adaptation of the skin after birth.The aim of this study was the definition of scanning electron microscopy markers of skin maturation in different age groups (birth to adulthood). We propose a semiquantitative score to analyse the maturation of the skin surface and a complementary evaluation of the distribution of corneodesmosin and corneodesmosomes.An electron microscopy isotropy (E.M.I.) score was performed in six age-groups to include fullterm neonates, babies, children and adults. The distribution of corneodesmosome remnants was analysed by corneodesmosin distribution with immunocytochemical corneocyte labelling.The E.M.I. score showed the highest anisotropy in neonates. The youngest groups displayed irregular and thick cell clusters composed of poorly individualized cells. In the older groups, the distribution of superficial corneocytes was more regular. The cells evenly covered the surface and displayed easily visualized single cell outlines. The distribution of immune-labelled corneodesmosome remnants and the corneocyte projected area showed a correlation between age and structural maturation. The observed evolution indicated a poorly controlled process of corneocyte desquamation in infants and confirmed the relative immaturity of the epidermal barrier up to 1-2 years after birth under basal conditions.Our study is the first attempt at semiquantitative evaluation of the micromorphology maturation of the epidermal surface at the ultrastructural level. The E.M.I. score and the associated pattern of corneodesmosome breakdown may be used as markers of the stratum corneum maturation.
Pathophysiological role and diuretic efficacy of atrial natriuretic peptide in renal patients.
Authors: L De Nicola, V Bellizzi, B Cianciaruso, R Minutolo, G Colucci, M Balletta, G Fuiano, G Conte
Journal: Journal of the American Society of Nephrology (1997)

It has been suggested that renal disease is characterized by the presence of resistance to the natriuretic effects of atrial peptide (ANP). In this study, plasma ANP (pANP) and renal function were evaluated during stepwise infusion of low ANP doses (2, 4, 8, and 16 ng/kg per min) in glomerulonephritic patients with (CRF) or without (GN) moderate renal failure, and in normal subjects (NOR), kept at low-sodium diet (LSD; 35 mEq NaCl/day). To assess the physiological ANP levels, pANP was also measured in the three groups after normal-sodium diet (NSD; 235 mEq NaCl/day). ANP did not affect systemic and renal perfusion at any of the doses tested; a significant increment of GFR was observed only in NOR and GN. The 2-, 4-, and 8-ng/kg doses increased pANP to values overlapping the physiological concentrations measured at NSD; this was associated with a dose-dependent increment of urinary excretion of sodium (UNaV) that reached analogous levels in the three groups. ANP accounted for approximately 40% of the UNaV increment evoked by NSD in patients and in normal subjects. The 16-ng/kg dose led to supraphysiological levels that induced a similar marked enhancement of UNaV (from the basal value of 0.12 +/- 0.02 to 0.42 +/- 0.08 mEq/min in CRF, from 0.13 +/- 0.02 to 0.73 +/- 0.08 in GN, and from 0.09 +/- 0.02 to 0.49 +/- 0.11 in NOR). In CRF, the normal natriuretic response to the highest dose was caused by a larger increase of fractional UNaV that was strictly dependent on the greater pANP increment, as demonstrated by similar changes in the fractional excretion of cGMP, and, in part, on the greater aldosterone decrease. In all groups, ANP also induced a dose-dependent urinary loss of phosphate, potassium, and urea, resulting in a significant 15 to 25% decrease in the plasma levels. Thus, in GN and CRF patients, ANP plays a significant role in the renal handling of sodium; moreover, the achievement of low supraphysiological pANP levels leads to a conspicuous natriuresis associated with unique extranatriuretic effects.
Increased apoptotic peripheral blood neutrophils in systemic lupus erythematosus: relations with disease activity, antibodies to double stranded DNA, and neutropenia
Authors: P A Courtney, A D Crockard, K Williamson, A E Irvine, R J Kennedy, A L Bell
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> To quantify the percentage of apoptotic peripheral blood neutrophils in systemic lupus erythematosus (SLE) and to determine the relations with disease activity and neutropenia. <h3>METHODS</h3> Neutrophil apoptosis in SLE patients (n =50) was assessed by flow cytometry using annexin V binding and fluorescent labelled anti-fas. Rheumatoid arthritis (RA, n =20) and inflammatory bowel disease patients (IBD, n =20) were studied as disease controls. <h3>RESULTS</h3> The percentage of apoptotic neutrophils, determined by annexin V binding, was increased in peripheral blood of SLE patients (median = 3.25%) compared with normal healthy donors (n =20, median = 1.20%) and disease controls (RA: median = 1.15%) (IBD: median = 1.15%). SLE neutrophil apoptosis correlated positively with lupus disease activity measured by SLAM score. SLE patients with increased antibodies to dsDNA (&gt;10 mg/ml) had increased apoptotic neutrophils. Eight of 14 neutropenic SLE patients had increased apoptotic neutrophils. Increased neutrophil fas expression compared with normal controls was observed in SLE, RA, and IBD. <h3>CONCLUSION</h3> Neutrophil fas expression is increased non-specifically in inflammatory disease. Increased circulating apoptotic neutrophils in SLE correlate positively with disease activity (SLAM) and may contribute to autoantigen excess including dsDNA.
High‐dose proinflammatory cytokines induce apoptosis of hair bulb keratinocytes <i>in vivo</i>
Authors: R. Rückert, G. Lindner, S. Bulfone‐Paus, R. Paus
Journal: British Journal of Dermatology (2000)

Background Hair loss following skin inflammation may in part be mediated by keratinocyte (KC) apoptosis. While the effects of different cytokines or other apoptosis stimulating agents such as interferon (IFN)-γ or tumour necrosis factor (TNF)-α on KC apoptosis in vitro have been addressed in several studies, little is known about the effects of proinflammatory cytokines on KC apoptosis in vivo. Objectives To study the effects of intradermally injected TNF-α, interleukin (IL)-1β and IFN-γ on KC apoptosis in the back skin of C57BL/6 mice. Methods Apoptosis in epidermal and hair bulb KCs was analysed by immunohistology using TUNEL staining. Results Injection of TNF-α induced a significantly higher number of apoptotic cells within the epidermis than vehicle; all three proinflammatory cytokines together further increased their number. Intrafollicular hair bulb KCs were much more susceptible to apoptosis induction by TNF-α or IL-1β; their injection significantly upregulated apoptosis after 6 h, which was further increased after 24 h. The combination of all cytokines together accelerated intrafollicular apoptosis after 6 h by doubling the number of apoptotic cells per hair bulb, compared with the effects of TNF-α or IL-1β alone. Conclusions These data suggest that programmed cell death of proliferating KCs in vivo can be induced by proinflammatory cytokines.
Metabolism of dietary sulphate: absorption and excretion in humans.
Authors: T Florin, G Neale, G R Gibson, S U Christl, J H Cummings
Journal: Gut (1991)

Dietary sulphate may affect colonic pathophysiology because sulphate availability determines in part the activity of sulphate reducing bacteria in the bowel. The main product of sulphate reducing bacterial oxidative metabolism, hydrogen sulphide, is potentially toxic. Although it is generally believed that the sulphate ion is poorly absorbed, there are no available data on how much sulphate reaches the colon nor on the relative contributions from diet and endogenous sources. To resolve these questions, balance studies were performed on six healthy ileostomists and three normal subjects chosen because they did not have detectable sulphate reducing bacteria in their faeces. The subjects were fed diets which varied in sulphate content from 1.6-16.6 mmol/day. Sulphate was measured in diets, faeces (ileal effluent in ileostomists), and urine by anion exchange chromatography with conductivity detection. Overall there was net absorption of dietary sulphate, with the absorptive capacity of the gastrointestinal tract plateauing at 5 mmol/day in the ileostomists and exceeding 16 mmol/day in the normal subjects. Endogenous secretion of sulphate in the upper gastrointestinal tract was from 0.96-2.6 mmol/day. The dietary contribution to the colonic sulphate pool ranged up to 9 mmol/day, there being linear identity between diet and upper gastrointestinal losses for intakes above 7 mmol/day. Faecal losses of sulphate were trivial (less than 0.5 mmol/day) in the normal subjects at all doses. It is concluded that diet and intestinal absorption are the principal factors affecting the amounts of sulphate reaching the colon. Endogenous secretion of sulphate by colonic mucosa may also be important in determining amounts of sulphate in the colon.
Knowledge about sports-related concussion: is the message getting through to coaches and trainers?
Authors: Peta E White, Joshua D Newton, Michael Makdissi, S John Sullivan, Gavin Davis, Paul McCrory, Alex Donaldson, Michael T Ewing, Caroline F Finch
Journal: British Journal of Sports Medicine (2013)

Aim The need for accurate diagnosis and appropriate return-to-play decisions following a concussion in sports has prompted the dissemination of guidelines to assist managing this condition. This study aimed to assess whether key messages within these guidelines are reflected in the knowledge of coaches and sports trainers involved in community sport. Methods An online knowledge survey was widely promoted across Australia in May–August 2012 targeting community Australian Football (AF) and Rugby League (RL) coaches and sports trainers. 260 AF coaches, 161 AF sports trainers, 267 RL coaches and 228 RL sports trainers completed the survey. Knowledge scores were constructed from Likert scales and compared across football codes and respondent groups. Results General concussion knowledge did not differ across codes but sports trainers had higher levels than did coaches. There were no significant differences in either concussion symptoms or concussion management knowledge across codes or team roles. Over 90% of respondents correctly identified five of the eight key signs or symptoms of concussion. Fewer than 50% recognised the increased risk of another concussion following an initial concussion. Most incorrectly believed or were uncertain that scans typically show damage to the brain after a concussion occurs. Fewer than 25% recognised, and &gt;40% were uncertain that younger players typically take longer to recover from concussion than adults. Conclusions The key messages from published concussion management guidelines have not reached community sports coaches and sports trainers. This needs to be redressed to maximise the safety of all of those involved in community sport.
Leukotriene A4 hydrolase: an anti-inflammatory role for a proinflammatory enzyme
Authors: R. J. Snelgrove
Journal: Thorax (2011)

Neutrophils represent a prominent source of pathology in an array of persistent pulmonary diseases. A recent article published in <i>Science</i> describes a novel anti-inflammatory pathway that degrades the neutrophil chemoattractant Pro-Gly-Pro (PGP) to limit neutrophilic inflammation of the lung. Degradation of PGP was mediated through the action of leukotriene A<sub>4</sub> hydrolase (LTA<sub>4</sub>H), an enzyme classically recognised for its capacity to generate another neutrophil chemoattractant, leukotriene B<sub>4</sub> (LTB<sub>4</sub>). The same enzyme therefore has opposing proinflammatory (LTB<sub>4</sub> generation) and anti-inflammatory (PGP degradation) activities that govern neutrophilic inflammation. Intriguingly, cigarette smoke, a key risk factor for the development of chronic obstructive pulmonary disease, impedes PGP degradation but not LTB<sub>4</sub> generation by LTA<sub>4</sub>H. Cigarette smoke therefore essentially converts LTA<sub>4</sub>H into an exclusively proinflammatory enzyme, whereby both PGP and LTB<sub>4</sub> can drive persistent neutrophila observed in chronic obstructive pulmonary disease. In recent years there has been significant pharmaceutical interest in the development of LTA<sub>4</sub>H inhibitors to alleviate LTB<sub>4</sub>-mediated pathologies. In light of these new findings, such strategies should be viewed with caution since they may inadvertently prevent PGP degradation and promote chronic neutrophilic inflammation.
Explaining Adherence Success in Sub-Saharan Africa: An Ethnographic Study
Authors: Norma C Ware, John Idoko, Sylvia Kaaya, Irene Andia Biraro, Monique A Wyatt, Oche Agbaji, Guerino Chalamilla, David R Bangsberg
Journal: PLoS Medicine (2009)

Background Individuals living with HIV/AIDS in sub-Saharan Africa generally take more than 90% of prescribed doses of antiretroviral therapy (ART). This number exceeds the levels of adherence observed in North America and dispels early scale-up concerns that adherence would be inadequate in settings of extreme poverty. This paper offers an explanation and theoretical model of ART adherence success based on the results of an ethnographic study in three sub-Saharan African countries. Methods and Findings Determinants of ART adherence for HIV-infected persons in sub-Saharan Africa were examined with ethnographic research methods. 414 in-person interviews were carried out with 252 persons taking ART, their treatment partners, and health care professionals at HIV treatment sites in Jos, Nigeria; Dar es Salaam, Tanzania; and Mbarara, Uganda. 136 field observations of clinic activities were also conducted. Data were examined using category construction and interpretive approaches to analysis. Findings indicate that individuals taking ART routinely overcome economic obstacles to ART adherence through a number of deliberate strategies aimed at prioritizing adherence: borrowing and “begging” transport funds, making “impossible choices” to allocate resources in favor of treatment, and “doing without.” Prioritization of adherence is accomplished through resources and help made available by treatment partners, other family members and friends, and health care providers. Helpers expect adherence and make their expectations known, creating a responsibility on the part of patients to adhere. Patients adhere to promote good will on the part of helpers, thereby ensuring help will be available when future needs arise. Conclusion Adherence success in sub-Saharan Africa can be explained as a means of fulfilling social responsibilities and thus preserving social capital in essential relationships.
Ex Vivo and In Vivo Regulation of Lipocalin-2, a Novel Adipokine, by Insulin
Authors: Bee K. Tan, Raghu Adya, Xiaoye Shan, Farhatullah Syed, Krzysztof C. Lewandowski, John P. O'Hare, Harpal S. Randeva
Journal: Diabetes Care (2008)

OBJECTIVE—Lipocalin-2, a novel adipokine, has been shown to be elevated in obese, insulin-resistant, and diabetic subjects. We therefore sought to study the ex vivo and in vivo effects of insulin on lipocalin-2 levels in humans. RESEARCH DESIGN AND METHODS—We investigated the in vivo effects of insulin (hyperinsulinemia) on circulating lipocalin-2 levels by enzyme-linked immunosorbent assay via a prolonged insulin-glucose infusion. The ex vivo effect of insulin on adipose tissue lipocalin-2 protein production and secretion into conditioned media was assessed by Western blotting and enzyme-linked immunosorbent assay, respectively. RESULTS—Hyperinsulinemic induction in human subjects significantly increased circulating lipocalin-2 levels (P &amp;lt; 0.01). Also, in omental adipose tissue explants, insulin caused a significant dose-dependent increase in lipocalin-2 protein production and secretion into conditioned media (P &amp;lt; 0.05, P &amp;lt; 0.01, respectively); these effects were negated by both phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase inhibitors. CONCLUSIONS—Lipocalin-2 is upregulated by insulin via phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways.