tbuckley/cabot-search huggingface dataset:
Antibiotic prescribing for discoloured sputum in acute cough/lower respiratory tract infection
Authors: C.C. Butler, M.J. Kelly, K. Hood, T. Schaberg, H. Melbye, M. Serra-Prat, F. Blasi, P. Little, T. Verheij, S. Mölstad, M. Godycki-Cwirko, P. Edwards, J. Almirall, A. Torres, U-M. Rautakorpi, J. Nuttall, H. Goossens, S. Coenen
Journal: European Respiratory Journal (2011)

We investigated whether discoloured sputum and feeling unwell were associated with antibiotic prescription and benefit from antibiotic treatment for acute cough/lower respiratory tract infection (LTRI) in a prospective study of 3,402 adults in 13 countries. A two-level model investigated the association between producing discoloured sputum or feeling generally unwell and an antibiotic prescription. A three-level model investigated the association between an antibiotic prescription and symptom resolution. Patients producing discoloured sputum were prescribed antibiotics more frequently than those not producing sputum (OR 3.2, 95% CI 2.1–5.0), unlike those producing clear/white sputum (OR 0.95, 95% CI 0.61–1.48). Antibiotic prescription was not associated with a greater rate or magnitude of symptom score resolution (as measured by a 13-item questionnaire completed by patients each day) among those who: produced yellow (coefficient 0.00; p = 0.68) or green (coefficient -0.01; p = 0.11) sputum; reported any of three categories of feeling unwell; or produced discoloured sputum and felt generally unwell (coefficient -0.01; p = 0.19). Adults with acute cough/LRTI presenting in primary care settings with discoloured sputum were prescribed antibiotics more often compared to those not producing sputum. Sputum colour, alone or together with feeling generally unwell, was not associated with recovery or benefit from antibiotic treatment.
Tandem duplication via light-strand synthesis may provide a precursor for mitochondrial genomic rearrangement
Authors: J. R. Macey, J. A. Schulte, A. Larson, T. J. Papenfuss
Journal: Molecular Biology and Evolution (1998)

A tandem duplication of the mitochondrial tRNA(Thr) and tRNA(Pro) genes in the amphisbaenian reptile Bipes biporus is the first case reported of a tandem duplication restricted to a single pair of tRNA genes in a vertebrate mitochondrial genome. Such duplications have been predicted, however, as intermediate steps in the evolution of observed mitochondrial genomic rearrangements through errors in light-strand replication. The tandem duplication reported here is evolutionarily associated with displacement of the origin for light-strand replication from its typical location in vertebrate mitochondrial genomes and loss of the dihydrouridine stem from the tRNA(Cys) gene; these factors implicate light-strand replicational errors in the tandem duplication of genic regions. Pseudogene formation in tandemly duplicated sequences appears to be an intermediate step in genomic rearrangement. However, formation of pseudogenes in the Bipes mitochondrial genome occurs in a pattern that precludes subsequent genomic rearrangement. Functional constraints placed on cleavage of mitochondrial transcripts by tRNA genes also may prevent mitochondrial genomic rearrangement.
Vitamin D and Cancer: Uncertainty Persists; Research Continues
Authors: J. Nicholas
Journal: JNCI Journal of the National Cancer Institute (2011)

The VITAL Trial Amid the many studies under way is a newly launched, large multicenter trial called VITAL (Vitamin D and Omega-3 Trial), investigating whether high doses of vitamin D and the omega-3 fatty acids found in fi sh oil can reduce the risk of developing cancer, heart disease, and stroke. Primary outcomes are incidence of these diseases after 5 years. VITAL is the fi rst large-scale randomized trial designed to test vitamin D’s role in preventing cancer and cardiovascular disease, Manson said. The trial is testing a higher dose of vitamin D than most previous studies and is “large enough to provide conclusive results.”
American Medicine and the'Inevitables in Its Future
Authors: Ward Darley
Journal: JAMA (1966)

As this nation's leadership looks to the future structure and function of its health and medical establishment, it is important to consider those phenomena that will be inevitable. Of course, the most basic inevitable will be change itself. One has only to look back 25 years to appreciate the exponential rate with which change has taken place and, barring a world catastrophe, it is inevitable that both the direction and speeed of this change will continue. The components of this change, all of which are inevitables in themselves, constitute a chain reaction, the links of which arrange themselves in the followingsequence: (1) increasing knowledge, (2) increasing specialism, (3) increasing demands for service, (4) increasing costs of service, (5) increasing shortages of personnel, (6) increasing complexity and efficiency in data processing and communication, and (7) increasing institutionalization (organization). Much can be said about these inevitables: why they represent inevitables (I offer
Aldosterone-Induced Activation of Signaling Pathways Requires Activity of Angiotensin Type 1a Receptors
Authors: Catherine A. Lemarié, Stefania M.C. Simeone, Anna Nikonova, Talin Ebrahimian, Marie-Eve Deschênes, Thomas M. Coffman, Pierre Paradis, Ernesto L. Schiffrin
Journal: Circulation Research (2009)

Rationale : Aldosterone has been shown to induce vascular damage, endothelial dysfunction, and myocardial fibrosis, which depend in part on activation of angiotensin II (Ang II)–mediated pathways. However, mechanisms underlying crosstalk between Ang II type 1 receptor (AT 1 R) and mineralocorticoid receptor (MR) are mostly unknown. Objectives : We tested whether the lack of Ang II type 1a receptor (AT 1a R) or Ang II type 1b receptor (AT 1b R) would decrease cellular effects induced by aldosterone. Methods and Results : We examined the effect of Ang II or aldosterone after transfection of mesenteric vascular smooth muscle cells (VSMCs) from C57Bl/6 mice with small interference RNA for AT 1a R, AT 1b R, or MR for 48 hours. Ang II and aldosterone separately induced ERK1/2, c-Jun NH2-terminal protein kinase (JNK), and nuclear factor (NF)-κB phosphorylation after a 20-minute stimulation. Small interference RNA for AT 1a R downregulated phosphorylation of ERK1/2, JNK, and NF-κB after aldosterone stimulation compared to controls. Downregulation of AT 1b R or MR only abolished the activation of NF-κB. In VSMCs from C57Bl/6 mice, aldosterone and Ang II induced the activation of the c-fos promoter from 30 minutes to 1 hour. This effect was blocked when using VSMCs from AT 1a R knockout mice. Conclusion : We show for the first time that nongenomic and genomic effects of aldosterone are differentially dependent on activity of both AT 1a R and AT 1b R. Our data suggest that aldosterone augments AT 1 R-dependent activation of ERK1/2, JNK, and NF-κB in VSMCs. We provide mechanistic understanding and experimental in vitro support for the benefit of combination therapy with dual blockade of AT 1 R and MR to treat hypertension and progression of heart failure as reported in clinical studies and animal models.
NHS's care.data scheme is cautionary tale for safe data use, say MPs
Authors: A. O'Dowd
Journal: BMJ (2014)

Mistakes made by the government over its care.data scheme should serve as a cautionary tale in efforts to make data systems clearer and safer, MPs have said.

MPs on the House of Commons Science and Technology Committee published a report on 28 November that called on social media companies and the government to simplify terms and conditions over use of personal data.1 Millions of people globally had signed up to social media platforms such as Facebook, Twitter, and LinkedIn, said the MPs, resulting …
Lineage Specification of Parietal Epithelial Cells Requires β-Catenin/Wnt Signaling
Authors: Stephan Grouls, Diana Margarita Iglesias, Nicolas Wentzensen, Marcus Johannes Moeller, Maxime Bouchard, Rolf Kemler, Paul Goodyer, Felix Niggli, Hermann-Josef Gröne, Wilhelm Kriz, Robert Koesters
Journal: Journal of the American Society of Nephrology (2011)

β-Catenin/Wnt signaling is essential during early inductive stages of kidney development, but its role during postinductive stages of nephron development and maturation is not well understood. In this study, we used Pax8Cre mice to target β-catenin deficiency to renal epithelial cells at the late S-shaped body stage and the developing collecting ducts. The conditional β-catenin knockout mice formed abnormal kidneys and had reduced renal function. The kidneys were hypoplastic with a thin cortex; a superficial layer of tubules was missing. A high proportion of glomeruli had small, underdeveloped capillary tufts. In these glomeruli, well differentiated podocytes replaced parietal epithelial cells in Bowman's capsule; capillaries toward the outer aspect of these podocytes mimicked the formation of glomerular capillaries. Tracing nephrogenesis in embryonic conditional β-catenin knockout mice revealed that these "parietal podocytes" derived from precursor cells in the parietal layer of the S-shaped body by direct lineage switch. Taken together, these findings demonstrate that β-catenin/Wnt signaling is important during the late stages of nephrogenesis and for the lineage specification of parietal epithelial cells.
<i>Interleukin 13</i>,<i>CD14</i>, pet and tobacco smoke influence atopy in three Dutch cohorts: the allergenic study
Authors: R. W. B. Bottema, N. E. Reijmerink, M. Kerkhof, G. H. Koppelman, F. F. Stelma, J. Gerritsen, C. Thijs, B. Brunekreef, C. P. van Schayck, D. S. Postma
Journal: European Respiratory Journal (2008)

Studying gene–environment interactions may elucidate the complex origins of atopic diseases but requires large study populations. Pooling data from several cohort studies may help but may also obscure findings. Gene–environment interactions in atopy development were studied and the benefits of pooling data were evaluated. Haplotype-tagging polymorphisms in the genes interleukin (IL)13 and CD14 were genotyped in 3,062 children from the following birth cohorts: the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study; the Prevention of Asthma in Children (PREVASC) study; and the Child, Parent, Health, Focus on Lifestyle and Predisposition (KOALA) study, and tested for association with total and specific immunoglobulin (Ig)E and interaction with tobacco smoke and pet exposure at ages 1, 2, 4 and 8 yrs by analysis of variance, Chi-squared tests and regression analyses. At all ages, in IL13 , minor alleles of rs1295685 and rs20541 were significantly associated with elevated IgE levels in pooled analyses. In CD14 , the rs2569190-TT and rs2569191-CC genotypes associated with lower IgE and decreased risk of sensitisation at 4 and 8 yrs in children exposed to pets, with an opposite effect in nonexposed children. Findings for IL13 and CD14 were comparable in separate cohorts. The present study indicates that atopy is importantly influenced by interleukin 13 at age 1–8 yrs and by CD14 in interaction with pet exposure at ages 4 and 8 yrs. Additionally, pooled data improved effect estimates and genetic effects could be detected in interaction with important environmental factors.
The efficacy and safety of KL4-surfactant in preterm infants with respiratory distress syndrome.
Authors: C G Cochrane, S D Revak, T A Merritt, G P Heldt, M Hallman, M D Cunningham, D Easa, A Pramanik, D K Edwards, M S Alberts
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The present study was undertaken to determine if a synthetic peptide, KLLLLKLLLLKLLLLKLLLLK (KL4), in which K = lysine and L = leucine, in an aqueous dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and improve gas exchange in premature human infants with respiratory distress syndrome (RDS). The KL4 peptide was synthesized to resemble the amino acid pattern of surfactant protein B (SP-B). Forty-seven infants with RDS were treated within 4 h of birth with the KL4-peptide/phospholipid mixture, called KL4-Surfactant. The average arterial-to-alveolar oxygen tension ratios (a/A O2) of 39 patients included in efficacy analyses rose from pretreatment values of 0.14 +/- 0.02 (mean +/- SEM) to 0.40 +/- 0.04 (normal value > or = 0.40) by 12 h of age. Mean airway pressures and oxygenation index values fell concomitantly, and expansion of the lungs was observed on radiographs. The median duration of mechanical ventilation was 5.0 d. Of the 39 included infants, 29 required only a single dose. Radiographic data indicate that those patients requiring a second instillation of KL4-Surfactant but not showing a sustained rise in a/A O2 ratios did, in fact, exhibit expansion of alveoli in the lung. There were no RDS-related deaths; the incidence of complications was no higher than found in other comparable published studies. The data demonstrate that the synthetic peptide, KL4, which mimics the hydrophobic and hydrophilic pattern of SP-B, when formulated in an aqueous dispersion with the phospholipids DPPC and POPG, creates a strong and durable surfactant activity as judged by expansion of pulmonary alveoli and improvement of gas exchange in infants with RDS.
Evidence for double resistance to permethrin and malathion in head lice: reply from authors
Authors: A.M.R. Downs, K.A. Stafford, I. Harvey, G.C. Coles
Journal: British Journal of Dermatology (2000)

Journal Article Evidence for double resistance to permethrin and malathion in head lice: reply from authors Get access A.M.R. Downs, A.M.R. Downs Department of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar K.A. Stafford, K.A. Stafford Veterinary Science and Search for other works by this author on: Oxford Academic Google Scholar I. Harvey, I. Harvey Department of Dermatology,Public Health, University of Bristol, Bristol BS2 8HW, U.K. Search for other works by this author on: Oxford Academic Google Scholar G.C. Coles G.C. Coles Veterinary Science and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 5, 1 May 2000, Page 1067, https://doi.org/10.1046/j.1365-2133.2000.03515.x Published: 01 May 2000
Prevalence of Abnormal Lipid Profiles and the Relationship With the Development of Microalbuminuria in Adolescents With Type 1 Diabetes
Authors: M. Loredana Marcovecchio, R. Neil Dalton, A. Toby Prevost, Carlo L. Acerini, Timothy G. Barrett, Jason D. Cooper, Julie Edge, Andrew Neil, Julian Shield, Barry Widmer, John A. Todd, David B. Dunger
Journal: Diabetes Care (2009)

OBJECTIVE To explore the prevalence of lipid abnormalities and their relationship with albumin excretion and microalbuminuria in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS The study population comprised 895 young subjects with type 1 diabetes (490 males); median age at the baseline assessment was 14.5 years (range 10–21.1), and median diabetes duration was 4.8 years (0.2–17). A total of 2,194 nonfasting blood samples were collected longitudinally for determination of total cholesterol, LDL cholesterol, HDL cholesterol, TG, and non-HDL cholesterol. Additional annually collected data on anthropometric parameters, A1C, and albumin-to-creatinine ratio (ACR) were available. RESULTS Total cholesterol, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol were higher in females than in males (all P &amp;lt; 0.001). A significant proportion of subjects presented sustained lipid abnormalities during follow-up: total cholesterol &amp;gt;5.2 mmol/l (18.6%), non-HDL cholesterol &amp;gt;3.4 mmol/l (25.9%), TG &amp;gt;1.7 mmol/l (20.1%), and LDL cholesterol &amp;gt;3.4 mmol/l (9.6%). Age and duration were significantly related to all lipid parameters (P &amp;lt; 0.001); A1C was independently related to all parameters (P &amp;lt; 0.001) except HDL cholesterol, whereas BMI SD scores were related to all parameters (P &amp;lt; 0.05) except total cholesterol. Total cholesterol and non-HDL cholesterol were independently related to longitudinal changes in ACR (B coefficient ± SE): 0.03 ± 0.01/1 mmol/l, P = 0.009, and 0.32 ± 0.014/1 mmol/l, P = 0.02, respectively. Overall mean total cholesterol and non-HDL cholesterol were higher in microalbuminuria positive (n = 115) than in normoalbuminuric subjects (n = 780): total cholesterol 4.7 ± 1.2 vs. 4.5 ± 0.8 mmol/l (P = 0.04) and non-HDL cholesterol 3.2 ± 1.2 vs. 2.9 ± 0.8 mmol/l (P = 0.03). CONCLUSIONS In this longitudinal study of adolescents with type 1 diabetes, sustained lipid abnormalities were related to age, duration, BMI, and A1C. Furthermore, ACR was related to both total cholesterol and non-HDL cholesterol, indicating a potential role in the pathogenesis of diabetic nephropathy.
Pulmonary hypertension, systemic lupus erythematosus, and the contraceptive pill.
Authors: G R Todd, E J McAteer, C M Jack, M Haire, S D Roberts, K D Buchanan
Journal: Annals of the Rheumatic Diseases (1985)

Pulmonary hypertension in systemic lupus erythematosus (SLE) in the absence of chronic parenchymal lung disease or pulmonary emboli is rare. We report such a case with an acute and rapidly progressive onset of symptoms in a patient who had started taking the contraceptive pill eight months previously.This article presents a case of pulmonary hyptertension in systemic lupus erythematosus in the absence of chronic parenchymal lung disease or pulmonary emboli. The patient, a 22-year old woman, experienced a rapidly progressive onset of symptoms 9 months after beginning oral contraceptive (OC) use for the 1st time. The mechanism of this type of pulmonary hypertension in lupus patients is unclear, but it may be caused by sustained vasoconstriction. In this case, it seems likely that OC use initiated the hypertensive episode. Before commencing OC use, the patient completed a normal pregnancy; the right ventricular hypertrophy observed at presentation is considered to have developed shortly after starting the pill. There are no similar cases in the literature.
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance – Part 35
Authors: N Lewis, M Keil, M K Ranchordas, L M Burke, S J Stear, L M Castell
Journal: British Journal of Sports Medicine (2012)

In part 35, we continue with S, and turn our attention to selenium, serine and sibutramine. Selenium is a trace element that is essential for health, whereas serine is a non-essential amino acid. However, to date, neither has been shown to be a necessary nutritional supplement for athletes to consume in addition to habitual dietary intake sources, as deficiency of both is unlikely to occur. By contrast, sibutramine is a weight-loss agent which was banned as a stimulant several years ago.

### N Lewis

Selenium (Se) is a trace element essential for human health, and deficiency is rare. Its essentiality is achieved through the functioning of 25 known selenoproteins in the form of selenocysteine, with enzymatic activities being assigned to 12 of the 25 proteins.1 Selenium is most well known as an antioxidant through its incorporation of glutathione peroxidase (GPx) of which there are several forms. Se deficiency gives rise to cardiomyopathy, skeletal muscle myopathy, osteoarthropathy, reduced immune function, certain cancers and viral disease.2 Skeletal muscle constitutes the main body pool of Se, comprising 50% of total body Se.3 The assessment of whole blood Se, plasma Se and red blood cell Se provides a less invasive method for the assessment of skeletal muscle Se content.3

The Se content of soil varies considerably depending on geographical locations.2 Se is found in various foods: meat and offal, seafood, cereals, nuts; with milk, dairy, fruit and vegetables being particularly low.

Selenium toxicity occurs at intakes >900 ug/d; Se deficiency …
Effect of intravenous immunoglobulin on inhibition of fibrinogen binding to platelets by sera from patients with immune thrombocytopenia
Authors: Mikio Kamiyama, Yuichi Yoshimura, Karen Chen, Yale S. Arkel
Journal: American Journal of Hematology (1993)

Abstract We previously described an ELISA to measure the inhibition of platelet glycoprotein llb/IIIa (GPIIb/IIIa) binding to fibrinogen due to immune complexes and/or anti‐platelet antibodies from patients with immune thrombocytopenia (ITP) or HIV‐related ITP. Circulating immune complexes (CIC) were the main factor in the inhibition of GPIIb/IIIa binding to fibrinogen in HIV‐related ITP, whereas in non‐HIV ITP, inhibition was only partially due to CIC; anti‐platelet antibodies specific to GPIIIa were also shown to play a role. In this study, we correlated the rise in the platelet count after intravenous immunoglobulin (IVIG) infusion with the decrease in inhibition of fibrinogen binding to GPIIb/IIIa by the sera of patients with ITP and HIV‐related ITP. In the majority of the patients' sera tested, as the platelet count increased following the administration of IVIG, the degree of inhibition of GPIIb/IIIa binding to fibrinogen decreased. We also observed a decrease and/or disappearance of the antibodies specific to GPIIb and/or GPIIIa after IVIG administration. In HIV‐seronegative ITP patients, the decrease or disappearance of anti‐platelet antibodies directly correlated with the decreased inhibition of GPIIb/IIIa binding to fibrinogen by the 2% PEG supernatants of sera which contained anti‐platelet antibodies. These findings suggest that IVIG directly affects the binding of CIC and anti‐platelet antibodies to platelets and thereby improves platelet survival. Our results also suggest that the anti‐idiotypic effect may contribute to IVIG's therapeutic action. In contrast, in the HIV‐seropositive group, the decreased inhibition by PEG precipitates after IVIG administration was more strongly associated with an increase in the platelet count. © 1993 Wiley‐Liss, Inc.
Altered erythrocyte membrane phosphorylation in psoriasis
Authors: R. KUMAR, VIRGINIA C. WEISS, D.P. WEST, LAURA A. CHIERO
Journal: British Journal of Dermatology (1983)

Autophosphorylation by [gamma-32P]ATP of erythrocyte membranes from controls, psoriatic patients and patients with skin disorders other than psoriasis was compared by polyacrylamide gel electrophoresis. Compared with controls, membranes from psoriatic patients showed significantly less 32P incorporation in the band 2 region (nomenclature of Fairbanks et al., 1971). In addition, psoriasis and some of the other skin diseases examined displayed decreased phosphorylation in the region of bands 2.9-3 and 4.5-4.8. A new polypeptide band in the 18-20,000 dalton region was also observed in the diseases examined. Altered epidermal plasma membranes have been implicated in the pathogenesis of psoriasis, and our findings suggest the defective plasma membranes may be a generalized phenomenon in this disorder.