tbuckley/cabot-search huggingface dataset:
Drosophila suzukii: The Genetic Footprint of a Recent, Worldwide Invasion
Authors: Jeffrey R. Adrion, Athanasios Kousathanas, Marta Pascual, Hannah J. Burrack, Nick M. Haddad, Alan O. Bergland, Heather Machado, Timothy B. Sackton, Todd A. Schlenke, Masayoshi Watada, Daniel Wegmann, Nadia D. Singh
Journal: Molecular Biology and Evolution (2014)

Native to Asia, the soft-skinned fruit pest Drosophila suzukii has recently invaded the United States and Europe. The eastern United States represents the most recent expansion of their range, and presents an opportunity to test alternative models of colonization history. Here, we investigate the genetic population structure of this invasive fruit fly, with a focus on the eastern United States. We sequenced six X-linked gene fragments from 246 individuals collected from a total of 12 populations. We examine patterns of genetic diversity within and between populations and explore alternative colonization scenarios using approximate Bayesian computation. Our results indicate high levels of nucleotide diversity in this species and suggest that the recent invasions of Europe and the continental United States are independent demographic events. More broadly speaking, our results highlight the importance of integrating population structure into demographic models, particularly when attempting to reconstruct invasion histories. Finally, our simulation results illustrate the general challenge in reconstructing invasion histories using genetic data and suggest that genome-level data are often required to distinguish among alternative demographic scenarios.
Bacterial biofilm within diseased pancreatic and biliary tracts
Authors: A Swidsinski
Journal: Gut (2005)

<b>Background:</b> Bacterial community structures in human pancreatic and biliary tracts were evaluated. <b>Methods:</b> Gall bladder stones from 153 patients, 20 gall bladder walls, six common duct stones, 52 biliary stents, 21 duodenal biopsies, nine pancreatic duct biopsies, and five bile ducts were investigated using fluorescence in situ hybridisation (FISH) with ribosomal RNA targeted Cy3/Cy5 (carbocyanine) labelled oligonucleotide probes. <b>Result:</b> Duodenal, gall bladder, and bile duct walls were free of bacteria. A dense multispecies bacterial biofilm was present within the pancreatic duct of patients with calcific pancreatitis and within biliary stents, irrespective of diagnosis. The concentration, density, and amenability of the biofilm to FISH and DNA staining declined progressively with the grade of stent occlusion. The lowest detectable bacterial concentrations were found by FISH in completely occluded stents and brown/mixed gall stones. Bacteria were not detectable with FISH in cholesterol gall stones. <b>Conclusions:</b> A wide range of different branches and groups of bacteria participate in the development of biofilms on the surfaces of foreign bodies, such as biliary stents, mixed gall stones, or calcific pancreatic ducts, but not on the surface of pure cholesterol gall stones. Occlusion of stents leads to progressive extinction of the biofilm and mummification of its components. Deposition of cholesterol or other substances within the biofilm matrix may be a novel mechanism of host defence against bacteria present in these biofilms.
Pharmacogenetics and Human Molecular Genetics of Opiate and Cocaine Addictions and Their Treatments
Authors: Mary Jeanne Kreek, Gavin Bart, Charles Lilly, K. Steven Laforge, David A. Nielsen
Journal: Pharmacological Reviews (2005)

Opiate and cocaine addictions are major social and medical problems that impose a significant burden on society. Despite the size and scope of these problems, there are few effective treatments for these addictions. Methadone maintenance is an effective and most widely used treatment for opiate addiction, allowing normalization of many physiological abnormalities caused by chronic use of short-acting opiates. There are no pharmacological treatments for cocaine addiction. Epidemiological, linkage, and association studies have demonstrated a significant contribution of genetic factors to the addictive diseases. This article reviews the molecular genetics and pharmacogenetics of opiate and cocaine addictions, focusing primarily on genes of the opioid and monoaminergic systems that have been associated with or have evidence for linkage to opiate or cocaine addiction. This evidence has been marshaled either through identification of variant alleles that lead to functional alterations of gene products, altered gene expression, or findings of linkage or association studies. Studies of polymorphisms in the μ opioid receptor gene, which encodes the receptor target of some endogenous opioids, heroin, morphine, and synthetic opioids, have contributed substantially to knowledge of genetic influences on opiate and cocaine addiction. Other genes of the endogenous opioid and monoaminergic systems, particularly genes encoding dopamine β-hydroxylase, and the dopamine, serotonin, and norepinephrine transporters have also been implicated. Variants in genes encoding proteins involved in metabolism or biotransformation of drugs of abuse and also of treatment agents are reviewed.
Oral Heparin Prevents Neointimal Hyperplasia After Arterial Injury
Authors: Frederick G.P. Welt, T. Cooper Woods, Elazer R. Edelman
Journal: Circulation (2001)

Background — In animal models, heparin delivered as a continuous intravenous infusion or via frequent (BID) subcutaneous dosing inhibits neointimal hyperplasia after balloon injury or stent implantation. However, human trials of subcutaneous heparin after percutaneous intervention have proven ineffective against restenosis. It may be that these failures are due to unfavorable heparin pharmacokinetics. Recently, the drug delivery agent sodium N -[8-(2-hydroxybenzoyl)amino] caprylate (SNAC) has been found to facilitate the gastric absorption of heparin. Methods and Results — To investigate the effects of orally delivered heparin on neointimal hyperplasia after varying forms of arterial injury, 57 New Zealand White rabbits underwent iliac artery balloon dilatation. In half of the rabbits, endovascular stents were implanted and heparin was delivered through a variety of methods. Arteries were harvested at 14 days. Neointimal area was assessed with computer-aided morphometry. After balloon injury, both intravenous (0.3 mg/kg per hour) and oral heparin (90 mg/kg BID) effectively inhibited neointimal hyperplasia (0.11±0.02 and 0.09±0.07 mm 2 , respectively, versus 0.16±0.06 mm 2 in control; P &lt;0.05). After stent implantation, intravenous administration of heparin (0.3 mg/kg per hour) effectively inhibited neointimal growth (0.35±0.05 mm 2 versus 0.51±0.09 mm 2 in control; P &lt;0.05), but oral heparin at 90 mg/kg BID and 180 mg/kg BID (0.48±0.04 and 0.49±0.08 mm 2 , respectively; P =NS versus control) did not. A dose of 120 mg/kg TID, however, was effective (0.40±0.10 mm 2 ; P &lt;0.05 versus control). Conclusions — These data suggest that oral heparin may be an effective therapy against restenosis after percutaneous intervention. Stented arteries required higher and more frequent dosing for efficacy. These data suggest that differences in the type of vascular injury must be considered in the design of drug delivery.
An evaluation of the dynamic qualities of isometric grip strength.
Authors: P S Helliwell, A Howe, V Wright
Journal: Annals of the Rheumatic Diseases (1988)

A strain gauged torsion dynamometer linked to a microprocessor was used to assess the dynamic qualities of isometric grip strength in patients with rheumatic diseases. Maximum grip strength, time to maximum grip, and percentage fatigue provide independent information on the grip. Time to maximum grip does not appear to be an objective correlate of subjective stiffness. The usefulness of these dynamic variables for the assessment of stiffness appears limited in arthritic disease, where pain may interfere with the maximum voluntary effort of the test.
A Comparison of Lipid and Glycemic Effects of Pioglitazone and Rosiglitazone in Patients With Type 2 Diabetes and Dyslipidemia
Authors: Ronald B. Goldberg, David M. Kendall, Mark A. Deeg, John B. Buse, Anthony J. Zagar, Jane A. Pinaire, Meng H. Tan, Mehmood A. Khan, Alfonso T. Perez, Scott J. Jacober
Journal: Diabetes Care (2005)

OBJECTIVE—Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone. RESEARCH DESIGN AND METHODS—We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals. RESULTS—Triglyceride levels were reduced by 51.9 ± 7.8 mg/dl with pioglitazone, but were increased by 13.1 ± 7.8 mg/dl with rosiglitazone (P &amp;lt; 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 ± 0.5 vs. 2.4 ± 0.5 mg/dl; P &amp;lt; 0.001) and the increase in LDL cholesterol was less (12.3 ± 1.6 vs. 21.3 ± 1.6 mg/dl; P &amp;lt; 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P &amp;lt; 0.001). LDL particle size increased more with pioglitazone (P = 0.005). CONCLUSIONS—Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.
Clinical and dosimetric factors associated with a prolonged feeding tube requirement in patients treated with chemoradiotherapy (CRT) for head and neck cancers
Authors: A.S. Gokhale, B.T. McLaughlin, J.C. Flickinger, S. Beriwal, D.E. Heron, R.L. Ferris, J. Johnson, M.K. Gibson, A. Argiris, R.P. Smith
Journal: Annals of Oncology (2009)

Patients treated with chemoradiotherapy (CRT) for head and neck cancers often require feeding tubes (FTs) due to toxicity. We sought to identify factors associated with a prolonged FT requirement.We retrospectively reviewed 80 patients treated with CRT for head and neck cancers. The pharyngeal constrictors (PCs), supraglottic larynx (SGL), and glottic larynx (GL) were contoured and the mean radiation doses and the volumes of each receiving >40, 50, 60, and 70 Gy (V40, V50, V60, and V70) were determined.A total of 33 of 80 patients required a FT either before or during the course of CRT. Fifteen patients required the FT for > or = 6 months. On univariate analysis, significant factors associated with a prolonged FT requirement were mean PC dose, PC-V60, PC-V70, SGL dose, SGL-V70, and advanced T3-T4 disease. Multivariate analyses found both PC-V70 and T3-T4 disease as significant factors .The proportions of patients requiring a FT > or = 6 months were 8% and 28% for treatment plans with PC-V70 <30% and > or = 30%, respectively.Increased radiation dose to the PCs is associated with a higher risk of a prolonged FT need. Dose sparing of the PC muscles may reduce this risk.
Where is SARS now?
Authors: P J M Openshaw
Journal: Thorax (2003)

The WHO and respective governments must be praised for their incisive and energetic leadership which has greatly limited the impact of SARS, but we can only guess what will happen next winter.

In February 2003 the World Health Organisation (WHO) received alarming news of antibiotic resistant community acquired pneumonia in Vietnam, Hong Kong, and Singapore of apparent viral origin. It named the disease “severe acute respiratory syndrome” (SARS) and issued urgent advice directed at reducing transmission and spread (http://www.who.int/csr/media/sars_wha.pdf). With unprecedented speed, the probable cause was identified as a novel coronavirus, now named SARS CoV. The imposition of draconian public health measures appears to have brought the disease under control, but there is still concern that, with over 8000 suspected or confirmed cases and contact networks reaching millions, there is every prospect that the disease will become endemic in China or spread to areas of the world in which it cannot be contained.

Although co-infection with SARS CoV and another agent has not been ruled out as the cause of SARS (particularly in “superspreaders” causing numerous secondary cases), SARS CoV alone seems likely to be the cause of most cases of SARS and can reproduce the disease in non-human primates.1,2 Coronaviruses have the distinction of containing the largest genome of all known RNA viruses. They are widespread throughout …
How to approach delusional infestation
Authors: P. Lepping, M. Huber, R. W. Freudenmann
Journal: BMJ (2015)

#### The bottom line

Delusional infestation (previously also known as delusional parasitosis or Ekbom’s syndrome) is a rare disorder, but it commonly poses disproportionate practical problems to healthcare systems.1 It is characterised by a patient’s fixed belief that his or her skin, body, or immediate environment is infested by small, living (or less often inanimate) pathogens despite the lack of any medical evidence for this.1 Delusional infestation is neither a single disease nor a single diagnostic entity. The classic form, primary delusional infestation, develops without any known cause or underling illness and meets criteria for a persistent delusional disorder (ICD-10 (international classification of diseases, 10th revision)) or delusional disorder somatic type (DSM-5 ( Diagnostic and Statistical Manual of Mental Disorders , fifth edition)). Approximately 60% of patients, however, have secondary forms of delusional infestation2 that occur in the context of substance misuse (such as cocaine, amphetamines, cannabis), dopaminergic medications, antibiotics, or during physical or psychiatric illnesses (such as delirium, dementia, depression, schizophrenia, stroke, and other medical conditions that affect the brain or cause pruritus).1 2

The neurobiology of delusional infestation is not fully understood. Studies point to dysfunction or structural brain damage in the frontal cortex, …
Apoptosis and the kidney.
Authors: J Savill
Journal: Journal of the American Society of Nephrology (1994)

Apoptosis is a programmed form of cell death mediating the precisely controlled deletion of "unwanted" cells. This review discusses the key features of this cell death program, emphasizing that apoptosis is regulated by factors extrinsic and intrinsic to the dying cell. Furthermore, because apoptosis leads to the swift phagocytic clearance of intact cells, tissues are protected against the noxious effect of cell contents. Apoptosis occurs in the developing and adult kidney, and nephrologists now need to consider whether abnormalities of this program may contribute to renal disease. Evidence suggests that such defects could contribute to developmental abnormalities including polycystic disease, induce autoimmunity to renal tissue, and exacerbate renal inflammation and scarring. Finally, apoptosis may offer new avenues for therapy.
NIH promotes use of lower cost drugs for hypertension
Authors: David Spurgeon
Journal: BMJ (2004)

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Dr Paul Whelton is worried because doctors are not implementing trial findings 

Credit: IAN JACKSON/WESTERN MORNING NEWS

The US National Institutes of Health is planning to use some 600 prominent doctors in the United States, Canada, and Puerto Rico to promote the use of lower cost drugs to treat hypertension.

Currently, the cost of antihypertensive drugs in the United States amounts to about $15bn (£8bn; €12bn), accounting for 10% of the country's total spending on drugs. The institutes' $3.7m initiative is the first time it has tried to promote a change in …

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Differential clinical outcomes after 1 year versus 5 years in a randomised comparison of zotarolimus-eluting and sirolimus-eluting coronary stents (the SORT OUT III study): a multicentre, open-label, randomised superiority trial
Authors: Michael Maeng, Hans Henrik Tilsted, Lisette Okkels Jensen, Lars Romer Krusell, Anne Kaltoft, Henning Kelbæk, Anton B Villadsen, Jan Ravkilde, Knud Nørregaard Hansen, Evald Høj Christiansen, Jens Aarøe, Jan Skov Jensen, Steen Dalby Kristensen, Hans Erik Bøtker, Leif Thuesen, Morten Madsen, Per Thayssen, Henrik Toft Sørensen, Jens Flensted Lassen
Journal: The Lancet (2014)
Screening for Cognitive Impairment in Older Adults: U.S. Preventive Services Task Force Recommendation Statement
Authors: Virginia A. Moyer
Journal: Annals of Internal Medicine (2014)

Description: Update of the 2003 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for dementia. Methods: The USPSTF reviewed the evidence on the benefits, harms, and sensitivity and specificity of screening instruments for cognitive impairment in older adults and the benefits and harms of commonly used treatment and management options for older adults with mild cognitive impairment or early dementia and their caregivers. Population: This recommendation applies to universal screening with formal screening instruments in community-dwelling adults in the general primary care population who are older than 65 years and have no signs or symptoms of cognitive impairment. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for cognitive impairment. (I statement)
Scanning electron microscope studies of solar elastosis
Authors: TAKUO TSUJI
Journal: British Journal of Dermatology (1980)

Scanning electron microscope findings of solar elastosis were compared with those of normal dermis in specimens digested by hyaluronidase and by autoclaving. Solar elastosis showed amorphous masses and broad fibres with irregular shapes and sizes in specimens digested by hyaluronidase, while it showed only fibrous structures in those after autoclaving. It is suggested that the origin of solar elastosis is elastic tissue.
ZAP-70 expression in acute lymphoblastic leukemia: association with the E2A/PBX1 rearrangement and the pre-B stage of differentiation and prognostic implications
Authors: Sabina Chiaretti, Anna Guarini, Maria Stefania De Propris, Simona Tavolaro, Stefania Intoppa, Antonella Vitale, Simona Iacobelli, Loredana Elia, Cristina Ariola, Jerome Ritz, Robin Foà
Journal: Blood (2005)
Structural mutation affecting intracellular transport and cell surface expression of murine class II molecules.
Authors: I J Griffith, N Nabavi, Z Ghogawala, C G Chase, M Rodriguez, D J McKean, L H Glimcher
Journal: The Journal of Experimental Medicine (1988)

We have selected Ia variants from the Ia+ (H-2d) M12.4.1 B cell lymphoma that are negative on the cell surface for one or both Ia isotypes. The molecular analysis of two such independently selected cell lines, M12.A2 and M12.C3, is reported here. This analysis revealed that the genes encoding Ad beta (M12.A2) and Ed beta (M12.C3) contained identical single-nucleotide transitions that resulted in the substitution of Ser (mutant) for Asn (wild-type) at residue 82/83 of the extracellular NH2-terminal (membrane distal) beta 1 domain. This conservative substitution caused a cytoplasmic accumulation of I-A or I-E molecules in the respective cell line although predicted secondary-structure analysis suggests a minimal effect on protein conformation. Thus, the mutation appears to have either created a negative signal that stops transport or eliminated a positive signal that is required for transport and targeting to the cell surface.
Phylogeographic variation in recombination rates within a global clone of methicillin-resistant Staphylococcus aureus
Authors: Santiago Castillo-Ramírez, Jukka Corander, Pekka Marttinen, Mona Aldeljawi, William P Hanage, Henrik Westh, Kit Boye, Zeynep Gulay, Stephen D Bentley, Julian Parkhill, Matthew T Holden, Edward J Feil
Journal: Genome biology (2012)

Abstract Background Next-generation sequencing (NGS) is a powerful tool for understanding both patterns of descent over time and space (phylogeography) and the molecular processes underpinning genome divergence in pathogenic bacteria. Here, we describe a synthesis between these perspectives by employing a recently developed Bayesian approach, BRATNextGen, for detecting recombination on an expanded NGS dataset of the globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clone ST239. Results The data confirm strong geographical clustering at continental, national and city scales and demonstrate that the rate of recombination varies significantly between phylogeographic sub-groups representing independent introductions from Europe. These differences are most striking when mobile non-core genes are included, but remain apparent even when only considering the stable core genome. The monophyletic ST239 sub-group corresponding to isolates from South America shows heightened recombination, the sub-group predominantly from Asia shows an intermediate level, and a very low level of recombination is noted in a third sub-group representing a large collection from Turkey. Conclusions We show that the rapid global dissemination of a single pathogenic bacterial clone results in local variation in measured recombination rates. Possible explanatory variables include the size and time since emergence of each defined sub-population (as determined by the sampling frame), variation in transmission dynamics due to host movement, and changes in the bacterial genome affecting the propensity for recombination.
LEUKOCYTES AND INTERFERON IN THE HOST RESPONSE TO VIRAL INFECTIONS
Authors: Lowell A. Glasgow
Journal: The Journal of Experimental Medicine (1965)

1. Investigation of the role of leukocytes in vaccinia virus infection is reported in an in vitro model, in the absence of an immune response. 2. Mouse leukocytes were shown to be capable of inhibiting the progression of vaccinia virus infection in primary mouse embryo fibroblast cultures. The degree of protection varied from slowing of spread of infection to complete control of the infection with eventual elimination of detectable virus and recovery of the culture. 3. Interferon production by leukocytes is thought to be an important factor in the observed protective effect.