tbuckley/cabot-search huggingface dataset:
Serum Levels of Receptors for Advanced Glycation End Products in Normal-Weight and Obese Children Born Small and Large for Gestational Age
Authors: Valentina Chiavaroli, Ebe D’Adamo, Cosimo Giannini, Tommaso de Giorgis, Stefania De Marco, Francesco Chiarelli, Angelika Mohn
Journal: Diabetes Care (2012)

OBJECTIVE To assess potential alterations in soluble and endogenous secretory receptors for advanced glycation end products (sRAGE and esRAGE) in normal-weight (NW) and obese (Ob) children born small (SGA) and large (LGA) compared with appropriate for gestational age (AGA) subjects and to explore if birth weight (BW), insulin resistance (IR), and obesity represent independent risk factors. RESEARCH DESIGN AND METHODS We categorized 130 prepubertal children into six groups according to BW and obesity and evaluated sRAGE, esRAGE, and homeostasis model assessment of IR. RESULTS sRAGE and esRAGE were lower in Ob SGA and LGA children than Ob AGA subjects (all P &amp;lt; 0.05), and in NW SGA and LGA children than NW AGA subjects (all P &amp;lt; 0.05). Interestingly, BW and IR were significantly and independently related to RAGE. CONCLUSIONS sRAGE and esRAGE are decreased in SGA and LGA children, and BW and IR seem to play an important role in the reduction of RAGE.
Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms
Authors: Fredrik Barrenäs, Sreenivas Chavali, Alexessander Alves, Lachlan Coin, Marjo-Riitta Jarvelin, Rebecka Jörnsten, Michael A Langston, Adaikalavan Ramasamy, Gary Rogers, Hui Wang, Mikael Benson
Journal: Genome biology (2012)

Complex diseases are associated with altered interactions between thousands of genes. We developed a novel method to identify and prioritize disease genes, which was generally applicable to complex diseases. We identified modules of highly interconnected genes in disease-specific networks derived from integrating gene-expression and protein interaction data. We examined if those modules were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies. First, we analyzed publicly available gene expression microarray and genome-wide association study (GWAS) data from 13, highly diverse, complex diseases. In each disease, highly interconnected genes formed modules, which were significantly enriched for genes harboring disease-associated SNPs. To test if such modules could be used to find novel genes for functional studies, we repeated the analyses using our own gene expression microarray and GWAS data from seasonal allergic rhinitis. We identified a novel gene, FGF2, whose relevance was supported by functional studies using combined small interfering RNA-mediated knock-down and gene expression microarrays. The modules in the 13 complex diseases analyzed here tended to overlap and were enriched for pathways related to oncological, metabolic and inflammatory diseases. This suggested that this union of the modules would be associated with a general increase in susceptibility for complex diseases. Indeed, we found that this union was enriched with GWAS genes for 145 other complex diseases. Modules of highly interconnected complex disease genes were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies.
Oral Preexposure Prophylaxis for HIV — Another Arrow in the Quiver?
Authors: Nelson L. Michael
Journal: New England Journal of Medicine (2010)

Despite the growing global access to life-extending antiretroviral drugs for the more than 33 million persons living with human immunodeficiency virus (HIV) infection, approximately 7000 new infections occur daily. This alarming number speaks to the critical need for effective approaches to HIV prevention.1 Early approaches to prevention were limited to the consistent use of barrier methods during sex,2 a reduction in the prevalence of HIV in the blood supply, behavior modification, postexposure prophylaxis, and awareness of HIV-infection status. Antiretroviral drugs that were provided to pregnant women with HIV infection were shown to dramatically reduce the risk of perinatal transmission,3 with . . .
Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus.
Authors: A R Waldorf, N Ruderman, R D Diamond
Journal: Journal of Clinical Investigation (1984)

To assess the influence of diabetes mellitus in predisposing to pulmonary mucormycosis, a murine model of streptozotocin-induced diabetes was used. Intranasal inoculation of Rhizopus oryzae into diabetic mice resulted in mucormycotic infection with histopathology resembling pulmonary mucormycosis observed in humans. There was no mortality nor infection in inoculated normal mice. Diabetic mice had fatal infections caused by R. oryzae but significantly reduced mortality following inoculation with Aspergillus fumigatus. These findings reflect the specific enhanced susceptibility to mucormycosis observed in human diabetics. Normal bronchoalveolar macrophages formed part of an efficient defense against R. oryzae by inhibiting germination, the critical step in the conversion of R. oryzae to its tissue invasive phase. Bronchoalveolar macrophages inhibited spore germination in vitro and appeared to help prevent germination in vivo. In contrast, spore germination occurred in diabetic mice following intranasal inoculation. Diabetic bronchoalveolar macrophages had a decreased ability to attach to hyphae. In diabetic mice, bronchoalveolar macrophages could damage spores or hyphae of R. oryzae, but serum factors appeared to both promote spore germination and impair attachment of macrophages to spores. This murine model of diabetes mellitus provides an opportunity for evaluation of the relative importance of cell and serum-mediated host factors in the pathogenesis of mucormycosis.
LOCALIZATION OF CONSCIOUSNESS AND EMOTION
Authors: Leland B. Alford
Journal: American Journal of Psychiatry (1933)

A series of cases exhibiting lesions in different parts of the brain were studied for any changes caused in consciousness and emotion or what seemed to be the physiological counterparts of these faculties. In no lesion of the right hemisphere (in hight-handed persons) was any consistent disturbance in these two faculties observed. Not one of 33 cases of left hemiplegia exhibited confusion and only three an equivocal emotional instability. Lesions of the frontal, parietal, occipital and temporal lobes on the left similarly caused no definite disorder of consciousness and emotion. In an extensive vascular lesion of Head's speech zone, despite jargon asphasia and apraxia, the patient remained generally wellbalanced, alert to happenings about him, and capable of appreciating their general import. Hence the conclusion that emotion and consciousness (in the sense of awareness alone) were not affected and therefore do not reside in this part of the cortex. It was eminently in the right hemiplegias, which generally arise from left capsular injuries, that definite and permanent confusion of consciousness was found (27 out of 55 cases of old hemiplegia). It seems, therefore, that an area somewhere in the left base is concerned with the maintenance of awareness. In these same right hemiplegias and in other lesions that certainly or inferentially affect basal structures directly or indirectly were found restlessness, irritability, delirium and other forms of instability, thus indicating that emotion is localized in the base and possibly is confined to the left side. All the conclusions are regarded as tentative and subject to revision in the light of further evidence. The method of following psychological faculties through a series of brain injuries is believed to be a useful one and worthy of wider employment.
Costs and benefits of statistical significance tests
Authors: Michael G. Shafto
Journal: Behavioral and Brain Sciences (1998)

Chow's book provides a thorough analysis of the confusing array of issues surrounding conventional tests of statistical significance. This book should be required reading for behavioral and social scientists. Chow concludes that the null-hypothesis significance-testing procedure (NHSTP) plays a limited, but necessary, role in the experimental sciences. Another possibility is that – owing in part to its metaphorical underpinnings and convoluted logic – the NHSTP is declining in importance in those few sciences in which it ever played a role.
Tetracycline therapy targets intracellular bacteria in the filarial nematode Litomosoides sigmodontis and results in filarial infertility
Authors: Achim Hoerauf, Kerstin Nissen-Pähle, Christel Schmetz, Kim Henkle-Dührsen, Mark L. Blaxter, Dietrich W. Büttner, Michaela Y. Gallin, Khaled M. Al-Qaoud, Richard Lucius, Bernhard Fleischer
Journal: Journal of Clinical Investigation (1999)

Intracellular bacteria have been described in several species of filarial nematodes, but their relationships with, and effects on, their nematode hosts have not previously been elucidated. In this study, intracellular bacteria were observed in tissues of the rodent parasite Litomosoides sigmodontis by transmission electron microscopy and by immunohistochemistry using antiendobacterial heat shock protein-60 antisera. Molecular phylogenetic analysis of the bacterial 16S ribosomal RNA gene, isolated by PCR, showed a close relationship to the rickettsial Wolbachia endobacteria of arthropods and to other filarial intracellular bacteria. The impact of tetracycline therapy of infected rodents on L. sigmodontis development was analyzed in order to understand the role(s) these bacteria might play in filarial biology. Tetracycline therapy, when initiated with L. sigmodontis infection, eliminated the bacteria and resulted in filarial growth retardation and infertility. If initiated after microfilarial development, treatment reduced filarial fertility. Treatment with antibiotics not affecting rickettsial bacteria did not inhibit filarial development. Acanthocheilonema viteae filariae were shown to lack intracellular bacteria and to be insensitive to tetracycline. These results suggest a mutualistic interaction between the intracellular bacteria and the filarial nematode. Investigation of such a mutualism in endobacteria-containing human filariae is warranted for a potential chemotherapeutic exploitation.
Reevaluation of the role of HDL in the anticoagulant activated protein C system in humans
Authors: Cecilia Oslakovic, Eva Norstrøm, Björn Dahlbäck
Journal: Journal of Clinical Investigation (2010)

HDL has anti-atherogenic properties, and plasma levels of HDL cholesterol correlate inversely with risk of coronary artery disease. HDL reportedly functions as a cofactor to the anticoagulant activated protein C (APC) in the degradation of factor Va (FVa). The aim of the present study was to elucidate the mechanism by which HDL functions as cofactor to APC. Consistent with a previous report, HDL isolated from human plasma by ultracentrifugation was found to stimulate APC-mediated degradation of FVa. However, further purification of HDL by gel filtration revealed that the stimulating activity was not a property of HDL. Instead, the stimulating activity eluted completely separately from HDL in the high-molecular-weight void volume fractions. The active portion of these fractions stimulated FVa degradation by APC and supported the assembly of factor Xa and FVa into a functional prothrombinase complex. Both the procoagulant and anticoagulant activities were blocked by addition of annexin V, suggesting that the active portion was negatively charged phospholipid membranes. These results demonstrate that HDL does not stimulate the APC/protein S effect and that the activity previously reported to be a property of HDL is instead caused by contaminating negatively charged phospholipid membranes.
Transplant-related mortality and long-term graft function are significantly influenced by cell dose in patients undergoing allogeneic marrow transplantation
Authors: Alida Dominietto, Teresa Lamparelli, Anna Maria Raiola, Maria Teresa Van Lint, Francesca Gualandi, Giovanni Berisso, Stefania Bregante, Carmen di Grazia, Monica Soracco, Anna Pitto, Francesco Frassoni, Andrea Bacigalupo
Journal: Blood (2002)
Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients
Authors: Ele Ferrannini, Elza Muscelli, Silvia Frascerra, Simona Baldi, Andrea Mari, Tim Heise, Uli C. Broedl, Hans-Juergen Woerle
Journal: Journal of Clinical Investigation (2014)

Background. Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower glycemia by enhancing urinary glucose excretion. The physiologic response to pharmacologically induced acute or chronic glycosuria has not been investigated in human diabetes.
Effects of erythropoietin on advanced pulmonary vascular remodelling
Authors: M. E. van Albada, G. J. du Marchie Sarvaas, J. Koster, M. C. Houwertjes, R. M. F. Berger, R. G. Schoemaker
Journal: European Respiratory Journal (2007)

Erythropoietin (EPO) mobilises endothelial progenitor cells and promotes neovascularisation in heart failure. The present authors studied the effects of EPO on pulmonary vascular and cardiac remodelling in a model for flow-associated pulmonary arterial hypertension (PAH). PAH was induced in adult male Wistar rats by the injection of monocrotaline combined with an abdominal aortocaval shunt 1 week later (PAH or experimental group). Immediately afterwards, rats were randomised into those who received treatment with EPO (PAH+EPO group) and controls. Pulmonary and systemic haemodynamics, and right ventricular and pulmonary vascular remodelling were evaluated 3 weeks later. Vascular occlusion of the intra-acinar pulmonary vessels (13.4+/-0.7 versus 16.7+/-1.3% in PAH+EPO and PAH, respectively) and medial wall thickness of the pre-acinar arteries (wall-to-lumen ratio 0.13+/-0.01 versus 0.17+/-0.01 in PAH+EPO and PAH, respectively) decreased after treatment with EPO. Moreover, right ventricular capillary density was increased by therapy (2,322+/-61 versus 2,100+/-63 capillaries x mm(-2) in PAH+EPO and PAH, respectively). Increased mean pulmonary arterial pressure and decreased right ventricular contractility in the model were not altered by EPO treatment. In this rat model of flow-associated pulmonary arterial hypertension, erythropoietin treatment beneficially affected pulmonary vascular and cardiac remodelling. These histopathological effects were not accompanied by significantly improved haemodynamics.
Trends in Opioid Analgesic Abuse and Mortality in the United States
Authors: Richard C. Dart, Hilary L. Surratt, Theodore J. Cicero, Mark W. Parrino, S. Geoff Severtson, Becki Bucher-Bartelson, Jody L. Green
Journal: New England Journal of Medicine (2015)

The use of prescription opioid medications has increased greatly in the United States during the past two decades; in 2010, there were 16,651 opioid-related deaths. In response, hundreds of federal, state, and local interventions have been implemented. We describe trends in the diversion and abuse of prescription opioid analgesics using data through 2013.We used five programs from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System to describe trends between 2002 and 2013 in the diversion and abuse of all products and formulations of six prescription opioid analgesics: oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol. The programs gather data from drug-diversion investigators, poison centers, substance-abuse treatment centers, and college students.Prescriptions for opioid analgesics increased substantially from 2002 through 2010 in the United States but then decreased slightly from 2011 through 2013. In general, RADARS System programs reported large increases in the rates of opioid diversion and abuse from 2002 to 2010, but then the rates flattened or decreased from 2011 through 2013. The rate of opioid-related deaths rose and fell in a similar pattern. Reported nonmedical use did not change significantly among college students.Postmarketing surveillance indicates that the diversion and abuse of prescription opioid medications increased between 2002 and 2010 and plateaued or decreased between 2011 and 2013. These findings suggest that the United States may be making progress in controlling the abuse of opioid analgesics. (Funded by the Denver Health and Hospital Authority.).
New tools in pulmonary rehabilitation
Authors: P.J. Wijkstra, J.B. Wempe
Journal: European Respiratory Journal (2011)

In patients with more severe chronic obstructive pulmonary disease (COPD), the benefits of rehabilitation might not be clear and, therefore, new treatment options have been developed to increase the benefits of rehabilitation. This review provides an overview of new approaches being developed as an addition to exercise training. In turn, the benefits of adding ventilatory support, oxygen, anabolics or neuromuscular stimulation to a rehabilitation programme will be discussed. While positive benefits for a number of these approaches have been found, many questions remain unsolved. Therefore, at present, we cannot recommend these new tools as part of the routine management of patients with COPD who start a rehabilitation programme.
RECENT APPROACHES TO INTRACELLULAR DELIVERY OF DRUGS AND DNA AND ORGANELLE TARGETING
Authors: Vladimir P. Torchilin
Journal: Annual Review of Biomedical Engineering (2006)

Intracellular delivery of various drugs, including DNA, and drug carriers can sharply increase the efficiency of various treatment protocols. However, the receptor-mediated endocytosis of drugs, drug carriers, and DNA results in their lysosomal delivery and significant degradation. The problem can be solved and therapy efficacy still further increased if the approaches for direct intracytoplasmic delivery that bypass the endocytic pathway are developed. This is especially important for many anticancer drugs (proapoptotic drugs whose primary action site is the mitochondrial membrane) and gene therapy (nuclear or mitochondrial genomes should be targeted). This review considers several current approaches for intracellular drug delivery: the use of pH-sensitive liposomes, the use of cell-penetrating proteins and peptides, and the use of immunoliposomes targeting intracellular antigens. Among intracellular targets, nuclei (gene therapy), mitochondria (proapoptotic cancer therapy and targeting of the mitochondrial genome), and lysosomes (lysosomal targeting of enzymes for the therapy of the lysosomal storage diseases) are considered. Examples of successful intracellular and organelle-specific delivery of biologically active molecules, including DNA, are presented; unanswered questions, challenges, and future trends are also discussed.
COPD exacerbations: definitions and classifications
Authors: S. Burge, J.A. Wedzicha
Journal: European Respiratory Journal (2003)

Chronic obstructive pulmonary disease (COPD) is defined independently of exacerbations, which are largely a feature of moderate-to-severe disease. This article is the result of a workshop that tried to define exacerbations of COPD for use in clinical, pharmacological and epidemiological studies. The conclusions represent the consensus of those present. This review describes definitions, ascertainment, severity assessments, duration and frequency, using varying sources of data including direct patient interview, healthcare databases and symptom diaries kept by patients in studies. The best general definition of a COPD exacerbation is the following: an exacerbation of COPD is a sustained worsening of the patient's condition, from the stable state and beyond normal day-to-day variations that is acute in onset and may warrant additional treatment in a patient with underlying COPD. A more specific definition for studies where a bacteriological cause of exacerbation is being studied is included, as well as simpler definitions for retrospective identification from database sources. Prospective diary card assessments are best recorded as changes from an agreed baseline, rather than absolute symptom severities. Diary cards identify many unreported exacerbations, which on average have similar severities to reported exacerbations. A scale for exacerbation severity is proposed that incorporates in- and outpatient assessments. Exacerbation duration, which also relates to severity, is defined from diary card reports. Healthcare utilisation is not an adequate substitute for severity, depending on many unrelated social and comorbidity factors. It is an outcome in its own right.
Olanzapine Long-Acting Injection: A 24-Week, Randomized, Double-Blind Trial of Maintenance Treatment in Patients With Schizophrenia
Authors: John M Kane, Holland C Detke, Dieter Naber, Gopalan Sethuraman, Daniel Y Lin, Richard F Bergstrom, David McDonnell
Journal: American Journal of Psychiatry (2009)

Objective The purpose of the present study was to evaluate the efficacy and tolerability of olanzapine long-acting injection for maintenance treatment of schizophrenia. Method Outpatients with schizophrenia who had maintained stability on an oral regimen of olanzapine (10, 15, or 20 mg/day) for 4 to 8 weeks were randomly assigned to 24 weeks of double-blind treatment with "low" (150 mg every 2 weeks; N=140), "medium" (405 mg every 4 weeks; N=318), or "high" (300 mg every 2 weeks; N=141) doses of olanzapine long-acting injection; a very low reference dose of olanzapine long-acting injection (45 mg every 4 weeks; N=144); or their stabilized dose of oral olanzapine (N=322). Rates of and time to psychotic exacerbation were estimated using Kaplan-Meier methodology. Results At 24 weeks, the majority of oral olanzapine-treated patients (93%), as well as most olanzapine long-acting injection-treated patients receiving high (95%), medium (90%), low (84%), and very low doses (69%), remained exacerbation free, with the therapeutic 4-week regimen (medium dose) and pooled 2-week regimen (low and high doses) demonstrating efficacy similar to that of oral olanzapine as well as to each other. The three standard long-acting doses were superior to the very low reference dose based on time to exacerbation. Incidence of weight gain ≥7% of baseline was 21% for oral olanza­pine compared with 21%, 15%, 16%, and 8% for the high, medium, low, and very low olanzapine long-acting treatment groups, respectively. No clinically significant differences were observed between the long-acting injection and oral olanzapine groups in general safety parameters. Few injection-site reactions occurred (3%). Two patients experienced sedation and delirium consistent with olanzapine overdose following possible accidental intravascular injection. Conclusions Olanzapine long-acting injection was efficacious in maintenance treatment of schizophrenia for up to 24 weeks, with a safety profile similar to oral olanzapine except for injection-related adverse events.
Enhancement of glomerular immune complex deposition by a circulating polycation.
Authors: J L Barnes, M A Venkatachalam
Journal: The Journal of Experimental Medicine (1984)

It is known that polycations bind to and neutralize glomerular polyanions. Here we examine the effect of the polycation polyethyleneimine (PEI) on glomerular deposition of preformed immune complexes. Bovine serum albumin (BSA)-anti-BSA immune complexes made in 40 times antigen excess were administered following intravenous injection of PEI. Glomerular localization of immune deposits was assessed by quantitative immunofluorescence and electron microscopy and compared to controls receiving diluent without PEI followed by the same dose in immune complexes. In rats receiving PEI, deposits were localized within the glomerular basement membrane (GBM) of all peripheral capillary walls and in the mesangium. In controls, deposits localized exclusively within the mesangium in smaller amounts than after PEI. Thus, neutralization of glomerular polyanion by a circulating polycation enhances the deposition and alters the distribution of immune complexes in glomeruli.