tbuckley/cabot-search huggingface dataset:
Evaluating Behavioral Interventions: Need for Randomized Controlled Trials
Authors: Thomas A. Peterman
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The impact of the acquired immunodeficiency syndrome (AIDS) epidemic may be influenced by the development of effective treatments, vaccines, or methods to assist behavior change. Prevention strategies may be guided by an assessment of the quality of evidence supporting different possible interventions. We wanted to assess the strength of evidence produced by studies of these interventions. To do this, we reviewed computerized abstracts (AIDSLINE) from the international AIDS conferences of 1989 through 1992 using the US Preventive Services Task Force hierarchy for strength of evidence.<sup>1</sup>Abstracts were first selected if they contained the words<i>trial</i>: (presence of a colon after the word means any ending to the word will be selected) with either<i>random: or control</i>:. Second, we selected abstracts containing the word cohort: with either<i>drug therapy</i>as a Medical Subject Heading or<i>behavior</i>: and<i>change</i>: or<i>vaccine</i>:. These abstracts were then reviewed independently by
Phospholipase A2 inhibition prevents mucosal damage associated with small intestinal ischaemia in rats.
Authors: T Otamiri, M Lindahl, C Tagesson
Journal: Gut (1988)

The influence of various inflammatory inhibitors on the damaging effects of ischaemia in the small intestinal mucosa has been investigated. A rat experimental model was used, in which a ligated loop of the distal ileum was subjected to ischaemia and revascularisation and the ensuing mucosal damage assessed by lysosomal enzyme release and intestinal permeability measurements. The mucosal content of malondialdehyde - a lipid peroxidation product - and its activity of myeloperoxidase - a neutrophil granulocyte marker was also determined. In the absence of inhibitor, ischaemia and revascularisation caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa and increased myeloperoxidase activity in the mucosa. All these effects were inhibited by the phospholipase A2 inhibitors, quinacrine and nordihydroguaiaretic acid (NDGA), while the lipoxygenase inhibitor, BW755C, had no influence and the cyclooxygenase inhibitor, indomethacin, potentiated the increases in mucosal permeability and N-acetyl-glucosaminidase release. BN 52021, a specific platelet activating factor antagonist, did not influence the myeloperoxidase activity, but it decreased the formation of malondialdehyde and the increases in mucosal permeability and N-acetyl-beta-glucosaminidase release, although not to the same extent as quinacrine and NDGA. These findings indicate that phospholipase A2 inhibition prevents mucosal damage associated with small intestinal ischaemia and suggest that at least part of the ischaemic damage is mediated by products of phospholipase A2 activity that are not arachidonic acid metabolites.
Improving MBW testing: Closed circuit washin with a novel bolus gas delivery reduces washin time and does not alter washout
Authors: Alex Horsley, Alan Bell
Journal: European Respiratory Journal (2014)

Background:  Multiple breath washout (MBW) is a sensitive measure of early airway dysfunction. A potential disadvantage of both SF 6  and N 2  washout is the time required to wash tracer into the lungs.   Methods:  All tests were performed sequentially on the same fast-responding Innocor MBW system (rise time 85ms). Washin was performed using 0.2% SF 6  in an open circuit, 1% SF 6  in a rebreathe (closed) circuit & 1% SF 6  in a closed circuit using a bolus to deliver all tracer in the 1st part of breath 1. Tests were performed in triplicate on healthy controls. A CO 2  scrubber was used for closed circuit tests.   Results:  Paired data are available on 10 controls (mean age 36yrs, 3M, Mean FEV 1  102%). There was no difference in LCI (Mean 6.69, 6.76, 6.68 with open, closed & bolus systems, p=0.88) or FRC (2.80, 2.79, 2.80L, p=0.99) between washin methods. Washin took a mean of 34 breaths (163secs) with open circuit vs 13 breaths (61secs) with closed circuit & 9 breaths (41secs) with bolus washin (Figure 1). Mean end-washin inspired CO2 was 1.6% (closed) and 1.3% (bolus).   Conclusion:  Closed circuit washin with an effective CO 2  scrubber does not affect washout endpoints in controls, and results in substantial time savings for test completion. No additional delay is required between tests. This can be further improved by using a novel bolus technique to deliver tracer. Testing in patient groups is ongoing.
Degradation of MDM2 by the Interaction between Berberine and DAXX Leads to Potent Apoptosis in MDM2-Overexpressing Cancer Cells
Authors: Xiaoling Zhang, Lubing Gu, Jiansha Li, Noopur Shah, Jing He, Lin Yang, Qun Hu, Muxiang Zhou
Journal: Cancer Research (2010)

Berberine, a natural product derived from a plant used in Chinese herbal medicine, is reported to exhibit anticancer effects; however, its mechanism of action is not clearly defined. Herein, we demonstrate that berberine induces apoptosis in acute lymphoblastic leukemia (ALL) cells by downregulating the MDM2 oncoprotein. The proapoptotic effects of berberine were closely associated with both the MDM2 expression levels and p53 status of a set of ALL cell lines. The most potent apoptosis was induced by berberine in ALL cells with both MDM2 overexpression and a wild-type (wt)-p53, whereas no proapoptotic effect was detected in ALL cells that were negative for MDM2 and wt-p53. In contrast to the conventional chemotherapeutic drug doxorubicin, which induces p53 activation and a subsequent upregulation of MDM2, berberine strongly induced persistent downregulation of MDM2 followed by a steady-state activation of p53. We discovered that downregulation of MDM2 in ALL cells by berberine occurred at a posttranslational level through modulation of death domain-associated protein (DAXX), which disrupted the MDM2-DAXX-HAUSP interactions and thereby promoted MDM2 self-ubiquitination and degradation. Given that MDM2-overexpressing cancer cells are commonly chemoresistant, our findings suggest that this naturally derived agent may have a highly useful role in the treatment of cancer patients with refractory disease.
The determinants of gene order conservation in yeasts
Authors: Juan F Poyatos, Laurence D Hurst
Journal: Genome biology (2007)

Why do some groups of physically linked genes stay linked over long evolutionary periods? Although several factors are associated with the formation of gene clusters in eukaryotic genomes, the particular contribution of each feature to clustering maintenance remains unclear.We quantify the strength of the proposed factors in a yeast lineage. First we identify the magnitude of each variable to determine linkage conservation by using several comparator species at different distances to Saccharomyces cerevisiae. For adjacent gene pairs, in line with null simulations, intergenic distance acts as the strongest covariate. Which of the other covariates appear important depends on the comparator, although high co-expression is related to synteny conservation commonly, especially in the more distant comparisons, these being expected to reveal strong but relatively rare selection. We also analyze those pairs that are immediate neighbors through all the lineages considered. Current intergene distance is again the best predictor, followed by the local density of essential genes and co-regulation, with co-expression and recombination rate being the weakest predictors. The genome duplication seen in yeast leaves some mark on linkage conservation, as adjacent pairs resolved as single copy in all post-whole genome duplication species are more often found as adjacent in pre-duplication species.Current intergene distance is consistently the strongest predictor of synteny conservation as expected under a simple null model. Other variables are of lesser importance and their relevance depends both on the species comparison in question and the fate of the duplicates following genome duplication.
Studies of Experimental Renal Failure in Dogs. I. Effect of 5/6 Nephrectomy on Concentrating and Diluting Capacity of Residual Nephrons*
Authors: Jack W. Coburn, Harvey C. Gonick, Milton E. Rubini, Charles R. Kleeman
Journal: Journal of Clinical Investigation (1965)

Two divergent theories have been offered to explain the concentrating and diluting defects of chronic renal disease.The conventional view at- tributes these abnormalities to damage to specific nephron sites and assumes a significant formation of urine by partially damaged nephrons.The al- ternative view postulates little or no function by damaged nephrons and attributes virtually all function to the remaining "intact nephrons."It is suggested that the increased solute excretion by these fewer normal nephrons interferes with the ability to concentrate and dilute urine (1, 2).This follows from the observations in normals, under conditions of both antidiuresis and water diuresis, that an increase in solute excretion causes urine osmolality to approach that of plasma (3-6).Data supporting this latter thesis have been ob- tained in an animal model with unilateral kidney disease.When concentrating and diluting abilities were expressed at equivalent rates of glomerular filtration, these functions were approximately equal in the diseased and contralateral normal kidney (2, 7).However, extrapolation of such data to *
Cholesterol Sensitivity of Endogenous and Myristoylated Akt
Authors: Rosalyn M. Adam, Nishit K. Mukhopadhyay, Jayoung Kim, Dolores Di Vizio, Bekir Cinar, Kelly Boucher, Keith R. Solomon, Michael R. Freeman
Journal: Cancer Research (2007)

Abstract The serine-threonine kinase, Akt, has been linked to cholesterol-sensitive signaling mechanisms, suggesting a possible means whereby cholesterol might affect tumor cell growth and survival. However, it has not been shown whether Akt itself, as distinct from upstream components of the pathway (e.g., membrane phosphoinositides), can be directly responsible for cholesterol-mediated effects. Consistent with this possibility, we identified an Akt1 subpopulation in cholesterol-rich lipid raft fractions prepared from LNCaP human prostate cancer cells. Phosphorylation of this Akt subspecies was ablated with methyl-β-cyclodextrin, a cholesterol-binding compound, under conditions where nonlipid raft-resident Akt was unaffected. A myristoylated Akt1 (MyrAkt1) fusion protein expressed in LNCaP cells was found to be highly enriched in lipid rafts, indicating that oncogenic Akt is overrepresented in cholesterol-rich membranes compared with wild-type Akt. Notably, lipid raft-resident MyrAkt1 exhibited a markedly distinct substrate preference compared with MyrAkt1 immunoprecipitated from cytosol and nonraft membrane fractions, suggesting a redirection of signal transduction when the protein is present in cholesterol-rich membranes. Expression of MyrAkt1 in LNCaP cells overcame their characteristic dependence on constitutive signaling through the phosphoinositide 3′-kinase pathway. This protective effect was substantially diminished with cyclodextrin treatment. Phosphorylation of Akt substrates in lipid raft fractions, but not in cytosol/nonraft membrane fractions, was ablated with cyclodextrin. In addition, in control (LacZ transfected) cells, lipid raft fractions were relatively enriched in phosphorylated Akt substrates. Collectively, these data show that a subpopulation of Akt is cholesterol sensitive and that the oncogenic effects conferred by myristoylation arise, in part, from the tendency of the membrane-targeted form of the protein to reside in cholesterol-rich membrane microdomains. [Cancer Res 2007;67(13):6238–46]
Sex and Clonality in the Little Fire Ant
Authors: Julien Foucaud, Denis Fournier, Jérôme Orivel, Jacques H. C. Delabie, Anne Loiseau, Julien Le Breton, Gaël J. Kergoat, Arnaud Estoup
Journal: Molecular Biology and Evolution (2007)

Reproduction systems are controlling the creation of new genetic variants as well as how natural selection can operate on these variants. Therefore, they had historically been one of the main foci of evolutionary biology studies. The little fire ant, Wasmannia auropunctata, has been found to display an extraordinary reproduction system, in which both males and female queens are produced clonally. So far, native sexual populations of W. auropunctata have not been identified. Our goals were to identify such sexual populations and investigate the origins of female parthenogenesis and male clonality. Using mitochondrial DNA and microsatellite markers in 17 native populations, we found that traditional sexual populations occurred in W. auropunctata and are likely the recent source of neighboring clonal populations. Queen parthenogenesis has probably evolved several times through mutational events. Male clonality is tightly linked to queen parthenogenesis and thus appears to be female controlled. Its origin could be accounted for by 2 mutually exclusive hypotheses: either by the expected coevolution of the 2 sexes (i.e., a variant of the maternal genome elimination hypothesis) or by a shared mechanistic origin (i.e., by the production of anucleate ovules by parthenogenetic queens). Our results also show that W. auropunctata males and females do not form separate evolutionary units and are unlikely to be engaged in an all-out battle of sexes. This work opens up new perspectives for studies on the adaptive significance and evolutionary stability of mixed sexual and clonal reproduction systems in living organisms.
Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice.
Authors: P A Jänne, S F Suchy, D Bernard, M MacDonald, J Crawley, A Grinberg, A Wynshaw-Boris, H Westphal, R L Nussbaum
Journal: Journal of Clinical Investigation (1998)

The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked human genetic disorder characterized by mental retardation, congenital cataracts, and renal tubular dysfunction. The Lowe syndrome gene, OCRL1, encodes a phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi complex. The pathogenesis of Lowe syndrome due to deficiency of a phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi complex is unknown. We have used targeted disruption in embryonic stem cells to make mice deficient in Ocrl1, the mouse homologue for OCRL1, as an animal model for the disease. Surprisingly, mice deficient in Ocrl1 do not develop the congenital cataracts, renal Fanconi syndrome, or neurological abnormalities seen in the human disorder. We hypothesized that Ocrl1 deficiency is complemented in mice by inositol polyphosphate 5-phosphatase (Inpp5b), an autosomal gene that encodes a phosphatidylinositol bisphosphate 5-phosphatase highly homologous to Ocrl1. We created mice deficient in Inpp5b; the mice were viable and fertile without phenotype except for testicular degeneration in males beginning after sexual maturation. We crossed mice deficient in Ocrl1 to mice deficient in Inpp5b. No liveborn mice or embryos lacking both enzymes were found, demonstrating that Ocrl1 and Inpp5b have overlapping functions in mice and suggesting that the lack of phenotype in Ocrl1-deficient mice may be due to compensating Inpp5b function.
STUDIES ON THE CORPUS CALLOSUM
Authors: ANDREW J. AKELAITIS
Journal: American Journal of Psychiatry (1945)

A peculiar type of behavior disorder consisting of an apparent conflict between the desired and the actually performed act is described in 2 epileptics following partial and complete callosal section. The psychobiological and psychoneurological aspects of this diagonistic type of dyspraxia is discussed. It is concluded that in the first case psychobiological factors played a major rôle in the etiology of the disorder, and that in the second case the diagonistic dyspraxia was probably an epileptic variant.
Exocrine pancreatic disease and the malabsorption syndrome in tropical Africa.
Authors: J G Banwell, M R Hutt, P J Leonard, V Blackman, D W Connor, P D Marsden, J Campbell
Journal: Gut (1967)

EDITORIAL, COMMENT The study of malabsorption in Uganda, East Africa, has revealed that the majority of patients who have steatorrhoea suffer from exocrine pancreatic disorders.The differing incidence of malabsorption syndromes in a hospital community in Kampala, Uganda, has been compared with the incidence in both temperate and tropical climates and the clinical and laboratory features of this syndrome are discussed.
The Manufacture of Recovery
Authors: Joel Tupper Braslow
Journal: Annual Review of Clinical Psychology (2013)

Recovery (also known as the “recovery orientation,” “recovery vision,” or “recovery philosophy”) has been the dominant paradigm shaping current mental health policy for the past decade. It is claimed to be a revolutionary departure from the past and a guide to policy that will transform outcomes of severe mental illness. This review looks critically at the history of recovery and examines the ways in which this history has shaped the values, beliefs, and practices of current recovery-based policies. Recovery is a treatment philosophy that emerged from the ruins of deinstitutionalization and the psychopharmaceutical revolution. Yet paradoxically, recovery reflects many of the same ideas that made deinstitutionalization and the era of psychopharmacology possible. Further, history reveals how the recovery movement is deeply indebted to and embedded within the sociocultural values of neoliberalism that have shaped public policy since the presidential election of Ronald Reagan in 1980.
Plasmodium vivax malaria in the UK
Authors: C. J. Gill
Journal: BMJ (2015)

New insights into an old enemy

Plasmodium falciparum malaria is so lethal and ubiquitous that one could easily forget that other species of malaria are globally important too. In particular, Plasmodium vivax , the main cause of relapsing malaria, affects up to 300 million people annually, and occurs in far wider and ecologically diverse settings than P falciparum .

Yet P vivax remains seriously understudied. Today, querying “ Plasmodium falciparum ” on PubMed generated 31 493 citations compared with only 6520 for “ Plasmodium vivax .” Recent data suggest that the epidemiology of P vivax may be shifting1 2 and that the parasite could be growing more virulent.3 4 But the evidence supporting these rests largely on small, cross sectional studies with limited geographical scope. Without large, systematically collected, geographically diverse, longitudinal datasets, we cannot be certain that these trends are for real, let alone try to explain them based on external forces, such as global warming or urbanisation.

In this context, the linked paper by Broderick and colleagues (doi:10.1136/bmj.h1703) is well timed.5 These authors analysed 27 years of data and over 50 000 clinical samples collected by the Public Health England Malaria Reference Laboratory. To enter the …
Outcome Predictors of Radical Prostatectomy in Patients With Prostate-Specific Antigen Greater Than 20 ng/ml: A European Multi-Institutional Study of 712 Patients
Authors: Martin Spahn, Steven Joniau, Paolo Gontero, Steffen Fieuws, Giansilvio Marchioro, Bertrand Tombal, Burkhard Kneitz, Chao-Yu Hsu, Katie Van Der Eeckt, Pia Bader, Detlef Frohneberg, Alessandro Tizzani, Hein Van Poppel
Journal: European Urology (2010)
Do MRI and ultrasound of the anterior pelvis correlate with, or predict, young football players’ clinical findings? A 4-year prospective study of elite academy soccer players
Authors: Philip Robinson, Andrew J Grainger, Elizabeth M A Hensor, Mark E Batt, Philip J O'Connor
Journal: British Journal of Sports Medicine (2014)

To prospectively follow a cohort of elite young male professional soccer players with sequential symptom questionnaires and imaging of the anterior pelvis to determine the prevalence and severity of imaging findings.34 male athletes (mean age 16.5 years) underwent clinical examination, history/symptom questionnaire, ultrasound and 1.5 T MRI of the anterior pelvis. Athletes then underwent annual questionnaire and ultrasound with MRI also performed every 18 months. Two experienced radiologists scored ultrasound (consensus) and MRI (independently) for abnormality including pubic bone, capsule and tendon oedema and scores correlated with symptoms and presence or absence of previous injuries.Over 4 years the participants fell from 34 to 22 in number with no withdrawals due to groin injury. On study entry no athletes had undergone previous hip or pelvic surgery. On MRI pubic bone oedema, secondary cleft, capsule/tendon oedema and enhancement did not differ substantively between players with and without history of previous injury. κ Analysis for MRI scoring showed excellent agreement (0.84-0.96) for pubic bone marrow oedema, secondary cleft, capsule/tendon oedema and enhancement. On ultrasound inguinal wall motion and adductor tendinopathy did not differ substantively between players with and without history of previous injury. Stability of imaging assessments over time showed no consistent difference.Pubic bone marrow and parasymphyseal findings (cleft, capsule/tendon oedema) on MRI or inguinal canal ballooning on ultrasound were frequently found in asymptomatic athletes and did not predict injury or symptom development.
Human adipocyte cholesterol. Concentration, localization, synthesis, and turnover.
Authors: P H Schreibman, R B Dell
Journal: Journal of Clinical Investigation (1975)

By analysis of 124 specimens in 16 different patients, isolated human adipocyte cholesterol concentration is highly correlated with fat cell size but not with plasma cholesterol concentration. Less than 6 percent of total cholesterol is esterified; after subcellular fractionation, 88 percent of the cholesterol is recovered in the triglyceride-rich supernatant oil. This latter finding supports the observation that fat cell cholesterol is determined by triglyceride content, and hence by fat cell size. After intravenous administrtion of radioactive cholesterol, the sum of a three-exponential equation was fit simultaneously to both the plasma and adipocyte specific activity time curves in six patients. In five of the six, a slowly turning over pool (pool 3) closely fit the adipocyte data. Two model structures, mammillary and catenary, were fitted to the data. There was no synthesis in pool 3 using a mammillary model but a mean 5.3 percent of the total body production rate was found in compartment 3 if a catenary model was assumed. Although a catenary model is biologically unlikely, it could not be excluded. Obesity is associated with an increased cholesterol synthetic rate equal to 20 mg/day for each kilogram of body fat. To test (by an independent method) if this synthesis might be occurring in adipose tissue, human fat cells were obtained under a wide variety of dietary conditions and incubated in vitro with radioactive glucose or acetate. Incorportation of these precursors into sterol could account for no more than 1 mg cholesterol synthesis/kg fat per day. These in vitro data taken together with the in vivo mammillary compartmental analysis data are compatible with the possiblity that the excess cholesterol synthesis of obesity occurs in pool 1, most likely from hepatic or intestinal sites.