tbuckley/cabot-search huggingface dataset:
Substitution Rates in a New Silene latifolia Sex-Linked Gene, SlssX/Y
Authors: Dmitry A. Filatov
Journal: Molecular Biology and Evolution (2004)

Dioecious white campion Silene latifolia has sex chromosomal sex determination, with homogametic (XX) females and heterogametic (XY) males. This species has become popular in studies of sex chromosome evolution. However, the lack of genes isolated from the X and Y chromosomes of this species is a major obstacle for such studies. Here, I report the isolation of a new sex-linked gene, Slss, with strong homology to spermidine synthase genes of other species. The new gene has homologous intact copies on the X and Y chromosomes (SlssX and SlssY, respectively). Synonymous divergence between the SlssX and SlssY genes is 4.7%, and nonsynonymous divergence is 1.4%. Isolation of a homologous gene from nondioecious S. vulgaris provided a root to the gene tree and allowed the estimation of the silent and replacement substitution rates along the SlssX and SlssY lineages. Interestingly, the Y-linked gene has higher synonymous and nonsynonymous substitution rates. The elevated synonymous rate in the SlssY gene, compared with SlssX, confirms our previous suggestion that the S. latifolia Y chromosome has a higher mutation rate, compared with the X chromosome. When differences in silent substitution rate are taken into account, the Y-linked gene still demonstrates significantly faster accumulation of nonsynonymous substitutions, which is consistent with the theoretical prediction of relaxed purifying selection in Y-linked genes, leading to the accumulation of nonsynonymous substitutions and genetic degeneration of the Y-linked genes.
Indoor Residual Spraying in Combination with Insecticide-Treated Nets Compared to Insecticide-Treated Nets Alone for Protection against Malaria: A Cluster Randomised Trial in Tanzania
Authors: Philippa A. West, Natacha Protopopoff, Alexandra Wright, Zuhura Kivaju, Robinson Tigererwa, Franklin W. Mosha, William Kisinza, Mark Rowland, Immo Kleinschmidt
Journal: PLoS Medicine (2014)

Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) of houses provide effective malaria transmission control. There is conflicting evidence about whether it is more beneficial to provide both interventions in combination. A cluster randomised controlled trial was conducted to investigate whether the combination provides added protection compared to ITNs alone.In northwest Tanzania, 50 clusters (village areas) were randomly allocated to ITNs only or ITNs and IRS. Dwellings in the ITN+IRS arm were sprayed with two rounds of bendiocarb in 2012. Plasmodium falciparum prevalence rate (PfPR) in children 0.5-14 y old (primary outcome) and anaemia in children <5 y old (secondary outcome) were compared between study arms using three cross-sectional household surveys in 2012. Entomological inoculation rate (secondary outcome) was compared between study arms. IRS coverage was approximately 90%. ITN use ranged from 36% to 50%. In intention-to-treat analysis, mean PfPR was 13% in the ITN+IRS arm and 26% in the ITN only arm, odds ratio = 0.43 (95% CI 0.19-0.97, n = 13,146). The strongest effect was observed in the peak transmission season, 6 mo after the first IRS. Subgroup analysis showed that ITN users were additionally protected if their houses were sprayed. Mean monthly entomological inoculation rate was non-significantly lower in the ITN+IRS arm than in the ITN only arm, rate ratio = 0.17 (95% CI 0.03-1.08).This is the first randomised trial to our knowledge that reports significant added protection from combining IRS and ITNs compared to ITNs alone. The effect is likely to be attributable to IRS providing added protection to ITN users as well as compensating for inadequate ITN use. Policy makers should consider deploying IRS in combination with ITNs to control transmission if local ITN strategies on their own are insufficiently effective. Given the uncertain generalisability of these findings, it would be prudent for malaria control programmes to evaluate the cost-effectiveness of deploying the combination.www.ClinicalTrials.gov NCT01697852 Please see later in the article for the Editors' Summary.
Project has been set up to explore ways of preventing wastage of doctors
Authors: J. Harvey, S. Seeley, H. Bichovsky, J. Winsland
Journal: BMJ (1996)

R P D Cooke and colleagues offer further sup- portive evidence for the adequacy of single doses of gentamicin in febrile neutropenic patients.Their approach of halving the dose if the trough concentration of gentamicin is 1-2 mg/l may be overcautious, since serum concentrations of aminoglycosides have not been shown to have much predictive value for efficacy or toxicity.5
Recurrent sarcoid granulomas in a transplanted lung derive from recipient immune cells: Fig. 1—
Authors: N. Milman, C. B. Andersen, C. M. Burton, M. Iversen
Journal: European Respiratory Journal (2005)

From 1992-2004, single lung transplantation has been performed in seven patients with end-stage pulmonary sarcoidosis at the Danish National Centre for Lung Transplantation. The objective was to assess whether recurrent sarcoid granulomas in the lung graft are derived from recipient or donor immune cells. Three patients had sarcoid recurrence in the lung graft, but none had clinically overt extra-thoracic sarcoidosis. Graft sex-mismatch was present in one patient, a 52-yr-old female having a lung graft from a male donor. In order to discriminate between recipient and donor cells fluorescence in situ hybridisation (FISH), using probes for both X- and Y-chromosomes, was applied on transbronchial lung biopsies (TBB) from the lung graft containing sarcoid granulomas. The recipient's explanted lung contained multiple active sarcoid granulomas. TBB from the implanted donor lung 5 months after transplantation showed sarcoid granulomas. FISH showed that the immune cells in the granulomas were X-chromosome positive and Y-chromosome negative and, therefore, were derived from the recipient. In conclusion, the results indicate that recurrent sarcoid granulomas in the transplanted lung are derived from recipient's immune cells, having colonised the lung allograft.
Age Is a Risk Factor for Chemotherapy-Induced Hepatopathy With Vincristine, Dactinomycin, and Cyclophosphamide
Authors: C. Arndt, D. Hawkins, J.R. Anderson, P. Breitfeld, R. Womer, W. Meyer
Journal: Journal of Clinical Oncology (2004)

To evaluate the spectrum of and determine the risk factors for the development of liver toxicity (hepatopathy) after therapy with vincristine, dactinomycin, and cyclophosphamide (VAC) for rhabdomyosarcoma in children and adolescents.We prospectively captured all events of hepatopathy occurring on the ongoing Children's Oncology Group intermediate risk protocol, D9803, for children with rhabdomyosarcoma. Patients enrolled onto this trial were randomly assigned to receive either VAC alone or VAC alternating with vincristine, topotecan, and cyclophosphamide. In addition, we reviewed the toxicity database and requested additional information for all patients with elevated bilirubin or transaminase levels. Risk factors were analyzed.Of 339 patients enrolled through August 2002, 18 developed hepatopathy. All events were captured by mandated toxicity reporting and filing of MedWatch forms, with no additional cases found after the additional search of the database. Four children died after developing this toxicity. All cases occurred after cycles of VAC (n = 16) or vincristine and cyclophosphamide with concomitant abdominal radiotherapy (n = 2). The onset of hepatopathy was 5 to 16 days from the start of a treatment cycle. For the 89 patients under 36 months of age, the risk of hepatopathy was 15%, with two deaths. For the 239 children 3 years of age or older, the risk for hepatopathy was 4%, with two deaths.The greatest risk factor for development of hepatopathy after VAC therapy was age. Dose modifications for younger children receiving VAC therapy are recommended.
Scheduled and unscheduled DNA synthesis in epidermal cells of hairless mice treated with immunosuppressive drugs and UVB-UVA irradiation
Authors: G.E. KELLY, W. MEIKLE, A.G.R. SHEIL
Journal: British Journal of Dermatology (1987)

The effects of the immunosuppressive drugs azathioprine, prednisolone and cyclosporin A, and UV irradiation on scheduled DNA synthesis, representing mitotic activity, and unscheduled DNA synthesis, representing DNA repair activity, in the skin of hairless mice were determined autoradiographically following intradermal administration of [3H]-thymidine. Azathioprine and prednisolone, and, to a lesser extent, cyclosporin A, were found to impair normal repair of UVR-induced DNA lesions in epidermal keratinocytes. Prednisolone, but not the other two drugs, further suppressed the normal delayed mitotic response in the skin following UVR. The depressive effects of these drugs, particularly the combined azathioprine/ prednisolone regime, on scheduled and unscheduled DNA synthesis are considered likely to predispose skin to mutagenic and carcinogenic processes.
Amino acid derivatives from <i>Lucilia sericata</i> excretions/secretions may contribute to the beneficial effects of maggot therapy via increased angiogenesis
Authors: A. Bexfield, A.E. Bond, C. Morgan, J. Wagstaff, R.P. Newton, N.A. Ratcliffe, E. Dudley, Y. Nigam
Journal: British Journal of Dermatology (2009)

Background Maggot therapy, utilizing the larvae of Lucilia sericata, has been reported to reduce the bacterial load within wounds and also to enhance wound healing. Maggot excretions/secretions (ES) have been shown to have a role in the success of maggot therapy. While the protein content of ES has been investigated, to date little research has focused on the small metabolites present in ES and their potential contribution to the therapy. Study of the molecular composition of the secretions and the potential bioactivities present will allow for a more detailed evaluation of the efficacy of maggot therapy. Objectives We studied the amino acid‐like compounds present in ES of L. sericata larvae in order to determine the compounds present and their potential role in the wound healing process. Methods These included thin‐layer chromatography/mass spectrometric analysis of ES to identify amino acid‐like components, a turbidometric assay to investigate their potential antibacterial activity and cell proliferation studies to investigate their potential mitogenic ability. Results Three prominent compounds were detected and identified as histidine, valinol and 3‐guanidinopropionic acid. While these amino acids were not shown to exhibit antibacterial activity, a proliferative effect on the growth of human endothelial cells, but not fibroblasts, was noted. Conclusions The demonstrated proliferative effect, selectively on endothelial cells, suggests that the amino acid‐like compounds present in maggot ES may have a role in wound healing, by stimulating angiogenesis.
Brief Report: Enrichment of Activated Group 3 Innate Lymphoid Cells in Psoriatic Arthritis Synovial Fluid
Authors: Emmerik F. A. Leijten, Tessa S. van Kempen, Marianne Boes, Jocea M. R. Michels‐van Amelsfort, Dirkjan Hijnen, Sarita A. Y. Hartgring, Joel A. G. van Roon, Mark H. Wenink, Timothy R. D. J. Radstake
Journal: Arthritis & Rheumatology (2015)

Innate lymphoid cells (ILCs) are a recently discovered group of cells that are essential to epithelial homeostasis and are implicated in psoriasis pathogenesis, yet they have never been reported in psoriatic arthritis (PsA).ILC classes and subsets were characterized in the peripheral blood (PB) of healthy controls, patients with psoriasis, and patients with PsA and in the synovial fluid (SF) of patients with PsA and patients with rheumatoid arthritis (RA). Cell surface marker expression and intracellular cytokine production following stimulation were analyzed using flow cytometry.ILCs were identified in the SF and were 4-fold more abundant in PsA SF than in PsA PB. Fewer CCR6+ ILCs were found in PsA PB than in healthy control PB, while PsA SF was enriched for CCR6+ ILCs compared to PsA PB and RA SF. Natural cytotoxicity receptor NKp44+ group 3 ILCs were rare in PB and RA SF, but abundant in PsA SF. Increased numbers of interleukin-17A (IL-17A)-producing ILCs were present in PsA SF compared to RA SF. CCR6, NKp44, and melanoma cell adhesion molecule (MCAM) were expressed on the cell surface of SF ILCs that produced IL-17A. The number of circulating NKp44+, CCR6+, and MCAM+ ILCs in blood was inversely correlated with PsA disease activity.Our findings indicate that PsA SF is enriched for group 3 ILCs that express CCR6 and NKp44, which distinguishes the synovial compartment from RA. The increased IL-17A production by SF ILCs indicates a novel role for ILCs in PsA.
Coagulation factor Va binds to human umbilical vein endothelial cells and accelerates protein C activation.
Authors: I Maruyama, H H Salem, P W Majerus
Journal: Journal of Clinical Investigation (1984)

In vitro the rate of protein C activation by thrombin is significantly accelerated by two distinct cofactors (a) the endothelial cell surface protein, thrombomodulin, and (b) human coagulation Factor Va. We have recently reported that the activity of Factor Va is contained in the 78,000-D light chain. In this study we have investigated the effects of Factor Va and its light chain on the activation of protein C in the presence of cultured endothelial cells. Thrombin-catalyzed protein C activation on human umbilical vein endothelial cells was enhanced by Factor Va. The ability of Factor Va to stimulate protein C activation on these cells was saturated at 50 nM Factor Va and was observed at several protein C concentrations. Isolated Factor Va light chain in concentrations up to 50 nM also accelerated protein C activation on endothelial cells, but higher concentrations inhibited the reaction. The effects of Factor Va or its light chain on protein C activation were also shown on a mouse hemangioma cell line but not on human fibroblasts nor on a human amelanotic melanoma cell line. Protein C activation on endothelial cells was partially inhibited by a goat anti-thrombomodulin antibody and further addition of a polyclonal rabbit anti-Factor V(Va) antibody resulted in additional inhibition. Endothelial cells grown in medium supplemented with human serum, devoid of Factor V coagulant activity, contained cell surface Factor V(Va) (approximately 15,000 molecules/cell) as measured by the binding of a monoclonal IgG directed against Factor V(Va). These cells also bound an additional 6,000-10,000 molecules Factor Va per cell as determined by direct binding studies using 125I-Factor Va. We suggest that thrombomodulin and Factor Va act in concert to regulate protein C activation on the surface of endothelial cells.
QT INTERVALS IN ATHLETES
Authors: CJ Milne, K Stewart, WS Hillis
Journal: British Journal of Sports Medicine (2013)

Aim To determine factors affecting the QT interval in athletes and find an improved means of QT correction (QTc) Method Data was gathered from the CAYA (Cardiovascular Assessment in Young Athletes) screening programme for athletes aged 35 and under. This included assessment of personal/family history, clinical examination, ECG and echocardiogram. This study used ECG data of heart rate, measured QT interval and Bazett 1 corrected QT interval (QTc). Athletes were divided into age groups and sex to provide age and sex related comparisons. Analysis was performed using co-efficients to determine significant factors affecting QTc. This was then added to linear regression models to provide a most accurate correlation of QT interval based on these factors. Results Complete data was held for 1545 athletes (1280 males, 265 females) aged 10–35. Overall data showed a mean age of 18.03. Heart rate varied from 34–123 bpm. Bazett QTc interval varied from 308–592 ms. Mean Bazett QTc of the males was 406.6 ms, and 422.5 ms. From the CAYA data, statistical significance was shown for the factors of age, sex and heart rate in determining QT interval. This provided the following conversion for most accurate determination of QT interval based on the statistically significant factors: QT=515.7–(1.984×HR)+(0.601×Age)+(9.33 if female) Conclusion QT interval is dependent on heart rate, sex and age, and all factors should be taken into account when determining QTc. The above formula provides the most accurate means of determining a QT interval based on an athlete's individual details. However, further work is ongoing to determine a new formula for means of QT correction that also accounts for these factors, as Bazett's does not. This will then allow a fairer comparison between individual athletes.
Trends in the Association of Poverty With Overweight Among US Adolescents, 1971-2004
Authors: Richard A. Miech, Shiriki K. Kumanyika, Nicolas Stettler, Bruce G. Link, Jo C. Phelan, Virginia W. Chang
Journal: JAMA (2006)

Prevalence of adolescent overweight in the United States has increased substantially during the past 3 decades. Whether socioeconomic disparities in adolescent overweight increased, decreased, or remained constant during this period is not known.To examine trends in adolescent overweight from 1971 to 2004 by family poverty status, as well as trends in potentially relevant eating and physical activity behaviors.Four cross-sectional, nationally representative surveys (US National Health and Nutrition Examination Surveys [NHANES] of 1971-1974, 1976-1980, 1988-1994, and 1999-2004) were examined for trends in the prevalence of overweight among adolescents aged 12 to 17 years by family poverty status.Prevalence of adolescent overweight, defined as body mass index at or above the 95th percentile for age and sex in the 2000 Centers for Disease Control and Prevention growth charts. Intermediate outcomes were physical inactivity in the past 30 days, proportion of caloric intake from sweetened beverages (24-hour recall), and whether respondent skipped breakfast (24-hour recall).Trends in the association of adolescent overweight with family poverty differed by age stratum (P = .01). In 12- to 14-year-old adolescents, prevalence did not significantly differ by family poverty status in any of the surveys; however, among non-Hispanic black adolescents, overweight prevalence increased faster in nonpoor vs poor families. In contrast, a widening disparity that disfavored adolescents from poor families was present in the 15- to 17-year-old adolescents. This trend was similar among male, female, non-Hispanic white, and non-Hispanic black adolescents, resulting in an overall prevalence of overweight in 1999-2004 more than 50% higher among adolescents in poor vs nonpoor families (23.3% vs 14.4%, respectively; P<.001). Additional analyses suggest that physical inactivity, sweetened beverage consumption, and skipping breakfast may contribute to these disparities.Trends of increasing overweight showed a greater impact in families living below the poverty line vs not living below the poverty line among older (15-17 years) but not younger (12-14 years) adolescents. Furthermore, physical inactivity, high consumption of sweetened beverages, and breakfast skipping may be candidate targets for prevention programs aimed at reducing this recently emerged disparity.
Reversal of Leukemia Virus-Induced Immunosuppression In Vitro by Peritoneal Macrophages2
Authors: Mauro Bendinelli, Glen S. Kaplan, Herman Friedman
Journal: JNCI Journal of the National Cancer Institute (1975)

When spleen cells from mice infected with Rowson-Parr virus (RPV) were cultivated with sheep red blood cells (SRBC), antibody plaque responses were markedly lower than those in similarly cultivated spleen cells from normal mice. Addition of as few as 103 spleen cells from RPV-infected mice to cultures of normal splenocytes markedly depressed the expected immune response. Although RPV-infected mice showed maximum immunodepression in vivo only during the first week after infection, their spleen cells, obtained later in the course of infection, depressed the immunologic responsiveness of normal splenocytes in vitro. Increased doses of SRBC or addition of bacterial lipopolysaccharide to cultures of spleen cells from immunodepressed, RPV-infected mice stimulated antibody formation, and near-normal numbers of antibody-producing cells were evident. Peritoneal exudate (PE) cells, but not thymus, bone marrow, or unfractionated spleen cells, restored immunocompetence to cultures of spleen cells from RPV-infected mice but did not affect the suppressive properties of the infected cells on normal splenocytes. The function of PE cell macrophages in restoring immunocompetence to infected spleen cells in cultures seemed related to a possible antigen-focusing activity of the cells; antibody-producing cell precursors in infected cultures seemed to be preferentially affected by the presence of normal PE cells.
Cytotoxic Anticancer Agents and Renal Impairment Study: The Challenge Remains
Authors: Atiqur Rahman, Robert M. White
Journal: Journal of Clinical Oncology (2006)

Although clinical trials for drug approval are conducted in patients with normal renal function, cancer patients in clinical practice may have compromised renal function because of the underlying disease or for other causes such as aging, diabetes, infectious and autoimmune diseases, or drug-related toxicities.2][3][4] Based on the data submitted in the new drug application for drug approval, the US Food and Drug Administration may require pharmacokinetic and safety studies in organ dysfunction patients postapproval for safe use of the drug.This practice is suboptimal, and definitely does not benefit the organ dysfunction patients who may have no available therapy at the launch of the drug.The US Food and Drug Administration reviews the results of the studies, and any other necessary information subsequently submitted for inclusion in the drug label.Absence of information in the drug label poses a significant challenge to the treating physicians on how to select appropriate drug doses for patients.In the era of oral and targeted therapy and in the adjuvant and prevention setting, when patients may be on daily continuous therapy, drug accumulation because of organ dysfunction can be severe and result in acute and long-term undesirable effects.][7] In this issue of the Journal of Clinical Oncology, Mita et al 8 report a study designed to define the dose of pemetrexed in advanced cancer patients with renal dysfunction.The study was a phase I, dose escalation, safety, and pharmacokinetic study to determine adequate pemetrexed starting dose in patients with compromised renal function.The study had four cohorts based on glomerular filtration rate (GFR) as a measure of renal function in the patients.GFR was measured by serum technetium-99m diethylenetriamine penta-acetic acid ( 99m Tc-DTPA) clearance.The GFR groupings were one through four with a GFR of Ն 60 mL/ min, 40 to 59 mL/min, 20 to 39 mL/min, and less than 20 mL/min, respectively; group 1 was subdivided, A and B, with GFRs Ն 80 mL/min and 60 to 79 mL/min, respectively, and group 3 was subdivided, A and B, with GFRs of 30 to 39 mL/min and 20 to 29 mL/min, respectively.The patients were treated with a 10-minute infusion of 150 to 600 mg/m 2 pemetrexed dose once every 3 weeks.Dose escalations were performed within each GFR group and were independent from the other GFR groups.