tbuckley/cabot-search huggingface dataset:
Novel phylogeny of whales revisited but not revised.
Authors: M C Milinkovitch, G Ortí, A Meyer
Journal: Molecular Biology and Evolution (1995)

Molecular phylogenetic data, if analyzed correctly, have the demonstrated capacity to resolve evolutionary relationships (i.e., the topology of phylogenetic trees) with confidence and can additionally suggest ages of lineages if assumptions about the rate of accumulation of mutations are accepted. Based on detailed maximumparsimony, neighbor-joining, and maximum-likelihood analyses of 930 base pairs (bp) of mitochondrial DNA ( mtDNA ) from 16 cetacean species (of 13 genera) and four outgroups, we (Milinkovitch et al. 1993) published a novel phylogenetic hypothesis which is in conflict with the classic division (Barnes et al. 1985) of living cetaceans into toothed whales and baleen whales. Our major finding was the suggestion that the suborder Odontoceti (toothed whales) is paraphyletic and, more specifically, that the sperm whales are more closely related to baleen whales (suborder Mysticeti) than to any other group of toothed whales. Further support for the (sperm whale + baleen whale) relationship derives from cladistic analyses of myoglobin amino-acid sequences (McKenna 1987; Czelusniak et al. 1990; Milinkovitch et al. 1993). Importantly, the sister-group relationship between sperm whales and baleen whales was recently reaffirmed by an expanded phylogenetic analysis (Milinkovitch et al. 1994) of 1,352 bp of mtDNA from 2 1 cetacean species (including a river dolphin and representatives of three baleen whale families) and several artiodactyl outgroup species. Independently, based on the analysis of 657 bp of the 16s mitochondrial gene from three cetacean species, Arnason et al. ( 1993 ) presented a neighbor-joining tree where the sperm whale is more closely related to the fin whale than to the only dolphin species included in that analysis. Although that result supports our hypothesis (Milinkovitch et al. 1993) of toothed whale paraphyly, Arnason et al. ( 1993) and Arnason and Gullberg ( 1994) concluded that it must be artifactual. Based on a new data set of complete cytochrome b DNA sequences ( 1,140 bp) fro-m 14 cetacean species (of 7 genera) and 1 outgroup, Arnason and Gullberg
A non-compulsory stewardship programme for the management of antifungals in a university-affiliated hospital
Authors: F. López-Medrano, R. San Juan, M. Lizasoain, M. Catalán, J.M. Ferrari, F. Chaves, C. Lumbreras, J.C. Montejo, A. Herreros de Tejada, J.M. Aguado
Journal: Clinical Microbiology and Infection (2012)
Late-breaking abstract: Bronchial allergen challenge with D. Pteronyssinus inhibit blood neutrophil apoptosis in patients with allergic asthma and rhinitis
Authors: Simona Lavinskiene, Jolanta Jeroch, Kestutis Malakauskas, Ieva Bajoriuniene, Edita Gasiuniene, Jurgita Jackute, Raimundas Sakalauskas
Journal: European Respiratory Journal (2011)

Background: Recent investigations suggest that neutrophils can play important role in the pathogenesis of allergic asthma and rhinitis.

Aim: To evaluate blood neutrophil apoptosis in patients with allergic asthma and rhinitis provoked with specific allergen.

Methods: Eight patients with allergic rhinitis (AR), four - with allergic asthma (AA) and six - healthy individuals (HI) were involved in to the study. All AR and AA patients had positive skin prick tests to D. Pteronyssinus and underwent bronchial allergen challenge (BAC) with standardized extracts of D. Pteronyssinus . Neutrophils were isolated from peripheral blood by density gradient centrifugation and annexin V-FITC was used to detect early apoptotic cells. Apoptosis was measured using FACSCalibur cytometer 24 h before BAC, 7 h and 24 h after BAC.

Results: Neutrophil apoptosis before and after BAC was more intensive in HI group compared to patients with AR and AA (table). Neutrophil apoptosis in AA group was more inhibited after BAC in comparison with AR group.

![Figure][1] 



Conclusions: Our preliminary results show that neutrophil apoptosis was decreased in patients with AA and AR compared to HI before and after BAC. This finding let us suggest, that specific allergen has inhibitory effect on neutrophil apoptosis and neutrophils may play an important role in allergic inflammatory process.

 [1]: pending:yes
Ifosfamide-containing chemotherapy in Ewing's sarcoma: The Second United Kingdom Children's Cancer Study Group and the Medical Research Council Ewing's Tumor Study.
Authors: A Craft, S Cotterill, A Malcolm, D Spooner, R Grimer, R Souhami, J Imeson, I Lewis
Journal: Journal of Clinical Oncology (1998)

PURPOSE To investigate the possibility that the substitution of ifosfamide for cyclophosphamide therapy for Ewing's sarcoma will improve survival over that seen in the first United Kingdom Children's Cancer Study Group (UKCCSG) Ewing's tumor study (ET-1). PATIENTS AND METHODS Between 1987 and 1993,243 patients (138 men or boys) were entered onto the study. The median age was 13.5 years (range, 1.5 to 27 years). The median follow-up was 58 months. Chemotherapy included four courses of vincristine 2 mg/m2; ifosfamide 9 g/m2; and doxorubicin 60 mg/m2 administered every 3 weeks. Treatment of the primary tumor was with surgery and/or radiotherapy followed by ifosfamide 6 g/m2; doxorubicin 60 mg/m2; and vincristine 2 mg/m2; with actinomycin D 1.5 mg/m2 substituted for doxorubicin after a total dose of 420 mg/m2. RESULTS Two hundred one patients had no metastases. One hundred eighteen patients had tumors of the axial skeleton and 125 patients had limb primary tumors. The major toxicities were hematologic and infective, but there were no toxic deaths. The overall survival rate was 62% (95% confidence interval [CI], 56 to 69) and relapse-free survival (RFS) 56% (95% CI, 49 to 62). For those with no metastases at diagnosis, the RFS rate was 62% and for those with metastases, 23%. Multivariate analysis showed age and site to have a significant effect on RFS. Pelvic sites had the worst RFS rate of 41%; other axial sites, 55%; and extremity tumors, 73%. Age younger than 10 years had an RFS rate of 86% versus 55% for older patients. The local relapse rate for axial tumors was 20% and for limb primary tumors was 2.4%. CONCLUSION The 5-year survival rate of 62% is improved compared with the 44% survival rate achieved in ET-1. This is probably caused by the use of higher doses of ifosfamide compared with relatively low doses of cyclophosphamide in ET-1.
Evaluation of reproductive capacity in germ cell tumor patients following treatment with cisplatin, etoposide, and bleomycin.
Authors: W T Stephenson, S M Poirier, L Rubin, L H Einhorn
Journal: Journal of Clinical Oncology (1995)

PURPOSE To evaluate the infertility rate in patients with germ cell tumors receiving chemotherapy with cisplatin, etoposide (VP-16), and bleomycin (PVP16B). PATIENTS AND METHODS Thirty patients were evaluated. All patients had undergone chemotherapy with two to four cycles of PVP16B. A single semen analysis was performed 24 to 78 months following initiation of chemotherapy. All 30 patients were continuously disease-free. Eight of these patients had also undergone nerve-sparing retroperitoneal lymph node dissection (RPLND). RESULTS The median sperm concentration was 33.9 x 10(6), with a median volume of 3.2 mL. The median total sperm count was 86.4 x 10(6). Oligospermia (&lt; 40 x 10(6) total sperm count) was found in 13 patients (43%), including six (20%) who were azoospermic. There was a high incidence of morphologically abnormal sperm, with only one patient having more than 50% normal spermatozoa. Only 13 patients (43%) had sperm motility greater than 50%. Five patients had positive semen antisperm immunoglobulin G (IgG). Eight patients fathered children, including three with document oligospermia. CONCLUSION Patients with germ cell tumors successfully treated with PVP16B chemotherapy are at substantial risk for persistent semen abnormalities. However, some patients with oligospermia will slowly recover and others are still capable of reproductive capacity despite continued oligospermia.
Attempted caveolae-mediated phagocytosis of surface-fixed micro-pillars by human osteoblasts
Authors: Caroline Moerke, Petra Mueller, Barbara Nebe
Journal: Biomaterials (2015)

Cells are sensitive to their underlying micro- and nano-topography, but the complex interplay is not completely understood especially if sharp edges and ridges of stochastically modified surfaces interfere with an attached cell body. Micro-topography offers cues that evoke a large range of cell responses e.g. altered adhesion behavior and integrin expression resulting in disturbed cell functions. In this study, we analyzed why osteoblastic cells mimic the underlying geometrical micro-pillar structure (5 × 5 × 5 μm, spacing of 5 μm) with their actin cytoskeleton. Interestingly, we discovered an attempted caveolae-mediated phagocytosis of each micro-pillar beneath the cells, which was accompanied by increased intracellular reactive oxygen species (ROS) production and reduced intracellular ATP levels. This energy consuming process hampered the cells in their function as osteoblasts at the interface. The raft-dependent/caveolae-mediated phagocytic pathway is regulated by diverse cellular components including caveolin-1 (Cav-1), cholesterol, actin cytoskeleton as well as actin-binding proteins like annexin A2 (AnxA2). Our results show a new aspect of osteoblast-material interaction and give insight into how cells behave on extraordinary micro-structures. We conclude that stochastically structured implants used in orthopedic surgery should avoid any topographical heights which induce phagocytosis to prevent their successful ingrowth.
Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma.
Authors: J E Gershenwald, M I Colome, J E Lee, P F Mansfield, C Tseng, J J Lee, C M Balch, M I Ross
Journal: Journal of Clinical Oncology (1998)

To determine the patterns of recurrence and causes of regional nodal basin failure in stage I or II melanoma patients who had a histologically negative sentinel lymph node (SLN) and whose regional nodal basins were not dissected following lymphatic mapping and SLN biopsy.The records of 344 patients with primary cutaneous melanoma who underwent lymphatic mapping and SLN biopsy between 1991 and 1995 at The University of Texas M.D. Anderson Cancer Center were reviewed. Of 322 patients who underwent successful lymphatic mapping procedures, 270 had histologically negative SLNs; mapped nodal basins were observed without further surgical intervention in 243 of these 270 patients. Recurrence patterns were analyzed from this cohort and a histologic reevaluation of all previously identified SLNs on which a biopsy had been taken was performed in patients who developed recurrent disease.Of 243 patients with a histologically negative SLN, 27 (11%) developed local, in-transit, regional nodal, and/or distant metastases after a median follow-up time of 35 months. Ten patients (4.1%) developed a nodal recurrence in the previously mapped basin, either solely or as a component of the first site of recurrence. Detailed analysis of the SLNs in these 10 patients demonstrated evidence of occult metastases in 80% by serial sectioning or immunohistochemical staining.Regional nodal failures in melanoma patients following a negative SLN biopsy are infrequent and to date have most commonly occurred because conventional histologic evaluation was unable to identify occult metastatic disease. These data provide further evidence that lymphatic mapping and SLN biopsy accurately reflect the status of the regional nodal basin. Specialized pathologic techniques are necessary to reduce further the already low false-negative rates and to improve disease staging.
Analysis of in vivo turnover of tau in a mouse model of tauopathy
Authors: Kaoru Yamada, Tirth K Patel, Katja Hochgräfe, Thomas E Mahan, Hong Jiang, Floy R Stewart, Eva-Maria Mandelkow, David M Holtzman
Journal: Molecular Neurodegeneration (2015)

Intracellular accumulation of tau as neurofibrillary tangles (NFTs) is the hallmark of Alzheimer's disease (AD) as well as in other tauopathies. Tau is present not only in the cytoplasm but also in the extracellular space such as cerebrospinal fluid (CSF) and brain interstitial fluid (ISF). Although clearance is one critical parameter leading to such intracellular/extracellular tau accumulation, in vivo turnover of tau has not been well characterized. The current study has attempted to precisely determine in vivo turnover rates of tau utilizing tet-off regulatable mice. In particular, we assessed intracellular tau and extracellular tau, soluble tau, insoluble tau and phosphorylated tau at certain sites utilizing a combination of in vivo microdialysis, biochemical analysis and specific ELISAs recognizing each species. To examine the effect of a tauopathy-associated mutation on tau clearance, half-lives of various tau species were compared between the mice with a FTDP-17 mutation that induces β-sheet formation, ΔK280 mutation (pro-aggregant mice) and control mice with additional β-sheet breaking mutations (anti-aggregant mice).Here we report that tau is metabolized at much slower turnover rates in vivo than in cell culture. We found that insoluble tau in pro-aggregant mice had a significantly slower half-life (t1/2 = ~34.2 days) than soluble tau (t1/2 = ~9.7 days). In contrast, soluble tau phosphorylated in the proline rich region was cleared faster than total soluble tau. When comparing pro-aggregant mice to anti-agregant mice, turnover rates of soluble tau species were not significantly different.The current study provides a comprehensive description of in vivo turnover of various tau species present in mice that express human tau. The turnover rate of soluble tau was not significantly altered between pro-aggregant mice and anti-aggregant mice. This suggests that altered conformation by ΔK280 does not have a major impact on clearance pathways for soluble tau. In contrast, different tau species displayed different half-lives. Turnover was significantly delayed for insoluble tau whereas it was accelerated for soluble tau phosphorylated in the proline rich region. These differences in susceptibilities to clearance suggest that aggregation and phosphorylation influences tau clearance which may be important in tau pathogenesis.
Tumors of Female Offspring of Mice Exposed Prenatally to Diethylstilbestrol&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Bruce E. Walker
Journal: JNCI Journal of the National Cancer Institute (1984)

Strain CD-1 female mice exposed prenatally to diethylstilbestrol (DES) (CAS: 56-53-1; alpha,alpha'-diethyl-4,4'-stilbenediol) were mated to unexposed males. Female offspring of these matings were raised to the stage of terminal illness. They were never exposed to DES and so have been referred to as "DES-lineage mice." Ten uterine adenocarcinomas and 5 ovarian cystadenocarcinomas were found in 40 DES-lineage mice. These findings were significantly different from the absence of such tumors in 24 "vehicle-lineage" mice whose mothers had received injections only of oil and alcohol. The types of tumors that commonly occur spontaneously in the CD-1 strain appeared with comparable frequency in the 2 groups of mice. The DES-lineage mice did not show the increased frequency of adenomyosis and squamous metaplasia of the uterus, nor the reduced frequency of corpora lutea seen in mice exposed prenatally to DES.
Patients Who Receive Androgen Deprivation Therapy Risk Adverse Cognitive Changes
Authors: Robert A. Gardiner, John Yaxley, Kenneth I. Pakenham, Heather Green, Peter Mactaggart, Roger Watson, Cheryl Swanson, David L. Nicol
Journal: Journal of Clinical Oncology (2015)

tion for adverse cognitive effects by a proportion of patients who received androgen-deprivation therapy (ADT). They compared 58 patients with nonlocalized or asymptomatic metastatic prostate cancer (PCa) who were about to commence ADT and observed the participants for 12 months; the findings were compared with those from a cohort of 84 men treated with prostatectomy alone and an additional 88 men who did not have a diagnosis of PCa. They found that participants in the ADT group were more likely to demonstrate impaired cognitive performance than contemporaries in the control/ reference groups over time. Baseline age, cognitive reserve, depressive symptoms, fatigue, and hot flush interference did not moderate the impact of ADT on impaired cognitive performance. In exploratory genetic analyses, GNB3 single nucleotide polymorphism rs1047776 wasassociatedwithincreasedratesofimpairedperformanceovertime in the ADT group. Whether or not ADT induces adverse cognitive changes in a proportionofpatientshasbeendisputedformanyyearsonthebasisof findings from longitudinal studies, including a number that received industry funding. To resolve the question, we undertook a randomized, controlled trial of 82 men with nonlocalized PCa who were allocated to leuprorelin (Lucrin), goserelin (Zoladex), cyproterone acetate(Androcur),ornotreatmentandwhowerereassessedat6and 12monthsafterbaseline;65participantscompleted6months,and62 of these continued for all 12 months of follow-up. 2,3 In addition to a nontreatment PCa control group, a noncancer community reference group was evaluated. Compared with baseline assessments, men who received ADT performedworseontwoof12testsofattentionandmemory;24of50 patients who were randomly assigned to active treatment and who were assessed 6 months later had a clinically significant decline in one ormorecognitivetests,butnotonepatientrandomlyassignedtoclose monitoringorfromthecommunityreferencegroupshowedadecline
The results of DOTS Plus project in Romania (2004-2010)
Authors: Ruxandra Delia Spataru, Mariana Andrei, Mihaela Stefan, Elmira Ibraim
Journal: European Respiratory Journal (2011)

Introduction: Although TB notification rate declined significantly in the last 8 years in Romania, from 142.2%ooo in 2002 to 90.5%ooo in 2010, MDR-TB cases still need a special attention (812 such cases have been reported in 2009). The DOTS Plus project funded by Global Fund and started in Romania in December 2004 has as purpose to provide high quality health services to a part of MDR-TB patients in Romania.

Aim and objectives: To analyze characteristics and treatment outcomes of MDR-TB cases enrolled in DOTS Plus project.

Methods: In the retrospective study have been enrolled 794 MDR-TB cases registered in DOTS Plus project between December 2004 and December 2010. Data have been collected from database of the project and National TB Register.

Results: From the total of 794 cases registered in the project and hospitalized in the 2 MDR-TB excellence centers in the country (57.5% in Bucharest and 42.5% in Bisericani), 67.7% were males and 32.3% females. Primary MDR was found in 26.6% of the cases. The DST pointed 49.3% with only HR resistance and 50.7% with other drug resistances (HR+1 to HR+5). 13 cases had XDR-TB. The ambulatory phase of the treatment was done at 119 TB dispensaries (62% from all TB dispensaries countrywide). The default rate decreased obviously from 31.5% in 2006 to 12.9% in 2008, consecutive to the distribution of different kind of incentives which improved treatment adherence. Success rate of the GLC patients (62%) was significantly higher then at the patients treated with NTP resources (24.2%).

Conclusions: The favorable evolution of MDR-TB patients enrolled in DOTS Plus project demonstrates real benefits and recommend its case MDR management extension to all MDR-TB cases in the country.
Abstract 1499: Angiotensin And Endothelin Systems - Important Players In Urotensin II Induced Myocardial Distensibility
Authors: Ana P Fontes-Sousa, Ana L Pires, Vera Monteiro-Cardoso, Adelino F Leite-Moreira
Journal: Circulation (2008)

Objective: Urotensin II (U-II) is a vasoactive peptide with important actions in the cardiovascular system. It was recently shown that it acutely decreases myocardial stiffness. Although angiotensin II (AngII) and endothelin-1 (ET-1) also modulate myocardial diastolic properties, their interaction with U-II at this level has not yet been investigated. Methods: Effects of increasing concentrations of U-II (10 – 8–10 – 6M) were studied in rabbit papillary muscles immersed in a modified Krebs solution (0.6Hz;1.8mM Ca2+;35°C) in the absence (n=12) and in presence of losartan, a selective competitive antagonist of AngII receptor type 1 (10 – 6M;n=8) or PD-145065, a nonselective endothelin receptor antagonist (10 – 6M;n=6). Calculated parameters: passive tension (PT), active tension (AT), maximum velocity of tension rise and decline (dT/dtmax and dT/dtmin, respectively) and muscle length. Results presented as mean±SEM (p&lt;0.05). Results: U-II induced a concentration dependent negative inotropic and lusitropic effects, decreasing at 10 – 6M 15.8±5.6%AT, 13.5±5.4%dT/dtmax and 18.1±4.5%%dT/dtmin. This effect was inhibited by losartan or PD-145065. Additionally, U-II induced a concentration dependent increase in passive muscle length of 1.0081±0.002L/ Lmax. Restoring muscle length to Lmax decreased 19.5±3.5%PT, indicating increased myocardial distensibility. In the presence of PD-145065, the maximal concentration of U-II only increased muscle length to 1.004±0.002%L/Lmax, which corresponded to a decrease of PT of just 11.6±2.7%. With losartan these effects of U-II were abolished. Conclusion: The acute increase in myocardial distensibility induced by U-II is attenuated by ET-1 receptor blockade and completely abolished in the presence of an AT1 antagonist. This interaction between U-II, AngII and ET-1 is a novel finding with potential pathophysiologic and therapeutic implications in heart failure that deserves further investigation.
Why patients who self monitor glucose might be more depressed
Authors: Lucy M Candib
Journal: BMJ (2008)

We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.Readers should consult the website for the full list of responses and any authors' replies, which usually arrive after our selection.patricia de la rosa/stone/getty images screening for type 2 diabetes Screen women with gestational diabetes for type 2 diabetesOne way to reduce type 2 diabetes would be to target women with gestational diabetes. 1Maternity services are increasingly screening women and treating gestational diabetes, after the demonstration of significant perinatal benefits. 2 Within 10 years, 35-60% of women with gestational diabetes will develop type 2 diabetes. 3These women are an already identified high risk group.Their children are also more likely to be obese and share a genetic propensity to type 2 diabetes. 4 Following up women with gestational diabetes allows the targeting of two high risk people without additional screening.Many health service contacts are made in the first year of a child's life, therefore interventions may be easily delivered.Also, many women are receptive to health advice around the time of a birth when new lifestyle patterns are being established.Improved follow-up of these women with promotion of diet, exercise, and pharmacology, together with prolongation of breast feeding and subsequent healthy infant feeding is likely to be effective for mother, child, and the health service.