Can we continue research in splenectomized dogs? Mycoplasma haemocanis: Old problem - New insight

We report the appearance of a Mycoplasma haemocanis infection in laboratory dogs, which has been reported previously, yet, never before in Europe. Outbreak of the disease was triggered by a splenectomy intended to prepare the dogs for a hemorrhagic shock study. The clinical course of the dogs was dramatic including anorexia and hemolytic anemia. Treatment included allogeneic transfusion, prednisone, and oxytetracycline. Systematic follow-up (n=12, blood smears, antibody testing and specific polymerase chain reaction) gives clear evidence that persistent eradication of M. haemocanis is unlikely. We, therefore, had to abandon the intended shock study. In the absence of effective surveillance and screening for M. haemocanis, the question arises whether it is prudent to continue shock research in splenectomized dogs. Copyright (C) 2004 S. Karger AG, Basel

Stem-cell competition

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62534/1/418025a.pd

A novel point-of-care testing strategy for sexually transmitted infections among pregnant women in high-burden settings: Results of a feasibility study in Papua New Guinea

© 2016 The Author(s). Sexually transmitted and genital infections in pregnancy are associated with an increased risk of adverse maternal and neonatal health outcomes. High prevalences of sexually transmitted infections have been identified among antenatal attenders in Papua New Guinea. Papua New Guinea has amongst the highest neonatal mortality rates worldwide, with preterm birth and low birth weight major contributors to neonatal mortality. The overall aim of our study was to determine if a novel point-of-care testing and treatment strategy for the sexually transmitted and genital infections Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Bacterial vaginosis (BV) in pregnancy is feasible in the high-burden, low-income setting of Papua New Guinea. Methods: Women attending their first antenatal clinic visit were invited to participate. CT/NG and TV were tested using the GeneXpert platform (Cepheid, USA), and BV tested using BVBlue (Gryphus Diagnostics, USA). Participants received same-day test results and antibiotic treatment as indicated. Routine antenatal care including HIV and syphilis screening were provided. Results: Point-of-care testing was provided to 125/222 (56 %) of women attending routine antenatal care during the three-month study period. Among the 125 women enrolled, the prevalence of CT was 20.0 %; NG, 11.2 %; TV, 37.6 %; and BV, 17.6 %. Over half (67/125, 53.6 %) of women had one or more of these infections. Most women were asymptomatic (71.6 %; 47/67). Women aged 24 years and under were more likely to have one or more STI compared with older women (odds ratio 2.38; 95 % CI: 1.09, 5.21). Most women with an STI received treatment on the same day (83.6 %; 56/67). HIV prevalence was 1.6 % and active syphilis 4.0 %. Conclusion: Point-of-care STI testing and treatment using a combination of novel, newly-available assays was feasible during routine antenatal care in this setting. This strategy has not previously been evaluated in any setting and offers the potential to transform STI management in pregnancy and to prevent their associated adverse health outcomes

D-Cbl Binding to Drk Leads to Dose-Dependent Down-Regulation of EGFR Signaling and Increases Receptor-Ligand Endocytosis

Proper control of Epidermal Growth Factor Receptor (EGFR) signaling is critical for normal development and regulated cell behaviors. Abnormal EGFR signaling is associated with tumorigenic process of various cancers. Complicated feedback networks control EGFR signaling through ligand production, and internalization-mediated destruction of ligand-receptor complexes. Previously, we found that two isoforms of D-Cbl, D-CblS and D-CblL, regulate EGFR signaling through distinct mechanisms. While D-CblL plays a crucial role in dose-dependent down-regulation of EGFR signaling, D-CblS acts in normal restriction of EGFR signaling and does not display dosage effect. Here, we determined the underlying molecular mechanism, and found that Drk facilitates the dose-dependent regulation of EGFR signaling through binding to the proline-rich motif of D-CblL, PR. Furthermore, the RING finger domain of D-CblL is essential for promoting endocytosis of the ligand-receptor complex. Interestingly, a fusion protein of the two essential domains of D-CblL, RING- PR, is sufficient to down-regulate EGFR signal in a dose-dependent manner by promoting internalization of the ligand, Gurken. Besides, RING-SH2Drk, a fusion protein of the RING finger domain of D-Cbl and the SH2 domain of Drk, also effectively down-regulates EGFR signaling in Drosophila follicle cells, and suppresses the effects of constitutively activated EGFR. The RING-SH2Drk suppresses EGFR signaling by promoting the endosomal trafficking of ligand-receptor complexes, suggesting that Drk plays a negative role in EGFR signaling by enhancing receptor endocytosis through cooperating with the RING domain of D-Cbl. Interfering the recruitment of signal transducer, Drk, to the receptor by the RING-SH2Drk might further reduces EGFR signaling. The fusion proteins we developed may provide alternative strategies for therapy of cancers caused by hyper-activation of EGFR signaling

Liquid-liquid critical point in supercooled silicon

A novel liquid-liquid phase transition has been proposed and investigated in a wide variety of pure substances recently, including water, silica and silicon. From computer simulations using the Stillinger-Weber classical empirical potential, Sastry and Angell [1] demonstrated a first order liquid-liquid transition in supercooled silicon, subsequently supported by experimental and simulation studies. Here, we report evidence for a liquid-liquid critical end point at negative pressures, from computer simulations using the SW potential. Compressibilities exhibit a growing maximum upon lowering temperature below 1500 K and isotherms exhibit density discontinuities below 1120 K, at negative pressure. Below 1120 K, isotherms obtained from constant volume-temperature simulations exhibit non-monotonic, van der Waals-like behavior signaling a first order transition. We identify Tc ~ 1120 +/- 12 K, Pc -0.60 +/- 0.15 GPa as the critical temperature and pressure for the liquid-liquid critical point. The structure of the liquid changes dramatically upon decreasing the temperature and pressure. Diffusivities vary over 4 orders of magnitude, and exhibit anomalous pressure dependence near the critical point. A strong relationship between local geometry quantified by the coordination number, and diffusivity, is seen, suggesting that atomic mobility in both low and high density liquids can usefully be analyzed in terms of defects in the tetrahedral network structure. We have constructed the phase diagram of supercooled silicon. We identify the lines of compressibility, density extrema (maxima and minima) and the spinodal which reveal the interconnection between thermodynamic anomalies and the phase behaviour of the system as suggested in previous works [2-9]Comment: (to be published in revised form); small corrections to previous version; Nature Physics 201

Acceptability of the Distress Thermometer and Problem List to community-based telephone cancer helpline operators, and to cancer patients and carers

Background Cancer can be a distressing experience for cancer patients and carers, impacting on psychological, social, physical and spiritual functioning. However, health professionals often fail to detect distress in their patients due to time constraints and a lack of experience. Also, with the focus on the patient, carer needs are often overlooked. This study investigated the acceptability of brief distress screening with the Distress Thermometer (DT) and Problem List (PL) to operators of a community-based telephone helpline, as well as to cancer patients and carers calling the service. Methods Operators (n = 18) monitored usage of the DT and PL with callers (cancer patients/carers, >18 years, and English-speaking) from September-December 2006 (n = 666). The DT is a single item, 11-point scale to rate level of distress. The associated PL identifies the cause of distress. Results The DT and PL were used on 90% of eligible callers, most providing valid responses. Benefits included having an objective, structured and consistent means for distress screening and triage to supportive care services. Reported challenges included apparent inappropriateness of the tools due to the nature of the call or level of caller distress, the DT numeric scale, and the level of operator training. Conclusions We observed positive outcomes to using the DT and PL, although operators reported some challenges. Overcoming these challenges may improve distress screening particularly by less experienced clinicians, and further development of the PL items and DT scale may assist with administration. The DT and PL allow clinicians to direct/prioritise interventions or referrals, although ongoing training and support is critical in distress screening

Trends in non-metastatic prostate cancer management in the Northern and Yorkshire region of England, 2000–2006

Background: Our objective was to analyse variation in non-metastatic prostate cancer management in the Northern and Yorkshire region of England. Methods: We included 21 334 men aged ⩾55, diagnosed between 2000 and 2006. Principal treatment received was categorised into radical prostatectomy (11%), brachytherapy (2%), external beam radiotherapy (16%), hormone therapy (42%) and no treatment (29%). Results: The odds ratio (OR) for receiving a radical prostatectomy was 1.53 in 2006 compared with 2000 (95% CI 1.26–1.86), whereas the OR for receiving hormone therapy was 0.57 (0.51–0.64). Age was strongly associated with treatment received; radical treatments were significantly less likely in men aged ⩾75 compared with men aged 55–64 years, whereas the odds of receiving hormone therapy or no treatment were significantly higher in the older age group. The OR for receiving radical prostatectomy, brachytherapy or external beam radiotherapy were all significantly lower in the most deprived areas when compared with the most affluent (0.64 (0.55–0.75), 0.32 (0.22–0.47) and 0.83 (0.74–0.94), respectively) whereas the OR for receiving hormone therapy was 1.56 (1.42–1.71). Conclusions: This study highlights the variation and inequalities that exist in the management of non-metastatic prostate cancer in the Northern and Yorkshire region of England

Clustering of smoking, alcohol drinking and cannabis use in adolescents in a rapidly developing country

BACKGROUND: Smoking, alcohol drinking and cannabis use ("risk behaviors") are often initiated at a young age but few epidemiological studies have assessed their joined prevalence in children in developing countries. This study aims at examining the joint prevalence of these behaviors in adolescents in the Seychelles, a rapidly developing country in the Indian Ocean. METHODS: Cross-sectional survey in a representative sample of secondary school students using an anonymous self-administered questionnaire (Global Youth Tobacco Survey). The questionnaire was completed by 1,321 (92%) of 1,442 eligible students aged 11 to 17 years. Main variables of interest included smoking cigarettes on ≥1 day in the past 30 days; drinking any alcohol beverage on ≥1 day in the past 30 days and using cannabis at least once in the past 12 months. RESULTS: In boys and girls, respectively, prevalence (95% CI) was 30% (26–34)/21% (18–25) for smoking, 49% (45–54)/48% (43–52) for drinking, and 17% (15–20)/8% (6–10) for cannabis use. The prevalence of all these behaviors increased with age. Smokers were two times more likely than non-smokers to drink and nine times more likely to use cannabis. Drinkers were three times more likely than non-drinkers to smoke or to use cannabis. Comparison of observed versus expected frequencies of combination categories demonstrated clustering of these risk behaviors in students (P < 0.001). CONCLUSION: Smoking, drinking and cannabis use were common and clustered among adolescents of a rapidly developing country. These findings stress the need for early and integrated prevention programs

Influence of the oxygen microenvironment on the proangiogenic potential of human endothelial colony forming cells

Therapeutic angiogenesis is a promising strategy to promote the formation of new or collateral vessels for tissue regeneration and repair. Since changes in tissue oxygen concentrations are known to stimulate numerous cell functions, these studies have focused on the oxygen microenvironment and its role on the angiogenic potential of endothelial cells. We analyzed the proangiogenic potential of human endothelial colony-forming cells (hECFCs), a highly proliferative population of circulating endothelial progenitor cells, and compared outcomes to human dermal microvascular cells (HMVECs) under oxygen tensions ranging from 1% to 21% O2, representative of ischemic or healthy tissues and standard culture conditions. Compared to HMVECs, hECFCs (1) exhibited significantly greater proliferation in both ischemic conditions and ambient air; (2) demonstrated increased migration compared to HMVECs when exposed to chemotactic gradients in reduced oxygen; and (3) exhibited comparable or superior proangiogenic potential in reduced oxygen conditions when assessed using a vessel-forming assay. These data demonstrate that the angiogenic potential of both endothelial populations is influenced by the local oxygen microenvironment. However, hECFCs exhibit a robust angiogenic potential in oxygen conditions representative of physiologic, ischemic, or ambient air conditions, and these findings suggest that hECFCs may be a superior cell source for use in cell-based approaches for the neovascularization of ischemic or engineered tissues